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Yao Z, Ren Y, Cao M, Li Y, Su X, Hu Z, Han P, Yuen HK, Cheung TT. Comparative analysis of hepatectomy for HCC with PVTT: Insights from a 30-year single-center experience: Hepatectomy for HCC with PVTT. Surg Oncol 2025; 60:102211. [PMID: 40120185 DOI: 10.1016/j.suronc.2025.102211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/20/2025] [Accepted: 03/06/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND AND AIM Portal vein tumor thrombosis (PVTT) is frequent in hepatocellular carcinoma (HCC). Although hepatectomy is the primary treatment for HCC, no consensus exists on its role in PVTT between Eastern and Western clinicians. This study aims to assess the efficacy of hepatectomy in HCC patients with PVTT by analyzing perioperative outcomes and prognosis. METHODS This retrospective, single-center study reviewed HCC patient data from Queen Mary Hospital, Hong Kong (1989-2020). Propensity score matching (PSM) was applied to match patients with and without PVTT undergoing hepatectomy, comparing perioperative and survival outcomes between groups. RESULTS Among 3981 HCC patients, 1842 had PVTT and were not operated (not-operated group), while 2139 underwent hepatectomy. Of the operated patients, 156 had PVTT (PVTT group) and 1983 did not (no-PVTT group). Median overall survival (mOS) in the not-operated group was 2.7 months, compared to 13.0 months in the PVTT group. After 1:3 PSM, the no-PVTT group (n = 468) had longer mOS (47.0 vs. 13.0 months, p < 0.001) and disease-free survival (10.6 vs. 4.2 months, p < 0.001). The PVTT group had longer operative times (449 vs. 390 min, p < 0.001), higher complication rates (37.8 % vs. 28.2 %, p = 0.024), and closer surgical margins (0.6 vs. 1.0 cm, p = 0.036), but similar hospital mortality (p = 0.898). mOS for low-AFP (<17400 ng/ml) and high-AFP (≥17400 ng/ml) patients was 16.2 vs. 8.2 months, respectively (p < 0.001). CONCLUSION Aggressive treatment of PVTT is necessary. For certain PVTT patients, hepatectomy may be potentially effective, with acceptable perioperative safety and seemingly no technical barriers.
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Affiliation(s)
- Zhicheng Yao
- Department of Hepatobiliary & Pancreatic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China; Department of Surgery, School of Clinical Medicine, The University of Hong Kong, 102 Pok Fu Lam Road, 999077, Hong Kong, China.
| | - Yupeng Ren
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
| | - Mingbo Cao
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
| | - Yuxuan Li
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
| | - Xiaorui Su
- Department of Hepatobiliary & Pancreatic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
| | - Ziyi Hu
- Department of Hepatobiliary & Pancreatic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
| | - Pei Han
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, 102 Pok Fu Lam Road, 999077, Hong Kong, China.
| | - Ho Kam Yuen
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, 102 Pok Fu Lam Road, 999077, Hong Kong, China.
| | - Tan To Cheung
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, 102 Pok Fu Lam Road, 999077, Hong Kong, China.
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Tada F, Hiraoka A, Ohama H, Kimura Y, Nakamura A, Matsuoka K, Matsuda T, Kato K, Murakawa K, Onishi K, Izumoto H, Kitahata S, Kanemitsu-Okada K, Kawamura T, Kuroda T, Hanaoka J, Watanabe J, Ohtani H, Miyake T, Yoshida O, Hirooka M, Miyata H, Tsubouchi E, Abe M, Matsuura B, Ninomiya T, Hiasa Y. Dynamic changes in the characteristics of hepatocellular carcinoma among Japanese patients: Increasing incidence of cases without liver fibrosis. Hepatol Res 2025. [PMID: 40402553 DOI: 10.1111/hepr.14208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2025] [Revised: 04/26/2025] [Accepted: 05/06/2025] [Indexed: 05/23/2025]
Abstract
AIM Dynamic changes in the characteristics of hepatocellular carcinoma (HCC) have been observed owing to the development of antiviral therapies and an aging society. This study aimed to evaluate the clinical features and prognosis of patients with HCC but without liver fibrosis (F0 HCC). METHODS From 2000 to 2023, 505 patients with HCC who underwent surgical resection as an initial treatment were enrolled and categorized into the F0 (n = 59) and fibrosis (F1-4, n = 446) groups based on their liver fibrosis status. Clinical features, tumor factors, and survival outcomes were retrospectively analyzed. Inverse probability weighting with propensity scores was used to control for baseline differences between the groups. RESULTS The proportion of F0 HCC (G1/G2/G3/G4 = 1.3/7.0/13.3/20.0%, p < 0.001) and nonviral (NBNC) HCC cases increased steadily over the study period. Patients in the F0 group were older and more likely to show solitary giant tumors; however, no significant differences were observed in tumor differentiation, microvascular invasion, or intrahepatic metastasis between the groups. After adjusting for baseline characteristics, the F0 group showed significantly improved overall survival and recurrence-free survival compared to the fibrosis group (adjusted median OS: not achieved vs. 90.6 months, p < 0.001; adjusted median RFS: 67.2 vs. 35.1 months, p < 0.001). CONCLUSIONS The increasing prevalence of NBNC HCC has contributed to an increase in the number of F0 HCC cases, demonstrating favorable prognoses post-curative treatment. Screening strategies tailored to detect F0 HCC are urgently needed to optimize outcomes, particularly for older patients and those with large tumors.
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Affiliation(s)
- Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Yuka Kimura
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Ayaka Nakamura
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kana Matsuoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Takuya Matsuda
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kanako Kato
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kazuya Murakawa
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kei Onishi
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hirofumi Izumoto
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Shogo Kitahata
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | | | - Tomoe Kawamura
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Taira Kuroda
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Jun Hanaoka
- Department of Surgery, Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Jota Watanabe
- Department of Surgery, Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hiromi Ohtani
- Department of Surgery, Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hideki Miyata
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Eiji Tsubouchi
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Bunzo Matsuura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Tomoyuki Ninomiya
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
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Moris D, Martinino A, Schiltz S, Allen PJ, Barbas A, Sudan D, King L, Berg C, Kim C, Bashir M, Palta M, Morse MA, Lidsky ME. Advances in the treatment of hepatocellular carcinoma: An overview of the current and evolving therapeutic landscape for clinicians. CA Cancer J Clin 2025. [PMID: 40392748 DOI: 10.3322/caac.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/10/2025] [Accepted: 04/11/2025] [Indexed: 05/22/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern-day practice-changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern-day practice-changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient-oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.
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Affiliation(s)
- Dimitrios Moris
- Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Alessandro Martinino
- Division of Abdominal Transplantation, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Sarah Schiltz
- Patient Advocate Steering Committee, National Cancer Institute Hepatobiliary Task Force, Los Gatos, California, USA
- Blue Faery, Simi Valley, California, USA
- Cancer CAREpoint, Los Gatos, California, USA
| | - Peter J Allen
- Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Andrew Barbas
- Division of Abdominal Transplantation, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Debra Sudan
- Division of Abdominal Transplantation, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Lindsay King
- Division of Gastroenterology and Hepatology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Carl Berg
- Division of Gastroenterology and Hepatology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Mustafa Bashir
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
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Takeda Y, Imamura H, Sano K, Ichida H, Yoshioka R, Mise Y, Matsuyama Y, Saiura A. The time to noncurative recurrence after liver resection as an appropriate surrogate measure for overall survival in patients with hepatocellular carcinoma. J Gastrointest Surg 2025; 29:101989. [PMID: 39952389 DOI: 10.1016/j.gassur.2025.101989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/29/2025] [Accepted: 02/08/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Patients with recurrent hepatocellular carcinoma after liver resection can often receive curative treatment, including repeat hepatic resection and local ablative therapy. However, recurrence typically becomes increasingly aggressive during the clinical course, characterized by cycles of recurrence and repeated treatment, ultimately resulting in noncurative patterns. METHODS Noncurative recurrence was defined as the presence of ≥4 liver nodules, macroscopic vascular invasion, and extrahepatic lesions. First, this study investigated the incidence of noncurative recurrence and survival after noncurative recurrence. Subsequently, this study examined survival after the initial recurrence in patients with curative and noncurative recurrences and compared them. Finally, this study investigated whether the time to noncurative recurrence serves as a surrogate for overall survival (OS) in 266 patients who underwent initial curative hepatectomy. RESULTS The 3-year cumulative incidences of noncurative recurrence were 15.6%, 6.0%, and 11.0% for ≥4 liver nodules, macroscopic vascular invasion, and extrahepatic lesions, respectively. The median postrecurrence survival estimates after these noncurative recurrences were 21, 17, and 8 months, respectively (P =.006). When analyzed exclusively in patients developing initial recurrence, the 3-year postrecurrence survival rates were 68.3% and 27.8% for patients with curative and noncurative recurrences, respectively (P =.003). The 3-year survival rate without noncurative recurrences was 71.9%, and the recurrence-free survival (RFS) and OS rates were 49.2% and 87.9%, respectively. The concordance index with OS was higher for time to noncurative recurrence than for RFS (0.88 vs 0.67, respectively). CONCLUSION Our findings suggest that the time to noncurative recurrence is a more suitable surrogate for OS than RFS.
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Affiliation(s)
- Yoshinori Takeda
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
| | - Katsuhiro Sano
- Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
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Sihardo L, Lalisang ANL, Syaiful RA, Putra AB, Mazni Y, Putranto AS, Lalisang TJM. Seizing tumor factors for mortality and survival outcomes following liver resection in Indonesia's hepatocellular carcinoma patients. Ann Hepatobiliary Pancreat Surg 2025; 29:11-20. [PMID: 39734304 PMCID: PMC11830890 DOI: 10.14701/ahbps.24-179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 12/31/2024] Open
Abstract
Backgrounds/Aims The 3-year mortality rate for hepatocellular carcinoma (HCC) in Indonesia was 94.4%. This underscores a significant health issue in Southeast Asia, particularly in Indonesia due to its large population. This study aimed to characterize the outcomes of liver resection for HCC at a National Referral Center in Indonesia. Methods Between 2010 and 2020, all patients with HCC undergoing liver resection were included as subjects. Variables collected included sex, age, hepatitis status, and tumor's characteristics. Mortality and survival were the primary outcomes of the study. Results Among seventy patients, the mortality rate was 71.4%, with a median overall survival of 19.0 months (95% confidence interval [95%CI]: 6.831.2). Thirty-one patients (44.3%) had extra-large HCC tumors (> 10 cm). Those with extra-large tumors had a lower median survival of 8.0 months. Child-Pugh B and Edmonson-Steiner grade 4 were associated with an increased mortality risk, with unadjusted hazard ratios (HRs) of 2.2 (95%CI: 1.14.3, p = 0.026) and 3.2 (95%CI: 1.37.7, p = 0.011), respectively. Multivariate analysis indicated that Child-Pugh class B significantly increased the risk of mortality, with an adjusted HR of 2.3 (95%CI: 1.05.2, p = 0.046). Conclusions While surgical resection is feasible for tumors of any size, most clinical features are not statistically significantly associated with survival outcomes. The prevalence of extra-large tumors among Indonesian HCC patients highlights the importance of early diagnosis and intervention. Surgical intervention at an earlier stage and with better grade tumors could potentially enhance survival outcomes.
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Affiliation(s)
- Lam Sihardo
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Arnetta Naomi Louise Lalisang
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Ridho Ardhi Syaiful
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Afid Brilliana Putra
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Yarman Mazni
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Agi Satria Putranto
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Toar Jean Maurice Lalisang
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
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Patauner S, Scotton G, Notte F, Frena A. Advanced hepatocellular carcinoma treatment strategies: Are transarterial approaches leading the way? World J Gastrointest Oncol 2025; 17:99834. [PMID: 39817134 PMCID: PMC11664626 DOI: 10.4251/wjgo.v17.i1.99834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 12/12/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with advanced stages posing significant treatment challenges. Although hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising modality for treating advanced HCC, particularly in Asian clinical practice, its adoption in Western medicine remains limited due to a lack of large-scale randomized controlled trials. This editorial reviews and comments on the meta-analysis conducted by Zhou et al, which evaluates the efficacy and safety of HAIC and its combination strategies for advanced HCC. The authors performed a comprehensive meta-analysis of various clinical trials and cohort studies comparing HAIC and its combinations to other first-line treatments, such as sorafenib and transarterial chemoembolization (TACE). In this work, HAIC showed significantly better results regarding overall survival and progression-free survival compared to sorafenib or TACE alone and their combination. HAIC in combination with lenvatinib, ablation, programmed cell death 1 inhibitors, and radiotherapy further enhanced patient outcomes, indicating a synergistic effect. This editorial focuses on the critical role of multimodal treatment strategies in managing advanced HCC. It advocates for a paradigm shift towards integrated treatment approaches to enhance survival rates and improve the quality of life in patients with advanced HCC.
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Affiliation(s)
- Stefan Patauner
- Department of General and Pediatric Surgery, Bolzano Central Hospital - SABES, Bolzano 39100, Trentino-Alto Adige, Italy
| | - Giovanni Scotton
- Department of General and Pediatric Surgery, Bolzano Central Hospital - SABES, Bolzano 39100, Trentino-Alto Adige, Italy
| | - Francesca Notte
- Department of General and Pediatric Surgery, Bolzano Central Hospital - SABES, Bolzano 39100, Trentino-Alto Adige, Italy
| | - Antonio Frena
- Department of General and Pediatric Surgery, Bolzano Central Hospital - SABES, Bolzano 39100, Trentino-Alto Adige, Italy
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Fujitani K, Kurokawa Y, Wada R, Takeno A, Kawabata R, Omori T, Imamura H, Hirao M, Endo S, Kawada J, Moon JH, Takiguchi S, Mori M, Eguchi H, Doki Y. Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival. Eur J Cancer 2024; 213:115080. [PMID: 39461056 DOI: 10.1016/j.ejca.2024.115080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/08/2024] [Accepted: 10/15/2024] [Indexed: 10/29/2024]
Abstract
OBJECTIVE Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. METHODS Patients with synchronous or metachronous LMGC received 2-4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. RESULTS Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1-71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9-34.0) and 34.9 % (95 % CI 22.2-50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1-3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16-6.35), P = 0.022; pN1-3: HR 9.11 (95 % CI, 1.22-68.2), P = 0.031). CONCLUSION R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. CLINICAL TRIAL REGISTRATION NUMBER UMIN 000011445 (https://www.umin.ac.jp/ctr/).
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Affiliation(s)
- Kazumasa Fujitani
- Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryohei Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | | | - Takeshi Omori
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Hiroshi Imamura
- Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Motohiro Hirao
- Department of Surgery, Osaka National Hospital, Osaka, Japan
| | - Shunji Endo
- Department of Surgery, Higashi-Osaka Medical Center, Higashi-Osaka, Japan
| | - Junji Kawada
- Department of Surgery, Kaizuka Municipal Hospital, Kaizuka, Japan
| | - Jeong Ho Moon
- Department of Surgery, Osaka 2nd Police Hospital, Osaka, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medicine, Nagoya, Japan
| | - Masaki Mori
- Tokai University School of Medicine, Isehara, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
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8
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Tu X, Zhang W, Li S, He Q, Li Y. Efficacy of hepatic arterial infusion chemotherapy in patients with primary liver cancer with portal vein tumor thrombosis: a comparative analysis of different perfusion chemotherapeutic regimens. Eur J Med Res 2024; 29:465. [PMID: 39294739 PMCID: PMC11411809 DOI: 10.1186/s40001-024-02053-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 09/08/2024] [Indexed: 09/21/2024] Open
Abstract
BACKGROUND Portal vein tumor thrombosis (PVTT) commonly occurs in patients with primary liver cancer (PLC). Transarterial chemoembolization (TACE) is a treatment for patients with PLC and PVTT. Some studies have shown that combining TACE therapy with hepatic arterial infusion chemotherapy (HAIC) might improve the survival rate of PLC patients with PVTT. However, few studies have compared the different regimens of PLC with PVTT. We aimed to compare the differences between the oxaliplatin + raltetrexed regimen and FOLFOX regimen. METHODS We divided the 248 patients into two groups. There were 60 patients in the oxaliplatin + ratitetrexed group and 74 patients in the FOLFOX group. The primary endpoints were OS and PFS. The secondary endpoints were ORR and adverse events. We used SPSS software, the Kaplan-Meier method, the t test, and the rank sum test to compare the differences between the two groups. RESULTS The median OS was 10.82 months in the oxaliplatin + raltitrexed group and 8.67 months in the FOLFOX group. The median PFS time was greater in the oxaliplatin + raltitrexed group (10.0 months) than that in the FOLFOX group (7.1 months). The ORR was greater in the oxaliplatin + raltitrexed group than that in the FOLFOX group (18.3% vs. 13.5%; P = 0.445). The DCR in the oxaliplatin + raltitrexed group was higher than that in the FOLFOX group (70.0% vs. 64.8%; P = 0.529). However, in the subgroup analysis, the difference between them was more significant in the type II PVTT subgroup. The OS was 12.08 months in the oxaliplatin + raltitrexed group and 7.26 months in the FOLFOX group (P = 0.008). The PFS was 11.68 months in the oxaliplatin + raltitrexed group and 6.26 months in the FOLFOX group (P = 0.014). In the right branch of type II PVTT, the OS was 13.54 months in the oxaliplatin + raltitrexed group and 6.89 months in the FOLFOX group (P = 0.015), and the PFS was 13.35 months in the oxaliplatin + raltitrexed group and 6.27 months in the FOLFOX group (P = 0.030). The incidence of adverse reactions was similar between the two groups. CONCLUSIONS Compared with the FOLFOX regimen, the oxaliplatin + raltitrexed chemoembolization regimen had longer OS, PFS time and ORR and DCR and it was safe and tolerable.
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Affiliation(s)
- Xinxin Tu
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, No. 74, Linjiang Road, Yuzhong District, Chongqing Municipality, 400010, People's Republic of China
| | - Wenfeng Zhang
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, No. 74, Linjiang Road, Yuzhong District, Chongqing Municipality, 400010, People's Republic of China
| | - Sipeng Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, No. 181, Hanyu Road, Shapingba District, Chongqing Municipality, 400010, People's Republic of China
| | - Qi He
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, No. 74, Linjiang Road, Yuzhong District, Chongqing Municipality, 400010, People's Republic of China
| | - Yue Li
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, No. 74, Linjiang Road, Yuzhong District, Chongqing Municipality, 400010, People's Republic of China.
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Abdelhamed W, El-Kassas M. Hepatitis B virus as a risk factor for hepatocellular carcinoma: There is still much work to do. LIVER RESEARCH (BEIJING, CHINA) 2024; 8:83-90. [PMID: 39959873 PMCID: PMC11771266 DOI: 10.1016/j.livres.2024.05.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 03/23/2024] [Accepted: 05/30/2024] [Indexed: 04/03/2025]
Abstract
Hepatitis B virus (HBV) infection is a significant health problem that can result in progression to liver cirrhosis, decompensation, and the development of hepatocellular carcinoma (HCC). On a country level, the prevalence of chronic HBV infection varies between 0.1% and 35.0%, depending on the locality and the population being investigated. One-third of all liver cancer fatalities worldwide are attributable to HBV. The adoption of standard birth-dose immunization exerted the most significant impact on the decline of HBV prevalence. HCC incidence ranges from 0.01% to 1.40% in noncirrhotic patients and from 0.9% to 5.4% annually, in the settings of liver cirrhosis. Although antiviral therapy significantly reduces the risk of developing HBV-related HCC, studies have demonstrated that the risk persists, and that HCC screening is still essential. This review discusses the complex relationship between HBV infection and HCC, recent epidemiological data, different aspects of clinical disease characteristics, and the impact of antiviral therapy in this context.
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Affiliation(s)
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Yang D, Chen X, Huang L, Wang X, Mao L, Lin L, Han H, Lu Q. Correlation between CEUS LI-RADS categorization of HCC < 20 mm and clinic-pathological features. Insights Imaging 2024; 15:110. [PMID: 38713251 PMCID: PMC11076425 DOI: 10.1186/s13244-024-01688-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 04/03/2024] [Indexed: 05/08/2024] Open
Abstract
OBJECTIVE To retrospectively evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) LI-RADS in liver nodules < 20 mm at high risk of hepatocellular carcinoma (HCC) and their correlation with clinic-pathological features. METHODS A total of 432 pathologically proved liver nodules < 20 mm were included from January 2019 to June 2022. Each nodule was categorized as LI-RADS grade (LR)-1 to LR-5 through LR-M according to CEUS LI-RADS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of CEUS LI-RADS were evaluated using pathological reference standard. Correlations between clinic-pathological features and CEUS LI-RADS categorization, together with major CEUS features, were further explored. RESULTS With LR-5 to diagnose HCC, the sensitivity, specificity, PPV, NPV, and AUC were 50.3%, 70.0%, 91.2%, 18.5%, and 0.601, respectively. The proportion of LR-5 in primary HCCs was significantly higher than that in recurrent ones (p = 0.014). HCC 10-19 mm showed significantly more frequent arterial phase hyper-enhancement (APHE) and late washout (p < 0.05) and less no-washout (p = 0.003) compared with those in HCC < 10 mm. Well-differentiated HCCs showed more frequent non-APHE and no-washout than moderate- and poor-differentiated HCCs (p < 0.05). Upgrading "APHE without washout" LR-4 nodules 10-19 mm with HCC history and "APHE with late mild washout" LR-4 nodules < 10 mm to LR-5 could improve the diagnostic performance of LR-5. The corresponding sensitivity, specificity, PPV, NPV, and AUC are 60.2%, 70.0%, 92.6%, 22.1%, and 0.651, respectively. CONCLUSIONS CEUS LI-RADS is valuable in the diagnosis of HCC < 20 mm and performance can be improved with the combination of clinic-pathological features. CRITICAL RELEVANCE STATEMENT CEUS LI-RADS was valuable in the diagnosis of HCC < 20 mm and its diagnostic performance can be improved by combining clinic-pathological features. Further research is needed to define its value in this set of lesions. KEY POINTS Contrast-enhanced ultrasound can detect small liver lesions where LI-RADS accuracy is uncertain. Many LI-RADS Grade-4 nodules were upgraded to Grade-5 by combining imaging with clinic-pathological factors. The reclassification of LI-RADS Grade-5 can improve sensitivity without decreasing positive predictive value.
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Affiliation(s)
- Daohui Yang
- Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Xuejun Chen
- Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Linjin Huang
- Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Lijuan Mao
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Lewu Lin
- Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Hong Han
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China.
- Shanghai Institute of Medical Imaging, Shanghai, China.
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11
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Long Y, Zeng Q, He X, Wu Y, Ye H, Xu J, Chen J, Yuan L, Li H, Li K. Anatomical thermal ablation as an alternative to surgical resection for subcapsular hepatocellular carcinoma. Abdom Radiol (NY) 2024; 49:1144-1153. [PMID: 38289353 DOI: 10.1007/s00261-023-04150-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 12/03/2023] [Accepted: 12/05/2023] [Indexed: 03/22/2024]
Abstract
PURPOSE To simulate the advantages of anatomical resection, a new strategy of anatomical thermal ablation was proposed. The objective of this study was to evaluate the clinical value of anatomical thermal ablation (ATA) to treat subcapsular hepatocellular carcinoma by comparing it with anatomical resection (AR) and non-anatomical resection (NAR). METHODS This retrospective cohort study enrolled hepatocellular carcinoma patients with subcapsular tumor diameter ≤ 50 mm treated by ATA or surgical resection at our center from October 2015 to December 2018. ATA features ablation of the Glisson capsule, ablation of the liver parenchyma between the tumor and hepatic veins or inferior vena cava and then puncture from the surrounding part to the central part of the tumor. Outcome parameters were compared. RESULTS Seventy-six patients were grouped into ATA group, 95 patients into AR group and 41 patients into NAR group. The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, 0.0% for ATA group, 0.0%, 1.4%, 1.4% for the AR group and 0.0%, 0.0%, and 0.0% for the NAR group, respectively (P = 0.449). The 1-, 2-, and 3-year progression-free survival rates were 90.6%, 80.9%, and 74.6% for ATA group, 91.5%, 80.2%, and 80.2% for the AR group and 82.9%, 73.8%, and 73.8% for the NAR group, respectively (P = 0.608). The 1-, 2-, and 3-year overall survival rates were 100.0%, 95.2%, and 95.2% for the ATA group, 96.8%, 95.6%, and 95.6% for the AR group and 97.6%, 95.0%, and 95.0% for the NAR group, respectively (P = 0.970). No difference was found in major complication rate among these groups (P = 0.091). CONCLUSION For subcapsular hepatocellular carcinoma, ATA could be an alternative to surgical resection with its comparable treatment effect and safety.
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Affiliation(s)
- Yinglin Long
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, 510630, Guangdong, China
| | - Qingjing Zeng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, 510630, Guangdong, China
| | - Xuqi He
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, 510630, Guangdong, China
| | - Yuxuan Wu
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, 510630, Guangdong, China
| | - Huolin Ye
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, 510630, Guangdong, China
| | - Jianliang Xu
- Department of Liver Surgery, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, China
| | - Jianning Chen
- Department of Pathology, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, China
| | - Lianxiong Yuan
- Department of Science and Research, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, China
| | - Hua Li
- Department of Liver Surgery, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, China
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road No. 600, Guangzhou, 510630, Guangdong, China.
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12
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Huang H, Cheng MQ, He DN, Xian MF, Zeng D, Wu SH, Li CQ, Ruan SM, Li MD, Lin MX, Lu MD, Kuang M, Wang W, Chen LD. US LI-RADS in surveillance for recurrent hepatocellular carcinoma after curative treatment. Eur Radiol 2023; 33:9357-9367. [PMID: 37460801 DOI: 10.1007/s00330-023-09903-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 03/24/2023] [Accepted: 04/19/2023] [Indexed: 11/26/2023]
Abstract
OBJECTIVES To investigate the performance of US LI-RADS in surveillance for recurrent hepatocellular carcinoma (RHCC) after curative treatment. MATERIALS AND METHODS This study enrolled 644 patients between January 2018 and August 2018 as a derivation cohort, and 397 patients from September 2018 to December 2018 as a validation cohort. The US surveillance after HCC curative treatment was performed. The US LI-RADS observation categories and visualization scores were analyzed. Four criteria using US LI-RADS or Alpha-fetoprotein (AFP) as the surveillance algorithm were evaluated. The sensitivity, specificity, and negative predictive value (NPV) were calculated. RESULTS A total of 212 (32.9%) patients in derivation cohort and 158 (39.8%) patients in validation cohort were detected to have RHCCs. The criterion of US-2/3 or AFP ≥ 20 µg/L had higher sensitivity (derivation, 96.7% vs 92.9% vs 81.1% vs 90.6%; validation, 96.2% vs 90.5% vs 80.4% vs 89.9%) and NPV (derivation, 95.7% vs 93.3% vs 88.0% vs 91.8%; validation, 94.6% vs 89.4% vs 83.6% vs 89.0%), but lower specificity (derivation, 35.9% vs 48.2% vs 67.6% vs 51.9%; validation, 43.5% vs 52.7% vs 66.1% vs 54.0%) than criterion of US-2/3, US-3, and US-3 or AFP ≥ 20 µg/L. Analysis of the visualization score subgroups confirmed that the sensitivity (89.2-97.6% vs 81.0-83.3%) and NPV(88.4-98.0% vs 80.0-83.3%) of score A and score B groups were higher than score C group in criterion of US-2/3 in both two cohorts. CONCLUSIONS In the surveillance for RHCC, US LI-RADS with AFP had a high sensitivity and NPV when US-2/3 or AFP ≥ 20 µg/L was considered a criterion. CLINICAL RELEVANCE STATEMENT The criterion of US-2/3 or AFP ≥ 20 µg/L improves sensitivity and NPV for RHCC surveillance, which provides a valuable reference for patients in RHCC surveillance after curative treatment. KEY POINTS • US LI-RADS with AFP had high sensitivity and NPV in surveillance for RHCC when considering US-2/3 or AFP ≥ 20 µg/L as a criterion. • After US with AFP surveillance, patients with US-2/3 or AFP ≥ 20 µg/L should perform enhanced imaging for confirmative diagnosis. Patients with US-1 or AFP < 20 µg/L continue to repeat US with AFP surveillance. • Patients with risk factors for poor visualization scores limited the sensitivity of US surveillance in RHCC.
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Affiliation(s)
- Hui Huang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Mei-Qing Cheng
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Dan-Ni He
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
- Department of Medical Ultrasonics, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Meng-Fei Xian
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Dan Zeng
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Shao-Hong Wu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Chao-Qun Li
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
- Department of Ultrasound Medicine, West China Xiamen Hospital of Sichuan University, Xiamen, China
| | - Si-Min Ruan
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Ming-De Li
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Man-Xia Lin
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Li-Da Chen
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.
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Kanzaki H, Ogasawara S, Okubo T, Itokawa N, Yoshino R, Fujimoto K, Kogure T, Yumita S, Ishino T, Ogawa K, Iwanaga T, Nakagawa M, Fujiwara K, Kojima R, Koroki K, Inoue M, Kobayashi K, Kanogawa N, Kiyono S, Nakamura M, Kondo T, Nakagawa R, Nakamoto S, Muroyama R, Itobayashi E, Atsukawa M, Kato J, Kato N. Cabozantinib for Advanced Hepatocellular Carcinoma in the Latest Real-World Practice: A Multicenter Retrospective Analysis. Drugs Real World Outcomes 2023; 10:513-520. [PMID: 37466822 PMCID: PMC10730490 DOI: 10.1007/s40801-023-00379-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Cabozantinib was found to be effective as a second- or third-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 CELESTIAL trial. So far, as immunotherapy has substituted molecular target agents as the primary systemic therapy for advanced HCC, cabozantinib is extensively used in the latest real-world clinical practice in a greatly different position than that shown by the CELESTIAL trial. In the current analysis, we examined the safety and effectiveness of cabozantinib administration in real-life settings for patients with advanced HCC. METHODS We retrospectively obtained data from patients with advanced HCC who received cabozantinib in three institutions in Japan between 14 September 2018 and 30 November 2021. RESULTS During the study period, 23 patients with advanced HCC received cabozantinib. Our cohort included 21.7% of patients with Child-Pugh class B, and 52.2% of patients in fourth line or later. The median progression-free survival of patients given cabozantinib was 3.7 months. Regarding patients with Child-Pugh class B or administration in fourth line or later, the discontinuation rate due to adverse events in patients who initialized at 40 or 20 mg was lower than those who initialized at 60 mg (42.9% versus 75.0%). Patients who were able to continue treatment with cabozantinib for more than 3 months were more likely to undergo dose reduction than those who did not (85.7% versus 25.0%). CONCLUSIONS Cabozantinib has recently been administered to a diverse range of patients, including those who were not enrolled in the CELESTIAL trial. Deliberate dose reduction could potentially offer clinical benefits to patients with impaired liver function. Furthermore, managing adverse events by reducing the dose could play a crucial role in extending the duration of treatment with cabozantinib. The preprint version of this work is available on https://www.researchsquare.com/article/rs-2655181/v1 .
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Affiliation(s)
- Hiroaki Kanzaki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Norio Itokawa
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Ryohei Yoshino
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Kentaro Fujimoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Tadayoshi Kogure
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Sae Yumita
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Takamasa Ishino
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Keita Ogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Terunao Iwanaga
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Miyuki Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Kisako Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Ryuta Kojima
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Keisuke Koroki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Masanori Inoue
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Naoya Kanogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Takayuki Kondo
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Ryo Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Ryosuke Muroyama
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Masanori Atsukawa
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Jun Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
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Hiraoka A, Kumada T, Tada T, Toyoda H, Kariyama K, Hatanaka T, Kakizaki S, Naganuma A, Itobayashi E, Tsuji K, Ishikawa T, Ohama H, Tada F, Nouso K, on behalf of the Real-life Practice Experts for HCC (RELPEC) Study Group. Attempt to Establish Prognostic Predictive System for Hepatocellular Carcinoma Using Artificial Intelligence for Assistance with Selection of Treatment Modality. Liver Cancer 2023; 12:565-575. [PMID: 38058420 PMCID: PMC10697750 DOI: 10.1159/000530078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 03/06/2023] [Indexed: 12/08/2023] Open
Abstract
INTRODUCTION Because of recent developments in treatments for hepatocellular carcinoma (HCC), methods for determining suitable therapy for initial or recurrent HCC have become important. This study used artificial intelligence (AI) findings to establish a system for predicting prognosis of HCC patients at time of reoccurrence based on clinical data as a reference for selection of treatment modalities. METHODS As a training cohort, 5,701 observations obtained at the initial and each subsequent treatment for recurrence from 1,985 HCC patients at a single center from 2000 to 2021 were used. The validation cohort included 5,692 observations from patients at multiple centers obtained at the time of the initial treatment. An AI calculating system (PRAID) was constructed based on 25 clinical factors noted at each treatment from the training cohort, and then predictive prognostic values for 1- and 3-year survival in both cohorts were evaluated. RESULTS After exclusion of patients lacking clinical data regarding albumin-bilirubin (ALBI) grade or tumor-node-metastasis stage of the Liver Cancer Study Group of Japan, 6th edition (TNM-LCSGJ 6th), ALBI-TNM-LCSGJ 6th (ALBI-T) and modified ALBI-T scores confirmed that prognosis for patients in both cohorts was similar. The area under the curve for prediction of both 1- and 3-year survival in the validation cohort was 0.841 (sensitivity 0.933 [95% CI: 0.925-0.940], specificity 0.517 [95% CI: 0.484-0.549]) and 0.796 (sensitivity 0.806 [95% CI: 0.790-0.821], specificity 0.646 [95% CI: 0.624-0.668]), respectively. CONCLUSION The present PRAID system might provide useful prognostic information related to short and medium survival for decision-making regarding the best therapeutic modality for both initial and recurrent HCC cases.
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Affiliation(s)
- Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuya Kariyama
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kazuhiro Nouso
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - on behalf of the Real-life Practice Experts for HCC (RELPEC) Study Group
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
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15
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Li Z, Xu Y, Qu W, Liu P, Zhu Y, Li H, Guo Y, Liu X. Efficacy and safety of hepatic arterial infusion chemotherapy combined with immune checkpoint inhibitors and tyrosine kinase inhibitors in advanced hepatocellular carcinoma: A systematic review and meta‑analysis. Oncol Lett 2023; 26:534. [PMID: 38020293 PMCID: PMC10655037 DOI: 10.3892/ol.2023.14121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 10/13/2023] [Indexed: 12/01/2023] Open
Abstract
At present, hepatic arterial infusion chemotherapy (HAIC) for the treatment of hepatocellular carcinoma (HCC) is often applied to patients who are not suitable or are unwilling to undergo surgical treatment. However, to the best of our knowledge, the efficacy and safety of HAIC combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in HCC have not been fully demonstrated. Published studies involving the treatment of patients with HCC with HAIC, ICIs and TKIs were searched from public databases, including PubMed, Embase, the Cochrane Library and Sinomed. Efficacy and safety data for each study, including progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were collected. The present study included 17 treatment groups from 15 studies, including 1,987 patients with HCC in the systematic review. The target population was dominated by those unsuitable for surgical treatment, with Barcelona Clinic Liver Cancer stage B or C, Eastern Cooperative Oncology Group performance status ≤2 and Child-Pugh score A or B. The results showed that the longest estimated median PFS (95% CI) in the HAIC + ICI/TKI therapy group (group C) was 9.37 months (95% CI, 6.81-11.93); in the HAIC therapy group (group B) was 7.45 months (95% CI, 6.45-8.46); and in the ICIs + other systemic therapies group (group A) was 5.92 months (95% CI, 5.31-6.54). There was no significant difference in the expected OS among the three groups, which may be because OS events were not reached in numerous studies during the follow-up time. The incidence of treatment-related adverse effects, such as increased AST [14/221 (6.33%)], increased ALT [13/221 (5.88%)], and decreased platelet count [13/221 (5.88%)], was not significantly increased in group C when compared with groups A or B (P>0.05). In conclusion, the effectiveness of HAIC + ICI/TKI for the treatment of advanced HCC was better than that of ICIs + other systemic therapies or HAIC alone. In addition, the incidence of AEs above grade 3 was not significantly higher compared with that in the other treatment groups, and the safety profile was good.
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Affiliation(s)
- Zixiong Li
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Yanping Xu
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Wenshu Qu
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Ping Liu
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Yan Zhu
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Hui Li
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Ying Guo
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Xiufeng Liu
- Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
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16
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Manea I, Iacob R, Iacob S, Cerban R, Dima S, Oniscu G, Popescu I, Gheorghe L. Liquid biopsy for early detection of hepatocellular carcinoma. Front Med (Lausanne) 2023; 10:1218705. [PMID: 37809326 PMCID: PMC10556479 DOI: 10.3389/fmed.2023.1218705] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 08/30/2023] [Indexed: 10/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients' stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.
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Affiliation(s)
- Ioana Manea
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Speranta Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Cerban
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Simona Dima
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Gabriel Oniscu
- Transplant Division, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
| | - Irinel Popescu
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Liliana Gheorghe
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
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17
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Shukla A, Jain A. Hepatocellular Carcinoma with Hepatic Vein and Inferior Vena Cava Invasion. J Clin Exp Hepatol 2023; 13:813-819. [PMID: 37693266 PMCID: PMC10482991 DOI: 10.1016/j.jceh.2023.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/15/2023] [Indexed: 09/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) invades intrahepatic vessels causing tumor thrombosis. Infrequently, there is involvement of the hepatic vein (HV) and inferior vena cava (IVC). In this review, we summarize the epidemiology, classification, clinical features, and management of HCC with HV and IVC invasion. While the involvement of HV and IVC usually portends an overall poor survival, selected patients may be candidates for aggressive treatment and thus improving outcomes.
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Affiliation(s)
- Akash Shukla
- Department of Gastroenterology, G.S.Medical College and KEM Hospital, Mumbai, India
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18
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Moriya K, Sato S, Nishimura N, Kawaratani H, Takaya H, Kaji K, Namisaki T, Uejima M, Nagamatsu S, Matsuo H, Yoshiji H. Efficacy of Serum Ferritin-Zinc Ratio for Predicting Advanced Liver Fibrosis in Patients with Autoimmune Hepatitis. J Clin Med 2023; 12:4463. [PMID: 37445498 PMCID: PMC10342266 DOI: 10.3390/jcm12134463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 06/29/2023] [Accepted: 07/02/2023] [Indexed: 07/15/2023] Open
Abstract
Background/Aims: The search for noninvasive biomarkers that can efficiently estimate the extent of liver fibrosis progression is ongoing. Although Fibrosis-4 (FIB-4), the aspartate transaminase-to-platelet ratio index (APRI), and the Forns index have been reported as useful biomarkers, their investigation in autoimmune hepatitis (AIH) is limited. This study aimed to examine the usefulness of these serological indices and a newly developed index in predicting liver fibrosis progression in AIH. Methods: The study analyzed data from 190 patients diagnosed with AIH at our institution between 1990 and 2015. Their histological liver fibrosis progression and clinical long-term prognosis were evaluated retrospectively (cohort 1). In 90 patients, receiver operating characteristic (ROC) curves were compared to choose severe fibrosis cases with respect to existing indices (FIB-4, APRI, and Forns index) and the ferritin-zinc ratio (cohort 2). Results: In cohort 1, liver-related death and hepatocellular carcinoma rates were significantly higher in the severe (n = 27) than in the mild (n = 63) fibrosis group (p = 0.0001 and 0.0191, respectively). In cohort 2, liver-related death in the severe fibrosis group was significantly frequent (p = 0.0071), and their ferritin-zinc ratio was higher (median 2.41 vs. 0.62, p = 0.0011). ROC analyses were performed to compare the ability of the ferritin-zinc ratio, FIB-4, APRI, and the Forns index to predict severe and mild fibrosis. Accordingly, areas under the ROC were 0.732, 0.740, 0.721, and 0.729, respectively. Conclusions: The serum ferritin-zinc ratio can noninvasively predict liver fibrosis progression in AIH and be applied to predict long-term prognosis.
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Affiliation(s)
- Kei Moriya
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
- Department of Gastroenterology, Nara Prefecture General Medical Center, 897-5, 2-Chome, Shichijo-Nishimachi, Nara 630-8581, Japan
| | - Shinya Sato
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
| | - Norihisa Nishimura
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
| | - Hideto Kawaratani
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
| | - Hiroaki Takaya
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
| | - Kosuke Kaji
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
| | - Masakazu Uejima
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
- Department of Gastroenterology, Nara Prefecture General Medical Center, 897-5, 2-Chome, Shichijo-Nishimachi, Nara 630-8581, Japan
| | - Shinsaku Nagamatsu
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
- Department of Gastroenterology, Nara Prefecture General Medical Center, 897-5, 2-Chome, Shichijo-Nishimachi, Nara 630-8581, Japan
| | - Hideki Matsuo
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
- Department of Gastroenterology, Nara Prefecture General Medical Center, 897-5, 2-Chome, Shichijo-Nishimachi, Nara 630-8581, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan; (S.S.); (N.N.); (H.K.); (H.T.); (K.K.); (T.N.); (M.U.); (S.N.); (H.M.); (H.Y.)
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19
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Hasegawa K, Takemura N, Yamashita T, Watadani T, Kaibori M, Kubo S, Shimada M, Nagano H, Hatano E, Aikata H, Iijima H, Ueshima K, Ohkawa K, Genda T, Tsuchiya K, Torimura T, Ikeda M, Furuse J, Akahane M, Kobayashi S, Sakurai H, Takeda A, Murakami T, Motosugi U, Matsuyama Y, Kudo M, Tateishi R. Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2021 version (5th JSH-HCC Guidelines). Hepatol Res 2023; 53:383-390. [PMID: 36826411 DOI: 10.1111/hepr.13892] [Citation(s) in RCA: 122] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/11/2023] [Accepted: 02/18/2023] [Indexed: 02/25/2023]
Abstract
The fifth version of the Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence-based medicine and partly to the Grading of Recommendations Assessment, Development and Evaluation system, which was published in October 2021 in Japanese. In addition to surveillance-diagnostic and treatment algorithms, a new algorithm for systemic therapy has been created, as multiple drugs for hepatocellular carcinoma can be currently selected. Here, new or revised algorithms and evidence on which the recommendations are based are described.
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Affiliation(s)
- Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Nobuyuki Takemura
- Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tatsuya Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Takeyuki Watadani
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Mitsuo Shimada
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Etsuro Hatano
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroshi Aikata
- Department of Medicine and Molecular Science, Hiroshima University Hospital, Hiroshima, Japan
| | - Hiroko Iijima
- Division of Gastroenterology and Hepatobiliary, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Higashi-osaka, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Junji Furuse
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Masaaki Akahane
- Department of Radiology, School of Medicine, International University of Health and Welfare, Otawara, Japan
| | - Satoshi Kobayashi
- Department of Quantum Medical Technology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Hideyuki Sakurai
- Department of Radiation Oncology, University of Tsukuba Faculty of Medicine, Tsukuba, Japan
| | - Atsuya Takeda
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Utaroh Motosugi
- Department of Diagnostic Radiology, Kofu Kyoritsu Hospital, Kofu, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Higashi-osaka, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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20
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Villalba-López F, Sáenz-Mateos LF, Sánchez-Lorencio MI, De La Orden-García V, Alconchel-Gago F, Cascales-Campos PA, García-Bernardo C, Noguera-Velasco JA, Baroja-Mazo A, Ramírez-Romero P. Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma. Sci Rep 2023; 13:5621. [PMID: 37024609 PMCID: PMC10079651 DOI: 10.1038/s41598-023-32879-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 04/04/2023] [Indexed: 04/08/2023] Open
Abstract
The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.
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Affiliation(s)
| | | | | | | | - Felipe Alconchel-Gago
- Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain
| | | | | | | | | | - Pablo Ramírez-Romero
- Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain
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21
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Xiang C, Xiao Y, Ma Z, Peng Y, Li X, Mao X, Li L. Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses. Asia Pac J Clin Oncol 2023; 19:e60-e70. [PMID: 35404506 DOI: 10.1111/ajco.13777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (> 5cm) or huge sizes (> 10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors. The aim of this study was to determine risk predictors of recurrence, patterns of recurrence, and survival rates for large and huge HCC patients who underwent curative liver resection. MATERIALS AND METHODS We retrospectively identified a subgroup of patients who underwent liver resection for HCC with diameters 5 cm or larger. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to investigate potential risk factors for recurrence and death. RESULTS Among 897 patients, the median follow-up was 48 (range, 5-140) months. The 1-, 3-, and 5-year RFS rates were 51.6%, 36.1%, and 30.1%, respectively, and OS rates were 80.2%, 55.4%, and 47.7%, respectively. Significant independent predictors of recurrence were preoperative satellite nodule (HR = 2.25; 95% CI, 1.17-4.31; p = .02), preoperative AFP levels above 400 ng/ml (HR = 1.23; 95% CI, 1.04-1.45; p = .01), resection margins of 1 cm or less (HR = 1.21; 95% CI, 1.00-1.46; p = .047), cirrhosis (HR = 2.64; 95% CI, 2.13-3.28; p < .001), and microvascular invasion (HR = 1.71; 95% CI, 1.45-2.20; p < .001). All of these except narrow resection margin were also independent risk factors of OS. CONCLUSIONS Hepatic resection for patients with large and huge HCC without hepatic vascular invasion, extrahepatic metastases, or severe chronic liver disease results in acceptable long-term outcomes.
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Affiliation(s)
- Cailing Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Department II of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yating Xiao
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, UCAS, Hangzhou, China
| | - Zhongzhi Ma
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yuchong Peng
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Xun Li
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xianhai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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22
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y. Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Cancer Med 2023; 12:7772-7783. [PMID: 36518086 PMCID: PMC10134356 DOI: 10.1002/cam4.5535] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022] Open
Abstract
AIM To investigate the possible correlation between the development of adverse events (AEs) and prognosis in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS A total of 286 patients with unresectable HCC treated with Atez/Bev as first-line systematic therapy were included. RESULTS Regarding treatment-related AEs, decreased appetite of any grade, proteinuria of any grade, and fatigue of any grade were found with a frequency of ≥20%. Multivariate analysis adjusted for immune-related liver injury, immune-related endocrine dysfunction, proteinuria, fatigue, decreased appetite, hypertension, sex, age, Eastern Cooperative Oncology Group performance status, HCC etiology, HCC stage, Child-Pugh score, and α-fetoprotein showed that hypertension of any grade (hazard ratio [HR], 0.527; 95% confidence interval [CI], 0.326-0.854; p = 0.009) and α-fetoprotein ≥100 ng/ml (HR, 1.642; 95% CI, 1.111-2.427; p = 0.013) were independently associated with progression-free survival. Multivariate analysis adjusted for the same AEs showed that fatigue (HR, 2.354; 95% CI, 1.299-4.510; p = 0.010) was independently associated with overall survival. Median progression-free survival was 6.5 months (95% CI, 5.2-8.1) in patients without hypertension of any grade and 12.6 months (95% CI, 6.7-not available) in patients with hypertension of any grade (p = 0.035). The overall survival was significantly shorter in patients in whom treatment-related fatigue of any grade was observed (p < 0.001). Regarding response rates, the disease control rate of patients who developed treatment-related hypertension (94.2%) was significantly higher than those who did not (79.1%) (p = 0.009). CONCLUSIONS Treatment-related hypertension is associated with good outcomes in patients with HCC treated with Atez/Bev.
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Wang L, Peng JL, Wu JZ. Nomogram to predict the prognosis of patients with AFP-negative hepatocellular carcinoma undergoing chemotherapy: A SEER based study. Medicine (Baltimore) 2023; 102:e33319. [PMID: 37000113 PMCID: PMC10063275 DOI: 10.1097/md.0000000000033319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 01/27/2023] [Accepted: 02/27/2023] [Indexed: 04/01/2023] Open
Abstract
This study aimed to formulate reliable nomograms for predicting the outcomes of α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after chemotherapy. HCC patients with normal AFP expression who received chemotherapy were screened and evaluated from the surveillance, epidemiology, and end results database. The prognostic factors for predicting outcomes of HCC patients undergoing chemotherapy were chosen by analyzing the results of Cox analyses. Then, a nomogram integrating the prognostic factors was established. The discrimination ability of the nomogram was evaluated with computation of area under the curve (AUC) and calibration curve. A total of 2424 patients with AFP-negative HCC undergoing chemotherapy were identified. The median overall survival (OS) for HCC patients undergoing chemotherapy was 33 months. Age, race, pathologic grade, N stage, M stage, surgery, and lung metastases were significantly linked to OS. These relevant factors were incorporated into the nomogram. AUC values of the prognostic nomogram for 3- and 5-year OS were 0.696 and 0.706 in the training groups, which were superior to those of the tumor node metastasis (TNM) stage (0.641 and 0.671) in training groups. The calibration curves indicated a high consistency between the predicted probability of nomograms and the actual observation. The validation groups produced AUC values of 0.674 and 0.736 for 3- and 5-year OS, which were superior to those of the TNM stage (0.601 and 0.637) in validation groups. The results revealed significantly unfavorable OS in the high-risk group (P < .001). Nomograms to accurately predict the OS for AFP-negative HCC patients after chemotherapy were established and exhibited a more accurate predication than the conventional TNM staging system.
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Affiliation(s)
- Lei Wang
- Department of Rehabilitation Medicine, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, People’s Republic of China
| | - Jin-Lin Peng
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People’s Republic of China
| | - Ji-Zhou Wu
- The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China
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Kanogawa N, Ogasawara S, Maruta S, Iino Y, Obu M, Ishino T, Ogawa K, Yumita S, Iwanaga T, Unozawa H, Nakagawa M, Fujiwara K, Sakuma T, Fujita N, Kojima R, Kanzaki H, Koroki K, Kobayashi K, Inoue M, Kiyono S, Nakamura M, Kondo T, Saito T, Nakagawa R, Nakamoto S, Muroyama R, Chiba T, Itobayashi E, Koma Y, Azemoto R, Kato J, Kato N. Use of ramucirumab for various treatment lines in real-world practice of patients with advanced hepatocellular carcinoma. BMC Gastroenterol 2023; 23:70. [PMID: 36906542 PMCID: PMC10007811 DOI: 10.1186/s12876-023-02674-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 02/13/2023] [Indexed: 03/13/2023] Open
Abstract
PURPOSE Ramucirumab was shown to be effective as a second-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein levels > 400 ng/mL in a worldwide phase 3 trial. Ramucirumab is used in patients pretreated with various systemic therapies in clinical practice. We retrospectively examined the treatment outcomes of ramucirumab administered to advanced HCC patients after diverse systemic therapies. METHODS Data were collected from patients with advanced HCC who received ramucirumab at three institutions in Japan. Radiological assessments were determined according to both Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and modified RECIST and the Common Terminology Criteria for Adverse Events version 5.0 was used to assess adverse events. RESULTS A total of 37 patients treated with ramucirumab between June 2019 and March 2021 were included in the study. Ramucirumab was administered as second, third, fourth, and fifth-line treatment in 13 (35.1%), 14 (37.8%), eight (21.6%), and two (5.4%) patients, respectively. Most patients (29.7%) who received ramucirumab as a second-line therapy were pretreated with lenvatinib. We found grade 3 or higher adverse events only in seven patients and no significant changes in the albumin-bilirubin score during ramucirumab treatment in the present cohort. The median progression-free survival of patients treated with ramucirumab was 2.7 months (95% confidence interval, 1.6-7.3). CONCLUSION Although ramucirumab is used for various lines of treatment other than second-line immediately after sorafenib, its safety and effectiveness were not significantly different from the findings of the REACH-2 trial.
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Affiliation(s)
- Naoya Kanogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan.
| | - Susumu Maruta
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Yotaro Iino
- Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan
| | - Masamichi Obu
- Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan
| | - Takamasa Ishino
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Keita Ogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Sae Yumita
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Terunao Iwanaga
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Hidemi Unozawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Miyuki Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Kisako Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Takafumi Sakuma
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Naoto Fujita
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Ryuta Kojima
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Hiroaki Kanzaki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Keisuke Koroki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Masanori Inoue
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Takayuki Kondo
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Tomoko Saito
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Ryo Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Ryosuke Muroyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Tetsuhiro Chiba
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Yoshihiro Koma
- Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan
| | - Ryosaku Azemoto
- Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan
| | - Jun Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-8670, Japan
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Tada T, Kumada T, Hiraoka A, Kariyama K, Tani J, Hirooka M, Takaguchi K, Atsukawa M, Fukunishi S, Itobayashi E, Tsuji K, Tajiri K, Ochi H, Ishikawa T, Yasuda S, Ogawa C, Toyoda H, Hatanaka T, Nishimura T, Kakizaki S, Kawata K, Shimada N, Tada F, Nouso K, Tsutsui A, Ohama H, Morishita A, Nagano T, Itokawa N, Okubo T, Arai T, Kosaka H, Imai M, Naganuma A, Nakamura S, Koizumi Y, Kaibori M, Iijima H, Hiasa Y, the Real‐life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group. New prognostic system based on inflammation and liver function predicts prognosis in patients with advanced unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A validation study. Cancer Med 2023; 12:6980-6993. [PMID: 36484470 PMCID: PMC10067064 DOI: 10.1002/cam4.5495] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 10/18/2022] [Accepted: 11/19/2022] [Indexed: 12/13/2022] Open
Abstract
AIM Recently, the neo-Glasgow prognostic score (GPS), a composite biomarker determined by the C-reactive protein level and albumin-bilirubin grade, was developed to predict outcomes in hepatocellular carcinoma (HCC) patients who undergo hepatic resection. The present research investigated whether the neo-GPS could predict prognosis in HCC patients treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS A total of 421 patients with HCC who were treated with Atez/Bev were investigated. RESULTS Multivariate Cox hazards analysis showed that a GPS of 1 (hazard ratio (HR), 1.711; 95% confidence interval (CI), 1.106-2.646) and a GPS of 2 (HR, 4.643; 95% CI, 2.778-7.762) were independently associated with overall survival. Conversely, multivariate Cox hazards analysis showed that a neo-GPS of 1 (HR, 3.038; 95% CI, 1.715-5.383) and a neo-GPS of 2 (HR, 5.312; 95% CI, 2.853-9.890) were also independently associated with overall survival in this cohort. Additionally, cumulative overall survival rates differed significantly by GPS and neo-GPS (p < 0.001). The neo-GPS, compared with the GPS, had a lower Akaike information criterion (1207 vs. 1,211, respectively) and a higher c-index (0.677 vs. 0.652, respectively) regarding to overall survival. In a subgroup analysis of patients considered to have a good prognosis as confirmed using a Child-Pugh score of 5 (p = 0.001), a neutrophil-to-lymphocyte ratio <3 (p = 0.001), or an α-fetoprotein level < 100 ng/mL (p < 0.001), those with a high neo-GPS (≥1) had a statistically poorer overall survival than those with a low neo-GPS. CONCLUSIONS The neo-GPS can predict prognosis in advanced unresectable HCC patients treated with Atez/Bev.
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Tumor stiffness measurement using magnetic resonance elastography can predict recurrence and survival after curative resection of hepatocellular carcinoma. Surgery 2023; 173:450-456. [PMID: 36481063 DOI: 10.1016/j.surg.2022.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 11/02/2022] [Accepted: 11/07/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection. METHODS Seventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach. RESULTS In multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07-1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27-5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02-1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11-21.90; P < .001) than those with tumor stiffness <5.81 kPa. CONCLUSION Preoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.
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27
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Kumagi T, Terao T, Kuroda T, Koizumi M, Imamura Y, Ohno Y, Yokota T, Azemoto N, Uesugi K, Kisaka Y, Tanaka Y, Shibata N, Miyata H, Miyake T, Hiasa Y. Patients with Chronic Liver Disease under Surveillance for Hepatocellular Carcinoma Have a Favorable Long-Term Outcome for Pancreatic Cancer Due to Early Diagnosis and High Resection Rate. Cancers (Basel) 2023; 15:cancers15030561. [PMID: 36765521 PMCID: PMC9913713 DOI: 10.3390/cancers15030561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/13/2023] [Accepted: 01/14/2023] [Indexed: 01/18/2023] Open
Abstract
Patients with viral hepatitis-related chronic liver disease (CLD) under surveillance for hepatocellular carcinoma (HCC) are often diagnosed with pancreatic cancer (PC) at an early stage. However, the long-term outcomes of these patients are unclear. We aimed to clarify the long-term outcomes of patients with PC with viral hepatitis-related CLD using a chart review. Data collection included the Union for International Cancer Control (UICC) stage at PC diagnosis, hepatitis B virus and hepatitis C virus status, and long-term outcomes. The distribution of the entire cohort (N = 552) was as follows: early stage (UICC 0-IB; n = 52, 9.5%) and non-early stages (UICC IIA-IV; n = 500, 90.5%). At diagnosis, the HCC surveillance group (n = 18) had more patients in the early stages than the non-surveillance group (n = 534) (50% vs. 8.0%), leading to a higher indication rate for surgical resection (72.2% vs. 29.8%) and a longer median survival time (19.0 months vs. 9.9 months). We confirmed that patients with viral hepatitis-related CLD under HCC surveillance were diagnosed with PC at an early stage. Because of the higher indication rate for surgical resection in these patients, they had favorable long-term outcomes for PC.
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Affiliation(s)
- Teru Kumagi
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
- Postgraduate Medical Education Center, Ehime University Hospital, To-on 791-0295, Japan
- Correspondence: ; Tel.: +81-89-960-5098
| | - Takashi Terao
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
- Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan
| | - Taira Kuroda
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
- Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan
| | - Mitsuhito Koizumi
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
| | - Yoshiki Imamura
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
| | - Yoshinori Ohno
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
- Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan
| | - Tomoyuki Yokota
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
| | - Nobuaki Azemoto
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
| | - Kazuhiro Uesugi
- Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama 791-0280, Japan
- Gastroenterology, Uwajima Municipal Hospital, Uwajima 798-8510, Japan
| | - Yoshiyasu Kisaka
- Gastroenterology, Uwajima Municipal Hospital, Uwajima 798-8510, Japan
- Gastroenterology, Matsuyama Shimin Hospital, Matsuyama 790-0067, Japan
| | - Yoshinori Tanaka
- Gastroenterology, Matsuyama Shimin Hospital, Matsuyama 790-0067, Japan
| | - Naozumi Shibata
- Internal Medicine, Niihama Prefectural Hospital, Niihama 792-0042, Japan
| | - Hideki Miyata
- Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan
| | - Teruki Miyake
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
| | - Yoichi Hiasa
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan
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Xiong M, Xu Y, Zhao Y, He S, Zhu Q, Wu Y, Hu X, Liu L. Quantitative analysis of artificial intelligence on liver cancer: A bibliometric analysis. Front Oncol 2023; 13:990306. [PMID: 36874099 PMCID: PMC9978515 DOI: 10.3389/fonc.2023.990306] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 02/03/2023] [Indexed: 02/18/2023] Open
Abstract
Objective To provide the current research progress, hotspots, and emerging trends for AI in liver cancer, we have compiled a relative comprehensive and quantitative report on the research of liver disease using artificial intelligence by employing bibliometrics in this study. Methods In this study, the Web of Science Core Collection (WoSCC) database was used to perform systematic searches using keywords and a manual screening strategy, VOSviewer was used to analyze the degree of cooperation between countries/regions and institutions, as well as the co-occurrence of cooperation between authors and cited authors. Citespace was applied to generate a dual map to analyze the relationship of citing journals and citied journals and conduct a strong citation bursts ranking analysis of references. Online SRplot was used for in-depth keyword analysis and Microsoft Excel 2019 was used to collect the targeted variables from retrieved articles. Results 1724 papers were collected in this study, including 1547 original articles and 177 reviews. The study of AI in liver cancer mostly began from 2003 and has developed rapidly from 2017. China has the largest number of publications, and the United States has the highest H-index and total citation counts. The top three most productive institutions are the League of European Research Universities, Sun Yat Sen University, and Zhejiang University. Jasjit S. Suri and Frontiers in Oncology are the most published author and journal, respectively. Keyword analysis showed that in addition to the research on liver cancer, research on liver cirrhosis, fatty liver disease, and liver fibrosis were also common. Computed tomography was the most used diagnostic tool, followed by ultrasound and magnetic resonance imaging. The diagnosis and differential diagnosis of liver cancer are currently the most widely adopted research goals, and comprehensive analyses of multi-type data and postoperative analysis of patients with advanced liver cancer are rare. The use of convolutional neural networks is the main technical method used in studies of AI on liver cancer. Conclusion AI has undergone rapid development and has a wide application in the diagnosis and treatment of liver diseases, especially in China. Imaging is an indispensable tool in this filed. Mmulti-type data fusion analysis and development of multimodal treatment plans for liver cancer could become the major trend of future research in AI in liver cancer.
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Affiliation(s)
- Ming Xiong
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yaona Xu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yang Zhao
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Si He
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qihan Zhu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yi Wu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaofei Hu
- Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Li Liu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China.,Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Sun H, Yang W, Zhou W, Zhou C, Liu S, Shi H, Tian W. Prognostic value of des-γ-carboxyprothrombin in patients with AFP-negative HCC treated with TACE. Oncol Lett 2022; 25:69. [PMID: 36644150 PMCID: PMC9827467 DOI: 10.3892/ol.2022.13655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 09/13/2022] [Indexed: 12/30/2022] Open
Abstract
In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease.
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Affiliation(s)
- Hanyao Sun
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Weizhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Chungao Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Haibin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China,Correspondence to: Dr Haibin Shi or Dr Wei Tian, Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, P.R. China, E-mail: , E-mail:
| | - Wei Tian
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China,Correspondence to: Dr Haibin Shi or Dr Wei Tian, Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, P.R. China, E-mail: , E-mail:
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Chen J, Zhou Z, Chen W, Khan AA, Liu Z, Wang K, Yang F, Xu X. Hepatocellular carcinoma complicated with huge posterior pancreas head lymph node metastasis and primary renal carcinoma: A case report. Front Oncol 2022; 12:989172. [PMID: 36568158 PMCID: PMC9773375 DOI: 10.3389/fonc.2022.989172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 11/24/2022] [Indexed: 12/13/2022] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) associated with extrahepatic primary malignancy (EHPM) is extremely rare, especially for those that involve primary renal cell carcinoma (PRC). Here we present a case of a 66-year-old male who was diagnosed with HCC complicated with lymph node metastasis at posterior pancreas head and PRC. Biopsy results of the liver and the lymph node confirmed the diagnosis of HCC. The disease progressions of both HCC and PRC are controlled effectively following the initiation of comprehensive therapy including pembrolizumab, lenvatinib, radiotherapy, and transcatheter arterial chemo-embolization (TACE). Ultimately, the patient had successfully access to surgery and complete response (CR) of all the tumors were achieved after surgery.
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Affiliation(s)
- Jun Chen
- The Four School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China,Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhiyi Zhou
- The Four School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China,Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenyan Chen
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Abid Ali Khan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhikun Liu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Fan Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China,*Correspondence: Xiao Xu,
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Li G, Shu B, Zheng Z, Yin H, Zhang C, Xiao Y, Yang Y, Yan Z, Zhang X, Yang S, Li G, Dong J. Safety and efficacy of radiotherapy combined with lenvatinib plus PD-1 inhibitors as neo-adjuvant therapy in hepatocellular carcinoma with portal vein thrombus: protocol of an open-label, single-arm, prospective, multi-center phase I trial. Front Oncol 2022; 12:1051916. [PMID: 36505833 PMCID: PMC9730694 DOI: 10.3389/fonc.2022.1051916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/04/2022] [Indexed: 11/26/2022] Open
Abstract
Background Surgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported. Methods This open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS). Discussion This trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT. Clinical trial registration https://clinicaltrials.gov/, identifier (NCT05225116).
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Affiliation(s)
- Guangxin Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Bin Shu
- Hepatopancereatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Zhuozhao Zheng
- Department of Radiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Hongfang Yin
- Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Chen Zhang
- Department of Radiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Ying Xiao
- Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Yanmei Yang
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Zhe Yan
- Hepatopancereatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Xiaofei Zhang
- Center for Clinical Epidemiology & Biostatistics, Beijing Tsinghua Changgung hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Shizhong Yang
- Hepatopancereatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China,*Correspondence: Shizhong Yang, ; Gong Li, lga02375@ btch.edu.cn; Jiahong Dong,
| | - Gong Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China,*Correspondence: Shizhong Yang, ; Gong Li, lga02375@ btch.edu.cn; Jiahong Dong,
| | - Jiahong Dong
- Hepatopancereatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China,Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China,*Correspondence: Shizhong Yang, ; Gong Li, lga02375@ btch.edu.cn; Jiahong Dong,
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Wang P, Yang S, Li C, Han X, Hong D, Shao H. Nomogram-based development and evaluation for predictions of 30-day and 1-year survival in patients with spontaneously ruptured hepatocellular carcinoma. BMC Cancer 2022; 22:1177. [PMCID: PMC9664604 DOI: 10.1186/s12885-022-10290-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 11/07/2022] [Indexed: 11/17/2022] Open
Abstract
Background Accurately predicting the prognosis of patients with spontaneously ruptured hepatocellular carcinoma (HCC) is crucial for effective clinical management. The aim of the present study was to establish and evaluate prediction models for 30-day and 1-year survival in patients with spontaneously ruptured HCC. Methods A total of 118 patients with spontaneous rupture HCC were enrolled. Univariate and multivariate analyses were performed using logistic-regression model and Cox proportional-hazard model. The identified indicators were used to establish prediction models, the performance of which we compared with those of commonly used liver disease scoring models. The survival possibilities of different risk categories were calculated using the newly developed models. Results Largest tumor size (LTS), serum albumin (ALB), total bilirubin (TBil), and serum creatinine were identified as independent predictors, which were used to establish a 30-day survival prediction model. LTS, BCLC staging, ALB, TBil, hepatectomy at rupture, and TACE during follow-up were identified as independent predictors of 1-year survival model. The 30-day survival model had sensitivity of 79.3%, specificity of 87.1%, and an AUC of 0.879, exhibiting better predictive performance than scores for Chronic Liver Failure Consortium Acute Decompensation score (CLIF-C ADs) and Model for End-stage Liver Disease (MELD). The 1-year survival model had sensitivity of 66.7%, specificity of 94.6%, and an AUC of 0.835, showing better predictive performance than Albumin–Bilirubin (ALBI), Child–Pugh, CLIF-C ADs, and MELD. After stratification, survival possibilities were 90.9 and 21.1% in low- and high-risk groups within 30 days, respectively, and 43.90, 4.35%, and 0 in low-, intermediate-, and high-risk groups at 1 year, respectively. Conclusions The established models exhibited good performance in predicting both 30-day and 1-year survival in patients with spontaneously ruptured HCC.
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Affiliation(s)
- Peng Wang
- grid.412636.40000 0004 1757 9485Department of Interventional Radiology, the First Hospital of China Medical University, Shenyang, China
| | - Shuping Yang
- grid.412636.40000 0004 1757 9485Department of Pain Medicine, the First Hospital of China Medical University, Shenyang, China
| | - Chao Li
- grid.412558.f0000 0004 1762 1794Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiangjun Han
- grid.412636.40000 0004 1757 9485Department of Interventional Radiology, the First Hospital of China Medical University, Shenyang, China
| | - Duo Hong
- grid.412636.40000 0004 1757 9485Department of Interventional Radiology, the First Hospital of China Medical University, Shenyang, China
| | - Haibo Shao
- grid.412636.40000 0004 1757 9485Department of Interventional Radiology, the First Hospital of China Medical University, Shenyang, China
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Ningarhari M, Mourad A, Delacôte C, Ntandja Wandji L, Lassailly G, Louvet A, Dharancy S, Mathurin P, Deuffic‐Burban S. Benefits of tailored hepatocellular carcinoma screening in patients with cirrhosis on cancer-specific and overall mortality: A modeling approach. Hepatol Commun 2022; 6:2964-2974. [PMID: 36004703 PMCID: PMC9512473 DOI: 10.1002/hep4.2059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 07/12/2022] [Accepted: 07/18/2022] [Indexed: 11/06/2022] Open
Abstract
To validate cancer screening programs, experts recommend estimating effects on case fatality rates (CFRs) and cancer-specific mortality. This study evaluates hepatocellular carcinoma (HCC) screening in patients with cirrhosis for those outcomes using a modeling approach. We designed a Markov model to assess 10-year HCC-CFR, HCC-related, and overall mortality per 100,000 screened patients with compensated cirrhosis. The model evaluates different HCC surveillance intervals (none, annual [12 months], semiannual [6 months], or quarterly [3 months]) and imaging modalities (ultrasound [US] or magnetic resonance imaging [MRI]) in various annual incidences (0.2%, 0.4%, or 1.5%). Compared to no surveillance, 6-month US reduced the 10-year HCC-CFR from 77% to 46%. With annual incidences of 0.2%, 0.4%, and 1.5%, the model predicted 281, 565, and 2059 fewer HCC-related deaths, respectively, and 187, 374, and 1356 fewer total deaths per 100,000 screened patients, respectively. Combining alpha-fetoprotein screening to 6-month US led to 32, 63, and 230 fewer HCC-related deaths per 100,000 screened patients for annual incidences of 0.2%, 0.4%, and 1.5%, respectively. Compared to 6-month US, 3-month US reduced cancer-related mortality by 14%, predicting 61, 123, and 446 fewer HCC-related deaths per 100,000 screened patients with annual incidences of 0.2%, 0.4%, and 1.5%, respectively. Compared to 6-month US, 6-month MRI (-17%) and 12-month MRI (-6%) reduced HCC-related mortality. Compared to 6-month US, overall mortality reductions ranged from -0.1% to -1.3% when using 3-month US or MRI. A US surveillance interval of 6 months improves HCC-related and overall mortality compared to no surveillance. A shorter US interval or using MRI could reduce HCC-CFR and HCC-related mortality, with a modest effect on overall mortality.
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Affiliation(s)
- Massih Ningarhari
- Centre Hospitalier Universitaire de Lille, Hôpital Huriez, Maladies de l'Appareil DigestifLilleFrance
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Abbas Mourad
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Claire Delacôte
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Line‐Carolle Ntandja Wandji
- Centre Hospitalier Universitaire de Lille, Hôpital Huriez, Maladies de l'Appareil DigestifLilleFrance
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Guillaume Lassailly
- Centre Hospitalier Universitaire de Lille, Hôpital Huriez, Maladies de l'Appareil DigestifLilleFrance
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Alexandre Louvet
- Centre Hospitalier Universitaire de Lille, Hôpital Huriez, Maladies de l'Appareil DigestifLilleFrance
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Sébastien Dharancy
- Centre Hospitalier Universitaire de Lille, Hôpital Huriez, Maladies de l'Appareil DigestifLilleFrance
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Philippe Mathurin
- Centre Hospitalier Universitaire de Lille, Hôpital Huriez, Maladies de l'Appareil DigestifLilleFrance
- Université de Lille, Institut national de la santé et de la recherche médicale (INSERM), InfiniteLilleFrance
| | - Sylvie Deuffic‐Burban
- Université Paris Cité and Université Sorbonne Paris Nord, INSERM, Infection, Antimicrobials, Modelling, EvolutionParisFrance
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Jang TY, Dai CY. Cutoff values of protein induced by vitamin K absence or antagonist II for diagnosing hepatocellular carcinoma. Medicine (Baltimore) 2022; 101:e30936. [PMID: 36181046 PMCID: PMC9524990 DOI: 10.1097/md.0000000000030936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a promising serum marker for hepatocellular carcinoma (HCC). There are limited data on its cutoff value in HCC for Taiwanese cirrhosis patients. This study aimed to investigate the diagnostic value of PIVKA-II levels in patients with suspected HCC. In total, 88 patients with chronic hepatitis and suspected HCC by ultrasound, elevated α-fetoprotein (AFP) or PIVKA-II levels were consecutively enrolled. Their baseline characteristics and findings on dynamic phases of computed tomography (CT) or magnetic resonance imaging (MRI) were examined. Sixty participants had cirrhosis and 34 had HCC. The median levels of PIVKA-II in non-cirrhosis and cirrhosis patients without or with HCC were 28.0, 48.0, and 847.0 mAU/mL, respectively. The optimal cutoff value of PIVKA-II in predicting HCC was 78.0 mAU/mL. Combining AFP with PIVKAII mildly increased its diagnostic performance for HCC, yielding higher specificity and positive predictive value. Significant factors predicting HCC in multivariate regression analysis were PIVKA >78.0 mAU/mL and fatty liver. Monitoring PIVKA-II level is suitable for noninvasively assessing HCC in patients with chronic hepatitis, particularly with AFP.
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Affiliation(s)
- Tyng-Yuan Jang
- PhD Program of Environmental and Occupational Medicine and Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Ping-Tung, Taiwan
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- *Correspondence: Chia-Yen Dai, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou Road, Kaohsiung City 807, Taiwan (e-mail: )
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Liu S, Sun L, Yao L, Zhu H, Diao Y, Wang M, Xing H, Lau WY, Guan M, Pawlik TM, Shen F, Xu M, Tong X, Yang T. Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis. J Clin Med 2022; 11:5075. [PMID: 36079006 PMCID: PMC9456633 DOI: 10.3390/jcm11175075] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/18/2022] [Accepted: 08/26/2022] [Indexed: 11/25/2022] Open
Abstract
Background and Aim: Alpha-fetoprotein (AFP), a lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), is a protein that is induced by vitamin K deficiency or antagonist-II (PIVKA-II) that has been clinically used as a serum biomarker for early detection and diagnosis of hepatocellular carcinoma (HCC). Diagnostic performance of each serum biomarker alone, or their combinations for the detection of hepatitis C virus (HCV)-associated HCC were compared. Methods: Serum AFP, AFP-L3, and PIVKA-II levels were evaluated in patients with HCV-associated HCC, and those with chronic HCV infection without HCC (HCV-controls). The areas under the curve (AUC), sensitivity, and specificity were compared to identify the diagnostic performance of each serum HCC biomarker alone or in combination. Results: Overall, 172 HCV controls and 105 patients with HCV-associated HCC were enrolled. The AFP, AFP-L3, and PIVKA-II levels were significantly increased among patients with HCV-associated HCC when compared with HCV patients without HCC (p < 0.001). When these biomarkers were analyzed individually, PIVKA-II revealed the best predictive performance (AUC: PIVKA-II 0.90 vs. AFP 0.80 vs. AFP-L3 0.69, p < 0.001). In evaluating the combinations of any two biomarkers, the best predictive performance was found in PIVKA-II + AFP (0.93 vs. AFP + AFP-L3 0.78, p = 0.001; and PIVKA-II + AFP-L3 0.89, p < 0.001), which had no difference compared to the predictive performance of the combination of all three serum biomarkers (AFP + AFP-L3 + PIVKA-II 0.93, p = 0.277). Similar results were identified in the subgroups of patients with HCV-induced cirrhosis, and among patients with early-stage HCC defined by BCLC and TNM staging. Conclusions: The addition of the PIVKA-II test to routine AFP test maybe provide a more suitable biomarker approach to detect HCV-induced HCC in patients with HCV infection undergoing HCC surveillance.
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Affiliation(s)
- Siyu Liu
- Department of Laboratory Medicine, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323050, China
| | - Liyang Sun
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Lanqing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yongkang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Mingda Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, China
| | - Mingcheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Min Xu
- Department of Interventional Radiology, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui 323050, China
| | - Xiangmin Tong
- Cancer Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
- Department of Laboratory, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323050, China
- The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’ s Hospital (People’ s Hospital of Hangzhou Medical College), No. 158, Shangtang Road, Hangzhou 310014, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
- Cancer Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
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Hidaka M, Hara T, Soyama A, Adachi T, Matsushima H, Tanaka T, Ishimaru H, Miyaaki H, Nakao K, Eguchi S. Long‐term outcomes of living‐donor liver transplantation, hepatic resection, and local therapy for hepatocellular carcinoma with three <3‐cm nodules in a single institute. JGH Open 2022; 6:539-546. [PMID: 35928699 PMCID: PMC9344587 DOI: 10.1002/jgh3.12783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 06/06/2022] [Accepted: 06/08/2022] [Indexed: 12/24/2022]
Abstract
Background and Aim Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living‐donor liver transplantation (LDLT) for small HCC in a single institute. Methods We compared the overall survival, recurrence‐free survival, and cancer‐specific survival rates in patients with three HCC nodules <3 cm in size among local therapy, which included radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial chemoembolization (TACE), and surgical treatment (HR and LDLT). Results One hundred and ninety‐seven patients with local therapy (109 RFA, 26 PEI, and 78 TACE), 107 with HR, and 66 with LDLT were enrolled in this study. There was no significant difference in OS among these groups. The recurrence‐free, cancer‐specific survival (CSS) of LDLT was superior to local therapy and HR. The prognostic factors for the survival were Child–Pugh (CP) Grade B and tumor marker for local therapy and multiple tumors and elevated ALT levels for HR. Conclusions For CP grade B patients with HCC of three <3‐cm nodule, LDLT could be considered because it resulted in better survival and CSS rates than local therapy.
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Affiliation(s)
- Masaaki Hidaka
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Takanobu Hara
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Akihiko Soyama
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Tomohiko Adachi
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Hajime Matsushima
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Takayuki Tanaka
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Hideki Ishimaru
- Department of Radiological Sciences Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Susumu Eguchi
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
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Tajiri K, Futsukaichi YH, Murayama A, Minemura M, Takahara T, Yasuda I. Chronic liver disease questionnaire to manage patients with chronic liver diseases. Hepatol Res 2022; 52:712-720. [PMID: 35505586 DOI: 10.1111/hepr.13774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/13/2022] [Accepted: 04/27/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Although patients with chronic liver disease (CLD) usually show few symptoms, they exhibit decreased health-related QOL (HRQOL) with occurrence complications including hepatocellular carcinoma (HCC). Health-related QOL is an important indicator in the management of CLD. The Chronic Liver Disease Questionnaire (CLDQ) was established as a tool for assessment of HRQOL. In this study, we evaluate its usefulness for the management of daily clinical practice. METHODS Patients (N = 190, median age 70 years old) treated between 2016 and 2019 were registered and prospectively followed-up with annual CLDQ. Associations of liver function and development of factors for admission or death were evaluated. RESULTS Of the 190 patients registered, median age 70 years old, 140 were Child-A, 121 were Fib-4 index >2.67 and showed 80 HCC. All 6 domains including Systemic Symptoms (SS) were negatively correlated with Child-Pugh score more than with albumin-bilirubin score and Fib-4 index. A hundred four admission events and 49 deaths were found during observation period, and median event-free survival was 34.3 months. Treatment for HCC was the most frequent cause of admission, and 37 liver-related deaths were found. Systemic Symptoms score 2 years after registration was decreased in both HCC- and non-HCC cohort. Systemic Symptoms decreased and SS < 4 might be predictive for event occurrence. CONCLUSIONS CLDQ is useful to assess HRQOL in patients with CLD and is well correlated with liver function especially Child-Pugh. Chronic Liver Disease Questionnaire might be useful to predict the prognosis of CLD and can be a tool of management in clinical practice.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | | | - Aiko Murayama
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Masami Minemura
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Terumi Takahara
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Ichiro Yasuda
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
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Interrater reliability and agreement of the liver imaging reporting and data system (LI-RADS) v2018 for the evaluation of hepatic lesions. Pol J Radiol 2022; 87:e316-e324. [PMID: 35892071 PMCID: PMC9288199 DOI: 10.5114/pjr.2022.117590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/15/2021] [Indexed: 12/13/2022] Open
Abstract
Purpose The liver imaging reporting and data system (LI-RADS) is a structured reporting system that categorizes hepatic observations according to major imaging features and lesion size, with an optional ancillary features contribution. This study aimed to evaluate inter-reader agreement of dynamic magnetic resonance imaging (MRI) using LI-RADS v2018 lexicon. Material and methods Forty-nine patients with 69 hepatic observations were included in our study. The major and ancillary features of each hepatic observation were evaluated by 2 radiologists using LI-RADS v2018, and the interreader agreement was allocated. Results The inter-reader agreement of major LI-RADS features was substantial; κ of non-rim arterial hyperenhancement, non-peripheral washout appearance, and enhancing capsule was 0.796, 0.799, and 0.772 (p < 0.001), respectively. The agreement of the final LI-RADS category was substantial with κ = 0.651 (p < 0.001), and weighted κ = 0.786 (p < 0.001). The inter-reader agreement of the ancillary features was substantial to almost perfect (k range from 0.718 to 1; p < 0.001). An almost perfect correlation was noted for the hepatic lesion size measurement with ICC = 0.977 (p < 0.001). Conclusions The major and ancillary features of the LI-RADS v2018, as well as the final category and lesions size, have substantial to almost perfect inter-reader agreement.
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Nakai M, Morikawa K, Hosoda S, Yoshida S, Kubo A, Tokuchi Y, Kitagataya T, Yamada R, Ohara M, Sho T, Suda G, Ogawa K, Sakamoto N. Pre-sarcopenia and Mac-2 binding protein glycosylation isomer as predictors of recurrence and prognosis of early-stage hepatocellular carcinoma. World J Hepatol 2022; 14:1480-1494. [PMID: 36158914 PMCID: PMC9376769 DOI: 10.4254/wjh.v14.i7.1480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/20/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The Mac-2 binding protein glycosylation isomer (M2BPGi), a fibrosis marker in various liver diseases, is reportedly a prognostic marker in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy.
AIM To evaluate whether the M2BPGi value, M2BP, and pre-sarcopenia before radiofrequency ablation (RFA) could be useful recurrence and prognostic markers in patients with early-stage HCC.
METHODS In total, 160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus (HCV)-positive and HCV-negative. Factors contributing to recurrence and liver-related death, including M2BP, M2BPGi, and skeletal muscle mass index, were statistically analyzed. Eighty-three patients were HCV-positive and 77 were HCV-negative.
RESULTS In HCV-positive patients, only des-γ-carboxy-prothrombin ≥ 23 mAU/mL was a significant poor prognostic factor affecting survival after RFA. In HCV-negative patients, M2BPGi ≥ 1.86 cutoff index was significantly associated with tumor recurrence, while M2BP was not. M2BPGi ≥ 1.86 cutoff index (hazard ratio, 4.89; 95% confidence interval: 1.97-12.18; P < 0.001) and pre-sarcopenia (hazard ratio, 3.34, 95% confidence interval: 1.19-9.37; P = 0.022) were independent significant poor prognostic factors in HCV-negative patients.
CONCLUSION In HCV-negative patients with primary HCC treated with RFA, lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period. Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients. These factors might be useful recurrence and prognostic markers for early-stage primary HCC.
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Affiliation(s)
- Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
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Li K, Long Y, He X, Wu Y, Xu J, Ye H, Xu E, Zeng Q, Chen J, Yuan L, Zheng R. Comparison of anatomical thermal ablation and routine thermal ablation for hepatocellular carcinoma≤50 mm: A propensity score matching. Hepatol Res 2022; 52:641-651. [PMID: 35506633 DOI: 10.1111/hepr.13772] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/27/2022] [Accepted: 04/17/2022] [Indexed: 02/08/2023]
Abstract
AIM The present study was to evaluated the clinical value of anatomical thermal ablation to treat hepatocellular carcinoma compared with routine thermal ablation. METHODS Hepatocellular carcinoma patients with tumor diameter ≤50 mm treated by thermal ablation at our center were retrospectively enrolled from October 2015 to December 2018. Enrolled patients were grouped into the anatomical ablation group and routine ablation group, respectively. To minimize the effects of potential confounders from selection bias, a propensity score matching was carried out. Technical efficacy, recurrence and survivals rates were compared. RESULTS Altogether 101 patients (119 lesions) were grouped into the anatomical ablation group and 101 patients (131 lesions) into the routine ablation group. The ablation zone volume of the anatomical ablation group was 36.8 (2.5-176.9) ml, significantly larger than that of the routine ablation group (28.5 [28.5 (2.8-184.3) ml] (p = 0.005)). Adjusted with propensity score matching, The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, and 0.0% for the anatomical ablation group and 6.9%, 10.1%, and 10.1% for the routine ablation group, respectively (p = 0.013). The cumulative 1-, 2-, and 3-year progression-free survival rates were 93.4%, 82.7%, and 79.0% for the anatomical ablation group, 74.2%, 56.9%, and 51.6% for the routine ablation group (p = 0.001). CONCLUSIONS Anatomical ablation could be a favorable ablation strategy to improve therapeutic effect of thermal ablation for HCC with visible feeding vessels and reserved liver function.
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Affiliation(s)
- Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yinglin Long
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuqi He
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuxuan Wu
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jianliang Xu
- Department of Liver Surgery, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Huolin Ye
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Erjiao Xu
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Ultrasound, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Qingjing Zeng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jianning Chen
- Department of Pathology, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lianxiong Yuan
- Department of Science and Research, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rongqin Zheng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Tajiri K, Ito H, Kawai K, Kashii Y, Hayashi Y, Murayama A, Minemura M, Takahara T, Shimizu Y, Yasuda I. Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma. World J Hepatol 2022; 14:1190-1199. [PMID: 35978673 PMCID: PMC9258255 DOI: 10.4254/wjh.v14.i6.1190] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/18/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients has a high risk of recurrence. Although eradication of HCV is expected to reduce this risk, the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals (DAAs). AIM To determine the risk factors for HCC recurrence in patients with HCV and a history of HCC. METHODS The risk of HCC recurrence in patients with a history of HCC and/or of HCC occurrence in patients without a history of HCC after DAA therapy was retrospectively analyzed in 311 HCV patients treated at our institution and several neighboring hospitals. The frequency and predictors of HCC recurrence/ occurrence after DAA treatment were included in these analyses. The clinical course of HCC before and after DAA treatment was also evaluated. RESULTS HCV patients with a history of HCC were older and had greater progression of liver fibrosis and diabetes than patients without a history of HCC. Median recurrence-free survival (RFS) was 1092 d in patients with a history of HCC, and post-DAA HCC recurrence/occurrence was observed in 29 patients (53.7%) with and 5 (1.9%) without a history of HCC over 6 years (P < 0.001). RFS in patients with a history of HCC did not differ significantly before and after DAA treatment. The frequency of HCC recurrence/occurrence in patients with a history of HCC was lower after than before DAA treatment. Multivariate analysis showed that the incidence rate of HCC recurrence/occurrence before DAA treatment was the only independent predictor of HCC recurrence/occurrence after DAA treatment. Liver function was well preserved and clinical course was good in patients with HCC recurrence/occurrence after DAA therapy. CONCLUSION DAA therapy in patients infected with HCV is also effective in patients with a history of HCC. Curative treatment for HCC is desirable before DAA therapy. The frequency of HCC recurrence/occurrence before DAA therapy was associated with a significantly increased risk of HCC recurrence after DAA therapy. Careful observation after DAA therapy is required in patients with a history of HCC.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan.
| | - Hiroyuki Ito
- Department of Gastroenterology, Takaoka Municipal Hospital, Takaoka 933-8550, Japan
| | - Kengo Kawai
- Gastroenterology Center, Nanto Municipal Hospital, Nanto 932-0211, Japan
| | - Yoshiro Kashii
- Department of Gastroenterology, Saiseikai Toyama Hospital, Toyama 931-8533, Japan
| | - Yuka Hayashi
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan
| | - Aiko Murayama
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan
| | - Masami Minemura
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan
| | - Terumi Takahara
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan
| | - Yukihiro Shimizu
- Gastroenterology Center, Nanto Municipal Hospital, Nanto 932-0211, Japan
| | - Ichiro Yasuda
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan
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Takamoto T, Nara S, Ban D, Nagashima D, Mizui T, Esaki M, Shimada K. Application of albumin-bilirubin grade and platelet count to indocyanine green-based criteria for hepatectomy: Predicting impaired liver function and postoperative outcomes of hepatocellular carcinoma. J Surg Oncol 2022; 126:680-688. [PMID: 35689605 DOI: 10.1002/jso.26982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/27/2022] [Accepted: 05/29/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Applicability of the albumin-bilirubin (ALBI) grade in preoperative decision-making criteria based on the indocyanine green retention (ICG) test remains unclear. This study aimed to predict abnormal ICG values using standard blood tests and evaluate the impact on postoperative outcomes among patients undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS Data on 949 consecutive HCC patients undergoing curative-intent hepatectomy between 1996 and 2014 were retrospectively assessed. A nomogram using preoperative standard blood tests was created to predict abnormal ICGR15 (>15%). RESULTS Three-hundred nine patients had abnormal ICGR15. Predictors of abnormal ICGR15 included in the nomogram were: ALBI grade >1 (hazard ratio [HR]: 2.16, 95% confidence interval [CI]: 1.59-2.94), platelet count <130 000/mm3 (HR: 2.27, 95% CI: 1.68-3.08), aspartate aminotransferase >50 (IU/L) (HR: 1.90, 95% CI: 1.29-2.81), and viral hepatitis infection (HR: 1.46, 95% CI: 1.03-2.07). The nomogram named the PLT-ALBI score was discriminative [C-statistics: 0.719 (0.684-0.754)], and reliable (Hosmer-Lemeshow Chi-Square: 9.05, p = 0.338). The higher PLT-ALBI score was associated with a more frequent incidence of clinically relevant posthepatectomy liver failure and poor overall survival. CONCLUSIONS The PLT-ALBI score is applicable in distinguishing HCC patients with abnormal ICGR15. Patients with higher PLT-ALBI score require more careful postoperative care, despite following the ICG criteria.
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Affiliation(s)
- Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Nagashima
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Naganuma A, Koizumi Y, Nakamura S, Joko K, Iijima H, Hiasa Y. Neutrophil-lymphocyte ratio predicts early outcomes in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: a multicenter analysis. Eur J Gastroenterol Hepatol 2022; 34:698-706. [PMID: 35170529 DOI: 10.1097/meg.0000000000002356] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To investigate whether neutrophil-to-lymphocyte ratio (NLR) can predict outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS A total of 249 patients with unresectable HCC treated with Atez/Bev were included. We analyzed survival and discontinuation of this therapy in this cohort. RESULTS Cumulative overall survival at 2, 4, 6, and 8 months was 97.6%, 94.9%, 88.9%, and 82.8%, respectively. Cumulative overall survival differed significantly between patients with low (<3.0) versus high (≥3.0) NLR (P = 0.001). Conversely, cumulative progression-free survival did not differ between patients with low versus high NLR. The distribution of response was 1.5% for complete response, 17.1% for partial response, 60.5% for stable disease, and 21.0% for progressive disease. Responses were not different between patients with low and high NLR. Regarding adverse events, immune-related liver injury of any grade and grade of at least 3, decreased appetite of any grade, grade of at least 3 proteinuria, and other adverse events of any grade differed significantly between patients with low and high NLR. There were 56, 18, and 2 patients who discontinued Atez/Bev therapy due to progression of disease, adverse event, and other reasons, respectively. The cumulative discontinuation rate for Atez/Bev therapy due to adverse events differed significantly between patients with low versus high NLR (P = 0.022). Cox proportional hazards modeling analysis with inverse probability weighting showed that NLR of at least 3.0 was significantly associated with overall survival (hazard ratio, 3.369; 95% confidence interval, 1.024-11.080). CONCLUSIONS NLR can predict outcomes in patients with unresectable HCC treated with Atez/Bev.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji
| | | | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi
| | | | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama
| | - Hironori Ochi
- Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki
| | - Chikara Ogawa
- Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa
| | - Kazuhito Kawata
- Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu
| | - Takaaki Tanaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama
| | - Hideko Ohama
- Department of Gastroenterology, Osaka Medical College, Osaka
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime
| | | | - Kouji Joko
- Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime
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Liu L, Tang C, Li L, Chen P, Tan Y, Hu X, Chen K, Shang Y, Liu D, Liu H, Liu H, Nie F, Tian J, Zhao M, He W, Guo Y. Deep learning radiomics for focal liver lesions diagnosis on long-range contrast-enhanced ultrasound and clinical factors. Quant Imaging Med Surg 2022; 12:3213-3226. [PMID: 35655832 PMCID: PMC9131334 DOI: 10.21037/qims-21-1004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 03/18/2022] [Indexed: 11/15/2023]
Abstract
BACKGROUND Routine clinical factors play an important role in the clinical diagnosis of focal liver lesions (FLLs); however, they are rarely used in computer-assisted diagnosis. Therefore, we developed a deep learning (DL) radiomics model, and investigated its effectiveness in diagnosing FLLs using long-range contrast-enhanced ultrasound (CEUS) cines and clinical factors. METHODS Herein, 303 patients with pathologically confirmed FLLs after surgery at three hospitals were retrospectively enrolled and divided into a training cohort (n=203), internal validation (IV) cohort (n=50) from one hospital with the ratio of 4:1, and external validation (EV) cohort (n=50) from the other two hospitals. Four DL radiomics models, namely Four Stream 3D convolutional neural network (FS3DU) (trained with CEUS cines only), FS3DU+A (trained with CEUS cines and alpha fetoprotein), FS3DU+H (trained with CEUS cines and hepatitis), and FS3DU+A+H (trained with CEUS cines, alpha fetoprotein, and hepatitis), were formed based on 3D convolutional neural networks (CNNs). They used approximately 20-s preoperative CEUS cines and/or clinical factors to extract spatiotemporal features for the classification of FLLs and the location of the region of interest. The area under curve of the receiver operating characteristic and diagnosis speed were calculated to evaluate the models in the IV and EV cohorts, and they were compared with those of two radiologists. Two-sided Delong tests were used to calculate the statistical differences between the models and radiologists. RESULTS FS3DU+A+H, which incorporated CEUS cines, hepatitis, and alpha fetoprotein, achieved the highest area under curve of 0.969 (95% CI: 0.901-1.000) and 0.957 (95% CI: 0.894-1.000) among radiologists and other models in IV and EV cohorts, respectively. A significant difference was observed when comparing FS3DU and radiologist 2 (all P<0.05). The diagnosis speed of all the models was the same (10.76 s per patient), and it was two times faster than those of the radiologists (radiologist 1: 23.74 and 27.75 s; radiologist 2: 25.95 and 29.50 s in IV and EV cohorts, respectively). CONCLUSIONS The proposed DL radiomics demonstrated excellent performance on the benign and malignant diagnosis of FLLs by combining CEUS cines and clinical factors. It could help the individualized characterization of FLLs, and enhance the accuracy of diagnosis in the future.
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Affiliation(s)
- Li Liu
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Chunlin Tang
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Lu Li
- CHISON Medical Technologies Co., LTD, Wuxi, China
| | - Ping Chen
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Ying Tan
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaofei Hu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Kaixuan Chen
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yongning Shang
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Deng Liu
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - He Liu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hongjun Liu
- Department of Digital Medicine, School of Biomedical Engineering and Medical Imaging, Third Military Medical University (Army Medical University), Chongqing, China
| | - Fang Nie
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, China
| | - Jiawei Tian
- Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | | | - Wen He
- Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yanli Guo
- Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Naganuma A, Aoki T, Koizumi Y, Nakamura S, Joko K, Hiasa Y, Kudo M. C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib. Sci Rep 2022; 12:8421. [PMID: 35589772 PMCID: PMC9120140 DOI: 10.1038/s41598-022-12058-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 04/18/2022] [Indexed: 11/08/2022] Open
Abstract
We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2-22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥ 0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495-2.452), Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.429), and α-fetoprotein ≥ 400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR (p < 0.001). Median progression-free survival was 7.5 (95% CI, 6.7-8.1) months. Multivariate analysis showed that age, CAR ≥ 0.108 (HR, 1.644; 95% CI, 1.324-2.043), and non-hepatitis B, non-hepatitis C etiology (HR, 0.726) were independently associated with progression-free survival. Cumulative progression-free survival differed significantly between patients with low versus high CAR (p < 0.001). CAR values were significantly higher as Japan Integrated Staging score increased (p < 0.001). In conclusion, CAR can predict outcomes in patients with unresectable HCC treated with lenvatinib.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, 1-12-1 Shimoteno, Himeji, Hyogo, 670-8540, Japan.
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Shinya Fukunishi
- Department of Gastroenterology, Osaka Medical College, Osaka, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Hironori Ochi
- Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Kazuhito Kawata
- Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takaaki Tanaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hideko Ohama
- Department of Gastroenterology, Osaka Medical College, Osaka, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, 1-12-1 Shimoteno, Himeji, Hyogo, 670-8540, Japan
| | - Kouji Joko
- Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
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Methyltransferase-like 3 Aggravates HCC Development via Mediating N6-Methyladenosine of Ubiquitin-Specific Protease 7. JOURNAL OF ONCOLOGY 2022; 2022:6167832. [PMID: 35571490 PMCID: PMC9098324 DOI: 10.1155/2022/6167832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 04/20/2022] [Indexed: 11/18/2022]
Abstract
We aimed to investigate the role of methyltransferase-like 3 (METTL3) in regulating HCC by mediating m6A level of ubiquitin-specific protease (USP7). METTL3 levels and m6A contents in HCC tissues and cells were detected. Potential correlations between METTL3 level and lymphatic metastasis, tumor size, tumor staging, and overall survival of HCC patients were analyzed. Moreover, its regulatory effects on proliferative, migratory, and invasive rates of HCC cells were examined. Potential methylation of USP7 in HCC was predicted using an online software, and the correlation between USP7 and METTL3 was assessed. METTL3 and m6A were increased both in HCC cells and tissues. High level of METTL3 was associated with the incidence of lymphatic metastasis, large tumor size, advanced tumor staging, and low overall survival of HCC. Silencing of METTL3 reduced proliferation, migration, and invasion rates. USP7 was predicted to have a methylation site regulated by METTL3. It was upregulated in HCC and associated with METTL3 level positively. USP7 silencing decreased proliferation, migration, and invasion rates of HCC cells. METTL3 promotes HCC to proliferate, migrate, and invade by regulating m6A methylation of USP7.
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Río Bártulos C, Senk K, Schumacher M, Plath J, Kaiser N, Bade R, Woetzel J, Wiggermann P. Assessment of Liver Function With MRI: Where Do We Stand? Front Med (Lausanne) 2022; 9:839919. [PMID: 35463008 PMCID: PMC9018984 DOI: 10.3389/fmed.2022.839919] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/25/2022] [Indexed: 12/12/2022] Open
Abstract
Liver disease and hepatocellular carcinoma (HCC) have become a global health burden. For this reason, the determination of liver function plays a central role in the monitoring of patients with chronic liver disease or HCC. Furthermore, assessment of liver function is important, e.g., before surgery to prevent liver failure after hepatectomy or to monitor the course of treatment. Liver function and disease severity are usually assessed clinically based on clinical symptoms, biopsy, and blood parameters. These are rather static tests that reflect the current state of the liver without considering changes in liver function. With the development of liver-specific contrast agents for MRI, noninvasive dynamic determination of liver function based on signal intensity or using T1 relaxometry has become possible. The advantage of this imaging modality is that it provides additional information about the vascular structure, anatomy, and heterogeneous distribution of liver function. In this review, we summarized and discussed the results published in recent years on this technique. Indeed, recent data show that the T1 reduction rate seems to be the most appropriate value for determining liver function by MRI. Furthermore, attention has been paid to the development of automated tools for image analysis in order to uncover the steps necessary to obtain a complete process flow from image segmentation to image registration to image analysis. In conclusion, the published data show that liver function values obtained from contrast-enhanced MRI images correlate significantly with the global liver function parameters, making it possible to obtain both functional and anatomic information with a single modality.
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Affiliation(s)
- Carolina Río Bártulos
- Institut für Röntgendiagnostik und Nuklearmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
| | - Karin Senk
- Institut für Röntgendiagnostik, Universtitätsklinikum Regensburg, Regensburg, Germany
| | | | - Jan Plath
- MeVis Medical Solutions AG, Bremen, Germany
| | | | | | | | - Philipp Wiggermann
- Institut für Röntgendiagnostik und Nuklearmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
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Sekiguchi S, Tsuchiya K, Yasui Y, Inada K, Kirino S, Yamashita K, Hayakawa Y, Osawa L, Higuchi M, Takaura K, Maeyashiki C, Kaneko S, Tamaki N, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Okamoto R, Kurosaki M, Izumi N. Clinical usefulness of geriatric assessment in elderly patients with unresectable hepatocellular carcinoma receiving sorafenib or lenvatinib therapy. Cancer Rep (Hoboken) 2022; 5:e1613. [PMID: 35302279 PMCID: PMC9675392 DOI: 10.1002/cnr2.1613] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 01/11/2022] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Therapeutic strategies for unresectable hepatocellular carcinoma (u-HCC) in geriatric patients are important for real-world practice. However, there remain no established biomarkers or therapeutic strategies regarding the best second-line agent after atezolizumab plus bevacizumab therapy. AIM In this study, we investigated the usefulness of modified Geriatric 8 (mG8) score in examining elderly patients (≥75 years old) with unresectable hepatocellular carcinoma (u-HCC) using sorafenib or lenvatinib as first-line therapy. METHODS AND RESULTS This study assessed 101 elderly patients with u-HCC for their mG8 score (excluding elements of age from 8 items) and classified them into 2 groups according to their mG8 score: ≥11 as the high-score group and ≤ 10 as the low-score group. Among those taking sorafenib, no significant differences were noted in overall survival (OS) and progression free survival (PFS) between low and high mG8 score groups. Only modified albumin-bilirubin (ALBI) grade (2b/3 vs. 1/2a: HR 0.34; 95% CI, 0.17-0.69; p = .0029) was significantly associated with OS. Among those taking lenvatinib, patients with a high mG8 score (n = 26) had longer survival than those with a low mG8 score (n = 10) (20.0 months vs. 7.7 months: HR 0.31, 95% CI 0.11-0.89; p = .029). Intrahepatic tumor volume (<50% vs. ≥50%: HR 16.7; 95% CI, 1.71-163; p = .016) and α-fetoprotein (AFP) (<400 vs. ≥400: HR 3.38; 95% CI 0.84-19.7; p = .031) remained significant factors independently associated with OS. CONCLUSIONS The mG8 score may contribute to making a decision when considering either sorafenib or lenvatinib as a treatment option for u-HCC in elderly patients.
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Affiliation(s)
- Shuhei Sekiguchi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Yutaka Yasui
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Kento Inada
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Sakura Kirino
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Koji Yamashita
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Yuka Hayakawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Leona Osawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Mayu Higuchi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Kenta Takaura
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Shun Kaneko
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan,NAFLD Research Center, Department of MedicineUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Jun Itakura
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Yuka Takahashi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Yasuhiro Asahina
- Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Ryuichi Okamoto
- Department of Gastroenterology and HepatologyTokyo Medical Dental UniversityBunkyo‐KuJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashino‐shiJapan
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Su TH, Peng CY, Chang SH, Tseng TC, Liu CJ, Chen CL, Liu CH, Yang HC, Chen PJ, Kao JH. Serum PIVKA-II and alpha-fetoprotein at virological remission predicts hepatocellular carcinoma in chronic hepatitis B related cirrhosis. J Formos Med Assoc 2022; 121:703-711. [PMID: 34452785 DOI: 10.1016/j.jfma.2021.08.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/18/2021] [Accepted: 08/02/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy. METHODS Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated. RESULTS Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73-4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35-4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards. CONCLUSION In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shan-Han Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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50
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Ibrahim ESH, Naguib H, Emara DM, El Sayed ET, Tawfik MMR. Assessment of serum Talin-1 in liver cirrhosis and hepatocellular carcinoma. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00184-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Early detection of hepatocellular carcinoma (HCC) is crucial for improving the survival rate for patients. Talin-1 is first identified as a cytoskeleton protein that is required for cell adhesion and motility and plays a role in tumor migration and metastasis. In the present work, we aimed to study the possible role of Talin1 compared to alpha fetoprotein (AFP) in the diagnosis and prognosis of HCC.
Methods
To achieve this goal, serum levels of Talin-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 90 patients divided into four groups. Group I: 30 patients with early HCC. Group II: 30 patients with late HCC according to Modified Barcelona-Clinic Liver Cancer (BCLC). Group III: 15 patients with liver cirrhosis, and group IV: 15 healthy controls. Receiver operating characteristics (ROC) curve analysis was used to create a predictive model for Talin-1 relative to AFP in HCC diagnosis.
Results
It was found that serum Talin-1 in HCC patients was significantly higher compared to its level in cirrhotic patients and the healthy control group. Talin-1 was superior to AFP regarding sensitivity, specificity, positive, and negative predictive value in the diagnosis of HCC. We also found a significant positive correlation between serum Talin-1 and the degree of tumor burden of HCC (BCLC staging), tumor size, and vascular invasion.
Conclusion
Talin-1 holds a promise as a potential marker for HCC diagnosis and prognosis.
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