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Jeon HJ, Yoon SK, Park B, Kim HS, Chae H, Kim H, Shin SH, Han IW, Heo JS, Lee O, Yoon SJ. Development and External Validation of a Nomogram Predicting Early Recurrence of Gallbladder Cancer Using Preoperatively Available Prognosticators: A Korean Multicenter Retrospective Study. Cancers (Basel) 2025; 17:1450. [PMID: 40361377 PMCID: PMC12071069 DOI: 10.3390/cancers17091450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 04/23/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Gallbladder cancer (GBC) is a rare and aggressive malignancy with poor prognosis and high recurrence rates, even after curative surgical resection. Early recurrence, defined as recurrence within one year after surgery, remains a major clinical concern. This study aimed to identify preoperative prognostic factors and develop a predictive model for early recurrence and overall survival in resected GBC patients. Methods: We retrospectively analyzed data from 251 patients who underwent curative-intent resection for GBC between 2008 and 2017. Logistic regression was used to identify preoperative factors associated with early recurrence. Significant variables were used to construct a nomogram, which was externally validated using a cohort of 176 patients from three independent tertiary centers. Results: The independent predictors of early recurrence included male sex, chronic liver disease, preoperative symptoms, elevated carcinoembryonic antigen (CEA), sarcopenic obesity, clinical T3 or higher stage, and suspected metastatic lymph nodes. The nomogram demonstrated strong predictive performance with an AUC of 0.872 (95% CI: 0.817-0.927) in internal validation and 0.703 (95% CI: 0.613-0.793) in external validation. Conclusions: We developed and externally validated a novel nomogram that predicts early recurrence in GBC using only preoperative factors. This model may support individualized risk assessment and aid surgeons and patients in shared decision-making prior to high-risk surgery.
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Affiliation(s)
- Hyun Jeong Jeon
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41404, Republic of Korea
| | - So Kyung Yoon
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Boram Park
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea;
- College of Medicine, Inha University, Incheon 22332, Republic of Korea
| | - Hyeong Seok Kim
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Hochang Chae
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Hongbeom Kim
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Sang Hyun Shin
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - In Woong Han
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Jin Seok Heo
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Okjoo Lee
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea
| | - So Jeong Yoon
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
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Shen TH, Yu X, Zhou C, Liu Y, Li QY, Li W, Jiang TH, Zhu YQ, Liu Y. Review of the mechanisms of the biliary-enteric axis in the development of cholangiocarcinoma. World J Clin Oncol 2025; 16:102374. [PMID: 40290694 PMCID: PMC12019280 DOI: 10.5306/wjco.v16.i4.102374] [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: 10/15/2024] [Revised: 01/07/2025] [Accepted: 02/13/2025] [Indexed: 03/26/2025] Open
Abstract
Cholangiocarcinoma (CCA) is a particularly aggressive and challenging type of cancer, known for its poor prognosis, which is worsened by the complex interplay of various biological and environmental factors that contribute to its development. Recently, researchers have increasingly focused on the significant role of the biliary-enteric communication of liver-gut axis in the pathogenesis of CCA, highlighting a complex relationship that has not been thoroughly explored before. This review aims to summarize the key concepts related to the biliary-enteric communication of liver-gut axis and investigate its potential mechanisms that may lead to the onset and progression of CCA, a disease that presents substantial treatment challenges. Important areas of focus will include the microbiome's profound influence, which interacts with host physiology in ways that may worsen cancer development; changes in bile acid metabolism that can create toxic environments favorable for tumor growth; the regulation of inflammatory processes that may either promote or inhibit tumor progression; the immune system's involvement, which is crucial in the body's response to cancer; and the complex interactions within metabolic pathways that can affect cellular behavior and tumor dynamics. By integrating recent research findings from various studies, we aim to explore the multifaceted roles of the biliary-enteric communication of liver-gut axis in CCA, providing new insights and perspectives for future research while identifying promising therapeutic targets that could lead to innovative treatment strategies aimed at improving patient outcomes in this challenging disease.
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Affiliation(s)
- Tian-Hao Shen
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Xue Yu
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Cheng Zhou
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Yu Liu
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Qiu-Ying Li
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Wei Li
- Department of Hepatological Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Ting-Hui Jiang
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Yong-Qiang Zhu
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Yan Liu
- Department of Interventional Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
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Cheng Y, Li X. Design of studies on neoadjuvant therapy for intrahepatic cholangiocarcinoma. Heliyon 2025; 11:e41356. [PMID: 39897772 PMCID: PMC11786635 DOI: 10.1016/j.heliyon.2024.e41356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 02/04/2025] Open
Abstract
The high recurrence rate and dismal prognosis of localized intrahepatic cholangiocarcinoma (ICC) indicate the unmet need for effective adjuvant and neoadjuvant therapy. In recent years, progress has been made in immunotherapy and targeted therapy for the treatment of advanced biliary tract cancer (BTC), leading to clinical exploration of the provision of these therapies in the perioperative period. Based on years of experience in clinical research on hepatobiliary cancers, the authors discuss the design of studies on neoadjuvant therapy for ICC, aiming to provide references for future neoadjuvant studies.
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Affiliation(s)
- Yuan Cheng
- Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China
| | - Xiangcheng Li
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
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Gaete MI, Meira Junior JDD, Loyola S, Meneses L, Dreyse J, Hevia J, Briceño E, Martinez J. OPTIMIZING PERIOPERATIVE CARE FOR PERIHILAR CHOLANGIOCARCINOMA: THE CRUCIAL ROLE OF MULTIDISCIPLINARY MANAGEMENT, NEOADJUVANT THERAPY, AND INTERVENTIONAL RADIOLOGY. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2025; 37:e1848. [PMID: 39813553 PMCID: PMC11729543 DOI: 10.1590/0102-6720202400054e1848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 10/24/2024] [Indexed: 01/18/2025]
Abstract
BACKGROUND Perihilar cholangiocarcinoma presents unique challenges in perioperative management, requiring a comprehensive approach to optimize patient outcomes. AIMS This case study focuses on the multidisciplinary management and innovative interventions performed in the perioperative care of a patient with hilar cholangiocarcinoma. METHODS A comprehensive assessment and treatment strategy involving neoadjuvant therapy and interventional radiology techniques were implemented. Neoadjuvant chemotherapy was administered to reduce tumor size and improve resectability. The crucial role of interventional radiology in managing postoperative complications is highlighted, particularly in the case of massive pulmonary embolism. RESULTS The neoadjuvant therapy successfully reduced tumor size, enabling an R0 surgical resection. Additionally, interventional radiology interventions, such as percutaneous pharmaco-mechanical thrombectomy, effectively addressed the life-threatening complication of massive pulmonary embolism. CONCLUSIONS This article highlights the importance of a collaborative, multidisciplinary approach in managing complex oncological surgeries, especially regarding the hospital's rescue capacity for severe postoperative complications. Emergent management with interventional radiology had a central role in resolving life-threatening complications.
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Affiliation(s)
- María Inés Gaete
- Pontificia Universidad Católica de Chile, Department of Digestive Surgery - Santiago, Chile
| | | | - Soledad Loyola
- Pontificia Universidad Católica de Chile, Department of Radiology - Santiago, Chile
| | - Luís Meneses
- Pontificia Universidad Católica de Chile, Department of Radiology - Santiago, Chile
| | - Jorge Dreyse
- Clínica las Condes, Center for Critical Patients - Santiago, Chile
| | - Joaquín Hevia
- Pontificia Universidad Católica de Chile, Department of Radiology - Santiago, Chile
| | - Eduardo Briceño
- Pontificia Universidad Católica de Chile, Department of Digestive Surgery - Santiago, Chile
| | - Jorge Martinez
- Pontificia Universidad Católica de Chile, Department of Digestive Surgery - Santiago, Chile
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Sarkhampee P, Ouransatien W, Lertsawatvicha N, Chansitthichock S, Wattanarath P. Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma. World J Surg Oncol 2024; 22:314. [PMID: 39605039 PMCID: PMC11600713 DOI: 10.1186/s12957-024-03596-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 11/17/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system, which can be classified into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). Surgical resection is the curative treatment for all subtypes of CCA. This study evaluates patients with CCA who underwent surgery and determines factors that impact their survival. METHODS We conducted a retrospective analysis of 720 patients diagnosed with CCA from October 2013 to December 2018. Patients were categorized into iCCA (n = 398), pCCA (n = 237), and dCCA (n = 85) based on tumor location. Data including demographic information, clinical presentation, treatment modalities, and survival statistics were collected and analyzed. RESULTS The overall resectability rate was 78.3%, with resectability highest in pCCA patients (83.5%). Overall median survival time (MST) was 11.6 months and varied among subtypes: iCCA 10.9 months, pCCA 11.2 months, and dCCA 15.4 months. Patients underwent curative-intent resection significantly improved survival compared to those with palliative resection or unresectable disease in all subtypes. R0 resection patients had better overall survival (OS) than R1 resection patients: 5-year survival rate of 20.2% vs. 4.3% in all CCA (p < 0.001), 21.4% vs. 7% in iCCA (p < 0.001), 17.2% vs. 0% in pCCA (p < 0.001), and 23.1% vs. 0% in dCCA (p = 0.105), respectively. Positive resection margin was an independent prognostic factor for OS in pCCA and iCCA. CONCLUSION Surgical resection is the only cure for CCA. Curative-intent resection is more effective than palliative resection in improving survival rates. When performing curative-intent resection, the goal is R0 resection. This is because it improves overall survival over R1 resection.
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Affiliation(s)
- Poowanai Sarkhampee
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand.
| | - Weeris Ouransatien
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
| | - Nithi Lertsawatvicha
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
| | - Satsawat Chansitthichock
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
| | - Paiwan Wattanarath
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
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Areewong S, Suppramote O, Prasopporn S, Jirawatnotai S. Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma. Cancer Cell Int 2024; 24:362. [PMID: 39501277 PMCID: PMC11539612 DOI: 10.1186/s12935-024-03548-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 10/26/2024] [Indexed: 11/08/2024] Open
Abstract
Cholangiocarcinoma (CCA) presents a formidable therapeutic challenge due to its extensive heterogeneity and plasticity, which inevitably lead to acquired resistance to current treatments. However, recent evidence suggests that acquired drug resistance is associated with a fitness cost resulting from the myriad of acquired alterations under the selective pressure of the primary treatment. Consequently, CCA patients with acquired resistance are more susceptible to alternative therapies that are ineffective as monotherapies. This phenomenon, termed "acquired vulnerability," has garnered significant interest in drug development, as the acquired alterations could potentially be exploited therapeutically. This review elucidates the modes of acquired vulnerability, methods for identifying and exploiting acquired vulnerabilities in cancer (particularly in CCA), and strategies to enhance the clinical efficacy of drug combinations by leveraging the principle of acquired vulnerability. Identifying acquired vulnerabilities may pave the way for novel drug combinations to effectively treat highly heterogeneous and adaptable malignancies such as CCA.
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Affiliation(s)
- Sirayot Areewong
- Siriraj Center of Research Excellence (SiCORE) for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Rd., 11th Floor Srisavarindhira Building, Bangkok Noi, 10700, Bangkok, Thailand
| | - Orawan Suppramote
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, 906 Kampangpetch 6 Rd., Talat Bang Khen, Lak Si, 10210, Bangkok, Thailand
| | - Sunisa Prasopporn
- Siriraj Center of Research Excellence (SiCORE) for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Rd., 11th Floor Srisavarindhira Building, Bangkok Noi, 10700, Bangkok, Thailand
| | - Siwanon Jirawatnotai
- Siriraj Center of Research Excellence (SiCORE) for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Rd., 11th Floor Srisavarindhira Building, Bangkok Noi, 10700, Bangkok, Thailand.
- Faculty of Pharmacy, Silpakorn University, 6 Ratchamankanai Road., Phra Pathom Chedi Sub-district, Mueang District, 73000, Nakhon Pathom, Thailand.
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Satapathy HS, Sehgal L, Bhardwaj M. Impact of Preoperative Chemotherapy on Postoperative Renal Dysfunction After Major Abdominal Surgery: A Prospective Observational Study. Cureus 2024; 16:e64116. [PMID: 39119380 PMCID: PMC11306644 DOI: 10.7759/cureus.64116] [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] [Accepted: 07/08/2024] [Indexed: 08/10/2024] Open
Abstract
Introduction The administration of anti-cancer drugs and major abdominal surgeries have been independently identified to have a negative effect on renal function. The objectives of the study are to determine the incidence of acute kidney injury (AKI) in patients undergoing major elective abdominal surgery following chemotherapy and identify the independent predictors of postoperative AKI among such cancer patients in a tertiary care cancer institute in North India. Methods The prospective observational study included 149 patients aged 18 years or more, scheduled for elective major abdominal cancer surgery. Based on the administration of preoperative chemotherapy, the participants were divided into two study cohorts (Group 1: received preoperative chemotherapy; Group 2: did not receive preoperative chemotherapy). Patients' preoperative characteristics, including the use of preoperative chemotherapeutic agents and intraoperative factors, were evaluated for associations with the development of AKI postoperatively using the Chi-square test and Mann-Whitney U test. Multivariable logistic regression was employed to identify the factors after adjusting for potential confounders. Results The overall incidence of postoperative AKI in major abdominal oncosurgery was 24.2% among our study participants, which was significantly higher among patients receiving preoperative chemotherapy (32.4%) as compared to those who did not receive preoperative chemotherapy (16%) (p=0.019). Besides preoperative chemotherapy, the present study also noted that high levels of preoperative urinary protein-to-creatinine ratio (UPCR) and intraoperative use of vasopressors were significantly associated with an increased risk of postoperative AKI development in the final model, after adjustment for all potential confounders. A preoperative UPCR≥0.345 predicted the development of postoperative AKI with 77.8% sensitivity and 83.2% specificity. Conclusion Considering the magnitude of the problem, identification of determinants of postoperative AKI in major abdominal surgeries in cancer patients may help anesthetists and surgeons in early detection of AKI, so that prompt precautionary measures can be put in place that can potentially impact prognosis.
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Affiliation(s)
| | - Lalit Sehgal
- Liver Transplant Anesthesia/Liver ICU, Manipal Hospital, New Delhi, IND
| | - Manoj Bhardwaj
- Anesthesia, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, IND
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Guo X, Wang J, Tian Y, Yang J, Wu S, Xin L, Feng Z, Niu G. Epigenetic silencing of miR-125a-3p promotes the progress of human cholangiocarcinoma via increasing CAC1 expression. Heliyon 2024; 10:e32528. [PMID: 38994075 PMCID: PMC11237926 DOI: 10.1016/j.heliyon.2024.e32528] [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: 01/21/2024] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 07/13/2024] Open
Abstract
We aimed to investigate the dysregulation of the microRNAs(miRNAs) in cholangiocarcinoma (CCA), including its impact on the homeostasis of the transcriptome and cellular behavior. MiRNAs serve as potent epigenetic regulators of transcriptional output, targeting various signaling pathways. This study aimed to investigate the expression level, epigenetic mechanism and function of miR-125a-3 in CCA. The study data showed that the expression level of miR125a-3p was decreased in CCA tissue samples and cell lines, and it was closely related to lymph node metastasis, tissue differentiation and TNM stage. The data demonstrate a strong association between decreased miR-125a-3p expression and poorer prognosis in cholangiocarcinoma patients. miR-125a-3p acts as a tumor suppressor by inhibiting the viability, migration and invasion of CCA cells. There are CpG islands in the promoter region of miR-125a-3p gene, and the methylation of the promoter region of miR-125a-3p gene leads to the transcriptional repression of miR-125a-3p. In addition, miR125a-3p can target and regulate CAC1 mRNA and protein expression in the downstream mechanism, and the high expression of CAC1 can promote the proliferation, migration and invasion of cholangiocarcinoma cells. These data demonstrate that miR-125a-3p promoter methylation leads to silencing of its expression. Mechanically, miR-125a-3p acts as a tumor suppressor and participates in the occurrence and development of CCA through targeting CAC1 gene expression. Therefore, miR-125a-3p may serve as a new target for the diagnosis, prognostic assessment or molecular therapy of CCA.
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Affiliation(s)
- Xiaojuan Guo
- Department of Pathology, Handan Center Hospital, Handan, 056002, China
| | - Jinxi Wang
- The Fourth Department of General Surgery, The First Hospital of Handan, Handan, 056002, China
| | - Yunxiao Tian
- Department of Pathology, Handan Center Hospital, Handan, 056002, China
| | - Jianhua Yang
- Department of Pathology, Handan Center Hospital, Handan, 056002, China
| | - Shiqian Wu
- Department of Pathology, Handan Center Hospital, Handan, 056002, China
| | - Lihui Xin
- Department of Pathology, Handan Center Hospital, Handan, 056002, China
| | - Zhe Feng
- Department of Function, Handan Center Hospital, Handan, 056002, China
| | - Guangxu Niu
- Department of Pathology, Handan Center Hospital, Handan, 056002, China
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Yamada R, Kuriyama N, Tanaka T, Nose K, Nakamura Y, Miwata T, Tsuboi J, Mizuno S, Nakagawa H. Inside stent placement is suitable for preoperative biliary drainage in patients with perihilar cholangiocarcinoma. BMC Gastroenterol 2024; 24:174. [PMID: 38769494 PMCID: PMC11106890 DOI: 10.1186/s12876-024-03266-z] [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: 10/25/2023] [Accepted: 05/15/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND/PURPOSE Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC. METHODS EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups. RESULTS Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0-3) vs. 1.88 (0-8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016). Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively). CONCLUSION Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.
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Affiliation(s)
- Reiko Yamada
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan.
| | - Naohisa Kuriyama
- Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Takamitsu Tanaka
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan
| | - Kenji Nose
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan
| | - Yoshifumi Nakamura
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan
| | - Tetsuro Miwata
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan
| | - Junya Tsuboi
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan
| | - Shugo Mizuno
- Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Hayato Nakagawa
- Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie-prefecture, 514-8507, Japan
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Kobayashi S, Nakachi K, Ikeda M, Konishi M, Ogawa G, Sugiura T, Yanagimoto H, Morinaga S, Wada H, Shimada K, Takahashi Y, Nakagohri T, Kamata K, Shimizu Y, Ajiki T, Hirano S, Gotohda N, Ueno M, Okusaka T, Furuse J. Feasibility of S-1 adjuvant chemotherapy after major hepatectomy for biliary tract cancers: An exploratory subset analysis of JCOG1202. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107324. [PMID: 38157649 DOI: 10.1016/j.ejso.2023.107324] [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: 10/31/2023] [Revised: 11/29/2023] [Accepted: 12/10/2023] [Indexed: 01/03/2024]
Abstract
INTRODUCTION Major hepatectomy (MH) may produce the impaired liver function and affect the feasibility of adjuvant chemotherapy in terms of early period after the surgery, but there have not been detailed investigations. JCOG1202 (UMIN000011688) is a randomized phase III trial demonstrating the superiority of adjuvant S-1 chemotherapy for biliary tract cancer (BTC). The aim of this study is to examine the influence of MH for BTC on adjuvant S-1. MATERIALS AND METHODS Of the total 424 patients, 207 received S-1 (S-1 arm) while the remaining 217 were not. We compared MH with non-major hepatectomy (NMH) for BTC. RESULTS In the S-1 arm, 42 had undergone MH, and 165 had undergone NMH. MH had similar pretreatment features to NMH, including the proportion of biliary reconstruction, to NMH, except for a lower platelet count (17.7 vs. 23.4 × 104/mm3, p < 0.0001) and lower serum albumin level (3.5 vs. 3.8 g/dL, p < 0.0001). The treatment completion proportion tended to be lower for MH than for NMH (59.5 % vs. 75.8 %; risk ratio, 0.786 [95 % confidence interval, 0.603-1.023], p = 0.0733), and the median dose intensity was lower as well (88.7 % vs. 99.6 %, p = 0.0358). The major reasons for discontinuation were biliary tract infections and gastrointestinal disorders after MH. The frequency of grade 3-4 biliary tract infection was 19.0 % in MH vs. 4.2 % in NMH. CONCLUSION The treatment completion proportion and dose intensity were lower in MH than in NMH. Caution should be exercised against biliary tract infections and gastrointestinal disorders during adjuvant S-1 after MH for BTC.
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Affiliation(s)
- Shogo Kobayashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Japan; Department of Gastroenterological Surgery, Osaka University, Japan
| | - Kohei Nakachi
- Department of Medical Oncology, Tochigi Cancer Center, Japan; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan
| | - Masaru Konishi
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan
| | - Gakuto Ogawa
- JCOG Data Center, National Cancer Center Hospital, Japan
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Japan
| | | | - Soichiro Morinaga
- Department of Hepato-Biliary and Pancreatic Surgery, Kanagawa Cancer Center, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshio Nakagohri
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Japan
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Japan
| | - Tetsuo Ajiki
- Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Hospital, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Hospital, Japan
| | - Naoto Gotohda
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Kanagawa Cancer Center, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Junji Furuse
- Department of Gastroenterology, Kanagawa Cancer Center, Japan
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11
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Pavlidis ET, Galanis IN, Pavlidis TE. New trends in diagnosis and management of gallbladder carcinoma. World J Gastrointest Oncol 2024; 16:13-29. [PMID: 38292841 PMCID: PMC10824116 DOI: 10.4251/wjgo.v16.i1.13] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/06/2023] [Accepted: 12/19/2023] [Indexed: 01/11/2024] Open
Abstract
Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.
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Affiliation(s)
- Efstathios T Pavlidis
- 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Ioannis N Galanis
- 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Theodoros E Pavlidis
- 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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12
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Sakamoto Y. Editorial for review series of adjuvant and neoadjuvant. Jpn J Clin Oncol 2023; 53:875-876. [PMID: 37567586 DOI: 10.1093/jjco/hyad104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 08/01/2023] [Indexed: 08/13/2023] Open
Affiliation(s)
- Yoshihiro Sakamoto
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan
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13
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Rissel M, Pohl J, Moosburner S, Gaßner JMGV, Horner R, Hillebrandt KH, Modest DP, Pratschke J, Sauer IM, Raschzok N. Effect of Preoperative Chemotherapy on the Isolation Outcome of Primary Human Hepatocytes. Tissue Eng Part C Methods 2023; 29:63-71. [PMID: 36694452 DOI: 10.1089/ten.tec.2022.0193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Primary human hepatocytes isolated from surgically resected liver tissue are an essential resource for pharmaceutical and toxicological studies. Patients undergoing partial liver resections have often received preoperative chemotherapy. The aim of our study was to investigate whether preoperative chemotherapy has effects on the outcome of cell isolation or the metabolic function of cultured hepatocytes. Liver specimens from 48 patients were used for hepatocyte isolation. Out of these, 21 patients had prior chemotherapy, with fluoropyrimidine-based regimen in 14 patients. Viability and cell yield as parameter for the outcome of isolation, as well as transaminase levels, urea or albumin secretion to the culture medium were not different between hepatocytes from pretreated and untreated donor. Furthermore, the transcription levels of cytochrome P450 (CYP) 1A2, CYP 2B6, and CYP 3A4 of cultured hepatocytes were not affected by prior chemotherapy of the tissue donors. In conclusion, hepatocytes from tissue donors that underwent fluoropyrimidine-based chemotherapy regimens before isolation seem to perform as well as hepatocytes without preoperative chemotherapy exposure. Our results suggest that hepatocytes from patients who received combination chemotherapy before liver resection are an uncompromised resource for pharmacological and toxicological studies. Impact statement Isolated primary human hepatocytes are an essential resource for pharmacological and toxicological studies. Our results present further evidence that isolated hepatocytes from patients who received combination chemotherapy before liver resection are an uncompromised resource for pharmacological and toxicological studies-especially when fluoropyrimidine-based regimens are used.
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Affiliation(s)
- Marco Rissel
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Julian Pohl
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Simon Moosburner
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany
| | - Joseph M G V Gaßner
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany
| | - Rosa Horner
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Karl H Hillebrandt
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany
| | - Dominik P Modest
- Department of Hematology, Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Cluster of Excellence Matters of Activity, Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Under Germany's Excellence Strategy-EXC 2025, Berlin, Germany
| | - Igor M Sauer
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Cluster of Excellence Matters of Activity, Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Under Germany's Excellence Strategy-EXC 2025, Berlin, Germany
| | - Nathanael Raschzok
- Department of Surgery, Experimental Surgery and Oncology, Cancer Immunology (CCM/CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany
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14
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Silver CM, Joung RH, Logan CD, Benson AB, Mahalingam D, D’Angelica MI, Bentrem DJ, Yang AD, Bilimoria KY, Merkow RP. Neoadjuvant therapy use and association with postoperative outcomes and overall survival in patients with extrahepatic cholangiocarcinoma. J Surg Oncol 2023; 127:90-98. [PMID: 36194064 PMCID: PMC9729397 DOI: 10.1002/jso.27112] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 09/18/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES Evidence for neoadjuvant therapy (NAT) in extrahepatic cholangiocarcinoma (eCCA) is limited. Our objectives were to: (1) characterize treatment trends, (2) identify factors associated with receipt of NAT, and (3) evaluate associations between NAT and postoperative outcomes. METHODS Retrospective cohort study of the National Cancer Database (2004-2017). Multivariable logistic regression assessed associations between NAT and postoperative outcomes. Stratified analysis evaluated differences between surgery first, neoadjuvant chemotherapy, and neoadjuvant chemoradiation (CRT). RESULTS Among 8040 patients, 417 (5.2%) received NAT. NAT increased during the study period 2.9%-8.4% (p < 0.001). Factors associated with receipt of NAT included age <50 (vs. >75, odds ratio [OR] 4.32, p < 0.001) and stage 3 disease (vs. 1, OR 1.68, p = 0.01). Compared with surgery first, patients who received NAT had higher odds of R0 resection (OR 1.49, p = 0.01) and lower 30-day mortality (OR 0.51, p = 0.04). On stratified analysis, neoadjuvant chemotherapy was not associated with differences in any outcomes. However, neoadjuvant CRT was associated with improvement in R0 resection (OR 3.52, <0.001) and median survival (47.8 vs. 25.3 months, log-rank < 0.001) compared to surgery first. CONCLUSIONS NAT, particularly neoadjuvant CRT, was associated with improved postoperative outcomes. These data suggest expanding the use of neoadjuvant CRT for eCCA.
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Affiliation(s)
- Casey M. Silver
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rachel H. Joung
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Charles D. Logan
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Al B. Benson
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
| | - Devalingam Mahalingam
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael I. D’Angelica
- Department of Surgery, Memorial Sloane Kettering Cancer Center, New York, New York, USA
| | - David J. Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Anthony D. Yang
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Karl Y. Bilimoria
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Ryan P. Merkow
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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15
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Safdar NZ, Hakeem AR, Faulkes R, James F, Mason L, Masson S, Powell J, Rowe I, Shetty S, Jones R, Spiers HVM, Halliday N, Baker J, Thorburn D, Prasad R, Parker R. Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma. Transpl Int 2022; 35:10802. [PMID: 36406780 PMCID: PMC9667791 DOI: 10.3389/ti.2022.10802] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/18/2022] [Indexed: 12/03/2022]
Abstract
Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1 years (14 days-18.6 years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4 years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.
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Affiliation(s)
- Nawaz Z. Safdar
- School of Medicine, University of Leeds, Leeds, United Kingdom
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Abdul R. Hakeem
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | | | - Fiona James
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Lisa Mason
- Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Steven Masson
- Newcastle Upon Tyne Hospitals, Newcastle, United Kingdom
| | - James Powell
- Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Ian Rowe
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Shishir Shetty
- University Hospitals Birmingham, Birmingham, United Kingdom
| | - Rebecca Jones
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Harry V. M. Spiers
- Roy Calne Transplant Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | | | | | | | - Raj Prasad
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Richard Parker
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
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16
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Yang X, Chen T, Hu J, Wang J, Yang D. HKI-272 contributes to gemcitabine-mediated anti-proliferative and anti-metastatic effects through EGFR suppression in gallbladder cancer. Mol Ther Oncolytics 2022; 27:126-140. [PMID: 36321135 PMCID: PMC9596964 DOI: 10.1016/j.omto.2022.10.004] [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: 04/21/2022] [Accepted: 10/05/2022] [Indexed: 11/06/2022] Open
Abstract
Gallbladder cancer (GBC) is a rare malignancy of the biliary system and characterized by early metastasis and poor prognosis. To date, no efficient treatment is available for GBC patients. Based on the data from cBioPortal, TIMER, and GDSC, we performed an unbiased screening with 25 candidate compounds that predominantly target ErbB family and identified HKI-272, a highly selective EGFR/ErbB2 inhibitor, displayed decreased IC50 values in three GBC cell lines. HKI-272 not only promoted gemcitabine-mediated anti-proliferative and pro-apoptotic effects and induced cell cycle arrest in GBC, but also enhanced gemcitabine-induced suppressive effects of GBC cell migration and invasion by inhibiting pathways downstream of EGFR. Furthermore, HKI-272, together with gemcitabine, effectively suppressed tumor growth and metastases in mouse models. Immunostaining and HE staining data from both primary tumor and lung metastasis indicated that the anti-proliferative and anti-metastatic effects were mediated through EGFR suppression. Moreover, the expression of EGFR, measured by both immunostaining and HE staining, was correlated with a poor prognosis in GBC. In addition, EGFR in tumor tissues are independent indicators for overall survival in GBC patients. Taken together, our findings suggest that HKI-272 could be a potential therapeutic agent and EGFR might serve as a potential biomarker for patients with GBC.
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Affiliation(s)
- Xuli Yang
- Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China
| | - Tao Chen
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jie Hu
- Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China
| | - Jian Wang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- Corresponding author Jian Wang, Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
| | - Dong Yang
- Department of Gastroenterology and Pancreatic Surgery, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu 211100, China
- Corresponding author Dong Yang, Department of Gastroenterology and Pancreatic Surgery, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu 211100, China.
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17
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Hamura R, Haruki K, Taniai T, Yanagaki M, Shirai Y, Furukawa K, Usuba T, Fujioka S, Okamoto T, Nakabayashi Y, Uwagawa T, Ikegami T. The impact of S-1 for the patient with lymph nodal metastasis biliary tract cancer as adjuvant chemotherapy: a multicenter database analysis. Int J Clin Oncol 2022; 27:1188-1195. [DOI: 10.1007/s10147-022-02165-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 03/24/2022] [Indexed: 12/26/2022]
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18
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Papamichail M, Pizanias M, Heaton ND, M P, M P, Nd H. Minimizing the risk of small-for-size syndrome after liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:113-133. [PMID: 34961675 DOI: 10.1016/j.hbpd.2021.12.005] [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: 06/21/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). DATA SOURCES This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. RESULTS Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. CONCLUSIONS With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.
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Affiliation(s)
- Michail Papamichail
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK.
| | - Michail Pizanias
- Department of General Surgery, Whittington Hospital, London N19 5NF, UK
| | - Nigel D Heaton
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Papamichail M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Pizanias M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Heaton Nd
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
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19
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Analysis of a Systemic Inflammatory Biomarker in Advanced Bile Tract Carcinoma Treated with Anti-PD-1 Therapy: Prognostic and Predictive Significance of Lung Immune Prognostic Index Score. JOURNAL OF ONCOLOGY 2022; 2022:1427779. [PMID: 35342416 PMCID: PMC8947875 DOI: 10.1155/2022/1427779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/20/2022] [Accepted: 02/22/2022] [Indexed: 11/18/2022]
Abstract
Background The application of immunotherapy is gradually increasing in advanced bile tract carcinoma (BTC), but only some patients could benefit from it. Validated biomarkers can screen out the beneficiaries. Therefore, the objective of this research is aimed at exploring the predictive value of lung immune prognostic index (LIPI) in advanced BTC patients receiving immunotherapy. Methods This study was conducted on 110 BTC patients. The cut-off value of the derived neutrophil-to-lymphocyte (dNLR) ratio was obtained by the ROC curves to predict the tumor progression rate at the 6th month. The high levels of dNLR (≥the cut-off value) and lactate dehydrogenase (≥the upper limit of normal) were considered to be two risk factors for LIPI. Based on these two risk factors, patients were categorized into 3 groups based on risk factors: 0 for the good group, 1 for the intermediate group, and 2 for the poor group. Due to the limited number of patients in the poor group, it was integrated into the intermediate group to be the intermediate/poor group. Finally, the subjects were divided into two groups: LIPI-good and LIPI-intermediate/poor. Results The results shed light on the 110 BTC patients' LIPI in advanced BTC patients receiving immunotherapy, indicating that the cut-off value of dNLR was 1.74. According to the risk stratification, 38 (34.5%) patients had a good LIPI score, whereas the LIPI score was intermediate/poor in 72 (65.5%). In addition, patients with good LIPI were related to longer progression-free survival (PFS) and overall survival (OS), compared to those with intermediate/poor LIPI (12.17 months vs. 3.17 months; 20.2 months vs. 8.7 months). According to multivariate analysis, the intermediate/poor LIPI group was independently correlated with over 2.3 times greater risk of tumor progression (HR = 2.301; 95% CI, 1.395-3.796; P = 0.001) and over 1.8 times greater risk of death (HR = 1.877; 95% CI, 1.076-3.275; P = 0.027) than the good group. Moreover, the result also revealed that there were significant differences of DCR for patients of the good group and the intermediate/poor group (86.8% vs. 65.3%; P = 0.012). Conclusion Finally, this study verifies, for the first time, that LIPI is an independent factor affecting the survival and clinical efficacy of advanced BTC patients receiving immunotherapy. It may be difficult for patients with intermediate/poor LIPI to benefit from immunotherapy.
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20
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Kim H, Kim R, Kim HR, Jo H, Kim H, Ha SY, Park JO, Park YS, Kim ST. HER2 Aberrations as a Novel Marker in Advanced Biliary Tract Cancer. Front Oncol 2022; 12:834104. [PMID: 35252005 PMCID: PMC8896348 DOI: 10.3389/fonc.2022.834104] [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: 12/13/2021] [Accepted: 01/18/2022] [Indexed: 11/13/2022] Open
Abstract
HER2 aberrations have been reported as a novel biomarker in HER2-directed therapy or as a prognostic marker in various tumor types. However, in advanced biliary tract cancer (BTC), there have been few studies regarding HER2 aberrations as a biomarker. We analyzed 121 advanced BTC patients who had been treated with Gemcitabine/Cisplatin (GP) as a 1st line therapy between November 2019 and April 2021. Next-generation sequencing (NGS), namely, HER2 aberrations was performed in all patients. The TruSight™ Oncology 500 assay from Illumina was used for the NGS panel. Among 121 patients with advanced BTC, HER2 aberrations were observed in 18 patients (14.9%). For subtypes of HER2 aberrations, point mutation was observed in 5 patients (27.8%), gene amplification in 11 patients (61.1%), and both point mutation and gene amplification in 2 patients (11.1%). The frequency of HER2 aberrations was significantly different according to the primary tumor (p = 0.009). In gallbladder cancer, HER2 aberrations were observed at a relatively high frequency (36.4%). The tumor response to GP did not differ between patients with and without HER2 aberrations (33.3%, vs. 26.2%, respectively, p = 0.571). The median progression-free survival (PFS) to GP was 4.7 months (95% CI, 4.0 to 5.5 months) in patients with HER2 aberrations and 7.0 months (95% CI, 5.2 to 8.8 months) without HER2 aberrations (p = 0.776). The median overall survival (OS) was not reached and not reached in patients with and without HER2 aberrations (p = 0.739), respectively. The univariate analysis for PFS to GP and OS showed that HER2 aberrations were not an independent factor for survival. This study showed that the HER2 aberrations were observed in 14.9% of advanced BTC and were not an independent biomarker for survival.
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Affiliation(s)
- Hongsik Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea
| | - Ryul Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hye Ryeon Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hyunji Jo
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hana Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Oh Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young Suk Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seung Tae Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Kunitoh H. Message from the Editor-in-Chief. Jpn J Clin Oncol 2022; 52:1-2. [PMID: 34978327 DOI: 10.1093/jjco/hyab190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Hideo Kunitoh
- Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, JapanEditor-in-Chief, Japanese Journal of Clinical Oncology
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22
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Xiao X, Zhou J, Fang M, Ji J, Huang C, Du F, Ai W, Wang Y, Gao Z, Qiu Z, Gao C. Quantitative detections of TP53 gene mutations improve the diagnosis and prognostic prediction of biliary tract cancers using droplet digital PCR. J Clin Lab Anal 2022; 36:e24103. [PMID: 34813121 PMCID: PMC8761443 DOI: 10.1002/jcla.24103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/28/2021] [Accepted: 10/29/2021] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE Biliary tract cancer (BTC) is a rare malignancy and lack of effective diagnostic and prognostic marker. Here, we aimed to investigate the clinical implication of TP53 mutation detection in BTC using droplet digital PCR (ddPCR). METHODS TP53 gene (loci p.R175H, p.R248Q, p.R248W, and p.R273H) mutation frequencies of 45 pairs of tumor tissues (TTs) and adjacent normal tissues (ANTTs) were analyzed, respectively, using ddPCR. Meanwhile, the same detections were conducted in plasma cell-free DNA (cfNDA) of 156 subjects including BTC, disease control (DC), and healthy controls (HC). The logistic regression algorithm was established to identify BTC. The correlations between mutations and clinicopathological features as well as the effects of TP53 mutation frequency on BTC prognosis were assessed. RESULTS The higher mutation of p.R175H was found in TTs compared with ANTT (p = 0.006). The mutation at p.R273H in cfDNA was also higher in BTC when compared with DC and HC (p < 0.05). The logistic algorithms combining p.R273H mutation demonstrated the higher diagnostic efficacy trend than carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) in identifying BTC from DC (the area under the curves of the algorithm: 0.845, 95% CI:0.775-0.914). The median overall survival (OS) and progression-free survival (PFS) were significantly shorter when the BTC patients harboring the p.R273H mutation (OS: p = 0.032; PFS: p = 0.046). CONCLUSION This study revealed for the first time that the quantitative TP53 mutations using the ddPCR might serve as a potential genetic biomarker for BTC diagnosis and prognosis assessment.
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Affiliation(s)
- Xiao Xiao
- Clinical Laboratory Medicine CenterYueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Jun Zhou
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Meng Fang
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Jun Ji
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Chenjun Huang
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Fei Du
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Wenchao Ai
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Ying Wang
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Zhiyuang Gao
- Clinical Laboratory Medicine CenterYueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Zhiquan Qiu
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
| | - Chunfang Gao
- Clinical Laboratory Medicine CenterYueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
- Department of Laboratory MedicineShanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
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Bahra M. [Surgical treatment of distal cholangiocarcinoma]. Chirurg 2021; 92:788-795. [PMID: 34232340 DOI: 10.1007/s00104-021-01453-2] [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] [Accepted: 06/01/2021] [Indexed: 10/20/2022]
Abstract
Distal cholangiocarcinoma accounts for about 20% of bile duct cancers, representing the third most common tumor entity among periampullary cancers, along with adenocarcinoma of the pancreas and carcinomas of the papilla of Vater. Precise diagnostics of tumor localization and exact knowledge of tumor-specific growth patterns are crucial for successful surgery. When planning the surgical procedure, the differential diagnosis of central bile duct cancer (Bismuth type I) or middle bile duct carcinoma must be considered. Although benign periampullary bile duct stenosis occurs in only 5% of cases, the presence of immunoglobulin G4-associated cholangitis (IAC) should be excluded in doubtful cases. Basically, in the presence of a distal cholangiocarcinoma, partial pancreatoduodenectomy is indicated analogous to the procedure for ductal adenocarcinoma of the pancreatic head. The 5‑year survival after resection is 20-25% and therefore comparable to adenocarcinoma of the pancreas. Local resection of middle bile duct carcinoma is no longer recommended due to inadequate surgical radicality. To date, perioperative treatment for downsizing does not play a relevant role for surgical treatment of distal cholangiocarcinoma. In the presence of a distal cholangiocarcinoma primary surgery with the aim of a R0 resection is the standard treatment of choice.
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Affiliation(s)
- Marcus Bahra
- Zentrum für Onkologische Oberbauchchirurgie und Robotik, Krankenhaus Waldfriede, Akademisches Lehrkrankenhaus der Charité, Argentinische Allee 40, 14163, Berlin, Deutschland.
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Posch F, Prinz F, Balihodzic A, Mayr C, Kiesslich T, Klec C, Jonas K, Barth DA, Riedl JM, Gerger A, Pichler M. MiR-200c-3p Modulates Cisplatin Resistance in Biliary Tract Cancer by ZEB1-Independent Mechanisms. Cancers (Basel) 2021; 13:cancers13163996. [PMID: 34439151 PMCID: PMC8392278 DOI: 10.3390/cancers13163996] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 08/03/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Biliary tract cancer is a rare malignancy with poor overall survival. The majority of patients are faced with advanced disease stage. Cisplatin-based treatment schedules represent the mainstay of first-line therapeutic strategy, yet only a small portion of patients develop a treatment response. One of the main reasons is acquired drug resistance. Previous studies correlated certain microRNAs (miRNAs), including miR-200c-3p, with drug resistance in various cancer types. However, limited knowledge exists about miR-200c-3p expression and cisplatin resistance in biliary tract cancer. Thus, the main aim of this study was to investigate the influence of miR-200c-3p on the cisplatin resistance in this cancer entity. We demonstrated that miR-200c-3p contributes to cisplatin resistance independently of its known influence on ZEB1 expression. Abstract Biliary tract cancer is a major global health issue in cancer-related mortality. Therapeutic options are limited, and cisplatin-based treatment schedules represent the mainstay of first-line therapeutic strategies. Although the gain of survival by the addition of cisplatin to gemcitabine is moderate, acquired cisplatin resistance frequently leads to treatment failures with mechanisms that are still poorly understood. Epithelial–mesenchymal transition (EMT) is a dynamic process that changes the shape, function, and gene expression pattern of biliary tract cancer cells. In this study, we explored the influence of the EMT-regulating miR-200c-3p on cisplatin sensitivity in biliary tract cancer cells. Using gain of function experiments, we demonstrated that miR-200c-3p regulates epithelial cell markers through the downregulation of the transcription factor ZEB1. MiR-200c-3p upregulation led to a decreased sensitivity against cisplatin, as observed in transient overexpression models as well as in cell lines stably overexpressing miR-200c-3p. The underlying mechanism seems to be independent of miR-200c-3p’s influence on ZEB1 expression, as ZEB1 knockdown resulted in the opposite effect on cisplatin resistance, which was abolished when ZEB1 knockdown and miR-200c-3p overexpression occurred in parallel. Using a gene panel of 40 genes that were previously associated with cisplatin resistance, two (Dual Specificity Phosphatase 16 (DUSP16) and Stratifin (SFN)) were identified as significantly (>2 fold, p-value < 0.05) up-regulated in miR-200c-3p overexpressing cells. In conclusion, miR-200c-3p might be an important contributor to cisplatin resistance in biliary tract cancer, independently of its interaction with ZEB1.
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Affiliation(s)
- Florian Posch
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
| | - Felix Prinz
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
- Research Unit “Non-Coding RNAs and Genome Editing in Cancer”, Division of Oncology, Medical University of Graz, 8036 Graz, Austria
| | - Amar Balihodzic
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
- Research Unit “Non-Coding RNAs and Genome Editing in Cancer”, Division of Oncology, Medical University of Graz, 8036 Graz, Austria
| | - Christian Mayr
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (C.M.); (T.K.)
- Department of Internal Medicine I, University Clinics Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria
| | - Tobias Kiesslich
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (C.M.); (T.K.)
- Department of Internal Medicine I, University Clinics Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria
| | - Christiane Klec
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
- Research Unit “Non-Coding RNAs and Genome Editing in Cancer”, Division of Oncology, Medical University of Graz, 8036 Graz, Austria
| | - Katharina Jonas
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
- Research Unit “Non-Coding RNAs and Genome Editing in Cancer”, Division of Oncology, Medical University of Graz, 8036 Graz, Austria
| | - Dominik A. Barth
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
- Research Unit “Non-Coding RNAs and Genome Editing in Cancer”, Division of Oncology, Medical University of Graz, 8036 Graz, Austria
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jakob M. Riedl
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
| | - Armin Gerger
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
| | - Martin Pichler
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (F.P.); (F.P.); (A.B.); (C.K.); (K.J.); (D.A.B.); (J.M.R.); (A.G.)
- Research Unit “Non-Coding RNAs and Genome Editing in Cancer”, Division of Oncology, Medical University of Graz, 8036 Graz, Austria
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Correspondence:
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25
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Comment on "Meta-analysis and Meta-regression of Survival after Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma". Ann Surg 2021; 274:e920-e921. [PMID: 34171876 DOI: 10.1097/sla.0000000000005016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Nara S, Esaki M, Ban D, Takamoto T, Mizui T, Shimada K. Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer. Expert Rev Gastroenterol Hepatol 2021; 15:537-545. [PMID: 33793366 DOI: 10.1080/17474124.2021.1911645] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 03/30/2021] [Indexed: 12/13/2022]
Abstract
Introduction: Although the safety of biliary tract cancer resection has improved over the years, the recurrence rate is still high, and the postoperative prognosis remains low after biliary tract cancer resection. Therefore, the development of effective adjuvant therapy is essential to improve treatment outcomes. Because biliary tract cancer is rare compared with other gastrointestinal cancers, there have been only a small number of clinical trials of adjuvant therapy. However, in recent years, the results of several large-scale randomized controlled trials have been published, and clinical trials investigating the efficacy of new regimens are currently ongoing.Areas covered: This review presents the results of previously published important phase II and III clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and discusses their interpretation. The future direction of new research on resectable biliary tract cancer treatment is also discussed.Expert opinion: The foundations of large-scale clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer are underway, and new trials will establish evidence of their effectiveness. Additionally, breakthroughs in treatment through genetic and molecular research are expected.
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Affiliation(s)
- Satoshi Nara
- 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
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Takamoto
- 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
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
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Reames BN, Rocha FG. Early Recurrence Following Resection of Distal Cholangiocarcinoma: A New Tool for the Toolbox. Ann Surg Oncol 2021; 28:4069-4071. [PMID: 33830359 DOI: 10.1245/s10434-021-09961-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 01/17/2023]
Affiliation(s)
- Bradley N Reames
- Division of Surgical Oncology, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Flavio G Rocha
- Division of Surgical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA
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Affiliation(s)
- Hideo Kunitoh
- Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan
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