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Takamoto T, Mihara Y, Nishioka Y, Ichida A, Kawaguchi Y, Akamatsu N, Hasegawa K. Surgical treatment for hepatocellular carcinoma in era of multidisciplinary strategies. Int J Clin Oncol 2025; 30:417-426. [PMID: 39907863 PMCID: PMC11842484 DOI: 10.1007/s10147-025-02703-7] [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: 12/01/2024] [Accepted: 01/07/2025] [Indexed: 02/06/2025]
Abstract
Hepatocellular carcinoma (HCC) remains a significant global health challenge, with over 800,000 new cases diagnosed annually. This comprehensive review examines current surgical approaches and emerging multidisciplinary strategies in HCC treatment. While traditional surgical criteria, such as the Barcelona Clinic Liver Cancer (BCLC) staging system, have been relatively conservative, recent evidence from high-volume Asian centers supports more aggressive surgical approaches in carefully selected patients. The review discusses the evolution of selection criteria, including the new "Borderline Resectable HCC" classification system, which provides more explicit guidance for surgical decision-making. Technical innovations have significantly enhanced surgical precision, including three-dimensional simulation, intraoperative navigation systems, and the advancement of minimally invasive approaches. The review evaluates the ongoing debate between anatomical versus non-anatomical resection and examines the emerging role of robotic surgery. In liver transplantation, expanded criteria beyond the Milan criteria show promising outcomes, while the integration of novel biomarkers and imaging techniques improves patient selection. The role of preoperative and adjuvant therapies is increasingly important, with recent trials demonstrating the potential of immune checkpoint inhibitors combined with anti-VEGF agents in both settings. Despite these advances, postoperative recurrence remains a significant challenge. The review concludes that successful HCC treatment requires a personalized approach, integrating surgical expertise with emerging technologies and systemic therapies while considering individual patient factors and regional variations in practice patterns.
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Affiliation(s)
- Takeshi Takamoto
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuichirou Mihara
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yujirou Nishioka
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Akihiko Ichida
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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Zhu J, Chu C, Li D, Zhang Y, Cheng Y, Lin H, Wang X, Liu J, Pang X, Cheng J, Liu G. Superior Fluorescent Nanoemulsion Illuminates Hepatocellular Carcinoma for Surgical Navigation. Front Bioeng Biotechnol 2022; 10:890668. [PMID: 35547157 PMCID: PMC9081524 DOI: 10.3389/fbioe.2022.890668] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/08/2022] [Indexed: 01/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, poses a severe threat to public health. Intraoperative fluorescence imaging provides a golden opportunity for surgeons to visualize tumor-involved margins, thereby implementing precise HCC resection with minimal damage to normal tissues. Here, a novel-acting contrast agent, which facilely bridges indocyanine green (ICG) and lipiodol using self-emulsifying nanotechnology, was developed for optical surgical navigation. Compared to clinically available ICG probe, our prepared nanoemulsion showed obviously red-shifted optical absorption and enhanced fluorescence intensity. Further benefiting from the shielding effect of lipiodol, the fluorescence stability and anti-photobleaching ability of nanoemulsion were highly improved, indicating a great capacity for long-lasting in vivo intraoperative imaging. Under the fluorescence guidance of nanoemulsion, the tumor tissues were clearly delineated with a signal-to-noise ratio above 5-fold, and then underwent a complete surgical resection from orthotopic HCC-bearing mice. Such superior fluorescence performances, ultrahigh tumor-to-liver contrast, as well as great bio-safety, warrants the great translational potential of nanoemulsion in precise HCC imaging and intraoperative navigation.
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Affiliation(s)
- Jing Zhu
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Chengchao Chu
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Dongsheng Li
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Yang Zhang
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Yi Cheng
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Huirong Lin
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Xiaoyong Wang
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Junxian Liu
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Xin Pang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Jingliang Cheng
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Gang Liu
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Hojo A, Nakayama H, Okamura Y, Higaki T, Moriguchi M, Aramaki O, Yamazaki S, Takayama T. Evaluation of Safety-Related Outcomes of One-Segment and More-Than-One-Segment High-Level Hepatectomy in Hepatocellular Carcinoma Based on the Japanese Board Certification System. World J Surg 2022; 46:1141-1150. [PMID: 35152323 PMCID: PMC8971149 DOI: 10.1007/s00268-022-06467-3] [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] [Accepted: 01/11/2022] [Indexed: 11/03/2022]
Abstract
Abstract
Background
We evaluated the impact of the Japanese board certification system for expert surgeons (JBCSES) on complications and survival outcomes in hepatectomy for hepatocellular carcinoma.
Methods
The postoperative outcomes of 493 patients who underwent high-level liver surgery involving one-segment (OSeg) hepatectomy and more-than-one-segment (MOSeg) resection were compared before and after JBCSES establishment. After the establishment of the JBCSES, the patients’ postoperative outcomes were compared using propensity score matching (PSM) to determine the influence of expert surgeons.
Results
The establishment of the JBCSES was associated with a decrease in the overall postoperative complication rates after high-level liver surgery from 50.2 to 38.1% (P = 0.008) and a decrease in Clavien–Dindo class ≥ IIIb complications from 10.2 to 5.0% (P = 0.035). The 90-day mortality rate decreased from 5.1 to 0.7% (P = 0.003), and the 5-year survival rate increased from 51.4 to 63.9% (P = 0.009). Using PSM, a comparison of OSeg hepatectomies that involved expert surgeons (n = 48) and those that did not (n = 48) showed significantly lower intraoperative blood loss in surgeries involving an expert surgeon (mean, 340 vs. 473 mL; P = 0.033). There were no significant differences in complication rates or long-term prognosis between these groups. A comparison of MOSeg hepatectomies that involved expert surgeons (n = 26) and those that did not (n = 26) showed no significant difference in surgical factors, complications, or overall survival between the two groups.
Conclusions
After establishment of the JBCSES, postoperative complication rates and mortality rates decreased and survival rates increased following liver surgery. Expert surgeon participation significantly decreased intraoperative blood loss during OSeg hepatectomies.
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Zhang S, Han Y, Zhu X, Shang S, Huang G, Zhang L, Niu G, Wang S, He X, Wan M. Feasibility of Using Ultrasonic Nakagami Imaging for Monitoring Microwave-Induced Thermal Lesion in Ex Vivo Porcine Liver. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:482-493. [PMID: 27894833 DOI: 10.1016/j.ultrasmedbio.2016.10.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 10/05/2016] [Accepted: 10/13/2016] [Indexed: 06/06/2023]
Abstract
The feasibility of using ultrasonic Nakagami imaging to evaluate thermal lesions induced by microwave ablation (MWA) in ex vivo porcine liver was explored. Dynamic changes in echo amplitudes and Nakagami parameters in the region of the MWA-induced thermal lesion, as well as the contrast-to-noise ratio (CNR) between the MWA-induced thermal lesion and the surrounding normal tissue, were calculated simultaneously during the MWA procedure. After MWA exposure, a bright hyper-echoic region appeared in ultrasonic B-mode and Nakagami parameter images as an indicator of the thermal lesion. Mean values of the Nakagami parameter in the thermal lesion region increased to 0.58, 0.71 and 0.91 after 1, 3 and 5 min of MVA. There were no significant differences in envelope amplitudes in the thermal lesion region among ultrasonic B-mode images obtained after different durations of MWA. Unlike ultrasonic B-mode images, Nakagami images were less affected by the shadow effect in monitoring of MWA exposure, and a fairly complete hyper-echoic region was observed in the Nakagami image. The mean value of the Nakagami parameter increased from approximately 0.47 to 0.82 during MWA exposure. At the end of the postablation stage, the mean value of the Nakagami parameter decreased to 0.55 and was higher than that before MWA exposure. CNR values calculated for Nakagami parameter images increased from 0.13 to approximately 0.61 during MWA and then decreased to 0.26 at the end of the post-ablation stage. The corresponding CNR values calculated for ultrasonic B-mode images were 0.24, 0.42 and 0.17. This preliminary study on ex vivo porcine liver suggested that Nakagami imaging have potential use in evaluating the formation of MWA-induced thermal lesions. Further in vivo studies are needed to evaluate the potential application.
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Affiliation(s)
- Siyuan Zhang
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Yuqiang Han
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Xingguang Zhu
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Shaoqiang Shang
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Guojing Huang
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Lei Zhang
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Gang Niu
- Department of Radiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Supin Wang
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Xijing He
- Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mingxi Wan
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
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Impact of Glissonean pedicle approach for centrally located hepatocellular carcinoma in mongolia. Int Surg 2016; 100:268-74. [PMID: 25692429 DOI: 10.9738/intsurg-d-14-00006.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Approaches to surgical resection of centrally located HCC remain controversial. Traditionally, hemi- or extended hepatectomy is suggested. However, it carries a high risk of postoperative complications in patients with cirrhosis. An alternative approach is Glissonean pedicle transection method. This study was conducted to assess the surgical and survival outcomes associated with central liver resection using the Glissonean pedicle transection. Sixty-nine patients with centrally located HCC were studied retrospectively. They were divided into conventional approach group with hemi- or extended hepatectomy, and Glissonean approach group with multisegmental central liver resection using the Glissonean pedicle transection. Glissonean pedicle transection method has comparable or superior surgical and survival outcomes to conventional hemi- or extended hepatectomy with regard to intraoperative bleeding, complications, hospital stay, and postoperative mortality and survival outcomes in patients with centrally located HCC. The 1-, 3-, and 5-year overall survival rates of the conventional approach group were 74%, 64%, and 55% respectively. For the Glissonean approach group, the 1 and 3-year overall survival rates were 86% and 61%, respectively. Glissonean pedicle transection method is a safe and effective surgical procedure in patients with centrally located HCC.
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Slotta JE, Kollmar O, Ellenrieder V, Ghadimi BM, Homayounfar K. Hepatocellular carcinoma: Surgeon's view on latest findings and future perspectives. World J Hepatol 2015; 7:1168-1183. [PMID: 26019733 PMCID: PMC4438492 DOI: 10.4254/wjh.v7.i9.1168] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 11/14/2014] [Accepted: 03/20/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver-derived malignancy with a high fatality rate. Risk factors for the development of HCC have been identified and are clearly described. However, due to the lack of tumor-specific symptoms, HCC are diagnosed at progressed tumor stages in most patients, and thus curative therapeutic options are limited. The focus of this review is on surgical therapeutic options which can be offered to patients with HCC with special regard to recent findings, not exclusively focused on surgical therapy, but also to other treatment modalities. Further, potential promising future perspectives for the treatment of HCC are discussed.
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Preoperative serum liver enzyme markers for predicting early recurrence after curative resection of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2015; 14:178-85. [PMID: 25865691 DOI: 10.1016/s1499-3872(15)60353-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Early recurrence of hepatocellular carcinoma (HCC) is associated with worse prognosis after liver resection. This study aimed to investigate the prognostic value of common liver enzyme markers in HCC early recurrence after curative hepatectomy and to establish a simple predictive model for HCC early recurrence. METHODS A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence (within 2 years) and non-early recurrence groups. Demographical characteristics, preoperative liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statistical significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase (LDH>206 U/L, HR=1.711, P=0.006), high aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT>0.96, HR=1.769, P=0.006), elevated alpha-fetoprotein (AFP<8.6 ng/mL, HR=2.079, P=0.007), small resection margin (≤1 cm, HR=2.354, P<0.001) and advanced TNM stage (TNM III-IV, HR=2.164, P<0.001) were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively (area under curve=0.741, 95% CI 0.674-0.800, P<0.0001). CONCLUSIONS Preoperative common liver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage better predicted early recurrence of HCC after curative resection in a simple multi-factor model.
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Hoang NH, Murad HY, Ratnayaka SH, Chen C, Khismatullin DB. Synergistic ablation of liver tissue and liver cancer cells with high-intensity focused ultrasound and ethanol. ULTRASOUND IN MEDICINE & BIOLOGY 2014; 40:1869-1881. [PMID: 24798386 DOI: 10.1016/j.ultrasmedbio.2014.02.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Revised: 02/03/2014] [Accepted: 02/20/2014] [Indexed: 06/03/2023]
Abstract
We investigated the combined effect of ethanol and high-intensity focused ultrasound (HIFU), first, on heating and cavitation bubble activity in tissue-mimicking phantoms and porcine liver tissues and, second, on the viability of HepG2 liver cancer cells. Phantoms or porcine tissues were injected with ethanol and then subjected to HIFU at acoustic power ranging from 1.2 to 20.5 W (HIFU levels 1-7). Cavitation events and the temperature around the focal zone were measured with a passive cavitation detector and embedded type K thermocouples, respectively. HepG2 cells were subjected to 4% ethanol solution in growth medium (v/v) just before the cells were exposed to HIFU at 2.7, 8.7 or 12.0 W for 30 s. Cell viability was measured 2, 24 and 72 h post-treatment. The results indicate that ethanol and HIFU have a synergistic effect on liver cancer ablation as manifested by greater temperature rise and lesion volume in liver tissues and reduced viability of liver cancer cells. This effect is likely caused by reduction of the cavitation threshold in the presence of ethanol and the increased rate of ethanol diffusion through the cell membrane caused by HIFU-induced streaming, sonoporation and heating.
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Affiliation(s)
- Nguyen H Hoang
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA
| | - Hakm Y Murad
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA
| | - Sithira H Ratnayaka
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA
| | - Chong Chen
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA
| | - Damir B Khismatullin
- Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.
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9
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Du ZG, Wei YG, Chen KF, Li B. Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients. Hepatobiliary Pancreat Dis Int 2014; 13:153-61. [PMID: 24686542 DOI: 10.1016/s1499-3872(14)60025-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection. METHODS A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence, and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS The cumulative recurrence-free survival rates at 1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and 28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase (before 2 years; n=164) and late phase (after 2 years; n=83). Cox's multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration (P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15 minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status (P=0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1 of the 2 early recurrence risk factors (multiplicity of tumors ≥ 2 and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6, respectively). CONCLUSIONS Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.
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Affiliation(s)
- Zheng-Gui Du
- Department of Liver and Vascular Surgery, Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China.
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Kyuno D, Kimura Y, Imamura M, Uchiyama M, Ishii M, Meguro M, Kawamoto M, Mizuguchi T, Hirata K. Pancreaticoduodenectomy for biliary tract carcinoma with situs inversus totalis: difficulties and technical notes based on two cases. World J Surg Oncol 2013; 11:312. [PMID: 24341840 PMCID: PMC3878620 DOI: 10.1186/1477-7819-11-312] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Accepted: 12/07/2013] [Indexed: 12/16/2022] Open
Abstract
Situs inversus totalis (SIT) denotes complete right-left inversion of the thoracic and abdominal viscera. Diagnosis and surgical procedures for abdominal pathology in patients with SIT are technically more complicated because of mirror-image transposition of the visceral organs. Moreover, SIT is commonly associated with cardiovascular and hepatobiliary malformations, which make hepatobiliary-pancreatic surgery difficult. Two cases of pancreaticoduodenectomy for biliary tract carcinoma in patients with SIT are presented. Both patients had an anomaly of the hepatic artery. Advanced diagnostic imaging techniques were very important for careful preoperative planning and to prevent misunderstanding of the arrangement of the abdominal viscera. This facilitated the surgical team's adaptation to the mirror image of the standard procedure and helped avoid intraoperative complications due to cardiovascular and hepatobiliary malformations associated with SIT. Pancreaticoduodenectomy in patients with SIT can be performed successfully with detailed preoperative assessment, use of effective techniques by the surgeon, and appropriate support by assistants.
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Affiliation(s)
- Daisuke Kyuno
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Yasutoshi Kimura
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Masafumi Imamura
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Motonobu Uchiyama
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Masayuki Ishii
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Makoto Meguro
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Masaki Kawamoto
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Toru Mizuguchi
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
| | - Koichi Hirata
- Departments of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 1-South, 16-West, Chuo-ku, Sapporo 060-8543, Japan
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Norsa'adah B, Nurhazalini-Zayani CGC. Epidemiology and Survival of Hepatocellular Carcinoma in North-east Peninsular Malaysia. Asian Pac J Cancer Prev 2013; 14:6955-9. [DOI: 10.7314/apjcp.2013.14.11.6955] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Loyer P, Bedhouche W, Huang ZW, Cammas-Marion S. Degradable and biocompatible nanoparticles decorated with cyclic RGD peptide for efficient drug delivery to hepatoma cells in vitro. Int J Pharm 2013; 454:727-37. [PMID: 23747504 DOI: 10.1016/j.ijpharm.2013.05.060] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Revised: 05/27/2013] [Accepted: 05/29/2013] [Indexed: 12/21/2022]
Abstract
Amphiphilic derivatives of poly(benzyl malate) were synthesized and characterized with the aim of being used as degradable and biocompatible building blocks for the design of functional nanoparticles (NPs). An anti-cancer model drug, doxorubicin, has been successfully encapsulated into the prepared NPs and its release profile has been evaluated in water and in culture medium. NPs bearing biotin molecules were prepared either for site-specific drug delivery via the targeting of biotin receptors overexpressed on the surface of several cancer cells, or for grafting biotinylated cyclic RGD peptide onto their surface using the strong and highly specific interactions between biotin and the streptavidin protein. We have shown that this binding did not affect dramatically the physico-chemical properties of the corresponding NPs. Cyclic RGD grafted fluorescent NPs were more efficiently uptaken by the HepaRG hepatoma cells than biotinylated fluorescent NPs. Furthermore, the targeting of HepaRG hepatoma cells with NPs bearing cyclic RGD was very efficient and much weaker for HeLa and HT29 cell lines confirming that cyclic RGD is a suitable targeting agent for liver cells. Our results also provide a new mean for rapid screening of short hepatotropic peptides in order to design NPs showing specific liver targeting properties.
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Affiliation(s)
- Pascal Loyer
- Inserm UMR S-991, Foie, Métabolismes et Cancer, Université de Rennes 1, Fédération de Recherche de Rennes Biosit, CHU Rennes, 35033 Rennes, France
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Mizuguchi T, Kawamoto M, Meguro M, Nakamura Y, Ota S, Hui TT, Hirata K. Prognosis and predictors of surgical complications in hepatocellular carcinoma patients with or without cirrhosis after hepatectomy. World J Surg 2013; 37:1379-1387. [PMID: 23479099 DOI: 10.1007/s00268-013-1989-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although poor liver function is associated with a high morbidity rate and poor prognosis in hepatocellular carcinoma (HCC) patients, the exact effects of liver pathology on the surgical outcomes of HCC patients are poorly understood. The purpose of this study was to assess how the liver pathology of HCC patients affects their prognosis and complications rate after liver resection. METHODS Between January 2006 and November 2010, 149 consecutive hepatocellular carcinoma patients, including 79 noncirrhosis patients and 70 cirrhosis patients, were enrolled in this study. RESULTS Among the noncirrhotic patients, operative time, fresh frozen plasma (FFP) transfusion requirement, tumor size, and serum retinol binding protein (RBP) levels were significantly higher in the complications group than in the complications-free groups. On the other hand, in the cirrhotic patients the prothrombin time (PT) and indocyanine green retention value at 15 min (ICGR15) of the complications group were significantly lower and higher, respectively, than those of the complications-free group. In the noncirrhotic patients, recurrence-free survival and overall survival did not differ between the complications and complications-free groups. On the other hand, in the cirrhotic patients, the recurrence-free survival and overall survival of the complications-free group were significantly longer than those of the complications group. CONCLUSIONS In the noncirrhotic patients, surgical complications had no prognostic effect, whereas they had a significant survival impact in the cirrhotic patients. The surgical strategy for HCC should be based on the patient's pathological background.
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Affiliation(s)
- Toru Mizuguchi
- Department of Surgery I, Sapporo Medical University Hospital, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, Hokkaido, 060-8543, Japan.
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Tanaka M, Masaki Y, Tanaka K, Miyazaki M, Kato M, Sugimoto R, Nakamura K, Aishima S, Shirabe K, Nakamuta M, Enjoji M, Kotoh K, Takayanagi R. Reduction of fatty acid oxidation and responses to hypoxia correlate with the progression of de-differentiation in HCC. Mol Med Rep 2013; 7:365-70. [PMID: 23178736 DOI: 10.3892/mmr.2012.1201] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Accepted: 11/16/2012] [Indexed: 12/16/2022] Open
Abstract
The prognosis of patients with hepatocellular carcinoma (HCC) may be improved by novel treatments focusing on the characteristic metabolic changes of this disease. Therefore, we analyzed the biological interactions of metabolic features with the degree of tumor differentiation and the level of malignant potential in 41 patients with completely resectable HCC. The expression levels in resected samples of mRNAs encoded by genes related to tumor metabolism and metastasis were investigated, and the correlation between these expression levels and degrees of differentiation was analyzed. Of the 41 patients, 2 patients had grade I, 27 had grade II, and 12 had grade III tumors. Reductions in the levels of 3-hydroxyacyl-CoA dehydrogenase (HADHA) and acyl-CoA oxidase (ACOX)-2 mRNAs, and increases in pyruvate kinase isoenzyme type M2 (PKM2) mRNA were significantly correlated with the progression of de-differentiation. Analysis of partial correlation coefficients showed that the level of PKM2 mRNA expression was significantly correlated with those of pro-angiogenic genes, vascular endothelial growth factor (VEGF) and ETS-1. Moreover, the levels of VEGF-A and ETS-1 mRNA expression were independently correlated with that of the epithelial-mesenchymal transition (EMT)‑related gene SNAIL. These findings suggest that reductions in fatty acid oxidation and responses to hypoxia may affect the progression of malignant phenotypes in HCC.
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Affiliation(s)
- Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
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15
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Expression of partitioning defective 3 (Par-3) for predicting extrahepatic metastasis and survival with hepatocellular carcinoma. Int J Mol Sci 2013; 14:1684-97. [PMID: 23322019 PMCID: PMC3565341 DOI: 10.3390/ijms14011684] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 01/04/2013] [Accepted: 01/06/2013] [Indexed: 01/05/2023] Open
Abstract
Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent risk factor of extrahepatic metastasis. Increased Par-3 expression in primary tumors was associated with poor five-year overall survival rates and was an independent prognostic factor on Cox regression analysis. In conclusion, we show for the first time that increased Par-3 expression is associated with distant metastasis and poor survival rates in patients with HCC. Par-3 may be a novel prognostic biomarker and therapeutic target for HCC.
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16
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Haga Y, Ikejiri K, Takeuchi H, Ikenaga M, Wada Y. Value of general surgical risk models for predicting postoperative liver failure and mortality following liver surgery. J Surg Oncol 2012; 106:898-904. [PMID: 22605669 DOI: 10.1002/jso.23160] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2012] [Accepted: 04/25/2012] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND OBJECTIVES This study evaluated the ability of general surgical models to predict postoperative morbidity and mortality in liver surgery. METHODS The postoperative course and mortality rates predicted by general surgical models were investigated in 960 patients who underwent hepatectomy or ablation therapy for primary or metastatic liver carcinoma. RESULTS The area under the receiver operative characteristic curve (95% confidence intervals) for detecting postoperative liver failure was 0.89 (0.84-0.94), 0.85 (0.78-0.92), and 0.78 (0.72-0.85) for the estimation of physiologic ability and surgical stress (E-PASS) model, the modified E-PASS (mE-PASS) model, and the Portsmouth Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) model, respectively, and those for detecting in-hospital mortality were 0.85 (0.76-0.93), 0.85 (0.78-0.92), and 0.79 (0.71-0.87), respectively. Nevertheless, all of the models overpredicted the overall mortality rate (by 2.3-fold for E-PASS, 2.3-fold for mE-PASS, and 2.9-fold for P-POSSUM). CONCLUSIONS The general surgical risk models demonstrated high discriminatory power for predicting postoperative outcomes in liver surgery, but overpredicted the overall mortality rate by more than twofold. Therefore, these models should be refined to make them more suitable for predicting liver surgery outcomes.
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Affiliation(s)
- Yoshio Haga
- Institute for Clinical Research, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
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17
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Hepatic resection using a liver-hanging maneuver and Glissonean pedicle transection for hepatocellular carcinoma in a patient with situs inversus totalis: report of a case. Surg Today 2012; 42:801-4. [PMID: 22391979 DOI: 10.1007/s00595-012-0156-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2011] [Accepted: 07/15/2011] [Indexed: 12/27/2022]
Abstract
Situs inversus totalis is a rare congenital anomaly in which the major abdominal organs are located as a mirror image of their normal positions. This poses much difficulty for surgeons. We describe how we performed the liver-hanging maneuver (LHM) for hepatocellular carcinoma (HCC) in a 59-year-old man with situs inversus totalis, to resolve the difficulty of the mirror-image location of his liver. The HCC was located in the right lateral sector. Although segmentectomy of segment 7 would normally be considered minimal for a curative treatment of HCC, this was relatively complicated in this patient. Thus, we performed an extended right lateral sectionectomy using the LHM to achieve a simple transection. The hepatic hilum was dissected using the Glissonean pedicle transection method. The operation time and intraoperative blood loss were 6 h 45 min and 471 ml, respectively. No blood product transfusion was required. The LHM and the hilar Glissonean pedicle approach proved effective for resolving the difficulties of performing surgery in a mirror image for HCC in a patient with situs inversus totalis.
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18
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Zero mortality in more than 300 hepatic resections: validity of preoperative volumetric analysis. Surg Today 2011; 42:435-40. [PMID: 22200757 DOI: 10.1007/s00595-011-0108-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Accepted: 04/20/2011] [Indexed: 02/07/2023]
Abstract
PURPOSE We reviewed a series of patients who underwent hepatic resection at our institution, to investigate the risk factors for postoperative complications after hepatic resection of liver tumors and for procurement of living donor liver transplantation (LDLT) grafts. METHODS Between April 2004 and August 2007, we performed 304 hepatic resections for liver tumors or to procure grafts for LDLT. Preoperative volumetric analysis was done using 3-dimensional computed tomography (3D-CT) prior to major hepatic resection. We compared the clinicopathological factors between patients with and without postoperative complications. RESULTS There was no operative mortality. According to the 3D-CT volumetry, the mean error ratio between the actual and the estimated remnant liver volume was 13.4%. Postoperative complications developed in 96 (31.6%) patients. According to logistic regression analysis, histological liver cirrhosis and intraoperative blood loss >850 mL were significant risk factors of postoperative complications after hepatic resection. CONCLUSIONS Meticulous preoperative evaluation based on volumetric analysis, together with sophisticated surgical techniques, achieved zero mortality and minimized intraoperative blood loss, which was classified as one of the most significant predictors of postoperative complications after major hepatic resection.
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Sumiyoshi T, Moriguchi M, Kanemoto H, Asakura K, Sasaki K, Sugiura T, Mizuno T, Uesaka K. Liver-specific contrast agent-enhanced magnetic resonance and ¹⁸F-fluorodeoxyglucose positron emission tomography findings of hepatocellular adenoma: report of a case. Surg Today 2011; 42:200-4. [PMID: 22160355 DOI: 10.1007/s00595-011-0067-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2010] [Accepted: 02/27/2011] [Indexed: 02/07/2023]
Abstract
We report a case of hepatocellular adenoma, focusing on the findings of liver-specific contrast agent-enhanced magnetic resonance imaging (MRI) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). The patient was a 37-year-old woman, referred to us after contrast-enhanced computed tomography showed a homogeneous, poorly enhanced liver tumor, 2.8 cm in diameter. Magnetic resonance imaging showed a liver mass with significant fatty change. The tumor increased in size to 3.3 cm over 9 months of follow-up. Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced MRI revealed spotty enhancement in the hypointense tumor in the hepatobiliary phase. Subsequent FDG-PET showed increased uptake of FDG (maximum standardized uptake value 5.0), which suggested the possibility of malignancy. The patient underwent partial hepatectomy, and histological examination of the resected specimen revealed a tumor composed of hepatocyte-like cells with minimal cellular atypia and significant diffuse fatty change. Based on these findings, we diagnosed hepatocellular adenoma.
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Affiliation(s)
- Tatsuaki Sumiyoshi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007 Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.
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20
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Intra-hepatic arterioportal shunt mimicking a metastatic liver tumor: report of a case. Surg Today 2011; 42:391-4. [PMID: 22143359 DOI: 10.1007/s00595-011-0079-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Accepted: 03/28/2011] [Indexed: 10/15/2022]
Abstract
The differential diagnosis of an arterioportal shunt (APS) is difficult and important. We report a case of an intra-hepatic APS mimicking a metastatic liver tumor on imaging scans in a patient without hepatic cirrhosis. The patient was a 64-year-old woman, who had undergone low anterior resection of the rectum for advanced rectal cancer, followed 2 months later by right hemihepatectomy, including the middle hepatic vein, for a synchronous metastatic liver tumor. About 2 years after the hepatectomy, a follow-up CT scan showed a new mass in the remnant liver, suggestive of a metastatic liver tumor, the assumption of which was further supported by an elevated serum carcinoembryonic antigen (CEA) level. However, the findings of magnetic resonance imaging were not consistent with a malignant tumor, and Doppler ultrasonography showed a low echoic area connected with the portal vein branch and the hepatic artery branch. Thus, we diagnosed intra-hepatic APS. The patient remains well without signs of growth of the hepatic lesion, although with fluctuating serum CEA levels.
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21
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Clinical impact of lymph node dissection in surgery for peripheral-type intrahepatic cholangiocarcinoma. Surg Today 2011; 42:147-51. [PMID: 22124809 DOI: 10.1007/s00595-011-0057-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Accepted: 02/07/2011] [Indexed: 12/16/2022]
Abstract
PURPOSE To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations. METHODS Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis. RESULTS Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups. CONCLUSIONS Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given.
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Imura S, Shimada M, Utsunomiya T, Morine Y, Ikemoto T, Mori H, Hanaoka J, Iwahashi S, Saito Y, Miyake H. Ultrasound-guided microwave coagulation assists anatomical hepatic resection. Surg Today 2011; 42:35-40. [PMID: 22075665 DOI: 10.1007/s00595-011-0006-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2010] [Accepted: 11/08/2010] [Indexed: 12/18/2022]
Abstract
PURPOSE We describe a new technique of ultrasound (US)-guided microwave coagulation (MC) of the Glissonean pedicle, performed before transection to control the inflow and select the resection area. This report introduces our procedure and evaluates the outcomes of patients treated using this technique. METHODS The Glissonean pedicles feeding the segment or cone unit were coagulated by US-guided MC, after which transection was performed. We used this US-guided MC technique to perform anatomical resections in 12 patients with hepatocellular carcinoma (MC group). We compared the outcomes of this group with those of a historical group of 10 patients who underwent conventional hepatectomy (control group). The two groups were well matched for age, tumor size, location, and type of hepatectomy. RESULTS The mean operative times were similar, but the mean blood loss was significantly lower the in MC group than in the control group. Recurrence developed in four patients from the MC group, but local recurrence was not observed. Bile leakage occurred in one patient from the MC group, but the incidences of postoperative complications did not differ between the groups. CONCLUSIONS Our procedure allows anatomical resection to be performed safely and easily, and helps prevent intrahepatic metastasis via portal flow during the transection.
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Affiliation(s)
- Satoru Imura
- Department of Surgery, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
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Taketomi A, Takeishi K, Mano Y, Toshima T, Motomura T, Aishima S, Uchiyama H, Yoshizumi T, Shirabe K, Maehara Y. Total resection of the right hepatic vein drainage area with the aid of three-dimensional computed tomography. Surg Today 2011; 42:46-51. [PMID: 22072147 DOI: 10.1007/s00595-011-0021-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2010] [Accepted: 01/11/2011] [Indexed: 02/07/2023]
Abstract
PURPOSE We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR-RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. METHODS Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). RESULTS The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. CONCLUSIONS THR-RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV.
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Affiliation(s)
- Akinobu Taketomi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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Liu TA, Jan YJ, Ko BS, Chen SC, Liang SM, Hung YL, Hsu C, Shen TL, Lee YM, Chen PF, Wang J, Shyue SK, Liou JY. Increased expression of 14-3-3β promotes tumor progression and predicts extrahepatic metastasis and worse survival in hepatocellular carcinoma. THE AMERICAN JOURNAL OF PATHOLOGY 2011; 179:2698-708. [PMID: 21967815 DOI: 10.1016/j.ajpath.2011.08.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2011] [Revised: 07/20/2011] [Accepted: 08/11/2011] [Indexed: 01/06/2023]
Abstract
14-3-3β is implicated in cell survival, proliferation, migration, and tumor growth; however, its clinical relevance in tumor progression and metastasis have never been elucidated. To evaluate the clinical significance of 14-3-3β, we analyzed the association of 14-3-3β expression and clinicopathologic characteristics in primary and subsequent metastatic tumors of hepatocellular carcinoma patients. 14-3-3β was expressed abundantly in 40 of 55 (70.7%) primary tumors. Increased 14-3-3β expression in primary tumors predicted a higher 5-year cumulative incidence of subsequent extrahepatic metastasis, and multivariate analysis revealed 14-3-3β overexpression was an independent risk factor for extrahepatic metastasis. Patients with increased 14-3-3β expression in primary tumors had worse 5-year overall survival rates, and 14-3-3β overexpression was an independent prognostic factor on Cox regression analysis. Furthermore, stably overexpressed 14-3-3β enhanced hepatocellular carcinoma cell migration and proliferation and increased anchorage-independent cell growth. In addition, in vivo study in a nude-mice model showed tumor formation significantly increased with 14-3-3β overexpression. In conclusion, this is the first report to show that increased 14-3-3β expression is associated with subsequent extrahepatic metastasis and worse survival rates, as well as cancer progression of hepatocellular carcinoma. Thus, 14-3-3β may be a novel prognostic biomarker and therapeutic target in hepatocellular carcinoma.
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Affiliation(s)
- Tzu-An Liu
- Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan
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Long-term survival after resection of mass-forming type intrahepatic cholangiocarcinoma directly infiltrating the transverse colon and sequential brain metastasis: Report of a case. Surg Today 2011; 41:1410-3. [DOI: 10.1007/s00595-010-4500-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2010] [Accepted: 06/21/2010] [Indexed: 11/27/2022]
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Toiyama Y, Inoue Y, Yasuda H, Yoshiyama S, Araki T, Miki C, Kusunoki M. Hepatocellular adenoma containing hepatocellular carcinoma in a male patient with familial adenomatous polyposis coli: Report of a case. Surg Today 2011; 41:1442-6. [PMID: 21922375 DOI: 10.1007/s00595-010-4451-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2010] [Accepted: 10/20/2010] [Indexed: 01/13/2023]
Abstract
Hepatocellular adenoma (HCA) is a benign condition occurring most frequently in young women using oral contraceptives. We herein report the first case of a 28-year-old man with familial adenomatous polyposis (FAP) who experienced hepatocellular carcinoma (HCC) within HCA. A preoperative computed tomography scan of the abdomen disclosed a tumor measuring 5.8 cm in diameter in the left lobe of the liver. A total proctocolectomy with construction of a linear stapled J-pouch, a hand-sewn ileoanal anastomosis and a liver tumor resection were performed. The pathology of the resected specimen confirmed the diagnosis of HCA containing HCC. Five cases of HCA have been reported that developed in patients with FAP, but this is the first case of HCA containing HCC. Hepatocellular adenomas occur due to the inactivation of hepatic nuclear factor 1α, but the mechanism underlying the malignant transformation from HCA to HCC could not be identified in this case.
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Affiliation(s)
- Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
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27
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Pelioid-type well-differentiated hepatocellular carcinoma in a patient with a history of taking oral contraceptives: Report of a case. Surg Today 2011; 41:1270-4. [DOI: 10.1007/s00595-010-4465-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2010] [Accepted: 06/13/2010] [Indexed: 12/18/2022]
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Inoue Y, Hayashi M, Katsumata T, Shibayama Y, Tanigawa N. Hepatocellular carcinoma with right atrial tumor thrombus: report of a case. Surg Today 2011; 41:1122-9. [PMID: 21773904 DOI: 10.1007/s00595-010-4443-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2010] [Accepted: 05/12/2010] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) with a tumor thrombus (TT) extending into the right atrium is generally regarded as a terminal-stage condition. We report a case of long-term survival following treatment of this complication with en bloc hepatectomy and resection of the thrombus under cardiopulmonary bypass. Our review of 19 similar cases reported in the literature found the following: that lung metastasis, the most critical prognostic factor, occurred in only 5 (27.8%) patients; that postoperative survival ranged from 18 days to 56 months, with a median survival of 11 months; and that 7 (38.9%) patients showed no signs of recurrence, with 4 (21.1%) surviving longer than 2 years. Thus, to prevent sudden death and extend the survival of patients with HCC and TT extending into the right atrium, we advocate simultaneous en bloc resection performed under cardiopulmonary bypass, provided distant metastasis and recurrence in the remnant liver are controlled.
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Affiliation(s)
- Yoshihiro Inoue
- Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
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29
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Takeishi K, Shirabe K, Toshima T, Ikegami T, Morita K, Fukuhara T, Motomura T, Mano Y, Uchiyama H, Soejima Y, Taketomi A, Maehara Y. De novo autoimmune hepatitis subsequent to switching from type 2b to type 2a alpha-pegylated interferon treatment for recurrent hepatitis C after liver transplantation: report of a case. Surg Today 2011; 41:1016-9. [PMID: 21748625 DOI: 10.1007/s00595-010-4392-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2009] [Accepted: 03/24/2010] [Indexed: 02/05/2023]
Abstract
Interferon (IFN), which is the only possible agent for recurrent hepatitis C after liver transplantation, may cause serious immune-related disorders. We report a case of de novo autoimmune hepatitis (AIH), which developed subsequent to switching from 2b pegylated interferon-α (peg-IFN) to 2a peg-IFN after living donor liver transplantation (LDLT). A 51-year-old man with hepatitis C-associated liver cirrhosis underwent LDLT. About 13 months after the initiation of antiviral therapy, in the form of type 2b peg-IFN with ribavirin, a negative serum hepatitis C virus (HCV)-RNA titer was confirmed. Thereafter, the 2b peg-IFN was switched to 2a peg-IFN, 3 months after which severe liver dysfunction developed, despite a constantly negative HCV-RNA. Liver biopsy showed portal and periportal inflammatory infiltrates including numerous plasma cells, indicating AIH. He was treated with steroid pulse treatment, followed by high-level immunosuppression maintenance, but eventually died of Pneumocystis pneumonitis 4 months after the diagnosis of de novo AIH.
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Affiliation(s)
- Kazuki Takeishi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Small intestinal metastasis from intrahepatic cholangiocarcinoma: report of a case. Surg Today 2011; 41:859-64. [PMID: 21626338 DOI: 10.1007/s00595-010-4358-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2010] [Accepted: 04/28/2010] [Indexed: 02/07/2023]
Abstract
Metastasis of the small intestine that derives from a primary hepatic neoplasm is rare. We encountered a case of intrahepatic cholangiocarcinoma (ICC) with jejunal metastasis after resection of a primary lesion. A 61-year-old male patient was referred to us with a diagnosis of liver tumors. Partial hepatectomy was performed, and the pathological diagnosis was ICC. Seventeen months after surgery, the patient was found to have a mass in the jejunum and lymph node swelling by positron emission tomography-computed tomography. The jejunal tumor was preoperatively diagnosed as a metastasis of ICC from a biopsy specimen obtained by double balloon endoscopy, and the tumor was resected. The patient received systemic chemotherapy but succumbed with ICC recurrence 46 months after the primary surgery. To the best of our knowledge, this case is the first report of jejunal recurrence of ICC. In addition, this report suggests the usefulness of double balloon endoscopy to make the correct diagnosis of the jejunal tumor.
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Abstract
Laparoscopic liver resection (LHR) has shown classical advantages of minimally invasive surgery over open counterpart. In spite of introduction in early 1990's only few centres worldwide adapted LHR to routine practice. It was due to considerable technical challenges and uncertainty about oncologic outcomes. Surgical instrumentation and accumulation of surgical experience has largely enabled to solve many technical considerations. Intraoperative navigation options have also been improved. Consequently indications have been drastically expanded nearly reaching criteria equal to open liver resection in expert centres. Recent studies have verified oncologic integrity of LHR. However, mastering of LHR is still a quite demanding task limiting expansion of this patient friendly technique. This emphasizes the necessity of systematic training for laparoscopic liver surgery. This article reviews the state of the art of laparoscopic liver surgery lightening burning issues of research and clinical practice.
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Affiliation(s)
- B Edwin
- Intervention Centre, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
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Soong RS, Yu MC, Chan KM, Chou HS, Wu TJ, Lee CF, Wu TH, Lee WC. Analysis of the recurrence risk factors for the patients with hepatocellular carcinoma meeting University of California San Francisco criteria after curative hepatectomy. World J Surg Oncol 2011; 9:9. [PMID: 21269525 PMCID: PMC3041689 DOI: 10.1186/1477-7819-9-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2010] [Accepted: 01/27/2011] [Indexed: 01/07/2023] Open
Affiliation(s)
- Ruey-Shyang Soong
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Ming-Chin Yu
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Kun-Ming Chan
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Hong-Shiue Chou
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Ting-Jung Wu
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Chen-Fang Lee
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Tsung-Han Wu
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Wei-Chen Lee
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
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Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome? BMC Cancer 2010; 10:535. [PMID: 20925965 PMCID: PMC2958946 DOI: 10.1186/1471-2407-10-535] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2010] [Accepted: 10/07/2010] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with "multiple tumors more than 5 cm", "major vascular invasion", "invasion of adjacent organs", and "perforation of visceral peritoneum". The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC. METHODS We retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital. Overall survival (OS) and cumulative recurrence rate (CRR) of the four categories of locally advanced HCC patients were compared. RESULTS In multivariate analysis, major vascular invasion was identified as the most significant factor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001) followed by cirrhosis status on OS, and was found to be the only independent factor of CRR (HR = 2.242, 95% CI 1.811-3.358, P < 0.001) in patients with locally advanced HCC. Among the four categories of locally advanced HCC, OS was significantly worse, and CRR was significantly higher in patients with HCC with major vascular invasion (pT3) than with multiple tumors more than 5 cm (pT3); or tumor invasion of adjacent organs (pT4); or perforation of visceral peritoneum (pT4). No significant differences were observed in OS or CRR between the latter three groups of patients. CONCLUSIONS HCC with major vascular invasion, which are classified as pT3 under the current TNM staging, have the worst prognosis when compared with the other categories of pT3-4 disease. There is a need to redefine the T classification and to stratify locally advanced HCC.
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Nanashima A, Tobinaga S, Abo T, Sakamoto I, Hayashi H, Sawai T, Takeshita H, Hidaka S, Nagayasu T. Usefulness of measuring hepatic functional volume using technetium-99m galactosyl serum albumin scintigraphy in hilar bile duct carcinoma. Clin J Gastroenterol 2010; 3:174-8. [PMID: 26190127 DOI: 10.1007/s12328-010-0151-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2010] [Accepted: 03/26/2010] [Indexed: 10/19/2022]
Abstract
This case involved a 75-year-old woman with obstructive jaundice who was diagnosed with hilar bile duct carcinoma. After endoscopic retrograde biliary drainage, the total bilirubin level was normalized. The indocyanine green test retention rate at 15 min (ICGR15) was 26%. The liver uptake ratio (LHL15) by technetium-99m galactosyl human serum albumin ((99m)Tc-GSA) liver scintigraphy was 0.87. Left hepatectomy was scheduled by CT volumetry. However, biliary drainage was insufficient, and the functional liver volume showed functional deterioration of the left liver. After percutaneous transhepatic biliary drainage, future remnant liver volume by (99m)Tc-GSA liver scintigraphy changed to 52% from 42%, and ICGR15 and LHL15 were improved to 16% and 0.914, respectively. Scheduled left hepatectomy was performed following the results of functional liver volume. The measurement of functional volume by (99m)Tc-GSA liver scintigraphy provides useful information with respect to segmental liver function for deciding operative indications.
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Affiliation(s)
- Atsushi Nanashima
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Syuuichi Tobinaga
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takafumi Abo
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ichiro Sakamoto
- Department of Radiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hideyuki Hayashi
- Department of Radiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Terumitsu Sawai
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Hiroaki Takeshita
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Shigekazu Hidaka
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takeshi Nagayasu
- Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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Yoshimura N, Okajima H, Ushigome H, Sakamoto S, Fujiki M, Okamoto M. Current status of organ transplantation in Japan and worldwide. Surg Today 2010; 40:514-25. [PMID: 20496132 DOI: 10.1007/s00595-009-4214-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2009] [Accepted: 11/09/2009] [Indexed: 12/19/2022]
Abstract
Recent advances in immunosuppressant therapy have dramatically reduced the frequency of acute rejection of organ transplants. Subsequently, the short-term graft survival rate has been improved, and ABO blood type-incompatible and existing anti-HLA antibody-positive kidney transplantation has been enabled, which has increased the availability of living kidney donors. Japan has a unique history and strategies of liver transplantation (LT) for various liver diseases. The outcomes of living donor liver transplantation (LDLT) in Japan is comparable to that of deceased donor liver transplantation (DDLT) in Western countries despite the relatively short history of LT. The main disadvantage of LT in Japan is donor shortage mainly due to the small number of available deceased donors. There are some disadvantages with LDLT in autoimmune liver diseases because of the dependence on blood relative donors. The first brain-dead pancreas transplantation (PTx) was performed in 2000. Since that time, 42 brain-dead PTx, 2 non-heart beating PTx, and 14 living donor PTx had been performed by the end of 2007. One of the 44 recipients of deceased donor PTx died of unknown causes 11 months after transplantation. Although most of the deceased donors in Japan were marginal and their condition was not favorable, the results of these cases were comparable to those of Western countries. Fourteen intestinal transplantations (ITx) had been performed by the end of 2007 in four transplant centers. There were 3 deceased donor and 11 live donor transplants. The original diseases included short bowel syndrome (n = 6), intestinal function disorder (n = 6), and retransplantation (n = 2). The graft and patient survival rate are 60% and 69%, respectively. Eight recipients survived and stopped parenteral nutrition with full-functioning grafts. Amendment of the Japanese law for the utilization of deceased donors should increase the number available donors in the future.
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Affiliation(s)
- Norio Yoshimura
- Department of Organ Transplant and Regenerative Surgery, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Hirokoji Kawaramachi, Kamigyo-ku, Kyoto, 602-0841, Japan
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