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Catalano G, Alaimo L, Chatzipanagiotou OP, Rashid Z, Kawashima J, Ruzzenente A, Aucejo F, Marques HP, Bandovas J, Hugh T, Bhimani N, Maithel SK, Kitago M, Endo I, Pawlik TM. Recurrence patterns and prediction of survival after recurrence for gallbladder cancer. J Gastrointest Surg 2025; 29:101997. [PMID: 39971095 DOI: 10.1016/j.gassur.2025.101997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/10/2025] [Accepted: 02/11/2025] [Indexed: 02/21/2025]
Abstract
BACKGROUND Gallbladder cancer (GBC) is associated with a poor prognosis. Recurrence patterns and their effect on survival remain ill-defined. This study aimed to analyze recurrence patterns and develop a machine learning (ML) model to predict survival after recurrence (SAR) of GBC. METHODS Patients who underwent curative-intent resection of GBC between 1999 and 2022 were identified using an international database. An Extreme Gradient Boosting ML model to predict SAR was developed and validated. RESULTS Among 348 patients, 110 (31.6%) developed disease recurrence during follow-up. The most common recurrence site was local (29.1%), followed by multiple site (26.4%), liver (21.8%), peritoneal (18.2%), and lung (0.05%). The median SAR was the longest in patients with lung recurrence (36.0 months), followed by those with local recurrence (15.7 months). In contrast, patients with peritoneal (8.9 months), liver (8.5 months), or multiple-site (6.4 months) recurrence had a considerably shorter SAR. Patients with multiple-site recurrence had a worse SAR than individuals with single-site recurrence (6.4 vs 11.10 months, respectively; P =.014). The model demonstrated good performance in the evaluation and bootstrapping cohorts (area under the receiver operating characteristic curve: 71.4 and 71.0, respectively). The most influential variables were American Society of Anesthesiologists classification, local recurrence, receipt of adjuvant chemotherapy, American Joint Committee on Cancer T and N categories, and developing early disease recurrence (<12 months). To enable clinical applicability, an easy-to-use calculator was made available (https://catalano-giovanni.shinyapps.io/SARGB). CONCLUSION Except for lung recurrence, SAR for GBC was poor. A subset of patients with less aggressive disease biology may have favorable SAR. ML-based SAR prediction may help individuate candidates for curative re-resection when feasible.
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Affiliation(s)
- Giovanni Catalano
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States; Division of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Laura Alaimo
- Division of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Odysseas P Chatzipanagiotou
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Zayed Rashid
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Federico Aucejo
- Department of Hepatopancreatobiliary and Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, OH, United States
| | - Hugo P Marques
- Department of Surgery, Hospital Curry Cabral, Lisbon, Portugal
| | - Joao Bandovas
- Department of Surgery, Hospital Curry Cabral, Lisbon, Portugal
| | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, Australia
| | - Nazim Bhimani
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, Australia
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, United States
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States.
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Kokuryo T, Koike Y, Yamaguchi J, Sunagawa M, Baba T, Watanabe N, Onoe S, Mizuno T, Ebata T. Accumulating Genetic Mutations from Primary to Secondary Biliary Tract Cancers: Analysis of Four Patients With Metachronous Biliary Tract Cancer Using Comprehensive Genomic Profiling. Cancer Genomics Proteomics 2025; 22:346-353. [PMID: 39993799 PMCID: PMC11880928 DOI: 10.21873/cgp.20505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/28/2024] [Accepted: 12/03/2024] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND/AIM Metachronous biliary tract cancer (BTC) is a rare occurrence after curative resection of primary BTC. The genetic alterations and pathogenesis associated with metachronous BTC remain poorly understood. PATIENTS AND METHODS We analyzed four patients with metachronous BTC who underwent resection at the Nagoya University Hospital between 2010 and 2024. Gene panel examination was performed on both primary and secondary tumors using next-generation sequencing. RESULTS The median interval between resection of the primary tumor and diagnosis of metachronous BTC was 24 months. Genetic alterations were observed in all paired primary and metachronous carcinomas. The number of genetic mutations was higher in metachronous lesions than in primary lesions. CDKN2A and SMAD4 were the most frequently mutated genes in all metachronous lesions. Common genetic mutations between primary and metachronous lesions were confirmed in all four cases, suggesting a common clonal origin. CONCLUSION This study demonstrated that characteristic genetic alterations and their accumulation play important roles in metachronous BTC. This suggests that the increasing burden of gene mutations may play a crucial role in the carcinogenesis of metachronous BTC. Further investigation is required to validate these findings and elucidate the underlying molecular mechanisms.
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Affiliation(s)
- Toshio Kokuryo
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshio Koike
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masaki Sunagawa
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Taisuke Baba
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobuyuki Watanabe
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shunsuke Onoe
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Kwon YJ, Min JH, Hwang JA, Kim SH, Kim YK, Kim H, Gu K, Lee JH, Shin J, Choi SY, Baek SY. Clinical significance of CA 19-9 elevation during postoperative surveillance for extrahepatic bile duct cancer: a nomogram-based approach for the prediction of short-term recurrence. HPB (Oxford) 2025; 27:195-205. [PMID: 39586759 DOI: 10.1016/j.hpb.2024.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/13/2024] [Accepted: 10/29/2024] [Indexed: 11/27/2024]
Abstract
BACKGROUND This study aimed to assess the significance of elevated carbohydrate antigen (CA) 19-9 in postoperative surveillance of extrahepatic bile duct cancer and to identify short-term recurrence predictors. METHODS This retrospective study included patients with elevated CA 19-9 post-curative surgery. Patients were categorized into positive and negative CT groups based on the detection of recurrence at CA 19-9 elevation. Short-term recurrence was defined as recurrence within 6 months in the negative CT group. We identified the factors associated with short-term recurrence and devised a predictive nomogram. RESULTS Among the 190 patients, 91 (47.9 %) exhibited tumor recurrence with CA 19-9 elevation (CT-positive group), whereas 99 (52.1 %) showed no recurrence (CT-negative group). In the CT-negative group (n = 99), 22 (22.2 %) experienced short-term tumor recurrence within 6 months. Preoperative CA 19-9 (odds ratio [OR]: 1.5, p = 0.016), postoperative CA 19-9 (OR: 1.9, p = 0.047), adjuvant treatment (OR: 3.5, p = 0.032), and the absence of inflammation (OR: 3.5, p = 0.045) were predictors of short-term recurrence. The area under the curve of the nomogram was 0.80 (95 % CI: 0.69-0.90). CONCLUSION Despite elevated CA 19-9 levels, approximately 50 % of patients exhibited no recurrence during postoperative surveillance for extrahepatic bile duct cancer. Factors influencing short-term recurrence encompass pre- and postoperative CA 19-9, adjuvant treatment, and inflammatory status.
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Affiliation(s)
- Yong Jae Kwon
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Hye Min
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Jeong Ah Hwang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seong Hyun Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Kon Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Honsoul Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyowon Gu
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong Hyun Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jaeseung Shin
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seo-Youn Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun-Young Baek
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
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Okamoto T, Takeda T, Sasaki T, Inoue Y, Mie T, Hirai T, Ishitsuka T, Yamada M, Nakagawa H, Furukawa T, Kasuga A, Ozaka M, Takahashi Y, Sasahira N. Liver Oligometastasis in Biliary Tract Cancer and Impact on Survival Outcomes. J Gastrointest Cancer 2024; 55:1530-1540. [PMID: 39145915 DOI: 10.1007/s12029-024-01098-4] [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: 08/06/2024] [Indexed: 08/16/2024]
Abstract
PURPOSE Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy. METHODS We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021. RESULTS Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4 months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7 months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7 months, P < 0.001). Age ≥ 75 years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5 μg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis. CONCLUSIONS Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery.
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Affiliation(s)
- Takeshi Okamoto
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan.
| | - Tsuyoshi Takeda
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Takashi Sasaki
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Yosuke Inoue
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Mie
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Tatsuki Hirai
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Takahiro Ishitsuka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Manabu Yamada
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Hiroki Nakagawa
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Takaaki Furukawa
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Akiyoshi Kasuga
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
| | - Yu Takahashi
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake Koto-Ku, Tokyo, 135-8550, Japan
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Zeng D, Wang Y, Wen N, Lu J, Li B, Cheng N. The prognostic value of preoperative peripheral blood inflammatory biomarkers in extrahepatic cholangiocarcinoma: a systematic review and meta-analysis. Front Oncol 2024; 14:1437978. [PMID: 39267826 PMCID: PMC11390462 DOI: 10.3389/fonc.2024.1437978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 07/30/2024] [Indexed: 09/15/2024] Open
Abstract
Background Recent evidence indicates that inflammation plays a major role in the pathogenesis and progression of CCA. This meta-analysis seeks to evaluate the prognostic implications of preoperative inflammatory markers, specifically NLR, PLR, and LMR, in patients with eCCA. By focusing on these preoperative biomarkers, this study aims to provide valuable insights into their prognostic value and potential utility in clinical practice. Methods For this analysis, comprehensive searches were conducted in PubMed, Embase, and Web of Science databases from inception to May 2024. The primary outcomes of interest focused on the association between the levels of NLR, PLR, and LMR and the prognosis of eCCA patients. Statistical analyses were conducted using STATA 17.0 software. Results The meta-analysis, involving 20 retrospective studies with 5553 participants, revealed significant correlations between preoperative biomarkers and the prognosis of eCCA patients. Elevated NLR, PLR, and decreased LMR levels were extensively studied regarding overall survival (OS) in eCCA patients. Elevated NLR was an independent predictor of poor OS (HR 1.86, p < 0.001), similar to elevated PLR (HR 1.76, p < 0.001), while decreased LMR predicted poor OS (HR 2.16, p < 0.001). Subgroup analyses based on eCCA subtypes and curative surgery status showed consistent results. Conclusions In conclusion, our study emphasizes the clinical significance of assessing NLR, PLR, and LMR preoperatively to predict patient prognosis. Elevated NLR and PLR values, along with decreased LMR values, were linked to poorer overall survival (OS). Large-scale prospective cohort studies are required to confirm their independent prognostic value in eCCA. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024551031.
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Affiliation(s)
- Di Zeng
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yaoqun Wang
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ningyuan Wen
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiong Lu
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bei Li
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Nansheng Cheng
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Sun Y, Jiang W, Duan R, Guan L. Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma. Front Pharmacol 2024; 15:1432603. [PMID: 39170710 PMCID: PMC11335543 DOI: 10.3389/fphar.2024.1432603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 07/29/2024] [Indexed: 08/23/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy of the liver, following hepatocellular carcinoma (HCC). Surgical resection remains the only potentially curative treatment for ICC. However, due to its high malignancy and propensity for postoperative recurrence, the prognosis for ICC is generally poor, and there is currently little standardized approach for adjuvant therapy following curative surgery. This article aims to explore adjuvant treatment strategies for ICC post-curative surgery by reviewing retrospective studies and clinical trials conducted in recent years. The analysis focuses on the effectiveness, challenges, and potential developments in the management of ICC post-surgery, considering the high recurrence rates and the need for improved therapeutic approaches to enhance patient outcomes. Additionally, we discuss the various types of adjuvant treatments that have been explored, including chemotherapy, radiation therapy, and targeted therapies. The goal is to provide a comprehensive overview of the current landscape and highlight promising directions for future research to improve survival and quality of life for ICC patients.
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Affiliation(s)
| | | | | | - Lianyue Guan
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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Holzner ML, Mazzaferro V, Busset MDD, Aldrighetti L, Ratti F, Hasegawa K, Arita J, Sapisochin G, Abreu P, Schoning W, Schmelzle M, Nevermann N, Pratschke J, Florman S, Halazun K, Schwartz ME, Tabrizian P. Is Repeat Resection for Recurrent Intrahepatic Cholangiocarcinoma Warranted? Outcomes of an International Analysis. Ann Surg Oncol 2024; 31:4397-4404. [PMID: 38334851 DOI: 10.1245/s10434-024-14975-w] [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: 10/12/2023] [Accepted: 01/12/2024] [Indexed: 02/10/2024]
Abstract
BACKGROUND Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.
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Affiliation(s)
- Matthew L Holzner
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Vincenzo Mazzaferro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
| | - Michele Droz Dit Busset
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Francesca Ratti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Phillipe Abreu
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Wenzel Schoning
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Mortiz Schmelzle
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Nora Nevermann
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Sander Florman
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Karim Halazun
- NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA
| | - Myron E Schwartz
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Parissa Tabrizian
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Suwanprinya C, Luvira V, Winaikosol K, Surakunprapha P, Punyavong P, Jenwitheesuk K, Pugkhem A, Pairojkul C. En bloc groin node resection reconstructed with external oblique flap for solitary metastatic cholangiocarcinoma: a case report. Clin J Gastroenterol 2024; 17:543-550. [PMID: 38517592 DOI: 10.1007/s12328-024-01943-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 02/24/2024] [Indexed: 03/24/2024]
Abstract
Cholangiocarcinoma requires complete surgical resection for cure. Even so, the recurrence and metastasis rates are high, and further treatment is typically through palliative systemic chemotherapy. Curative-intent resection of metastatic site may provide survival benefit in selected cases. However, there were no previous reports of groin node dissection in cholangiocarcinoma. We have reported the first case of intrahepatic mass-forming cholangiocarcinoma with isolated synchronous groin node metastasis, successfully treated with resection of the liver mass followed by groin node resection, reconstructed with musculofascial flap. A 73-year-old man presented with right upper quadrant abdominal pain radiating to the right groin for two months. Magnetic resonance cholangiopancreatography revealed a 3.1 × 1.2 cm enhancing mass between hepatic segment 4 and the anterior peritoneum, invading the abdominal wall. Computed tomography of the abdomen revealed a 2.4 × 2.2 cm focal enhancing mass at the anterior aspect of the right lower abdominal wall, just anterior to the right inguinal ligament and iliac vessel. He underwent en bloc resection of hepatic segment 4, gallbladder, and anterior abdominal wall, and the histology result is cholangiocarcinoma. After systemic chemotherapy, he underwent en bloc resection of the right groin mass, reconstructed with external oblique musculofascial flap. The patient was able to achieve a 20-month recurrence free survival after the final operation. This case has demonstrated that in a carefully selected case, resection of distant metastasis cholangiocarcinoma can provide survival benefits, even in the rare site of metastasis.
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Affiliation(s)
- Chalisa Suwanprinya
- General Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
| | - Vor Luvira
- General Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Kengkart Winaikosol
- Plastic & Reconstructive Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Palakorn Surakunprapha
- Plastic & Reconstructive Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Pattama Punyavong
- Plastic & Reconstructive Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Kamonwan Jenwitheesuk
- Plastic & Reconstructive Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Ake Pugkhem
- General Surgery Unit, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chawalit Pairojkul
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Maki H, Kawaguchi Y, Nagata R, Mihara Y, Ichida A, Ishizawa T, Akamatsu N, Kaneko J, Arita J, Hasegawa K. Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval. Hepatol Res 2023; 53:1224-1234. [PMID: 37559185 DOI: 10.1111/hepr.13951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 07/22/2023] [Accepted: 08/01/2023] [Indexed: 08/11/2023]
Abstract
AIM The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC. METHODS This study included patients who underwent hepatectomy for ICC during 1995-2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed. RESULTS A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11-0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05-5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95-1.00, p = 0.067) were significantly associated with longer OS after recurrence. CONCLUSIONS Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.
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Affiliation(s)
- Harufumi Maki
- Hepato-Biliary-Pancreatic Surgery Division, and 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, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Rihito Nagata
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuichiro Mihara
- Hepato-Biliary-Pancreatic Surgery Division, and 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, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, and 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, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, and 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, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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10
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Iseki M, Mizuma M, Unno M, Maruyama H, Akagi S, Shimoda M, Uemura K, Inoue T, Shiomi H, Watanabe M, Kobayashi M, Matsuda A, Mizuuchi Y, Aoki T, Shinkawa H, Takahata R, Makino K, Arai H, Yokoyama Y, Takeda S, Yaguchi Y, Kitagawa Y. Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study. Surgery 2023; 174:1145-1152. [PMID: 37599194 DOI: 10.1016/j.surg.2023.05.019] [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: 01/05/2023] [Revised: 05/05/2023] [Accepted: 05/24/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.
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Affiliation(s)
- Masahiro Iseki
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hiroshi Maruyama
- Department of Surgery, Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan; Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan
| | - Shinji Akagi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Mazda Hospital, Hiroshima, Japan
| | - Mitsugi Shimoda
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastroenterological Surgery, Ibaraki Medical Center, Tokyo Medical University, Ibaraki, Japan
| | - Kenichiro Uemura
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan
| | - Toru Inoue
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastrointestinal Surgery, Osaka City General Hospital, Japan
| | - Hisanori Shiomi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Nagahama Red Cross Hospital, Shiga, Japan
| | - Manabu Watanabe
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Minako Kobayashi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Infection Control and Prevention, Nippon Medical School, Musashikosugi Hospital, Kanagawa, Japan
| | - Akihisa Matsuda
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Yusuke Mizuuchi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Taku Aoki
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Hiroji Shinkawa
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Hepatobiliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Japan
| | - Risa Takahata
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Medical Risk Management and Infection Control, National Defense Medical Collage, Saitama, Japan
| | - Kenta Makino
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Graduate School of Medicine, Kyoto University, Japan
| | - Hiroki Arai
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Japan
| | - Yasuyuki Yokoyama
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Digestive Surgery, Nippon Medical School Musashikosugi Hospital, Kanagawa, Japan
| | - Shigeru Takeda
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Japan
| | - Yoshihisa Yaguchi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Sassa General Hospital, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan; The Japan Society of Surgical Infection, Tokyo, Japan
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11
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Guo YL, Guo JX, Zhao JG, Bao YN. Analysis of the efficacy and factors influencing survival of adjuvant radiotherapy for stage II-III biliary tract carcinoma. World J Surg Oncol 2023; 21:339. [PMID: 37880729 PMCID: PMC10601315 DOI: 10.1186/s12957-023-03209-0] [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: 03/30/2023] [Accepted: 10/03/2023] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND To determine the efficacy of adjuvant radiotherapy for stage II-III biliary tract carcinoma. METHODS We retrospectively analyzed the data of 37 patients who underwent radical resection of biliary tract carcinomas at the Affiliated Hospital of Inner Mongolia Medical University between 2016 and 2020. We analyzed survival differences between patients who did (n = 17) and did not (n = 20) receive postoperative adjuvant radiotherapy by using Kaplan-Meier analysis. The log-rank test and Cox univariate analysis were used. The Cox proportional risk regression model was used for the multifactorial analysis of factors influencing prognosis. RESULTS The median survival time (28.9 vs. 14.5 months) and the 1-year (82.40% vs. 55.0%) and 2-year survival rates (58.8% vs. 25.0%) were significantly higher among patients who received adjuvant radiotherapy than among those who did not (χ2 = 6.381, p = 0.012). Multifactorial analysis showed that pathological tumor type (p = 0.004), disease stage (p = 0.021), and adjuvant radiotherapy (p = 0.001) were independent prognostic factors in biliary tract carcinoma. Subgroup analyses showed that compared to no radiotherapy, adjuvant radiotherapy significantly improved median survival time in patients with stage III disease (21.6 vs. 12.7 months; p = 0.017), positive margins (28.9 vs. 10.5 months; p = 0.012), and T3 or T4 tumors (26.8 vs. 16.8 months; p = 0.037). CONCLUSION Adjuvant radiotherapy significantly improved the survival of patients with biliary tract carcinoma, and is recommended especially for patients with stage III disease, positive surgical margins, or ≥ T3.
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Affiliation(s)
- Yan-Ling Guo
- Department of Radiotherapy, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, China
| | - Jia-Xing Guo
- Department of Radiotherapy, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, China
| | - Jian-Guo Zhao
- Department of Radiotherapy, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, China
| | - Ying-Na Bao
- Department of Radiotherapy, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, China.
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12
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Sumiyoshi T, Uemura K, Shintakuya R, Okada K, Serikawa M, Ishii Y, Arihiro K, Murakami Y, Murashita J, Takahashi S. Prognostic impact of lung recurrence in patients with biliary tract cancer. Langenbecks Arch Surg 2023; 408:290. [PMID: 37522989 DOI: 10.1007/s00423-023-03015-y] [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: 03/14/2023] [Accepted: 07/11/2023] [Indexed: 08/01/2023]
Abstract
PURPOSE This study aimed to evaluate the prognostic impact of the initial recurrence site following resection for biliary tract carcinoma (BTC), focusing on lung recurrence. METHODS The clinical data of patients with recurrent BTC who underwent curative intent surgery between March 2009 and December 2021 were retrospectively analyzed. The prognosis of patients with recurrent BTC was investigated in each recurrence site. Eligible patients were classified into two groups according to lung or non-lung recurrence. Clinicopathological factors, survival after recurrence, and overall survival were compared between the two groups. Independent factors associated with survival after recurrence were investigated using multivariate analysis. RESULTS Of 119 patients, the initial recurrence site was local in 26 (21.8%) patients, liver in 19 (16.8%), peritoneum in 14 (11.8%), lymph node in 12 (10.1%), lung in 11 (9.2%), multiple organs in 32 (26.9%), and others in 5 (4.2%). The survival period after recurrence in patients with lung recurrence was significantly longer than those in patients with other six recurrence patterns. The median survival after recurrence was 34.3 and 9.3 months in lung recurrence and non-lung recurrence groups, respectively (p < 0.0001); that after initial surgery was 50.8 and 26.4 months, respectively (p = 0.0383). Multivariate analysis revealed that lung recurrence and normal albumin level at recurrence were independently associated with survival after recurrence (Hazard Ratio (HR), 0.291; p = 0.0128; HR, 0.476; p = 0.00126, respectively). CONCLUSIONS Survival period after recurrence was significantly longer in patients with lung recurrence.
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Affiliation(s)
- Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Ryuta Shintakuya
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Digestive Disease Center, Hiroshima Memorial Hospital, Hiroshima, Japan
| | | | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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13
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Can repeated surgical resection offer a chance of cure for recurrent cholangiocarcinoma? Langenbecks Arch Surg 2023; 408:102. [PMID: 36826620 DOI: 10.1007/s00423-023-02839-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 02/13/2023] [Indexed: 02/25/2023]
Abstract
INTRODUCTION The incidence of cholangiocarinoma (CCA), as well as the related mortality rate, has progressively increased over the last decades. Nevertheless improvement in patient management, diagnosis and therapies, recurrence rate remains high (50-70%) with a low 5-year survival (7-20%). Palliative chemotherapy and best supportive care are the treatment of choice in case of recurrence. In recent years, some reports have been published on repeated resection suggesting a survival benefit. The aim of this study was to evaluate the long-term outcome of all repeated resections for recurrent CCA in our institution. MATERIALS AND METHODS We performed a retrospective analysis of all data recorded in our prospective maintained database of all patients who underwent repeated resection for recurrence of any type of CCA (intrahepatic, perihilar, distal, and gallbladder) with curative intent in our institution. RESULTS Between 1997 and 2017, twenty-six patients underwent repeated surgical resection for recurrent CCA. Median time to first recurrence was 20 months. Site of recurrence was liver in 18 patients (70%), lymph nodes in 6 (23%), and lungs in 2 (7%). Twenty-five patients (96%) underwent upfront surgical resection of the recurrence, while one received preoperative chemotherapy. Median overall and disease-free survival from repeated surgical resection was 21 and 18 months with a 1-, 3-, and 5-year survival of 87, 41, 29% and 75%, 27%, and 17% respectively. Five patients (21%) did not experience recurrence after repeated surgical resection after a median follow-up of 73 months. CONCLUSIONS Repeated surgical resection of recurrent CCAs is feasible with good postoperative results and can lead to an increase in survival.
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14
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Ohaegbulam KC, Koethe Y, Fung A, Mayo SC, Grossberg AJ, Chen EY, Sharzehi K, Kardosh A, Farsad K, Rocha FG, Thomas CR, Nabavizadeh N. The multidisciplinary management of cholangiocarcinoma. Cancer 2023; 129:184-214. [PMID: 36382577 DOI: 10.1002/cncr.34541] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/11/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022]
Abstract
Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.
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Affiliation(s)
- Kim C Ohaegbulam
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Yilun Koethe
- Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Alice Fung
- Department of Diagnostic Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Skye C Mayo
- Department of Surgical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Aaron J Grossberg
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Emerson Y Chen
- Division of Hematology/Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Kaveh Sharzehi
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, Oregon, USA
| | - Adel Kardosh
- Division of Hematology/Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Khashayar Farsad
- Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Flavio G Rocha
- Department of Surgical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Charles R Thomas
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA.,Department of Radiation Oncology, Dartmouth School of Medicine, Hanover, New Hampshire, USA
| | - Nima Nabavizadeh
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
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15
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Fernández L, Gastaca M, Alonso E, Prieto M, Ruiz P, Ventoso A, Palomares I, Perfecto A, Valdivieso A. Surgical treatment for recurrent cholangiocarcinoma: a single-center series. Front Oncol 2023; 13:1169133. [PMID: 37143948 PMCID: PMC10152064 DOI: 10.3389/fonc.2023.1169133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 03/29/2023] [Indexed: 05/06/2023] Open
Abstract
Purpose The present study aims to assess the results obtained after surgical treatment of cholangiocarcinoma (CC) recurrences. Methods We carried out a single-center retrospective study, including all patients with recurrence of CC. The primary outcome was patient survival after surgical treatment compared with chemotherapy or best supportive care. A multivariate analysis of variables affecting mortality after CC recurrence was performed. Results Eighteen patients were indicated surgery to treat CC recurrence. Severe postoperative complication rate was 27.8% with a 30-day mortality rate of 16.7%. Median survival after surgery was 15 months (range 0-50) with 1- and 3-year patient survival rates of 55.6% and 16.6%, respectively. Patient survival after surgery or CHT alone, was significantly better than receiving supportive care (p< 0.001). We found no significant difference in survival when comparing CHT alone and surgical treatment (p=0.113). Time to recurrence of <1 year, adjuvant CHT after resection of the primary tumor and undergoing surgery or CHT alone versus best supportive care were independent factors affecting mortality after CC recurrence in the multivariate analysis. Conclusion Surgery or CHT alone improved patient survival after CC recurrence compared to best supportive care. Surgical treatment did not improve patient survival compared to CHT alone.
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Affiliation(s)
- Laura Fernández
- General Surgery Department, Hospital de Urduliz, Urduliz, Spain
| | - Mikel Gastaca
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
- Facultad de Medicina y Odontología, Universidad del País Vasco/ Euskal Herriko Unibertsitatea (UPV/EHU), Leioa, Spain
- *Correspondence: Mikel Gastaca, ;
| | - Eva Alonso
- General Surgery Department, Hospital Universitario Cruces, Bilbao, Spain
| | - Mikel Prieto
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
- Facultad de Medicina y Odontología, Universidad del País Vasco/ Euskal Herriko Unibertsitatea (UPV/EHU), Leioa, Spain
| | - Patricia Ruiz
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
| | - Alberto Ventoso
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
| | - Ibone Palomares
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
| | - Arkaitz Perfecto
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
| | - Andrés Valdivieso
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao, Spain
- Facultad de Medicina y Odontología, Universidad del País Vasco/ Euskal Herriko Unibertsitatea (UPV/EHU), Leioa, Spain
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Mashiko T, Ogasawara T, Masuoka Y, Ei S, Takahashi S, Mori M, Koyanagi K, Yamamoto S, Nakagohri T. Indications for resection of recurrent lesions in patients with distal cholangiocarcinoma based on prognostic factors: a single-institute retrospective study and brief literature review. BMC Surg 2022; 22:423. [PMID: 36503431 PMCID: PMC9743743 DOI: 10.1186/s12893-022-01879-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND To evaluate the effectiveness of surgery for recurrent distal cholangiocarcinoma and determine surgical indications based on prognostic factors for the recurrence of distal cholangiocarcinoma. METHODS We analysed the outcomes of 101 patients who underwent surgical resection for distal cholangiocarcinoma between 2000 and 2018. The clinicopathological factors and prognosis of primary and recurrent distal cholangiocarcinoma were investigated. RESULTS Of the 101 patients with resected distal cholangiocarcinoma, 52 (51.5%) had relapsed. Seven (13.5%) and 45 patients (86.5%) underwent resection of recurrent lesions and palliative therapy, respectively. There were no major complications requiring therapeutic intervention after metastasectomy. The median overall survival in patients with and without surgery for recurrent lesions was 83.0 (0.0-185.6) and 34 months (19.0-49.0), respectively. Therefore, patients who had undergone surgery for recurrent lesions had a significantly better prognosis (p = 0.022). Multivariate analyses of recurrent distal cholangiocarcinoma revealed that recurrence within one year was an independent predictor of poor survival. Resection of recurrent lesions improved prognosis. CONCLUSIONS Radical resection in recurrent distal cholangiocarcinoma may improve the prognosis in selected patients. Although time to recurrence is considered an important factor, the small number of cases of recurrence and resection of recurrent lesions in this study makes it difficult to conclude which patients are best suited for resection of recurrent lesions. This issue requires clarification in a multicentre prospective study, considering patients' background, such as the recurrence site and number of metastases.
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Affiliation(s)
- Taro Mashiko
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
| | - Toshihito Ogasawara
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Yoshihito Masuoka
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Shigenori Ei
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Shinichiro Takahashi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kazuo Koyanagi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Seiichiro Yamamoto
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Toshio Nakagohri
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
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Matsuyama R, Mori R, Ota Y, Homma Y, Yabusita Y, Hiratani S, Murakami T, Sawada Y, Miyake K, Shimizu Y, Kumamoto T, Endo I. Impact of Gemcitabine Plus S1 Neoadjuvant Chemotherapy on Borderline Resectable Perihilar Cholangiocarcinoma. Ann Surg Oncol 2022; 29:2393-2405. [PMID: 34994885 DOI: 10.1245/s10434-021-11206-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/30/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Surgical resection is the only curative strategy for perihilar cholangiocarcinoma (PHC), but recurrence rates are high even after purported curative resection. This study aimed to evaluate the efficacy and safety of gemcitabine/S-1 (GS) combination chemotherapy in the neoadjuvant setting. METHODS In an open-label, single-arm, phase 2 study, neoadjuvant chemotherapy (NAC) with GS, repeated every 21 days, was administered for three cycles to patients with histologic or cytologically confirmed borderline resectable (BR) PHC who were eligible for inclusion in the study. In this study, BR PHC was defined as positive for lymph node metastasis and for cancerous vascular invasion or Bismuth type 4 on preoperative imaging. The primary end point consisted of the 3- and 5-year survival rates. The secondary end points were feasibility, resection rate, and pathologic effect. RESULTS The study enrolled 60 patients between January 2011 and December 2016. With respect to toxicity, the major adverse effect was neutropenia, which reached grade 3 or 4 in 53.3% of cases. The overall disease control rate was 91.3%. The median survival time for the entire cohort was 30.3 months. For all the patients, the estimated 3-year survival rate was 44.1%, and the 5-year survival rate was 30.0%. Resection with curative intent was performed for 43 (71%) of the 60 patients. For 81% of the resected patients, R0 resection was performed, and Clavien-Dindo grade 3 complications or a higher morbidity rate was seen in 41% of the patients. The median survival time was 50.1 months for the resected and 14.8 months for the unresected patients. For the resected patients, the estimated 3-year survival rate was 55.8%, and the estimated 5-year survival rate was 36.4%. CONCLUSIONS Gemcitabine/S-1 combination NAC has promising efficacy and good tolerability for patients with BR PHC.
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Affiliation(s)
- Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
| | - Ryutaro Mori
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yohei Ota
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yuki Homma
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yasuhiro Yabusita
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Seigo Hiratani
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takashi Murakami
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kentaro Miyake
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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OUP accepted manuscript. Br J Surg 2022; 109:580-587. [DOI: 10.1093/bjs/znac075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 02/23/2022] [Indexed: 11/13/2022]
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Bekki Y, Von Ahrens D, Takahashi H, Schwartz M, Gunasekaran G. Recurrent Intrahepatic Cholangiocarcinoma - Review. Front Oncol 2021; 11:776863. [PMID: 34746017 PMCID: PMC8567135 DOI: 10.3389/fonc.2021.776863] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/01/2021] [Indexed: 12/15/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy after hepatocellular carcinoma. While surgical resection with negative margin is the only curative treatment, ICC has very high rate of recurrence, up to 60-70% after curative resection. We reviewed the current data available on risk factors for ICC recurrence, recurrence pattern (location and timing), treatment options, and future directions. The risk factors for recurrence include elevated preoperative CA19-9, presence of liver cirrhosis, nodal metastasis, positive margins, and vascular invasion. Understanding different recurrence patterns, timing course, and risk factors for early recurrence is important to tailor postoperative surveillance and select treatment strategies including systemic or locoregional therapy. Re-resection can be considered for a selected patient population at experienced centers, and can yield long-term survival. ICC remains a dismal disease given the high likelihood of recurrence. Advances in our understanding of the genomic landscape of ICC are beginning to identify targetable alterations in ICC in subsets of patients that allow for personalized treatment.
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Affiliation(s)
- Yuki Bekki
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Dagny Von Ahrens
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Hideo Takahashi
- Department of Surgery, Mount Sinai South Nassau, Oceanside, NY, United States
| | - Myron Schwartz
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Ganesh Gunasekaran
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, United States.,Department of Surgery, Mount Sinai South Nassau, Oceanside, NY, United States
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Tsukamoto T, Kodai S, Tajima T, Kanazawa A, Takahama M, Mikami S. Laparoscopic liver resection with open partial resection of the thoracoabdominal wall for cancer along the transhepatic biliary drainage tract: A case report. Int J Surg Case Rep 2021; 88:106497. [PMID: 34656929 PMCID: PMC8521238 DOI: 10.1016/j.ijscr.2021.106497] [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: 09/18/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 11/25/2022] Open
Abstract
Introduction and importance Recently, laparoscopic liver resection has been established as a standard procedure for a certain group of hepatic resections; its indications and procedures have been expanding. Case presentation A 67-year-old woman was referred with a chief complaint of left subcostal pain. Eight years and nine months before, she underwent pancreatoduodenectomy for cancer of the ampulla of Vater after endoscopic retrograde biliary drainage for obstructive jaundice. A trans-anastomotic internal-external retrograde transhepatic biliary drainage (RTBD) catheter was placed intraoperatively. Based on radiological findings, intrahepatic cholangiocarcinoma, or local recurrence of cancer of the ampulla of Vater, invading the anterior thoracoabdominal wall, diaphragm, and pericardium, without distant metastasis, were considered. Laparoscopic lateral segmentectomy of the liver combined with open en bloc resection of the invaded portion of the anterior thoracoabdominal wall with costal cartilage, diaphragm, and pericardium was performed. The postoperative course was uneventful, and the patient was discharged 17 days post-surgery. The patient died of cancer recurrence 46 months later. Clinical discussion The cancer invaded along the RTBD tract. Although the mechanisms of carcinogenesis remain unclear, transhepatic biliary drainage is a risk factor for cancer invasion along the tract. Laparoscopic liver resection before open thoracoabdominal wall resection ensured clear delineation of the cancer margins invading the thoracoabdominal wall and minimized the defect of the thoracoabdominal wall. Conclusion Laparoscopic liver resection for hepatic cancer invading adjacent structures or organs would be feasible and useful in selected patients, even if resection of the invaded area is performed by open surgery.
Cancer developed along the retrograde transhepatic biliary drainage tract after pancreatoduodenectomy. Laparoscopic liver resection and simultaneous open en bloc partial resection of the thoracoabdominal wall was performed. The patient’s 46-month survival post-operation was relatively long for recurrent cancer of the ampulla of Vater.
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Affiliation(s)
- Tadashi Tsukamoto
- Department of Hepatobiliary-pancreatic Surgery, Osaka City General Hospital, Osaka, Japan; Department of Surgery, Osaka City Juso Hospital, Osaka, Japan.
| | - Shintaro Kodai
- Department of Hepatobiliary-pancreatic Surgery, Osaka City General Hospital, Osaka, Japan
| | - Tetsuzo Tajima
- Department of Hepatobiliary-pancreatic Surgery, Osaka City General Hospital, Osaka, Japan
| | - Akishige Kanazawa
- Department of Hepatobiliary-pancreatic Surgery, Osaka City General Hospital, Osaka, Japan
| | - Makoto Takahama
- Department of Respiratory Surgery, Osaka City General Hospital, Osaka, Japan
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Sakata J, Nomura T, Aono T, Kitami C, Yokoyama N, Minagawa M, Takizawa K, Miura K, Hirose Y, Ichikawa H, Nagahashi M, Shimada Y, Kobayashi T, Wakai T. Oncological outcomes of surgery for recurrent biliary tract cancer: who are the best candidates? HPB (Oxford) 2021; 23:1371-1382. [PMID: 33558069 DOI: 10.1016/j.hpb.2021.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 12/05/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease. METHODS A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%). RESULTS In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p < 0.001). Surgery was an independently prognostic factor (p < 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%). CONCLUSION Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.
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Affiliation(s)
- Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Tatsuya Nomura
- Department of Gastrointestinal Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
| | - Takashi Aono
- Department of Surgery, Niigata Prefectural Central Hospital, Joetsu, Japan.
| | - Chie Kitami
- Department of Surgery, Nagaoka Chuo General Hospital, Nagaoka, Japan.
| | - Naoyuki Yokoyama
- Department of Gastrointestinal Surgery, Niigata City General Hospital, Niigata, Japan.
| | | | - Kazuyasu Takizawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Masayuki Nagahashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Takashi Kobayashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
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22
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Koh M, Park JH, Yoo C, Yoon SM, Jung J, Ryoo BY, Chang HM, Kim KP, Jeong JH, Kim JH. Radiation therapy for recurrent extrahepatic bile duct cancer. PLoS One 2021; 16:e0253285. [PMID: 34133471 PMCID: PMC8208553 DOI: 10.1371/journal.pone.0253285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/01/2021] [Indexed: 12/30/2022] Open
Abstract
PURPOSE More than half of patients with bile duct cancer (BDC) develop recurrence even after curative resection. Recurrent BDC has a poor prognosis, and no optimal treatment modality has been established. We therefore analyzed our experience on the survival outcomes of radiation therapy (RT) for recurrent extrahepatic bile duct cancer (EHBDC). PATIENTS AND METHODS We retrospectively analyzed the records of patients with recurrent EHBDC who underwent concurrent chemoradiation therapy (CCRT) or RT alone at our institution between January 2001 and June 2015. Freedom from locoregional progression (FFLP), progression-free survival (PFS), and overall survival (OS) were assessed, and univariate and multivariate analyses were performed to identify the prognostic factors. RESULTS A total of 76 patients were included in the analysis. The median OS was 16 months and the rates of 2-year FFLP, PFS, and OS were 61%, 25%, and 33%, respectively. Among the evaluable patients, the first site of failure was the locoregional area in 16 patients, distant metastasis in 27, and both sites in 8. On univariate analysis, disease-free interval (p = 0.012) and concurrent chemotherapy (p = 0.040) were found as significant prognostic factors for OS. One patient with CCRT developed a grade 3 hematologic toxicity, and two patients experienced late grade 3 toxicities including duodenal ulcer bleeding and obstruction. CONCLUSIONS RT for recurrent EHBDC showed favorable survival and local control with limited treatment-related toxicities. Considering that the most common pattern of failure was distant metastasis, further studies on the optimal scheme of chemotherapy and RT are warranted.
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Affiliation(s)
- Minji Koh
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin-hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- * E-mail:
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Min Yoon
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinhong Jung
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Heung-Moon Chang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyu-pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Takahashi D, Mizuno T, Yokoyama Y, Igami T, Yamaguchi J, Onoe S, Watanabe N, Maeda O, Ando M, Ebata T. Adjuvant S-1 vs gemcitabine for node-positive perihilar cholangiocarcinoma: A propensity score-adjusted analysis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:716-726. [PMID: 34087061 DOI: 10.1002/jhbp.1005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 05/10/2021] [Accepted: 05/29/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND The efficacy of adjuvant chemotherapy for biliary cancers remains controversial because of conflicting results from previous phase 3 studies that used different key drugs and enrolled patients with heterogeneous tumor sites and disease stages. Fluoropyrimidine seems more beneficial than gemcitabine (GEM) combination regimens in the adjuvant setting; however, data comparing the survival benefit between GEM- and fluoropyrimidine-based regimens are lacking. METHODS Patients who underwent resection for node-positive perihilar cholangiocarcinoma were included. The patients who underwent adjuvant chemotherapy were divided into the S-1 and GEM groups according to the regimen. The recurrence-free survival (RFS) and the overall survival (OS) were compared between the groups and adjusted with propensity scores generated from 14 potentially confounding clinicopathological factors. RESULTS In total, 186 patients (Surgery alone, n = 71; S-1, n = 60; GEM, n = 55) were included. The S-1 and GEM completion rates were 75% and 65%, respectively. Among the patients who underwent adjuvant therapy, the RFS was longer in the S-1 group patients than the GEM group patients (median, 24.4 months vs 14.9 months; P = .044) whereas the OS was not significantly different between the groups (median, 48.5 months vs 35.0 months; P = .324). After propensity score adjustment, the differences in RFS and OS between the groups were more evident (HR: 2.696, 95% CI: 1.739-4.180 P < .001; HR: 1.988, 95% CI: 1.221-3.238, P < .001, respectively). CONCLUSIONS Compared with adjuvant GEM monotherapy, adjuvant S-1 monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients.
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Affiliation(s)
- Daigoro Takahashi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shunsuke Onoe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobuyuki Watanabe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Osamu Maeda
- Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan
| | - Masahiko Ando
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Stefano M, Prosperi E, Fugazzola P, Benini B, Bisulli M, Coccolini F, Mastronardi C, Palladino A, Tomasoni M, Agnoletti V, Giampalma E, Ansaloni L. Case Report: Cytoreductive Surgery and HIPEC Associated With Liver Electrochemotherapy in a Cholangiocarcinoma Patient With Peritoneal Carcinomatosis and Liver Metastasis Case Report. Front Surg 2021; 8:624817. [PMID: 33816544 PMCID: PMC8018578 DOI: 10.3389/fsurg.2021.624817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/18/2021] [Indexed: 01/10/2023] Open
Abstract
Introduction: Cholangiocarcinoma (CCA) is the second most common primary tumor of the liver, and the recurrence after hepatic resection (HR), the only curative therapy, is linked with a worse prognosis. Systemic chemotherapy (SC) and liver loco-regional treatments, like trans-arterial chemoembolization (TACE) or radio embolization (TARE), have been employed for the treatment of unresectable intrahepatic metastasis (IM) with benefit on overall survival (OS), but SC has a limited effect on peritoneal metastasis (PM). In the last years, novel treatments like electrochemotherapy (ECT) with bleomycine (BLM) for IM and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) for PM have been applied in small series but with encouraging results. We hereby describe the first synchronous application of ECT and CRS and HIPEC for the treatment of a patient with IM and PM from CCA. Case Description: A 47-year-old male patient with CCA underwent HR followed by adjuvant SC. After 14 months, for the occurrence of IM, the patient underwent a second HR and SC. Nonetheless, a new recurrence occurred and a third attempt of HR was proposed. Due to the intraoperative finding of unresectable IM with PM, no resective procedure was performed and the patient was referred to our center. CRS and HIPEC with cisplatin and mitomycin for PM and ECT with BLM on a bulky metastasis of the hepatic hilum were performed after 38 months from the first HR. The length of hospital stay was 19 days. At the computed tomography (CT) performed 11 days after treatment complete necrosis of the treated IM was detected. Results: CT scan after 3 and 6 months and magnetic resonance after 9 months were performed. Necrosis of the treated IM nor PM but progression of the residual liver lesions was observed. After 3 months, the patient received SC and underwent TACE after 8 months and TARE after 9 months for the residual liver metastases. At 14 months from CRS and HIPEC, the patient is alive, in good condition, and with stability of the disease. Conclusions: The association of ECT and CRS and HIPEC could be safe and effective for the treatment of unresectable recurrent intrahepatic CCA with PM.
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Affiliation(s)
- Mauro Stefano
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Enrico Prosperi
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Paola Fugazzola
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Beatrice Benini
- Anesthesia and Intensive Care Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Marcello Bisulli
- Interventional Radiology Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Federico Coccolini
- General Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Costantino Mastronardi
- Anesthesia and Intensive Care Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Alessandro Palladino
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Matteo Tomasoni
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Vanni Agnoletti
- Anesthesia and Intensive Care Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Emanuela Giampalma
- Interventional Radiology Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Luca Ansaloni
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
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Kim H, Kim J, Byeon S, Jang KT, Hong JY, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK, Kim ST. Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer. Oncology 2021; 99:365-372. [PMID: 33730723 DOI: 10.1159/000514404] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 01/07/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. PATIENTS AND METHODS We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity. RESULTS Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer. CONCLUSION This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.
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Affiliation(s)
- Hyera Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Division of Hematology-Oncology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, Republic of Korea
| | - Jinchul Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seonggyu Byeon
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kee-Taek Jang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Yong Hong
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeeyun Lee
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Se Hoon Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joon Oh Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Suk Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ho Yeong Lim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Ki Kang
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seung Tae Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea,
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Chen M, Li S, Topatana W, Lv X, Cao J, Hu J, Lin J, Juengpanich S, Shen J, Cai X. Development and Validation of a Nomogram for Predicting Survival in Gallbladder Cancer Patients With Recurrence After Surgery. Front Oncol 2021; 10:537789. [PMID: 33505902 PMCID: PMC7829964 DOI: 10.3389/fonc.2020.537789] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 11/20/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The management of gallbladder cancer (GBC) patients with recurrence who need additional therapy or intensive follow-up remains controversial. Therefore, we aim to develop a nomogram to predict survival in GBC patients with recurrence after surgery. METHODS A total of 313 GBC patients with recurrence from our center was identified as a primary cohort, which were randomly divided into a training cohort (N = 209) and an internal validation cohort (N = 104). In addition, 105 patients from other centers were selected as an external validation cohort. Independent prognostic factors, identified by univariate and multivariable analysis, were used to construct a nomogram. The performance of this nomogram was measured using Harrell's concordance index (C-index) and calibration curves. RESULTS Our nomogram was established by four factors, including time-to-recurrence, site of recurrence, CA19-9 at recurrence, and treatment of recurrence. The C-index of this nomogram in the training, internal and external validation cohort was 0.871, 0.812, and 0.754, respectively. The calibration curves showed an optimal agreement between nomogram prediction and actual observation. Notably, this nomogram could accurately stratify patients into different risk subgroups, which allowed more significant distinction of Kaplan-Meier curves than that of using T category. The 3-year post-recurrence survival (PRS) rates in the low-, medium-, and high-risk subgroups from the external validation cohort were 53.3, 26.2, and 4.1%, respectively. CONCLUSION This nomogram provides a tool to predict 1- and 3-year PRS rates in GBC patients with recurrence after surgery.
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Affiliation(s)
- Mingyu Chen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Engineering Research Center of Cognitive Healthcare of Zhejiang Province, Hangzhou, China
| | - Shijie Li
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Win Topatana
- Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaozhong Lv
- Department of General Surgery, First People’s Hospital, Mudanjiang, China
| | - Jiasheng Cao
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiahao Hu
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Lin
- Department of General Surgery, Longyou People’s Hospital, Quzhou, China
| | | | - Jiliang Shen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
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Yamamoto M, Yoshida M, Furuse J, Sano K, Ohtsuka M, Yamashita S, Beppu T, Iwashita Y, Wada K, Nakajima TE, Sakamoto K, Hayano K, Mori Y, Asai K, Matsuyama R, Hirashita T, Hibi T, Sakai N, Tabata T, Kawakami H, Takeda H, Mizukami T, Ozaka M, Ueno M, Naito Y, Okano N, Ueno T, Hijioka S, Shikata S, Ukai T, Strasberg S, Sarr MG, Jagannath P, Hwang TL, Han HS, Yoon YS, Wang HJ, Luo SC, Adam R, Gimenez M, Scatton O, Oh DY, Takada T. Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:1-25. [PMID: 33200538 DOI: 10.1002/jhbp.868] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/30/2020] [Accepted: 11/08/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.
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Affiliation(s)
- Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare, School of Medicine, Ichikawa, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan
| | - Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shingo Yamashita
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Yukio Iwashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Keita Wada
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Takako Eguchi Nakajima
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
- Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, Kyoto University Hospital, Kyoto, Japan
| | - Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Koichi Hayano
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasuhisa Mori
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koji Asai
- Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokoama, Japan
| | - Teijiro Hirashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nozomu Sakai
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tsutomu Tabata
- Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Hiroyuki Takeda
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Takuro Mizukami
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Masato Ozaka
- Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makoto Ueno
- Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Yoichi Naito
- Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Naohiro Okano
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan
| | - Takayuki Ueno
- Breast Surgical Oncology, Cancer Institute Hospital, Tokyo, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | | | - Tomohiko Ukai
- Division of Public Health, Osaka Institute of Public Health, Higashinari, Japan
| | - Steven Strasberg
- Section of HPB Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | | | | | - Tsann-Long Hwang
- Division of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Ho-Seong Han
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yoo-Seok Yoon
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | | | - Shao-Ciao Luo
- Taichung Veterans General Hospital, Taichung, Taiwan
| | - René Adam
- AP HP Paul Brousse Hospital, University Paris Sud, Villejuif, France
| | - Mariano Gimenez
- Docencia Asistencia Investigación en Cirugía Invasiva Mínima Foundation, General and Minimally Invasive Surgery, University of Buenos Aires, Viamonte, Argentina
- Institute of Image-Guided Surgery, Strasbourg, France
| | - Olivier Scatton
- Department of Hepatobiliary Surgery and Liver Transplantation, APHP Pitié-Salpêtrière Hospital, Sorbonne Université, CRSA, Paris, France
| | - Do-Youn Oh
- Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Tadahiro Takada
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
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Bartsch F, Eberhard J, Rückert F, Schmelzle M, Lehwald-Tywuschik N, Fichtner-Feigl S, Gaedcke J, Oldhafer KJ, Oldhafer F, Diener M, Mehrabi A, Settmacher U, Becker T, Keck T, Friess H, Strücker B, Opitz S, Lemke J, Schnitzbauer A, Lang H. Repeated resection for recurrent intrahepatic cholangiocarcinoma: A retrospective German multicentre study. Liver Int 2021; 41:180-191. [PMID: 32997886 DOI: 10.1111/liv.14682] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/15/2020] [Accepted: 09/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tumour recurrence is common after resection of intrahepatic cholangiocarcinoma (ICC). Repeated resection is a potential curative treatment, but outcomes are not well-defined thus far. The aim of this retrospective multicentre cohort study was to show the feasibility and survival of repeated resection of ICC recurrence. METHODS Data were collected from 18 German hepato-pancreatico-biliary centres for patients who underwent repeated exploration of recurrent ICC between January 2008 and December 2017. Primary end points were overall (OS) and recurrence-free survival from the day of primary and repeated resection. RESULTS Of 156 patients who underwent repeated exploration for recurrent ICC, 113 underwent re-resection. CA19-9 prior to primary resection, R status of first liver resection and median time to recurrence were significant determinants of repeated resectability. Median OS in the repeated resection group was 65.2 months, with consecutive 1-, 3- and 5-year OS of 98%, 78% and 57% respectively. After re-exploration, median OS from primary resection was 46.7 months, with a consecutive 1-, 3- and 5-year OS of 95%, 55% and 22% respectively. From the day of repeated resection, the median OS was 36.8 months, with a consecutive 1-, 3- and 5-year OS of 86%, 51% and 34% respectively. Minor morbidity (grade I+II) was present in 27%, grade IIIa-IVb morbidity in 20% and mortality in 3.5% of patients. CONCLUSION Repeated resection of ICC has acceptable morbidity and mortality and seems to be associated with improved long-term survival. Structured follow-up after resection of ICC is necessary for early identification of these patients.
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Affiliation(s)
- Fabian Bartsch
- Department of General, Visceral and Transplant Surgery - University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Johannes Eberhard
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Felix Rückert
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moritz Schmelzle
- Department of Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | | | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Medical Center, University of Freiburg, Freiburg, Germany
| | - Jochen Gaedcke
- Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany
| | - Karl J Oldhafer
- Division of Hepatopancreatobiliary (HPB) Surgery, Department of Surgery, Asklepios Hospital Barmbek, Semmelweis University, Hamburg, Germany
| | - Felix Oldhafer
- Department of General, Visceral and Transplant Surgery, Medizinische Hochschule Hannover, Hannover, Germany
| | - Markus Diener
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Utz Settmacher
- Clinic for General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | - Thomas Becker
- Department for General, Visceral-, Thoracic-, Transplantation-, and Pediatric Surgery, University Hospital Schleswig Holstein, Kiel, Germany
| | - Tobias Keck
- Department of Surgery, University Medical Center Schleswig-Holstein, Luebeck, Germany
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Benjamin Strücker
- Department of General, Visceral and Transplantation Surgery, Universitätsklinikum Münster, Münster, Germany
| | - Sabine Opitz
- Department of Surgery, Regensburg University Medical Center, Regensburg, Germany
| | - Johannes Lemke
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - Andreas Schnitzbauer
- Department of General and Visceral Surgery, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/Main, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery - University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
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Lang H. Surgical Approach to Recurrent Cholangiocarcinoma. Visc Med 2020; 37:26-31. [PMID: 33718481 DOI: 10.1159/000513711] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 12/11/2020] [Indexed: 12/17/2022] Open
Abstract
Background For recurrent cholangiocarcinoma, systemic chemotherapy is the standard of care. Repeated resection is a potential curative treatment, but data are scarce and outcomes are not well defined so far. Summary In the last decade there has been an increasing number of reports suggesting a survival benefit and even cure after repeated surgery. This is particularly true for intrahepatic cholangiocarcinoma, where repeated resections offer similar or even better results than the first resection. In selected cases even a third liver resection is possible. In contrast, in perihilar and distal cholangiocarcinoma, repeated resection is only rarely possible. Although the improved outcome might be attributed to a careful patient selection and a favorable tumor biology, repeated surgical treatment should be attempted whenever possible. This necessitates a structured follow-up after resection. Key Message Surgical resection offers the chance for prolonged survival and even for cure in recurrent cholangiocarcinoma. Hence, it is of the utmost importance to better understand the routes of metastases and to define factors qualifying for resection. Whether different patterns of recurrence reflect biological heterogeneity requires further investigation.
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Affiliation(s)
- Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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30
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Kamada Y, Hori T, Yamamoto H, Harada H, Yamamoto M, Yamada M, Yazawa T, Tani M, Sato A, Tani R, Aoyama R, Sasaki Y, Zaima M. Surgical treatment of gallbladder cancer: An eight-year experience in a single center. World J Hepatol 2020; 12:641-660. [PMID: 33033570 PMCID: PMC7522563 DOI: 10.4254/wjh.v12.i9.641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 07/10/2020] [Accepted: 07/18/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is the most common biliary malignancy and has the worst prognosis, but aggressive surgeries [e.g., resection of the extrahepatic bile duct (EHBD), major hepatectomy and lymph node (LN) dissection] may improve long-term survival. GBC may be suspected preoperatively, identified intraoperatively, or discovered incidentally on histopathology. AIM To present our data together with a discussion of the therapeutic strategies for GBC. METHODS We retrospectively investigated nineteen GBC patients who underwent surgical treatment. RESULTS Nearly all symptomatic patients had poor outcomes, while suspicious or incidental GBCs at early stages showed excellent outcomes without the need for two-stage surgery. Lymph nodes around the cystic duct were reliable sentinel nodes in suspicious/incidental GBCs. Intentional LN dissection and EHBD resection prevented metastases or recurrence in early-stage GBCs but not in advanced GBCs with metastatic LNs or invasion of the nerve plexus. All patients with positive surgical margins (e.g., the biliary cut surface) showed poor outcomes. Hepatectomies were performed in sixteen patients, nearly all of which were minor hepatectomies. Metastases were observed in the left-sided liver but not in the caudate lobe. We may need to reconsider the indications for major hepatectomy, minimizing its use except when it is required to accomplish negative bile duct margins. Only a few patients received neoadjuvant or adjuvant chemoradiation. There were significant differences in overall and disease-free survival between patients with stages ≤ IIB and ≥ IIIA disease. The median overall survival and disease-free survival were 1.66 and 0.79 years, respectively. CONCLUSION Outcomes for GBC patients remain unacceptable, and improved therapeutic strategies, including neoadjuvant chemotherapy, optimal surgery and adjuvant chemotherapy, should be considered for patients with advanced GBCs.
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Affiliation(s)
- Yasuyuki Kamada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Tomohide Hori
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan.
| | - Hidekazu Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Hideki Harada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Michihiro Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masahiro Yamada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Takefumi Yazawa
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masaki Tani
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Asahi Sato
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Ryotaro Tani
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Ryuhei Aoyama
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Yudai Sasaki
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masazumi Zaima
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
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Nakahashi K, Ebata T, Yokoyama Y, Igami T, Mizuno T, Yamaguchi J, Onoe S, Watanabe N, Nagino M. How long should follow-up be continued after R0 resection of perihilar cholangiocarcinoma? Surgery 2020; 168:617-624. [PMID: 32665142 DOI: 10.1016/j.surg.2020.04.068] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/20/2020] [Accepted: 04/29/2020] [Indexed: 01/03/2023]
Abstract
BACKGROUND Although several studies have been conducted on the patterns of recurrence in resected perihilar cholangiocarcinoma, the appropriate follow-up period after resection is still controversial. METHODS Consecutive patients who underwent an R0 resection of perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively, focusing on the time and site of initial recurrence. A Cox proportional hazards model was used for multivariate analysis. RESULTS During the study period, 404 patients underwent R0 resection, of whom 242 patients (59.9%) developed a recurrence. The most common site of recurrence was locoregional, followed by peritoneum and liver. Approximately 70% of patients were asymptomatic when recurrence was detected. The median survival time in all cohorts was 4.8 years, and the estimated cumulative probability of recurrence was 54.3% at 5 years and 65.7% at 10 years. Multivariate analyses revealed that lymph node metastasis (hazard ratio 2.80, P < .001) and microscopic venous invasion (hazard ratio, 1.70, P < .001) were independent risk factors for recurrence-free survival. The cumulative probability of recurrence in 84 patients with 2 risk factors was nearly 90% at 5 years; even in the 178 patients without risk factors, the probability at 5 years was 30%, and thereafter, the probability of recurrence gradually increased, reaching nearly 50% at 10 years. No trends in the time and site of recurrence were detected. CONCLUSION Approximately 60% of patients with perihilar cholangiocarcinoma experience recurrence after R0 resection. Even in patients without an independent risk for recurrence, the recurrence probability is high, reaching nearly 50% at 10 years. Thus, close surveillance for 10 years is necessary even after R0 resection of perihilar cholangiocarcinoma.
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Affiliation(s)
- Koichi Nakahashi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shunsuke Onoe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobuyuki Watanabe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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Wakai T, Nagahashi M, Shimada Y, Prasoon P, Sakata J. Genetic analysis in the clinical management of biliary tract cancer. Ann Gastroenterol Surg 2020; 4:316-323. [PMID: 32724874 PMCID: PMC7382432 DOI: 10.1002/ags3.12334] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/24/2020] [Accepted: 03/12/2020] [Indexed: 12/15/2022] Open
Abstract
Biliary tract cancer (BTC) is clinically and pathologically heterogeneous and responds inadequately to treatment. A small section of patients develop resectable disease, although the relapse rates are high; the benefits of adjuvant capecitabine chemotherapy for BTC are now understood, and gemcitabine-based combination chemotherapy is the first line of therapeutic strategy for BTC; however, alternative therapy for BTC is not known. Genomic profiling can provide detailed information regarding the carcinogenesis, identification, and therapy for BTC. Currently, confirmed restorative targets for BTC are lacking. In this review, we aimed to analyze the preclinical and clinical implications of a spectrum of genomic alterations associated with new potentially remedial targets. We focused on eight draggable genes for BTC, which were described as having evidence of therapeutic impact (evidence level 2A-3B) based on the clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment; these include ERBB2, NTRK1, RNF43, CDK6, CDKN2B, FGFR2, IDH1, and IDH2. Moreover, some of the BTC present microsatellite instability, hypermutation, and germline variants, which we also reviewed. Finally, we discussed the therapeutic options based on the next-generation sequencing findings in BTC. Studies have demonstrated that BTC includes subgroups with individually distinct driver mutations, most of which will be targeted with new treatment plans.
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Affiliation(s)
- Toshifumi Wakai
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Masayuki Nagahashi
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Yoshifumi Shimada
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Pankaj Prasoon
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Jun Sakata
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
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Nakanishi Y, Okamura K, Tsuchikawa T, Nakamura T, Noji T, Asano T, Matsui A, Tanaka K, Murakami S, Ebihara Y, Kurashima Y, Narasaki H, Amano T, Shichinohe T, Hirano S. Time to Recurrence After Surgical Resection and Survival After Recurrence Among Patients with Perihilar and Distal Cholangiocarcinomas. Ann Surg Oncol 2020; 27:4171-4180. [PMID: 32363510 DOI: 10.1245/s10434-020-08534-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. PATIENTS AND METHODS The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. RESULTS During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. CONCLUSIONS Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes.
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Affiliation(s)
- Yoshitsugu Nakanishi
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
| | - Keisuke Okamura
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Toshimichi Asano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Aya Matsui
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Soichi Murakami
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Yuma Ebihara
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Yo Kurashima
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Hajime Narasaki
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Toraji Amano
- Clinical Research and Medical Innovation Centre, Hokkaido University Hospital, Sapporo, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
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Morino K, Yoh T, Seo S. ASO Author Reflections: Defining Oligometastatic Recurrence in Biliary Tract Cancer. Ann Surg Oncol 2020; 27:1918. [PMID: 32170479 DOI: 10.1245/s10434-020-08339-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Indexed: 11/18/2022]
Affiliation(s)
- Koshiro Morino
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tomoaki Yoh
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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Ren B, Guo Q, Yang Y, Liu L, Wei S, Chen W, Tian Y. A meta-analysis of the efficacy of postoperative adjuvant radiotherapy versus no radiotherapy for extrahepatic cholangiocarcinoma and gallbladder carcinoma. Radiat Oncol 2020; 15:15. [PMID: 31941520 PMCID: PMC6964081 DOI: 10.1186/s13014-020-1459-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 01/05/2020] [Indexed: 12/13/2022] Open
Abstract
Objective The benefit of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma (EHCC) and gallbladder carcinoma (GBC) is unclear, with conflicting results from nonrandomized studies. We reported a meta-analysis to determine the impact of adjuvant radiotherapy on survival. Methods PubMed, EMBASE, Cochrane Library and CNKI databases were searched to identify clinical trials of postoperative ART versus no radiotherapy for EHCC and GBC. The obtained data were analyzed using RevMan 5.3 and Stata 14.0 statistical software. Differences between two groups were estimated by calculating the odds ratio (OR) and 95% confidence interval (CI). Results A total of 21 clinical trials involving 1465 EHCC and GBC patients were selected according to the inclusion and exclusion criteria and included in this meta-analysis. The meta-analysis showed the following: The 5-year overall survival (OS) rate was higher in the ART group than in the no radiotherapy group (OR = 0.63; 95% CI = 0.50–0.81, p = 0.0002). The 5-year OS rate was significantly higher for those with lymph node-positive disease (OR = 0.15; 95% CI 0.07–0.35; p < 0.00001) and margin-positive disease (OR = 0.40; 95% CI 0.19–0.85; p = 0.02) in the ART group than in the no radiotherapy group. ART had a tendency to bring benefit to the 5-year OS of patients with margin-negative disease but the difference was not statistically significant (OR = 0.57, 95% CI 0.30–1,07, p = 0.08). The local recurrence rate was significantly lower in the ART group than in the no radiotherapy group (OR = 0.54; 95% CI = 0.38–0.76, p = 0.0004), and there was no significant difference in the distant metastasis rate between the two groups (OR = 1.33; 95% CI = 0.95–1.87, p = 0.10). Conclusions A meta-analysis of the existing study results showed that compared with no radiotherapy, ART is an effective postoperative treatment for EHCC and GBC.
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Affiliation(s)
- Bixin Ren
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.,Suzhou Key Laboratory for Radiation Oncology, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
| | - Qi Guo
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.,Suzhou Key Laboratory for Radiation Oncology, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
| | - Yongqiang Yang
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.,Suzhou Key Laboratory for Radiation Oncology, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
| | - Lei Liu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.,Suzhou Key Laboratory for Radiation Oncology, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
| | - Shaohua Wei
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
| | - Wei Chen
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
| | - Ye Tian
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China. .,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China. .,Suzhou Key Laboratory for Radiation Oncology, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China.
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Morino K, Seo S, Yoh T, Fukumitsu K, Ishii T, Taura K, Morita S, Kaido T, Uemoto S. Proposed Definition for Oligometastatic Recurrence in Biliary Tract Cancer Based on Results of Locoregional Treatment: A Propensity-Score-Stratified Analysis. Ann Surg Oncol 2020; 27:1908-1917. [PMID: 31939034 DOI: 10.1245/s10434-020-08207-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Oligometastatic recurrence involves relapsed tumors for which locoregional treatment (LT) may yield a survival benefit. However, there are no clear criteria for selecting patients for LT or determining the effects of LT in recurrent biliary tract cancer (BTC). The aim of this retrospective study is to assess the effects of LT on survival outcomes and to identify potential criteria for selecting LT in recurrent BTC. PATIENTS AND METHODS In the present work, 232 consecutive patients with recurrent BTC who initially underwent curative surgery between 1996 and 2015 were evaluated. The primary outcome was length of survival after recurrence (SAR). Propensity score stratification with various tumor-related factors was used to identify patients who would likely benefit from LT. RESULTS Among the cohort, 60 (25.9%) patients underwent LT, whereas 172 (74.1%) patients did not. The multivariate Cox model identified carbohydrate antigen 19-9 levels of > 50 U/mL, multiorgan recurrence, tumor number > 3, tumor size > 30 mm, and early recurrence (≤ 1 year) as independent predictors of poor SAR (P < 0.001 for each factor). In the propensity-score-stratified analysis, LT was associated with survival benefits for patients representing single-organ recurrence with at most three tumors and late-onset recurrence (> 1 year) (median SAR: 48.6 vs. 14.2 months, n = 33 vs. n = 34, hazard ratio: 0.10, 95% confidence interval: 0.04-0.20, P < 0.001). CONCLUSIONS Patients with recurrent BTC may benefit from LT if they have single-organ recurrence with at most three tumors and late-onset recurrence. We propose that these patients may have clinically relevant "oligometastatic recurrence" of BTC.
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Affiliation(s)
- Koshiro Morino
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Tomoaki Yoh
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ken Fukumitsu
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Effectiveness of surgery for recurrent cholangiocarcinoma: A single center experience and brief literature review. Am J Surg 2020; 219:175-180. [DOI: 10.1016/j.amjsurg.2019.02.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 02/04/2019] [Accepted: 02/05/2019] [Indexed: 12/22/2022]
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Parietal recurrence of hiliar cholangiocarcinoma: Is percutaneous transhepatic biliary drainage the best choice in patients with hiliar cholangiocarcinoma? Cir Esp 2019; 98:368-370. [PMID: 31607380 DOI: 10.1016/j.ciresp.2019.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 08/08/2019] [Accepted: 08/16/2019] [Indexed: 11/22/2022]
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Inagaki C, Maeda D, Kimura A, Otsuru T, Iwagami Y, Nishida N, Sakai D, Shitotsuki R, Yachida S, Doki Y, Satoh T. Gallbladder cancer harboring ERBB2 mutation on the primary and metastatic site: A case report. World J Gastrointest Oncol 2019; 11:761-767. [PMID: 31558980 PMCID: PMC6755105 DOI: 10.4251/wjgo.v11.i9.761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 08/06/2019] [Accepted: 08/28/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Bile duct cancer constitutes gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICA), and extrahepatic cholangiocarcinoma (ECA). These three entities show morphological and immunohistochemical resemblance so that it is difficult to differentiate between primary ICA and liver metastasis of GBC, which sometimes becomes a point of discussion in clinical practice. Although these cancers demonstrate significant differences in their mutational landscape, several reports demonstrated shared genomic alteration in paired primary and metastatic site aids in distinguishing metastatic recurrence from second primary cancers.
CASE SUMMARY We present a 73-year-old female patient who underwent curative resection for GBC harboring epidermal growth factor receptor 2 (ERBB2) activating mutation on next-generation sequencing (NGS)-based genomic testing. One year later, a hepatic lesion was observed on follow-up imaging and she underwent surgical resection for a pathological diagnosis. The histological findings of the hepatic lesion were similar to those of the primary lesion. Additionally, using NGS panel testing, the hepatic lesion was found to have ERBB2 activating mutation, which is the identical mutation detected in the sequencing result of the primary site. ERBB2 activating mutation occurs more frequently in GBC than ICA and ECA. Therefore, in the present case, we think this molecular finding potentiated the diagnosis of the liver mass toward a metastatic recurrence. Additionally, this patient underwent HER2-targeted treatment with lapatinib in combination with capecitabin and obtained clinical benefit.
CONCLUSION This case illustrated NGS panel usefulness in distinguishing GBC recurrence from second primary cancer and HER2-targeted agent efficacy on ERBB2 mutated GBC.
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Affiliation(s)
- Chiaki Inagaki
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Daichi Maeda
- Department of Clinical Genomics, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Akie Kimura
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Toru Otsuru
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Naohiro Nishida
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Daisuke Sakai
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
- Center for Cancer Genomics and Personalized Medicine, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Ryo Shitotsuki
- Center for Cancer Genomics and Personalized Medicine, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Shinichi Yachida
- Department of Cancer Genome Informatics, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita 5650871, Osaka, Japan
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Kitano Y, Yamashita YI, Nakao Y, Itoyama R, Yusa T, Umezaki N, Tsukamoto M, Yamao T, Miyata T, Nakagawa S, Okabe H, Imai K, Chikamoto A, Ishiko T, Baba H. Clinical Significance of PD-L1 Expression in Both Cancer and Stroma Cells of Cholangiocarcinoma Patients. Ann Surg Oncol 2019; 27:599-607. [PMID: 31407173 DOI: 10.1245/s10434-019-07701-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND The clinical significance of programmed death 1 and its ligand (PD-L1) as therapeutic targets has been reported previously. This study aimed to investigate the clinical impact of PD-L1 expression in cancer and stroma cells in cholangiocarcinoma (CCA). METHODS The study enrolled 177 consecutive CCA patients who underwent curative resection between 2005 and 2014. Expression of PD-L1 in CCA and stroma cells was assayed by immunohistochemistry, and their relationships with patient clinicopathologic characteristics and prognoses were evaluated. Tumor-infiltrating immune cells (CD66b+ neutrophils [TANs] and CD163+ M2 macrophages [TAMs]) also were assayed by immunohistochemistry, and their relationship with PD-L1 expression in cancer and stroma cells was evaluated. RESULTS Among the 177 analyzed CCA cases, PD-L1 expression was identified in cancer cells in 54 cases (30.5%) and in stroma cells in 77 cases (43.5%). The patients with positive PD-L1 expression in cancer and stroma cells had worse overall survival rates than those negative for PD-L1 (cancer cells: hazard ratio [HR] 2.08; P = 0.0004; stroma cells: HR 1.84; P = 0.003). Moreover, the patients with PD-L1-positive cancer cells had higher rates of PD-L1 expression in stroma cells (P < 0.0001) and higher numbers of TANs (P = 0.0003) and TAMs (P = 0.004) than those with low PD-L1 expression. In the multivariate analysis, PD-L1 expression in both cancer and stroma cells (HR 2.20; P = 0.002) was an independent predictor of poor overall survival. CONCLUSIONS The study showed PD-L1 expressed in both CCA and stromal cells and demonstrated that its expression may affect numbers of TANs and TAMs and play a pivotal role in CCA outcomes.
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Affiliation(s)
- Yuki Kitano
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yosuke Nakao
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Toshihiko Yusa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Naoki Umezaki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masayo Tsukamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takanobu Yamao
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tatsunori Miyata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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Mori S, Aoki T, Park K, Shiraki T, Sakuraoka Y, Iso Y, Kato M, Kubota K. Impact of preoperative percutaneous transhepatic biliary drainage on post‐operative survival in patients with distal cholangiocarcinoma. ANZ J Surg 2019; 89:E363-E367. [DOI: 10.1111/ans.15329] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/16/2019] [Accepted: 05/20/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Shozo Mori
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Taku Aoki
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Kyung‐Hwa Park
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Takayuki Shiraki
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Yuki Sakuraoka
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Yukihiro Iso
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Masato Kato
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
| | - Keiichi Kubota
- Department of Gastroenterological SurgeryDokkyo Medical University Mibu Tochigi, Japan
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Bartsch F, Paschold M, Baumgart J, Hoppe-Lotichius M, Heinrich S, Lang H. Surgical Resection for Recurrent Intrahepatic Cholangiocarcinoma. World J Surg 2019; 43:1105-1116. [PMID: 30523392 DOI: 10.1007/s00268-018-04876-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Although after R0 resection of intrahepatic cholangiocarcinoma (ICC) recurrence is frequent, most guidelines do not address strategies for this. The aim of this study was to analyze the outcome of repeated resection and to determine criteria when repeated resection is reasonable. METHODS Between 2008 and 2016, we consecutively collected all cases of ICC (n = 176) in a prospective database and further analyzed them with a focus on tumor recurrence, its surgical treatment, overall survival and recurrence-free survival. RESULTS Overall, a total of 22 explorations were performed for recurrent ICC in 17 patients. Resection rate was 18 repeated resections in 13 patients. Three patients underwent repeated resection twice and one patient three times. Recurrence was solitary in 7 patients and multifocal in 11 re-resected cases. Median overall survival (OS) of patients who underwent repeated resection was 65.2 months (interquartile range 37-126.5) with a 5-year OS rate of 62%, calculated from primary resection. Patients who underwent repeated resections had a significant better OS compared to those receiving chemotherapy, transarterial chemoembolization, selective internal radiotherapy, radiofrequency ablation or best supportive care (p < 0.001). CONCLUSION Repeated resection of recurrent ICC is reasonable and associated with an improved survival. Re-exploration should be considered as long as resection is technically possible.
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Affiliation(s)
- Fabian Bartsch
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Markus Paschold
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Janine Baumgart
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Maria Hoppe-Lotichius
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Stefan Heinrich
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
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Sarcopenia Affects Systemic and Local Immune System and Impacts Postoperative Outcome in Patients with Extrahepatic Cholangiocarcinoma. World J Surg 2019; 43:2271-2280. [DOI: 10.1007/s00268-019-05013-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Kawaguchi K, Taniguchi T, Fukui T, Nakamura S, Yokoi K. Radiological findings and surgical outcomes of pulmonary metastases originating from biliary tract carcinoma. Gen Thorac Cardiovasc Surg 2019; 67:962-968. [PMID: 30980226 DOI: 10.1007/s11748-019-01122-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 04/05/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Metastasis to the lungs arising from biliary tract carcinoma (BTC) is extremely rare, and the patient characteristics and prognosis are not well known. We aimed to identify the imaging findings of pulmonary metastases originating from BTC and the eligible indications for surgical treatment. METHODS Fifteen patients who underwent pulmonary resection for metastases originating from BTC were retrospectively analyzed. RESULTS The primary sites included cholangiocarcinoma (n = 12) and gallbladder carcinoma (n = 3), and all cases were histologically diagnosed as well to moderately differentiated adenocarcinomas. The median disease-free interval between resection for the primary site and the detection of pulmonary metastasis was 30 months (range 0-144 months). Nine patients had a single lesion, and six had multiple lesions. As features of pulmonary lesions on thin-section computed tomography (CT), many appeared as solid nodules with smooth margins, whereas six lesions were concomitant with spiculation or pleural indentation, three with air bronchogram or ground-glass attenuation, and one with intra-tumoral cavity, and six cases with solitary pulmonary lesion were diagnosed as primary lung cancer before metastasectomy. The 3-year survival rate in the 11 patients who underwent complete metastasectomy was 45%. A disease-free interval of more than 3 years (p = 0.03) and single lesion (p < 0.01) were significant prognostic factors. CONCLUSIONS The CT findings of pulmonary metastases from BTCs sometimes resemble the characteristic findings of primary lung cancer. A long disease-free interval and single lesion are therefore considered to be good surgical indicators.
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Affiliation(s)
- Koji Kawaguchi
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Tetsuo Taniguchi
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.,Division of Thoracic Surgery, Komaki City Hospital, Komaki, Japan
| | - Takayuki Fukui
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Shota Nakamura
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Kohei Yokoi
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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Sano K, Yamamoto M, Mimura T, Endo I, Nakamori S, Konishi M, Miyazaki M, Wakai T, Nagino M, Kubota K, Unno M, Sata N, Yamamoto J, Yamaue H, Takada T. Outcomes of 1,639 hepatectomies for non-colorectal non-neuroendocrine liver metastases: a multicenter analysis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2018; 25:465-475. [PMID: 30311741 DOI: 10.1002/jhbp.587] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Whether non-colorectal non-neuroendocrine liver metastasis (NCNNLM) should be treated surgically remains unclear. METHODS Data regarding 1,639 hepatectomies performed between 2001 and 2010 for 1,539 patients with NCNNLM were collected from 124 institutions. Patient characteristics, types of primary tumor, characteristics of liver metastases, and post-hepatectomy outcomes were analyzed. RESULTS The five most frequent primary tumors were gastric carcinoma (540 patients [35%]), gastrointestinal stromal tumor (204 patients [13%]), biliary carcinoma (150 patients [10%]), ovarian cancer (107 patients [7%]), and pancreatic carcinoma (77 patients [5%]). R0/1 hepatectomy was achieved in 90% of patients, with 1.5% in-hospital mortality rate. Overall and disease-free survival rates of 1,465 patients included in survival analysis were 41% and 21%, respectively, at 5 years, and 28% and 15%, respectively, at 10 years. Five-year survival associated with the five frequent primary tumors were 32%, 72%, 17%, 52%, and 31%, respectively, and factors predictive of a poor outcome differed by the primary tumor type. CONCLUSIONS Our data indicated that hepatectomy is safe for NCNNLM and that patient prognoses vary depending on the type of primary tumors. Indications for hepatectomy should be determined with reference to survival rates and risk factors specific to each of the various types of primary tumor.
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Affiliation(s)
- Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University Hospital, Tokyo, Japan
| | - Tetsushige Mimura
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Shoji Nakamori
- Department of Hepatobiliary-Pancreatic Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan
| | - Masaru Konishi
- Department of Hepatobiliary-Pancreatic Surgery, National Cancer Center Hospital East, Tokyo, Japan
| | - Masaru Miyazaki
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Mibu, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Naohiro Sata
- Department of Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Junji Yamamoto
- Department of Surgery, National Defense Medical College, Tokorozawa, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Tadahiro Takada
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
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Yoshikawa M, Ikemoto T, Morine Y, Imura S, Saito Y, Yamada S, Teraoku H, Takata A, Yoshimoto T, Shimada M. Aggressive resection of metachronous triple biliary cancer. THE JOURNAL OF MEDICAL INVESTIGATION 2018; 64:299-304. [PMID: 28955001 DOI: 10.2152/jmi.64.299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Radical resection of recurrent cholangiocellular carcinoma (CCC) is rare. To date, only two patients have been reported to undergo major hepatectomy twice after pancreatoduodenectomy (PD) for metachronous CCC. This report describes a patient who underwent three metachronous radical resections of CCC with curative intent, consisting of PD followed by two hepatectomies, for cancer of the middle bile duct. A 60 year old male, who had undergone a distal gastrectomy for duodenal ulcer perforation in 23 years ago, underwent PD (Honjo method) for middle bile duct cancer (papillary adenocarcinoma) in 20 years ago at another hospital. In 12 years ago, he was referred to our hospital for further examinations of hepatic tumors and was diagnosed with CCC (S6, solitary, 4 cm). He underwent S6 subsegmentectomy of the liver. Pathological examination revealed a poorly differentiated CCC, considered a second primary cancer. In 6 years ago, subsequent follow up as an outpatient revealed repeated cholangitis, with CT showing a hilar mass caused by obstructive jaundice. He was diagnosed with a hilar cholangioma, and underwent hepatectomy and hepaticojejunostomy, which were safe despite surgical difficulties caused by severe adhesions and re-anastomosis. Pathological examination showed a well-differentiated CCC, considered the third primary cancer. The lung metastasis was revealed in 28 months after the last operation, however he has survived after partial lung resection without further metastasis. J. Med. Invest. 64: 299-304, August, 2017.
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Affiliation(s)
- Masato Yoshikawa
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Yuji Morine
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Satoru Imura
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Yu Saito
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Shinichiro Yamada
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Hiroki Teraoku
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Atsushi Takata
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Toshiaki Yoshimoto
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University Graduate Shool of Biomedical Sciences
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Sakamoto T, Honjo S, Morimoto M, Amisaki M, Arai Y, Tokuyasu N, Ashida K, Saito H, Nosaka K, Fujiwara Y. Successful resection of a slow-growing synchronous pulmonary metastasis from distal cholangiocarcinoma resected 3.5 years after initial surgery: a case report. J Med Case Rep 2018; 12:136. [PMID: 29784024 PMCID: PMC5963088 DOI: 10.1186/s13256-018-1671-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 03/28/2018] [Indexed: 12/27/2022] Open
Abstract
Background A few reports have described the effectiveness of resection for recurrent cholangiocarcinoma. However, none have described resection of synchronous pulmonary metastasis from distal cholangiocarcinoma. We report the first case, to the best of our knowledge, of a slow-growing synchronous pulmonary metastasis from distal cholangiocarcinoma resected 3.5 years after the initial surgery. Case presentation A 67-year-old Japanese man with a diagnosis of distal cholangiocarcinoma was referred to our hospital. Thickening of the distal bile duct and an air-space pattern in the upper lobe of the left lung were detected by preoperative computed tomography. He underwent pancreaticoduodenectomy for the distal cholangiocarcinoma. Follow-up chest computed tomography demonstrated that the air-space pattern in the left lung had gradually enlarged. Thoracoscopic left S6 segmentectomy with lymph node dissection was performed 3.5 years after the initial surgery. Histopathology of the resected specimen revealed a solitary metastasis from distal cholangiocarcinoma with lepidic growth. We diagnosed the patient with a solitary synchronous pulmonary metastasis from distal cholangiocarcinoma. Conclusions Surgical resection might offer better long-term survival to patients with synchronous pulmonary metastasis from distant cholangiocarcinoma than nonsurgical treatments. Pulmonary metastasis from distal cholangiocarcinoma may exhibit a lepidic pattern. Therefore, because of the possibility of synchronous pulmonary metastasis, pulmonary resection should be considered for patients with lepidic lesions who have been diagnosed with distal cholangiocarcinoma.
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Affiliation(s)
- Teruhisa Sakamoto
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Soichiro Honjo
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
| | - Masaki Morimoto
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Masataka Amisaki
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Yosuke Arai
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Naruo Tokuyasu
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Keigo Ashida
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Hiroaki Saito
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Kanae Nosaka
- Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan
| | - Yoshiyuki Fujiwara
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
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Yamada M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, Yamaguchi J, Nagino M. Pulmonary Metastasis After Resection of Cholangiocarcinoma: Incidence, Resectability, and Survival. World J Surg 2018; 41:1550-1557. [PMID: 28105527 DOI: 10.1007/s00268-017-3877-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND There are few reports on pulmonary metastasis from cholangiocarcinoma; therefore, its incidence, resectability, and survival are unclear. METHODS Patients who underwent surgical resection for cholangiocarcinoma, including intrahepatic, perihilar, and distal cholangiocarcinoma were retrospectively reviewed, and this study focused on patients with pulmonary metastasis. RESULTS Between January 2003 and December 2014, 681 patients underwent surgical resection for cholangiocarcinoma. Of these, 407 patients experienced disease recurrence, including 46 (11.3%) who developed pulmonary metastasis. Of these 46 patients, 9 underwent resection for pulmonary metastasis; no resection was performed in the remaining 37 patients. R0 resection was achieved in all patients, and no complications related to pulmonary metastasectomy were observed. The median time to recurrence was significantly longer in the 9 patients who underwent surgery than in the 37 patients without surgery (2.5 vs 1.0 years, p < 0.010). Survival after surgery for primary cancer and survival after recurrence were significantly better in the former group than in the latter group (after primary cancer: 66.7 vs 0% at 5 years, p < 0.001; after recurrence: 40.0 vs 8.7% at 3 years, p = 0.003). Multivariate analysis identified the time to recurrence and resection for pulmonary metastasis as independent prognostic factors for survival after recurrence. CONCLUSION Resection for pulmonary metastasis originating from cholangiocarcinoma can be safely performed and confers survival benefits for select patients, especially those with a longer time to recurrence after initial surgery.
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Affiliation(s)
- Mihoko Yamada
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Gen Sugawara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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Komaya K, Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, Yamaguchi J, Nagino M. Recurrence after curative-intent resection of perihilar cholangiocarcinoma: analysis of a large cohort with a close postoperative follow-up approach. Surgery 2018; 163:732-738. [PMID: 29336813 DOI: 10.1016/j.surg.2017.08.011] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 08/18/2017] [Accepted: 08/30/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND Although several studies have been conducted on the patterns of recurrence in resected perihilar cholangiocarcinoma, they have many limitations. The aim of this study was to investigate recurrence after resection and to evaluate prognostic factors on the time to recurrence and recurrence-free survival. METHODS Consecutive patients who underwent curative-intent resection of perihilar cholangiocarcinoma between 2001 and 2012 were reviewed retrospectively. The Cox proportional hazards model was used for multivariable analysis. RESULTS In the study period, 402 patients underwent resection of perihilar cholangiocarcinoma (R0, n = 340; R1, n = 62). Radial margin positivity (n = 43, 69%) was the most common reason for R1 resection. The median follow-up of survivors was 7.4 years. The cumulative recurrence probability was higher in R1 than in R0 resection (86% vs 57% at 5 years, P < .001). Seventeen R0 patients had a recurrence over 5 years after resection. There was no difference in median survival time after recurrence between R0 and R1 resection (10 vs 7 months). The proportion of isolated locoregional recurrence was higher in R1 than in R0 resection (37% vs 16%, P < .001), whereas the proportion of distant recurrence was similar. In R0 resection, the independent prognostic factors for time to recurrence and recurrence-free survival were microscopic venous invasion and lymph node metastasis. CONCLUSION More than half of patients with perihilar cholangiocarcinoma experience recurrence after R0 resection. These recurrences occur frequently within 5 years but occasionally after 5 years, which emphasizes the need for close and long-term surveillance. Adjuvant strategies should be considered, especially for patients with nodal metastasis or venous invasion even after R0 resection.
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Affiliation(s)
- Kenichi Komaya
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Gen Sugawara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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50
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Abstract
Cholangiocarcinomas (CC) are rare tumors which usually present late and are often difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic CCs may be increasing worldwide. In this chapter, we review the risk factors, clinical presentation, and management of cholangiocarcinoma.
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