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Andraus W, Tustumi F, Santana AC, Pinheiro RSN, Waisberg DR, Lopes LD, Arantes RM, Santos VR, de Martino RB, D'Albuquerque LAC. Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review. Hepatobiliary Pancreat Dis Int 2024; 23:139-145. [PMID: 38310060 DOI: 10.1016/j.hbpd.2024.01.003] [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: 08/16/2023] [Accepted: 01/19/2024] [Indexed: 02/05/2024]
Abstract
BACKGROUND Perihilar cholangiocarcinoma (phCCC) is a dismal malignancy. There is no consensus regarding the best treatment for patients with unresectable phCCC. The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice. DATA SOURCES The search was conducted in PubMed, Embase, Cochrane, and LILACS. The related references were searched manually. Inclusion criteria were: reports in English or Portuguese literature that a) patients with confirmed diagnosis of phCCC; b) patients treated with a curative intent; c) patients with the outcomes of liver resection and liver transplantation. Case reports, reviews, letters, editorials, conference abstracts and papers with full-text unavailability were excluded from the analysis. RESULTS Most of the current literature is based on observational retrospective studies with low grades of evidence. Liver resection has better long-term outcomes than systemic chemotherapy or palliation therapy and liver transplantation is a good alternative for selected patients with unresectable phCCC. All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahepatic diseases. As a general rule, patients presenting with a tumor having a longitudinal size > 3 cm or extending below the cystic duct, lymph node disease, confirmed extrahepatic dissemination; intraoperatively diagnosed metastatic disease; a history of other malignancies within the last five years, and did not complete chemoradiation regimen and were medically unfit should not be considered for transplantation. Some of these criteria should be individually assessed. Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers, and any decision-making must be based on a multidisciplinary evaluation. CONCLUSIONS phCCC is a complex condition with high morbidity. Surgical therapies, including hepatectomy and liver transplantation, are the best option for better long-term disease-free survival.
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Affiliation(s)
- Wellington Andraus
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil.
| | - Francisco Tustumi
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Alexandre Chagas Santana
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | | | - Daniel Reis Waisberg
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Liliana Ducatti Lopes
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Rubens Macedo Arantes
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Vinicius Rocha Santos
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
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Bröring TS, Wagner KC, von Hahn T, Oldhafer KJ. Parenchyma-Preserving Hepatectomy in Perihilar Cholangiocarcinoma: A Chance for Critical Patients? Visc Med 2024; 40:53-60. [PMID: 38584859 PMCID: PMC10995988 DOI: 10.1159/000537884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 02/15/2024] [Indexed: 04/09/2024] Open
Abstract
Introduction Surgery for perihilar cholangiocarcinoma (pCCA) is associated with high rates of postoperative morbidity and mortality. Extended liver resection (EXT) increases R0 resection rate and survival; however, patients with high perioperative risk are not suitable for extended resection. This study aimed to compare overall survival and surgical morbidity in patients with extended liver resection and parenchyma-preserving hepatectomy (PPH). Methods Between January 2010 and November 2020, 113 consecutive patients with pCCA underwent surgery at our institution. Eighty-two patients were resected in curative intent. Sixty-four patients received extended liver resection, and 18 patients PPH. Outcomes of resections were evaluated. Results There was no significant difference in overall survival in patients with PPH compared to extended liver resection (log-rank p = 0.286). Patients with PPH experienced lower rates of postoperative morbidity and mortality. There was no case of in-house mortality in PPH-resected patients compared to 10 cases (16%) in patients that received EXT (p = 0.073). Conclusion PPH shows similar overall survival with lower rates of postoperative morbidity and mortality. Our findings support the role of a PPH, in selected patients with pCCA, that are not suitable for extended resection due to increased perioperative risk.
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Affiliation(s)
- Tobias S. Bröring
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Kim C. Wagner
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Thomas von Hahn
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
- Department of Gastroenterology and Interventional Endoscopy, Asklepios Hospital Barmbek, Hamburg, Germany
| | - Karl J. Oldhafer
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
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Kodali S, Connor AA, Thabet S, Brombosz EW, Ghobrial RM. Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions. Hepatobiliary Pancreat Dis Int 2024; 23:129-138. [PMID: 37517983 DOI: 10.1016/j.hbpd.2023.07.007] [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: 04/04/2023] [Accepted: 07/21/2023] [Indexed: 08/01/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a rare biliary tract cancer with high mortality rate. Complete resection of the iCCA lesion is the first choice of treatment, with good prognosis after margin-negative resection. Unfortunately, only 12%-40% of patients are eligible for resection at presentation due to cirrhosis, portal hypertension, or large tumor size. Liver transplantation (LT) offers margin-negative iCCA extirpation for patients with unresectable tumors. Initially, iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes. Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA. Another selection criterion is the tumor response to neoadjuvant therapy. Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy. Another index that helps predict the treatment outcome is the biomarker. Improved survival outcomes have also opened the door for living donor LT for iCCA. Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection. The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.
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Affiliation(s)
- Sudha Kodali
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA; JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX 77030, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Ashton A Connor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA; JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX 77030, USA; Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, USA
| | | | | | - R Mark Ghobrial
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA; JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX 77030, USA; Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA; Department of Surgery, Weill Cornell Medical College, New York, NY, USA.
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Liang L, Li C, Wang MD, Xing H, Diao YK, Jia HD, Lau WY, Pawlik TM, Zhang CW, Shen F, Huang DS, Yang T. The value of lymphadenectomy in surgical resection of perihilar cholangiocarcinoma: a systematic review and meta-analysis. Int J Clin Oncol 2021; 26:1575-1586. [PMID: 34160742 DOI: 10.1007/s10147-021-01967-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 06/03/2021] [Indexed: 12/25/2022]
Abstract
Surgical resection is the only potentially curative treatment for patients with resectable perihilar cholangiocarcinoma (PHC). There is still no consensus on the value of lymphadenectomy despite evidence indicating lymph node (LN) status is an important prognostic indicator for postoperative long-term survival. We sought to perform a meta-analysis to summarize the current evidence on the value of lymphadenectomy among patients undergoing surgery for PHC. The PubMed (OvidSP), Embase and Cochrane Library were systematically searched for studies published before July 2020 that reported on lymphadenectomy at the time of surgery for PHC after curative surgery. 7748 patients from 28 studies were included in the meta-analysis. No survival benefit was identified with increased number of LN resected (all P > 0.05). Meanwhile, overall LN status was an important prognostic factor. Patients with lymph node metastasis had a pooled estimate hazard ratio of death that was over two-fold higher than patients without lymph node metastasis (HR 2.07, 95% CI 1.65-2.59, P < 0.001). The examination of 5 LNs on histology was associated with better staging of lymph node status and stratification of patients into positive or negative LN groups. While the extent of LN dissection was not associated with a survival benefit, examination of more than 5 LNs better staged patients into positive or negative LN groups with a lower risk of nodal understaging.
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Affiliation(s)
- Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, 310014, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Hang-Dong Jia
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
- Faculty of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, ShatinHong Kong SAR, N.T, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Cheng-Wu Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, 310014, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Dong-Sheng Huang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China.
- School of Clinical Medicine, Hangzhou Medical College No, 481, Binwen Road, Hangzhou, 310014, Zhejiang, China.
| | - Tian Yang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, 310014, Zhejiang, China.
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China.
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
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Liang L, Li C, Jia HD, Diao YK, Xing H, Pawlik TM, Lau WY, Shen F, Huang DS, Zhang CW, Yang T. Prognostic factors of resectable perihilar cholangiocarcinoma: a systematic review and meta-analysis of high-quality studies. Ther Adv Gastrointest Endosc 2021; 14:2631774521993065. [PMID: 33629062 PMCID: PMC7882763 DOI: 10.1177/2631774521993065] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 01/14/2021] [Indexed: 02/06/2023] Open
Abstract
Data on prognostic factors associated with outcome following resection of perihilar cholangiocarcinoma vary. We sought to define and characterize current available evidence on prognostic factors associated with perihilar cholangiocarcinoma after resection. The PubMed, Embase, and Cochrane library were systematically searched for relevant studies published before December 2019. Prognostic factors were identified from multivariate regression analyses in studies. Only high-quality studies were included (Newcastle-Ottawa Scale > 6 stars). A total of 45 studies involving 7338 patients were analyzed. The meta-analysis demonstrated that serum bilirubin levels (hazard ratio: 1.76, 95% confidence interval: 1.27-2.44), serum CA19-9 levels (hazard ratio: 1.32, 95% confidence interval: 1.05-1.65), tumor size (hazard ratio: 1.27, 95% confidence interval: 1.04-1.55), major vascular involvement (hazard ratio: 1.61, 95% confidence interval: 1.09-2.38), distance metastasis (hazard ratio: 17.60, 95% confidence interval: 2.01-154.09), perioperative blood transfusion (hazard ratio: 1.36, 95% confidence interval: 1.15-1.62), T-stage (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61), lymph node metastasis (hazard ratio: 2.06, 1.83-2.31), resection margin status (hazard ratio: 2.34, 95% confidence interval: 1.89-2.89), not-well histology differentiation (hazard ratio: 2.03, 95% confidence interval: 1.69-2.44), perineural invasion (hazard ratio: 2.37, 95% confidence interval: 1.59-3.55), and lymphovascular invasion (hazard ratio: 1.41, 95% confidence interval: 1.15-1.73) were prognostic factors for poorer overall survival. Adjuvant chemotherapy (hazard ratio: 0.37, 95% confidence interval: 0.25-0.55) had a positive effect on prolonged overall survival. In addition, positive resection margin status (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61) and lymph node metastasis (hazard ratio: 2.06, 95% confidence interval: 1.83-2.31) were associated with poorer disease-free survival. The prognostic factors identified in the present meta-analysis can be used to characterize patients in clinical practice and enrich prognostic tools, which could be included in future trial designs and generate hypotheses to be tested in future research to promote personalized treatment.
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Affiliation(s)
- Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Hang-Dong Jia
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Yong-Kang Diao
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
- Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Dong-Sheng Huang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China
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Gaspersz MP, Buettner S, van Vugt JLA, de Jonge J, Polak WG, Doukas M, Ijzermans JNM, Koerkamp BG, Willemssen FEJA. Evaluation of the New American Joint Committee on Cancer Staging Manual 8th Edition for Perihilar Cholangiocarcinoma. J Gastrointest Surg 2020; 24:1612-1618. [PMID: 30756314 PMCID: PMC7359130 DOI: 10.1007/s11605-019-04127-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/16/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND The aim was to compare the prognostic accuracy of cross-sectional imaging of the 7th and 8th editions of the American Joint Committee on Cancer(AJCC) staging system for perihilar cholangiocarcinoma(PHC). METHODS All patients with PHC between 2002 and 2014 were included. Imaging at the time of presentation was reassessed and clinical tumor-node-metastasis (cTNM) stage was determined according to the 7th and 8th editions of the AJCC staging system. Comparison of the prognostic accuracy was performed using the concordance index (c-index). RESULTS A total of 248 PHC patients were included;45 patients(18.1%) underwent a curative-intent resection, whereas 203 patients(81.9%) did not because they were unfit for surgery or were diagnosed with locally advanced or metastatic disease during workup. Prognostic accuracy was comparable between the 7th and 8th editions (c-index 0.57 vs 0.58). For patients who underwent a curative-intent resection, the prognostic accuracy of the 8th edition (0.67) was higher than the 7th (0.65). For patients who did not undergo a curative-intent resection, the prognostic accuracy was poor in both the 7th as the 8th editions (0.54 vs 0.57). CONCLUSION The 7th and 8th editions of the AJCC staging system for PHC have comparable prognostic accuracy. Prognostic accuracy was particularly poor in unresectable patients.
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Affiliation(s)
- Marcia P. Gaspersz
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Jeroen L. A. van Vugt
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Wojciech G. Polak
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jan N. M. Ijzermans
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - François E. J. A. Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
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Lee J, Gangi A. Regional Therapies in Hepatocellular Carcinoma and Cholangiocarcinoma. CANCER REGIONAL THERAPY 2020:311-322. [DOI: 10.1007/978-3-030-28891-4_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Giuliante F, Gauzolino R, Vellone M, Ardito F, Murazio M, Nuzzo G. Liver Resection for Intrahepatic Cholangiocarcinoma. TUMORI JOURNAL 2019; 91:487-92. [PMID: 16457147 DOI: 10.1177/030089160509100608] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Aims and Background Intrahepatic cholangiocarcinoma (IHCC) is the second most common primary liver cancer, representing 10% of all primary liver malignancies. Despite the increase in its incidence, this tumor remains extremely rare in Western countries and few reports detailing experience with surgical resection have been published. The aim of this study was to analyze the experience with resection of IHCC in our center. Methods From 1987 to 2003 we observed 35 patients with IHCC; 15 of them (42.8%) were submitted to hepatic resection. IHCCs accounted for 13% of all liver resections for primary liver tumors carried out at our center during this period. According to the classification of the Liver Cancer Study Group of Japan, the tumors were classified as “mass-forming” in 14 cases and as “periductal” in one case. Major resections were performed in ten cases and minor resections in five cases. In the patient with a periductal tumor a major resection was performed along with excision of the main biliary confluence. In 14 cases (93.3%) tumor-free resection margins were obtained. Results The intraoperative mortality was nil and the postoperative mortality 6.6%. The postoperative morbidity rate was 21.4%. The mean overall survival was 38.4 months, with 86% and 49% one- and three-year survival rates, respectively. Patients with mass-forming tumors and curative resections (R0) (mean survival 40.8 months; one- and three-year survival rates 92.3% and 52.7%), and those with TNM stage I-II tumors (mean survival 43.7 months; one- and three-year survival rates 100% and 66.7%) had a longer survival. The patient with the periductal tumor and R1 resection died after seven months. Conclusions These results support a surgical approach based on accurate selection of patients with IHCC and aimed at radical resection whenever possible. The good survival rates observed in R0 resections emphasize the role of radical surgery as the only chance of cure for patients with this tumor.
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Affiliation(s)
- Felice Giuliante
- Department of Surgical Sciences, Unit of Hepatobiliary Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.
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Dondorf F, Uteβ F, Fahrner R, Felgendreff P, Ardelt M, Tautenhahn HM, Settmacher U, Rauchfuβ F. Liver Transplant for Perihilar Cholangiocarcinoma (Klatskin Tumor): The Essential Role of Patient Selection. EXP CLIN TRANSPLANT 2019; 17:363-369. [PMID: 29911960 DOI: 10.6002/ect.2018.0024] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES Perihilar cholangiocarcinoma (Klatskin tumor) is a rare tumor entity, which is diagnosed late due to uncharacteristic symptoms. The therapeutic strategy for cure is still liver resection. Liver transplant in cases of locally irresectable tumors represents an alternative potential curative therapy for a select group of patients. MATERIALS AND METHODS We present our data of 22 patients with irresectable Klatskin tumors who received transplants between 1996 and 2015. We analyzed relevant prognostic factors for the selection of patients to be transplanted to ensure an acceptable overall survival and reviewed known and established selection criteria. RESULTS Four factors (age, tumor size, serum level of carbohydrate antigen 19-9, percutaneous transhepatic cholangiodrainage) could be detected for possible patient selection. Positive lymph node status and advanced tumor stage according to the Union for International Cancer Control were confirmed as negative prognostic factors for survival after transplant. CONCLUSIONS Liver transplant is a curative therapy for selected patients with irresectable Klatskin tumors, but further prospective studies are urgently needed.
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Affiliation(s)
- Felix Dondorf
- From the Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
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10
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Gaspersz MP, Buettner S, Roos E, van Vugt JLA, Coelen RJS, Vugts J, Wiggers JK, Allen PJ, Besselink MG, Busch ORC, Belt EJ, D'Angelica MI, DeMatteo RP, de Jonge J, Kingham TP, Polak WG, Willemssen FEJA, van Gulik TM, Jarnagin WR, Ijzermans JNM, Groot Koerkamp B. A preoperative prognostic model to predict surgical success in patients with perihilar cholangiocarcinoma. J Surg Oncol 2018; 118:469-476. [PMID: 30132904 DOI: 10.1002/jso.25174] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 06/27/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. STUDY DESIGN Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. RESULTS In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). CONCLUSION Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage.
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Affiliation(s)
- Marcia P Gaspersz
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Eva Roos
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jeroen L A van Vugt
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Robert J S Coelen
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jaynee Vugts
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jimme K Wiggers
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Eric J Belt
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | | | - Ronald P DeMatteo
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - T Peter Kingham
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - François E J A Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - William R Jarnagin
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Jan N M Ijzermans
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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11
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van Vugt JLA, Gaspersz MP, Coelen RJS, Vugts J, Labeur TA, de Jonge J, Polak WG, Busch ORC, Besselink MG, IJzermans JNM, Nio CY, van Gulik TM, Willemssen FEJA, Groot Koerkamp B. The prognostic value of portal vein and hepatic artery involvement in patients with perihilar cholangiocarcinoma. HPB (Oxford) 2018; 20:83-92. [PMID: 28958483 DOI: 10.1016/j.hpb.2017.08.025] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 08/05/2017] [Accepted: 08/29/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although several classifications of perihilar cholangiocarcinoma (PHC) include vascular involvement, its prognostic value has not been investigated. Our aim was to assess the prognostic value of unilateral and main/bilateral involvement of the portal vein (PV) and hepatic artery (HA) on imaging in patients with PHC. METHODS All patients with PHC between 2002 and 2014 were included regardless of stage or management. Vascular involvement was defined as apparent tumor contact of at least 180° to the PV or HA on imaging. Kaplan-Meier method with log-rank test was used to compare overall survival (OS) between groups. Cox regression was used for multivariable analysis. RESULTS In total, 674 patients were included with a median OS of 12.2 (95% CI 10.6-13.7) months. Patients with unilateral PV involvement had a median OS of 13.3 (11.0-15.7) months, compared with 14.7 (11.7-17.6) in patients without PV involvement (p = 0.12). Patients with main/bilateral PV involvement had an inferior median OS of 8.0 (5.4-10.7, p < 0.001) months. Median OS for patients with unilateral HA involvement was 10.6 (9.3-12.0) months compared with 16.9 (13.2-20.5) in patients without HA involvement (p < 0.001). Patients with main/bilateral HA involvement had an inferior median OS of 6.9 (3.3-10.5, p < 0.001). Independent poor prognostic factors included unilateral and main/bilateral HA involvement, but not PV involvement. CONCLUSION Both unilateral and main HA involvement are independent poor prognostic factors for OS in patients presenting with PHC, whereas PV involvement is not.
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Affiliation(s)
- Jeroen L A van Vugt
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
| | - Marcia P Gaspersz
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Robert J S Coelen
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jaynee Vugts
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Tim A Labeur
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Chung Y Nio
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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12
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Buettner S, Ethun CG, Poultsides G, Tran T, Idrees K, Isom CA, Weiss M, Fields RC, Krasnick B, Weber SM, Salem A, Martin RC, Scoggins CR, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Koerkamp BG, Maithel SK, Pawlik TM. Surgical Site Infection Is Associated with Tumor Recurrence in Patients with Extrahepatic Biliary Malignancies. J Gastrointest Surg 2017; 21:1813-1820. [PMID: 28913712 PMCID: PMC5905431 DOI: 10.1007/s11605-017-3571-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 08/29/2017] [Indexed: 01/31/2023]
Abstract
BACKGROUND Surgical site infections (SSI) are one of the most common complications after hepato-pancreato-biliary surgery. Infectious complications may lead to an associated immune-modulatory effect that inhibits the body's response to cancer surveillance. We sought to define the impact of SSI on long-term prognosis of patients undergoing surgical resection of extrahepatic biliary malignancies (EHBM). METHODS Patients undergoing surgery for EHBM between 2000 and 2014 were identified using a large, multi-center, national cohort dataset. Recurrence free survival (RFS) was calculated and a multivariable Cox proportional hazards model was utilized to identify potential risk factors for RFS including SSI. RESULTS Seven hundred twenty-eight patients included in the analytic cohort; 236 (32.4%) patients had perihilar cholangiocarcinoma, 241 (33.1%) gallbladder cancer, and 251 (34.5%) distal cholangiocarcinoma. A major resection, liver resection, was performed in 205 (28.3%) patients, while 110 (15.2%) patients had a pancreaticoduodenectomy. The overall incidence of morbidity was 55.8%; among the 397 patients who experienced a complication, 161 patients specifically had an SSI. The SSI occurred as an infection of the surgical site (n = 70, 9.6%) or formation of an abscess in the operative bed (n = 91, 12.5%). SSI was associated with long-term survival as patients who experienced an SSI had a median RFS of 19.5 months compared with 30.5 months for those patients who did not have an SSI (HR 1.40, 95% CI 1.08-1.80; p = 0.01). Among 279 patients who had EHBM that had no associated lymph node metastases, well-to-moderate tumor differentiation, as well as an R0 resection margin, SSI remained associated with worse RFS (HR 1.84, 95% CI 1.03-3.29; p = 0.038), as well as overall survival (HR 1.87, 95% CI 1.18-2.97; p = 0.008). CONCLUSION SSI was a relatively common occurrence following surgery for EHBM as 1 in 10 patients experienced an SSI. In addition to standard tumor-specific factors, the occurrence of postoperative SSI was adversely associated with long-term survival.
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Affiliation(s)
- Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Cecilia G. Ethun
- Department of Surgery, Emory University School of Medicine, Atlanta, GA
| | - George Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Thuy Tran
- Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Kamran Idrees
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Chelsea A. Isom
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD
| | - Ryan C. Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Bradley Krasnick
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Sharon M. Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Ahmed Salem
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | | | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, NC
| | | | - Carl Schmidt
- Department of Surgery, Ohio State University, Columbus, OH
| | - Eliza Beal
- Department of Surgery, Ohio State University, Columbus, OH
| | | | - Rivfka Shenoy
- Department of Surgery, New York University, New York, NY
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands
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13
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Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases. HPB (Oxford) 2017; 19:735-740. [PMID: 28549744 PMCID: PMC5907486 DOI: 10.1016/j.hpb.2017.04.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 04/18/2017] [Accepted: 04/25/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. METHODS Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers. RESULTS In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09-2.69) were independent poor prognostic factors in the resected cohort. CONCLUSION Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.
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14
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Currie BM, Soulen MC. Decision Making: Intra-arterial Therapies for Cholangiocarcinoma-TACE and TARE. Semin Intervent Radiol 2017; 34:92-100. [PMID: 28579676 DOI: 10.1055/s-0037-1602591] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in recent years and now represents the second most common primary hepatic cancer in the United States. The prognosis is dismal without surgical resection. In patients ineligible to receive curative treatments, locoregional therapies represent a diverse array of techniques that can stabilize or reverse tumor progression to improve overall survival and reduce tumor-related symptoms. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have been demonstrated to be efficacious methods for this patient population. Deciding between these two options is challenging. This article reviews the differences in patient selection, preprocedural evaluation, financial considerations and availability, quality of life, and rates of complications and overall survival.
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Affiliation(s)
- Brian M Currie
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael C Soulen
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
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15
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Esnaola NF, Meyer JE, Karachristos A, Maranki JL, Camp ER, Denlinger CS. Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma. Cancer 2016; 122:1349-69. [PMID: 26799932 DOI: 10.1002/cncr.29692] [Citation(s) in RCA: 190] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 08/18/2015] [Accepted: 08/19/2015] [Indexed: 12/13/2022]
Abstract
Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. © 2016 American Cancer Society.
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Affiliation(s)
- Nestor F Esnaola
- Department of Surgery, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania
| | - Joshua E Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania
| | - Andreas Karachristos
- Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania
| | - Jennifer L Maranki
- Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania
| | - E Ramsay Camp
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - Crystal S Denlinger
- Department of Hematology/Oncology, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania
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16
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Simo KA, Halpin LE, McBrier NM, Hessey JA, Baker E, Ross S, Swan RZ, Iannitti DA, Martinie JB. Multimodality treatment of intrahepatic cholangiocarcinoma: A review. J Surg Oncol 2016; 113:62-83. [DOI: 10.1002/jso.24093] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Accepted: 10/31/2015] [Indexed: 02/06/2023]
Affiliation(s)
- Kerri A. Simo
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Laura E. Halpin
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Nicole M. McBrier
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
| | | | - Erin Baker
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Samuel Ross
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Ryan Z. Swan
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - David A. Iannitti
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - John B. Martinie
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
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17
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Sapisochín G, Fernández de Sevilla E, Echeverri J, Charco R. Liver transplantation for cholangiocarcinoma: Current status and new insights. World J Hepatol 2015; 7:2396-2403. [PMID: 26464755 PMCID: PMC4598610 DOI: 10.4254/wjh.v7.i22.2396] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 08/12/2015] [Accepted: 09/18/2015] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic (iCCA), perihiliar (phCCA) and distal. Initial experiences with orthotopic liver transplantation (OLT) for patients with iCCA and phCCA had very poor results and this treatment strategy was abandoned. In the last decade, thanks to a strict selection process and a neoadjuvant chemoradiation protocol, the results of OLT for patients with non-resectable phCCA have been shown to be excellent and this strategy has been extended worldwide in selected transplant centers. Intrahepatic cholangiocarcinoma is a growing disease in most countries and can be diagnosed both in cirrhotic and in non-cirrhotic livers. Even though OLT is contraindicated in most centers, recent investigations analyzing patients that were transplanted with a misdiagnosis of HCC and were found to have an iCCA have shown encouraging results. There is some information suggesting that patients with early stages of the disease could benefit from OLT. In this review we analyze the current state-of-the-art of OLT for cholangiocarcinoma as well as the new insights and future perspectives.
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18
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Hong MJ, Cheon YK, Lee EJ, Lee TY, Shim CS. Long-term outcome of photodynamic therapy with systemic chemotherapy compared to photodynamic therapy alone in patients with advanced hilar cholangiocarcinoma. Gut Liver 2014; 8:318-23. [PMID: 24827630 PMCID: PMC4026651 DOI: 10.5009/gnl.2014.8.3.318] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Background/Aims Patients with cholangiocarcinoma usually present at an advanced stage, and more than 50% of cases are not resectable at the time of diagnosis. Recently, photodynamic therapy (PDT) has been proposed as a palliative and neoadjuvant modality. We evaluated whether combination of PDT and chemotherapy is more effective than PDT alone. Methods In total, 161 patients with cholangiocarcinoma diagnosed between February 1999 and September 2009 were evaluated. Sixteen patients were treated with PDT and chemotherapy (group A), and 58 were treated with PDT (group B). Results The median survival was 538 days (95% confidence interval [CI], 475.3 to 600.7) in group A and 334 days (95% CI, 252.5 to 415.5) in group B (p=0.05). Lymph node metastasis status, serum bilirubin of pretreatment, tumor node metastasis stage, treatment method (PDT with chemotherapy vs PDT alone), time to PDT and the number of PDT sessions were prognostic factors with statistical significance in the univariate analysis. A multivariate analysis showed that PDT with chemotherapy and more than two sessions of PDT were significant independent predictors of longer survival in advanced cholangiocarcinoma (hazard ratio [HR], 2.23; 95% CI, 1.18 to 4.20; p=0.013 vs HR, 1.79; 95% CI, 1.044 to 3.083; p=0.034). Conclusions PDT with chemotherapy results in longer survival than PDT alone.
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Affiliation(s)
- Mi Jin Hong
- Department of Internal Medicine, Digestive Disease Centre, Konkuk University School of Medicine, Seoul, Korea
| | - Young Koog Cheon
- Department of Internal Medicine, Digestive Disease Centre, Konkuk University School of Medicine, Seoul, Korea
| | - Eung Jun Lee
- Department of Internal Medicine, Digestive Disease Centre, Konkuk University School of Medicine, Seoul, Korea
| | - Tae Yoon Lee
- Department of Internal Medicine, Digestive Disease Centre, Konkuk University School of Medicine, Seoul, Korea
| | - Chan Sup Shim
- Department of Internal Medicine, Digestive Disease Centre, Konkuk University School of Medicine, Seoul, Korea
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Singal A, Welling TH, Marrero JA. Role of liver transplantation in the treatment of cholangiocarcinoma. Expert Rev Anticancer Ther 2014; 9:491-502. [DOI: 10.1586/era.09.5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Rauchfuss F, Scheuerlein H, Götz M, Dittmar Y, Voigt R, Heise M, Settmacher U. [Hepatocellular carcinoma and cholangiocarcinoma]. Chirurg 2010; 81:941-953. [PMID: 20827454 DOI: 10.1007/s00104-009-1864-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma and cholangiocarcinoma are relatively rare tumors of the gastrointestinal tract in western Europe but their incidence has been increased in recent years. Newly diagnosed intrahepatic lesions or intrahepatic cholestasis require extensive laboratory tests and imaging studies in order to confirm the diagnosis of hepatocellular carcinoma, intrahepatic or extrahepatic cholangiocarcinoma. The treatment options range from liver resection or liver transplantation to conservative measures (in cases of non-resectable lesions). This review article aims to provide an overview on the diagnostic options and the subsequent treatment.
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Affiliation(s)
- F Rauchfuss
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Friedrich-Schiller-Universität Jena, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Deutschland.
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21
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Cholangiocarcinoma: has there been any progress? CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2010; 24:52-7. [PMID: 20186357 DOI: 10.1155/2010/704759] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma is the second most common primary hepatic tumour after hepatocellular carcinoma. Primary sclerosing cholangitis is one of the most commonly recognized risk factors for cholangiocarcinoma; however, approximately 90% of patients have no identifiable risk factors. Extrahepatic type is its most common presentation. Cholangiocarcinoma is considered to be a devastating disease, with a poor survival rate and few therapeutic options. Although surgical resection has been considered the best treatment option for localized cholangiocarcinoma, local recurrences of this cancer are very common, and imply persistent micro-metastatic disease in lymph nodes or at surgical margins, even after extended surgical resection. Consequently, the five year survival rate after attempted curative resection is only 20% to 40%. Early studies of liver transplantation for cholangiocarcinoma did not show a survival benefit and, currently, this tumour is considered to be an absolute contraindication for liver transplantation in most transplant centres worldwide. Recently, neoadjuvant chemoradiation in combination with liver transplantation for highly selected patients with cholangiocarcinoma has shown impressive results, with five-year survival rates at approximately 76% to 82%--similar to other standard indications for liver transplantation, such as hepatocellular carcinoma or hepatitis C-induced cirrhosis. However, this success of liver transplantation applies to only a subset of patients and most of the data originated from a single centre. Wider application of this strategy, especially for patients with potentially resectable disease, will require validation by other centres.
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22
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Morise Z, Sugioka A, Tokoro T, Tanahashi Y, Okabe Y, Kagawa T, Takeura C. Surgery and chemotherapy for intrahepatic cholangiocarcinoma. World J Hepatol 2010; 2:58-64. [PMID: 21160974 PMCID: PMC2998957 DOI: 10.4254/wjh.v2.i2.58] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2009] [Revised: 01/14/2010] [Accepted: 01/21/2010] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma, arising from bile duct epithelium, is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), including hilarcholangiocarcinoma. Recently, there has been a worldwide increase in the incidence and mortality from ICC. Complete surgical resection is the only approach to cure the patients with ICC. However, locoregional extension of these tumors is usually advanced with intrahepatic and lymph-node metastases at the time of diagnosis. Resectability rates are quite low and variable (18%-70%). The five-year survival rate after surgical resection was reported to be 20%-40%. Median survival time after ICC resection was 12-37.4 mo. Only a small number of ICC cases, accompanied with ECC, gall bladder carcinoma, and ampullary carcinoma, have been reported in the studies of chemotherapy due to the rarity of the disease. However, in some reports, significant anti-cancer effects were achieved with a response rate of up to 40% and a median survival of one year. Although recurrence rate after hepatectomy is high for the patients with ICC, the residual liver and the lung are the main sites of recurrence after tentative curative surgical resection. Several patients in our study had a long-term survival with repeated surgery and chemotherapy. Repeated surgery, combined with new effective regimens of chemotherapy, could benefit the survival of ICC patients.
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Affiliation(s)
- Zenichi Morise
- Zenichi Morise, Atsushi Sugioka, Takamasa Tokoro, Yoshinao Tanahashi, Yasuhiro Okabe, Tadashi Kagawa, Chinatsu Takeura, Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
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Retrospective analysis of histopathologic prognostic factors after hepatectomy for intrahepatic cholangiocarcinoma. Cancer J 2009; 15:257-61. [PMID: 19556914 DOI: 10.1097/ppo.0b013e31819e3312] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to investigate histopathologic prognostic factors in patients with intrahepatic cholangiocarcinoma (ICC) whose tumors were resected to determine the optimal surgical strategies. METHODS One hundred and two ICC patients who underwent laparotomy from July 1998 to December 2000 were followed up successfully. Histopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on the outcome. RESULTS The 1-, 3-, and 5-year survival rates after surgery were 56.9%, 25.5%, and 16.9%, respectively. The average survival duration was 21.91 +/- 20.17 months. In univariate analysis, the presence of lymph node (LN) metastasis, number of LNs with metastases, presence of intrahepatic metastasis, curative resection, and TNM stage were significant risk factors for survival. Multivariate analysis revealed that intrahepatic metastasis, noncurative resection, and TNM stage IVa were independent prognostic factors. CONCLUSIONS The histopathologic characteristics of intrahepatic metastasis were closely related to poor prognosis in ICC patients. Extensive hepatectomy with LN dissection may offer the only chance for long-term survival in patients with ICC.
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R0 liver resections for primary malignant liver tumors in the noncirrhotic liver: a diagnosis-related analysis. Dig Dis Sci 2009; 54:887-94. [PMID: 18712480 DOI: 10.1007/s10620-008-0408-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2008] [Accepted: 06/18/2008] [Indexed: 12/23/2022]
Abstract
BACKGROUND Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. RESULTS Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. CONCLUSIONS R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.
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Zhou XD, Tang ZY, Fan J, Zhou J, Wu ZQ, Qin LX, Ma ZC, Sun HC, Qiu SJ, Yu Y, Ren N, Ye QH, Wang L, Ye SL. Intrahepatic cholangiocarcinoma: report of 272 patients compared with 5,829 patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2009; 135:1073-80. [PMID: 19294418 DOI: 10.1007/s00432-009-0547-y] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2008] [Accepted: 01/08/2009] [Indexed: 02/07/2023]
Abstract
PURPOSE To clarify clinicopathologic differences between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), and identify potential factors influencing survival after hepatectomy for ICC. METHODS Comparison of clinicopathologic data was made between patients who underwent hepatectomy for ICC (n = 272) and HCC (n = 5,829) during the same period. Twenty-five clinicopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on prognosis of ICC. RESULTS Compared with patients with HCC, ICC patients were more common in females and more elderly, had a lower proportion of asymptomatic tumors, lower serum alpha-fetoprotein, higher serum carcinoembryonic antigen, carbohydrate antigen 19-9 and alkaline phosphatase levels; lower incidence of hepatitis history, associated cirrhosis and serum hepatitis B surface antigen; lower proportion of small tumors, well-encapsulated tumors and tumor emboli in the portal vein; higher proportion of single tumor, perihila lymph node involvement and poor differentiation; and less frequency of limited resection (all, P < 0.0001). Distant metastasis was less frequent in patients with ICC (P = 0.027). A total of 5-years overall and disease-free survival (in brackets) after resection was 26.4% (13.1%) and 44.5% (33.1%) (P < 0.0001, P < 0.0001) for patients with ICC and HCC, respectively. Factors influencing survival after resection of ICC can be divided mainly into two categories: early detection of asymptomatic ICC (P < 0.0001) and curative resection (P = 0.002). CONCLUSION ICC Patients have distinct clinicopathologic features as compared with HCC patients. Surgery remains the only effective treatment for ICC. Early detection of asymptomatic ICC and curative resection were the key to achieve optimal survival.
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Affiliation(s)
- Xin-Da Zhou
- Liver Cancer Institute, Zhong Shan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, China.
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Lang H, Sotiropoulos GC, Sgourakis G, Schmitz KJ, Paul A, Hilgard P, Zöpf T, Trarbach T, Malagó M, Baba HA, Broelsch CE. Operations for intrahepatic cholangiocarcinoma: single-institution experience of 158 patients. J Am Coll Surg 2009; 208:218-28. [PMID: 19228533 DOI: 10.1016/j.jamcollsurg.2008.10.017] [Citation(s) in RCA: 153] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2008] [Revised: 10/05/2008] [Accepted: 10/08/2008] [Indexed: 12/20/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is a rare primary liver malignancy. Until now, outcomes and prognostic factors after liver resection for these tumors have not been well-documented. STUDY DESIGN Between April 1998 and December 2006, a total of 158 patients underwent surgical exploration in our institution for intended liver resection of ICC. Prospectively collected data of patients undergoing liver resection (n = 83) were analyzed with regard to preoperative findings, operative details, perioperative morbidity and mortality, pathologic findings, outcomes measured by tumor recurrence and survival, and prognostic factors for outcomes. RESULTS Tumors were solitary in 47 patients. R0 resections were achieved in 53 patients. Vascular infiltration and lymph node metastasis were detected in 41% and 34%, respectively. After resection, the calculated 1-, 3-, and 5-year-survival rates were 71%, 38%, and 21%, respectively, with corresponding rates of 83%, 50%, and 30% in R0 resections. For 14 variables evaluated, only gender (p = 0.008), Union Internationale Contre le Cancer stage (p = 0.014), and R classification (p = 0.001) showed predictive value in the multivariate Cox proportional hazard regression. CONCLUSIONS Results presented outline that an R0 resection leads to substantially prolonged survival in ICC and represents the considerable input of the surgeon to the outcomes of these patients. Union Internationale Contre le Cancer stage remains an important factor.
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Affiliation(s)
- Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
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Lee DH, Lee JM, Kim KW, Park HS, Kim SH, Lee JY, Han JK, Choi BI. MR imaging findings of early bile duct cancer. J Magn Reson Imaging 2009; 28:1466-75. [PMID: 19025934 DOI: 10.1002/jmri.21597] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To retrospectively evaluate the MR imaging features of early bile duct cancer and to correlate them with the clinicopathologic findings. MATERIALS AND METHODS This retrospective study was approved by our institutional review board, and informed consent was waived. Seventeen patients with surgically proven early bile duct cancer who had undergone preoperative MR cholangiopancreatography with gadolinium-enhanced MR imaging, were included in this study. Two, experienced radiologists evaluated the MR images in consensus regarding the following findings: tumor number and morphology; signal intensity of the tumor; sharpness of the outer border of the bile duct wall; enhancement pattern of the tumor; and the presence of enlarged peribiliary lymph nodes. Another radiologist measured the SNR of the tumor and bile duct wall on gadolinium-enhanced MRI during the dynamic phases to evaluate the tumor enhancement degree. RESULTS In all patients, MR imaging demonstrated single or multiple intraluminal bile duct masses showing a sharply defined outer margin. The most common enhancement pattern of the biliary lesions showed heterogeneous amorphous enhancement or heterogeneous enhancement with central, dot-like structures or vascular structures (76.5%, 13/17 patients). The difference of SNR between bile duct and tumor was greatest in the equilibrium phase (P < 0.05). CONCLUSION MRCP combined with dynamic contrast-enhanced MRI can be useful for detecting early bile duct cancers. Common MR findings of early bile duct cancer include one or more inhomogeneously enhancing intraductal masses with clear outer margins and preservation of the bile duct wall.
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Affiliation(s)
- Dong Ho Lee
- Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea
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Yedibela S, Demir R, Zhang W, Meyer T, Hohenberger W, Schönleben F. Surgical treatment of mass-forming intrahepatic cholangiocarcinoma: an 11-year Western single-center experience in 107 patients. Ann Surg Oncol 2008; 16:404-12. [PMID: 19037702 DOI: 10.1245/s10434-008-0227-1] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2008] [Revised: 09/29/2008] [Accepted: 09/29/2008] [Indexed: 12/26/2022]
Abstract
Hepatic resection is the only cure for intrahepatic cholangiocellular carcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcome of patients with ICC. We retrospectively studied the records of 67 patients who underwent laparotomy for ICC from January 1995 through December 2005. Univariate and multivariate analyses were conducted for several variables to evaluate their influence on the outcome. Forty-five patients underwent hepatic resection. In 19 patients, the tumors were found to be unresectable at the time of laparotomy. Median 2- and 5-year survival rates in the 45 resected patients were 62% and 35%, respectively. For 36 patients who underwent curative resection, the 2- and 5-year survival were 67% and 41%, respectively; with a median survival of 43 months. The overall 5-year recurrence-free survival was 30%. The 90-day postoperative mortality rate was 4% and morbidity 28%. Multivariate analyses confirmed resection margin, lymph node involvement, blood loss, and blood transfusion to be independent significant variables for overall survival. Predictors of longer recurrence-free survival were lymph node involvement, vascular infiltration, blood loss, and transfusion. Surgical treatment of ICC by curative hepatic resection in patients without nodal invasion provides good long-term results. In contrast, incomplete tumor removal does not provide a survival benefit. An improved quality of preoperative staging was able to increase the resectability rate to acceptable 70%.
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Affiliation(s)
- Süleyman Yedibela
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Germany.
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Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.
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Hammill CW, Wong LL. Intrahepatic cholangiocarcinoma: a malignancy of increasing importance. J Am Coll Surg 2008; 207:594-603. [PMID: 18926465 DOI: 10.1016/j.jamcollsurg.2008.04.031] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2008] [Revised: 04/14/2008] [Accepted: 04/22/2008] [Indexed: 02/07/2023]
Affiliation(s)
- Chet W Hammill
- Departments of Surgery, University of Hawaii John A Burns School of Medicine, and Hawaii Medical Center-East, Honolulu, HI 96817, USA
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Konstadoulakis MM, Roayaie S, Gomatos IP, Labow D, Fiel MI, Miller CM, Schwartz ME. Aggressive surgical resection for hilar cholangiocarcinoma: is it justified? Audit of a single center's experience. Am J Surg 2008; 196:160-9. [PMID: 18466862 DOI: 10.1016/j.amjsurg.2007.07.033] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2007] [Revised: 07/12/2007] [Accepted: 07/12/2007] [Indexed: 02/06/2023]
Abstract
BACKGROUND The current study presents our experience with resectional surgery for patients with hilar cholangiocarcinoma (HC). METHODS Medical records of 73 HC patients who were referred to our department between 1988 and 2006 were reviewed. Resectability rate, surgical mortality, and factors contributing to survival were investigated. RESULTS Resectional surgery was performed in 59 patients (80.8%), 51 of whom (86.4%) underwent major hepatic resection. Negative margins were obtained in 35 of 51 patients (68.6%) and were associated with right-sided hepatectomy (80% vs 20%, P = .049). In-hospital mortality and morbidity were 6.8% and 25.4%, respectively. One-, 3- and 5-year survival rates after liver resection were 86%, 48.9%, and 34.9%, respectively. Histologic differentiation, left-sided hepatectomy, and inferior vena cava resection independently predicted survival. Patients undergoing R1 hepatectomy had significantly improved 5-year survival rates compared with patients who were unresectable (P <.01). CONCLUSIONS Major hepatic resections with concomitant vascular resection and reconstruction, when needed, are justified for patients with Bismuth type III and IV hilar cholangiocarcinoma with negative nodes. Reluctance to incorporate segments V and/or VIII into a left lobectomy often results in tumor-positive margins and unfavorable prognosis. Resections for hilar lesions less than stage IVB, even when resulting in microscopically positive margins, confer prolonged survival compared with untreated patients. The results are further improved for patients with well-differentiated HC.
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Affiliation(s)
- Manousos M Konstadoulakis
- Recanati-Miller Transplantation Institute, Hippocration Hospital of Athens, Athens Medical School, Athens, Greece.
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Konstadoulakis MM, Roayaie S, Gomatos IP, Labow D, Fiel MI, Miller CM, Schwartz ME. Fifteen-year, single-center experience with the surgical management of intrahepatic cholangiocarcinoma: Operative results and long-term outcome. Surgery 2008; 143:366-74. [DOI: 10.1016/j.surg.2007.10.010] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2006] [Revised: 09/27/2007] [Accepted: 10/12/2007] [Indexed: 01/04/2023]
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Becker NS, Rodriguez JA, Barshes NR, O'Mahony CA, Goss JA, Aloia TA. Outcomes analysis for 280 patients with cholangiocarcinoma treated with liver transplantation over an 18-year period. J Gastrointest Surg 2008; 12:117-22. [PMID: 17963015 DOI: 10.1007/s11605-007-0335-4] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2007] [Accepted: 09/07/2007] [Indexed: 02/06/2023]
Abstract
Cholangiocarcinoma is an aggressive malignancy with 5-year survival rates<15%. Selected patients present with localized but unresectable disease and are candidates for orthotopic liver transplantation (OLT). The purpose of this study was to evaluate a multi-institutional experience with liver transplantation for this malignancy. Two hundred eighty patients with cholangiocarcinoma treated with OLT from 1987 to 2005 were identified in The United Network for Organ Sharing database. Patient and allograft survivals were calculated and the potential prognostic value of multiple clinicopathologic variables was assessed. At a median follow-up interval of 452 days (range: 0-6,166 days), 1- and 5-year patient survivals were 74 and 38%, respectively, with 49 actual 5-year survivors and 21 actual 10-year survivors. Posttransplant 1- and 5-year allograft survivals were 69 and 36%, respectively. Study variables associated with improved survivals included diagnosis of cholangiocarcinoma pre-OLT [5-year overall survival (OS): 68 vs. 20% for patients with incidental diagnoses at the time of OLT, p<0.001] and OLT after 1993 (5-year OS: 45 vs. 30% pre-1994, p<0.01). In contrast, the diagnosis of concomitant primary sclerosing cholangitis did not impact survivals (5-year OS: 41 vs. 50% without primary sclerosing cholangitis, p=0.402). Selected cholangiocarcinoma patients treated with OLT experience a survival benefit. Diagnosis of cancer prior to OLT allows for better staging and pre-OLT therapy that may translate into improved outcomes. These data support the continued development of multimodality cholangiocarcinoma treatment protocols that include OLT.
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Affiliation(s)
- Natasha S Becker
- Michael E. DeBakey Department of Surgery, Division of Hepatobiliary Surgery and Abdominal Transplantation, Baylor College of Medicine, 1709 Dryden, Suite 15.37, Houston, TX 77030, USA
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Cancer of the Liver and Bile Ducts. Oncology 2007. [DOI: 10.1007/0-387-31056-8_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg 2007; 11:1488-96; discussion 1496-7. [PMID: 17805937 DOI: 10.1007/s11605-007-0282-0] [Citation(s) in RCA: 184] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2007] [Accepted: 07/29/2007] [Indexed: 01/31/2023]
Abstract
The prognosis of patients with cholangiocarcinoma historically has been poor, even after surgical resection. Although data from some single-institution series indicate improvement over historical results, survival after surgical therapy for cholangiocarcinoma has not been investigated in a population-based study. We used the Surveillance, Epidemiology, and End Results database to identify patients who underwent surgery for cholangiocarcinoma from 1973 through 2002. Multivariate modeling of survival after surgery for intrahepatic cholangiocarcinoma showed an improvement in survival only within the last decade studied, resulting in a cumulative 34.4% improvement in survival from 1992 through 2002. In contrast, multivariate modeling of survival after surgery for extrahepatic cholangiocarcinoma revealed a 23.3% increase in adjusted survival per each decade studied, resulting in a cumulative 53.7% improvement from 1973 through 2002. We conclude that survival after surgery for extrahepatic cholangiocarcinoma has dramatically improved since 1973. Patients with intrahepatic cholangiocarcinoma, however, have achieved an improvement in survival largely confined to more recent years. We suggest that these trends are largely caused by developments in imaging technology, improvements in patient selection, and advances in surgical techniques.
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Affiliation(s)
- Hari Nathan
- Department of Surgery, The Johns Hopkins University School of Medicine, Room 442, Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231-1000, USA
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Ohta R, Yamashita YI, Taketomi A, Kitagawa D, Kuroda Y, Itoh S, Aishima SI, Maehara Y. Reduced expression of focal adhesion kinase in intrahepatic cholangiocarcinoma is associated with poor tumor differentiation. Oncology 2007; 71:417-22. [PMID: 17687194 DOI: 10.1159/000107109] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Accepted: 06/01/2007] [Indexed: 11/19/2022]
Abstract
OBJECTIVE Focal adhesion kinase (FAK) expression has been linked to tumor cell invasion and metastasis, but its role in intrahepatic cholangiocarcinoma (ICC) has not been addressed. The goal of this study was to investigate FAK expression in ICC and to assess whether its expression is correlated with clinicopathological factors or prognosis in patients with ICC. METHODS FAK expression was examined using immunohistochemistry with sections from 56 resected ICC specimens. The correlations between FAK expression and clinical outcome were assessed. RESULTS The patients were divided into two groups according to the degree of FAK expression: high FAK group (n = 16) and low FAK group (n = 40). A lower expression of FAK was correlated with tumor size, poor differentiation, lymph node metastasis, vascular invasion, and intrahepatic metastasis. In the low FAK expression group, multiple recurrence and distant metastases were more prevalent than in the high FAK expression group. The overall and disease-free survival analysis indicated worse outcomes of the low FAK expression group (p < 0.01). CONCLUSIONS A low expression of FAK in ICC is associated with a poor outcome after a surgical resection.
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Affiliation(s)
- Ryuji Ohta
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Abstract
OBJECTIVE To assess long-term survival and prognostic factors in a large series of patients with bile duct cancer. SUMMARY BACKGROUND DATA The incidence of bile duct cancer is low but increasing. Determinants of survival vary in the literature, due to a lack of sufficient numbers of patients in most series. METHODS We studied 564 consecutive patients with bile duct cancer operated upon between 1973 and 2004. Patients were divided into intrahepatic, perihilar, and distal groups. Principle outcome measures were complications, 30-day mortality, and survival. RESULTS Of the 564 patients, 44 (8%) had intrahepatic, 281 (50%) had perihilar, and 239 (42%) had distal tumors. Approximately half (294, 52%) were treated before 1995, while 270 (48%) were treated thereafter. The perioperative mortality rate was 4%. In log-rank analyses, survival was higher in the later time period (P = 0.002), in patients with intrahepatic disease (P = 0.001), with negative resection margins (P < 0.001), with well/moderately differentiated tumors (P < 0.001), and those with negative lymph nodal status (P < 0.001). In multivariate analysis, negative margins (P < 0.001), tumor differentiation (P < 0.001), and negative nodal status (P < 0.001), but not tumor diameter, were significant independent prognostic factors. In R0-resected patients, lymph node status (P < 0.001), but not tumor diameter, histology, or differentiation, further predicted survival. The median survivals for R0-resected intrahepatic, perihilar, and distal tumors were 80, 30, and 25 months, respectively, and the 5-year survivals were 63%, 30%, and 27%, respectively. CONCLUSION R0 resection remains the best chance for long-term survival, and lymph node status is the most important prognostic factor following R0 resection.
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DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD, Choti MA, Yeo CJ, Schulick RD. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 2007; 245:755-62. [PMID: 17457168 PMCID: PMC1877058 DOI: 10.1097/01.sla.0000251366.62632.d3] [Citation(s) in RCA: 1005] [Impact Index Per Article: 55.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To assess long-term survival and prognostic factors in a large series of patients with bile duct cancer. SUMMARY BACKGROUND DATA The incidence of bile duct cancer is low but increasing. Determinants of survival vary in the literature, due to a lack of sufficient numbers of patients in most series. METHODS We studied 564 consecutive patients with bile duct cancer operated upon between 1973 and 2004. Patients were divided into intrahepatic, perihilar, and distal groups. Principle outcome measures were complications, 30-day mortality, and survival. RESULTS Of the 564 patients, 44 (8%) had intrahepatic, 281 (50%) had perihilar, and 239 (42%) had distal tumors. Approximately half (294, 52%) were treated before 1995, while 270 (48%) were treated thereafter. The perioperative mortality rate was 4%. In log-rank analyses, survival was higher in the later time period (P = 0.002), in patients with intrahepatic disease (P = 0.001), with negative resection margins (P < 0.001), with well/moderately differentiated tumors (P < 0.001), and those with negative lymph nodal status (P < 0.001). In multivariate analysis, negative margins (P < 0.001), tumor differentiation (P < 0.001), and negative nodal status (P < 0.001), but not tumor diameter, were significant independent prognostic factors. In R0-resected patients, lymph node status (P < 0.001), but not tumor diameter, histology, or differentiation, further predicted survival. The median survivals for R0-resected intrahepatic, perihilar, and distal tumors were 80, 30, and 25 months, respectively, and the 5-year survivals were 63%, 30%, and 27%, respectively. CONCLUSION R0 resection remains the best chance for long-term survival, and lymph node status is the most important prognostic factor following R0 resection.
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Affiliation(s)
- Michelle L DeOliveira
- Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA
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Slupski MW, Szczylik C, Jasinski MK. Unexpected response to systemic chemotherapy in case of primarily nonresectable advanced disseminated intrahepatic cholangiocarcinoma. World J Surg Oncol 2007; 5:36. [PMID: 17376238 PMCID: PMC1839091 DOI: 10.1186/1477-7819-5-36] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2006] [Accepted: 03/21/2007] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Cholangiocellular cancers account for about 10-15% of primary liver cancers. Prognosis is poor, with expected survival of less than 5% at five-year. CASE PRESENTATION The case described shows remission of a disseminated cholangiocellular carcinoma (focal changes in liver, metastases to lungs) after neoadjuvant chemotherapy. The initial diagnosis was based on ultrasound examination and confirmed with computer tomography. Tumour biopsy and histopathological examination revealed cholangiocellular carcinoma. The patient underwent chemotherapy. After remission of lesions in lungs and reduction/regression of tumours in liver to one focal change, right lobe liver resection was performed. The histopathological examination did not reveal any viable carcinoma cells, only necrotic tissues in place of the primary tumour as well as in local portal vein branches was seen. Thirty months after the operation the patient is in a good overall condition and no recurrence has been observed. CONCLUSION Appropriate neoadjuvant chemotherapy may allow radical resection in a previously unresectable cholangiocellular cancer.
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Affiliation(s)
- Maciej W Slupski
- Department of Transplantology and General Surgery, Nicolaus Copernicus University, Curie-Sklodowskiej 9, Bydgoszcz, Poland
| | - Cezary Szczylik
- Department of Oncology CSK WAM, Szaserow 128, Warsaw, Poland
| | - Milosz K Jasinski
- Department of Transplantology and General Surgery, Nicolaus Copernicus University, Curie-Sklodowskiej 9, Bydgoszcz, Poland
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Hong YS, Lee J, Lee SC, Hwang IG, Choi SH, Heo JS, Park JO, Park YS, Lim HY, Kang WK. Phase II study of capecitabine and cisplatin in previously untreated advanced biliary tract cancer. Cancer Chemother Pharmacol 2006; 60:321-8. [PMID: 17143602 DOI: 10.1007/s00280-006-0380-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2006] [Accepted: 10/26/2006] [Indexed: 12/27/2022]
Abstract
BACKGROUND Biliary tract cancer is one of the most aggressive and chemotherapy-refractory tumors. Although only curative treatment modality is surgery, most patients are not suitable for surgery due to advanced stage of the disease at diagnosis. Thus most patients with biliary tract cancer are possible candidates for palliative chemotherapy. The standard chemotherapeutic regimen is still to be defined, however. We performed a phase II study of combination chemotherapy with capecitabine and cisplatin in these patients to evaluate efficacy and toxicity of the regimen. METHODS Patients with previously untreated metastatic, recurrent, or inoperable biliary tract cancer were enrolled. Eligible patients were screened as following: (1) histologically confirmed, (2) age between 18 and 75 years, (3) at least one measurable lesion according to RECIST criteria, (4) ECOG performance status <or=2, (5) a life expectancy of at least 3 months, and (6) adequate laboratory values. Patients received capecitabine (2,500 mg/m2/day, days 1 to 14) and cisplatin (60 mg/m2, day 1) every 3 weeks. Response was assessed for every two cycles of chemotherapy and treatment was stopped when tumor had progressed or stable with no further response. RESULTS Thirty-two patients were enrolled, 20 (62.5%) were male and 12 (37.5%) were female and the median age was 54 years (33-71 years). Fifteen patients (46.9%) had gallbladder cancer, 13 (40.6%) had intrahepatic cholangiocarcinoma, and 4 (12.5%) had extrahepatic biliary cancer. The most frequent metastatic sites were lymph nodes (20/32, 62.5%) and liver (28/32, 56.3%). No complete response was observed and partial response was observed in 13/32 patients. By the intent-to-treat analysis, the overall response rate was 40.6% (95% CI, 23.7-59.4) with 0 CR and 13 PRs. Stable disease was observed in 3 patients (9.4%), and 11 patients (34.4%) had progressive disease. The median time to progression was 3.5 months (95% CI, 1.3-5.8), and the median overall survival was 12.4 months (95% CI, 6.3-18.5) after the median follow-up duration of 9.5 months (4.8-26.1 months). A total of 108 cycles of chemotherapy was delivered. Grade 3 hematologic toxicities included neutropenia (5, 15.6%), anemia (1, 3.1%), and thrombocytopenia (1, 3.1%) per patient, and no grade 4 hematologic toxicities were observed. Grade 3 non-hematologic toxicities included hyperbilirubinemia (2, 6.3%), increase of alkaline phosphatase (2, 6.3%), hand-foot syndrome (2, 6.3%), anorexia, and diarrhea (1, 3.1%) per patient, respectively. There was no treatment-related death. CONCLUSION The combination chemotherapy of capecitabine and cisplatin demonstrated a promising antitumor activity with mild toxicity profile in patients with advanced biliary tract cancer.
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Affiliation(s)
- Yong Sang Hong
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, South Korea
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Margarit C, Escartín A, Bellmunt J, Allende E, Bilbao I. [Peripheral cholangiocarcinoma: results of surgical treatment]. GASTROENTEROLOGIA Y HEPATOLOGIA 2006; 29:215-23. [PMID: 16584691 DOI: 10.1157/13085990] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Peripheral cholangiocarcinoma (PC) is an uncommon primary hepatic tumor that represents 10% of hepatic resections for primary malignant tumors in our experience. PATIENTS AND METHODS From 1988 to 2004, 29 patients with a diagnosis of PC were treated in our unit. One patient was treated with chemoembolization and the remainder underwent surgery. In 7 patients, hepatectomy was not performed due to the presence of an extrahepatic tumor or massive hepatic invasion. The resectability index was 75%. Twenty-one patients underwent radical excision of PC and comprised the study group. RESULTS The mean age was 60 years with a slight predominance of women. Sixty-two patients were symptomatic and tumoral markers were elevated in 58%. PC developed in normal liver in 15 patients, in cirrhotic liver in 2 patients and in the context of chronic hepatitis in 4 patients. The mean tumoral size was 7 cm (between 1.6 and 13 cm). Multiple tumors were found in 3 patients, invasion of the hepatic hilum lymph nodes was found in 8 patients and vascular invasion was observed in a further 8 patients. Major hepatectomy was performed in 90% of the patients; radical lymphadenectomy of the hepatic hilum was performed in 15 patients and excision of the extrahepatic biliary tract followed by Roux-en-Y hepaticojejunostomy in 4 patients. Operative mortality occurred in 3 patients (14%); one cirrhotic patient died 4 days after surgery from cardiovascular causes and 2 patients died from liver failure after extensive hepatectomies that included resection of the inferior vena cava and suprahepatic veins. Complications occurred in 33% of the patients. Ten patients (47%) died. Of these, 6 died from tumoral recurrence. Tumoral recurrence occurred in 9 patients (5 hepatic and 4 extrahepatic). Hepatic recurrences were treated with radiofrequency ablation in 2 patients and chemotherapy in 5 patients. The median survival was 11 months. Actuarial survival at 1, 3 and 5 years was 60%, 47% and 47% respectively. Disease-free survival at 1, 3 and 5 years was 50%, 31% and 31% respectively. In univariate analysis, significant risk factors for mortality were lymphatic invasion and a resection margin of less than 1 cm. In multivariate analysis, negative factors for tumoral recurrence were lymphatic invasion, satellitosis, and poor tumoral delimitation. CONCLUSION Surgical treatment of PC through radical hepatic resection with margins of more than 1 cm in patients without nodal invasion provides good results with a 5-year survival of 79%.
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Affiliation(s)
- C Margarit
- Unidad de Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General, Hospital Vall d'Hebron, Barcelona, Spain
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Schmeding M, Neumann U, Neuhaus P. Colonic metastasis of Klatskin tumor: Case report and discussion of the current literature. World J Gastroenterol 2006; 12:5393-5. [PMID: 16981275 PMCID: PMC4088212 DOI: 10.3748/wjg.v12.i33.5393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We report the case of a 65-year old male patient who initially presented with recurrent episodes of upper abdominal pain, lack of appetite and weight loss. Abdominal ultrasound indicated enlarged intrahepatic bile ducts, abdominal CT scan and ERC were performed and bile duct carcinoma (Klatskin Type III b) was diagnosed. The tumor was located in the segments 2,3,4 and 1 with possible invasion of the left intrahepatic portal vein. Both the segments 2 and 3 of the liver were atrophic and displayed a cholestatic bile duct system. Preoperatively an intraductal stent was placed in the left bile duct using ERC to drain the left hepatic lobe. A specimen of the ascites present preoperatively displayed no malignant cells. After evaluation of the preoperatively obtained data left hepatic resection was planned. Following laparotomy we found local peritoneal carcinosis in the ligamentum hepatoduodenale with lymphatic nodules that tested positive for cholangiocellular carcinoma in online pathological examination. In the course of further exploration of the abdomen a solid tumor was detected in the sigmoid colon. Regarding the advanced stage of the neoplasm it was decided to cancel hemihepatectomy and perform sigmoid resection only in order to guarantee uncomplicated intestinal passage. The sigmoid colon was removed by a typical resection technique with end-to-end anastomosis. Histological examination of the resected sigmoid revealed transmural manifestation of a malignant neoplastic process with both a tubular and a solid growth pattern in conformity with metastasis of a Klatskin tumor. The mucosal layer showed no neoplastic alteration. Peritoneal carcinosis is a common phenomenon in the dissemination pattern of advanced-stage Klatskin tumors, yet to our knowledge this is the first case of intramural colonic growth following peritoneal metastasis.
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Affiliation(s)
- M Schmeding
- Klinik fuer Allgemein-, Visceral- und Transplantationschirurgie, Charite Campus Virchow Klinikum, Augustenburger Platz 1, Berlin 13533, maximilian, Germany.
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Lang H, Sotiropoulos GC, Brokalaki E, Frühauf NR, Radü J, Paul A, Wohlschlaeger J, Baba HA, Malagó M, Broelsch CE. [Surgical therapy of intrahepatic cholangiocellular carcinoma]. Chirurg 2006; 77:53-60. [PMID: 16170505 DOI: 10.1007/s00104-005-1069-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy. Tumor resection is the treatment of choice, but so far the value of hepatic resection has not been well defined. We report results with an aggressive surgical approach for the treatment of this tumor entity. PATIENTS AND METHODS Between April 1998 and June 2004, 54 liver resections were performed in 120 patients with ICC. In 24 patients, 39 additional procedures were performed: resection of hilar bifurcation (n=18), partial resection of diaphragm (n=6), vascular resection and reconstruction (n=15). RESULTS There were 30 R0, 21 R1, and three R2 resections. After R1/R2 resection and explorative laparotomy, the median survival times are 9 months and 6 months, respectively. Following R0 resection, the calculated median survival is 46 months, and the 1-, 3-, and 5-year survival rates are 83%, 58%, and 48%, respectively. CONCLUSION The presented data show that R0 resection leads to a significant prolongation of survival in patients with ICC. In contrast, incomplete tumor removal does not provide a survival benefit. These results justify an aggressive surgical approach to achieve a R0 resection. The low resectability rate of less than 50% underlines the need for improved preoperative staging.
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Affiliation(s)
- H Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen.
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Kim ST, Park JO, Lee J, Lee KT, Lee JK, Choi SH, Heo JS, Park YS, Kang WK, Park K. A Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. Cancer 2006; 106:1339-1346. [PMID: 16475213 DOI: 10.1002/cncr.21741] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The authors performed a Phase II study of combination chemotherapy with gemcitabine and cisplatin in patients with inoperable biliary tract cancer to evaluate efficacy and toxicity of this combination. In addition, the correlation between the CA 19-9 response and clinical outcome was analyzed. METHODS The eligibility criteria for this study were 1) histologically or cytologically confirmed inoperable biliary tract cancer in patients with metastatic or recurrent disease; 2) age between 18 and 70 years; 3) at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; 4) an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2; 5) a life expectancy of at least 3 mos; and 6) adequate bone marrow, hepatic, and renal function. The patients received gemcitabine (1250 mg/m(2), Days 1 and 8) and cisplatin (60 mg/m(2), Day 1) every 3 weeks. Tumor response was assessed by RECIST criteria every 2 cycles of chemotherapy. Treatment was continued until progression of disease was documented. RESULTS Twenty-nine patients were enrolled. The median age of these patients was 52 years (range, 37 to 69 yrs), and the median ECOG performance status was 1. No complete response was observed, and 10 of 29 patients had partial responses. The overall response rate was 34.5% (95% confidence interval [CI], 17.9-54.3) for the intent-to-treat analysis. Stable disease was observed in 4 (13.8%) patients and progressive disease in 13 (44.8%) patients. The median follow-up time was 10.0 months (95% CI, 7.2-12.8). The median time to progression (TTP) was 3.0 months (95% CI, 2.12-3.88), and the median overall survival was 11 months (95% CI, 5.49-16.5). Although these results showed a better response rate (57.1 % vs. 27.3%) and survival (12 vs. 10 mos) in patients with a decline in CA 19-9 of at least 25%, these data were statistically not significant. In addition, there was a significant positive correlation between the increment in CA 19-9 values and tumor progression as determined with RECIST criteria (r = 0.96, P < 0.01). However, there was no definite correlation between the CA 19-9 response and the response according to RECIST criteria (P = 0.087). National Cancer Institute (NCI) common toxicity criteria (CTC) Grade 3 or 4 hematologic toxicities included neutropenia in 4 (14%) patients and anemia in 1 (3%) patient. Two of 4 patients with Grade 3 or 4 neutropenia had febrile episodes (7%) and required hospital admissions. NCI-CTC Grade 3 or 4 nonhematologic toxicity included nausea in 1 (3%) patient. There were no treatment-related deaths. CONCLUSION The combination chemotherapy with gemcitabine and cisplatin in inoperable biliary tract cancer was tolerable for most patients and showed modest response rates. The role of CA 19-9 monitoring as a surrogate biomarker in patients with BTC treated with gemcitabine chemotherapy should be further investigated.
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Affiliation(s)
- Seung Tai Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea
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Lim JH, Jang KT, Choi D, Lee WJ, Lim HK. Early bile duct carcinoma: comparison of imaging features with pathologic findings. Radiology 2006; 238:542-8. [PMID: 16396837 DOI: 10.1148/radiol.2382042105] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE To retrospectively evaluate the imaging features of early bile duct carcinoma and to compare these features with histopathologic findings. MATERIALS AND METHODS The institutional review board did not require its approval or informed patient consent for this study. Twenty-one patients (13 men, eight women; mean age, 60 years; range, 48-75 years) with early bile duct carcinoma that was surgically resected and histopathologically confirmed were included. Ultrasonography (US) was performed in 15 patients, computed tomography (CT) in 21, cholangiography in 18, and magnetic resonance (MR) cholangiography in six. Two radiologists retrospectively reviewed imaging features by consensus; they compared growth pattern of tumors, integrity of the bile duct wall that harbored the tumor, and periductal infiltration with histopathologic findings. RESULTS Pathologic specimens showed intraluminal tumor growth in all cases. Tumors were confined to the mucosa in 11 patients and involved the fibromuscular layer in 10 patients. In four of the 10 intrahepatic cholangiocarcinomas, four of the five hilar cholangiocarcinomas, and six of the six extrahepatic cholangiocarcinomas, there were intraductal tumor masses and the wall of the tumor-bearing bile ducts was preserved without periductal infiltration on US and CT images. On cholangiograms and MR cholangiograms, tumors were better delineated but the wall invasion could not be evaluated. No difference in image findings was found between carcinoma confined to the mucosa and carcinoma involving the fibromuscular layer. CONCLUSION Imaging features of early bile duct carcinoma are a tumor mass in the bile duct lumen and integrity of the tumor-bearing bile duct wall without infiltration outside the wall.
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Affiliation(s)
- Jae Hoon Lim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
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Foja S, Goldberg M, Schagdarsurengin U, Dammann R, Tannapfel A, Ballhausen WG. Promoter methylation and loss of coding exons of the fragile histidine triad (FHIT) gene in intrahepatic cholangiocarcinomas. Liver Int 2005; 25:1202-8. [PMID: 16343073 DOI: 10.1111/j.1478-3231.2005.01174.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
AIMS About 10-30% of primary liver cancers represent intrahepatic cholangiocarcinomas (IHCC). Since chromosomal losses of 3p are detectable in about 40% of cholangiocarcinomas our study aimed at the identification of mechanisms leading to functional deletion of tumor suppressor genes in this region. Our efforts focussed on genomic losses and epigenetic inactivation of two tumor suppressor genes, the fragile histidine triad (FHIT) and the ras association domain family 1 (RASSF1A) genes, both located on the short arm of chromosome 3. METHODS Methylation-specific PCR (MSP) and combined bisulfite-dependent restriction analysis (COBRA) were applied to detect epigenetic silencing of gene promoters. Genomic duplex PCR was used to identify exon losses of the FHIT gene. Nineteen paraffin-embedded samples of intrahepatic cholangiocarcinomas were studied. RESULTS Here we report for the first time that in addition to frequent losses of the exons 5 and 6, hypermethylation of the FHIT promoter occured in a significant portion of IHCC. Methylation specific PCR (MSP) detected epigenetic inactivation of the FHIT/FRA3B locus in 8 of 19 (42%) cases. Combined bisulfite restriction analysis (COBRA) revealed that high levels of methylated FHIT promoter sequences were present in 6 of the 8 methylation positive samples. In agreement with previous reports MSP identified hypermethylation of the RASSF1A gene in 13 of 19 (68%) IHCC specimens examined. CONCLUSIONS Epigenetic silencing of the FHIT tumor suppressor gene is a novel inactivation mechanism to be considered in the development of intrahepatic cholangiocarcinomas. However, a statistically significant inverse correlation between K-Ras activation and RASSF1A inactivation was not found.
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Affiliation(s)
- S Foja
- Universitätsklinik und Poliklinik für Innere Medizin I, Sektion Molek. GI Onkologie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany
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Puhalla H, Schuell B, Pokorny H, Kornek GV, Scheithauer W, Gruenberger T. Treatment and outcome of intrahepatic cholangiocellular carcinoma. Am J Surg 2005; 189:173-7. [PMID: 15720985 DOI: 10.1016/j.amjsurg.2004.11.009] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2004] [Accepted: 07/20/2004] [Indexed: 01/06/2023]
Abstract
BACKGROUND Treating intrahepatic cholangiocarcinoma (ihCCC) tumor resection leads to the best patient survival. The aim of this study was to investigate prognostic factors in resected patients. METHODS This was a clinical observational series of 31 resected patients with ihCCC. Univariate analysis of clinical and pathologic factors in relation to patient survival and tumor recurrence were performed. Possible benefit of chemotherapy, although not given randomly, was investigated separately. RESULTS The median follow-up time was 37.3 months. Of 31 resected patients a tumor-free resection (R0) was achieved in 26; 2 patients died postoperatively. Chemotherapy was administered to 19 patients. Overall survival was significantly better in patients with R0 resection, negative lymph nodes, a solitary tumor, and a width of resection margin greater than 3 mm. Recurrence-free survival was prolonged in patients with negative lymph nodes, early International Union Against Cancer (UICC) stages and solitary tumors. In UICC stages III and IV, patients receiving chemotherapy experienced a better overall survival. CONCLUSIONS Impact of various parameters on recurrence-free and overall survival was identified; a possible beneficial effect of adjuvant chemotherapy in advanced tumor stages was observed. A prospective, randomized trial is necessary to fully evaluate the role of adjuvant therapy.
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Affiliation(s)
- Harald Puhalla
- Department of General Surgery, General Hospital, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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Lang H, Sotiropoulos GC, Frühauf NR, Dömland M, Paul A, Kind EM, Malagó M, Broelsch CE. Extended hepatectomy for intrahepatic cholangiocellular carcinoma (ICC): when is it worthwhile? Single center experience with 27 resections in 50 patients over a 5-year period. Ann Surg 2005; 241:134-43. [PMID: 15622001 PMCID: PMC1356856 DOI: 10.1097/01.sla.0000149426.08580.a1] [Citation(s) in RCA: 139] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To evaluate the role of extended hepatectomy in locally advanced intrahepatic cholangiocarcinoma (ICC). SUMMARY BACKGROUND DATA ICC is a rare tumor which has to be clearly distinguished from hepatocellular carcinoma and extrahepatic bile duct carcinoma. It is believed that long-term survival can only be achieved by surgical resection. METHODS Between April 1998 and March 2003, 50 patients with locally advanced ICC (tumor involvement of more than 4 liver segments) underwent surgical exploration. Data were analyzed with regard to patients' characteristics, intraoperative details, pathologic findings, and outcome measured by tumor recurrence, treatment of recurrence, and survival. RESULTS Resectability rate was 27 of 50 (54%). There were 19 extended right and 8 extended left hepatectomies. In addition, in 16 patients the following 29 procedures were performed: resection of hilar bifurcation (n = 12), partial resection of diaphragm (n = 6), partial resection of vena cava (n = 4), resection and reinsertion of left liver vein (n = 1), portal vein resection (n = 5), resection and reconstruction of right hepatic artery (n = 1). Complete tumor removal (R0-resection) was achieved in 16 patients. In 11 cases, there was microscopic tumor at the cutting margin (R1-resection). Following resection, the overall 1- and 3-year-survival rates were 69% and 55%. After R1-resection and explorative laparotomy, median survival was 5 and 7 months, respectively. Following R0-resection, the calculated median survival and 1- and 3-year-survival rates are 46 months, 94% and 82% (P = 0.0039; log-rank test). Tumor recurred in 6 of 16 patients, and so far 2 patients died of recurrence 28 and 46 months after operation. CONCLUSIONS R0-resection can provide prolonged survival, even in patients with advanced ICC. In particular in solitary tumors without vascular invasion (UICC stage I, sixth classification) there is a major chance for long-term survival and cure. The poor results after R1-resection and the high operative morbidity do not justify palliative resections but underline the need for an improved preoperative assessment of resectability, as well as an aggressive intraoperative approach, to achieve complete tumor resection.
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Affiliation(s)
- Hauke Lang
- Department of General Surgery and Transplantation, University Hospital Essen, Hufelandstr. 55, D-45122 Essen, Germany.
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Kirchhoff T, Zender L, Merkesdal S, Frericks B, Malek N, Bleck J, Kubicka S, Baus S, Chavan A, Manns MP, Galanski M. Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver. World J Gastroenterol 2005; 11:1091-5. [PMID: 15754387 PMCID: PMC4250696 DOI: 10.3748/wjg.v11.i8.1091] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.
METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2 cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.
RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.
CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.
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Affiliation(s)
- Timm Kirchhoff
- Department of Diagnostic Radiology, OE 8220, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
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Rai R, Manas D, Rose J. Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation - a case report. World J Gastroenterol 2005; 11:612-3. [PMID: 15641158 PMCID: PMC4250823 DOI: 10.3748/wjg.v11.i4.612] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To report the use of radiofrequency ablation in the treatment of recurrent cholangiocarcinoma in the transplanted liver.
METHODS: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after transplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation.
RESULTS: She survived for 18 mo following the recurrence of her tumour.
CONCLUSION: Radiofrequency ablation can be used safely in the transplanted liver to treat recurrent tumour.
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Affiliation(s)
- Rakesh Rai
- HPB Surgery and Liver Transplant Unit, Freeman Hospital, Newcastle, UK.
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