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1
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Rawal N, Hariprasad G, Bandyopadhyay S, Dash NR, Kumar S, Das P, Dey S, Khan MA, Ranjan A, Chopra A, Saluja S, Hussain S, Rath GK, Kaur T, Tanwar P. Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach. BIOMOLECULES & BIOMEDICINE 2024; 25:115-143. [PMID: 39284282 PMCID: PMC11647257 DOI: 10.17305/bb.2024.10704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 06/17/2024] [Accepted: 06/17/2024] [Indexed: 12/14/2024]
Abstract
The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography-assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from ten cases each of GBC and inflammatory lesions, with technical duplicates. Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan-Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real-time-polymerase chain reaction (RT-PCR). Out of 5714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables. Prognostic factors, such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival (OS). Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.
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Affiliation(s)
- Neetu Rawal
- Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Gururao Hariprasad
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | - Sabyasachi Bandyopadhyay
- Proteomics Laboratory, Centralized Core Research Facility, All India Institute of Medical Sciences, New Delhi, India
| | - Nihar Ranjan Dash
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Sunil Kumar
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sharmistha Dey
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | - Maroof Ahmad Khan
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Amar Ranjan
- Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Anita Chopra
- Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Sundeep Saluja
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Hospital, New Delhi, India
| | - Showket Hussain
- Division of Molecular Oncology, National Institute of Cancer Prevention and Research, Indian Council of Medical Research, New Delhi, India
| | - GK Rath
- Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Tanvir Kaur
- Division of Non-Communicable Diseases, Indian Council of Medical Research, New Delhi, India
| | - Pranay Tanwar
- Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
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Kato T, Okada K, Baba Y, Yasuda M, Ohshima Y, Takase K, Watanabe Y, Watanabe Y, Aikawa M, Okamoto K, Koyama I. Preoperative prognostic stratification and prediction of long-term outcomes after pancreatoduodenectomy for distal cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108691. [PMID: 39366161 DOI: 10.1016/j.ejso.2024.108691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 09/13/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Patients with distal cholangiocarcinoma (DCC) frequently receive adjuvant chemotherapy in preoperative and postoperative settings, but prediction of prognostic risk at the time of treatment selection remains challenging. METHODS This single-center retrospective study enrolled DCC patients who underwent initial pancreatoduodenectomy (PD) between 2009 and 2022. Preoperative clinical parameters were collected, and Cox regression analysis was used to identify risk factors for overall survival (OS). RESULTS Among 170 patients examined, the median tumor depth was 10 mm, and 37 % of the patients were diagnosed with pT3. Overall, 46 % of patients had lymph node metastasis. The median and 5-year OS was 58.2 months and 50 %, respectively. Multivariate analysis revealed tumor size on computed tomography (CT) ≥15 mm and main pancreatic duct (MPD) dilatation (≥3 mm) as independent risk factors for OS among various preoperative parameters; the prognosis was stratified based on these two parameters. Patients with one risk factor had similar outcomes (5-year OS: 39 %) to pStage IIB DCC (pT2N1 or pT3), while those with two risk factors had a prognosis akin to pStage IIIA (pN2), with a high early recurrence rate of 64 % (5-year OS: 8 %). Among non-risk group patients with low carbohydrate antigen (CA)19-9 levels (<37 U/mL), the prognosis was comparable (5-year OS: 72 %) to those with pStage I DCC. CONCLUSION A simple stratification approach was developed to predict long-term postoperative outcomes. To improve poor prognosis, intensive therapy, including neoadjuvant chemotherapy, should be considered for patients with two risk factors.
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Affiliation(s)
- Tomotaka Kato
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Katsuya Okada
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan.
| | - Yasutaka Baba
- Diagnostic Radiology, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Masanori Yasuda
- Pathology, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Yuhei Ohshima
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Kenichiro Takase
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Yuichiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Masayasu Aikawa
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Kojun Okamoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Isamu Koyama
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
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3
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Takaoka S, Hamada T, Takahara N, Fukuda R, Hakuta R, Ishigaki K, Kanai S, Kurihara K, Matsui H, Michihata N, Nishio H, Noguchi K, Oyama H, Saito T, Sato T, Suzuki T, Suzuki Y, Tange S, Fushimi K, Nakai Y, Yasunaga H, Fujishiro M. Body mass index and survival among patients with advanced biliary tract cancer: a single-institutional study with nationwide data-based validation. J Gastroenterol 2024; 59:732-743. [PMID: 38896254 DOI: 10.1007/s00535-024-02124-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Excess body weight may modulate the progression of various cancer types. The prognostic relevance of body mass index (BMI) has not been fully examined in patients with biliary tract cancer. METHODS Using a single-institutional cohort of 360 patients receiving gemcitabine-based chemotherapy for advanced biliary tract cancer, we examined the association of BMI with overall survival (OS). Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for OS according to BMI. The findings were validated using a Japanese nationwide inpatient database including 8324 patients treated at 201 hospitals. RESULTS In the clinical cohort, BMI was not associated with OS (Ptrend = 0.34). Compared to patients with BMI = 18.5-24.9 kg/m2, patients with BMI < 18.5 kg/m2 and ≥ 25.0 kg/m2 had adjusted HRs for OS of 1.06 (95% CI, 0.78-1.45) and 1.01 (95% CI, 0.74-1.39), respectively. There was no evidence on a non-linear relationship between BMI and OS (Pnonlinearity = 0.63). In the nationwide cohort, the null findings were validated (Ptrend = 0.18) with adjusted HRs of 1.07 (95% CI, 0.98-1.18) for BMI < 18.5 kg/m2 and 1.05 (95% CI, 0.96-1.14) for BMI ≥ 25.0 kg/m2 (vs. BMI = 18.5-24.9 kg/m2). In the clinical cohort, BMI was not associated with progression-free survival (Ptrend = 0.81). CONCLUSIONS BMI was not associated with survival outcomes of patients with advanced biliary tract cancer. Further research is warranted incorporating more detailed body composition metrics to explore the prognostic role of adiposity in biliary tract cancer.
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Affiliation(s)
- Shinya Takaoka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Rintaro Fukuda
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryunosuke Hakuta
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sachiko Kanai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo City, Tokyo, 113-8655, Japan
| | - Kohei Kurihara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Nobuaki Michihata
- Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroto Nishio
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kensaku Noguchi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroki Oyama
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsunori Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yukari Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shuichi Tange
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo City, Tokyo, 113-8655, Japan.
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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de Savornin Lohman E, Belkouz A, Nuliyalu U, Groot Koerkamp B, Klümpen HJ, de Reuver P, Nathan H. Adjuvant treatment for the elderly patient with resected gallbladder cancer: a SEER-Medicare analysis. J Gastrointest Oncol 2022; 13:3227-3239. [PMID: 36636087 PMCID: PMC9830355 DOI: 10.21037/jgo-22-348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 10/14/2022] [Indexed: 11/27/2022] Open
Abstract
Background In patients with resected gallbladder cancer (GBC), the role of adjuvant chemotherapy (aCT) remains ill-defined, especially in elderly patients. This study evaluates the value of aCT in elderly patients with GBC and assesses response according to tumor stage. Methods Patients of ≥65 years of age with resected GBC diagnosed from 2004-2015 were identified using a Surveillance, Epidemiology and End Results (SEER)/Medicare linked database. After propensity score matching, survival of patients treated with aCT was compared to survival of patients who did not receive aCT using Kaplan-Meier and Cox proportional hazards analysis. Results Of 2,179 patients with resected GBC, 876 (25%) received aCT. In the full cohort of 810 propensity-score matched patients, survival did not differ between patients treated with aCT (17.6 months ) and without aCT (19.5 months, P=0.7720). Subgroup analysis showed that survival was significantly better after aCT in T3/T4 disease (12.3 vs. 7.2 months, P=0.013). Interaction analysis showed that benefit of aCT was primarily seen in combined T3/T4, node-positive disease (HR 0.612 , P=0.006). Conclusions In this large cohort of elderly patients with resected GBC, aCT was not associated with increased survival. However, aCT may provide a survival benefit in T3/4, node-positive disease.
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Affiliation(s)
- Elise de Savornin Lohman
- Department of Surgery, Radboudumc, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, the Netherlands;,Department of Surgery, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI, USA
| | - Ali Belkouz
- Department of Medical Oncology, Amsterdam University Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Usha Nuliyalu
- Department of Surgery, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Doctor M olewaterplein 40, 3015 GD, Rotterdam, the Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Amsterdam University Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Philip de Reuver
- Department of Surgery, Radboudumc, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, the Netherlands
| | - Hari Nathan
- Department of Surgery, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI, USA
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5
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Sahara K, Tsilimigras DI, Toyoda J, Miyake K, Ethun CG, Maithel SK, Abbott DE, Poultsides GA, Hatzaras I, Fields RC, Weiss M, Scoggins C, Isom CA, Idrees K, Shen P, Yabushita Y, Matsuyama R, Endo I, Pawlik TM. Defining the Risk of Early Recurrence Following Curative-Intent Resection for Distal Cholangiocarcinoma. Ann Surg Oncol 2021; 28:4205-4213. [PMID: 33709171 DOI: 10.1245/s10434-021-09811-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 02/19/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC. PATIENTS AND METHODS Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset. RESULTS Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)]. CONCLUSIONS Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.
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Affiliation(s)
- Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.,Division of Surgical Oncology, Health Services Management and Policy, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Diamantis I Tsilimigras
- Division of Surgical Oncology, Health Services Management and Policy, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Junya Toyoda
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kentaro Miyake
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Daniel E Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | | | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Chelsea A Isom
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Yasuhiro Yabushita
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Division of Surgical Oncology, Health Services Management and Policy, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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6
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Patyutko YI, Polyakov AN, Podluzhnyi DV, Syskova AY, Sagaidak IV, Kotel'nikov AG, Sergeeva ON, Pokataev IA. [Cholangiocellular cancer: the state of the problem and ways to improve the results of surgical treatment]. Khirurgiia (Mosk) 2018:30-37. [PMID: 30560842 DOI: 10.17116/hirurgia201812130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
AIM To improve the outcomes in patients with resectable biliary cancer. MATERIAL AND METHODS There were 263 procedures for cholangiocellular carcinoma (CCC) for the period 1998—2017. Adjuvant chemotherapy was performed in 102 (38.8%) patients. Extensiveliver resections (78.9%) prevailed for intrahepatic cholangiocellular carcinoma (n=128), 6 (4.7%) patients required vascular resection. Seventy-seven pancreatoduodenectomies were performed for common bile duct cancer, portal vein resection was done in 8 (10.4%) patients. In case of Klatskin tumor (n=58) liver resection combined with bile duct resection (n=52) prevailed. Portal vein resection was done in 16 (27.6%) patients. RESULTS Postoperative morbidity in patients with intrahepatic CCC was revealed in 68 (53.1%) cases, mortality — in 5 (3.9%) cases. Among patients with Klatskin tumor morbidity was revealed in 51 (87.9%) cases, mortality — in 6 (10.3%) cases. In patients with common bile duct cancer morbidity was revealed in 53 (68.8%) cases, mortality — in 4 (5.2%) cases. In whole cohort median overall survival was 30 months. R0-resection was associated with better long-term results (median 37 months) compared with R1—R2 resection (20 months; p=0.01). Lymph node involvement is associated with significantly worse prognosis (p=0.016), however 5-year survival is observed (25.6%). Adjuvant chemotherapy in R0-resection significantly improved long-term results: median was 46 months (vs. 30 in group without chemotherapy; p=0.02). In intrahepatic CCC patients multiple lesions or mechanical jaundice did not aggravate long-term results. CONCLUSION R0-resection including lymphadenectomy, resection of adjacent organs and vessels is advisable for CCC. Isolated bile duct resection should be used as an exception. Adjuvant therapy improved long-term results. Multiple lymph node lesion or bile duct infiltration are not contraindications to surgery in intrahepatic CCC patients.
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Affiliation(s)
- Yu I Patyutko
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - A N Polyakov
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - D V Podluzhnyi
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - A Yu Syskova
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - I V Sagaidak
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - A G Kotel'nikov
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - O N Sergeeva
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
| | - I A Pokataev
- N.N. Blokhin National Medical Cancer Research Center of Healthcare Ministry of the Russia, Moscow, Russia
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7
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Chang WW, Hsiao PK, Qin L, Chang CL, Chow JM, Wu SY. Treatment outcomes for unresectable intrahepatic cholangiocarcinoma: Nationwide, population-based, cohort study based on propensity score matching with the Mahalanobis metric. Radiother Oncol 2018; 129:284-292. [PMID: 30279046 DOI: 10.1016/j.radonc.2018.09.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/15/2018] [Accepted: 09/15/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE No prospective randomized trials have been conducted to date to evaluate the efficacy of palliation of pain or jaundice without treatment, definitive concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiotherapy (CTRT), or chemotherapy (CT) alone for treating unresectable intrahepatic cholangiocarcinoma (ICC). We designed a nationwide, population-based, cohort study to determine the effects of different treatments on patients with unresectable ICC using propensity score matching (PSM) with the Mahalanobis metric. PATIENTS AND METHODS We classified patients with unresectable ICC from the Taiwan Cancer Registry database into the following 4 treatment groups: group 1, definitive CCRT; group 2, sequential CTRT; group 3, no treatment (palliative therapy for relief of pain, pruritus, or jaundice); and group 4, CT alone. Confounding factors among the 4 treatment groups were minimized through propensity score matching (PSM). RESULTS After PSM, the final cohort consisted of 844 patients (211 patients in each of the 4 groups). In both univariable and multivariable Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) derived for groups 1 and 2 compared with group 4 were 0.65 (0.59-0.71) and 0.95 (0.83-1.48), respectively. Furthermore, an aHR (95% CI) of 2.25 (1.89-2.67) was derived for significant independent prognostic risk factors for poor overall survival for group 3 compared with group 4. CONCLUSIONS Definitive CCRT is the optimal therapy for patients with unresectable ICC without distant metastasis.
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Affiliation(s)
- Wei-Wen Chang
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Ping-Kun Hsiao
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Lei Qin
- School of Statistics, University of International Business and Economics, Beijing, China
| | - Chia-Lun Chang
- Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Jyh-Ming Chow
- Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Szu-Yuan Wu
- Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biotechnology, Chinese Culture University, YangMingShan, Taipei 11114, Taiwan.
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8
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Pellino A, Loupakis F, Cadamuro M, Dadduzio V, Fassan M, Guido M, Cillo U, Indraccolo S, Fabris L. Precision medicine in cholangiocarcinoma. Transl Gastroenterol Hepatol 2018; 3:40. [PMID: 30148225 PMCID: PMC6087799 DOI: 10.21037/tgh.2018.07.02] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 07/03/2018] [Indexed: 12/19/2022] Open
Abstract
Cholangiocarcinoma is one of the epithelial cancers with the poorest prognosis and the narrowest therapeutic choice in humans. Compared with other cancer types, cholangiocarcinoma has been often neglected by oncology and liver research studies, thereby leaving many issues unsolved. Apart from the early and marked aggressiveness, one of the main reasons of the still unsatisfying clinical management of cholangiocarcinoma is its wide tumor heterogeneity needing more than other diseases a 'precision medicine' approach. In this regard, in the last few years there has been an awakening of interest aimed at dissecting the complex molecular and genomic profile of cholangiocarcinoma. Thus, a range of molecular players have been recently identified as putative mechanistic determinants of cholangiocarcinoma invasiveness, encompassing tyrosine kinase receptors, metabolic enzymes, transcription factors, small GTPases, ubiquitin ligases, and chromatin-remodelling proteins, whose aberrant expression may derive from stochastic mutations as well as from pro-oncogenic paracrine signals released by the stromal microenvironment, which is particularly exuberant in cholangiocarcinoma. Herein, we sought to overview the most relevant observations unravelling the genomic landscape of cholangiocarcinoma, and the prognostic and predictive biomarkers that consequently have been emerging. Then, we will discuss innovative treatment approaches derived from conventional chemotherapy, targeted therapies, antiangiogenic therapies and immunotherapy, and how they are opening new avenues towards a precision medicine in cholangiocarcinoma.
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Affiliation(s)
- Antonio Pellino
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy
| | - Fotios Loupakis
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Maria Guido
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy
| | - Stefano Indraccolo
- Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Luca Fabris
- Department of Molecular Medicine (DMM), University of Padua, Padua, Italy
- Department of Internal Medicine, Yale Liver Center (YLC), School of Medicine, Yale University New Haven, CT, USA
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Kang J, Lee SH, Son JH, Lee JW, Choi YH, Choi JH, Paik WH, Ryu JK, Kim YT. Body mass index and weight change during initial period of chemotherapy affect survival outcome in advanced biliary tract cancer patients. PLoS One 2018; 13:e0195118. [PMID: 29608578 PMCID: PMC5880377 DOI: 10.1371/journal.pone.0195118] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 03/17/2018] [Indexed: 01/10/2023] Open
Abstract
Background The impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy. Methods Between January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated. Results Median overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23–24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436–0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168–1.986, p = 0.046) was associated with a shorter in overall survival. Conclusion Overweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients.
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Affiliation(s)
- Jinwoo Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Gastroenterolgy and Hepatology, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- * E-mail:
| | - Jun Hyuk Son
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Jae Woo Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Mediplex Sejong Hospital, Gyeyang-gu, Incheon, Korea
| | - Young Hoon Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jin Ho Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
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Warner WA, Ramcharan W, Harnanan D, Umakanthan S, Maharaj R. A case of distal extrahepatic cholangiocarcinoma with two positive resection margins. Oncol Lett 2016; 12:4075-4079. [PMID: 27895774 DOI: 10.3892/ol.2016.5174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 08/25/2016] [Indexed: 11/05/2022] Open
Abstract
Cholangiocarcinoma is an uncommon primary malignancy of the biliary tract that is challenging to diagnose and treat effectively due to its relatively silent and late clinical presentation. The present study reports a case of a 60-year-old male with distal extrahepatic cholangiocarcinoma with a 3-week history of painless obstructive jaundice symptoms and subjective weight loss. Imaging revealed an obstructing lesion in the common bile duct, just distal to the entrance of the cystic duct. Pathology revealed moderately differentiated cholangiocarcinoma with two positive proximal resection margins. The two positive resection margins presented a challenge during surgery and points to an urgent need for further studies to better illuminate diagnostic and therapeutic options for patients with similar clinicopathological presentation.
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Affiliation(s)
- Wayne A Warner
- Division of Oncology, Siteman Cancer Center, Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Wesley Ramcharan
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
| | - Dave Harnanan
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
| | - Srikanth Umakanthan
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
| | - Ravi Maharaj
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
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Gérard S, Bréchemier D, Lefort A, Lozano S, Abellan Van Kan G, Filleron T, Mourey L, Bernard-Marty C, Rougé-Bugat ME, Soler V, Vellas B, Cesari M, Rolland Y, Balardy L. Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review. J Nutr Health Aging 2016; 20:878-888. [PMID: 27709238 DOI: 10.1007/s12603-015-0653-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. METHOD We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. RESULTS Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. CONCLUSIONS Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.
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Affiliation(s)
- S Gérard
- Stéphane Gérard, CHU Purpan, Gérontopôle, Pavillon Junod, 170 avenue de Casselardit 31059 Toulouse Cedex 09, France, Tel: +33 6 78 94 44 22, Fax: +33 5 61 77 64 14, E-mail address:
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12
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Ting CF, Huang WH, Feng CL, Yu CJ, Peng CY, Su WP, Lai HC, Cheng KS, Chuang PH, Kao JT. Clinical factors associated with the survival of patients with intrahepatic cholangiocarcinoma. ADVANCES IN DIGESTIVE MEDICINE 2015. [DOI: 10.1016/j.aidm.2014.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
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13
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da Costa Miranda V, Braghiroli MI, Faria LDBB, Siqueira SAC, Sabbaga J, Hoff PM, Riechelmann RP. ERCC1 in advanced biliary tract cancer patients treated with chemotherapy: prognostic and predictive roles. J Gastrointest Cancer 2014; 45:80-6. [PMID: 24326865 DOI: 10.1007/s12029-013-9568-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown. METHODS We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross-complementing gene-1) on tumor response and also examined several clinical and laboratory prognostic factors for overall survival. RESULTS From January 2009 to July 2011, 72 patients were identified; their median overall survival was 9.5 months. Independent variables associated with shorter survival identified by the multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95% CI 3.4 to 20.7; p < 0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95% CI 1.6 to 55.3; p = 0.012). Pathology slides were available from 44 patients: 23 (52%) stained positive for ERCC1 on IHC (score ≥0.5). In this subgroup, expression of ERCC-1 was not prognostic and was not associated with either clinical benefit (partial response and stable disease) or tumor response (partial response only) to chemotherapy. CONCLUSIONS In this cohort of unselected patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2-3 and/or multiple comorbidities had worse survival.
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Affiliation(s)
- Vanessa da Costa Miranda
- Disciplina de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 251,12o andar, São Paulo, SP, 01246-000, Brazil
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14
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Wirasorn K, Ngamprasertchai T, Chindaprasirt J, Sookprasert A, Khantikaew N, Pakkhem A, Ungarereevittaya P. Prognostic factors in resectable cholangiocarcinoma patients: Carcinoembryonic antigen, lymph node, surgical margin and chemotherapy. World J Gastrointest Oncol 2013; 5:81-87. [PMID: 23671735 PMCID: PMC3648667 DOI: 10.4251/wjgo.v5.i4.81] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2012] [Revised: 03/05/2013] [Accepted: 03/15/2013] [Indexed: 02/05/2023] Open
Abstract
AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors.
METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation, tumor data, and receiving adjuvant chemotherapy were determined by uni- and multivariate analysis.
RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3- year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time.
CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.
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15
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Pracht M, Le Roux G, Sulpice L, Mesbah H, Manfredi S, Audrain O, Boudjema K, Raoul JL, Boucher E. Chemotherapy for inoperable advanced or metastatic cholangiocarcinoma: retrospective analysis of 78 cases in a single center over four years. Chemotherapy 2012; 58:134-41. [PMID: 22572213 DOI: 10.1159/000337289] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Accepted: 02/16/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND Systemic chemotherapy is the treatment of choice for inoperable (advanced or metastatic) cholangiocarcinoma. According to phase II and III trials, regimens combining 5-fluorouracil (5FU) or gemcitabine with a platinum salt have provided an overall response rate of 12-50% with a median overall survival of 5-16 months. METHODS This was a retrospective analysis of 78 consecutive cases of inoperable cholangiocarcinoma treated by palliative chemotherapy from July 2005 to November 2009 in one center. We firstly aimed to evaluate the impact of palliative chemotherapy in terms of survival and secondly to analyze possible related prognostic factors. RESULTS This cohort included 25 female and 53 male patients, with a mean age of 60.8 ± 11.4 years. Intrahepatic and extrahepatic cholangiocarcinoma were observed in 57 and 21 patients, respectively. First-line chemotherapy regimens were as follows: gemcitabine (n = 7), gemcitabine plus oxaliplatin (with or without cetuximab; n = 62) and 5FU plus cisplatin (n = 9). None of the patients achieved a complete response. The partial response rate was 35.9% (27/78), and the stable disease rate was 26.9% (21/78), giving a disease control rate of 62.8%. At the time of this analysis, with a median follow-up of 18 months, 13 patients were survivors. Median overall survival was 10 months [95% confidence interval (CI) 7-12], and median progression-free survival was 7 months (95% CI 6-8). Upon univariate analysis, only the distribution of the disease was significantly linked with prognosis, with a median overall survival of 10 months (95% CI 10-24) for solitary tumors versus 7 months (95% CI 6-11) in the case of infiltrative or multifocal tumors (p = 0.039). CONCLUSION The disease control rate, overall survival and progression free-survival in this single-center retrospective study were in agreement with earlier reports. Specific features of this cohort were a large proportion of cholangiocarcinoma with associated cirrhosis (n = 30/78, 38.5%), mostly intrahepatic (n = 25/30, 83.5%). This confirms the increasing incidence of intrahepatic localization and the epidemiological link recently reported between intrahepatic biliary tract carcinoma and cirrhosis.
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Affiliation(s)
- Marc Pracht
- Medical Oncology Unit, Comprehensive Cancer Center Eugène Marquis, Rennes, France
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16
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Shen WF, Zhong W, Liu Q, Sui CJ, Huang YQ, Yang JM. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma after curative surgery: retrospective control study. World J Surg 2011; 35:2083-91. [PMID: 21698503 DOI: 10.1007/s00268-011-1171-y] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Effects of adjuvant transcatheter arterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) radical surgery have never been evaluated. METHODS A retrospective analysis was conducted on 125 ICC patients who had undergone operations with curative intent in Shanghai Eastern Hepatobiliary Surgery Hospital from July 2002 to December 2003. Of these patients, 53 underwent adjuvant TACE (TACE group) and 72 did not (non-TACE group). Adjuvant TACE was performed one time 1.5-2.0 months after the operation. RESULTS Follow-up was performed at a median of 18 months (range 3-96 months). There was no significant recurrence-free survival (RFS) difference between the TACE and non-TACE groups (P = 0.659). The 1-, 3-, and 5-year overall survival (OS) rates were 69.8, 37.7, and 28.3%, respectively, for the TACE group and 54.2, 25.0, and 20.8%, respectively, for the non-TACE group (P = 0.045). Among 54 patients with a recurrence time of ≤ 3 months, the OS rate of the TACE group was better than that of the non-TACE group (P < 0.001). For 59 patients with a recurrence time later than the median RFS, no significant RFS difference was found between the TACE and non-TACE groups (P = 0.681). These results indicate that TACE could not delay recurrence but could prolong the OS of patients with early recurrence. CONCLUSIONS Adjuvant TACE after radical surgery was associated with better survival among the ICC patients with early recurrence.
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Affiliation(s)
- W F Shen
- Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China
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Zografos GN, Farfaras A, Zagouri F, Chrysikos D, Karaliotas K. Cholangiocarcinoma: principles and current trends. Hepatobiliary Pancreat Dis Int 2011; 10:10-20. [PMID: 21269929 DOI: 10.1016/s1499-3872(11)60001-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a lethal cancer of the biliary epithelium, originating from the liver (intrahepatic), at the confluence of the right and left hepatic ducts (hilar) or in the extrahepatic bile ducts. It is a rare malignancy associated with poor prognosis. DATA SOURCES We searched the PubMed/MEDLINE database for relevant articles published from 1989 to 2008. The search terms used were related to "cholangiocarcinoma" and its "treatment". Although no language restrictions were imposed initially, for the full-text review and final analysis, our resources only permitted the review of articles published in English. This review deals with the treatment of cholangiocarcinoma, the principles and the current trends. RESULTS The risks and prognostic factors, symptoms and differential diagnosis are thoroughly discussed. In addition, the tools of preoperative diagnosis such as endoscopic retrograde cholangiopancreatography, digital image analysis, fluorescence in situ hybridization and magnetic resonance cholangiopancreatography are reviewed. Moreover, the treatment of CCA is discussed. CONCLUSIONS The only curative treatment available is surgical management. Unfortunately, many patients present with unresectable tumors, the majority of whom die within a year of diagnosis. Surgical treatment involves major resections of the liver, pancreas and bile duct, with considerable mortality and morbidity. However, in selected cases and where indicated, appropriate management with aggressive surgery may achieve a good outcome with a prolonged survival expectancy.
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Affiliation(s)
- George N Zografos
- Third Department of Surgery, Athens General Hospital, Athens, Greece
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Abstract
Hilar cholangiocarcinoma is a rare tumor with poor prognosis. Surgical resection provides the only possibility for cure. Due to the central anatomic localization within the liver hilum, established guidelines of oncologic surgery are difficult to apply. Advances in hepatobiliary imaging and surgical strategies to treat this disease have resulted in improved postoperative outcomes. However, selection of extended hepatectomy or vascular resection or not as well as the efficacy of chemiotherapy remain great challenges to hepatobiliary surgeons. Here, we will review the recent advances in the management of hilar cholangiocarcinoma.
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Fernández-Ruiz M, Guerra-Vales JM, Colina-Ruizdelgado F. Comorbidity negatively influences prognosis in patients with extrahepatic cholangiocarcinoma. World J Gastroenterol 2009; 15:5279-86. [PMID: 19908335 PMCID: PMC2776854 DOI: 10.3748/wjg.15.5279] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the outcome and prognostic factors in a series of patients with extrahepatic cholangiocarcinoma and determine the impact of comorbidity on survival.
METHODS: A retrospective analysis of 68 patients with extrahepatic cholangiocarcinoma (perihilar, n = 37; distal, n = 31) seen at a single tertiary-care institution during the period 1999-2003 was performed. Data on presentation, management, and outcome were assessed by chart review. Pathologic confirmation was obtained in 37 cases (54.4%). Comorbidity was evaluated by using the Charlson comorbidity index (CCI).
RESULTS: Mean age at diagnosis was 73.4 ± 11.5 years. Jaundice was the most common symptom presented (86.8%). Median CCI score was 1 (range, 0 to 4). Nineteen patients (27.9%) underwent tumor resection. Palliative biliary drainage was performed in 39 patients (57.4%), and 6 patients (8.8%) received only best supportive care. Tumor-free margin status (R0) was achieved in 15 cases (78.9% of resection group). Baseline serum carbohydrate antigen 19-9 (CA 19-9) level was revealed to be an independent predictor of surgical treatment (P = 0.026). Overall median survival was 3.1 ± 0.9 mo, with 1- and 2-year survival rates of 21% and 7%, respectively. In the univariate analysis, tumor resection, CCI score, and serum CA 19-9 levels correlated significantly with outcome. In the multivariate analysis, only resection (HR 0.10; 95% CI, 0.02-0.51, P = 0.005) and a CCI score ≥ 2 (HR 3.36; 95% CI, 1.0-10.9, P = 0.045) were found to independently predict survival.
CONCLUSION: Tumor resection and comorbidity emerged as significant prognostic variables in extrahepatic cholangiocarcinoma. Comorbidity evaluation instruments should be applied in the clinical management of such patients.
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Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma. Dig Liver Dis 2009; 41:605-8. [PMID: 19168405 DOI: 10.1016/j.dld.2008.11.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2008] [Revised: 10/27/2008] [Accepted: 11/13/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS To investigate the clinical significance of serum Tu M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma. METHODS The tumour markers (Tu M2-PK and CA19-9) in 115 patients with cholangiocarcinoma, 85 patients with benign disease and 120 blood donors were detected by ELISA. RESULTS The levels of serum Tu M2-PK and CA19-9 were markedly higher in the patients with cholangiocarcinoma than in controls (P<0.05). Tu M2-PK showed more sensitivity (84.2%) and specificity (90%) than CA19-9 (68.4%) and (75%). CONCLUSIONS Tu M2-PK may be used as a valuable diagnosis marker in cholangiocarcinoma.
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Braicu C, Burz C, Berindan-Neagoe I, Balacescu O, Tantau M, Cristea V, Irimie A. Molecular Markers in the Pathogenesis of Cholangiocarcinoma: Potential for Early Detection and Selection of Appropriate Treatment. Gastroenterology Res 2009; 2:132-140. [PMID: 27933122 PMCID: PMC5139703 DOI: 10.4021/gr2009.06.1299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/17/2009] [Indexed: 12/27/2022] Open
Abstract
Cholangiocarcinoma (CC) is a primary malignancy that arises from cholangiocytes, the epithelial cells lining the bile duct livers. The worldwide incidence of CC is increasing and despite of combined therapeutic strategies, its prognosis remains poor. Till now surgery remains the only curative treatment modality. Over the past years, several important studies have yielded new insights into the molecular mechanisms of cholangiocarcinoma. This review focused on critical molecular player during the development from inflammation and cellular and molecular pathogenesis of this disease. The novel prophylactic and therapeutic approach deals especially the molecules involved in inflammation of cholangiocite or those related to promotion and progression of CC. The elucidation of their specific effects and interaction of this complex mechanism will accelerate the development of new biomarker for early detection and predictor factors outcome in CC.
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Affiliation(s)
| | - Claudia Burz
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Cancer Institut "I Chiricuta", Cluj-Napoca, Romania; University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | | | - Marcel Tantau
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Victor Cristea
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Alexandru Irimie
- Cancer Institut "I Chiricuta", Cluj-Napoca, Romania; University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
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