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Elmeligy HA, Azzam AM, Ossama Y, Rady M. New technique of end to side two layered and stented duct to mucosa pancreaticojejunostomy with omental wrapping during Whipple operation. BMC Surg 2025; 25:201. [PMID: 40346483 PMCID: PMC12063378 DOI: 10.1186/s12893-025-02893-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 04/01/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND A leaking pancreaticojejunal anastomosis is typically the cause of major problems following pancreaticoduodenectomy. To stop fistula formation, omental flaps were positioned around the pancreaticojejunal anastomosis. METHODS Forty-eight individuals who had pancreaticoduodenectomy procedures performed between March 2022 and March 2024 were examined. Based on the placement of a stent and omental flaps around the pancreaticojejunal anastomosis, the patients were split into two groups: group A, consisting of twenty-four patients, did not get omental wrapping and stenting, and group B, consisting of twenty-four patients, received omental wrapping with stent inside the pancreaticojejunal anastomosis. To evaluate the efficacy of the omental flap operation in preventing postoperative pancreatic fistula and other complications, perioperative data from both groups was examined. RESULTS There were no discernible variations in the clinical traits of the two groups. Group B experienced considerably lower occurrences of postoperative pancreatic fistula (20.8% vs. 4.2%), post-pancreatectomy hemorrhage (4.2% vs. 0%), biliary fistula (4.2% vs. 0%), and delayed gastric emptying (12.5% vs. 4.2%). Group B had a considerably lower overall morbidity rate (41.7% vs. 8.3%) and shorter hospital stay (15.3 vs. 10.9 days) than to group A. CONCLUSION Following pancreaticoduodenectomy, pancreatic stent and omental flaps around the pancreatic anastomosis can lower the risk of postoperative pancreatic fistula, post-pancrectomy bleeding, and delayed gastric emptying. This straightforward and efficient treatment can decrease the overall morbidity following pancreaticoduodenectomy. TRIAL REGISTRATION The trial registration was recorded as ClinicalTrial.gov Identifier No.: NCT06630910 on 10/05/2024. Our study also adheres to the Declaration of Helsinki.
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Affiliation(s)
- Hesham A Elmeligy
- General Surgery Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt.
| | - Ahmed M Azzam
- Environmental Research Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
| | - Yousra Ossama
- Pathology Department, October 6 University, Giza, Egypt
| | - Mahmoud Rady
- General Surgery Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
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Huang JC, Ma YW, Wang HX, Lang R, Jiang T. Prognostic impact of albumin-bilirubin score in predicting the long-term survival of distal cholangiocarcinoma after radical surgery. World J Surg Oncol 2025; 23:160. [PMID: 40275372 PMCID: PMC12023418 DOI: 10.1186/s12957-025-03813-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 04/14/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND The Albumin-Bilirubin Score (ALBI) serves as an indicator of nutritional status and is a widely recognized prognostic biomarker in cancer patients. The purpose of this research is to evaluate the association between ALBI and survival outcomes in patients with distal cholangiocarcinoma (dCCA) after radical surgery, and develop a nomogram model based on the ALBI to predict individual survival. METHODS A total of 177 individuals with dCCA receiving surgery from Jan 2011 to Jan 2022 were enrolled in the research. The association between ALBI and clinicopathologic factors was investigated. The impact of ALBI on recurrence-free survival (RFS) and overall survival (OS) was evaluated by Kaplan-Meier curves and Cox proportional hazards models. Nomograms based on ALBI and other prognostic variables screened by multivariate analysis were produced in predicting RFS and OS of dCCA patients following radical surgery, and the nomograms were evaluated by the consistency index (C-index), calibration curve and decision curve analysis (DCA) curve. RESULTS The optimal cut-off value for ALBI was -1.67, and the area under the ROC curve (AUC) was 0.71. The High-ALBI group had a considerably shorter RFS and OS (P < 0.001). Multivariate analysis revealed that the ALBI, degree of differentiation, portal vein invasion, and lymph node invasion were significant prognostic factors for RFS, and that the ALBI, CA19-9, degree of differentiation, lymph node invasion, and portal vein invasion were significant prognostic factors for OS. The nomograms were constructed based on these significant prognostic factors. The calibration curves displayed good consistency between actual and predicted probability. Nomograms based on these variables have better discriminant ability in predicting RFS and OS compared with the American Joint Committee on Cancer (AJCC) TNM stage. Moreover, the scores predicted by the nomogram enabled patient stratification into low-points and high-points groups. Kaplan-Meier curves demonstrated that patients in the high-points group had considerably better prognoses than those in the low-points group (p < 0.001). CONCLUSION ALBI was an independent prognostic factor in predicting RFS and OS of dCCA patients after radical surgery. The nomograms based on ALBI can provide reliable, personalized survival prediction for dCCA.
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Affiliation(s)
- Jin-Can Huang
- Hepatobiliary, Pancreas & Spleen Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - You-Wei Ma
- Hepatobiliary, Pancreas & Spleen Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Han-Xuan Wang
- Hepatobiliary, Pancreas & Spleen Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, P. R. China
| | - Ren Lang
- Hepatobiliary, Pancreas & Spleen Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, P. R. China.
| | - Tao Jiang
- Hepatobiliary, Pancreas & Spleen Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, P. R. China.
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Zu Z, Zhang C, Shi J, Chen K, Tang H, Hu K, Liu E, Ji C, Feng R, Shi X, Zhai W. Single-cell analysis reveals that GFAP + dedifferentiated Schwann cells promote tumor progress in PNI-positive distal cholangiocarcinoma via lactate/HMGB1 axis. Cell Death Dis 2025; 16:215. [PMID: 40148311 PMCID: PMC11950304 DOI: 10.1038/s41419-025-07543-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 02/08/2025] [Accepted: 03/17/2025] [Indexed: 03/29/2025]
Abstract
Distal cholangiocarcinoma (dCCA) is a highly lethal malignancy that accounts for approximately 40% of patients with primary cholangiocarcinoma. Remarkable cellular heterogeneity and perineural invasion (PNI) are two typical features of dCCA. Deciphering the complex interplay between neoplastic and neural cells is crucial for understanding the mechanisms propelling PNI-positive dCCA progression. Herein, we conduct single-cell RNA sequencing on 24,715 cells from two pairs of PNI-positive dCCA tumors and adjacent tissues, identifying eight unique cell types. Malignant cells exhibit significant inter- and intra-tumor heterogeneity. We delineate the compositional and functional phenotypes of five Schwann cell (SC) subsets in PNI-positive dCCA. Moreover, our analyses reveal two potential cell subtypes critical to forming PNI: NEAT1+ malignant cells characterized by hypoxic propensity and GFAP+ dedifferentiated SCs featuring hypermetabolism. Further bioinformatics uncover extensive cellular interactions between these two subpopulations. Functional experiments confirm that lactate in the hypoxic tumor microenvironment can induce GFAP-dedifferentiation in SCs, which promotes cancer cell invasion and progression through upregulating HMGB1. Taken together, our findings offer a thorough characterization of the transcriptional profile in PNI-positive dCCA and unveil potential therapeutic targets for dCCA PNI.
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Affiliation(s)
- Ziyang Zu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Chong Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Jianxiang Shi
- Precision Medicine Center, Henan Institute of Medical and Pharmaceutical Sciences & BGI College, Zhengzhou University, Zhengzhou, 450052, China
| | - Kunlun Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Hongwei Tang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Henan Engineering Technology Research Center of Organ Transplantation, Zhengzhou Engineering Laboratory of Organ Transplantation Technique and Application, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Kaizhao Hu
- Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Laboratory Animal Center, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, China
| | - Enchi Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Chengyang Ji
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Ruo Feng
- Department of Histology and Embryology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Xiaojing Shi
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Laboratory Animal Center, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, China.
| | - Wenlong Zhai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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Byrling J, Andersson B. Prediction of survival after pancreatoduodenectomy for distal cholangiocarcinoma: independent external validation of a prognostic model for 3-year overall survival in Sweden. Scand J Gastroenterol 2025; 60:158-164. [PMID: 39754339 DOI: 10.1080/00365521.2024.2447518] [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: 09/15/2024] [Revised: 11/20/2024] [Accepted: 12/18/2024] [Indexed: 01/06/2025]
Abstract
OBJECTIVES The only treatment with curative potential for distal cholangiocarcinoma (dCCA) is radical surgery which can be complemented with adjuvant chemotherapy. The aim of the present study was to perform an independent external validation of a prognostic model for 3-year overall survival based on routine clinicopathological variables for patients treated with pancreatoduodenectomy for dCCA. MATERIALS AND METHODS All patients with a histopathological confirmed dCCA that underwent pancreatoduodenectomy in Sweden from 2009 through 2019 were identified in the Swedish National Registry for Pancreatic and Periampullary Cancer. Model performance was estimated using the C-index and calibration plots. RESULTS In total 220 patients were included in the study. The median survival was 33 months (IQR 26-40) and 3-year survival rate 47% (95% CI 40-53%). The prognostic model had a C-index of 0.69 (95% CI 0.62-0.72). Calibration plots revealed overestimated risk of death across risk groups in the full cohort. Calibration was good in the subgroup of patients that did not receive adjuvant treatment. CONCLUSIONS The prognostic model showed reasonable discriminative ability but some miscalibration likely since the effect of adjuvant treatment is not included in the model. Given that the model was developed in cohorts treated prior to the current adjuvant standard of care the model can be used to estimate baseline risk prior to risk/benefit decision for adjuvant treatment as well as stratification for clinical trials but with a risk to underestimate 3-year overall survival for patients that receive adjuvant treatment.
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Affiliation(s)
- Johannes Byrling
- Department of Oncology, Skåne University Hospital, Lund
- Department of Clinical Sciences Lund, Surgery, Lund University
| | - Bodil Andersson
- Department of Clinical Sciences Lund, Surgery, Lund University
- Department of Surgery, Skåne University Hospital, Lund, Sweden
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Hu J, Shi Y, Jin L, Yi S, Chen J, Wan D, Ye W, Chen J, Zhang Y, Jiang Y, Duan B, Dong Y. Predicting survival rates: the power of prognostic nomograms in distal cholangiocarcinoma. Front Oncol 2025; 15:1478836. [PMID: 39931085 PMCID: PMC11807801 DOI: 10.3389/fonc.2025.1478836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 01/06/2025] [Indexed: 02/13/2025] Open
Abstract
Objective The purpose of this research is to establish a prognostic nomogram for patients with distal cholangiocarcinoma (dCCA). Methods We obtained clinical data from 2401 patients diagnosed with distal cholangiocarcinoma (dCCA) between 2010 and 2020 from the Surveillance, Epidemiology, and End Results database. These patients were randomly assigned to either the training or validation group in a ratio of 6:4. 228 patients were enrolled from 9 hospitals in China as the external validation cohort. Univariate and multifactorial Cox regression analyses were conducted to ascertain prognostic factors and prognostic nomograms were developed utilizing LASSO logistic regression analysis. We used the calibration curve, and area under the curve to validate the nomograms. Decision curve analysis was used to evaluate the model and its clinical applicability. Results The findings demonstrated that Grade, M stages, Surgery, and Chemotherapy emerged as autonomous prognostic factors for the survival of individuals with dCCA. The developed nomograms exhibited satisfactory accuracy in forecasting 1-year, 3-year, and 5-year survival probabilities. Furthermore, the calibration curves indicated a strong concordance between the anticipated and observed outcomes. The AUC of the nomogram for 1-year, 3-year, 5 year overall survival (OS) predication were 0.809 (95%CI 78.5-83.3), 0.79 (95%CI 75.8-82.2) and 0.761 ((95%CI 72.3-80.0) in the training cohort, 0.79 (95%CI 75.9-82.0), 0.73 (95%CI 68.5-77.5), and 0.732(95%CI 68.0-78.3) in internal test cohort, 0.862 (95%CI 81.7-90.7),0.83 (95%CI 76.4-89.6),and 0.819(95%CI 74.6-89.2) in external test cohort. Conclusion The nomograms that have been suggested demonstrate strong predictive capability. These tools can assist medical professionals in assessing the prognosis of patients with dCCA and in devising more accurate treatment strategies for them.
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Affiliation(s)
- Jiangfeng Hu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuping Shi
- Department of Nephrology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lihua Jin
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Suhong Yi
- Department of Gastroenterology, Xinyu People’s Hospital, Xinyu, Jiangxi, China
| | - Jinsuo Chen
- Department of Hepatobiliary and Pancreatic Surgery, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Dadong Wan
- Department of Gastroenterology, Fuyang Women & Children’s Hospital, Fuyang, Anhui, China
| | - Weixin Ye
- Department of Gastroenterology, Xining Second People’s Hospital, Xining, Qinghai, China
| | - Jingnan Chen
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yajing Zhang
- Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yang Jiang
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Bensong Duan
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuwei Dong
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Omouri-Kharashtomi M, Alemohammad SY, Moazed N, Afzali Nezhad I, Ghoshouni H. Prognostic value of albumin-bilirubin grade in patients with cholangiocarcinoma: a systematic review and meta-analysis. BMC Gastroenterol 2025; 25:19. [PMID: 39815213 PMCID: PMC11736951 DOI: 10.1186/s12876-025-03596-6] [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: 04/24/2024] [Accepted: 01/07/2025] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a type of cancer that develops in the biliary tract. CCA accounts for 10% of primary hepatic cancers and is characterized by its aggressive nature and poor prognosis. This systematic review and meta-analysis aims to assess the prognostic value of the novel hepatic function assessment measure known as albumin-bilirubin (ALBI) grade in patients with CCA. METHOD A comprehensive search was conducted on PubMed, Web of Science, Embase, and Scopus databases until August 11, 2023. Studies examining the prognostic impact of ALBI grade in patients with CCA were included. The prognostic effect was evaluated using hazard ratio (HR) with 95% confidence intervals (CI). The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The final meta-analysis was performed using R version 4.3.1. RESULTS The final meta-analysis included 13 studies with 3,434 patients. In univariate analysis (HR = 1.90, 95% CI: 1.65-2.19, P < 0.01) and multivariate analysis (HR = 1.88, 95% CI: 1.41-2.52, P < 0.01), higher ALBI grade was associated with lower overall survival (OS) in patients with intrahepatic CCA (ICCA). Higher ALBI grade was also correlated with decreased recurrence-free survival (RFS), with an HR of 1.63 (95% CI: 1.36-1.97, P < 0.01). Subgroup analysis of different ALBI grade comparisons showed consistent findings with our pooled data. CONCLUSION A high ALBI grade indicates poor OS and RFS in patients with CCA especially intrahepatic type. ALBI should be considered a reliable and clinically useful prognostic indicator. REGISTRATION PROSPERO ID: CRD42022379877.
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Affiliation(s)
| | | | - Negin Moazed
- Student Research Committee, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Inas Afzali Nezhad
- Student Research Committee, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Hamed Ghoshouni
- Cardiovascular Epidemiology Research Center, Rajaie Cardiovascular Institute, Tehran, Iran.
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Lederer AK, Görrissen N, Nguyen TT, Kreutz C, Rasel H, Bartsch F, Lang H, Endres K. Exploring the effects of gut microbiota on cholangiocarcinoma progression by patient-derived organoids. J Transl Med 2025; 23:34. [PMID: 39789543 PMCID: PMC11716211 DOI: 10.1186/s12967-024-06012-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 12/19/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Recent research indicates a role of gut microbiota in development and progression of life-threatening diseases such as cancer. Carcinomas of the biliary ducts, the so-called cholangiocarcinomas, are known for their aggressive tumor biology, implying poor prognosis of affected patients. An impact of the gut microbiota on cholangiocarcinoma development and progression is plausible due to the enterohepatic circulation and is therefore the subject of scientific debate, however evidence is still lacking. This review aimed to discuss the suitability of complex cell culture models to investigate the role of gut microbiota in cholangiocarcinoma progression. MAIN BODY Clinical research in this area is challenging due to poor comparability of patients and feasibility reasons, which is why translational models are needed to understand the basis of tumor progression in cholangiocarcinoma. A promising approach to investigate the influence of gut microbiota could be an organoid model. Organoids are 3D cell models cultivated in a modifiable and controlled condition, which can be grown from tumor tissue. 3D cell models are able to imitate physiological and pathological processes in the human body and thus contribute to a better understanding of health and disease. CONCLUSION The use of complex cell cultures such as organoids and organoid co-cultures might be powerful and valuable tools to study not only the growth behavior and growth of cholangiocarcinoma cells, but also the interaction with the tumor microenvironment and with components of the gut microbiota.
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Affiliation(s)
- Ann-Kathrin Lederer
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany.
- Center for Complementary Medicine, Department of Medicine II, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, 79106, Freiburg, Germany.
| | - Nele Görrissen
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Tinh Thi Nguyen
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, 55131, Mainz, Germany
- Institute of Molecular Biology (IMB), 55128, Mainz, Germany
| | - Clemens Kreutz
- Institute of Medical Biometry and Statistics (IMBI), Faculty of Medicine and Medical Center, 79106, Freiburg, Germany
| | - Hannah Rasel
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Fabian Bartsch
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Kristina Endres
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, 55131, Mainz, Germany
- Faculty of Computer Sciences and Microsystems Technology, University of Applied Sciences Kaiserslautern, 66482, Zweibrücken, Germany
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Litjens G, Nakamoto A, Brosens LAA, Maas MC, Scheenen TWJ, Zámecnik P, van Geenen EJM, Prokop M, van Laarhoven KJHM, Hermans JJ. Ferumoxtran-10-enhanced MRI for pre-operative metastatic lymph node detection in pancreatic, duodenal, or periampullary adenocarcinoma. Eur Radiol 2024; 34:7973-7984. [PMID: 38907886 PMCID: PMC11557713 DOI: 10.1007/s00330-024-10838-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/18/2024] [Accepted: 04/26/2024] [Indexed: 06/24/2024]
Abstract
OBJECTIVES To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology. METHODS Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs. RESULTS Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively. CONCLUSION USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma. CLINICAL RELEVANCE STATEMENT Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy. REGISTRATION The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 . KEY POINTS LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.
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Affiliation(s)
- Geke Litjens
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Atsushi Nakamoto
- Department of Radiology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Lodewijk A A Brosens
- Department of Pathology, Radboud University Medical Center, Nijmegen, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marnix C Maas
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tom W J Scheenen
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Patrik Zámecnik
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Erwin J M van Geenen
- Department of Gastroenterology and Hepatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mathias Prokop
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Kees J H M van Laarhoven
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - John J Hermans
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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Sarkhampee P, Ouransatien W, Lertsawatvicha N, Chansitthichock S, Wattanarath P. Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma. World J Surg Oncol 2024; 22:314. [PMID: 39605039 PMCID: PMC11600713 DOI: 10.1186/s12957-024-03596-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 11/17/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system, which can be classified into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). Surgical resection is the curative treatment for all subtypes of CCA. This study evaluates patients with CCA who underwent surgery and determines factors that impact their survival. METHODS We conducted a retrospective analysis of 720 patients diagnosed with CCA from October 2013 to December 2018. Patients were categorized into iCCA (n = 398), pCCA (n = 237), and dCCA (n = 85) based on tumor location. Data including demographic information, clinical presentation, treatment modalities, and survival statistics were collected and analyzed. RESULTS The overall resectability rate was 78.3%, with resectability highest in pCCA patients (83.5%). Overall median survival time (MST) was 11.6 months and varied among subtypes: iCCA 10.9 months, pCCA 11.2 months, and dCCA 15.4 months. Patients underwent curative-intent resection significantly improved survival compared to those with palliative resection or unresectable disease in all subtypes. R0 resection patients had better overall survival (OS) than R1 resection patients: 5-year survival rate of 20.2% vs. 4.3% in all CCA (p < 0.001), 21.4% vs. 7% in iCCA (p < 0.001), 17.2% vs. 0% in pCCA (p < 0.001), and 23.1% vs. 0% in dCCA (p = 0.105), respectively. Positive resection margin was an independent prognostic factor for OS in pCCA and iCCA. CONCLUSION Surgical resection is the only cure for CCA. Curative-intent resection is more effective than palliative resection in improving survival rates. When performing curative-intent resection, the goal is R0 resection. This is because it improves overall survival over R1 resection.
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Affiliation(s)
- Poowanai Sarkhampee
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand.
| | - Weeris Ouransatien
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
| | - Nithi Lertsawatvicha
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
| | - Satsawat Chansitthichock
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
| | - Paiwan Wattanarath
- Department of Surgery, Sunpasitthiprasong Hospital, 122 Sunpasit Road, Nai Mueang Subdistrict, Mueang Ubon Ratchathani District, Ubon Ratchathani, 34000, Thailand
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10
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Perez M, Palnaes Hansen C, Burdio F, Sanchez-Velázquez P, Giuliani A, Lancellotti F, de Liguori-Carino N, Malleo G, Marchegiani G, Podda M, Pisanu A, De Luca GM, Anselmo A, Siragusa L, Kobbelgaard Burgdorf S, Tschuor C, Cacciaguerra AB, Koh YX, Masuda Y, Hao Xuan MY, Seeger N, Breitenstein S, Grochola FL, Di Martino M, Secanella L, Busquets J, Dorcaratto D, Mora-Oliver I, Ingallinella S, Salvia R, Abu Hilal M, Aldrighetti L, Ielpo B. A machine learning predictive model for recurrence of resected distal cholangiocarcinoma: Development and validation of predictive model using artificial intelligence. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108375. [PMID: 38795677 DOI: 10.1016/j.ejso.2024.108375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/20/2024] [Accepted: 04/27/2024] [Indexed: 05/28/2024]
Abstract
INTRODUCTION Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA. MATERIAL AND METHODS This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm. RESULTS Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/. CONCLUSIONS This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.
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Affiliation(s)
- Marc Perez
- Hepato Pancreato Biliary Division, Hospital Del Mar, Universitat Pompeu Fabra, Barcelona, Spain.
| | | | - Fernando Burdio
- Hepato Pancreato Biliary Division, Hospital Del Mar, Universitat Pompeu Fabra, Barcelona, Spain.
| | | | - Antonio Giuliani
- Unit of General Surgery, San Giuseppe Moscati Hospital, Aversa, Italy.
| | - Francesco Lancellotti
- Department of Hepato-Pancreato-Biliary Surgery, Manchester Royal Infirmary, University of Manchester, Manchester, United Kingdom.
| | - Nicola de Liguori-Carino
- Department of Hepato-Pancreato-Biliary Surgery, Manchester Royal Infirmary, University of Manchester, Manchester, United Kingdom.
| | - Giuseppe Malleo
- Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy.
| | - Giovanni Marchegiani
- Hepato Biliary Pancreatic (HPB) and Liver Transplant Surgery, Department of Surgery, Oncology and Gastroenterology (DiSCOG), Padova University, Padova, Italy.
| | - Mauro Podda
- Department of Surgical Science, University of Cagliari, Cagliari, Italy.
| | - Adolfo Pisanu
- Department of Surgical Science, University of Cagliari, Cagliari, Italy.
| | - Giuseppe Massimiliano De Luca
- University of Bari "A. Moro", Department of Biomedical Sciences and Human Oncology, Unit of Academic General Surgery " V. Bonomo", Bari, Italy.
| | - Alessandro Anselmo
- Department of Surgery, HPB and Transplant Surgery Unit, Policlinico Tor Vergata, Rome, Italy.
| | - Leandro Siragusa
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
| | | | - Christoph Tschuor
- Department of Surgery, Rigshospitalet, University of Copenhagen, Denmark.
| | - Andrea Benedetti Cacciaguerra
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy.
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.
| | - Yoshio Masuda
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.
| | - Mark Yeo Hao Xuan
- HPB Unit, Department of Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
| | - Nico Seeger
- HPB Unit, Department of Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
| | - Stefan Breitenstein
- HPB Unit, Department of Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
| | - Filip Lukasz Grochola
- HPB Unit, Department of Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
| | - Marcello Di Martino
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
| | | | | | - Dimitri Dorcaratto
- Department of General Surgery, Biomedical Research Institute INCLIVA, Hospital Clínico Universitario, University of Valencia, Spain.
| | - Isabel Mora-Oliver
- Department of General Surgery, Biomedical Research Institute INCLIVA, Hospital Clínico Universitario, University of Valencia, Spain.
| | | | - Roberto Salvia
- Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Italy.
| | | | | | - Benedetto Ielpo
- Hepato Pancreato Biliary Division, Hospital Del Mar, Universitat Pompeu Fabra, Barcelona, Spain.
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11
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Uijterwijk BA, Lemmers DH, Ghidini M, Wilmink JW, Zaniboni A, Fusai GK, Zerbi A, Koerkamp BG, Luyer M, Ghorbani P, Salvia R, White S, Ielpo B, Goh BKP, Boggi U, Kazemier G, House MG, Mavroeidis VK, Björnsson B, Mazzola M, Serradilla M, Korkolis D, Alseidi A, Roberts KJ, Soonawalla Z, Pessaux P, Fisher WE, Koek S, Kent TS, Vladimirov M, Bolm L, Jamieson N, Dalla Valle R, Kleeff J, Mazzotta A, Suarez Muñoz MA, Cabús SS, Ball CG, Berger AC, Ferarri C, Besselink MG, Hilal MA. The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study. Br J Cancer 2024; 131:117-125. [PMID: 38806725 PMCID: PMC11231293 DOI: 10.1038/s41416-024-02692-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 03/25/2024] [Accepted: 04/10/2024] [Indexed: 05/30/2024] Open
Abstract
BACKGROUND Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.
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Affiliation(s)
- Bas A Uijterwijk
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
- Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Daniël H Lemmers
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Michele Ghidini
- Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Alberto Zaniboni
- Department of Medical Oncology, Fondazione Poliambulanza, Brescia, Italy
| | | | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Department of Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Misha Luyer
- Catharina Hospital Eindhoven, Department of Surgery, Eindhoven, Netherlands
| | - Poya Ghorbani
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Roberto Salvia
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Steven White
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | | | - Brian K P Goh
- Singapore General Hospital, Department of Hepatopancreatobiliary and Transplant Surgery, Duke-National University of Singapore, Singapore, Singapore
| | - Ugo Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Geert Kazemier
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
| | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Vasileios K Mavroeidis
- Department of Academic Surgery, The Royal Marsden Hospital, London, UK
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Bergthor Björnsson
- Department of Surgery in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Michele Mazzola
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Mario Serradilla
- Department of Surgery, Miguel Servet University Hospital, Zargosa, Spain
| | - Dimitris Korkolis
- Department of Surgery, Hellenic Anticancer Hospital 'Saint Savvas', Athens, Greece
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason, Seattle, WA, USA
| | - Keith J Roberts
- Faculty of medicine, University of Birmingham, Birmingham, UK
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Patrick Pessaux
- Hepatobiliary and Pancreatic Surgical Unit, Nouvel Hôpital Civil (NHC), Strasbourg, France
| | | | - Sharnice Koek
- Fiona Stanley Hospital, Department of Surgery, Perth, WA, Australia
| | - Tara S Kent
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Miljana Vladimirov
- Department of General Surgery, Paracelsus Medical University Nürnberg, 90419, Nürnberg, Germany
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, campus Lübeck, Lübeck, Germany
| | - Nigel Jamieson
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | | | - Jorg Kleeff
- Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Alessandro Mazzotta
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | | | | | - Chad G Ball
- Department of Surgery, University of Calgary, Calgary, AB, Canada
| | - Adam C Berger
- Department of Surgery, Jefferson Medical College, Philadelphia, USA
| | - Clarissa Ferarri
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Mohammed Abu Hilal
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
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12
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Busquets J, Secanella L, Cifre P, Sorribas M, Serrano T, Martínez-Carnicero L, Leiva D, Laquente B, Salord S, Peláez N, Fabregat J. Prognostic risk factors in 113 patients undergoing cephalic duodenopancreatectomy for distal cholangiocarcinoma. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:448-456. [PMID: 37827384 DOI: 10.1016/j.gastrohep.2023.09.009] [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: 03/05/2023] [Revised: 06/25/2023] [Accepted: 09/22/2023] [Indexed: 10/14/2023]
Abstract
INTRODUCTION Distal cholangiocarcinoma is a malignant epithelial neoplasia that affects the extrahepatic bile ducts, below the cystic duct. No relevant relationship between perioperative factors and worse long-term outcome has been proved. OBJECTIVE To analyze the risk factors for mortality and long-term recurrence of distal cholangiocarcinoma in resected patients. MATERIALS AND METHODS A single-center prospective database of patients operated on for distal cholangiocarcinoma between 1990 and 2021 was analyzed in order to investigate mortality and recurrence factors. RESULTS One hundred and thirteen patients have undergone surgery, with mean actuarial survival of 100.2 (76-124) months after resection. The bivariate study did not show differences between patients depending on age or preoperative variables studied. When multivariate analysis was performed, the presence of affected adenopathy was a risk factor for long-term mortality. The presence of affected lymph nodes, tumor recurrence, and biliary fistula during the postoperative period implied worse actuarial survival when comparing the Kaplan-Meier curves. CONCLUSIONS The presence of affected lymph nodes influence the prognosis of the disease. The occurrence of biliary fistula during postoperative cholangiocarcinoma distal could aggravate long-term outcomes, a finding that should be reaffirmed in future studies.
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Affiliation(s)
- Juli Busquets
- Unitat de Cirurgia Hepatobiliopancreàtica, Servei de Cirurgia General i Digestiva, Hospital Universitari de Bellvitge, Barcelona, España; Departament de Ciències Clíniques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, España; Research Group of Hepato-biliary and Pancreatic Diseases, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España.
| | - Luís Secanella
- Unitat de Cirurgia Hepatobiliopancreàtica, Servei de Cirurgia General i Digestiva, Hospital Universitari de Bellvitge, Barcelona, España; Research Group of Hepato-biliary and Pancreatic Diseases, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España; Departament d'Infermeria Fonamental i Medicoquirúrgica, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, España
| | - Paula Cifre
- Unitat de Cirurgia Hepatobiliopancreàtica, Servei de Cirurgia General i Digestiva, Hospital Universitari de Bellvitge, Barcelona, España; Departament de Ciències Clíniques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, España
| | - María Sorribas
- Unitat de Cirurgia Hepatobiliopancreàtica, Servei de Cirurgia General i Digestiva, Hospital Universitari de Bellvitge, Barcelona, España; Research Group of Hepato-biliary and Pancreatic Diseases, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
| | - Teresa Serrano
- Servei de Anatomia Patològica, Hospital Universitari de Bellvitge, Barcelona, España
| | | | - David Leiva
- Servei de Radiodiagnòstic, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Berta Laquente
- Servei d'Oncologia Mèdica, Instituto Catalán de Oncología. Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
| | - Silvia Salord
- Research Group of Hepato-biliary and Pancreatic Diseases, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España; Servei de Gastroenterologia, Hospital Universitari de Bellvitge, Barcelona, España
| | - Nuria Peláez
- Unitat de Cirurgia Hepatobiliopancreàtica, Servei de Cirurgia General i Digestiva, Hospital Universitari de Bellvitge, Barcelona, España; Research Group of Hepato-biliary and Pancreatic Diseases, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
| | - Juan Fabregat
- Unitat de Cirurgia Hepatobiliopancreàtica, Servei de Cirurgia General i Digestiva, Hospital Universitari de Bellvitge, Barcelona, España; Research Group of Hepato-biliary and Pancreatic Diseases, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
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13
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Wilbur HC, Soares HP, Azad NS. Neoadjuvant and adjuvant therapy for biliary tract cancer: Advances and limitations. Hepatology 2024:01515467-990000000-00725. [PMID: 38266282 DOI: 10.1097/hep.0000000000000760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/31/2023] [Indexed: 01/26/2024]
Abstract
Biliary tract cancers (BTC) are a rare and aggressive consortium of malignancies, consisting of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma. While most patients present with metastatic disease, a minority of patients with BTC are eligible for curative surgical resection at the time of presentation. However, these patients have poor 5-year overall survival rates and high rates of recurrence, necessitating the improvement of the neoadjuvant and adjuvant treatment of BTC. In this review, we assess the neoadjuvant and adjuvant clinical trials for the treatment of BTC and discuss the challenges and limitations of clinical trials, as well as future directions for the treatment of BTC.
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Affiliation(s)
- H Catherine Wilbur
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Heloisa P Soares
- Division of Oncology, Department of Internal Medicine Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA
| | - Nilofer S Azad
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
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14
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Uijterwijk BA, Lemmers DHL, Bolm L, Luyer M, Koh YX, Mazzola M, Webber L, Kazemier G, Bannone E, Ramaekers M, Ielpo B, Wellner U, Koek S, Giani A, Besselink MG, Abu Hilal M. Long-term Outcomes After Laparoscopic, Robotic, and Open Pancreatoduodenectomy for Distal Cholangiocarcinoma: An International Propensity Score-matched Cohort Study. Ann Surg 2023; 278:e570-e579. [PMID: 36730852 DOI: 10.1097/sla.0000000000005743] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE This study aimed to compare surgical and oncological outcomes after minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). BACKGROUND A dCCA might be a good indication for MIPD, as it is often diagnosed as primary resectable disease. However, multicenter series on MIPD for dCCA are lacking. METHODS This is an international multicenter propensity score-matched cohort study including patients after MIPD or OPD for dCCA in 8 centers from 5 countries (2010-2021). Primary outcomes included overall survival (OS) and disease-free interval (DFI). Secondary outcomes included perioperative and postoperative complications and predictors for OS or DFI. Subgroup analyses included robotic pancreatoduodenectomy (RPD) and laparoscopic pancreatoduodenectomy (LPD). RESULTS Overall, 478 patients after pancreatoduodenectomy for dCCA were included of which 97 after MIPD (37 RPD, 60 LPD) and 381 after OPD. MIPD was associated with less blood loss (300 vs 420 mL, P =0.025), longer operation time (453 vs 340 min; P <0.001), and less surgical site infections (7.8% vs 19.3%; P =0.042) compared with OPD. The median OS (30 vs 25 mo) and DFI (29 vs 18) for MIPD did not differ significantly between MIPD and OPD. Tumor stage (Hazard ratio: 2.939, P <0.001) and administration of adjuvant chemotherapy (Hazard ratio: 0.640, P =0.033) were individual predictors for OS. RPD was associated with a higher lymph node yield (18.0 vs 13.5; P =0.008) and less major morbidity (Clavien-Dindo 3b-5; 8.1% vs 32.1%; P =0.005) compared with LPD. DISCUSSION Both surgical and oncological outcomes of MIPD for dCCA are acceptable as compared with OPD. Surgical outcomes seem to favor RPD as compared with LPD but more data are needed. Randomized controlled trials should be performed to confirm these findings.
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Affiliation(s)
- Bas A Uijterwijk
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, The Netherlands
| | - Daniël H L Lemmers
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, The Netherlands
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Misha Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Michele Mazzola
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Laurence Webber
- Department of Surgery, Fiona Stanley Hospital, Perth, Australia
| | - Geert Kazemier
- Cancer Center Amsterdam, The Netherlands
- Department of Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands
| | - Elisa Bannone
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
| | - Mark Ramaekers
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Benedetto Ielpo
- Hepatobiliary and Pancreatic Surgery Unit, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain
| | - Ulrich Wellner
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Sharnice Koek
- Department of Surgery, Fiona Stanley Hospital, Perth, Australia
| | - Alessandro Giani
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, The Netherlands
| | - Mohammed Abu Hilal
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
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15
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Möhring C, Khan O, Zhou T, Sadeghlar F, Mahn R, Kaczmarek DJ, Dold L, Toma M, Marinova M, Glowka TR, Matthaei H, Manekeller S, Kalff JC, Strassburg CP, Weismüller TJ, Gonzalez-Carmona MA. Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy. Front Oncol 2023; 13:1227036. [PMID: 37711210 PMCID: PMC10497756 DOI: 10.3389/fonc.2023.1227036] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/31/2023] [Indexed: 09/16/2023] Open
Abstract
Background and aims Extrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT. Method All patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared. Results Patients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group. Conclusion Additional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.
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Affiliation(s)
- Christian Möhring
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Oliver Khan
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Taotao Zhou
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | | | - Robert Mahn
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | | | - Leona Dold
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Marieta Toma
- Department of Pathology, University Hospital of Bonn, Bonn, Germany
| | - Milka Marinova
- Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany
| | - Tim R. Glowka
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | - Hanno Matthaei
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | | | - Jörg C. Kalff
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | | | - Tobias J. Weismüller
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
- Department of Gastroenterology and Oncology, Vivantes Humboldt Hospital, Berlin, Germany
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16
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Ogasawara H, Yoshizawa T, Oshima K, Ogasawara K, Kubota S, Goto S, Morohashi S, Wakiya T, Kimura N, Ishido K, Kijima H, Hakamada K. Three-dimensional analysis of perineural invasion in extrahepatic cholangiocarcinoma using tissue clearing. Pathol Oncol Res 2023; 29:1611284. [PMID: 37425091 PMCID: PMC10323134 DOI: 10.3389/pore.2023.1611284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 06/14/2023] [Indexed: 07/11/2023]
Abstract
Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.
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Affiliation(s)
- Hirokazu Ogasawara
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Tadashi Yoshizawa
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Kiyoko Oshima
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Kenta Ogasawara
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Shunsuke Kubota
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Shintaro Goto
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Satoko Morohashi
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Norihisa Kimura
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Keinosuke Ishido
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hiroshi Kijima
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
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17
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Nakagohri T, Takahashi S, Ei S, Masuoka Y, Mashiko T, Ogasawara T, Hirabayashi K. Prognostic Impact of Margin Status in Distal Cholangiocarcinoma. World J Surg 2023; 47:1034-1041. [PMID: 36735046 DOI: 10.1007/s00268-023-06889-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/25/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND A positive ductal margin is strongly associated with poor survival in patients with distal cholangiocarcinoma. However, the significance of the radial margin status and its effect on survival are not fully clarified. METHODS All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between January 2000 and December 2018 at Tokai University Hospital were retrospectively analyzed. Positive margins were divided into positive ductal margin and positive radial margin. RESULTS One hundred and eight consecutive patients with distal cholangiocarcinoma underwent pancreatoduodenectomy. Margin-negative R0 resection was performed in 85 patients (79%). Twenty-three patients (21%) had a positive resection margin (R1 resection). The 5-year survival rate and median overall survival for patients with R0 resection and those with R1 resection was 64%, 98 months and 25%, 26 months, respectively. There was a significant difference in survival between patients with R0 resection and those with R1 resection (p < 0.001). Patients with positive radial margin (n = 10) had a significantly worse outcome than those with positive ductal margin (n = 13) (p = 0.016). Univariate analysis showed that R1 resection, lymph node metastasis, tumor depth, portal vein invasion, pancreatic invasion, lymphatic invasion, and venous invasion were significant prognostic factors. Multivariate analysis confirmed that R1 resection and nodal involvement were significant independent prognostic indicators after surgical resection for distal cholangiocarcinoma. CONCLUSIONS Positive surgical margin and nodal involvement were the strongest predictors of poor survival in patients with distal cholangiocarcinoma. Patients with a positive radial margin had a significantly worse outcome than those with a positive ductal margin.
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Affiliation(s)
- Toshio Nakagohri
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa Prefecture, 259-1193, Japan.
| | - Shinichiro Takahashi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa Prefecture, 259-1193, Japan
| | - Shigenori Ei
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa Prefecture, 259-1193, Japan
| | - Yoshihito Masuoka
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa Prefecture, 259-1193, Japan
| | - Taro Mashiko
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa Prefecture, 259-1193, Japan
| | - Toshihito Ogasawara
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa Prefecture, 259-1193, Japan
| | - Kenichi Hirabayashi
- Department of Pathology, Toyama University School of Medicine, 3190 Gohuku, Toyama, Toyama Prefecture, 930-8555, Japan
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18
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KAWAHARA RYUICHI, MIDORIKAWA RYUUTA, TANIWAKI SHINICHI, KOJIMA SATOKI, KANNO HIROKI, YOSHITOMI MUNEHIRO, NOMURA YORIKO, GOTO YUICHI, SATOU TOSHIHIRO, SAKAI HISAMUNE, ISHIKAWA HIROTO, HISAKA TORU, YASUNAGA MASAFUMI, SAKAUE TAKAHIKO, USHIJIMA TOMOYUKI, YASUMOTO MAKIKO, OKABE YOSHINOBU, TANIGAWA MASAHIKO, NAITOU YOSHIKI, YANO HIROHISA, OKUDA KOJI. Prognostic Factors for Distal Bile Duct Carcinoma After Surgery. Kurume Med J 2023. [PMID: 37005293 DOI: 10.2739/kurumemedj.ms682002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023]
Abstract
BACKGROUND Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.
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Affiliation(s)
| | | | | | - SATOKI KOJIMA
- Department of Surgery, Kurume University School of Medicine
| | - HIROKI KANNO
- Department of Surgery, Kurume University School of Medicine
| | | | - YORIKO NOMURA
- Department of Surgery, Kurume University School of Medicine
| | - YUICHI GOTO
- Department of Surgery, Kurume University School of Medicine
| | | | - HISAMUNE SAKAI
- Department of Surgery, Kurume University School of Medicine
| | | | - TORU HISAKA
- Department of Surgery, Kurume University School of Medicine
| | | | - TAKAHIKO SAKAUE
- Division of Gastroeterology, Kurume University School of Medicine
| | | | - MAKIKO YASUMOTO
- Division of Gastroeterology, Kurume University School of Medicine
| | - YOSHINOBU OKABE
- Division of Gastroeterology, Kurume University School of Medicine
| | | | - YOSHIKI NAITOU
- Department of Pathology, Kurume University School of Medicine
| | - HIROHISA YANO
- Department of Pathology, Kurume University School of Medicine
| | - KOJI OKUDA
- Department of Surgery, Kurume University School of Medicine
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19
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van Tienderen GS, Rosmark O, Lieshout R, Willemse J, de Weijer F, Elowsson Rendin L, Westergren-Thorsson G, Doukas M, Groot Koerkamp B, van Royen ME, van der Laan LJ, Verstegen MM. Extracellular matrix drives tumor organoids toward desmoplastic matrix deposition and mesenchymal transition. Acta Biomater 2023; 158:115-131. [PMID: 36427688 DOI: 10.1016/j.actbio.2022.11.038] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/31/2022] [Accepted: 11/16/2022] [Indexed: 11/25/2022]
Abstract
Patient-derived tumor organoids have been established as promising tools for in vitro modelling of multiple tumors, including cholangiocarcinoma (CCA). However, organoids are commonly cultured in basement membrane extract (BME) which does not recapitulate the intricacies of the extracellular matrix (ECM). We combined CCA organoids (CCAOs) with native tumor and liver scaffolds, obtained by decellularization, to effectuate a model to study the interaction between epithelial tumor cells and their surrounding ECM. Decellularization resulted in removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin, including stiffness and presence of desmoplasia. The transcriptome of CCAOs in a tumor scaffold much more resembled that of patient-paired CCA tissue in vivo compared to CCAOs cultured in BME or liver scaffolds. This was accompanied by an increase in chemoresistance to clinically-relevant chemotherapeutics. CCAOs in decellularized scaffolds revealed environment-dependent proliferation dynamics, driven by the occurrence of epithelial-mesenchymal transition. Furthermore, CCAOs initiated an environment-specific desmoplastic reaction by increasing production of multiple collagen types. In conclusion, convergence of organoid-based models with native ECM scaffolds will lead to better understanding of the in vivo tumor environment. STATEMENT OF SIGNIFICANCE: The extracellular matrix (ECM) influences various facets of tumor behavior. Understanding the exact role of the ECM in controlling tumor cell fate is pertinent to understand tumor progression and develop novel therapeutics. This is particularly the case for cholangiocarcinoma (CCA), whereby the ECM displays a distinct tumor environment, characterized by desmoplasia. However, current models to study the interaction between epithelial tumor cells and the environment are lacking. We have developed a fully patient-derived model encompassing CCA organoids (CCAOs) and human decellularized tumor and tumor-free liver ECM. The tumor ECM induced recapitulation of various aspects of CCA, including migration dynamics, transcriptome and proteome profiles, and chemoresistance. Lastly, we uncover that epithelial tumor cells contribute to matrix deposition, and that this phenomenon is dependent on the level of desmoplasia already present.
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Affiliation(s)
- Gilles S van Tienderen
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Oskar Rosmark
- Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Ruby Lieshout
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jorke Willemse
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Floor de Weijer
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Linda Elowsson Rendin
- Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden
| | | | - Michail Doukas
- Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Martin E van Royen
- Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Luc Jw van der Laan
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Monique Ma Verstegen
- Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
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20
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Okada KI, Kawai M, Hirono S, Miyazawa M, Kitahata Y, Ueno M, Hayami S, Ikoma A, Sonomura T, Wan K, Shimokawa T, Yamaue H. Radiological Shape of the Tumor Predicts Progression and Survival in Resected Extrahepatic Cholangiocarcinoma. J Gastrointest Surg 2023:10.1007/s11605-023-05614-y. [PMID: 36749559 DOI: 10.1007/s11605-023-05614-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 01/27/2023] [Indexed: 02/08/2023]
Abstract
BACKGROUND The histological features and radiological shape of extrahepatic cholangiocarcinoma (eCCA) have not been widely studied in relation to prognosis. Multi-detector computed tomography (MDCT) is thought to be useful in diagnosis of progress and tumor distribution; it can also show morphological differences (round, triangular, and square forms) at the tumoral obstruction sites. Histological types of eCCA may be revealed, with potential association with tumor growth and survival. METHODS We examined the distribution of tumor radiological shape subtypes on MDCT. The surgical outcomes of consecutive patients with eCCA who underwent macroscopic curative resection were reviewed. RESULTS CT subtypes in 109 patients were 62 triangular, 35 square, and 12 round. There were clear prognostic differences in long-term survival rates (P < 0.001); 5-year survival rates were 100% in round, 64% in triangular, and 19% in square types. There was no recurrence in any cases of round-type tumor at the site of obstruction. Depth of tumor invasion and rates of nodal involvement were significantly higher in triangular and square-type tumors than in round-type tumors. In papillary adenocarcinoma, radiological obstructions were round type in seven patients (78%) and triangular type in two patients (22%). In tubular adenocarcinoma, all round-type tumors were well differentiated, the ratio of square-type tumors increasing as the degree of differentiation decreased from "well" to "moderate," and "poor" respectively (23%, 39%, 57%; P = 0.033). CONCLUSIONS Tumor radiological shape predicts tumor progression, histological type, and survival in eCCA. This information may be helpful in preoperative radiological staging on MDCT.
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Affiliation(s)
- Ken-Ichi Okada
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan.
| | - Manabu Kawai
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Seiko Hirono
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Motoki Miyazawa
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Yuji Kitahata
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Akira Ikoma
- Department of Radiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Tetsuo Sonomura
- Department of Radiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Ke Wan
- Clinical Study Support Center, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Toshio Shimokawa
- Clinical Study Support Center, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama, 641-8510, Japan
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21
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Silver CM, Joung RH, Logan CD, Benson AB, Mahalingam D, D’Angelica MI, Bentrem DJ, Yang AD, Bilimoria KY, Merkow RP. Neoadjuvant therapy use and association with postoperative outcomes and overall survival in patients with extrahepatic cholangiocarcinoma. J Surg Oncol 2023; 127:90-98. [PMID: 36194064 PMCID: PMC9729397 DOI: 10.1002/jso.27112] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 09/18/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES Evidence for neoadjuvant therapy (NAT) in extrahepatic cholangiocarcinoma (eCCA) is limited. Our objectives were to: (1) characterize treatment trends, (2) identify factors associated with receipt of NAT, and (3) evaluate associations between NAT and postoperative outcomes. METHODS Retrospective cohort study of the National Cancer Database (2004-2017). Multivariable logistic regression assessed associations between NAT and postoperative outcomes. Stratified analysis evaluated differences between surgery first, neoadjuvant chemotherapy, and neoadjuvant chemoradiation (CRT). RESULTS Among 8040 patients, 417 (5.2%) received NAT. NAT increased during the study period 2.9%-8.4% (p < 0.001). Factors associated with receipt of NAT included age <50 (vs. >75, odds ratio [OR] 4.32, p < 0.001) and stage 3 disease (vs. 1, OR 1.68, p = 0.01). Compared with surgery first, patients who received NAT had higher odds of R0 resection (OR 1.49, p = 0.01) and lower 30-day mortality (OR 0.51, p = 0.04). On stratified analysis, neoadjuvant chemotherapy was not associated with differences in any outcomes. However, neoadjuvant CRT was associated with improvement in R0 resection (OR 3.52, <0.001) and median survival (47.8 vs. 25.3 months, log-rank < 0.001) compared to surgery first. CONCLUSIONS NAT, particularly neoadjuvant CRT, was associated with improved postoperative outcomes. These data suggest expanding the use of neoadjuvant CRT for eCCA.
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Affiliation(s)
- Casey M. Silver
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rachel H. Joung
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Charles D. Logan
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Al B. Benson
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
| | - Devalingam Mahalingam
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael I. D’Angelica
- Department of Surgery, Memorial Sloane Kettering Cancer Center, New York, New York, USA
| | - David J. Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Anthony D. Yang
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Karl Y. Bilimoria
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Ryan P. Merkow
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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22
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Tjaden C, Hinz U, Klaiber U, Heger U, Springfeld C, Goeppert B, Schmidt T, Mehrabi A, Strobel O, Berchtold C, Schneider M, Diener M, Neoptolemos JP, Hackert T, Büchler MW. Distal Bile Duct Cancer: Radical (R0 > 1 mm) Resection Achieves Favorable Survival. Ann Surg 2023; 277:e112-e118. [PMID: 34171863 PMCID: PMC9762700 DOI: 10.1097/sla.0000000000005012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Evaluation of the outcome after resection for distal bile duct cancer (DBC) with focus on the impact of microscopic histopathological resection status R0 (>1 mm) versus R1 (≤1 mm) vs R1 (direct). SUMMARY BACKGROUND DATA DBC is a rare disease for which oncologic resection offers the only chance of cure. METHODS Prospectively collected data of consecutive patients undergoing pancreaticoduodenectomy for DBC were analyzed. Histopathological resection status was classified according to the Leeds protocol for pancreatic ductal adeno carcinoma (PDAC) (PDAC; R0 >1 mm margin clearance vs R1 ≤1 mm vs R1 direct margin involvement). RESULTS A total of 196 patients underwent pancreaticoduodenectomy for DBC. Microscopic complete tumor clearance (R0>1 mm) was achieved in 113 patients (58%). Median overall survival (OS) of the entire cohort was 37 months (5- and 10-year OS rate: 40% and 31%, respectively). After R0 resection, median OS increased to 78 months with a 5-year OS rate of 52%. Negative prognostic factors were age >70 years ( P < 0.0001, hazard ratio (HR) 2.48), intraoperative blood loss >1000 mL ( P = 0.0009, HR 1.99), pN1 and pN2 status ( P = 0.0052 and P = 0.0006, HR 2.14 and 2.62, respectively) and American Society of Anesthesiologists score >II ( P = 0.0259, HR 1.61). CONCLUSIONS This is the largest European single-center study of surgical treatment for DBC and the first to investigate the prognostic impact of the revised PDAC resection status definition in DBC. The results show that this definition is valid in DBC and that "true" R0 resection (>1 mm) is a key factor for excellent survival. In contrast to PDAC, there was no survival difference between R1 (≤1 mm) and R1 (direct).
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Affiliation(s)
- Christine Tjaden
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Ulla Klaiber
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Ulrike Heger
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, Heidelberg University Hospital, Heidelberg, Germany; and
| | - Benjamin Goeppert
- Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Christoph Berchtold
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus Diener
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - John P Neoptolemos
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
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23
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Mashiko T, Ogasawara T, Masuoka Y, Ei S, Takahashi S, Mori M, Koyanagi K, Yamamoto S, Nakagohri T. Indications for resection of recurrent lesions in patients with distal cholangiocarcinoma based on prognostic factors: a single-institute retrospective study and brief literature review. BMC Surg 2022; 22:423. [PMID: 36503431 PMCID: PMC9743743 DOI: 10.1186/s12893-022-01879-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND To evaluate the effectiveness of surgery for recurrent distal cholangiocarcinoma and determine surgical indications based on prognostic factors for the recurrence of distal cholangiocarcinoma. METHODS We analysed the outcomes of 101 patients who underwent surgical resection for distal cholangiocarcinoma between 2000 and 2018. The clinicopathological factors and prognosis of primary and recurrent distal cholangiocarcinoma were investigated. RESULTS Of the 101 patients with resected distal cholangiocarcinoma, 52 (51.5%) had relapsed. Seven (13.5%) and 45 patients (86.5%) underwent resection of recurrent lesions and palliative therapy, respectively. There were no major complications requiring therapeutic intervention after metastasectomy. The median overall survival in patients with and without surgery for recurrent lesions was 83.0 (0.0-185.6) and 34 months (19.0-49.0), respectively. Therefore, patients who had undergone surgery for recurrent lesions had a significantly better prognosis (p = 0.022). Multivariate analyses of recurrent distal cholangiocarcinoma revealed that recurrence within one year was an independent predictor of poor survival. Resection of recurrent lesions improved prognosis. CONCLUSIONS Radical resection in recurrent distal cholangiocarcinoma may improve the prognosis in selected patients. Although time to recurrence is considered an important factor, the small number of cases of recurrence and resection of recurrent lesions in this study makes it difficult to conclude which patients are best suited for resection of recurrent lesions. This issue requires clarification in a multicentre prospective study, considering patients' background, such as the recurrence site and number of metastases.
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Affiliation(s)
- Taro Mashiko
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
| | - Toshihito Ogasawara
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Yoshihito Masuoka
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Shigenori Ei
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Shinichiro Takahashi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kazuo Koyanagi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Seiichiro Yamamoto
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Toshio Nakagohri
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
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Lv TR, Wang JM, Ma WJ, Hu YF, Dai YS, Jin YW, Li FY. The consistencies and inconsistencies between distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: A systematic review and meta-analysis. Front Oncol 2022; 12:1042493. [PMID: 36578941 PMCID: PMC9791204 DOI: 10.3389/fonc.2022.1042493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/09/2022] [Indexed: 12/14/2022] Open
Abstract
Objective To evaluate the consistencies and inconsistencies between distal cholangiocarcinoma (DCCA) and pancreatic ductal adenocarcinoma (PDCA) regarding their biological features and long-term prognosis. Methods PubMed, the Cochrane Library, and EMBASE were searched to find comparative studies between DCCA and PDCA. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. Results Eleven studies with 4,698 patients with DCCA and 100,629 patients with PDCA were identified. Pooled results indicated that patients with DCCA had a significantly higher rate of preoperative jaundice (p = 0.0003). Lymphatic metastasis (p < 0.00001), vascular invasion (p < 0.0001), and peri-neural invasion (p = 0.005) were more frequently detected in patients with PDCA. After curative pancreaticoduodenectomy (PD), a significantly higher R0 rate (p < 0.0001) and significantly smaller tumor size (p < 0.00001) were detected in patients with DCCA. Patients with DCCA had a more favorable overall survival (OS) (p < 0.00001) and disease-free survival (DFS) (p = 0.005) than patients with PDCA. However, postoperative morbidities (p = 0.02), especially postoperative pancreatic fistula (POPF) (p < 0.00001), more frequently occurred in DCCA. Conclusion Patients with DCCA had more favorable tumor pathological features and long-term prognosis than patients with PDCA. An early diagnosis more frequently occurred in patients with DCCA. However, postoperative complications, especially POPF, were more frequently observed in patients with DCCA.
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Affiliation(s)
| | | | | | | | | | | | - Fu-Yu Li
- *Correspondence: Yan-Wen Jin, ; Fu-Yu Li,
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25
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Skalicky P, Urban O, Ehrmann J, Svebisova H, Klos D, Tesarikova J, Neoral C, Knapkova K, Lovecek M. The short- and long-term outcomes of pancreaticoduodenectomy for distal cholangiocarcinoma. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2022; 166:386-392. [PMID: 34467956 DOI: 10.5507/bp.2021.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/24/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal cholangiocarcinoma (DCC) patients to identify potential prognostic factors. PATIENTS AND METHODS A retrospective cohort study of 32 consecutive DCC patients treated with pancreaticoduodenectomy between 2009-2017. The clinicopathological and histopathological data were evaluated for prognostic factors using the univariable Cox regression analysis. The Overall Survival (OS) was estimated using the Kaplan-Meier analysis. RESULTS The study comprised a total of 32 patients, with a mean age of 65.8 (± 9.0) years at the time of surgery. R0 resection was achieved in 25 (86.2%) patients, 19 (65.5%) patients received adjuvant oncological therapy. The OS rates at 1, 3 and 5 years were 62.5%, 37.5% and 21.9%, respectively. The 90-day mortality was 3/32 (9.4%) accounting for one-fourth of the first-year mortality rate. The median OS was 28.5 months. The only statistically significant prognostic factor was vascular resection, which was associated with worse OS in the univariable analysis (HR: 3.644; 95%-CI: 1.179-11.216, P=0.025). An age less than 65 years, ASA grade I/II, hospital stay of fewer than 15 days, R0 resection, lymph node ratio less than 0.2 and adjuvant oncological therapy tended to be associated with better OS but without statistically significant relevance. CONCLUSION The main factor directly influencing the survival of DCC patients is surgical complications. Surgical mortality comprises a significant group of patients, who die in the first year following pancreaticoduodenectomy. Vascular resection is the most important negative prognostic factor for long-term survival.
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Affiliation(s)
- Pavel Skalicky
- Department of Surgery I, University Hospital Olomouc, Czech Republic
| | - Ondrej Urban
- Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Jiri Ehrmann
- Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Hana Svebisova
- Department of Oncology, University Hospital Olomouc, Czech Republic
| | - Dusan Klos
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Jana Tesarikova
- Department of Surgery I, University Hospital Olomouc, Czech Republic
| | - Cestmir Neoral
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Katerina Knapkova
- Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Martin Lovecek
- Department of Surgery I, University Hospital Olomouc, Czech Republic
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Zhu Y, Zu G, Wu D, Zhang Y, Yang Y, Wu H, Chen X, Chen W. Comparison of laparoscopic and open pancreaticoduodenectomy for the treatment of distal cholangiocarcinoma: A propensity score matching analysis. Front Oncol 2022; 12:1057337. [PMID: 36465359 PMCID: PMC9715962 DOI: 10.3389/fonc.2022.1057337] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 10/31/2022] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND There are few studies comparing the oncological outcomes of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for distal cholangiocarcinoma (DCC). Our objective was to assess the short-term efficacy and long-term survival of LPD and OPD in patients with DCC. METHODS The data of 124 DCC patients who underwent LPD or OPD at the Third Affiliated Hospital of Soochow University from May 2010 to May 2021 were retrospectively analyzed. Propensity score matching was performed to balance the two groups of baseline characteristics. After 1:1 matching, the overall survival (OS) of the two groups was compared by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to identify independent predictors of OS. RESULTS The original cohort consisted of 124 patients. Nineteen patients were excluded because of incomplete baseline or follow-up data, and the remaining 105 patients were divided into two cohorts (45 in the LPD group and 60 in the OPD group). The LPD group showed more favorable results in OS analysis (LPD vs. OPD, 56.4 [46.2-66.5] vs. 48.9 [36.4-61.4], months, P=0. 01). PSM analysis identified 30 pairs of patients, and differences between matching groups were still significant (LPD vs. OPD, 67.9[58.2-77.6] vs. 47.4[31.4-67.5], months, P=0.002). Moreover, the LPD group experienced less intraoperative bleeding (LPD vs. OPD, 292.67 vs. 519.17 mL, P=0.002). Univariate analysis showed that surgical modality (P=0.012), carbohydrate antigen 19-9 (P=0.043), carcinoembryonic antigen (P=0.003), neutrophil-to-lymphocyte ratio (P=0.012), blood transfusion (P=0.031), clinically relevant postoperative pancreatic fistula (P<0.001) and lymphatic metastasis (P=0.004) were predictors of OS. Multivariate Cox analysis demonstrated that carbohydrate antigen 19-9 (P=0.048), carcinoembryonic antigen (P=0.031) and lymphatic metastasis (P=0.023) were independent predictive factors of OS. However, adjuvant therapy had no significant effect on the OS of DCC patients after radical pancreaticoduodenectomy (P>0.05). CONCLUSIONS For DCC patients, LPD may be a more recommended procedure because of its advantages over OPD in terms of intraoperative bleeding and long-term survival.
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Affiliation(s)
- Yuwen Zhu
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Guangchen Zu
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Di Wu
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Yue Zhang
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Yang Yang
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Xuemin Chen
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Weibo Chen
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
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Perez M, Hansen CP, Burdio F, Pellino G, Pisanu A, Salvia R, Di Martino M, Abu Hilal M, Aldrighetti L, Ielpo B. Lymph Node Ratio Nomogram-Based Prognostic Model for Resected Distal Cholangiocarcinoma. J Am Coll Surg 2022; 235:703-712. [PMID: 36102558 DOI: 10.1097/xcs.0000000000000299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Several variables have been described as prognostic factors for resected distal cholangiocarcinoma (dCC), including lymph node metastases (N status) and lymph node ratio (LNR). The present study aimed to evaluate the prognostic value of LNR on survival and to establish a novel prognostic nomogram to predict the cancer-specific recurrence-free survival (RFS) of dCC. STUDY DESIGN Between December 2006 and September 2020, 415 consecutive patients who underwent pancreaticoduodenectomy (PD) for dCC in 10 centers were identified. Multivariate Cox analysis was used to identify all independent risk factors among several prognostic factors. A nomogram was then developed and assessed by integrating the independent prognostic factors into the model, and the concordance index (C-index) was used to evaluate its performance. RESULTS According to Cox regression multivariate analysis, a nomogram based on independent prognostic factor for RFS was performed including LNR 15 (hazard ratio [HR] 2.442, 95% CI 1.348-4.425, p = 0.003), perineural invasion (HR 3.100, 95% CI 1.183-8.122, p = 0.025), differentiation grade (HR 2.100, 95% CI 1.172-4.143, p = 0.021), and radicality of PD (HR 2.276, 95% CI 1.223-4.234, p = 0.009). The C-index of the nomogram, tailored based on the previous significant factors, was 0.8. CONCLUSIONS LNR15 yields a high prognostic efficiency for RFS. The nomogram based on LNR can provide an accurate prognosis assessment for patients with resected dCC.
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Affiliation(s)
- Marc Perez
- From the Hepato Pancreato Biliary Division, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain (Perez, Burdio, Ielpo)
| | | | - Fernando Burdio
- From the Hepato Pancreato Biliary Division, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain (Perez, Burdio, Ielpo)
| | - Gianluca Pellino
- Colorectal Surgery, Vall d'Hebron University Hospital, Barcelona, Spain (Pellino)
- Department of Advanced Medical and Surgical Sciences, Università Degli Studi Della Campania "Luigi Vanvitelli," Naples, Italy (Pellino)
| | - Adolfo Pisanu
- Department of Surgical Science, University of Cagliari, Cagliari, Italy (Pisanu)
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, the Pancreas Institute, University of Verona Hospital Trust, Italy (Salvia)
| | - Marcello Di Martino
- Hepatobiliary Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigacion Sanitaria Princesa (IIS-IP), Universidad Autonoma de Madrid (UAM), Madrid, Spain (Di Martino)
- Division of Hepatobiliary and Liver Transplantation Surgery. A.O.R.N. Cardarelli, Napoli, Italy (Di Martino)
| | - Mohammad Abu Hilal
- Department of Surgery, Fondazione Poliambulanza, Brescia, Italy (Abu Hilal)
| | - Luca Aldrighetti
- Department of Surgery, Ospedale San Raffaele, Milan, Italy (Aldrighetti)
| | - Benedetto Ielpo
- From the Hepato Pancreato Biliary Division, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Spain (Perez, Burdio, Ielpo)
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28
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Factors influencing apparent diffusion coefficient value in extrahepatic cholangiocarcinoma: A retrospective study. Eur J Radiol 2022; 157:110603. [DOI: 10.1016/j.ejrad.2022.110603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 10/28/2022] [Accepted: 11/06/2022] [Indexed: 11/12/2022]
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Gorji L, Beal EW. Surgical Treatment of Distal Cholangiocarcinoma. Curr Oncol 2022; 29:6674-6687. [PMID: 36135093 PMCID: PMC9498206 DOI: 10.3390/curroncol29090524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/05/2022] [Accepted: 09/08/2022] [Indexed: 12/03/2022] Open
Abstract
Distal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract and has a poor prognosis. dCCA is often clinically silent and patients commonly present with locally advanced and/or distant disease. For patients identified with early stage, resectable disease, surgical resection with negative margins remains the only curative treatment strategy available. However, despite appropriate treatment and diligent surveillance, risk of recurrence remains high with nearly 50% of patients experiencing recurrence at 5 years subsequent to surgical resection; therefore, it is prudent to continue to optimize neoadjuvant and adjuvant therapies in order to reduce the risk of recurrence and improve overall survival. In this review, we discuss the clinical presentation, workup and surgical treatment of dCCA.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, USA
| | - Eliza W. Beal
- Departments of Oncology and Surgery, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
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30
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Macias RIR, Cardinale V, Kendall TJ, Avila MA, Guido M, Coulouarn C, Braconi C, Frampton AE, Bridgewater J, Overi D, Pereira SP, Rengo M, Kather JN, Lamarca A, Pedica F, Forner A, Valle JW, Gaudio E, Alvaro D, Banales JM, Carpino G. Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions. Gut 2022; 71:1669-1683. [PMID: 35580963 DOI: 10.1136/gutjnl-2022-327099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023]
Abstract
Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers.
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Affiliation(s)
- Rocio I R Macias
- Experimental Hepatology and Drug Targeting (HEVEPHARM) group, University of Salamanca, IBSAL, Salamanca, Spain
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Timothy J Kendall
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Matias A Avila
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain
| | - Maria Guido
- Department of Medicine - DIMED, University of Padua, Padua, Italy
| | - Cedric Coulouarn
- UMR_S 1242, COSS, Centre de Lutte contre le Cancer Eugène Marquis, INSERM University of Rennes 1, Rennes, France
| | - Chiara Braconi
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Adam E Frampton
- Department of Clinical and Experimental Medicine, University of Surrey, Guildford, Surrey, UK
| | - John Bridgewater
- Department of Medical Oncology, UCL Cancer Institute, London, UK
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Stephen P Pereira
- Institute for Liver & Digestive Health, University College London, London, UK
| | - Marco Rengo
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Jakob N Kather
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Angela Lamarca
- Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Federica Pedica
- Department of Pathology, San Raffaele Scientific Institute, Milan, Italy
| | - Alejandro Forner
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- BCLC group, Liver Unit, Hospital Clínic Barcelona. IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Juan W Valle
- Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Jesus M Banales
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, San Sebastian, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, University of Rome 'Foro Italico', Rome, Italy
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Umezawa S, Kobayashi S, Otsubo T. Low preoperative psoas muscle mass index is a risk factor for distal cholangiocarcinoma recurrence after pancreatoduodenectomy: a retrospective analysis. World J Surg Oncol 2022; 20:176. [PMID: 35655260 PMCID: PMC9161607 DOI: 10.1186/s12957-022-02627-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 05/06/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND This study aimed to investigate whether preoperative muscle mass is associated with the recurrence of distal cholangiocarcinoma after pancreatoduodenectomy (PD). METHODS We retrospectively examined 88 patients who had undergone PD for distal cholangiocarcinoma. The preoperative psoas muscle mass index (PMI) was measured using computed tomography as an index of muscle mass. We performed multivariate analysis of factors influencing early recurrence and developed a prognostic survival model using independent risk factors for recurrence. RESULTS The cut-off PMI values for recurrence within 1 year of surgery, determined from the receiver operating characteristic curve, were 5.90 cm2/m2 in males and 3.98 cm2/m2 in females. Multivariate analysis of effects associated with early recurrence within 1 year indicated that low PMI (odds ratio [OR] 9.322; 95% confidence interval [CI] 2.832 - 30.678; p = 0.0002) and lymph node metastasis (OR 5.474; 95% CI 1.620 - 18.497; p = 0.0062) were independent risk factors, and the median recurrence-free survival (RFS) of the low and high PMI groups were 21.6 and 81.0 months, respectively (p = 0.0214). The median RFS for zero, one, and two risk factors of low PMI and lymph node metastasis were as follows: zero variables, median not reached; one variable, 15.3 months; two variables: 6 months. CONCLUSIONS Low preoperative PMI may be a risk factor for distal cholangiocarcinoma recurrence after PD. TRIAL REGISTRATION The Institutional Review Board of St. Marianna University School of Medicine approved this study prior to commencement of data collection and analysis on October 9, 2020 (IRB no. 5006) and waived the informed consent requirement.
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Affiliation(s)
- Saori Umezawa
- grid.412764.20000 0004 0372 3116Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511 Japan
| | - Shinjiro Kobayashi
- grid.412764.20000 0004 0372 3116Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511 Japan
| | - Takehito Otsubo
- grid.412764.20000 0004 0372 3116Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511 Japan
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32
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Development and external validation of a prediction model for overall survival after resection of distal cholangiocarcinoma. Br J Cancer 2022; 126:1280-1288. [PMID: 35039626 PMCID: PMC9042862 DOI: 10.1038/s41416-021-01687-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 10/01/2021] [Accepted: 12/23/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model for 3-year OS after pancreatoduodenectomy for dCCA. METHODS The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009-2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008-2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy). RESULTS Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01-1.03), pT (HR 1.43, 95% CI 1.07-1.90) and pN category (pN1: HR 1.78, 95% CI 1.37-2.32; pN2: HR 2.21, 95% CI 1.63-3.01), resection margin status (HR 1.79, 95% CI 1.39-2.29) and tumour differentiation (HR 2.02, 95% CI 1.62-2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%). CONCLUSIONS The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from Western European countries on their prognosis, and may be used to stratify patients for clinical trials.
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It is the lymph node ratio that determines survival and recurrence patterns in resected distal cholangiocarcinoma. A multicenter international study. Eur J Surg Oncol 2022; 48:1576-1584. [DOI: 10.1016/j.ejso.2022.02.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/30/2022] [Accepted: 02/05/2022] [Indexed: 12/26/2022] Open
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Lee JM, Kim H, Sohn HJ, Choi YJ, Kang JS, Han Y, Kwon W, Jang JY. Comparison of oncologic outcomes of extrahepatic cholangiocarcinoma according to tumor location: perihilar cholangiocarcinoma versus distal bile duct cancer. Ann Surg Treat Res 2022; 102:100-109. [PMID: 35198513 PMCID: PMC8831089 DOI: 10.4174/astr.2022.102.2.100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/24/2021] [Accepted: 01/10/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose Extrahepatic cholangiocarcinoma is distinguished into perihilar cholangiocarcinoma (PHC) and distal bile duct cancer (DBC). The studies for each subtype have been conducted separately. This study compared oncological outcomes between PHC and DBC. Methods From 2001 to 2017, patients who underwent surgery at Seoul National University Hospital for PHC or DBC were enrolled. T stage was reclassified for tumor extent as ‘confined to’ or ‘beyond’ the bile duct (BD). In survival analysis, stage matching was performed based on tumor extent and lymph node (LN) metastasis. Results There were 680 patients enrolled: 295 with PHC and 385 with DBC. The R0 resection rate was higher in DBC (77.3% vs. 89.9%, P = 0.001). Tumors confined to BD were more common in PHC (61.7% vs. 37.7%, P = 0.001). The 5-year survival rate (5YSR) was higher in DBC patients (30.8% vs. 47.8%, P = 0.001). After stage matching, DBC patients showed better 5YSR for tumors confined to BD/LN(–) (47.1% vs. 64.3%), confined to BD/LN(+) (22.0% vs. 35.0%), beyond BD/LN(–) (21.9% vs. 49.8%), and beyond BD/LN(+) (9.6% vs. 26.9%). The overall recurrence rate was higher in PHC (59.7% vs. 51.9%, P = 0.045), with no difference in the recurrence types between two groups. Radiation therapy was effective for patients with advanced stage disease (5YSR: 35.8% vs. 29.5%, P = 0.022); adjuvant chemotherapy was effective for patients receiving R1 resection (5YSR: 37.3% vs. 13.2%, P = 0.040). Conclusion Differences were identified in oncological outcomes between PHC and DBC, including pathologic findings and survival outcomes.
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Affiliation(s)
- Jung Min Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Ju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoo Jin Choi
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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A novel method for predicting perineural invasion of distal cholangiocarcinoma on multidetector-row computed tomography. Surg Today 2021; 52:774-782. [PMID: 34817682 DOI: 10.1007/s00595-021-02405-3] [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: 06/09/2021] [Accepted: 08/16/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE Excessive perineural invasion (PNI) is associated with a high risk of radial margin (RM) positivity and a poor prognosis for patients with distal cholangiocarcinoma (DCC). This study evaluates a new method of predicting the extent of PNI preoperatively. METHODS The subjects of this retrospective study were 201 patients who underwent resection for DCC between 2002 and 2018. This study identified the 'periductal enation sign' (PES), defined as the surrounding soft tissue enhancement that appears as an enation from the circumference of the enhanced extrahepatic bile duct on multidetector-row computed tomography (MDCT) scans, as a predictor of PNI. We analyzed the outcomes of the patients in relation to the presence or absence of the PES on MDCT scans. RESULTS The PES in the PNI-positive group was significantly longer than that in the PNI-negative group. As the length of the PES extended, the grade of PNI increased. A positive PES was defined as a PES length of ≥ 2.0 mm. Patients with a positive PES were more frequently positive for RM (23.7% vs. 2.1%) and locoregional recurrence (23.7% vs. 6.3%) and exhibited significantly poorer overall survival than those with a negative PES (30.2% vs. 54.6% at 5 years). CONCLUSIONS The presence and extent of PNI can be predicted easily and effectively by the PES length. A positive PES was associated with poor local controllability and a poor prognosis.
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Li R, Lu Z, Sun Z, Shi X, Li Z, Shao W, Zheng Y, Song J. A Nomogram Based on the Log Odds of Positive Lymph Nodes Predicts the Prognosis of Patients With Distal Cholangiocarcinoma After Surgery. Front Surg 2021; 8:757552. [PMID: 34765638 PMCID: PMC8575715 DOI: 10.3389/fsurg.2021.757552] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 09/27/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Lymph node (LN) metastasis is considered one of the most important risk factors affecting the prognosis of distal cholangiocarcinoma (DCC). This study aimed to demonstrate the superiority of log odds of positive lymph nodes (LODDS) compared with other LN stages, and to establish a novel prognostic nomogram to predict the cancer-specific survival (CSS) of DCC. Methods: From the Surveillance, Epidemiology and End Results (SEER) database, the data of 676 patients after DCC radical operation were screened, and patients were randomly divided into training (n = 474) and validation sets (n = 474). The prognostic evaluation performance of the LODDS and American Joint Commission on Cancer (AJCC) N stage and lymph node ratio (LNR) were compared using the Akaike information criteria, receiver operating characteristic area under the curve (AUC), and C-index. Multivariate Cox analysis was used to screen independent risk factors, and a LODDS-based nomogram prognostic staging model was established. The nomogram's precision was verified by C-index, calibration curves, and AUC, and the results were compared with those of the AJCC TNM staging system. Results:Compared with the other two stages of LN metastasis, LODDS was most effective in predicting CSS in patients with DCC. Multivariate analysis proved that LODDS, histologic grade, SEER historic stage, and tumor size were independent risk factors for DCC. The C-index of the nomogram, based on the above factors, in the validation set was 0.663. The 1-, 3-, and 5-y AUCs were 0.735, 0.679, and 0.745, respectively. Its good performance was also verified by calibration curves. In addition, the C-index and Kaplan-Meier analysis showed that the nomogram performed better than the AJCC TNM staging system. Conclusion:For postoperative patients with DCC, the LODDS stage yielded better prognostic efficiency than the AJCC N and LNR stages. Compared with the AJCC TNM staging system, the nomogram, based on the LODDS, demonstrated superior performance.
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Affiliation(s)
- Rui Li
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.,9th Department, Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhenhua Lu
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.,The Key Laboratory of Geriatrics, National Center of Gerontology, National Health Commission, Beijing Institute of Geriatrics, Beijing Hospital, Beijing, China.,Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhen Sun
- 9th Department, Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.,Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaolei Shi
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhe Li
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Weiwei Shao
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yangyang Zheng
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Jinghai Song
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Beijing Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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Jiang T, Lyu SC, Zhou L, Wang J, Li H, He Q, Lang R. Carbohydrate antigen 19-9 as a novel prognostic biomarker in distal cholangiocarcinoma. World J Gastrointest Surg 2021; 13:1025-1038. [PMID: 34621478 PMCID: PMC8462080 DOI: 10.4240/wjgs.v13.i9.1025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 06/18/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Distal cholangiocarcinoma (DCC) presents as one of the relatively rare malignant tumors in the digestive system and has a poor long-term prognosis. Curative resection is currently the most appropriate therapy for patients with DCC because of the lack of effective adjuvant therapies. Therefore, it is important to accurately predict the prognosis for formulating a reasonable treatment plan and avoiding unnecessary surgical trauma.
AIM To minimize the interference of obstructive jaundice on carbohydrate antigen 19-9 (CA19-9) level by adapting CA19-9 to γ-glutamyltransferase (GGT) as an indicator, to determine the strong associations between CA19-9/GGT and postoperative neoplasm recurrence and long-term outcome of DCC.
METHODS We enrolled 186 patients who were diagnosed with DCC between January 2010 and December 2019 and performed radical excision with strict criteria as follows in our hospital. Receiver operating characteristic curves were drawn according to preoperative CA19-9/GGT and 1-year survival. Based on this, patients were divided into two groups (group 1, low-ratio, n = 81; group 2, high-ratio, n = 105). Afterwards, by the way of univariate and multivariate analysis, the risk factors influencing postoperative tumor recrudesce and long-term prognosis of patients with DCC were screened out.
RESULTS Optimum cut-off value of CA19-9/GGT was 0.12. Patients in group 2 represented higher CA19-9 and lymphatic metastasis rate accompanied by lower GGT, when compared with group 1 (P < 0.05). The 1-, 3- and 5-year overall survival rates of patients in groups 1 and 2 were 88.3%, 59.2% and 48.1%, and 61.0%, 13.6% and 13.6%, respectively (P = 0.000). Multivariate analysis indicated that CA19-9/GGT, lymphatic metastasis and tumor differentiation were independent risk factors for tumor recurrence and long-term prognosis of DCC.
CONCLUSION Elevation of CA19-9/GGT performed better as a biomarker of aggressive carcinoma and predictor of poor clinical outcomes by reducing the effect of obstruction of biliary tract on CA19-9 concentration in patients with DCC.
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Affiliation(s)
- Tao Jiang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Lin Zhou
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Jing Wang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Han Li
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
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Bahra M. [Surgical treatment of distal cholangiocarcinoma]. Chirurg 2021; 92:788-795. [PMID: 34232340 DOI: 10.1007/s00104-021-01453-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2021] [Indexed: 10/20/2022]
Abstract
Distal cholangiocarcinoma accounts for about 20% of bile duct cancers, representing the third most common tumor entity among periampullary cancers, along with adenocarcinoma of the pancreas and carcinomas of the papilla of Vater. Precise diagnostics of tumor localization and exact knowledge of tumor-specific growth patterns are crucial for successful surgery. When planning the surgical procedure, the differential diagnosis of central bile duct cancer (Bismuth type I) or middle bile duct carcinoma must be considered. Although benign periampullary bile duct stenosis occurs in only 5% of cases, the presence of immunoglobulin G4-associated cholangitis (IAC) should be excluded in doubtful cases. Basically, in the presence of a distal cholangiocarcinoma, partial pancreatoduodenectomy is indicated analogous to the procedure for ductal adenocarcinoma of the pancreatic head. The 5‑year survival after resection is 20-25% and therefore comparable to adenocarcinoma of the pancreas. Local resection of middle bile duct carcinoma is no longer recommended due to inadequate surgical radicality. To date, perioperative treatment for downsizing does not play a relevant role for surgical treatment of distal cholangiocarcinoma. In the presence of a distal cholangiocarcinoma primary surgery with the aim of a R0 resection is the standard treatment of choice.
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Affiliation(s)
- Marcus Bahra
- Zentrum für Onkologische Oberbauchchirurgie und Robotik, Krankenhaus Waldfriede, Akademisches Lehrkrankenhaus der Charité, Argentinische Allee 40, 14163, Berlin, Deutschland.
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Feasibility of magnetic resonance imaging-based radiomics features for preoperative prediction of extrahepatic cholangiocarcinoma stage. Eur J Cancer 2021; 155:227-235. [PMID: 34391055 DOI: 10.1016/j.ejca.2021.06.053] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 06/11/2021] [Accepted: 06/29/2021] [Indexed: 01/03/2023]
Abstract
AIM The aim of this study is to develop and test radiomics models based on magnetic resonance imaging (MRI) to preoperatively and respectively predict the T stage, perineural invasion, and microvascular invasion of extrahepatic cholangiocarcinoma (eCCA) through a non-invasive approach. METHODS This research included 101 eCCA patients (29-83 years; 45 females and 56 males) between August 2011 and December 2019. Radiomics features were retrospectively extracted from T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient map using MaZda software. The region of interest was manually delineated in the largest section on four MRI images as ground truth while keeping 1-2 mm margin to tumor border, respectively. Pretreatment, dimension reduction method, and classifiers were used to establish radiomics signatures for assessing three pathological characteristics of eCCA. Finally, independent training and testing datasets were used to assess radiomics signature performance based on receiver operating characteristic curve analysis, accuracy, precision, sensitivity, and specificity. RESULTS This study extracted 1208 radiomics features from four MRI images of each patient. The best performing radiomics signatures for assessing the T stage, perineural invasion, and microvascular invasion were respectively produced by L1_normalization + linear discriminant analysis (LDA) + logistic regression, Box_Cox transformer + LDA + K-nearest neighbor, and L2_normalization + LDA + AdaBoost. The area under the curve values of the radiomics signatures for predicting the training and testing cohorts in each subgroup were respectively 1 and 0.962 (T stage), 1 and 1 (both perineural invasion and microvascular invasion). CONCLUSION These proposed radiomic models based on MR images had powerful performance and high potential in predicting T stage, perineural, and microvascular invasion of eCCA. REPORTING GUIDELINES/RESEARCH DESIGN Prognostic study.
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Tamura S, Yamamoto Y, Sugiura T, Okamura Y, Ito T, Ashida R, Ohgi K, Sasaki K, Sugino T, Uesaka K. The evaluation of the 8th and 7th edition of the American joint committee on cancer tumor classification for distal cholangiocarcinoma: the proposal of a modified new tumor classification. HPB (Oxford) 2021; 23:1209-1216. [PMID: 33358564 DOI: 10.1016/j.hpb.2020.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 10/03/2020] [Accepted: 12/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The 7th and 8th editions of the American Joint Committee on Cancer (AJCC) tumor (T) classification of distal cholangiocarcinoma (DCC), which are based on either layer or depth, may not accurately stratify patient survival. METHODS A total of 121 patients who underwent resection for DCC between 2002 and 2016 were analyzed. The impact of the AJCC staging system on survival was examined and a new T classification was established based on independent prognostic factors. RESULTS Regarding overall survival, the optimal depth of invasion (DOI) cut-off value (8 mm) was the only independent prognostic factor. Regarding the relapse-free survival (RFS), a DOI >8 mm, portal vein (PV) invasion, and duodenal or pancreatic invasion were independent prognostic factors. A new T classification was developed as follows: T1, no invasion of adjacent organs; T2, invasion of the duodenum or pancreas; T3, invasion >8 mm into the bile duct wall; and T4, invasion of the PV or arteries. There were no significant differences in RFS according to the 8th edition of the AJCC. However, significant differences were observed in the RFS between T1 and T2 and between T2 and T3. CONCLUSION A new T classification based on the layer and depth may be more feasible.
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Affiliation(s)
- Shunsuke Tamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Keiko Sasaki
- Division of Pathology, Shizuoka Cancer Center, Japan
| | | | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
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Garnier J, Ewald J, Poizat F, Traversari E, Marchese U, Palen A, Delpero JR, Turrini O. Prospective Evaluation of Resection Margins Using Standardized Specimen Protocol Analysis among Patients with Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma. J Clin Med 2021; 10:jcm10153247. [PMID: 34362031 PMCID: PMC8348230 DOI: 10.3390/jcm10153247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/09/2021] [Accepted: 07/21/2021] [Indexed: 11/16/2022] Open
Abstract
PURPOSE Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin. METHODS From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC (n = 288) or DC (n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm; however, clearances of 0 and 1.5 mm were also evaluated. RESULTS Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p < 0.01), and received less neoadjuvant treatment (p < 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC (p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC. CONCLUSION Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.
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Affiliation(s)
- Jonathan Garnier
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
- Correspondence:
| | - Jacques Ewald
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Flora Poizat
- Department of Pathology, Institut Paoli-Calmettes, 13009 Marseille, France;
| | - Eddy Traversari
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Ugo Marchese
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Anais Palen
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Jean Robert Delpero
- Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, 13009 Marseille, France; (J.R.D.); (O.T.)
| | - Olivier Turrini
- Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, 13009 Marseille, France; (J.R.D.); (O.T.)
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Chin KM, Di Martino M, Syn N, Ielpo B, Hilal MA, Goh BKP, Koh YX, Prieto M. Re-appraising the role of lymph node status in predicting survival in resected distal cholangiocarcinoma - A meta-analysis and systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:1267-1277. [PMID: 33549378 DOI: 10.1016/j.ejso.2021.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/22/2020] [Accepted: 01/06/2021] [Indexed: 02/08/2023]
Abstract
This systematic review and meta-analysis aimed to confirm the prognostic value of lymph node ratio (LNR), and determine an optimal LNR cut-off for overall survival (OS) in patients with distal cholangiocarcinoma (DCC) undergoing curative surgery. We additionally aimed to provide a consolidated review of current evidence regarding prognostic significance of positive lymph node count (PLNC) and total lymph node count (TLNC). A systematic search of PubMed, EMBASE and Cochrane Library was conducted from inception to October 2020. Studies were included into meta-analysis if there was histological diagnosis, curative surgery, restriction to DCC and relevant LNR results. Quality assessment was performed using the Newcastle Ottawa Scale. Findings for 1228 patients were pooled across 6 studies. Meta-analysis delineated a dose-effect gradient in which higher LNR cut-offs correlated with larger pooled hazard ratios: 0<LNR<0.2 (HR 1.54; 95% CI 1.08-2.20; p = 0.02), LNR>0.2 (HR 3.26; 95% CI 2.07-5.13; p < 0.00001) and LNR>0.4 (HR 3.59; 95% CI 2.31-5.58; p < 0.00001) when compared against a control group of LNR = 0. LNR of 0.2 (HR 2.12; 95% CI: 1.57-2.86; p < 0.0001) was found to be a significant and ideal cut-off for prognostication of poorer OS. A review of current literature reveals an ongoing debate regarding the comparative prognostic value of differing PLNC cut-offs (0/1/3 versus 0/1/4). TLNC of 10-13 is widely reported to be the minimum necessary to ensure improved long term outcomes. PLNC and LNR are strong prognostic factors for OS in DCC. An ideal LNR cut-off of 0.2 is most significantly associated with poorer OS.
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Affiliation(s)
- Ken Min Chin
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore
| | - Marcello Di Martino
- Hepatopancreatobiliary Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Calle de Diego de León, 62, 28006 Madrid, Spain
| | - Nicholas Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore
| | - Benedetto Ielpo
- Hepatopancreatobiliary Unit, Parc Salut Mar Hospital, Barcelona, Passeig Marítim de La Barceloneta 25, 08003, Spain
| | - Mohammad Abu Hilal
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Via Leonida Bissolati, 57, 25124, Italy
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore 10 Medical Drive, 117597, Singapore; Duke NUS Medical School, Singapore (8 College Rd, 169857, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore 10 Medical Drive, 117597, Singapore; Duke NUS Medical School, Singapore (8 College Rd, 169857, Singapore.
| | - Mikel Prieto
- Hepatobiliary Surgery and Liver Transplant Unit, Cruces University Hospital, Cruces Plaza, S/N, 48903 Barakaldo, Bizkaia, Spain; BioCruces Research Institute, University of the Basque Country Cruces Plaza, 48903 Barakaldo, Bizkaia, Spain
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Burasakarn P, Higuchi R, Yazawa T, Uemura S, Izumo W, Matsunaga Y, Yamamoto M. Hepatic artery resection without reconstruction in pancreatoduodenectomy. Langenbecks Arch Surg 2021; 406:2081-2090. [PMID: 33932159 DOI: 10.1007/s00423-021-02178-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 04/18/2021] [Indexed: 11/30/2022]
Abstract
PURPOSE It has been reported that there are left and right hepatic arterial arcades via the blood vessels around the hilar bile duct; therefore, when the hilar bile duct is preserved, hepatic artery reconstruction may not be necessary. We compared the short-term and long-term outcomes in patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy (PD) with right hepatic artery resection without right hepatic artery reconstruction (RHAR group) with those patients who underwent conventional PD. METHODS All data were retrospectively collected from patient records. A 1:4-propensity score-matched case-control study was conducted in patients with distal cholangiocarcinoma who received treatment at Tokyo Women's Medical University from February 1985 to April 2015. RESULTS There was no statistical difference in the overall morbidity rate between the two groups. No patient in the RHAR group (10 patients) had liver failure, liver abscess, or cholangitis in the postoperative period; one patient died postoperatively because of a bleeding pseudoaneurysm in the gastroduodenal artery. The PD group (40 patients) had a significantly better median time regarding the recurrence (34 vs. 11 months, p=0.027) and 5-year disease-free survival (35% vs. 10%, p=0.027) rates than the RHAR group, which may be attributed to the presence of a more severe disease in patients in the RHAR group. CONCLUSION We concluded that pancreaticoduodenectomy with right hepatic artery resection without reconstruction has a comparable overall morbidity rate with that of a conventional pancreaticoduodenectomy surgery and may be performed as an alternative procedure when tumor invasion of the right hepatic artery is suspected.
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Affiliation(s)
- Pipit Burasakarn
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.,Division of HPB Surgery, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Yutaro Matsunaga
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
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Lyu S, Wang F, Ren Z, Cao D, He Q. Long-term survival in patients with distal cholangiocarcinoma after pancreaticoduodenectomy combined with portal vein system resection and reconstruction. Langenbecks Arch Surg 2021; 406:1917-1924. [PMID: 33871714 DOI: 10.1007/s00423-021-02177-x] [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: 01/20/2021] [Accepted: 04/13/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE Pancreaticoduodenectomy combined with portal vein resection for distal cholangiocarcinoma is rarely reported because it is a rare disease. We developed a program to evaluate the vascular invasion type, operation procedure, and long-term survival of distal cholangiocarcinoma patients with portal vein invasion. METHODS We retrospectively reviewed data for 123 distal cholangiocarcinoma patients after pancreaticoduodenectomy between January 2013 and December 2019. Portal vein system invasion was confirmed pathologically in 17 patients. RESULTS Multivariable Cox regression identified tumor differentiation degree, portal vein system invasion, and lymph node metastasis as independent risk factors affecting long-term survival. The 1- and 2-year overall survival rates for patients without and with portal vein system invasion were 79.7% and 58.9%, and 48.6% and 10.8%, respectively. Median overall survival in patients without and with portal vein system invasion was 33 months and 12 months, respectively. CONCLUSION Portal vein system invasion is an important independent risk factor affecting long-term survival in patients with distal cholangiocarcinoma. Pancreaticoduodenectomy combined with portal vein system resection and reconstruction did not increase the incidence of perioperative complications or mortality.
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Affiliation(s)
- Shaocheng Lyu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China
| | - Fangfei Wang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China
| | - Zhangyong Ren
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China
| | - Di Cao
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China.
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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Nara S, Esaki M, Ban D, Takamoto T, Shimada K, Ioka T, Okusaka T, Ishii H, Furuse J. Adjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials. Jpn J Clin Oncol 2021; 50:1353-1363. [PMID: 33037430 DOI: 10.1093/jjco/hyaa170] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 08/21/2020] [Indexed: 12/14/2022] Open
Abstract
Cancer originating in the biliary tract can be classified as bile duct cancer (cholangiocarcinoma), gallbladder cancer, or ampullary cancer. Bile duct cancer is further divided to intrahepatic, perihilar and distal bile duct subtypes according to the anatomical location of the tumor. The biological characteristics of each tumor are heterogeneous. However, because of the rarity of each disease, the efficacy of new drugs has been tested in groups of patients with different biliary tract cancers. In patients with metastatic or recurrent biliary tract cancer, recent randomized clinical trials revealed the non-inferiority of gemcitabine + S-1 and the superiority of gemcitabine + cisplatin + S-1 compared with gemcitabine + cisplatin in terms of overall survival, thereby establishing a new standard treatment. In the field of adjuvant therapy for biliary tract cancer, the British BILCAP (capecitabine compared with observation in resected biliary tract cancer) study revealed longer median overall survival in the capecitabine group than in the observation group in the per-protocol analysis (but not in the intention-to-treat analysis), bringing a shift toward postoperative management. Several other studies of adjuvant therapy are ongoing, and they may lead to reforms in treatment strategy for resectable biliary tract cancer in the future. The use of neoadjuvant therapy for biliary tract cancer is in its infancy, but it is expected to overcome the limitations of adjuvant therapy for this malignancy. In this review, we summarized the evidence available from clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and described ongoing clinical trials.
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Affiliation(s)
- Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Tatsuya Ioka
- Oncology Center, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi Ube-shi, Yamaguchi, 755-8505, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Hiroshi Ishii
- Division of Gastroenterology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
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Kontis EA. Biology of Liver Tumors and Outcomes of Liver Surgery. ANESTHESIA FOR HEPATICO-PANCREATIC-BILIARY SURGERY AND TRANSPLANTATION 2021:303-313. [DOI: 10.1007/978-3-030-51331-3_18] [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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Gunasekaran G, Bekki Y, Lourdusamy V, Schwartz M. Surgical Treatments of Hepatobiliary Cancers. Hepatology 2021; 73 Suppl 1:128-136. [PMID: 32438491 DOI: 10.1002/hep.31325] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 04/24/2020] [Accepted: 05/13/2020] [Indexed: 12/15/2022]
Abstract
Hepatobiliary cancers which include hepatocellular carcinoma (HCC) and biliary tract cancers (i.e., cholangiocarcinoma and gallbladder carcinoma) are associated with significant morbidity and mortality based on the stage of the disease at presentation. With improved screening for hepatobiliary malignancies in patients with risk factors and with widespread use of laparoscopic cholecystectomy, hepatobiliary malignancies, including incidental diagnosis of gallbladder carcinoma, are on the rise. Definitive treatment of hepatobiliary malignancies include surgical resection, ablation, and liver transplantation. However, management of these cancers is challenging due to the complex hepatobiliary anatomy and the need for meticulous perioperative management especially in patients with advanced liver disease. The management and prognosis of hepatobiliary malignancies vary widely based on the stage of presentation, with surgical options providing the possibility of definitive cure in patients presenting with early-stage disease. Surgical resection for HCC results in good outcomes if performed in ideal candidates. For patients with early HCC who are not candidates for surgical resection, ablation and liver transplantation should be considered. Similarly, surgical resection is also the definitive treatment for biliary tract cancers, and liver transplantation can be curative in selected patients with perihilar cholangiocarcinoma after neoadjuvant chemoradiotherapy. The role of routine adjuvant chemotherapy and radiotherapy is not clearly established, but adjuvant therapies can offer better outcomes in patients with advanced disease at presentation. Outcomes of surgical management of hepatobiliary cancers seem to be improving. Given the complex decision-making process involved, multidisciplinary evaluation is essential to provide and coordinate the best treatments for these patients.
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Affiliation(s)
- Ganesh Gunasekaran
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY
| | - Yuki Bekki
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY
| | | | - Myron Schwartz
- Division of Liver Surgery, Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY
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The prognostic impact of skeletal muscle status and bone mineral density for resected distal cholangiocarcinoma. Clin Nutr 2020; 40:3552-3558. [PMID: 33358552 DOI: 10.1016/j.clnu.2020.12.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/27/2020] [Accepted: 12/09/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND & AIMS The preoperative body composition and bone mineral density (BMD) have been reported as prognostic factors for several cancers. However, the prognostic impact of the preoperative body composition and BMD for resected distal cholangiocarcinoma (DCC) remains unclear. METHODS A total of 111 patients who underwent pancreatoduodenectomy for DCC between 2002 and 2017 were analyzed. The skeletal muscle index (SMI) and BMD were measured by preoperative computed tomography. The optimal cut-off value of the body composition and BMD were selected based on the minimum P-value obtained by the log-rank test. The prognostic significance of the preoperative body composition and BMD was investigated using multivariate analysis. RESULTS The median values of the SMI (45.7 vs. 36.7 cm2/m2, P < 0.001) and BMD (128.5 vs. 101.0 Hounsfield units [HU], P = 0.005) in male and female were significantly different. The optimal cut-off values for the SMI were 55 cm2/m2 in male and 36 cm2/m2 in female, and those for the BMD were 75 HU in male and 74 HU in female. A multivariate analysis identified low SMI (hazard ratio [HR], 4.340; P = 0.044), low BMD (HR, 5.333; P < 0.001) and microscopic venous invasion (HR, 2.019; P = 0.026) as independent prognostic factors for the survival. CONCLUSIONS A preoperative low SMI and low BMD were independent prognostic factors for resected DCC.
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Ji F, Kang Q, Wang L, Liu L, Ke Y, Zhu Y, Zhang N, Xiong S, Li Y, Zou H. Prognostic significance of the neutrophil-to-lymphocyte ratio with distal cholangiocarcinoma patients. Medicine (Baltimore) 2020; 99:e22827. [PMID: 33120809 PMCID: PMC7581158 DOI: 10.1097/md.0000000000022827] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The present study aimed to investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in distal cholangiocarcinoma (DCC) following radical surgery. METHODS The clinicopathological data of 59 patients with DCC were retrospectively reviewed. Patients were treated by radical surgery and diagnosed by postoperative pathology at the Second Affiliated Hospital of Kunming Medical University (Yunnan, China), between July 2015 and December 2017. The optimal cut-off value for the NLR was determined by generating receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the risk factors and independent risk factors influencing the prognosis of patients with DCC. RESULTS According to the ROC curve, the optimal cut-off value for the NLR was 2.933. The results of Kaplan-Meier survival analysis and the Cox proportional hazards model showed that carbohydrate antigen 125, NLR, perineural, vascular and fat invasion, regional lymph node metastasis, and the American Joint Committee on Cancer stage were risk factors for DCC; the only independent risk factor to affect the prognosis of DCC patients was the NLR. CONCLUSIONS The preoperative NLR plays an important guiding role in evaluating the prognosis of patients with DCC, and an increase in the NLR is associated with poor patient prognosis.
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Affiliation(s)
- Fengming Ji
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
- Urology Department of The Affiliated Children's Hospital of Kunminng Medical University, Kunming Chlidren's Hospital, Key Laboratory of Children's Major Disease Research, Kunming Medical University
| | - Qiang Kang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Lianmin Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Lixin Liu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Yang Ke
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Ya Zhu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Naiqiang Zhang
- Department of General Surgery, Kunming Traditional Chinese Medicine Hospital, Kunming, Yunnan, PR China
| | - Shifeng Xiong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Yuehua Li
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
| | - Hao Zou
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital
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