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Dayyan F, Zamani F, Ajdarkosh H, Khoonsari M, Faraji A, Nikkhah M, Nourian A, Safarnezhad Tameshkel F, Sobhrakhshankhah E. The prognostic role of albumin-bilirubin grade in the mortality of extrahepatic cholangiocarcinoma patients. BMC Gastroenterol 2025; 25:383. [PMID: 40389833 PMCID: PMC12090579 DOI: 10.1186/s12876-025-03979-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 05/07/2025] [Indexed: 05/21/2025] Open
Abstract
OBJECTIVE Cholangiocarcinoma (CCA) has a low survival rate of 5-17%, despite advancements in diagnosis and treatment. Liver function impacts disease prognosis, and the albumin-bilirubin (ALBI) score is a new assessment model for this purpose. While research suggests a correlation between ALBI score, liver failure and mortality in intrahepatic CCA (iCCA), predicting outcomes for extrahepatic CCA (eCCA) is challenging. Our objective was to assess the prognostic role of ALBI grade in predicting overall survival of eCCA patients. METHODS Patients with diagnosis of eCCA who had visited Firuzgar Hospital from 2015 to 2019 were consecutively included in the study. These individuals had previously undergone Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) or ERCP brush cytology followed by surgery. Exclusion criteria were patients with benign bile duct strictures, prior biliary tract surgery, concurrent liver disease impacting liver tests, inadequate data, or inconsistent monitoring. Clinical data of patients were collected to calculate ALBI score which was subsequently divided into three distinct grades (grade 1: ≤-2.60, grade 2: > -2.60 to ≤ - 1.39, grade 3: >-1.39). Kaplan-Meier analysis and Cox regression model were used to analyze overall survival, 1-, 3- and 5-year survival and parameters affecting patient survival. RESULTS In this study, 80 patients with diagnosis of eCCA with a median age of 67 (58.25-74) years (67.5% male) who visited Firuzgar Hospital from 2015 to 2019 were included. The average survival time of patients was 13.9 ± 16.4 months, and the 1-year, 3-year, and 5-year survival rates of patients were 36.6%, 27.1%, and 15.8%, respectively. The results showed that ALBI grade, Aspartate Aminotransferase (AST), white blood cell (WBC) and international normalized ratio (INR) have significant effects on the survival of patients (all P < 0.05). Based on the results of Cox regression, the risk of mortality due to CCA in patients with ALBI grade 3 (HR = 1.87, P = 0.0111), AST > 82.5 (HR = 1.90, P = 0.0091), WBC > 7.70 × 109/L (HR = 2.46, P = 0.0004), and INR > 1.08 (HR = 1.78, P = 0.0202) increases significantly. CONCLUSION We showed that ALBI grade, AST > 82.5 units/L, and INR > 1.08 can be used as predictive factors of survival in cholangiocarcinoma patients.
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Affiliation(s)
- Fatemeh Dayyan
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmoodreza Khoonsari
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Faraji
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mehdi Nikkhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akram Nourian
- Department of Pediatrics, Faculty of Medical, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Elham Sobhrakhshankhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
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McCarty TR, Shah R, Allencherril RP, Moon N, Njei B. The Role of Artificial Intelligence Combined With Digital Cholangioscopy for Indeterminant and Malignant Biliary Strictures: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2025:00004836-990000000-00421. [PMID: 39998988 DOI: 10.1097/mcg.0000000000002148] [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: 01/10/2024] [Accepted: 01/22/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND Current endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopic-based diagnostic sampling for indeterminant biliary strictures remain suboptimal. Artificial intelligence (AI)-based algorithms by means of computer vision in machine learning have been applied to cholangioscopy in an effort to improve diagnostic yield. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic performance of AI-based diagnostic performance of AI-associated cholangioscopic diagnosis of indeterminant or malignant biliary strictures. METHODS Individualized searches were developed in accordance with PRISMA and MOOSE guidelines, and meta-analysis according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve (SROC). RESULTS Five studies (n=675 lesions; a total of 2,685,674 cholangioscopic images) were included. All but one study analyzed a deep learning AI-based system using a convoluted neural network (CNN) with an average image processing speed of 30 to 60 frames per second. The pooled sensitivity and specificity were 95% (95% CI: 85-98) and 88% (95% CI: 76-94), with a diagnostic accuracy (SROC) of 97% (95% CI: 95-98). Sensitivity analysis of CNN studies (4 studies, 538 patients) demonstrated a pooled sensitivity, specificity, and accuracy (SROC) of 95% (95% CI: 82-99), 88% (95% CI: 72-95), and 97% (95% CI: 95-98), respectively. CONCLUSIONS Artificial intelligence-based machine learning of cholangioscopy images appears to be a promising modality for the diagnosis of indeterminant and malignant biliary strictures.
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Affiliation(s)
- Thomas R McCarty
- Houston Methodist Hospital, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston, TX
- Weill Cornell Medical College, New York, NY
- Texas A&M University, School of Medicine, Bryan College Station, TX
| | - Raj Shah
- The Ohio State University, Wexler School of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Columbus, OH
| | - Ronan P Allencherril
- Houston Methodist Hospital, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston, TX
| | - Nabeel Moon
- Houston Methodist Hospital, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston, TX
| | - Basile Njei
- Yale University School of Medicine, Investigative Medicine Program, Yale Institute for Global Health, Section of Digestive Diseases, New Haven, CT
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Jorgenson LC, Torbenson MS, Halfdanarson TR, Kankeu Fonkoua LA, Tran NH, Roberts LR, Smoot RL, Goenka AH, Thompson SM. Immunohistochemical basis for FAP as a candidate theranostic target across a broad range of cholangiocarcinoma subtypes. FRONTIERS IN NUCLEAR MEDICINE (LAUSANNE, SWITZERLAND) 2024; 4:1480471. [PMID: 39664608 PMCID: PMC11631625 DOI: 10.3389/fnume.2024.1480471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/14/2024] [Indexed: 12/13/2024]
Abstract
Purpose The aims of this study were to evaluate and compare fibroblast activation protein (FAP) expression and localization in surgically resected cholangiocarcinoma (CCA), primary and metastatic hepatocellular carcinoma (HCC), hepatocellular adenoma (HCA), and focal nodular hyperplasia (FNH), and to identify any association between CCA clinical or pathologic features and FAP expression. Materials and methods FAP immunostaining from surgically resected CCA (N = 58), primary intrahepatic and extrahepatic metastatic HCC (N = 148), HCA (N26), and FNH (N = 19) was scored (negative, weak positive, moderate positive or strong positive) from tissue microarrays. FAP expression was compared between groups. CCA FAP expression was compared to clinical and tumor pathology features. Results Moderate-strong FAP expression in the tumor stroma was present in 93.1% of CCA, 60.7% of extrahepatic metastatic HCC, 29.6% of primary HCC, 21.1% of FNH, and 11.6% of HCA. Moderate-strong FAP expression in tumor stroma was significantly more prevalent in CCA than HCC (p < 0.001), metastatic HCC (p = 0.005), HCA (p < 0.001) and FNH (p < 0.001). FAP was expressed in the stroma of all but one CCA (1.7%), and FAP expression in CCA tumor stroma was not associated with any clinical or tumor pathology features (p > 0.05, all). Conclusion FAP is expressed in the stroma of a high proportion (93%) of primary CCA independent of patient clinical or tumor pathology features. As such, these data provide the tissue basis for systematically evaluating FAP as a theranostic target across a broad range of CCA subtypes.
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Affiliation(s)
| | - Michael S. Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | | | | | - Nguyen H. Tran
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, United States
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Rory L. Smoot
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, United States
| | - Ajit H. Goenka
- Department of Radiology, Mayo Clinic, Rochester, MN, United States
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De B, Dogra P, Zaid M, Elganainy D, Sun K, Amer AM, Wang C, Rooney MK, Chang E, Kang HC, Wang Z, Bhosale P, Odisio BC, Newhook TE, Tzeng CWD, Cao HST, Chun YS, Vauthey JN, Lee SS, Kaseb A, Raghav K, Javle M, Minsky BD, Noticewala SS, Holliday EB, Smith GL, Koong AC, Das P, Cristini V, Ludmir EB, Koay EJ. Measurable imaging-based changes in enhancement of intrahepatic cholangiocarcinoma after radiotherapy reflect physical mechanisms of response. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.09.11.24313334. [PMID: 39314943 PMCID: PMC11419200 DOI: 10.1101/2024.09.11.24313334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
Background Although escalated doses of radiation therapy (RT) for intrahepatic cholangiocarcinoma (iCCA) are associated with durable local control (LC) and prolonged survival, uncertainties persist regarding personalized RT based on biological factors. Compounding this knowledge gap, the assessment of RT response using traditional size-based criteria via computed tomography (CT) imaging correlates poorly with outcomes. We hypothesized that quantitative measures of enhancement would more accurately predict clinical outcomes than size-based assessment alone and developed a model to optimize RT. Methods Pre-RT and post-RT CT scans of 154 patients with iCCA were analyzed retrospectively for measurements of tumor dimensions (for RECIST) and viable tumor volume using quantitative European Association for Study of Liver (qEASL) measurements. Binary classification and survival analyses were performed to evaluate the ability of qEASL to predict treatment outcomes, and mathematical modeling was performed to identify the mechanistic determinants of treatment outcomes and to predict optimal RT protocols. Results Multivariable analysis accounting for traditional prognostic covariates revealed that percentage change in viable volume following RT was significantly associated with OS, outperforming stratification by RECIST. Binary classification identified ≥33% decrease in viable volume to optimally correspond to response to RT. The model-derived, patient-specific tumor enhancement growth rate emerged as the dominant mechanistic determinant of treatment outcome and yielded high accuracy of patient stratification (80.5%), strongly correlating with the qEASL-based classifier. Conclusion Following RT for iCCA, changes in viable volume outperformed radiographic size-based assessment using RECIST for OS prediction. CT-derived tumor-specific mathematical parameters may help optimize RT for resistant tumors.
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Affiliation(s)
- Brian De
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prashant Dogra
- Mathematics in Medicine Program, Department of Medicine, Houston Methodist Research Institute, Houston, TX, USA
- Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA
| | - Mohamed Zaid
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Dalia Elganainy
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kevin Sun
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed M. Amer
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Charles Wang
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael K. Rooney
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Enoch Chang
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hyunseon C. Kang
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zhihui Wang
- Mathematics in Medicine Program, Department of Medicine, Houston Methodist Research Institute, Houston, TX, USA
- Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA
- Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA
| | - Priya Bhosale
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruno C. Odisio
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy E. Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D. Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hop S. Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun S. Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicholas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sunyoung S. Lee
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Kaseb
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kanwal Raghav
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Milind Javle
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D. Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sonal S. Noticewala
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emma B. Holliday
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Grace L. Smith
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Albert C. Koong
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prajnan Das
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Vittorio Cristini
- Mathematics in Medicine Program, Department of Medicine, Houston Methodist Research Institute, Houston, TX, USA
- Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA
- Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA
- Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ethan B. Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene J. Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Lee G, Kim DW, Smart AC, Horick NK, Eyler CE, Roberts HJ, Pathak P, Goyal L, Franses J, Heather JM, Hwang WL, Grassberger C, Klempner SJ, Drapek LC, Allen JN, Blaszkowsky LS, Parikh AR, Ryan DP, Clark JW, Hong TS, Wo JY. Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma. Am J Clin Oncol 2024; 47:373-382. [PMID: 38767086 DOI: 10.1097/coc.0000000000001108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
OBJECTIVE The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia. CONCLUSIONS HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.
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Affiliation(s)
- Grace Lee
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Daniel W Kim
- Inova Mather Proton Centre, Inova Schar Cancer Institute, VA
| | - Alicia C Smart
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Nora K Horick
- Massachusetts General Hospital Biostatistics Center, Boston, MA
| | - Christine E Eyler
- Department of Radiation Oncology, Duke University Medical Center, Durham, NC
| | - Hannah J Roberts
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Priyadarshini Pathak
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Lipika Goyal
- Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, CA
| | - Joseph Franses
- Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL
| | - James M Heather
- Massachusetts General Hospital Cancer Center and Harvard Medical School Department of Medicine, Boston, MA
| | - William L Hwang
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | | | - Samuel J Klempner
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Lorraine C Drapek
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Jill N Allen
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Lawrence S Blaszkowsky
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Aparna R Parikh
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - David P Ryan
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Jeffrey W Clark
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
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Cotchim S, Kongkaew S, Thavarungkul P, Kanatharana P, Limbut W. A dual-electrode label-free immunosensor based on in situ prepared Au-MoO 3-Chi/porous graphene nanoparticles for point-of-care detection of cholangiocarcinoma. Talanta 2024; 272:125755. [PMID: 38364561 DOI: 10.1016/j.talanta.2024.125755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 02/01/2024] [Accepted: 02/05/2024] [Indexed: 02/18/2024]
Abstract
A novel label-free electrochemical immunosensor was prepared for the detection of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) as biomarkers of cholangiocarcinoma (CCA). A nanocomposite of gold nanoparticles, molybdenum trioxide, and chitosan (Au-MoO3-Chi) was layer-by-layer assembled on the porous graphene (PG) modified a dual screen-printed electrode using a self-assembling technique, which increased surface area and conductivity and enhanced the adsorption of immobilized antibodies. The stepwise self-assembling procedure of the modified electrode was further characterized morphologically and functionally. The electroanalytical detection of biomarkers was based on the interaction between the antibody and antigen of each marker via linear sweep voltammetry using ferrocyanide/ferricyanide as an electrochemical redox indicator. Under optimized conditions, the fabricated immunosensor showed linear relationships between current change (ΔI) and antigen concentrations in two ranges: 0.0025-0.1 U mL-1 and 0.1-1.0 U mL-1 for CA19-9, and 0.001-0.01 ng mL-1 and 0.01-1.0 ng mL-1 for CEA. The limits of detection (LOD) were 1.0 mU mL-1 for CA19-9 and 0.5 pg mL-1 for CEA. Limits of quantitation (LOQ) were 3.3 mU mL-1 for CA19-9 and 1.6 pg mL-1 for CEA. The selectivity of the developed immunosensor was tested on mixtures of antigens and was then successfully applied to determine CA19-9 and CEA in human serum samples, producing satisfactory results consistent with the clinical method.
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Affiliation(s)
- Suparat Cotchim
- Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Division of Physical Science, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
| | - Supatinee Kongkaew
- Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Division of Physical Science, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
| | - Panote Thavarungkul
- Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Division of Physical Science, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
| | - Proespichaya Kanatharana
- Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Division of Physical Science, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
| | - Warakorn Limbut
- Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; Forensic Science Innovation and Service Center, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
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Czekay RP, Higgins CE, Aydin HB, Samarakoon R, Subasi NB, Higgins SP, Lee H, Higgins PJ. SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment. Cells 2024; 13:796. [PMID: 38786020 PMCID: PMC11119900 DOI: 10.3390/cells13100796] [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: 04/04/2024] [Revised: 05/03/2024] [Accepted: 05/03/2024] [Indexed: 05/25/2024] Open
Abstract
A heterogenous population of inflammatory elements, other immune and nonimmune cells and cancer-associated fibroblasts (CAFs) are evident in solid malignancies where they coexist with the growing tumor mass. In highly desmoplastic malignancies, CAFs are the prominent mesenchymal cell type in the tumor microenvironment (TME), where their presence and abundance signal a poor prognosis. CAFs play a major role in the progression of various cancers by remodeling the supporting stroma into a dense, fibrotic matrix while secreting factors that promote the maintenance of cancer stem-like characteristics, tumor cell survival, aggressive growth and metastasis and reduced sensitivity to chemotherapeutics. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Identifying the molecular underpinnings for such multidirectional crosstalk among the various normal and neoplastic cell types in the TME may provide new targets and novel opportunities for therapeutic intervention. This review highlights recent concepts regarding the complexity of CAF biology in cholangiocarcinoma, a highly desmoplastic cancer. The discussion focuses on CAF heterogeneity, functionality in drug resistance, contributions to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.
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Affiliation(s)
- Ralf-Peter Czekay
- Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA; (R.-P.C.); (C.E.H.); (R.S.); (S.P.H.)
| | - Craig E. Higgins
- Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA; (R.-P.C.); (C.E.H.); (R.S.); (S.P.H.)
| | - Hasan Basri Aydin
- Department of Pathology & Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA; (H.B.A.); (N.B.S.); (H.L.)
| | - Rohan Samarakoon
- Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA; (R.-P.C.); (C.E.H.); (R.S.); (S.P.H.)
| | - Nusret Bekir Subasi
- Department of Pathology & Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA; (H.B.A.); (N.B.S.); (H.L.)
| | - Stephen P. Higgins
- Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA; (R.-P.C.); (C.E.H.); (R.S.); (S.P.H.)
| | - Hwajeong Lee
- Department of Pathology & Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA; (H.B.A.); (N.B.S.); (H.L.)
| | - Paul J. Higgins
- Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA; (R.-P.C.); (C.E.H.); (R.S.); (S.P.H.)
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Zeng XT, Liang X, Hong ZL, Chen S, Yang JC, Lin YC, Wu SS. Initial investigation on ultrasound-guided percutaneous biopsy of lesions in the first hepatic hilum with fusion of ultrasound and multimodal imaging cognitive guidance. Front Oncol 2024; 14:1297153. [PMID: 38720805 PMCID: PMC11077297 DOI: 10.3389/fonc.2024.1297153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 03/21/2024] [Indexed: 05/12/2024] Open
Abstract
Purpose This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment. Methods We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions. Results The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61). Conclusion Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.
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Affiliation(s)
- Xian-Tao Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Xia Liang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Zhi-Liang Hong
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Sheng Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Jian-Chuan Yang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Yu-cheng Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Ultrasonography, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China
| | - Song-Song Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
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9
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Gupta A, Sahai P, Prasad M, Yadav HP, Srivastava G, Nakhro N, Kumar G, Sharma N. Treatment Response and Survival with Chemotherapy for Unresectable, Nonmetastatic Cholangiocarcinoma. Euroasian J Hepatogastroenterol 2024; 14:5-8. [PMID: 39022199 PMCID: PMC11249901 DOI: 10.5005/jp-journals-10018-1396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/11/2023] [Indexed: 07/20/2024] Open
Abstract
Background and objectives Limited studies have dwelt upon the treatment of unresectable, nonmetastatic cholangiocarcinoma as a separate entity. Hence, the management protocols are not clearly defined for this subgroup of patients. We aimed to analyze patients treated for unresectable, nonmetastatic cholangiocarcinoma. Materials and methods We analyzed the treatment of patients with unresectable, nonmetastatic cholangiocarcinoma retrospectively. Results A total of 162 cases of cholangiocarcinoma were reported to our center from 2016 to 2019, out of which 54 were unresectable and nonmetastatic. Thirty patients opted for treatment and were the subjects of this study. Of 30 patients, 24 had hyperbilirubinemia, out of which 10 received chemotherapy after biliary drainage procedure. Out of 30 patients, a total of 16 patients had received chemotherapy, while 14 did not. Gemcitabine/Cisplatin was the first-line chemotherapy administered to 9 patients, whereas 5 received Gemcitabine/Capecitabine and 2 received single-agent gemcitabine. Partial response was documented in 6 patients, and 4 patients had stable disease. The median overall survival was 12.04 months in patients who had received chemotherapy and 6.02 months in those who did not receive chemotherapy (p = 0.005). The median progression-free survival was 6.53 months for patients who had received chemotherapy. The aHR for mortality with chemotherapy compared with no chemotherapy was 0.353 (95% CI: 0.154-0.807). Conclusion The study data demonstrate that gemcitabine combined with cisplatin- or capecitabine-based chemotherapy prolongs survival in patients with unresectable and nonmetastatic cholangiocarcinoma. In patients with cholangiocarcinoma associated with jaundice, biliary drainage procedure enables giving chemotherapy. Hyperbilirubinemia persisting despite drainage procedures portends poor prognosis and represents an unmet need. How to cite this article Gupta A, Sahai P, Prasad M, et al. Treatment Response and Survival with Chemotherapy for Unresectable, Nonmetastatic Cholangiocarcinoma. Euroasian J Hepato-Gastroenterol 2024;14(1):5-8.
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Affiliation(s)
- Ajay Gupta
- Department of Medical Oncology, Indraprastha Apollo Hospital, New Delhi, India
| | - Puja Sahai
- Department of Radiation Oncology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Manya Prasad
- Department of Epidemiology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Hanuman Prasad Yadav
- Department of Radiation Oncology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Gagan Srivastava
- Department of Medical Oncology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Nuneno Nakhro
- Department of Medical Oncology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Guresh Kumar
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Namita Sharma
- Department of Medical Oncology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
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Rafat M, Kohsarian M, Bahiraei M, Nikpoor AR. A Comprehensive Study on Signal Transduction and Therapeutic Role of miR-877 in Human Cancers. Adv Biomed Res 2023; 12:118. [PMID: 37434921 PMCID: PMC10331537 DOI: 10.4103/abr.abr_412_21] [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: 12/31/2021] [Revised: 05/07/2022] [Accepted: 05/16/2022] [Indexed: 07/13/2023] Open
Abstract
MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence in order to reach the molecular mechanism and clinical significance of miR-877 in different types of cancer. Dysregulation of miR-877 level in various types of malignancies as bladder cancer, cervical cancer, cholangiocarcinoma, colorectal cancer (CRC), gastric cancer, glioblastoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma, laryngeal squamous cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), oral squamous cell carcinoma, ovarian cancer (OC), pancreatic ductal adenocarcinoma, and renal cell carcinoma (RCC) have reported, significantly increase or decrease in its level, which can be indicated to its function as oncogene or tumor suppressor. MiR-877 is involved in cell proliferation, migration, and invasion through cell cycle pathways in cancer. MiR-877 could be potential a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-877 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis.
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Affiliation(s)
- Milad Rafat
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mahdis Kohsarian
- Department of Biology, Faculty of Science, Guilan University, Rasht, Iran
| | - Mohamad Bahiraei
- Department of Radiology, Besat Hospital, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Amin R. Nikpoor
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
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Ning Z, Yang L, Yan X, Wang D, Hua Y, Shi W, Lin J, Meng Z. Effect and mechanism of Lenvatinib@H-MnO2-FA drug delivery system in targeting intrahepatic cholangiocarcinoma. Curr Pharm Des 2022; 28:743-750. [PMID: 35049427 DOI: 10.2174/1381612828666220113161712] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 12/14/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND To investigate the effects of the Lenvatinib@H-MnO2-FA administration system on the proliferation and apoptosis of Intrahepatic cholangiocarcinoma (ICC) and the underlying molecular mechanism. MATERIALS AND METHODS In this research, hollow MnO2 (H-MnO2) was synthesized via the modified Stöber method, and H-MnO2 was modified with polyethylene glycol-bis (Amine) (NH2-PEG-NH2) and folic acid (FA) to obtain H-MnO2-PEG-FA (H-MnO2-FA). Lenvatinib was coated in the hollow cavity of H-MnO2-PEG-FA to further form a nanometre drug-carrying system (lenvatinib@H-MnO2-PEG-FA). Lenvatinib@H-MnO2-FA was characterized through transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FT-IR) was used to verify that Lenvatinib was loaded on nanoparticles. Functionally, confocal laser scanning microscopy (CLSM), 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine the effect of lenvatinib@H-MnO2-FA on the proliferation and apoptosis of ICC cells (9810 cells). Finally, the protein levels of Raf-1MEK1/2-ERK1/2 signalling pathway components were detected through Western blotting analysis. RESULTS We successfully synthesised a Lenvatinib@H-MnO2-PEG-FA administration system. The resulting nanomaterials had excellent biological stability and improved targeting effects. Functionally, lenvatinib@H-MnO2-FA inhibited the proliferation of 9810 cells. The Bcl-2 protein level was significantly downregulated, and the caspase-3 protein level was significantly upregulated, indicating that lenvatinib@H-MnO2-PEG-FA promoted the apoptosis of 9810 cells. Mechanistically, Lenvatinib@H-MnO2-FA increased the phosphorylation levels of Raf, MEK1/2 and ERK1/2. CONCLUSIONS H-MnO2-FA can more effectively deliver Lenvatinib to inhibit proliferation and promote apoptosis in ICC, could be the promising drug delivery nano-vehicles for delivery drugs.
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Affiliation(s)
- Zhouyu Ning
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Lina Yang
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xia Yan
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Dan Wang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yongqiang Hua
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Weidong Shi
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Junhua Lin
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiqiang Meng
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
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Abstract
Biliary strictures have several etiologies that can broadly be classified into benign and malignant causes. The clinical presentation is variable with strictures identified incidentally on imaging or during the evaluation of routine laboratory abnormalities. Symptoms and cholangitis lead to imaging that can diagnose biliary strictures. The diagnosis and medical management of biliary strictures will be discussed in this article.
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Affiliation(s)
- Terrance Rodrigues
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Justin R Boike
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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13
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Yu Y, Huang S, Chen J, Yu F, Zhang L, Xiang X, Deng J, Fang Z, Li J, Xiong J. An Assessment of Combination of the Camrelizumab With Chemotherapy in Metastatic Biliary Tract Cancers. Cancer Control 2021; 28:10732748211017165. [PMID: 33982628 PMCID: PMC8204626 DOI: 10.1177/10732748211017165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Monoclonal antibodies that target the PD-1 receptor are emerging as promising therapeutic candidates for the treatment of biliary tract cancers (BTCs). The purpose of the current study was to assess the combination of the camrelizumab with chemotherapy as a first-line treatment for metastatic BTCs. METHODS We conducted a prospective single-arm pilot study of PD-1 antibody (camrelizumab 3 mg/kg d1, Q2 W or Q3 W) combined with different chemotherapy regimens as first-line treatment for BTCs. Efficacy endpoints were objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Treatment-related adverse events (TRAEs) were also evaluated. RESULTS Fourteen patients with histologically confirmed BTCs were evaluated. The ORR was 14.3% (95% CI: 1.8 to 42.8) and the DCR was 64.3% (95%CI: 41.7 to 86.9). The median PFS was 6.5 months (95% CI: 3.8 to 9.2), and the 6- and 12-month PFS rates were 61.6% and 12.3%, respectively. The median OS was 9.9 months (95% CI: 7.6 to 12.2), and the 6-and 12-month OS rates were 74.5% and 26.6%, respectively. All patients displayed at least 1 TRAE., and Grade 3 or 4 TRAEs occurred in 6 (42.86%) patients. CONCLUSIONS Camrelizumab combined with chemotherapy as first-line treatment for metastatic BTCs demonstrated acceptable safety and efficacy in our pilot study. These findings warrant prospective controlled clinical trials comparing combinations of camrelizumab and chemotherapy to standard regimens.
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Affiliation(s)
- Yi Yu
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Shanshan Huang
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Jun Chen
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Feng Yu
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Lin Zhang
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Xiaojun Xiang
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Jun Deng
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Ziling Fang
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Junhe Li
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Jianping Xiong
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
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14
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Epidemiology of HPB malignancy in the elderly. Eur J Surg Oncol 2021; 47:503-513. [PMID: 32360064 DOI: 10.1016/j.ejso.2020.03.222] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 03/17/2020] [Accepted: 03/26/2020] [Indexed: 02/08/2023] Open
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Cha BH, Jang MJ, Lee SH. Survival Benefit of Intraductal Radiofrequency Ablation for Malignant Biliary Obstruction: A Systematic Review with Meta-Analysis. Clin Endosc 2021; 54:100-106. [PMID: 33445841 PMCID: PMC7939762 DOI: 10.5946/ce.2020.254] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 10/27/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Cholangiocarcinoma (CCA) is a rare but aggressive disease with a poor survival. Recent trials have shown improved survival with intraductal radiofrequency ablation (RFA) therapy. We performed a systematic review with meta-analysis to determine the survival benefit of endoscopic RFA for unresectable extrahepatic CCA with malignant biliary obstruction (MBO). METHODS A systematic search from 1970 to 2020 was performed in MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials. gov. We selected eligible studies reporting relative risks, hazard ratios (HRs), or odds ratios, adjusted by controlling for confounding factors of survival rate and stent patency duration, among patients with extrahepatic CCA with MBO treated with RFA with stent insertion or stent insertion only. RESULTS A total of eight trials (three randomized and five nonrandomized) with a total of 420 patients were included in the metaanalysis. Pooled overall survival analysis favored RFA treatment with stent insertion (HR, 0.47; 95% confidence interval [CI], 0.34- 0.64; I2=47%; p=0.09); however, no significant difference was found in the duration of stent patency between the groups (HR, 0.79; 95% CI, 0.57-1.09; I2=7%; p=0.36). CONCLUSION RFA therapy with stent insertion may confer a survival benefit compared with stent insertion only in patients with CCA and MBO.
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Affiliation(s)
- Byung Hyo Cha
- Division of Internal Medicine, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates
| | - Myoung-Jin Jang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Risk factors to differentiate between benign proximal biliary strictures and perihilar cholangiocarcinoma. HPB (Oxford) 2020; 22:1753-1758. [PMID: 32321675 DOI: 10.1016/j.hpb.2020.03.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 03/10/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to evaluate potential risk factors associated with benign lesions and perihilar cholangiocarcinoma (PHC) in patients presenting with proximal biliary strictures (PBS). METHODS Patients with PBS who were referred to a specialist HPB centre between 2008 and 2016 were identified. Patients with primary sclerosing cholangitis, metastatic PHC or hilar obstruction by a peripheral tumour were excluded. The final diagnosis was determined either by (1) resection histology or (2) combination of biopsy and clinical course. Multivariable analysis of clinical, laboratory and radiological data was undertaken to identify independent predictors of benign and malignant lesions. RESULTS 155 consecutive patients were identified, including 25 patients (16%) with benign PBS. Abdominal pain (odds ratio [OR] 3.36; p = 0.027), serum CA19.9 < 100 U/ml (OR 10.35; p = 0.001), and absence of mass on imaging (OR 4.66; p = 0.004) were all associated with the presence of benign lesions on multivariable analysis. CONCLUSIONS This study has identified several independent variables that may differentiate between benign and malignant proximal biliary strictures. A larger multi-institutional study would be warranted to validate these findings, and to develop a risk score to stratify patients with suspected PHC.
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Martin Huertas R, Fuentes-Mateos R, Serrano Domingo JJ, Corral de la Fuente E, Rodríguez-Garrote M. Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report. World J Clin Oncol 2020; 11:844-853. [PMID: 33200077 PMCID: PMC7643189 DOI: 10.5306/wjco.v11.i10.844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/31/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors. Most patients have advanced-stage or unresectable disease at presentation, and the systemic therapies have limited efficacy. Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free taxane that has been approved for the treatment of some cancers such as breast, non-small cell lung and pancreatic cancer, however it has not been applied to treat cholangiocarcinoma. We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma, yet no phase 3 trials have been made.
CASE SUMMARY A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma. Surgery was performed, followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine; although, the gemcitabine was suspended due to allergic reaction after two cycles. In April 2019, metastatic cholangiocarcinoma relapse was diagnosed, and a first-line treatment with FOLFOX scheme was started. Eight cycles were administered, producing an initial clinical improvement and decrease in blood tumor marker levels. Radiological and serological progression was noted in September 2019. As a second-line treatment, FOLFIRI was not recommended due to risk of worsening the patient’s tumor-related diarrhea. A combination therapy with gemcitabine was not feasible, as the patient had previously suffered from an allergic reaction to this treatment. We decided to use nab-paclitaxel as a second-line treatment, and four cycles were administered. Both clinical and serological responses were observed, and a radiological mixed response was also noted.
CONCLUSION Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy, which should be studied in combination with other types of treatment (chemotherapy, fibroblast growth factor receptor inhibitors).
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Affiliation(s)
| | - Raquel Fuentes-Mateos
- Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid 28034, Spain
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Mazloom A, Ghalehsari N, Gazivoda V, Nimkar N, Paul S, Gregos P, Rateshwar J, Khan U. Role of Immune Checkpoint Inhibitors in Gastrointestinal Malignancies. J Clin Med 2020; 9:E2533. [PMID: 32781500 PMCID: PMC7463795 DOI: 10.3390/jcm9082533] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/28/2020] [Accepted: 07/31/2020] [Indexed: 12/24/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid and hematological malignancies. ICIs are not only able to produce long and durable responses, but also very well tolerated by patients. There are several approved indications of use of ICIs in treatment of metastatic gastrointestinal malignancies including gastric, esophageal, colorectal and hepatocellular carcinoma. In addition, ICIs can be used in microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB) tumors in chemotherapy-resistant setting. Despite having good efficacy and superior safety profile, ICIs are clinically active in small subset of patients, therefore, there is a huge unmet need to enhance their efficacy and discover new predictive biomarkers. There are several ongoing clinical trials that are exploring the role of ICIs in various gastrointestinal cancers either as single agent or in combination with chemotherapy, radiation therapy, targeted agents or other immunotherapeutic agents. In this review, we discuss the published and ongoing trials for ICIs in gastrointestinal malignancies, including esophageal, gastric cancer, pancreatic, hepatocellular, biliary tract, colorectal and anal cancers. Specifically, we focus on the use of ICIs in each line of therapy and discuss the future directions of these agents in each type of gastrointestinal cancer.
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Affiliation(s)
- Anita Mazloom
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
| | - Nima Ghalehsari
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
| | - Victor Gazivoda
- Department of Surgery, Maimonides Medical Center, Brooklyn, NY 11219, USA;
| | - Neil Nimkar
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
| | - Sonal Paul
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
| | - Peter Gregos
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
| | - Janice Rateshwar
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
| | - Uqba Khan
- Department of Medicine, NewYork-Presbyterian Brooklyn Methodist Hospital—Weill Cornell Medicine, Brooklyn, NY 11215, USA; (A.M.); (N.G.); (N.N.); (S.P.); (P.G.); (J.R.)
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The effect and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma: an updated meta-analysis. World J Surg Oncol 2020; 18:174. [PMID: 32682432 PMCID: PMC7368977 DOI: 10.1186/s12957-020-01904-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 06/02/2020] [Indexed: 02/08/2023] Open
Abstract
Background The effect and safety of preoperative biliary drainage (PBD) in patients with perihilar cholangiocarcinoma are still controversial; the aim of our study is to evaluate all aspects of PBD. Methods All included studies featured PBD versus non-PBD (NPBD) groups were from 1996 to 2019 and were extracted from Cochrane Library, Embase, PubMed, and Science Citation Index Expanded. Results Sixteen studies met the inclusion criteria and were included in this analysis. PBD may lead to a significantly higher incidence of overall morbidities (OR 0.67, 95% CI 0.53, 0.85; P = 0.0009) and intraoperative transfusions (OR 0.72, 95% CI 0.55, 0.94; P = 0.02); moreover, bile leakage (OR 0.58, 95% CI 0.24, 1.41; P = 0.04), infection (OR 0.31, 95% CI 0.20, 0.47; P < 0.00001), and cholangitis (OR 0.18, 95% CI 0.007, 0.48; P = 0.0007) are also related to PBD. However, NPBD was associated with more frequent hepatic insufficiency (OR 3.09, 95% CI 1.15, 8.31; P = 0.03). In the subgroup meta-analysis, the differences in the outcomes of bile leakage and overall morbidity lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was above 15 mg/dl. Conclusion Meta-analysis demonstrated that compared to NPBD, PBD is associated with a greater risk of several kinds of infection and morbidities, but its ability to reduce postoperative hepatic insufficiency cannot be ignored. In patients with a high TSB concentration, PBD tends to be a better choice. However, these results need to be confirmed in a future prospective randomized trial with large samples to clarify the effects and find a specific TSB concentration for PBD.
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Aquina CT, Pawlik TM, Ejaz A. Cholangiocarcinoma: three different entities based on location. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:738. [PMID: 32647663 PMCID: PMC7333109 DOI: 10.21037/atm.2020.03.167] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Christopher T Aquina
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Aslam Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
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21
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Lamarca A, Barriuso J, McNamara MG, Valle JW. Molecular targeted therapies: Ready for "prime time" in biliary tract cancer. J Hepatol 2020; 73:170-185. [PMID: 32171892 DOI: 10.1016/j.jhep.2020.03.007] [Citation(s) in RCA: 254] [Impact Index Per Article: 50.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/02/2020] [Accepted: 03/03/2020] [Indexed: 12/13/2022]
Abstract
The prognosis for patients with biliary tract cancers (cholangiocarcinoma and gallbladder cancer) is poor, while the incidence of these cancers is increasing. Most patients are diagnosed with advanced disease when treatment options are limited to palliative approaches, mainly focused on chemotherapy. In recent years, novel treatment targets of relevance to biliary tract cancers, mainly present in patients with intrahepatic cholangiocarcinoma, have been identified and are rapidly changing the field. These include fibroblast growth factor receptor (FGFR) fusions and isocitrate dehydrogenase (IDH)-1 and -2 mutations which are each present in around 10-20% of patients with intrahepatic cholangiocarcinoma. In addition, inhibition of other pathways/molecules is currently being explored, including human epidermal growth factor receptor (HER) family members, the Wnt pathway, neurotropic tyrosine kinase receptor (NTRK) fusions and BRAF mutations. The IDH1 inhibitor ivosidenib has already been tested in a phase III clinical trial in pretreated cholangiocarcinoma and showed benefit in terms of progression-free survival. Multiple FGFR inhibitors have consistently shown high response rates in phase II/III trials, especially for patients harbouring FGFR2 fusions. Herein, we provide an overview of the status of targeted therapies in biliary tract cancers, discussing the current clinical development of IDH and FGFR inhibitors in detail, as well as reviewing current caveats and future steps.
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Affiliation(s)
- Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
| | - Jorge Barriuso
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Mairéad G McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
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Fukasawa Y, Takano S, Fukasawa M, Maekawa S, Kadokura M, Shindo H, Takahashi E, Hirose S, Kawakami S, Hayakawa H, Yamaguchi T, Nakayama Y, Inoue T, Sato T, Enomoto N. Form-Vessel Classification of Cholangioscopy Findings to Diagnose Biliary Tract Carcinoma's Superficial Spread. Int J Mol Sci 2020; 21:ijms21093311. [PMID: 32392821 PMCID: PMC7246671 DOI: 10.3390/ijms21093311] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 04/29/2020] [Accepted: 05/05/2020] [Indexed: 12/15/2022] Open
Abstract
We aimed to evaluate a newly developed peroral cholangioscopy (POCS) classification system by comparing classified lesions with histological and genetic findings. We analyzed 30 biopsied specimens from 11 patients with biliary tract cancer (BTC) who underwent POCS. An original classification of POCS findings was made based on the biliary surface's form (F factor, 4 grades) and vessel structure (V-factor, 3 grades). Findings were then compared with those of corresponding biopsy specimens analyzed histologically and by next-generation sequencing to identify somatic mutations. In addition, the histology of postoperative surgical stumps and preoperative POCS findings were compared. Histological malignancy rate in biopsied specimens increased with increasing F- and V-factor scores (F1, 0%; F1, 25%; F3, 50%; F4, 62.5%; p = 0.0015; V1, 0%; V2, 20%; V3, 70%; p < 0.001). Furthermore, we observed a statistically significant increase of the mutant allele frequency of mutated genes with increasing F- and V-factor scores (F factor, p = 0.0050; V-factor, p < 0.001). All surgical stumps were accurately diagnosed using POCS findings. The F-V classification of POCS findings is both histologically and genetically valid and will contribute to the methods of diagnosing the superficial spread of BTC tumors.
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23
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Lamarca A, Edeline J, McNamara MG, Hubner RA, Nagino M, Bridgewater J, Primrose J, Valle JW. Current standards and future perspectives in adjuvant treatment for biliary tract cancers. Cancer Treat Rev 2020; 84:101936. [PMID: 31986437 DOI: 10.1016/j.ctrv.2019.101936] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 11/23/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Abstract
Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60-70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies. Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community. This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.
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Affiliation(s)
- Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
| | - Julien Edeline
- Department of Medical Oncology, Centre Eugene Marquis, Rennes, France
| | - Mairéad G McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Richard A Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Masato Nagino
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - John Bridgewater
- Department of Medical Oncology, UCL Cancer Institute, London, United Kingdom
| | - John Primrose
- Department of Surgery, University of Southampton, Southampton, United Kingdom
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
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24
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Aghaie Meybodi M, Shakoor D, Nanavati J, Ichkhanian Y, Vosoughi K, Brewer Gutierrez OI, Kalloo AN, Singh V, Kumbhari V, Ngamruengphong S, Khashab MA. Unilateral versus bilateral endoscopic stenting in patients with unresectable malignant hilar obstruction: a systematic review and meta-analysis. Endosc Int Open 2020; 8:E281-E290. [PMID: 32118102 PMCID: PMC7035140 DOI: 10.1055/a-1067-4326] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 10/16/2019] [Indexed: 02/06/2023] Open
Abstract
Background and study aims Endoscopic stent placement is used for palliative management of unresectable malignant hilar obstruction, which could be achieved by either unilateral or bilateral stent insertion. Materials and methods A literature search was performed to identify studies that reported outcomes of metallic biliary stent placement in patients with malignant hilar obstruction. Weighted pooled rates (WPR) along with 95 % confidence intervals (95 %CI) were calculated to determine and compare outcomes including technical and functional success, early and late adverse events, post procedure cholangitis, and stent occlusion between two groups. Results A total of 21 studies with 1292 patients were included. WPR of technical success was significantly higher in the unilateral group (97 %, 95 %CI: 93 -98 %) vs. bilateral group (89 %, 95 %CI: 84 -92 %) ( P = 0.0.003). WPR for functional success in the unilateral and bilateral groups were 96 % (95 %CI: 91 -98 %) and 94 % (95 %CI: 91 -97 %), respectively ( P = 0.48). The rate of early and late complications was comparable between the two groups. Conclusion In patients with unresectable malignant hilar obstruction, unilateral and bilateral metallic stenting techniques are comparable in terms of efficacy and safety.
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Affiliation(s)
- Mohamad Aghaie Meybodi
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Delaram Shakoor
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Maryland, United States
| | - Julie Nanavati
- Welch Medical Library, Johns Hopkins University, Baltimore, Maryland, United States
| | - Yervant Ichkhanian
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Kia Vosoughi
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Olaya I. Brewer Gutierrez
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Anthony N. Kalloo
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Vikesh Singh
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Vivek Kumbhari
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Saowanee Ngamruengphong
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
| | - Mouen A. Khashab
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States,Corresponding author Mouen Khashab MD, Associate Professor of Medicine, Director of Therapeutic Endoscopy Division of Gastroenterology and HepatologyJohns Hopkins Medical Institutions1800 Orleans StSheikh Zayad 7E Rm 7125GBaltimore, MD 21224+1-443-287-1960
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25
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Watanabe Y, Matsuyama Y, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, Takayama T, Nakashima O, Kudo M. Effect of surgical margin width after R0 resection for intrahepatic cholangiocarcinoma: A nationwide survey of the Liver Cancer Study Group of Japan. Surgery 2020; 167:793-802. [PMID: 32044110 DOI: 10.1016/j.surg.2019.12.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/13/2019] [Accepted: 12/18/2019] [Indexed: 01/22/2023]
Abstract
BACKGROUND Data are inconsistent regarding the effects of a wide surgical margin for intrahepatic cholangiocarcinoma on recurrence-free survival and overall survival. This study was performed to investigate the effect of surgical margin width in patients undergoing R0 resection for intrahepatic cholangiocarcinoma, using a nationwide database in Japan. METHODS In total, 635 patients with intrahepatic cholangiocarcinoma who were treated by an R0 resection from 2000 to 2007 were identified from the database of a Japanese nationwide survey. Patients were divided into quartiles of the surgical margin width as follows: marginal (<1 mm), narrow (1-4 mm), intermediate (5-9 mm), and wide groups (≥10 mm). Multivariable Cox regression models for recurrence-free survival and overall survival were constructed with adjustment for preoperative and postoperative clinicopathologic factors. RESULTS Compared with the marginal group, the risk-adjusted hazard ratios (95% confidence intervals) in the narrow, intermediate, and wide groups for recurrence-free survival were 0.92 (0.62-1.37), 0.91 (0.61-1.37), and 0.81 (0.56-1.17), and those for overall survival were 0.79 (0.51-1.24), 0.93 (0.59-1.47), and 0.70 (0.46-1.08), respectively. In 398 patients without lymph node metastasis, the hazard ratios for overall survival were 0.62 (0.34-1.11), 0.63 (0.34-1.17), and 0.51 (0.29-0.90), and those of mass-forming type intrahepatic cholangiocarcinoma were 0.48 (0.21-1.08), 0.43 (0.19-0.96), and 0.40 (0.19-0.82), respectively. CONCLUSION Surgical margin width appears to have a limited effect on the prognosis of intrahepatic cholangiocarcinoma except in patients without lymph node metastasis, where a wide surgical margin is associated with favorable outcomes. This survival benefit of a wide surgical margin is especially apparent for the mass-forming type intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Saitama, Japan; Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan
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Ahmed O, Lee JH. SEMS Insertion for Hilar Stricture: Who, When, and Why? ADVANCED ERCP FOR COMPLICATED AND REFRACTORY BILIARY AND PANCREATIC DISEASES 2020:69-78. [DOI: 10.1007/978-981-13-0608-2_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Turan İ, Özütemiz AÖ, Ersöz G, Karasu Z, Günşar F, Tekin F, Çoker A, Sözbilen EM, Ünalp Ö, Uguz A, Göker E, Yılmaz F, Nart D, Caner A, Haydaroğlu A, Akarca US. Karaciğer, safra kesesi ve safra yolu kanserlerinde epidemiyoloji ve sağ kalım özellikleri. EGE TIP DERGISI 2019. [DOI: 10.19161/etd.668367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Jung P, Cho EH, Kim SB, Kim RG. Comparison of the clinical results of surgical resection for extrahepatic cholangiocarcinomas: Hilar cholangiocarcinoma and mid-to-distal cholangiocarcinoma. Ann Hepatobiliary Pancreat Surg 2019; 23:319-326. [PMID: 31824996 PMCID: PMC6893051 DOI: 10.14701/ahbps.2019.23.4.319] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 07/17/2019] [Accepted: 07/25/2019] [Indexed: 11/30/2022] Open
Abstract
Backgrounds/Aims Hilar cholangiocarcinomas (HLC) are known to have worse prognoses than mid-to-distal cholangiocarcinomas (CBDC). We analyzed the clinical results of surgical resections for extrahepatic cholangiocarcinomas to validate the differences in the prognoses of HLC and CBDC. Methods Two hundred and eighty-one patients underwent curative surgical resections for extrahepatic cholangiocarcinomas at the Department of Surgery in the Korea Cancer Center Hospital. Among them, we analyzed the T2 and T3 patients and compared the clinical results between those with HLC (n=74) and those with CBDC (n=65). Results The rate of R1 resections was significantly higher in the HLC patients compared to the CBDC patients (31.1% vs 12.3%, p=0.006). The overall survival rate of the T2/T3 patients was lower in the HLC group than in the CBDC group (24.5% vs 51.7, p=0.039). The recurrence-free survival rate was 23.3% in the HCL patients and 50.9% in the CBDC patients (p=0.06). In the subgroup analysis, the survival rates were not different in patients who had lymph node metastases or in patients who underwent R1 resections between the HLC and CBDC patients. Poor independent prognostic factors for the overall and recurrence-free survival rates in the T2/T3 extrahepatic cholangiocarcinoma patients were the presence of lymph node metastases and the hilar locations of tumor. Conclusions HLC patients had poorer prognoses than CBDC patients. However, in patients with lymph node metastases, the prognosis was poor and was not different between the HLC and CBDC patients. Other adjuvant treatment methods are needed for extrahepatic cholangiocarcinoma patients with lymph node metastases to improve their prognoses.
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Affiliation(s)
- Pyung Jung
- Department of Surgery, Korean Cancer Center Hospital, Seoul, Korea
| | - Eung-Ho Cho
- Department of Surgery, Korean Cancer Center Hospital, Seoul, Korea
| | - Sang-Bum Kim
- Department of Surgery, Korean Cancer Center Hospital, Seoul, Korea
| | - Ryoung-Go Kim
- Department of Surgery, Dongnam Institution of Radiological and Medical Science, Busan, Korea
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Turgeon MK, Maithel SK. Cholangiocarcinoma: a site-specific update on the current state of surgical management and multi-modality therapy. Chin Clin Oncol 2019; 9:4. [PMID: 31500433 DOI: 10.21037/cco.2019.08.09] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 08/07/2019] [Indexed: 12/14/2022]
Abstract
Biliary tract cancers (BTC) are rare, heterogeneous malignancies that include cholangiocarcinoma and gallbladder cancer (GBC). Cholangiocarcinoma subtypes differ by anatomic location and molecular profile. Currently, resection with lymphadenectomy is the only curative treatment of locally advanced cholangiocarcinoma. Given the high risk of recurrence, multi-modality therapy spanning surgery, chemotherapy, and radiation therapy should be considered. Current data is discordant and there is limited prospective data to support an optimal treatment regimen, though recent studies have demonstrated the utility of adjuvant chemotherapy and chemoradiation in specific settings and patient populations. There is a potential role for neoadjuvant chemotherapy in patients with resectable disease or chemoradiation in select patients with unresectable, locally advanced disease. Randomized clinical trials are necessary to establish the effectiveness of therapies specific to disease sites, especially with the emerging role of immunotherapy and targeted therapy to actionable mutations.
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Affiliation(s)
- Michael K Turgeon
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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Mukai Y, Matsuyama R, Koike I, Kumamoto T, Kaizu H, Homma Y, Takano S, Sawada Y, Sugiura M, Yabushita Y, Ito E, Sato M, Endo I, Hata M. Outcome of postoperative radiation therapy for cholangiocarcinoma and analysis of dose-volume histogram of remnant liver. Medicine (Baltimore) 2019; 98:e16673. [PMID: 31374045 PMCID: PMC6709052 DOI: 10.1097/md.0000000000016673] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.
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Affiliation(s)
| | - Ryusei Matsuyama
- Departments of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan
| | | | - Takafumi Kumamoto
- Departments of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan
| | | | - Yuki Homma
- Departments of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan
| | | | - Yu Sawada
- Departments of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan
| | | | - Yasuhiro Yabushita
- Departments of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan
| | - Eiko Ito
- Department of Radiation Oncology
| | | | - Itaru Endo
- Departments of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan
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Caparica R, Lengelé A, Bekolo W, Hendlisz A. FOLFIRI as second-line treatment of metastatic biliary tract cancer patients. Autops Case Rep 2019; 9:e2019087. [PMID: 31528622 PMCID: PMC6738847 DOI: 10.4322/acr.2019.087] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 05/10/2019] [Indexed: 12/24/2022]
Abstract
The combination of cisplatin and gemcitabine is the standard first-line treatment of metastatic biliary tract cancer (BTC) patients. The benefit of second-line chemotherapy in these patients is controversial. This study aims to evaluate the activity of FOLFIRI (fluorouracil and irinotecan) after failure to the first-line platinum and gemcitabine-based chemotherapy in metastatic BTC patients. We present a single-institution, retrospective cohort study. Patients with locally advanced or metastatic BTC who progressed after at least one line of chemotherapy, consecutively treated at our Institution between 2007 and 2017 were included. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), clinical benefit rate (CBR) and safety profile of FOLFIRI. Twelve patients were included in the analysis, with a median follow up of 5 months (95% CI 2.77-7.20). The median number of cycles received was 3 (range 1 to 9). Four grade 3 toxicities were recorded; no grade 4 toxicities and no treatment-related deaths occurred. The median PFS was 1.7 months (95% CI; 0.66-2.67), and median OS was 5 months (95% CI; 2.77-7.20). Two patients presented stable disease, providing a CBR of 17%. We concluded that FOLFIRI presented a favorable toxicity profile and a modest activity in metastatic BTC patients who had progressed to platinum and gemcitabine and may be considered in patients who are able to tolerate additional lines of chemotherapy. Immunotherapy and targeted therapies selected according to the tumoral genomic profile are promising alternatives to improve the outcomes of second-line treatment in BTC.
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Affiliation(s)
- Rafael Caparica
- Institut Jules Bordet and Université Libre de Bruxelles (ULB), Department of Medical Oncology, Brussels, Belgium
| | | | - Winnie Bekolo
- Douala General Hospital, University of Douala, Cameroon
| | - Alain Hendlisz
- Institut Jules Bordet and Université Libre de Bruxelles (ULB), Department of Medical Oncology, Brussels, Belgium
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Uhlig J, Sellers CM, Cha C, Khan SA, Lacy J, Stein SM, Kim HS. Intrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database. Ann Surg Oncol 2019; 26:1993-2000. [PMID: 30693451 DOI: 10.1245/s10434-019-07175-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Indexed: 12/22/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate socioeconomic discrepancies in current treatment approaches and survival trends among patients with intrahepatic cholangiocarcinoma (ICC). METHODS The 2004-2015 National Cancer Database was retrospectively analyzed for histopathologically proven ICC. Treatment predictors were evaluated using multinomial logistic regression and overall survival via multivariable Cox models. RESULTS Overall, 12,837 ICC patients were included. Multiple factors influenced treatment allocation, including age, education, comorbidities, cancer stage, grade, treatment center, and US state region (multivariable p < 0.05). The highest surgery rates were observed in the Middle Atlantic (28.7%) and lowest rates were observed in the Mountain States (18.4%). Decreased ICC treatment likelihood was observed for male African Americans with Medicaid insurance and those with low income (multivariable p < 0.05). Socioeconomic treatment discrepancies translated into decreased overall survival for patients of male sex (vs. female; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.16-1.26, p < 0.001), with low income (< $37,999 vs. ≥ $63,000 annually; HR 1.07, 95% CI 1.01-1.14, p = 0.032), and with Medicaid insurance (vs. private insurance; HR 1.13, 95% CI 1.04-1.23, p = 0.006). Both surgical and non-surgical ICC management showed increased survival compared with no treatment, with the longest survival for surgery (5-year overall survival for surgery, 33.5%; interventional oncology, 11.8%; radiation oncology/chemotherapy, 4.4%; no treatment, 3.3%). Among non-surgically treated patients, interventional oncology yielded the longest survival versus radiation oncology/chemotherapy (HR 0.73, 95% CI 0.65-0.82, p < 0.001). CONCLUSIONS ICC treatment allocation and outcome demonstrated a marked variation depending on socioeconomic status, demography, cancer factors, and US geography. Healthcare providers should address these discrepancies by providing surgery and interventional oncology as first-line treatment to all eligible patients, with special attention to the vulnerable populations identified in this study.
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Affiliation(s)
- Johannes Uhlig
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.,Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Goettingen, Germany
| | - Cortlandt M Sellers
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA
| | - Charles Cha
- Division of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.,Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA
| | - Sajid A Khan
- Division of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.,Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA
| | - Jill Lacy
- Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.,Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Stacey M Stein
- Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.,Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Hyun S Kim
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA. .,Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. .,Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
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Xiong JP, Long JY, Xu WY, Bian J, Huang HC, Bai Y, Xu YY, Zhao HT, Lu X. Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery. World J Gastrointest Oncol 2019; 11:39-47. [PMID: 30984349 PMCID: PMC6451927 DOI: 10.4251/wjgo.v11.i1.39] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 10/29/2018] [Accepted: 12/05/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in cholangiocarcinoma (CCA) subjects receiving surgery.
METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics (including AAPR) were analyzed to determine predictors of post-operative overall survival and recurrence-free survival (RFS). In addition, univariate and multivariate Cox proportional hazards models were conducted, followed by application of time-dependent receiver operating curves to identify the optimal cut-off.
RESULTS Univariate and multivariate analyses revealed both decreased overall survival [hazard ratio (HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival (HR: 2.31, 95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥ 0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253 (83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low (< 0.41) AAPR group, which were significantly lower than those in the high (≥ 0.41) AAPR group (81.7%, 53.9%, and 33.4%, respectively) (P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.
CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.
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Affiliation(s)
- Jian-Ping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jun-Yu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wei-Yu Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Han-Chun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yi Bai
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yi-Yao Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hai-Tao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Habermehl G, Ko J. Cutaneous Metastases: A Review and Diagnostic Approach to Tumors of Unknown Origin. Arch Pathol Lab Med 2018; 143:943-957. [PMID: 30605024 DOI: 10.5858/arpa.2018-0051-ra] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Cutaneous metastases from a distant malignancy are a diagnostic challenge for pathologists. Secondary involvement of the skin by a metastatic process portends a much worse clinical prognosis than any primary cutaneous malignant mimickers. Immunohistochemical staining methods continue to evolve and are of paramount importance in diagnosis. OBJECTIVE.— To review the clinical, histopathologic, and immunohistochemical staining patterns for commonly encountered entities and discuss potential pitfalls in diagnosis. A practical guide useful in approaching cutaneous metastases of unknown primary is outlined. DATA SOURCES.— An extensive search and review of literature in PubMed was performed, processed, and condensed. CONCLUSIONS.— Cutaneous metastases have broad histopathologic patterns. They are nearly always dermal based, with an overall foreign appearance. They can be single papules/nodules or multiple in number, mimicking an inflammatory or infectious process. Ultimately, immunohistochemistry remains an essential diagnostic tool, and clinical correlation is paramount in the workup of these entities.
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Affiliation(s)
- Gabriel Habermehl
- From the Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio
| | - Jennifer Ko
- From the Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio
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Xiong J, Yin Z, Xu W, Shen Z, Li Y, Lu X. Alcoholic liver disease and risk of cholangiocarcinoma: a systematic review and meta-analysis. Onco Targets Ther 2018; 11:8211-8219. [PMID: 30538490 PMCID: PMC6251364 DOI: 10.2147/ott.s184444] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Background With the purpose of elevating the risk of cholangiocarcinoma (CCA), alcoholic liver disease (ALD) was shown. Nonetheless, the findings were controversial. Herein, a meta-analysis and a systematic review were conducted to study the relation as mentioned above. Methods This study searched PubMed, EMBASE, and SI Web of Science carefully for the related studies published prior to March 2018, followed by the random-effects model to calculate the values of pooled risk ratio with 95% CIs. In addition, the analyses of sensitivity and subgroup were carried out to further confirm the stability of the outcomes. Results Seven articles, consisting of 413,483 healthy controls and 8,962 CCA patients, were included in this meta-analysis. When compared with normal controls, patients with ALD had an enhanced 3.92-fold CCA risk, with studies being heterogeneous (95% CI =1.96–5.07; OR =3.92; I2 =70.2%). However, subgroup analysis showed that ALD had the enhanced risk of intrahepatic cholangiocarcinoma (ICC), instead of extrahepatic cholangiocarcinoma (ECC) (ICC: 95% CI =3.06–5.92, OR =4.49; ECC: 95% CI =0.90–3.35, OR =2.12). Additionally, when the analysis was stratified by the geographic area, positive association was observed only in western countries rather than eastern countries (western nations: 95% CI =3.34–6.96, OR =5.15; eastern nations: 95% CI =0.38–3.91, OR =2.14). And no essential bias was published. Conclusion ALD was greatly associated with the enhanced risk of CCA by 3.92-fold, especially in the ICC.
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Affiliation(s)
- Jianping Xiong
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China, ;
| | - ZiJun Yin
- Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Weiyu Xu
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China, ;
| | - Zheng Shen
- Department of Orthopaedics, Anhui No. 2 Provincial People's Hospital, Hefei 230041, China
| | - Ye Li
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China, ;
| | - Xin Lu
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China, ;
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Sumiyoshi T, Shima Y, Okabayashi T, Negoro Y, Shimada Y, Iwata J, Matsumoto M, Hata Y, Noda Y, Sui K, Sueda T. Chemoradiotherapy for Initially Unresectable Locally Advanced Cholangiocarcinoma. World J Surg 2018; 42:2910-2918. [PMID: 29511872 DOI: 10.1007/s00268-018-4558-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. METHODS Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy. Fourteen of the 15 patients received oral S-1 chemotherapy. Radiotherapy was administered with 50 Gy for each patient. After chemoradiotherapy, the resectability of each cholangiocarcinoma was reexamined. RESULTS Of the 15 patients with initially unresectable locally advanced cholangiocarcinoma, 11 (73.3%) were judged to have resectable cholangiocarcinoma after chemoradiotherapy, and received radical hepatectomy (R0 resection in 9 patients). Among the 11 patients who underwent surgical resection, 4 had recurrence-free survival and the median survival time (MST) was 37 months. The overall 1-, 2-, and 5-year survival rates were 80.8, 70.7 and 23.6%, respectively. Among the 4 patients who were unable to receive surgery, 3 died of the primary disease and the MST was 10 months. The overall 1- and 2-year survival rates were 37.5 and 0%, respectively. Patients who received radical surgery had significantly longer survival time than those who were unable to receive surgery (p = 0.027). CONCLUSIONS Chemoradiotherapy allowed patients with initially unresectable locally advanced cholangiocarcinomas to be reclassified as surgical candidates in a substantial proportion. Chemoradiotherapy might be one of the treatment options for similarly advanced cholangiocarcinomas.
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Affiliation(s)
- Tatsuaki Sumiyoshi
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan.
| | - Yasuo Shima
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan
| | - Takehiro Okabayashi
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan
| | - Yuji Negoro
- Department of Medical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Yasuhiro Shimada
- Department of Medical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Jun Iwata
- Departments of Diagnostic Pathology, Kochi Health Sciences Center, Kochi, Japan
| | - Manabu Matsumoto
- Departments of Diagnostic Pathology, Kochi Health Sciences Center, Kochi, Japan
| | - Yasuhiro Hata
- Departments of Radiology, Kochi Health Sciences Center, Kochi, Japan
| | - Yoshihiro Noda
- Departments of Radiology, Kochi Health Sciences Center, Kochi, Japan
| | - Kenta Sui
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan
| | - Taijiro Sueda
- Department of Surgery, Applied Life Sciences Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Xiong J, Xu W, Bian J, Huang H, Bai Y, Xu Y, Lu X, Zhao H. Aspirin use is associated with a reduced risk of cholangiocarcinoma: a systematic review and meta-analysis. Cancer Manag Res 2018; 10:4095-4104. [PMID: 30323665 PMCID: PMC6173493 DOI: 10.2147/cmar.s173197] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Aspirin has been revealed to probably decrease the risk of cholangiocarcinoma (CCC), which, nevertheless, is of controversy. To this end, a systematic review and meta-analysis was performed to investigate the above-described association. Methods We thoroughly searched PubMed, EMBASE, and ISI Web of Science for relevant studies published prior to October 2017, followed by random-effects model for calculation of pooled ORs and corresponding 95% CIs. Additionally, subgroup and sensitivity analyses were carried out to confirm whether the outcomes were stable. Results Nine articles, consisting of 12,535 CCC patients and 92,97,450 healthy controls, were enrolled in this study. We demonstrated a significantly decreased risk of CCC in those using aspirin, with studies being heterogeneous (OR=0.69; CI=0.43–0.94; I2=97.4%). Moreover, this relationship was detected only in case-control studies (OR=0.65; 95% CI=0.38–0.93), rather than cohort studies (OR=0.94; 95% CI=0.70–1.27). Besides, in separated analysis of intrahepatic CCC and extrahepatic CCC, aspirin was more strongly correlated with a declined risk of intrahepatic CCC (OR=0.33, 95% CI=0.26–0.39; I2=93.6%) than the risk of extrahepatic CCC (OR=0.56, 95% CI=0.41–0.73; I2=0%). Conclusion Collectively, the aspirin administration was correlated with a significant 31% decreased risk of CCC, particularly in the intrahepatic CCC.
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Affiliation(s)
- Jianping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Weiyu Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Hanchun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Yi Bai
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China, ;
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Chang WW, Hsiao PK, Qin L, Chang CL, Chow JM, Wu SY. Treatment outcomes for unresectable intrahepatic cholangiocarcinoma: Nationwide, population-based, cohort study based on propensity score matching with the Mahalanobis metric. Radiother Oncol 2018; 129:284-292. [PMID: 30279046 DOI: 10.1016/j.radonc.2018.09.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/15/2018] [Accepted: 09/15/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE No prospective randomized trials have been conducted to date to evaluate the efficacy of palliation of pain or jaundice without treatment, definitive concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiotherapy (CTRT), or chemotherapy (CT) alone for treating unresectable intrahepatic cholangiocarcinoma (ICC). We designed a nationwide, population-based, cohort study to determine the effects of different treatments on patients with unresectable ICC using propensity score matching (PSM) with the Mahalanobis metric. PATIENTS AND METHODS We classified patients with unresectable ICC from the Taiwan Cancer Registry database into the following 4 treatment groups: group 1, definitive CCRT; group 2, sequential CTRT; group 3, no treatment (palliative therapy for relief of pain, pruritus, or jaundice); and group 4, CT alone. Confounding factors among the 4 treatment groups were minimized through propensity score matching (PSM). RESULTS After PSM, the final cohort consisted of 844 patients (211 patients in each of the 4 groups). In both univariable and multivariable Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) derived for groups 1 and 2 compared with group 4 were 0.65 (0.59-0.71) and 0.95 (0.83-1.48), respectively. Furthermore, an aHR (95% CI) of 2.25 (1.89-2.67) was derived for significant independent prognostic risk factors for poor overall survival for group 3 compared with group 4. CONCLUSIONS Definitive CCRT is the optimal therapy for patients with unresectable ICC without distant metastasis.
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Affiliation(s)
- Wei-Wen Chang
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Ping-Kun Hsiao
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Lei Qin
- School of Statistics, University of International Business and Economics, Beijing, China
| | - Chia-Lun Chang
- Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Jyh-Ming Chow
- Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Szu-Yuan Wu
- Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biotechnology, Chinese Culture University, YangMingShan, Taipei 11114, Taiwan.
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Xiong J, Lu X, Xu W, Bai Y, Huang H, Bian J, Zhang L, Long J, Xu Y, Wang Z, Zhao H. Metabolic syndrome and the risk of cholangiocarcinoma: a hospital-based case-control study in China. Cancer Manag Res 2018; 10:3849-3855. [PMID: 30288116 PMCID: PMC6161710 DOI: 10.2147/cmar.s175628] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background Metabolic syndrome is regarded as a risk factor for hepatocellular carcinoma. However, no research has been conducted to investigate the association between metabolic syndrome and cholangiocarcinoma (CCA), especially in the Chinese population. Herein, a hospital-based case–control study was carried out in China to explore the association between metabolic syndrome and CCA risk. Patients and methods In this study, 303 CCA patients (136 intrahepatic cholangiocarcinoma [ICC] and 167 extrahepatic cholangiocarcinoma [ECC]) were included, who were observed at Peking Union Medical College Hospital (PUMCH), from 2002 to 2014. Healthy controls were randomly selected from the database of PUMPH Health Screening Center. We retrospectively extracted metabolic syndrome and other possible risk factors from clinical records, followed by investigation of the relationship with CCA via calculation of ORs and 95% CIs using logistic regression analysis. Results Metabolic syndrome was significantly and positively correlated with all CCA subtypes, with adjusted ORs (AORs) of 0.35 (95% CI =0.29–0.42) and 0.29 (95% CI =0.19–0.44) for ICC and ECC, respectively (both P<0.001). Dyslipoproteinemia harbored a stronger relationship with ICC (OR =3.16; 95% CI =2.12–4.71) than ECC (OR =1.87; 95% CI =1.27–2.77), whereas hypertension harbored a stronger association with ECC (OR =3.09; 95% CI =2.09–4.58) than ICC (OR =2.06; 95% CI =1.32–3.21). Obesity was related to both ICC and ECC, with similar ORs, while diabetes was only related to ICC (OR =4.59; 95% CI =2.78–7.58), but not ECC (OR =0.97; 95% CI =0.49–1.94). Conclusion Metabolic syndrome was significantly related to a 1.86-fold elevated CCA risk.
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Affiliation(s)
- Jianping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Weiyu Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Yi Bai
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Hanchun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Lei Zhang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Junyu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Yiyao Xu
- Health Screening Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Zhenjie Wang
- Health Screening Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China,
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Liu JG, Wu J, Wang J, Shu GM, Wang YJ, Lou C, Zhang J, Du Z. Endoscopic Biliary Drainage Versus Percutaneous Transhepatic Biliary Drainage in Patients with Resectable Hilar Cholangiocarcinoma: A Systematic Review and Meta-Analysis. J Laparoendosc Adv Surg Tech A 2018; 28:1053-1060. [PMID: 29641365 DOI: 10.1089/lap.2017.0744] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hilar cholangiocarcinoma (HCCA) is a rare tumor, usually associated with obstructive jaundice and unfavorable prognosis. Obstructive jaundice can affect the liver, kidney, heart, and the immune system of the patients. Currently, controversy exists in whether preoperative biliary drainage (PBD) is of any benefit to the patients, and the best way for PBD in patients with resectable HCCA of malignant biliary obstruction remains to be determined. OBJECTIVES To compare the clinical outcomes and effectiveness of endoscopic biliary drainage (EBD) treatment with those of percutaneous transhepatic biliary drainage (PTBD) treatment in patients with malignant biliary obstruction caused by resectable HCCA. MATERIALS AND METHODS The databases including MEDLINE, EMBASE, PubMed, CBM (China Biological Medicine Database), and CNKI were employed to identify the clinic trials on EBD versus PTBD for malignant biliary obstruction associated with resectable HCCA from January 2008 to October 2017. A systematic review and meta-analysis were carried out. RESULTS Six trials were identified and included in this study. Overall, the differences in technical success rate, R0 resection, incidence of total complication after resection, postoperative hospitalization time, resection time, and recurrence were not statistically significant between the EBD group and PTBD group (all P > .05). However, the incidence of total complications after EBD treatment is higher than that after PTBD treatment (P < .05). CONCLUSION For patients with obstructive jaundice associated with HCCA, current evidence indicate no superiority of PTBD over EBD regarding clinical feasibility and success rate, but data suggest a better clinical safety of PTBD compared with EBD in short-term postoperation. In long-term evaluation, the differences in clinical outcomes are not statistically significant between PTBD and EBD.
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Affiliation(s)
- Jun-Guo Liu
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
| | - Jing Wu
- 2 Department of Ultrasonography, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin Medical University , Tianjin, China
| | - Jun Wang
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
| | - Gui-Ming Shu
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
| | - Yi-Jun Wang
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
| | - Cheng Lou
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
| | - Jinjuan Zhang
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
| | - Zhi Du
- 1 Department of Surgery, Third Central Hospital of Tianjin, Third Central Clinical College of Tianjin Medical University , Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China
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ACGH detects distinct genomic alterations of primary intrahepatic cholangiocarcinomas and matched lymph node metastases and identifies a poor prognosis subclass. Sci Rep 2018; 8:10637. [PMID: 30006612 PMCID: PMC6045619 DOI: 10.1038/s41598-018-28941-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 07/03/2018] [Indexed: 12/17/2022] Open
Abstract
Lymph node metastases (LNM) are an important prognostic factor for patients with intrahepatic cholangiocarcinoma, but underlying genetic alterations are poorly understood. Whole genome array comparative genomic hybridization (aCGH) was performed in 37 tumors and 14 matched LNM. Genomic analyses of tumors confirmed known and identified new (gains in 19q) copy number alterations (CNA). Tumors with LNM (N1) had more alterations and exclusive gains (3p, 4q, 5p, 13q) and losses (17p and 20p). LNM shared most alterations with their matched tumors (86%), but 79% acquired new isolated gains [12q14 (36%); 1p13, 2p23, 7p22, 7q11, 11q12, 13q13 and 14q12 (>20%)]. Unsupervised clustering revealed a poor prognosis subclass with increased alterations significantly associated to tumor differentiation and survival. TP53 and KRAS mutations occurred in 19% of tumors and 6% of metastases. Pathway analyses revealed association to cancer-associated pathways. Advanced tumor stage, microvascular/perineural invasion, and microscopic positive resection margin (R1) were significantly correlated to metastases, while N1-status, R1-resection, and poor tumor differentiation were significantly correlated to survival. ACGH identified clear differences between N0 (no LNM) and N1 tumors, while N1 tumors and matched LNM displayed high clonality with exclusive gains in the metastases. A novel subclass with increased CNAs and poor tumor differentiation was significantly correlated to survival.
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Yue C, Yang M, Tian Q, Mo F, Peng J, Ma Y, Huang Y, Wang D, Wang Y, Hu Z. IGFBP7 is associated to prognosis and could suppress cell survival in cholangiocarcinoma. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2018; 46:817-825. [PMID: 29991293 DOI: 10.1080/21691401.2018.1470524] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Chunyan Yue
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China
- Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China
| | - Manyi Yang
- National Key Laboratory of Nanobiological Technology, Xiangya hospital, Central South University, Changsha, China
| | - Qinggang Tian
- Department of General Surgery, Baotou Eighth Hospital, Baotou, China
| | - Fongming Mo
- National Key Laboratory of Nanobiological Technology, Xiangya hospital, Central South University, Changsha, China
| | - Jian Peng
- National Key Laboratory of Nanobiological Technology, Xiangya hospital, Central South University, Changsha, China
| | - Yan Ma
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China
| | - Yanning Huang
- National Key Laboratory of Nanobiological Technology, Xiangya hospital, Central South University, Changsha, China
| | - Dongcui Wang
- National Key Laboratory of Nanobiological Technology, Xiangya hospital, Central South University, Changsha, China
| | - Yuehua Wang
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China
| | - Zhiyuan Hu
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China
- Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China
- Center for Neuroscience Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China
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Intrahepatic Cholangiocarcinoma Masquerading as Acute Fatty Liver of Pregnancy: A Case Report and Review of the Literature. Case Reports Hepatol 2018; 2018:6939747. [PMID: 29682369 PMCID: PMC5846373 DOI: 10.1155/2018/6939747] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Accepted: 01/09/2018] [Indexed: 12/26/2022] Open
Abstract
Cholangiocarcinoma (CCA) is an uncommon cancer and accounts only for 3% of all gastrointestinal malignancies. In this report, we present a case of an intrahepatic cholangiocarcinoma masquerading as acute fatty liver of pregnancy (AFLP). A 38-year-old female who is 36-week pregnant presented with a 1-week history of headache, nausea, vomiting, and right upper abdominal pain, along with hepatomegaly. Laboratory investigations were remarkable for mild leukocytosis, hyperbilirubinemia, proteinuria, and elevated transaminases and prothrombin time. Ultrasound of the liver revealed hepatomegaly, fatty infiltration, and a right hepatic lobe mass. Based on the overall picture, AFLP was suspected, and the patient underwent delivery by Cesarean section. However, bilirubin and liver enzyme levels gradually increased after delivery. MRI revealed a large dominant hepatic mass along with multiple satellite lesions in both lobes. Biopsy revealed the presence of intrahepatic CCA. CCA presenting during pregnancy is extremely rare with only 9 other cases reported in the literature. Therefore, the signs and symptoms can be easily confused with other more common disorders that occur during pregnancy.
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Validation of Feasibility of Magnetic Resonance Imaging for the Measurement of Depth of Tumor Invasion in Distal Bile Duct Cancer According to the New American Joint Committee on Cancer Staging System. Acad Radiol 2017; 24:1526-1534. [PMID: 28780173 DOI: 10.1016/j.acra.2017.06.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/21/2017] [Accepted: 06/12/2017] [Indexed: 12/14/2022]
Abstract
RATIONALE AND OBJECTIVES This study aimed to develop and validate a method for measuring the depth of tumor invasion (DoI) using magnetic resonance imaging (MRI) and to investigate the diagnostic performance of the measured DoI for stratifying tumor (T) classification in patients with distal bile duct cancer according to the new American Joint Committee on Cancer staging system. MATERIALS AND METHODS Fifty-four patients (30 men and 24 women; age range, 43-81 years) with distal bile duct cancer were enrolled. A study coordinator first developed a "provisional method" for measuring DoI on T2-weighted MRI. Subsequently, after compensating for defects, the "improved method" was developed. Two reviewers independently measured DoI and assessed its correlations with the histopathologic reference standard using intraclass correlation coefficient (ICC). The study population was grouped according to the DoI for T classification based on the new staging system for evaluation of diagnostic predictive values. RESULTS The ICC values between the radiologic and the histopathologic DoI were calculated. Using the "improved method," the ICC for the coordinator's DoI was very good (ICC, 0.885), which was a significantly higher value than that obtained using the "provisional method" (ICC, 0.501, P = .00000); and for two reviewers' DoIs, the ICC values were good (ICC, 0.752 and 0.784, respectively). The overall accuracy of MRI for stratifying bile duct tumors using DoI was 87.0% and 85.2%, respectively. CONCLUSIONS This newly developed method reliably measured DoI on T2-weighted MRI and can be used for preoperative T classification of patients with distal bile duct cancer according to the new staging system.
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Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers. Invest New Drugs 2017; 36:156-162. [DOI: 10.1007/s10637-017-0492-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 07/11/2017] [Indexed: 01/06/2023]
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Xiong J, Wang Y, Huang H, Bian J, Wang A, Long J, Zheng Y, Sang X, Xu Y, Lu X, Zhao H. Systematic review and meta-analysis: cholecystectomy and the risk of cholangiocarcinoma. Oncotarget 2017; 8:59648-59657. [PMID: 28938668 PMCID: PMC5601764 DOI: 10.18632/oncotarget.19570] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Accepted: 07/19/2017] [Indexed: 12/15/2022] Open
Abstract
Studies have reported that cholecystectomy may increase the risk of cholangiocarcinoma. However, this association is controversial. Thus, we conducted a systematic review and meta-analysis to explore the relationship between cholecystectomy and the risk of cholangiocarcinoma. Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science published before February 2017. We used the random effects model proposed by DerSimonian and Laird to quantify the relationship between cholecystectomy and risk of cholangiocarcinoma. Publication bias was evaluated using funnel plots, Begg's and Egger's tests. Subgroup and sensitivity analyses were performed to validate the stability of the results. 16 articles, comprising 220,376 patients with cholecystectomy and 562,392 healthy controls, were included in our research. Our meta-analysis suggested that the risk of cholangiocarcinoma was significantly higher in the cholecystectomized patients in comparison with healthy controls, with heterogeneity among studies (summary odds ratio [OR] = 0.72; confidence interval [CI] = 0.55-0.90; I2 = 69.5%). Additionally, this association was also observed in cohort studies (OR = 0.83; 95% CI = 0.73-0.94) and case-control studies (OR = 0.60; 95% CI = 0.40-0.80). However, When the intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma were analyzed separately, the present study only indicated cholecystectomy was associated with increased the risk of extrahepatic cholangiocarcinoma (OR = 1.19; 95% CI = 0.32-2.05), rather than intrahepatic cholangiocarcinoma (OR = 1.19; 95% CI = 0.32-2.05). In conclusion, cholecystectomy was associated with a significant 54% increase in the risk of cholangiocarcinoma, especially in the extrahepatic cholangiocarcinoma.
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Affiliation(s)
- Jianping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yaqin Wang
- Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Hanchun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Anqiang Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Junyu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Ying Zheng
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau SAR, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
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Oliveira IS, Kilcoyne A, Everett JM, Mino-Kenudson M, Harisinghani MG, Ganesan K. Cholangiocarcinoma: classification, diagnosis, staging, imaging features, and management. Abdom Radiol (NY) 2017; 42:1637-1649. [PMID: 28271275 DOI: 10.1007/s00261-017-1094-7] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Cholangiocarcinoma is a relatively uncommon malignant neoplasm with poor prognosis. The distinction between extrahepatic and intrahepatic subtypes is important as epidemiological features, biologic and pathologic characteristics, and clinical course are different for both entities. This review study focuses on the role imaging plays in the diagnosis, classification, staging, and post-treatment assessment of cholangiocarcinoma.
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Affiliation(s)
- Irai S Oliveira
- Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
- Department of Radiology, Hospital Sírio-Libanês, São Paulo, SP, 01308-050, Brazil.
| | - Aoife Kilcoyne
- Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA
| | - Jamie M Everett
- Department of Pathology, Massachusetts General Hospital Harvard Medical School, Boston, MA, 02114, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital Harvard Medical School, Boston, MA, 02114, USA
| | - Mukesh G Harisinghani
- Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA
| | - Karthik Ganesan
- Department of Radiology, Sir HN - Reliance Foundation Hospital, Mumbai, 400004, India
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Coelho R, Silva M, Rodrigues-Pinto E, Cardoso H, Lopes S, Pereira P, Vilas-Boas F, Santos-Antunes J, Costa-Maia J, Macedo G. CA 19-9 as a Marker of Survival and a Predictor of Metastization in Cholangiocarcinoma. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2017; 24:114-121. [PMID: 28848795 PMCID: PMC5553366 DOI: 10.1159/000452691] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 09/26/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cholangiocarcinoma is the second most frequent primitive liver malignancy and is responsible for 3% of the malignant gastrointestinal neoplasms. The aims of this study were to determine the association of serum levels of CA 19-9 at diagnosis with other clinical data and serum liver function tests and to identify possible factors that influence the survival rates during follow-up. METHODS Retrospective observational study of 89 patients with a diagnosis of cholangiocarcinoma followed at the Department of Gastroenterology during 5 years. Statistical analyses were performed using SPSS version 20.0. RESULTS Patients were followed up for a median time of 127 days (IQR: 48-564), and the median age at diagnosis was 71.0 years (IQR: 62.0-77.5). The median survival rate was 14.0 months (IQR: 4.3-23.7), and the mortality rate was 79%. Patients with CA 19-9 levels ≥103 U/L had lower albumin levels and higher levels of alanine aminotransferase and γ-glutamyltransferase. CA 19-9 levels ≥103 U/L were associated with a higher probability of metastization (p = 0.001) and lower rates of treatment with curative intent (p = 0.024). In a multivariate analysis, CA 19-9 levels <103 U/L and surgery were independent predictors of survival. CONCLUSION Predictive factors for overall survival were identified, namely presence of metastasis, surgery, and chemotherapy. CA 19-9 levels ≥103 U/L were predictive factors for survival and metastization.
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Affiliation(s)
- Rosa Coelho
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Marco Silva
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Eduardo Rodrigues-Pinto
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Hélder Cardoso
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Susana Lopes
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Pedro Pereira
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Filipe Vilas-Boas
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - João Santos-Antunes
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - José Costa-Maia
- Department of Surgery, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar de São João, Porto, Portugal
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Liu H, Cen X, Suo T, Cai X, Yuan X, Shen S, Liu H, Li Y. Trends and Hospital Variations in Surgical Outcomes for Cholangiocarcinoma in New York State. World J Surg 2017; 41:525-537. [PMID: 27785554 DOI: 10.1007/s00268-016-3733-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND This population-based study examined surgical outcomes and hospital and post-acute care resource use after operations of cholangiocarcinoma during 2005-2012. STUDY DESIGN Using New York State hospital claims, we identified subjects with intrahepatic tumor who underwent hepatectomy only (n = 2089), subjects with perihilar tumor who underwent hepatectomy and biliary-enteric anastomosis (BEA; n = 389) or BEA only (n = 3721), and subjects with distal cholangiocarcinoma undergoing pancreatectomy or pancreaticoduodenectomy (n = 228). We performed trend analyses for each group and calculated overall risk-adjusted mortality, complication, and 30-day readmission rates for hospitals using multivariable logistic regressions. RESULTS Mortality rate was roughly 12 % over years for perihilar cases undergoing hepatectomy and BEA, significantly higher than the rates of other 3 groups (p = 0.000). The overall complication rate was 40 % for subjects undergoing both hepatectomy and BEA, more than doubling the rate for subjects undergoing hepatectomy or BEA alone (p = 0.000). Average LOS declined markedly for perihilar cases undergoing hepatectomy and BEA (from 21 days in 2005 to 16 days in 2012) and subjects with distal cholangiocarcinoma (from 22 days in 2005 to 16 days in 2012), but other outcomes did not change dramatically. Risk-adjusted hospital outcome rates varied substantially. CONCLUSIONS Surgical patients with cholangiocarcinoma incur considerable mortality, postoperative complications, and resource uses, especially among those undergoing hepatectomy and BEA for perihilar tumors.
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Affiliation(s)
- Han Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Xi Cen
- Department of Public Health Sciences, Division of Health Policy and Outcomes Research, University of Rochester Medical Center, 265 Crittenden Blvd., CU 420644, Rochester, NY, 14642, USA
| | - Tao Suo
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
| | - Xueya Cai
- Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Saunders Research Building 4208, 601 Elmwood Ave, Box 630, Rochester, NY, 14642, USA
| | - Xuewen Yuan
- Sinyoo Information Technology (Shanghai) Co., Ltd., Shanghai, China
| | - Sheng Shen
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Houbao Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Yue Li
- Department of Public Health Sciences, Division of Health Policy and Outcomes Research, University of Rochester Medical Center, 265 Crittenden Blvd., CU 420644, Rochester, NY, 14642, USA
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