|
1
|
Kim J, Lee YS, Lee JC, Hwang JH. Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study. BMC Gastroenterol 2025; 25:138. [PMID: 40045214 PMCID: PMC11883955 DOI: 10.1186/s12876-025-03746-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 02/28/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Choledocholithiasis has been reported to be associated with the occurrence of cholangiocarcinoma (CCA); however, the association has not yet been sufficiently demonstrated. This study aimed to evaluate the association between choledocholithiasis (common bile duct stones) and CCA. METHODS This nationwide retrospective cohort study used the Health Insurance Review and Assessment database of individuals diagnosed with choledocholithiasis between 2008 and 2009 in South Korea. Individuals were stratified by age, and CCA was categorized into extrahepatic CCA (ECA) and intrahepatic CCA (ICA). The standardized incidence ratio (SIR) was calculated to compare CCA incidence between patients with choledocholithiasis and the general population. RESULTS The study enrolled 20,808 patients with choledocholithiasis (52.35% men and 47.65% women; male-to-female ratio: 1.09:1). Over a 10-year follow-up period, CCA occurred in 548 (2.64%) patients, comprising 238 (1.14%) ECA cases and 310 (1.48%) ICA cases. The SIR was 25.23 (95% confidence interval [CI]: 21.98-28.85) for ECA and 24.64 (95% CI: 21.87-27.73) for ICA. Statistical significance persisted even after excluding cases within the first 2 years from the index date, with an SIR of 18.63 (95% CI: 16.23-21.28) for ICA and 12.73 (95% CI: 10.50-15.30) for ECA. The SIRs peaked in patients diagnosed with choledocholithiasis at the age of 70-79 years (SIR 16.61, 95% CI: 11.83-22.69) for ECA and 60-69 years (SIR 29.27, 95% CI: 23.53-36.03) for ICA. CONCLUSION Our study demonstrated a significant association between choledocholithiasis and cholangiocarcinoma, particularly those in their 70s for ECA and 60s for ICA. However, causation cannot be established due to the retrospective design.
Collapse
Affiliation(s)
- Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Yoon Suk Lee
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, 170, Juhwa-ro, Ilsanseo-gu, Goyang, South Korea.
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| |
Collapse
|
|
2
|
Jin S, Jiang N, Zhao JM, Xiao Y, Wang SY, Xiang CH, Lu Q, Shan SQ, Ruan HT, Yu SQ, Zeng JP, Yang SZ, Li L, Dong JH. Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma - a case-control study based on liver panoramic digital pathology. Int J Surg 2025; 111:31-39. [PMID: 39166939 PMCID: PMC11745584 DOI: 10.1097/js9.0000000000002040] [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: 04/19/2024] [Accepted: 08/01/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research. MATERIALS AND METHODS This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10×10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC. RESULTS The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15 000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in the liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI ( P <0.0001, P =0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100%, 100%, and 69%, respectively. CONCLUSION The presence of DIHI in most PHCCs was a significant factor for the poor survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.
Collapse
Affiliation(s)
- Shuo Jin
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Nan Jiang
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Jing-Min Zhao
- Department of Pathology and Hepatology, The Fifth Medical Centre of Chinese PLA General Hospital
| | - Ying Xiao
- Department of Pathology, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China
| | - Si-Yuan Wang
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Can-Hong Xiang
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Qian Lu
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Si-Qiao Shan
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Hao-Tian Ruan
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Shao-Qing Yu
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Jian-Ping Zeng
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Shi-Zhong Yang
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| | - Li Li
- Department of Pathology, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China
| | - Jia-Hong Dong
- HepatopancreLatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Institute for Precision Medicine, Tsinghua University, Beijing, China
| |
Collapse
|
|
3
|
Sato R, Matsumoto K, Kinugasa H, Tomiya M, Tanimoto T, Ohto A, Harada K, Hattori N, Obata T, Matsumi A, Miyamoto K, Morimoto K, Terasawa H, Fujii Y, Uchida D, Tsutsumi K, Horiguchi S, Kato H, Kawahara Y, Otsuka M. Virtual indigo carmine chromoendoscopy images: a novel modality for peroral cholangioscopy using artificial intelligence technology (with video). Gastrointest Endosc 2024; 100:938-946.e1. [PMID: 38879044 DOI: 10.1016/j.gie.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 05/29/2024] [Accepted: 06/05/2024] [Indexed: 08/24/2024]
Abstract
BACKGROUND AND AIMS Accurately diagnosing biliary strictures is crucial for surgical decisions, and although peroral cholangioscopy (POCS) aids in visual diagnosis, diagnosing malignancies or determining lesion margins via this route remains challenging. Indigo carmine is commonly used to evaluate lesions during GI endoscopy. We aimed to establish the utility of virtual indigo carmine chromoendoscopy (VICI) converted from POCS images using artificial intelligence. METHODS This single-center, retrospective study analyzed 40 patients with biliary strictures who underwent POCS using white-light imaging (WLI) and narrow-band imaging (NBI). A cycle-consistent adversarial network was used to convert the WLI into VICI of POCS images. Three experienced endoscopists evaluated WLI, NBI, and VICI via POCS in all patients. The primary outcome was the visualization quality of surface structures, surface microvessels, and lesion margins. The secondary outcome was diagnostic accuracy. RESULTS VICI showed superior visualization of the surface structures and lesion margins compared with WLI (P < .001) and NBI (P < .001). The diagnostic accuracies were 72.5%, 87.5%, and 90.0% in WLI alone, WLI and VICI simultaneously, and WLI and NBI simultaneously, respectively. WLI and VICI simultaneously tended to result in higher accuracy than WLI alone (P = .083), and the results were not significantly different from WLI and NBI simultaneously (P = .65). CONCLUSIONS VICI in POCS proved valuable for visualizing surface structures and lesion margins and contributed to higher diagnostic accuracy comparable to NBI. In addition to NBI, VICI may be a novel supportive modality for POCS.
Collapse
Affiliation(s)
- Ryosuke Sato
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan.
| | - Hideaki Kinugasa
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Masahiro Tomiya
- Business Strategy Division, Ryobi Systems Co, Ltd, Okayama, Japan
| | | | - Akimitsu Ohto
- Business Strategy Division, Ryobi Systems Co, Ltd, Okayama, Japan
| | - Kei Harada
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Nao Hattori
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Taisuke Obata
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Akihiro Matsumi
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Kazuya Miyamoto
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Kosaku Morimoto
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Hiroyuki Terasawa
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Yuki Fujii
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Daisuke Uchida
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Koichiro Tsutsumi
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Shigeru Horiguchi
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Yoshiro Kawahara
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| |
Collapse
|
|
4
|
Jeon SK, Lee JM, Yoo J, Park S, Joo I, Yoon JH, Lee KB. Intraductal papillary neoplasm of the bile duct: diagnostic value of MRI features in differentiating pathologic subclassifications-type 1 versus type 2. Eur Radiol 2024; 34:4674-4685. [PMID: 38114846 DOI: 10.1007/s00330-023-10491-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 10/10/2023] [Accepted: 10/25/2023] [Indexed: 12/21/2023]
Abstract
OBJECTIVES To identify MRI features for differentiating type 2 from type 1 intraductal papillary neoplasms of bile duct (IPNB) and assessing malignant potential of IPNB. METHODS This retrospective study included 60 patients with surgically proven IPNB who had undergone preoperative MRI between January 2007 and December 2020. All surgical specimens were reviewed retrospectively to classify types 1 and 2 IPNBs and assess tumor grade. Significant MRI features for differentiating type 2 (n = 40) from type 1 IPNB (n = 20); and for IPNB with an associated invasive carcinoma (n = 43) from intraepithelial neoplasia (n = 17) were determined using logistic regression analysis. RESULTS An associated invasive carcinoma was more frequently found in type 2 than in type 1 IPNB (85.0% [34/40] vs. 45.0% [9/20], p = 0.003). At univariable analysis, MRI features including extrahepatic location, no dilatation of tumor-bearing segment of bile duct, isolated upstream bile duct dilatation, and single lesion were associated with type 2 IPNB (all p ≤ 0.012). At multivariable analysis, significant MRI findings for differentiating type 2 from type 1 IPNB were extrahepatic location and no dilatation of tumor-bearing segment of bile duct (odds ratio [OR], 7.24 and 46.40, respectively). At univariable and multivariable analysis, tumor size ≥ 2.5 cm (OR, 8.45), bile duct wall thickening (OR, 4.82), and irregular polypoid or nodular tumor shape (OR, 6.44) were significant MRI features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia. CONCLUSION MRI with MR cholangiopancreatography may be helpful in differentiating type 2 IPNB from type 1 IPNB and assessing malignant potential of IPNB. CLINICAL RELEVANCE STATEMENT Preoperative MRI with MR cholangiopancreatography may be helpful in differentiating type 2 intraductal papillary neoplasms of bile duct (IPNB) from type 1 IPNB and assessing malignant potential of IPNB. KEY POINTS • In terms of tumor grade, the incidence of invasive carcinoma was significantly higher in type 2 intraductal papillary neoplasm of the bile duct (IPNB) than in type 1 IPNB. • At MRI, extrahepatic location and no dilatation of tumor-bearing segment are significant features for differentiating type 2 IPNBs from type 1 IPNBs. • At MRI, large tumor size, bile duct wall thickening, and irregular polypoid or nodular tumor shape are significant features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia.
Collapse
Affiliation(s)
- Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehangno, Jongno-Gu, Seoul, 03080, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehangno, Jongno-Gu, Seoul, 03080, Korea.
| | - Jeongin Yoo
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehangno, Jongno-Gu, Seoul, 03080, Korea
| | - Sungeun Park
- Department of Radiology, Konkuk University Medical Center, Seoul, South Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehangno, Jongno-Gu, Seoul, 03080, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehangno, Jongno-Gu, Seoul, 03080, Korea
| | - Kyoung Bun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, South Korea
| |
Collapse
|
|
5
|
Yu L, Xiu W, Yue A, Hao X, Jiang Z, Wu J, Dong Q. Cholangiocarcinoma identified in perforated choledochal cyst in a 3-year-old boy. BMC Pediatr 2024; 24:243. [PMID: 38580968 PMCID: PMC10996131 DOI: 10.1186/s12887-024-04709-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 03/13/2024] [Indexed: 04/07/2024] Open
Abstract
Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.
Collapse
Affiliation(s)
- Lun Yu
- Department of Paediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Wenli Xiu
- Department of Paediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Aimei Yue
- Department of Paediatrics, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Xiwei Hao
- Department of Paediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Zhong Jiang
- Department of Paediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Jie Wu
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Qian Dong
- Department of Paediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
| |
Collapse
|
|
6
|
Nagashima D, Esaki M, Nara S, Ban D, Takamoto T, Mizui T, Shimada K, Hiraoka N. Novel insights into the intraepithelial spread of extrahepatic cholangiocarcinoma: clinicopathological study of 382 cases on extrahepatic cholangiocarcinoma. Front Oncol 2023; 13:1216097. [PMID: 37664071 PMCID: PMC10470634 DOI: 10.3389/fonc.2023.1216097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/27/2023] [Indexed: 09/05/2023] Open
Abstract
Background Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive disease and consisted of conventional eCCA and intraductal papillary neoplasm of the bile duct (IPNB). Intraepithelial spread (IES) of cancer cells beyond the invasive area is often observed in IPNBs; however, the prevalence of IES remains to be examined in conventional eCCAs. Here, we evaluated the clinicopathological features of eCCAs according to tumor location, with a focus on the presence of IES. The IES extension was also compared among biliary tract cancers (BTCs). Methods We examined the prevalence and clinicopathological significance of IES in eCCAs (n=382) and the IES extension of BTCs, including gallbladder (n=172), cystic duct (n=20), and ampullary cancers (n=102). Results Among the invasive eCCAs, IPNB had a higher rate of IES (89.2%) than conventional eCCAs (57.0%). Among conventional eCCAs, distal eCCAs (75.4%) had a significantly higher prevalence of IES than perihilar eCCAs (41.3%). The presence of IES was associated with a significantly higher survival rate in patients with distal eCCAs (P=0.030). Extension of the IES into the cystic duct (CyD) in distal eCCAs that cancer cells reached the junction of the CyD was a favorable prognostic factor (P<0.001). The association of survival with IES, either on the extrahepatic bile duct or on the CyD, differed depending on the tumor location and type of eCCA. The extension properties of IES were also dependent on different types of tumors among BTCs; usually, the IES incidence became higher than 50% in the tissues that the tumor developed, whereas IES extension to other tissues decreased the incidence. Conclusion Thus, eCCAs have different clinicopathological characteristics depending on the tumor location and type.
Collapse
Affiliation(s)
- Daisuke Nagashima
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
- Department of Molecular Oncology, Jikei University Graduate School of Medicine, Tokyo, Japan
- Division of Innovative Pathology and Laboratory Medicine, National Cancer Center Exploratory Oncology Research & Clinical Trial Center (EPOC), Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Nobuyoshi Hiraoka
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
- Department of Molecular Oncology, Jikei University Graduate School of Medicine, Tokyo, Japan
- Division of Innovative Pathology and Laboratory Medicine, National Cancer Center Exploratory Oncology Research & Clinical Trial Center (EPOC), Tokyo, Japan
| |
Collapse
|
|
7
|
Kawashima H, Ohno E, Ishikawa T, Mizutani Y, Iida T, Yamamura T, Kakushima N, Furukawa K, Nakamura M. Endoscopic management of perihilar cholangiocarcinoma. Dig Endosc 2022; 34:1147-1156. [PMID: 35377509 DOI: 10.1111/den.14317] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/25/2022] [Accepted: 04/01/2022] [Indexed: 02/08/2023]
Abstract
Endoscopic management for perihilar cholangiocarcinoma (PHCC) is evolving toward more accurate diagnosis and safer drainage. In imaging, it is important to diagnose the entire lesion using multidetector-row computed tomography to determine resectability and optimal surgical planning, followed by local diagnosis using endoscopic retrograde cholangiopancreatography. Video peroral cholangioscopy and probe-based confocal laser endomicroscopy have been newly introduced as diagnostic imaging methods and are being applied clinically. In transpapillary forceps biopsy for PHCC diagnosis, the location in the bile duct (for mapping biopsy) and the number of biopsy samples should be determined depending on resectability, the morphological type, and future surgical planning. Preoperative drainage has shifted from percutaneous transhepatic biliary drainage to endoscopic nasobiliary drainage given the possibility of seeding metastasis. In addition, considering potential patient discomfort from a nasal tube, the usefulness of the placement of a plastic stent above the papilla (inside stent) as a bridging therapy for surgery has been reported. For drainage of unresectable PHCC, the improved prognosis due to advances in chemotherapy has necessitated a strategy that accounts for reintervention. Thus, in addition to uncovered self-expandable metallic stents (SEMS), exchangeable slim fully covered SEMS and inside stents have started to be used. In addition to the conventional transpapillary approach, an endoscopic ultrasonography-guided approach has been introduced, and a combination of both methods has also been proposed. To improve the quality of life and prognosis of PHCC patients, endoscopists need to understand and be able to use the various methods of endoscopic management for PHCC.
Collapse
Affiliation(s)
- Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Naomi Kakushima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
| |
Collapse
|
|
8
|
Converted-hepatopancreatoduodenectomy for an intraoperative positive ductal margin after pancreatoduodenectomy in distal cholangiocarcinoma. Langenbecks Arch Surg 2022; 407:2843-2852. [PMID: 35931877 DOI: 10.1007/s00423-022-02598-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 06/20/2022] [Indexed: 10/16/2022]
Abstract
PURPOSE Pancreatoduodenectomy (PD) is the standard treatment for distal cholangiocarcinoma, and a negative ductal margin (DM0) is indispensable for the long-term survival. When intraoperative frozen sections of ductal margin after PD are positive, converted-hepatopancreatoduodenectomy (C-HPD) is the final option available to gain an additional ductal margin. However, the efficacy of C-HPD remains unclear. METHODS Patients who underwent PD or C-HPD for distal cholangiocarcinoma between 2002 and 2019 were analyzed. The type of hepatectomy in C-HPD was restricted to left hepatectomy to prevent posthepatectomy liver failure. RESULTS Of 203 patients who underwent PD for distal cholangiocarcinoma, 49 patients exhibited intraoperative positive ductal margin (DM1) after PD. Eleven patients underwent C-HPD for intraoperative DM1 after PD, in which intraoperative DM1 with invasive carcinoma (DM1inv) was observed in 3 patients, and intraoperative DM1 with carcinoma in situ (DM1cis) was observed in 8 patients. The median additional ductal margin yielded by C-HPD was 9 mm (interquartile range 7-13 mm). C-HPD eradicated intraoperative DM1inv in 3 patients, with 2 patients showing DM0 and 1 patient showing DM1cis. Regarding 8 patients who underwent C-HPD for intraoperative DM1cis, 4 patients had DM0, but the others had DM1cis. C-HPD was associated with a high complication rate, but no mortality was observed. The median survival time of patients who underwent C-HPD was 48.8 months. CONCLUSION C-HPD was able to safely eradicate intraoperative DM1inv after PD. However, the length of the resected bile duct according to C-HPD may not be sufficient to remove intraoperative DM1cis after PD.
Collapse
|
|
9
|
Cancerization of ducts in hilar cholangiocarcinoma. Virchows Arch 2022; 481:1-10. [PMID: 35527321 DOI: 10.1007/s00428-022-03333-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 04/03/2022] [Accepted: 04/27/2022] [Indexed: 12/27/2022]
Abstract
Invasive cancers that arise from ductal structures can infiltrate and colonize pre-existing ducts in a process referred to as cancerization of ducts (COD). COD in cholangiocarcinoma is an under-studied process whose clinical significance remains poorly understood. Even though both cancerized ducts and biliary intraepithelial neoplasias (BilINs) show dysplastic changes, hallmarks of COD are (i) an abrupt transition from the normal/reactive epithelium to severe dysplasia and (ii) close proximity to invasive carcinoma with similar cytologic features. We investigated 113 cases of surgically resected hilar cholangiocarcinoma and identified COD in 37 cases (33%). Using immunohistochemistry, we found that COD and adjacent invasive carcinoma had a concordant pattern of p53 and SMAD4 staining in 95% (21/22) and 100% (21/21) of cases, respectively. In contrast, BilINs and cancerized ducts showed significantly lower levels of concordance in p53 and SMAD4 staining at 44% (8/18) and 47% (8/17) of cases, respectively (P = 0.0007 and 0.0001, respectively). By univariate analysis, positive lymph node metastasis (P = 0.027), positive final bile duct margin (P = 0.021), and the presence of COD (P = 0.020) were associated with decreased overall survival. We further performed multivariate analysis to demonstrate that positive lymph node metastasis (P = 0.031), positive final bile duct margin (P = 0.035), and COD (P = 0.0051) were correlated with decreased overall survival. Together, our study highlights that COD is a clinically significant process in hilar cholangiocarcinoma that can be identified using morphological criteria in conjunction with p53 and SMAD4 immunolabeling.
Collapse
|
|
10
|
Jiang N, Wang SY, Xiang CH, Yu SQ, Xiao Y, Zhou CY, Zeng JP, Jin S. Patterns of Caudate Lobe Invasion of Hilar Cholangiocarcinoma: A Panoramic Histologic Study of Liver. Ann Surg Oncol 2022; 29:6804-6812. [PMID: 35802216 DOI: 10.1245/s10434-022-11964-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/05/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND At present, caudate lobectomy (CL) in hilar cholangiocarcinoma (HCCA) was controversial. Our study was designed to investigate the features of caudate lobe invasion (CLI) by whole-mount histologic large sections (WHLS). METHODS A total of 46 HCCA patients underwent hemihepatectomy or trisectionectomy combined with CL were included. Serial WHLS (120 mm × 100 mm) were collected, and the relationship between caudate lobe and tumor was retained to determine the incidence of CLI. Hematoxylin and eosin (HE) and immunohistochemical (IHC) staining were completed to further explore the pathway of CLI. RESULTS The whole region of the Glisson system in caudate lobe and hilar area can be clearly displayed by WHLS, and 32 (32/46 69.6%) patients were identified with CLI. There were three different pathways of CLI with panoramic IHC staining. The most common pathway is through the fibrous connective tissue along Glisson system (20/32 62.5%, without carcinoma in bile ducts). The Bismuth type, tumor size, vascular invasion, pathological type, and hepatic invasion were related to the CLI (p < 0.05). CONCLUSIONS The incidence and distribution of CLI provided histologic evidence for CL in HCCA. Based on the invasion pathway, it is necessary to assess the fibrous connective tissue in Glisson system of caudate lobe in pathological research and practice.
Collapse
Affiliation(s)
- Nan Jiang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Si-Yuan Wang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Can-Hong Xiang
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Shao-Qing Yu
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Ying Xiao
- Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Cheng-Yao Zhou
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Jian-Ping Zeng
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
| | - Shuo Jin
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
| |
Collapse
|
|
11
|
Zhou Q, Dong G, Zhu Q, Qiu Y, Mao L, Chen J, Zhou K, Hu A, He J. Modification and comparison of CT criteria in the preoperative assessment of hepatic arterial invasion by hilar cholangiocarcinoma. Abdom Radiol (NY) 2021; 46:1922-1930. [PMID: 33159559 DOI: 10.1007/s00261-020-02849-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 10/23/2020] [Accepted: 10/30/2020] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To compare the diagnostic performance of three CT criteria and two signs in evaluating hepatic arterial invasion by hilar cholangiocarcinoma. METHODS In this study, we retrospectively reviewed the CT images of 85 patients with hilar cholangiocarcinoma. Modified Loyer's, Lu's, and Li's standards were used to evaluate hepatic arterial invasion by hilar cholangiocarcinoma with the reference of intraoperative findings and/or the postoperative pathological diagnosis. Arterial tortuosity and contact length were also evaluated. RESULTS Loyer's, Lu's, and Li's standards showed sensitivities of 91.7%, 90.3%, and 72.2%, specificities of 94.0%, 94.5%, and 95.6%, and accuracies of 93.3%, 93.3%, and 89.0%, respectively, in evaluating hepatic arterial invasion by hilar cholangiocarcinoma. Loyer's and Lu's standards and contact length performed better than Li's standard (P < 0.001). Arterial tortuosity performed worse than other criteria (P < 0.001). The CT criteria performed best in evaluating proper hepatic arterial invasion compared with the left and right hepatic artery. When the cut-off contact length of 6.73 mm was combined with Loyer's standard, 4 false-negative cases could be avoided. CONCLUSIONS Loyer's and Lu's standards and the contact length performed best in evaluating hepatic arterial invasion by hilar cholangiocarcinoma on preoperative CT images, particularly in assessing the proper hepatic artery. Arterial tortuosity could serve as an important supplement. The combination of the contact length and Loyer's standard could improve the diagnostic performance.
Collapse
Affiliation(s)
- Qun Zhou
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China
| | - Guoqiang Dong
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China
| | - Qiongjie Zhu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China
| | - Yudong Qiu
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China
| | - Liang Mao
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China
| | - Kefeng Zhou
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China.
| | - Anning Hu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China.
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China.
| |
Collapse
|
|
12
|
Dilek ON, Güngör F, Acar T, Atay A, Karasu Ş, Bağ H, Dilek FH. The Role of Portoenterostomy with Aggressive Hilar Dissection in Biliary Tract Tumors: Report of Case Series and Review of the Literature. Indian J Surg 2021; 83:114-120. [PMID: 32410790 PMCID: PMC7222060 DOI: 10.1007/s12262-020-02259-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 04/24/2020] [Indexed: 11/05/2022] Open
Abstract
Hepaticojejunostomy is a challenging and complex procedure to be done with confidence in conditions that contain a large number of segmental bile ducts. Portoenterostomy can be defined as the joining of multiple bile ducts into a single cavity using segmenter bile duct ends, stents, and surrounding connective tissues. During surgery, in cases with advanced stage biliary tract tumors that cannot be performed hepatectomy, after aggressive dissections to provide a negative surgical margin, a large number of segmental bile ducts can be revealed and needs to ensure the continuity of bile flow. Here, our clinical series of portoenterostomy (PE) in which we applied in patients who had aggressive hilar dissection and resection for hilar cholangiocarcinomas and biliary tract tumors were discussed. The study included 15 patients who underwent PE for biliary tract tumors and hilar cholangiocarcinomas between 2015 and 2019. Six of the patients had a tumor-negative surgical margin, with a mean follow-up of 14.4 months (range 2 to 28 months). Nine of the patients had a tumor-positive surgical margin, with a mean follow-up of 7.7 months (range 2 to 17 months). Portoenterostomy instead of hepaticojejunostomy in small and multiple biliary radicles and bile duct cancers has been successfully performed in 15 patients of bile duct cancer and Klatskin tumor. In the presence of active inflammation, fibrosis, major bile duct trauma, and thin bile duct radicles, this method, which is described in detail, provides an excellent salvage surgical procedure with less morbidity.
Collapse
Affiliation(s)
- Osman Nuri Dilek
- Department of Surgery, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| | - Feyyaz Güngör
- Department of Surgery, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| | - Turan Acar
- Department of Surgery, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| | - Arif Atay
- Department of Surgery, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| | - Şebnem Karasu
- Department of Radiology, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| | - Halis Bağ
- Department of Surgery, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| | - Fatma Hüsniye Dilek
- Department of Pathology, Atatürk Research and Education Hospital, İzmir Katip Celebi University, İzmir, Turkey
| |
Collapse
|
|
13
|
Nagino M, Hirano S, Yoshitomi H, Aoki T, Uesaka K, Unno M, Ebata T, Konishi M, Sano K, Shimada K, Shimizu H, Higuchi R, Wakai T, Isayama H, Okusaka T, Tsuyuguchi T, Hirooka Y, Furuse J, Maguchi H, Suzuki K, Yamazaki H, Kijima H, Yanagisawa A, Yoshida M, Yokoyama Y, Mizuno T, Endo I. Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 28:26-54. [PMID: 33259690 DOI: 10.1002/jhbp.870] [Citation(s) in RCA: 134] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. METHODS In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. CONCLUSIONS This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.
Collapse
Affiliation(s)
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Hideyuki Yoshitomi
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, Koshigaya, Japan
| | - Taku Aoki
- Second Department of Surgery, Dokkyo Medical University, Mibu, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoki Ebata
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masaru Konishi
- Department of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Kazuaki Shimada
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroaki Shimizu
- Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Toshio Tsuyuguchi
- Department of Gastroenterology, Chiba Prefectural Sawara Hospital, Sawara, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Gastroenterological Oncology, Fujita Health University, Toyoake, Japan
| | - Junji Furuse
- Department of Medical Oncology, Faculty of Medicine, Kyorin University, Mitaka, Japan
| | - Hiroyuki Maguchi
- Education and Research Center, Teine-Keijinkai Hospital, Sapporo, Japan
| | - Kojiro Suzuki
- Department of Radiology, Aichi Medical University, Nagakute, Japan
| | - Hideya Yamazaki
- Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Kijima
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Akio Yanagisawa
- Department of Pathology, Japanese Red Cross Kyoto Diichi Hospital, Kyoto, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic & Gastrointestinal Surgery, International University of Health and Welfare, Ichikawa, Japan
| | - Yukihiro Yokoyama
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
| |
Collapse
|
|
14
|
Elahi M, Rakhshan V. MED15, transforming growth factor beta 1 (TGF-β1), FcγRIII (CD16), and HNK-1 (CD57) are prognostic biomarkers of oral squamous cell carcinoma. Sci Rep 2020; 10:8475. [PMID: 32439976 PMCID: PMC7242386 DOI: 10.1038/s41598-020-65145-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 04/24/2020] [Indexed: 12/22/2022] Open
Abstract
Owing to the high incidence and mortality of oral squamous cell carcinoma (OSCC), knowledge of its diagnostic and prognostic factors is of significant value. The biomarkers 'CD16, CD57, transforming growth factor beta 1 (TGF-β1), and MED15' can play crucial roles in tumorigenesis, and hence might contribute to diagnosis, prognosis, and treatment. Since there was no previous study on MED15 in almost all cancers, and since the studies on diagnostic/prognostic values of the other three biomarkers were a few in OSCC (if any) and highly controversial, this study was conducted. Biomarker expressions in all OSCC tissues and their adjacent normal tissues available at the National Tumor Bank (n = 4 biomarkers × [48 cancers + 48 controls]) were estimated thrice using qRT-PCR. Diagnostic values of tumors were assessed using receiver-operator characteristic (ROC) curves. Factors contributing to patients' survival over 10 years were assessed using multiple Cox regressions. ROC curves were used to estimate cut-off points for significant prognostic variables (α = 0.05). Areas under the curve pertaining to diagnostic values of all markers were non-significant (P > 0.15). Survival was associated positively with tumoral upregulation of TGF-β1 and downregulation of CD16, CD57, and MED15. It was also associated positively with younger ages, lower histological grades, milder Jacobson clinical TNM stages (and lower pathological Ns), smaller and thinner tumors, and surgery cases not treated with incisional biopsy (Cox regression, P < 0.05). The cut-off point for clinical stage -as the only variable with a significant area under the curve- was between the stages 2 and 3. Increased TGF-β1 and reduced CD16, CD57, and MED15 expressions in the tumor might independently favor the prognosis. Clinical TNM staging might be one of the most reliable prognostic factors, and stages above 2 can predict a considerably poorer prognosis.
Collapse
Affiliation(s)
- Maryam Elahi
- Department of Oral Pathology, Alborz University of Medical Sciences, Karaj, Iran
| | - Vahid Rakhshan
- Department of Cognitive Neuroscience, Institute for Cognitive Science Studies, Tehran, Iran.
| |
Collapse
|
|
15
|
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.
Collapse
|
|
16
|
Noji T, Okamura K, Tanaka K, Nakanishi Y, Asano T, Nakamura T, Tsuchikawa T, Hirano S. Surgical technique and results of intrapancreatic bile duct resection for hilar malignancy (with video). HPB (Oxford) 2018; 20:1145-1149. [PMID: 29941288 DOI: 10.1016/j.hpb.2018.05.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 05/13/2018] [Accepted: 05/17/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hilar malignancy can occasionally be associated with high grade dysplasia (HGD) adjacent to invasive malignancy. For patients with HGD extending into the intrapancreatic bile duct, the authors adopted intrapancreatic bile duct resection (IP-BDR). The aims of this study were to compare the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF), distal R0 resection and local recurrence within the distal bile duct remnant for patients undergoing extrahepatic bile duct resection without pancreaticoduodenectomy (with or without IP-BDR). METHODS Patients who presented with hilar malignancy and underwent extrahepatic bile duct resection without pancreaticoduodenectomy between January 2005 and December 2016 were identified and the outcomes retrospectively evaluated. RESULTS Of 217 patients who met the inclusion criteria 62 (29%) patients underwent IP-BDR. There was a significant difference between patients undergoing standard resection vs. IP-BDR in terms of CR-POPF (5% (8/155) patients: vs 18% (11/62), p < 0.001). There were no significant differences between two groups of R0 status on distal margin (5% (8/155) patients: vs 10% (6/62), p = 0.359). No patient developed recurrence within the residual intrapancreatic bile duct. DISCUSSION The incidence of CR-POPF after IP-BDR for hilar malignancies was 18%. IP-BDR was associated with CR-POF, but does not appear to alter survival or local recurrence rate.
Collapse
Affiliation(s)
- Takehiro Noji
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan.
| | - Keisuke Okamura
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Yoshitsugu Nakanishi
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Toshimichi Asano
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| |
Collapse
|
|
17
|
Ueda J, Yoshida H, Mamada Y, Taniai N, Yoshioka M, Hirakata A, Kawano Y, Mizuguchi Y, Shimizu T, Kanda T, Takata H, Kondo R, Uchida E. Evaluation of positive ductal margins of biliary tract cancer in intraoperative histological examination. Oncol Lett 2018; 16:6677-6684. [PMID: 30405808 DOI: 10.3892/ol.2018.9479] [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: 10/22/2017] [Accepted: 09/13/2018] [Indexed: 12/22/2022] Open
Abstract
At present the only method available to confirm microscopic infiltration of cancer into ductal margins during surgery, is intraoperative histological examination. In the present study, the status of the surgical margins and postoperative course were evaluated to determine any correlation between remnant carcinoma and postoperative survival. All consecutive patients who underwent resection for biliary tract cancer between January 2004 and May 2012 were identified from a database. Positive margin cases were divided into two groups, invasive carcinoma and carcinoma in situ (CIS). Immunohistochemical staining targeting Ki67 and p53 for positive margins was performed. Cases of major vessel invasion were significantly increased in the positive group compared with the negative group. The recurrence rate was significantly lower in the CIS group compared with the invasive group. The survival rate was significantly increased in the CIS group compared with the invasive group. The expression levels of p53 and Ki67 were significantly increased in the invasive group compared with the CIS group. No statistical correlations were observed between the expression of p53 or Ki67 and the survival or recurrence of disease. In the positive group, resected margin status was the principal factor associated with recurrence-free survival according to Cox-regression analysis. In conclusion, the status of the resected margins in the positive group was the most important factor for postoperative survival and recurrence in cholangiocarcinoma, not immunohistochemical staining targeting Ki67 and p53.
Collapse
Affiliation(s)
- Junji Ueda
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan.,Department of Surgery, Nippon Medical School Tamanagayama Hospital, Tokyo 206-8512, Japan
| | - Hiroshi Yoshida
- Department of Surgery, Nippon Medical School Tamanagayama Hospital, Tokyo 206-8512, Japan
| | - Yasuhiro Mamada
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Nobuhiko Taniai
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Masato Yoshioka
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Atsushi Hirakata
- Department of Surgery, Nippon Medical School Tamanagayama Hospital, Tokyo 206-8512, Japan
| | - Youichi Kawano
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Yoshiaki Mizuguchi
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Tetsuya Shimizu
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Tomohiro Kanda
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Hideyuki Takata
- Department of Surgery, Nippon Medical School Tamanagayama Hospital, Tokyo 206-8512, Japan
| | - Ryota Kondo
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| | - Eiji Uchida
- Department of Surgery, Nippon Medical School, Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
| |
Collapse
|
|
18
|
Nakanuma Y, Uchida T, Sato Y, Uesaka K. An S100P-positive biliary epithelial field is a preinvasive intraepithelial neoplasm in nodular-sclerosing cholangiocarcinoma. Hum Pathol 2016; 60:46-57. [PMID: 27984121 DOI: 10.1016/j.humpath.2016.10.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Revised: 10/08/2016] [Accepted: 10/14/2016] [Indexed: 12/21/2022]
Abstract
Nodular-sclerosing cholangiocarcinoma (NS-CCA) is a common CCA of the intrahepatic large, perihilar, and distal bile ducts. Intraepithelial biliary neoplasms, such as the mucosal extension of carcinoma and preinvasive neoplastic lesions (ie, biliary intraepithelial neoplasia) reportedly occur in the bile ducts around CCA. In the present study, we collectively refer to these intraepithelial lesions as "intraepithelial neoplasms of the bile duct (IENBs)". We examined the IENBs in 57 surgically resected cases of NS-CCA. S100P immunostaining was used to help detect IENBs. The IENBs formed field(s) of continuous neoplastic biliary epithelial cells and showed a flat, micropapillary, or papillotubular configuration. IENBs could be classified into 3 categories based on their atypia: group A (neoplastic but not enough for malignancy), B (neoplastic and sufficiently well differentiated for high-grade dysplasia), and C (overtly malignant and variably differentiated). IENB was found in 31 of 57 cases, with group C the most common (26 cases) followed by group B (22 cases) and group A (16 cases). The expression of cancer-related molecules and MIB-1 index of groups A and B differed from those of invasive CCA, whereas these features of group C were relatively similar to those of invasive CCA. In conclusion, IENB was not infrequently found in NS-CCA and could be classified into 3 grades. Preinvasive lesions (biliary intraepithelial neoplasias) are likely to be found in groups A and B, whereas cancerization would be included in group C. The classification of IENB may be useful for future studies of the preinvasive intraepithelial neoplastic lesions of NS-CCAs.
Collapse
Affiliation(s)
- Yasuni Nakanuma
- Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.
| | - Tsuneyuki Uchida
- Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan; Department of Hepatobiliary Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan
| | - Katsuhiko Uesaka
- Department of Hepatobiliary Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan
| |
Collapse
|
|
19
|
Kurahara H, Maemura K, Mataki Y, Sakoda M, Iino S, Kawasaki Y, Mori S, Kijima Y, Ueno S, Shinchi H, Takao S, Natsugoe S. Relationship between the surgical margin status, prognosis, and recurrence in extrahepatic bile duct cancer patients. Langenbecks Arch Surg 2016; 402:87-93. [PMID: 27491729 DOI: 10.1007/s00423-016-1491-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 07/29/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE The purpose of this retrospective study was to evaluate the relationship between the surgical margin status of the bile duct and the prognosis and recurrence of extrahepatic bile duct (EHBD) cancer. METHODS The clinical data of 100 patients who underwent surgery for EHBD cancer between February 2002 and September 2014 were analyzed. The ductal margin status was classified into the following three categories: negative (D-N), positive with carcinoma in situ (D-CIS), and positive with invasive carcinoma (D-INV). RESULTS The number of patients with D-N, D-CIS, and D-INV was 69, 16, and 15, respectively. Local recurrence rates of patients with D-CIS (56.3 %) and D-INV (66.7 %) were significantly higher compared to those of patients with D-N (10.1 %; P < 0.001). D-CIS was a significant predictor of shorter recurrence-free survival (RFS). Lymph node metastasis (P = 0.037) and D-INV (P = 0.008) were independent predictors of shorter disease-specific survival (DSS). The prognostic relevance of the ductal margin status was high, particularly in patients without lymph node metastasis. CONCLUSION The surgical margin status of the bile duct was significantly associated with RFS, DSS, and the recurrence site.
Collapse
Affiliation(s)
- Hiroshi Kurahara
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
| | - Kosei Maemura
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yuko Mataki
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Masahiko Sakoda
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Satoshi Iino
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yota Kawasaki
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shinichiro Mori
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yuko Kijima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shinichi Ueno
- Department of Clinical Oncology, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Hiroyuki Shinchi
- Department of Health Sciences, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Sonshin Takao
- Frontier Science Research Center, Graduate School of Medical Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan
| |
Collapse
|
|
20
|
Jang KT, Ahn S. Tumoral Versus Flat Intraepithelial Neoplasia of Pancreatobiliary Tract, Gallbladder, and Ampulla of Vater. Arch Pathol Lab Med 2016; 140:429-36. [DOI: 10.5858/arpa.2015-0319-ra] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—The identification of a precursor lesion is important to understanding the histopathologic and genetic alterations in carcinogenesis. There are a plethora of terminologies that describe precursor lesions of the pancreatobiliary tract, ampulla of Vater, and gallbladder. The current terminologies for precursor lesions may make it difficult to understand the tumor biology. Here, we propose the concept of tumoral and flat intraepithelial neoplasia to improve our understanding of precursor lesions of many epithelial organs, including the pancreatobiliary tract, ampulla of Vater, and gallbladder.
Objective.—To understand the dichotomous pattern of tumoral and flat intraepithelial neoplasia in carcinogenesis of pancreatobiliary tract, ampulla of Vater, and gallbladder.
Data Sources.—Review of relevant literatures indexed in PubMed.
Conclusions.—Tumoral intraepithelial neoplasia presents as an intraluminal or intraductal, mass-forming, polypoid lesion or a macroscopic, visible, cystic lesion without intracystic papillae. Microscopically, tumoral intraepithelial neoplasia shows various proportions of papillary and tubular architecture, often with a mixed pattern, such as papillary, tubular, and papillary-tubular. The malignant potential depends on the degree of dysplasia and the cell phenotype of the epithelium. Flat intraepithelial neoplasia presents as a flat or superficial, spreading, mucosal lesion that is frequently accompanied by an invasive carcinoma. Tumoral and flat intraepithelial neoplasias are not homogeneous entities and may exhibit histopathologic spectrum changes and different genetic profiles. Although intraepithelial neoplasia showed a dichotomous pattern in the tumoral versus flat types, they can coexist. Tumoral and flat intraepithelial neoplasia can be interpreted as part of a spectrum of changes in the carcinogenesis pathway of each organ.
Collapse
Affiliation(s)
| | - Sangjeong Ahn
- From the Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (Dr Jang); and the Department of Pathology, Pusan National University Hospital and the Pusan National University School of Medicine, and the Biomedical Research Institute, Pusan National University Hospital, Pusan, Korea (Dr Ahn)
| |
Collapse
|
|
21
|
Maeda S, Morikawa T, Takadate T, Suzuki T, Minowa T, Hanagata N, Onogawa T, Motoi F, Nishimura T, Unno M. Mass spectrometry-based proteomic analysis of formalin-fixed paraffin-embedded extrahepatic cholangiocarcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:683-91. [PMID: 25917007 DOI: 10.1002/jhbp.262] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Accepted: 04/21/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Extrahepatic cholangiocarcinoma is very difficult to diagnose at an early stage, and has a poor prognosis. Novel markers for diagnosis and optimal treatment selection are needed. However, there has been very limited data on the proteome profile of extrahepatic cholangiocarcinoma. This study was designed to unravel the proteome profile of this disease and to identify overexpressed proteins using mass spectrometry-based proteomic approaches. METHODS We analyzed a discovery set of formalin-fixed paraffin-embedded tissues of 14 extrahepatic cholangiocarcinomas using shotgun mass spectrometry, and compared proteome profiles with those of seven controls. Then, selected candidates were verified by quantitative analysis using scheduled selected reaction monitoring-based mass spectrometry. Furthermore, immunohistochemical staining used a validation set of 165 cases. RESULTS In total, 1,992 proteins were identified and 136 proteins were overexpressed. Verification of 58 selected proteins by quantitative analysis revealed 11 overexpressed proteins. Immunohistochemical validation for 10 proteins showed positive rates of S100P (84%), CEAM5 (75%), MUC5A (62%), OLFM4 (60%), OAT (42%), CAD17 (41%), FABPL (38%), AOFA (30%), K1C20 (25%) and CPSM (22%) in extrahepatic cholangiocarcinomas, which were rarely positive in controls. CONCLUSIONS We identified 10 proteins associated with extrahepatic cholangiocarcinoma using proteomic approaches. These proteins are potential targets for future diagnostic biomarkers and therapy.
Collapse
Affiliation(s)
- Shimpei Maeda
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.,Department of Surgery, South Miyagi Medical Center, Miyagi, Japan
| | - Takanori Morikawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tatsuyuki Takadate
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takashi Suzuki
- Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takashi Minowa
- Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Japan
| | - Nobutaka Hanagata
- Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Japan
| | - Tohru Onogawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| |
Collapse
|
|
22
|
Tsuchikawa T, Hirano S, Okamura K, Matsumoto J, Tamoto E, Murakami S, Nakamura T, Ebihara Y, Kurashima Y, Shichinohe T. Advances in the surgical treatment of hilar cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2015; 9:369-74. [PMID: 25256146 DOI: 10.1586/17474124.2015.960393] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
With the improvement of perioperative management and surgical techniques as well as the accumulation of knowledge on the oncobiological behavior of bile duct carcinoma, the long-term prognosis of hilar cholangiocarcinoma has been improving. In this article, the authors review the recent developments in surgical strategies for hilar cholangiocarcinoma, focusing on diagnosis for characteristic disease extension, perioperative management to reduce postoperative morbidity and mortality, surgical techniques for extended curative resection and postoperative adjuvant therapy.
Collapse
Affiliation(s)
- Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N-15 W-7, Sapporo 060-8638, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray. Br J Cancer 2014; 111:1363-72. [PMID: 25077440 PMCID: PMC4183847 DOI: 10.1038/bjc.2014.415] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Revised: 06/25/2014] [Accepted: 07/01/2014] [Indexed: 01/03/2023] Open
Abstract
Background: Epithelial–mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial–mesenchymal transition is proposed to occur in various developmental processes and cancer progression. ‘Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC). Methods: We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n=117) using immunohistochemistry on tissue microarrays. Results: Univariate and multivariate analyses revealed that, in addition to N classification (P=0.0420), the expression of E-cadherin (P=0.0208), N-cadherin (P=0.0038) and S100A4 (P=0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P=0.0143) in patients with EHCC. Conclusions: These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance.
Collapse
|
|
24
|
Soares KC, Kamel I, Cosgrove DP, Herman JM, Pawlik TM. Hilar cholangiocarcinoma: diagnosis, treatment options, and management. Hepatobiliary Surg Nutr 2014; 3:18-34. [PMID: 24696835 DOI: 10.3978/j.issn.2304-3881.2014.02.05] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 12/30/2013] [Indexed: 12/16/2022]
Abstract
Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6(th) decade of life. Of the 3,000 cases seen annually in the United States, less than one half of these tumors are resectable. A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. Patients typically present with abdominal pain, pruritis, weight loss, and jaundice. Computed topography (CT), magnetic resonance imaging (MRI), and ultrasound (US) are used to characterize biliary lesions. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) assess local ductal extent of the tumor while allowing for therapeutic biliary drainage. MRCP has demonstrated similar efficacies to PTC and ERCP in identifying anatomic extension of tumors with less complications. Treatment consists of surgery, radiation, chemotherapy and photodynamic therapy. Biliary drainage of the future liver remnant should be performed to decrease bilirubin levels thereby facilitating future liver hypertrophy. Standard therapy consists of surgical margin-negative (R0) resection with extrahepatic bile duct resection, hepatectomy and en bloc lymphadenectomy. Local resection should not be undertaken. Lymph node invasion, tumor grade and negative margins are important prognostic indicators. In instances where curative resection is not possible, liver transplantation has demonstrated acceptable outcomes in highly selected patients. Despite the limited data, chemotherapy is indicated for patients with unresectable tumors and adequate functional status. Five-year survival after surgical resection of HC ranges from 10% to 40% however, recurrence can be as high as 50-70% even after R0 resection. Due to the complexity of this disease, a multi-disciplinary approach with multimodal treatment is recommended for this complex disease.
Collapse
Affiliation(s)
- Kevin C Soares
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ihab Kamel
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David P Cosgrove
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Joseph M Herman
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- 1 Department of Surgery, Division of Surgical Oncology, 2 Department of Radiology, 3 Department of Oncology, 4 Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
25
|
Surgical outcome of hilar plate resection: extended hilar bile duct resection without hepatectomy. J Gastrointest Surg 2014; 18:1131-7. [PMID: 24627257 DOI: 10.1007/s11605-014-2490-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Accepted: 02/25/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND We have done curative or palliative extended extrahepatic bile duct resection at the level of the hilar plate for selected patients with cholangiocarcinoma with hilar spreading, calling this procedure "hilar plate resection" (HPR), but the results of evaluating the clinical benefits of HPR for cholangiocarcinoma with hilar spreading have not been reported. PATIENTS AND METHODS Fifty-two patients with cholangiocarcinoma underwent HPR: the curative procedure was performed in 28 patients (cHPR group) and the palliative in 24 patients (pHPR group). In the same period, 128 patients with cholangiocarcinoma underwent major hepatectomy with intrahepatic cholangiojejunostomy (Hx group). These groups were compared in terms of post-operative complications and survival. RESULTS There were no significant differences in the rate of patients with post-operative complications and in post-operative hospital stay. The overall cumulative 5-year survival rates for each procedure (Hx group, cHPR group and pHPR group) were 40, 38 and 11 %, respectively. There was no significant difference between the Hx and cHPR groups in survival rates (p = 0.87). CONCLUSION In conclusion, HPR appears to be safe and feasible for selected patients with cholangiocarcinoma. However, the indications for HPR should be restricted.
Collapse
|
|
26
|
Han IW, Jang JY, Lee KB, Kang MJ, Kwon W, Park JW, Chang YR, Kim SW. Clinicopathological analysis and prognosis of extrahepatic bile duct cancer with a microscopic positive ductal margin. HPB (Oxford) 2014; 16:575-81. [PMID: 24308425 PMCID: PMC4048079 DOI: 10.1111/hpb.12193] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Accepted: 10/01/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND The fate of a microscopic positive ductal margin (MPDM) of extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to analyse the clinicopathological features of EHBD cancer with MPDM and to identify the prognostic factors associated with survival. METHODS Between 1995 and 2007, a retrospective analysis of 464 patients who had undergone surgical resection for EHBD cancer was conducted. Clinicopathological factors likely to influence survival were assessed using univariate and multivariate analysis. RESULTS One hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and 18 months, respectively. Adverse prognostic factors were 'IC' on the resection margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033). Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year survival rate 19.7 compared with 2.8%, P = 0.011). CONCLUSIONS The presence of MPDM is an important prognostic factor in EHBD cancer. When a ductal resection margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important.
Collapse
Affiliation(s)
- In Woong Han
- Department of Surgery, Dongguk University College of MedicineGoyang, South Korea
| | - Jin-Young Jang
- Department of Surgery & Cancer Research Institute, Seoul National University College of MedicineSeoul, South Korea
| | - Kyoung Bun Lee
- Department of Pathology, Seoul National University College of MedicineSeoul, South Korea
| | - Mee Joo Kang
- Department of Surgery & Cancer Research Institute, Seoul National University College of MedicineSeoul, South Korea
| | - Wooil Kwon
- Department of Surgery & Cancer Research Institute, Seoul National University College of MedicineSeoul, South Korea
| | - Jae Woo Park
- Department of Surgery & Cancer Research Institute, Seoul National University College of MedicineSeoul, South Korea
| | - Ye Rim Chang
- Department of Surgery & Cancer Research Institute, Seoul National University College of MedicineSeoul, South Korea
| | - Sun-Whe Kim
- Department of Surgery & Cancer Research Institute, Seoul National University College of MedicineSeoul, South Korea
| |
Collapse
|
|
27
|
A novel technique for endoscopic transpapillary "mapping biopsy specimens" of superficial intraductal spread of bile duct carcinoma (with videos). Gastrointest Endosc 2014; 79:1020-5. [PMID: 24674353 DOI: 10.1016/j.gie.2014.01.040] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 01/22/2014] [Indexed: 01/03/2023]
|
|
28
|
Sato Y, Sasaki M, Harada K, Aishima S, Fukusato T, Ojima H, Kanai Y, Kage M, Nakanuma Y, Tsubouchi H. Pathological diagnosis of flat epithelial lesions of the biliary tract with emphasis on biliary intraepithelial neoplasia. J Gastroenterol 2014; 49:64-72. [PMID: 23616173 DOI: 10.1007/s00535-013-0810-5] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 04/04/2013] [Indexed: 02/04/2023]
Abstract
Flat epithelial lesions of the biliary tract cannot be detected by the image analysis, and the diagnosis entirely depends on pathological examination. The biliary tract is often affected by inflammatory conditions, and the resultant changes of the biliary epithelium make it difficult to differentiate them from neoplasia. Thus, the pathological diagnosis of biliary flat epithelial lesions can be challenging. In the biliary tract, there are several forms of intraepithelial neoplasia of the flat type, and biliary intraepithelial neoplasia (BilIN) is known as one of such lesions that represent the multistep cholangiocarcinogenesis. In this article, the diagnostic criteria and the differential diagnosis of biliary flat epithelial lesions, particularly focusing on BilIN, were presented and discussed to provide help to advance clinical and research applications of the BilIN system.
Collapse
Affiliation(s)
- Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8640, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Castellano-Megías VM, Ibarrola-de Andrés C, Colina-Ruizdelgado F. Pathological aspects of so called "hilar cholangiocarcinoma". World J Gastrointest Oncol 2013; 5:159-170. [PMID: 23919110 PMCID: PMC3731529 DOI: 10.4251/wjgo.v5.i7.159] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 04/14/2013] [Accepted: 05/19/2013] [Indexed: 02/05/2023] Open
Abstract
Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, “hilar and perihilar CC” are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.
Collapse
|
|
30
|
Impact of macroscopic morphology, multifocality, and mucin secretion on survival outcome of intraductal papillary neoplasm of the bile duct. J Gastrointest Surg 2013; 17:931-8. [PMID: 23371308 DOI: 10.1007/s11605-013-2151-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Accepted: 01/16/2013] [Indexed: 01/31/2023]
Abstract
BACKGROUND Intraductal papillary neoplasms of the bile duct (IPNB) are relatively rare disease with favorable prognosis. The authors investigated clinicopathologic characteristics and prognostic factors of IPNB in viewpoint of macroscopic morphology and multiplicity. METHODS Data were collected from 84 patients who underwent surgery at Seoul National University Hospital with diagnosis of IPNB from 2000 to 2009. RESULTS Median follow-up was 41.8 months and 75 (89.3 %) had invasive cancer. Tumors were confined to the bile duct in 45 patients (53.6 %) and 8 (9.5 %) had lymph node metastasis. Curative resection was achieved in 70 patients (89.3 %). Mucin secretion was identified in 23 (28.0 %) and 43 (51.2 %) had multiple tumors. Multiple IPNB had poor prognosis compared with single IPNB (5-year survival rate 50.7 vs. 85.9 %; P = 0.011). Positive resection margin (P = 0.046) and multiplicity (P = 0.038) were independent prognostic factors of IPNB after multivariate analysis. Mucin secretion had no impact on survival outcome (P = 0.595). The disease-free survival rate was significantly lower in multiple IPNB compared with single IPNB (5-year disease free survival rates 36.1 vs. 74.1 %; P = 0.026). CONCLUSION Multiplicity is a common feature of IPNB and has a negative impact on prognosis. Current WHO classification for IPNB needs consideration for macroscopic morphology and multiplicity considering its prognostic impact of IPNB.
Collapse
|
|
31
|
Precancerous lesions of the biliary tree. Best Pract Res Clin Gastroenterol 2013; 27:285-97. [PMID: 23809246 DOI: 10.1016/j.bpg.2013.04.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 04/14/2013] [Indexed: 01/31/2023]
Abstract
The neoplasms of the biliary tree include the carcinomas of the intra- and extrahepatic bile ducts, the gallbladder and the ampulla. Two types of precancerous lesions precede these adenocarcinomas: the flat and non-tumour forming type that is called biliary intraepithelial neoplasia, and the papillary and tumour-forming type that has been named intraductal papillary neoplasm of the bile duct. Rarely also biliary mucinous cystic neoplasm can give rise to invasive biliary adenocarcinomas. This review discusses the pathological, molecular, epidemiological, clinical and prognostic features of the precancerous biliary lesions, separated according to their origin in the bile ducts, the ampulla and the gall bladder.
Collapse
|
|
32
|
Sato Y, Harada K, Sasaki M, Nakanuma Y. Histological characteristics of biliary intraepithelial neoplasia-3 and intraepithelial spread of cholangiocarcinoma. Virchows Arch 2013; 462:421-7. [PMID: 23446751 DOI: 10.1007/s00428-013-1384-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Revised: 12/13/2012] [Accepted: 02/11/2013] [Indexed: 10/27/2022]
Abstract
The increasing grades of biliary intraepithelial neoplasia (BilIN) reflect multistep carcinogenesis of cholangiocarcinoma, BilIN-3 representing the carcinoma in situ stage. A different form of in situ growth form of cancer cells is the intraepithelial spreading of cholangiocarcinoma cells. We examined the histological characteristics of carcinoma in situ in the biliary tract on 64 partial hepatectomy specimens with a diagnosis of hepatolithiasis. We distinguished two forms of carcinoma in situ: BilIN-3 and intraepithelial spread of carcinoma (IES). BilIN-3 is defined by epithelial atypia gradually decreasing towards the transition to adjacent normal biliary epithelium. In IES, the lesion shows an abrupt transition to normal biliary epithelium, in which the intraepithelial carcinoma then tends to spread. BilIN-3 and IES were observed in 17 (94 %) and seven (39 %), respectively, in cases of invasive cholangiocarcinoma (n = 18), and neither of them was observed in cases without invasive cholangiocarcinoma (n = 46). Most lesions of BilIN-3 and IES microscopically showed a flat or pseudopapillary pattern. The less frequent micropapillary configuration was noted more often in BilIN-3. BilIN-3 was not observed in septal and small intrahepatic bile ducts, while IES was regularly observed in such bile ducts. Immunohistochemical analysis showed p53 to be expressed significantly more frequently in IES (29 %) than in BilIN-3 (8 %). In conclusion, carcinoma in situ in the biliary tract is morphologically heterogeneous, and it is important to distinguish BilIN-3 and intraepithelial carcinoma spreading as distinct lesions, to better understand their biology.
Collapse
Affiliation(s)
- Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan
| | | | | | | |
Collapse
|
|
33
|
Ganeshan D, Moron FE, Szklaruk J. Extrahepatic biliary cancer: New staging classification. World J Radiol 2012; 4:345-52. [PMID: 22937214 PMCID: PMC3430732 DOI: 10.4329/wjr.v4.i8.345] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 07/19/2012] [Accepted: 07/26/2012] [Indexed: 02/06/2023] Open
Abstract
Tumor staging defines the point in the natural history of the malignancy when the diagnosis is made. The most common staging system for cancer is the tumor, node, metastases classification. Staging of cancers provides useful parameters in the determination of the extent of disease and prognosis. Cholangiocarcinoma are rare and refers to cancers that arise from the biliary epithelium. These tumors can occur anywhere along the biliary tree. These tumors have been previously divided into extrahepatic and intrahepatic lesions. Until recently the extrahepatic bile duct tumors have been considered as a single entity per American Joint Commission on Cancer (AJCC) staging classification. The most recent changes to the AJCC classification of bile duct cancers divide the tumors into two major categories: proximal and distal tumors. This practical classification is based on anatomy and surgical management. High quality cross-sectional computed tomography (CT) and/or magnetic resonance (MR) imaging of the abdomen are essential information to accurately stage this tumors. Imaging plays an important role in diagnosis, localization, staging and optimal management of cholangiocarcinoma. For example, it helps to localize the tumor to either perihilar or distal bile duct, both of which have different management. Further, it helps to accurately stage the disease and identify the presence of significant nodal and distant metastasis, which may preclude surgery. Also, it helps to identify the extent of local invasion, which has a major impact on the management. For example, extensive involvement of hepatic duct reaching up to second-order biliary radicals or major vascular encasement of portal vein or hepatic arteries precludes curative surgery and patient may be managed by palliative therapy. Further, imaging helps to identify any anatomical variations in the hepatic arterial or venous circulation and biliary ductal system, which is vital information for surgical planning. This review presents relevant clinical presentation and imaging acquisition and presentation for the accurate staging classification of bile duct tumors based on the new AJCC criteria. This will be performed with the assistance of anatomical diagrams and representative CT and MR images. The image interpretation must include all relevant imaging information for optimum staging. Detailed recommendations on the items required on the radiology report will be presented.
Collapse
|
|
34
|
Hirano S, Tanaka E, Tsuchikawa T, Matsumoto J, Shichinohe T, Kato K. Techniques of biliary reconstruction following bile duct resection (with video). JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2012; 19:203-9. [PMID: 22081253 PMCID: PMC3311849 DOI: 10.1007/s00534-011-0475-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In several clinical situations, including resection of malignant or benign biliary lesions, reconstruction of the biliary system using the Roux-en-Y jejunum limb has been adopted as the standard procedure. The basic technique and the procedural knowledge essential for most gastroenterological surgeons are described in this article, along with a video supplement. Low complication rates involving anastomotic insufficiency or stricture can be achieved by using proper surgical techniques, even following small bile duct reconstruction. Using the ropeway method to stabilize the bile duct and jejunal limb allows precise mucosa-to-mucosa anastomosis with interrupted sutures of the posterior row of the anastomosis. Placement of a transanastomotic stent tube is the second step. The final step involves suturing the anterior row of the anastomosis. In contrast to the lower extrahepatic bile duct, the wall of the hilar or intrahepatic bile duct can be recognized within the fibrous connective tissue in the Glissonean pedicle. The portal side of the duct should be selected for the posterior wall during anastomosis owing to its thickness. Meticulous inspection to avoid overlooking small bile ducts could decrease the chance of postoperative intractable bile leakage. In reconstruction of small or fragile branches, a transanastomotic stent tube could work as an anchor for the anastomosis.
Collapse
Affiliation(s)
- Satoshi Hirano
- Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-8638, Japan.
| | | | | | | | | | | |
Collapse
|
|
35
|
Abdelghani YA, Arisaka Y, Masuda D, Takii M, Ashida R, Makhlouf MM, Fouad YM, Tsuji M, Kurisu Y, Higuchi K. Bile aspiration cytology in diagnosis of bile duct carcinoma: factors associated with positive yields. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2012; 19:370-378. [PMID: 21785970 DOI: 10.1007/s00534-011-0419-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE In bile duct carcinoma (BDC) patients, bile aspiration cytology (BAC) is an established method for cytodiagnosis. However, almost all previous reports investigated the biliary strictures caused not only by BDC but also by gallbladder and pancreatic carcinomas. Therefore, BAC in BDC patients only has not yet been investigated sufficiently. The aim of this study was to evaluate the actual sensitivity of BAC and to evaluate the factors that affect positive yields of BAC in patients with defined BDC. METHODS Data on 47 consecutive patients with definite BDC, who underwent BAC via endoscopic nasobiliary drainage (ENBD) or percutaneous transhepatic cholangiodrainage (PTCD), were retrospectively collected. Fourteen factors were studied for association with positive BAC. RESULTS The number of cytological samplings ranged from 1 to 14 times. The cumulative diagnostic yield was 72.3% (34/47), and 32 positive results were obtained at a maximum of six samplings. Independent factors associated with positive BAC were perihilar location, stricture length ≥ 2 cm, and macroscopic papillary type. CONCLUSION In BDC patients with ENBD or PTCD, repeated BAC is useful, and six times was the optimum number of repeat samplings. Although the sensitivity of BAC is not sufficient for the preoperative diagnosis of malignant biliary stricture, the three independent factors noted above predict positive yields and indicate whether or not BAC should be repeated up to six times.
Collapse
Affiliation(s)
- Yasser A Abdelghani
- Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 568-8686, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Sclabas GM, Barton JG, Smyrk TC, Barrett DA, Khan S, Kendrick ML, Reid-Lombardo KM, Donohue JH, Nagorney DM, Que FG. Frequency of subtypes of biliary intraductal papillary mucinous neoplasm and their MUC1, MUC2, and DPC4 expression patterns differ from pancreatic intraductal papillary mucinous neoplasm. J Am Coll Surg 2011; 214:27-32. [PMID: 22112419 DOI: 10.1016/j.jamcollsurg.2011.09.025] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Revised: 09/27/2011] [Accepted: 09/30/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Biliary intraductal papillary mucinous neoplasm (B-IPMN) has been proposed as a unique clinicopathologic disease with distinct histopathologic features, although wide acceptance remains controversial. A recent consensus conference classified pancreatic IPMN (P-IPMN) into 4 subtypes (ie, gastric, intestinal, pancreatobiliary, oncocytic) based on morphologic appearance and mucin (MUC) staining properties. The aim of this study was to determine whether B-IPMN has similar histopathologic and immunologic subtypes to P-IPMN. STUDY DESIGN Specific immunostaining for MUC1, MUC2, and deleted for pancreas cancer, locus 4 were performed on specimens from 19 patients with a histopathologic diagnosis of B-IPMN. Immunostaining patterns of B-IPMN were correlated with histopathology. RESULTS Based on histopathology, the following subtypes of B-IPMN were identified: pancreatobiliary n = 9 (47%), intestinal n = 8 (42%), oncocytic n = 2 (11%), and gastric n = 0 (0%). Pancreatobiliary and oncocytic subtypes of B-IPMN were positive for MUC1 and negative for MUC2, and intestinal subtypes were positive for MUC2 and negative for MUC1. Thirteen of the 19 B-IPMN were associated with invasive carcinoma; loss of deleted for pancreas cancer, locus 4 was found in 6 of 13 invasive components and in 3 of 19 noninvasive components of B-IPMN. Five-year survival for patients with resected B-IPMN and invasive carcinoma was 38%, which is similar to that for resected P-IPMN with invasive carcinoma. CONCLUSIONS Histopathologic subtypes and type-specific MUC expression patterns of B-IPMN resemble those of P-IPMN. MUC1 expression and/or absence of MUC2 expression, which correlate with aggressive features of P-IPMN, were found in B-IPMN and correlate with invasive B-IPMN. Loss of deleted for pancreas cancer, locus 4 parallels the findings observed in P-IPMN. These findings provide additional support that B-IPMN is a unique entity with similarities to main duct P-IPMN.
Collapse
Affiliation(s)
- Guido M Sclabas
- Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN 55905, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Extensively spreading intraepithelial bile duct carcinoma causing multiple bile duct strictures: report of three cases. Surg Today 2011; 41:1674-9. [PMID: 21969205 DOI: 10.1007/s00595-011-4508-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2010] [Accepted: 01/27/2011] [Indexed: 10/17/2022]
Abstract
Extensive intraepithelial spread of bile duct carcinoma is a common feature, seen in approximately 18% of all cases. However, this spread is rarely accompanied by bile duct strictures. We herein describe three cases of bile duct carcinoma with multiple bile duct strictures due to extensive intraepithelial spread. In all three cases, the spread of intraepithelial cancer extended into the epithelium of the peribiliary glands along the intrahepatic bile ducts with marked fibrosis on histopathological examination. It is speculated that peribiliary gland involvement by superficially spreading bile duct cancer and subsequent obstructive glandular inflammation with fibrosis might cause intrahepatic bile duct strictures even without interstitial cancer invasion.
Collapse
|
|
38
|
Outcome of surgical treatment of hilar cholangiocarcinoma: a special reference to postoperative morbidity and mortality. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2009; 17:455-62. [PMID: 19820891 DOI: 10.1007/s00534-009-0208-1] [Citation(s) in RCA: 121] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2009] [Accepted: 09/01/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND/PURPOSE Radical resection for hilar cholangiocarcinoma is still associated with significant morbidity and mortality. The aim of this study was to analyze short-term surgical outcomes and to validate our strategies, including preoperative management and selection of operative procedure. METHODS We surgically treated 146 consecutive patients with hilar cholangiocarcinoma with a management strategy consisting of preoperative biliary drainage, portal vein embolization, and selection of operative procedure based on tumor extension and hepatic reserve. Major hepatectomy was conducted in 126 patients, and caudate lobectomy or hilar bile duct resection in 20 patients. RESULTS The overall 5-year survival rate was 35.5%, with overall in-hospital mortality and morbidity rates of 3.4 and 44%, respectively. Hyperbilirubinemia (total bilirubin >5 mg/dL, persisted for >7 postoperative days) and liver abscess were the most frequent complications. Five among 9 patients with liver failure (total bilirubin >10 mg/dL) encountered in-hospital mortality. Four out of 5 mortality patients had suffered circulatory impairment of the remnant liver due to other complications. Multivariate analysis revealed that operative time is a single independent significant predictive factor (odds ratio, 1.005; 95% confidence interval, 1.000-1.010, P = 0.04) for postoperative complications. CONCLUSIONS Aggressive resection for hilar cholangiocarcinoma, performed in accordance with strict management strategy, achieved acceptably low mortality. Prolonged operative time was a risk for morbidity following hepatobiliary resection.
Collapse
|
|
39
|
Hong SM, Pawlik TM, Cho H, Aggarwal B, Goggins M, Hruban RH, Anders RA. Depth of tumor invasion better predicts prognosis than the current American Joint Committee on Cancer T classification for distal bile duct carcinoma. Surgery 2009; 146:250-7. [PMID: 19628081 DOI: 10.1016/j.surg.2009.02.023] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2009] [Accepted: 02/27/2009] [Indexed: 01/04/2023]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) T classification system for cholangiocarcinoma does not take into account the unique pathologic features of the bile duct. As such, the current AJCC T classification for distal cholangiocarcinoma may be inaccurate. METHODS A total of 147 patients with distal cholangiocarcinoma were identified from a single institution database. The prognostic importance of depth of tumor invasion relative to the AJCC T classification system was assessed. RESULTS The AJCC T classification was T1 (n = 11, 7.5%), T2 (n = 6, 4.1%), T3 (n = 73, 49.7%), or T4 (n = 57, 38.8%). When cases were analyzed according to depth of tumor invasion, most lesions were > or =5 mm (<5 mm, 9.5%; range, 5-12, 51.0%; >12 mm, 39.5%). The AJCC T classification was not associated with survival outcome (median survival, T1, 40.1 months; T2, 14.8 months; T3, 16.5 months; T4, 20.2 months; P = .17). In contrast, depth of tumor invasion was associated with a worse outcome as tumor depth increased (median survival, <5 mm, not reached; range, 5-12, 28.9 months; >12 mm, 12.9 months; P = .001). On multivariate analyses, tumor depth remained the factor most associated with outcome (<5 mm; hazard ratio [HR] = referent vs 5-12 mm; HR = 3.8 vs >12 mm; HR = 6.7 mm; P = .001). CONCLUSION The AJCC T classification for distal cholangiocarcinoma does not accurately predict prognosis. Depth of the bile duct carcinoma invasion is a better alternative method to determine prognosis and should be incorporated into the pathologic assessment of resected distal cholangiocarcinoma.
Collapse
Affiliation(s)
- Seung-Mo Hong
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Yoshitomi H, Furukawa K, Mitsuhashi N, Takeuchi D, Takayashiki T, Suda K, Miyazaki M. Surgical strategy for mucin-producing bile duct tumor. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2009; 17:236-40. [PMID: 19649559 DOI: 10.1007/s00534-009-0152-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2009] [Accepted: 04/30/2009] [Indexed: 12/15/2022]
Abstract
Tumors with copious mucin production within the intra- or extrahepatic bile ducts have been reported as mucin-producing bile duct tumors (MPBTs). Because mucin produced by these tumors causes recurrent cholangitis and obstructive jaundice, surgical resection should be indicated even if these tumors are regarded as benign. In order to choose the appropriate surgical procedure, exact preoperative assessment of tumor location and cancer extension is important, especially evaluation of the extent of superficial spreading through cholangioscopic observation and biopsy. In principle, MPBTs should be resected in a manner similar to that employed for other types of bile duct carcinomas. That is, major hepatectomy with or without extrahepatic bile duct resection or pancreaticoduodenectomy should be chosen as the surgical procedure, and intraoperative frozen section at the stumps of the bile duct is essential. On the other hand, when precise diagnosis is completed preoperatively and the lesion is diagnosed as adenoma or carcinoma with invasion confined to the ductal wall and limited superficial spreading, limited resections preserving organ functions as much as possible can be considered as a choice among surgical procedures. All ten patients with MPBT resected at our institution according to these strategies are still alive without tumor recurrence, with a median survival of 48.0 months.
Collapse
Affiliation(s)
- Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba, 260-8670, Japan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Nakanishi Y, Kondo S, Zen Y, Yonemori A, Kubota K, Kawakami H, Tanaka E, Hirano S, Itoh T, Nakanuma Y. Impact of residual in situ carcinoma on postoperative survival in 125 patients with extrahepatic bile duct carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2009; 17:166-73. [DOI: 10.1007/s00534-009-0127-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2009] [Accepted: 05/12/2009] [Indexed: 01/04/2023]
Affiliation(s)
- Yoshitsugu Nakanishi
- Department of Surgical Oncology; Hokkaido University Graduate School of Medicine; Kita-15, Nishi-7, Kita-ku Sapporo 060-8638 Japan
- Department of Surgical Pathology; Hokkaido University Hospital; Sapporo Japan
- Department of Human Pathology; Kanazawa University Graduate School of Medicine; 13-1 Takaramachi Kanazawa 920-8640 Japan
| | - Satoshi Kondo
- Department of Surgical Oncology; Hokkaido University Graduate School of Medicine; Kita-15, Nishi-7, Kita-ku Sapporo 060-8638 Japan
| | - Yoh Zen
- Department of Human Pathology; Kanazawa University Graduate School of Medicine; 13-1 Takaramachi Kanazawa 920-8640 Japan
| | - Atsuya Yonemori
- Department of Surgical Oncology; Hokkaido University Graduate School of Medicine; Kita-15, Nishi-7, Kita-ku Sapporo 060-8638 Japan
- Department of Surgical Pathology; Hokkaido University Hospital; Sapporo Japan
| | - Kanako Kubota
- Department of Surgical Pathology; Hokkaido University Hospital; Sapporo Japan
| | - Hiroshi Kawakami
- Department of Gastroenterology; Hokkaido University Graduate School of Medicine; Kita-15, Nishi-7, Kita-ku Sapporo 060-8638 Japan
| | - Eiichi Tanaka
- Department of Surgical Oncology; Hokkaido University Graduate School of Medicine; Kita-15, Nishi-7, Kita-ku Sapporo 060-8638 Japan
| | - Satoshi Hirano
- Department of Surgical Oncology; Hokkaido University Graduate School of Medicine; Kita-15, Nishi-7, Kita-ku Sapporo 060-8638 Japan
| | - Tomoo Itoh
- Department of Surgical Pathology; Hokkaido University Hospital; Sapporo Japan
| | - Yasuni Nakanuma
- Department of Human Pathology; Kanazawa University Graduate School of Medicine; 13-1 Takaramachi Kanazawa 920-8640 Japan
| |
Collapse
|
|
42
|
Konishi M, Ochiai A, Ojima H, Hasebe T, Mano M, Ohta T, Ito I, Sasaki K, Yasukawa S, Shimada K, Iwasaki M, Yanagisawa A. A new histological classification for intra-operative histological examination of the ductal resection margin in cholangiocarcinoma. Cancer Sci 2009; 100:255-60. [PMID: 19068088 PMCID: PMC11158709 DOI: 10.1111/j.1349-7006.2008.01043.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
The purpose of this study was to establish a standard histological classification for intra-operative histological examination of ductal resection margins in cholangiocarcinoma to distinguish between epithelial and intramural lesions and to clarify correlations between the new classification and clinical outcomes. Intra-operative diagnosis of ductal margins was performed for 357 stumps from 216 patients undergoing surgical resection of cholangiocarcinoma at the National Cancer Center, Japan. Three expert pathologists reviewed the materials and established a histological classification defined by grade of atypia. The new classification comprised four categories: 'insufficient', insufficient for diagnosis due to distortion of specimen; 'negative for malignancy', no atypia suggestive of neoplasia; 'undetermined lesion', specimen showing either cellular or structural atypia; and 'positive for malignancy', specimen showing both cellular and structural atypia. Each category was defined to distinguish between epithelial and intramural lesions. Validity and reproducibility of the proposed classification were found to be moderate to substantial. Multivariate analyses using the clinicopathological factors identified to be associated with overall survival by univariate analyses indicated that patients diagnosed with 'positive for malignancy' in intramural lesions of the proximal margin displayed significant poor prognosis. Meanwhile, in patients diagnosed with 'positive for malignancy' or 'undetermined lesion' in epithelial lesions of the proximal margin, no difference in overall survival was apparent compared to patients diagnosed with 'negative for malignancy'. We propose new histological classification for intra-operative histological examination of ductal resection margins in cholangiocarcinoma that shows a correlation with patients' prognosis and should facilitate the determination of ductal resection margin status for cholangiocarcinoma.
Collapse
Affiliation(s)
- Masaru Konishi
- Upper Gastric Surgery Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha,Kashiwa, Chiba, Japan.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Ojima H, Kanai Y, Iwasaki M, Hiraoka N, Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T, Sakamoto M, Hirohashi S. Intraductal carcinoma component as a favorable prognostic factor in biliary tract carcinoma. Cancer Sci 2009; 100:62-70. [PMID: 19038006 PMCID: PMC11159250 DOI: 10.1111/j.1349-7006.2008.01009.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2008] [Revised: 09/09/2008] [Accepted: 09/16/2008] [Indexed: 11/29/2022] Open
Abstract
The aim of this study is to evaluate the prognostic impact of an intraductal carcinoma component and bile duct resection margin status in patients with biliary tract carcinoma. An intraductal carcinoma component was defined as carcinoma within the bile duct outside the main tumor nodule consisting of a subepithelial invasive component. Surgically resected materials from 214 patients were evaluated by histological observations. Seventy-nine patients (36.9%) with an intraductal carcinoma component infrequently developed large tumors and infrequently showed deep invasion and venous, lymphatic and perineural involvement in the main tumor nodule. An intraductal carcinoma component was inversely correlated with advanced clinical stage, and was shown to be a significantly favorable prognostic factor by both univariate and multivariate analyses. Proximal (hepatic) side bile duct resection margin status was categorized into negative for tumor cells, positive with only an intraductal carcinoma component [R1 (is)], and positive with a subepithelial invasive component (R1). Forty-five patients (21.0%) with an R1 resection margin had a poorer prognosis than 148 patients (69.2%) with a negative resection margin, whereas 21 patients (9.8%) with an R1 (is) resection margin did not. In patients with an R1 resection margin, the risk of anastomotic recurrence was higher, and the period until anastomotic recurrence was shorter, than in patients with an R1 (is) resection margin. Surgeons should not be persistent in trying to achieve a negative surgical margin when the intraoperative frozen section diagnosis is R1 (is), and can choose a safe surgical procedure to avoid postoperative complications.
Collapse
Affiliation(s)
- Hidenori Ojima
- Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|