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Yong YSS, Lee ZR, Soh YTN, Low SCA. Preoperative Imaging Assessment and Staging of Perihilar Cholangiocarcinoma: Tips and Pitfalls. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2025; 86:45-67. [PMID: 39958497 PMCID: PMC11822288 DOI: 10.3348/jksr.2024.0055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 07/30/2024] [Accepted: 10/01/2024] [Indexed: 02/18/2025]
Abstract
This article outlines the systematic radiological approach preoperative evaluation of perihilar cholangiocarcinoma (pCCA) using CT and MRI to provide key information regarding the suitability for curative surgical resection. It discusses older classification systems (Bismuth-Corlette, Memorial Sloan Kettering Cancer Center T staging) and follows the Korean Society of Abdominal Radiology 2019 consensus recommendations for step-by-step assessment. The correlation between radiological, surgical, and pathological findings is illustrated through a pictorial review of pathologically proven cases. Benign and malignant mimics of pCCA are included to provide a comprehensive overview.
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Affiliation(s)
- Yu Shan Stephanie Yong
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
| | - Zhuyi Rebekah Lee
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
| | - Yock Teck Nicholas Soh
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
| | - Su Chong Albert Low
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
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Otsuka S, Sugiura T, Ashida R, Ohgi K, Yamada M, Kato Y, Yumiko K, Ohike N, Sugino T, Uesaka K. Subdivision of pT1N0 (American Joint Committee on Cancer 8th edition) distal cholangiocarcinoma for adjuvant chemotherapy consideration. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:559-568. [PMID: 38946012 DOI: 10.1002/jhbp.12010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
BACKGROUND The adjuvant S-1 trial affirmed adjuvant chemotherapy for biliary tract cancer but excluded pT1N0 distal cholangiocarcinoma (DCC) according to the seventh edition of the American Joint Committee on Cancer (AJCC) classification. The introduction of tumor depth of invasion (DOI) for T-classification in the eighth edition complicates identifying DCC patients less likely to benefit from adjuvant chemotherapy. METHODS Our cohort consisted of 185 patients with DCC who underwent pancreaticoduodenectomy between 2002 and 2019. We compared clinicopathological factors and survival outcomes between pT1N0 patients in the seventh edition and those in the eighth edition. New DOI cutoffs for subdividing pT1N0 (8th edition) patients were evaluated to identify patients less likely to benefit from adjuvant chemotherapy. RESULTS Transitioning to the eighth edition increased in pT1N0 cases from eight to 46. The 5-year cumulative recurrence rates of them were 14.3% for the seventh edition and 28.3% for the eighth edition. We proposed a DOI cutoff of <2 mm, at which the 5-year cumulative recurrence rate was 11.5%. CONCLUSION The eighth AJCC classification revealed that a significant proportion of pT1N0 DCC patients were at risk for recurrence. A DOI cutoff of <2 mm may be considered to potentially improve patient selection for adjuvant chemotherapy.
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Affiliation(s)
- Shimpei Otsuka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Mihoko Yamada
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yoshiyasu Kato
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kageyama Yumiko
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Nobuyuki Ohike
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
- Department of Pathology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Takashi Sugino
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
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Yoshii H, Izumi H, Fujino R, Kurata M, Inomoto C, Sugiyama T, Nakagohri T, Nomura E, Mukai M, Tajiri T. Subserosal Layer and/or Pancreatic Invasion Based on Anatomical Features as a Novel Prognostic Indicator in Patients with Distal Cholangiocarcinoma. Diagnostics (Basel) 2023; 13:3406. [PMID: 37998542 PMCID: PMC10670817 DOI: 10.3390/diagnostics13223406] [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: 10/05/2023] [Revised: 10/27/2023] [Accepted: 11/02/2023] [Indexed: 11/25/2023] Open
Abstract
The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.
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Affiliation(s)
- Hisamichi Yoshii
- Department of Gastroenterological Surgery, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan
| | - Hideki Izumi
- Department of Gastroenterological Surgery, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan
| | - Rika Fujino
- Department of Gastroenterological Surgery, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan
| | - Makiko Kurata
- Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan (T.S.); (T.T.)
| | - Chie Inomoto
- Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan (T.S.); (T.T.)
| | - Tomoko Sugiyama
- Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan (T.S.); (T.T.)
| | - Toshio Nakagohri
- Department of Gastroenterological Surgery, Tokai University Hospital, Isehara 259-1193, Japan
| | - Eiji Nomura
- Department of Gastroenterological Surgery, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan
| | - Masaya Mukai
- Department of Gastroenterological Surgery, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan
| | - Takuma Tajiri
- Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan (T.S.); (T.T.)
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Kawakatsu S, Mizuno T, Yamaguchi J, Watanabe N, Onoe S, Sunagawa M, Baba T, Igami T, Yokoyama Y, Imaizumi T, Ebata T. The Goal of Intraoperative Blood Loss in Major Hepatobiliary Resection for Perihilar Cholangiocarcinoma: Saving Patients From a Heavy Complication Burden. Ann Surg 2023; 278:e1035-e1040. [PMID: 37051914 DOI: 10.1097/sla.0000000000005869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
OBJECTIVE To determine the goal of intraoperative blood loss in hepatectomy for perihilar cholangiocarcinoma. BACKGROUND Although massive bleeding can negatively affect the postoperative course, the target value of intraoperative bleeding to reduce its adverse impact is unknown. METHODS Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were included. Intraoperative blood loss was adjusted for body weight [adjusted blood loss (aBL)], and the overall postoperative complications were evaluated by the comprehensive complication index (CCI). The impact of aBL on CCI was assessed by the restricted cubic spline regression. RESULTS A total of 425 patients were included. The median aBL was 17.8 (interquartile range, 11.8-26.3) mL/kg, and the CCI was 40.6 (33.7-49.5). Sixty-three (14.8%) patients had an aBL<10 mL/kg, nearly half (45.4%) of the patients were in the range of 10 ≤aBL<20 mL/kg, and 37 (8.7%) patients had an aBL >40 mL/kg. The spline regression analysis showed a nonlinear incremental association between aBL and CCI; CCI remained flat with an aBL under 10 mL/kg; increased significantly with an aBL ranging from 10 to 20 mL/kg; grew gradually with an aBL over 20 mL/kg. These inflection points of ~10 and 20 mL/kg were almost consistent with the cutoff values identified by the recursive partitioning technique. After adjusting for other risk factors for the postoperative course, the spline regression identified a similar model. CONCLUSIONS aBL had a nonlinear aggravating effect on CCI after hepatectomy for perihilar cholangiocarcinoma. The primary goal of aBL should be <10 mL/kg to minimize CCI.
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Affiliation(s)
- Shoji Kawakatsu
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobuyuki Watanabe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shunsuke Onoe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masaki Sunagawa
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Taisuke Baba
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takahiro Imaizumi
- Department of Advanced Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Bajracharya AD, Shrestha S, Kim HS, Nahm JH, Park K, Park JS. Retrospective analysis of 8th edition American Joint Cancer Classification: Distal cholangiocarcinoma. Ann Hepatobiliary Pancreat Surg 2023; 27:251-257. [PMID: 37128850 PMCID: PMC10472119 DOI: 10.14701/ahbps.22-134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/06/2023] [Accepted: 02/14/2023] [Indexed: 05/03/2023] Open
Abstract
Backgrounds/Aims This is a retrospective analysis of whether the 8th edition American Joint Committee on Cancer (AJCC) was a significant improvement over the 7th AJCC distal extrahepatic cholangiocarcinoma classification. Methods In total, 111 patients who underwent curative resection of mid-distal bile duct cancer from 2002 to 2019 were included. Cases were re-classified into 7th and 8th AJCC as well as clinicopathological univariate and multivariate, and Kaplan-Meier survival curve and log rank were calculated using R software. Results In patient characteristics, pancreaticoduodenectomy/pylorus preserving pancreaticoduodenectomy had better survival than segmental resection. Only lymphovascular invasion was found to be significant (hazard ratio 2.01, p = 0.039) among all clinicopathological variables. The 8th edition AJCC Kaplan Meier survival curve showed an inability to properly segregate stage I and IIA, while there was a large difference in survival probability between IIA and IIB. Conclusions The 8th distal AJCC classification did resolve the anatomical issue with the T stage, as T1 and T3 showed improvement over the 7th AJCC, and the N stage division of the N1 and N2 category was found to be justified, with poorer survival in N2 than N1. Meanwhile, in TMN staging, the 8th AJCC was able differentiate between early stage (I and IIA) and late stage (IIB and III) to better explain the patient prognosis.
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Affiliation(s)
- Atish Darshan Bajracharya
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Suniti Shrestha
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyung Sun Kim
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Hae Nahm
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kwanhoon Park
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Joon Seong Park
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Jun SY, Shin JH, Chun J, Kang HJ, Hong SM. The T Category of Distal Extrahepatic Bile Duct Carcinoma: A Comparative Analysis With Invasive Tumor Thickness. Am J Surg Pathol 2022; 46:907-920. [PMID: 35288524 DOI: 10.1097/pas.0000000000001884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The T category of distal extrahepatic bile duct carcinoma (DBDC) is based on invasion depth from the basal lamina to the deepest infiltrating tumor cells. Recently, invasive tumor thickness (ITT) was proposed, defined as maximal vertical distance of invasive tumor components regardless of the basal lamina. We compared the predictive value of T category, and ITT grading in 424 surgically resected DBDCs. DBDCs were categorized as 6 Tis (1.4%), 134 T1 (<5 mm; 31.6%), 204 T2 (5 to 12 mm; 48.1%), and 80 T3 (>12 mm; 18.9%). With ITT, there were 6 G0 (no invasion; 1.4%), 3 G1 (<1 mm; 0.7%), 90 G2 (≥1 and <5 mm; 21.2%), 188 G3 (≥5 and <10 mm; 44.4%), and 137 G4 (≥10 mm; 32.3%). The 5-year survival rates of T1, T2, and T3 were 58.9%, 44.2%, and 18.2%, and those of ITT G1, G2, G3, and G4 were 33.3%, 54.1%, 51.6%, and 26.7%, respectively. The T category discriminated patient survival by overall (P<0.001) and pairwise (T1 vs. T2, P=0.007; T2 vs. T3, P<0.001) comparisons. ITT grading distinguished survival by overall and between G3-G4 (both P<0.001), with no survival differences observed between G1-G2 and G2-G3 comparisons. The T category more accurately discriminated patient survival than ITT grading. To determine the T category for DBDCs, (1) longitudinal sectioning on gross examination, especially for DBDCs with large papillary or nodular growth patterns; (2) evaluation of serial sections or alternative hematoxylin and eosin slides; (3) use of a straight or curved baseline depending on the shape of the peritumoral normal bile duct wall and/or the basal lamina of the peritumoral normal biliary epithelia/biliary intraepithelial neoplasias are recommended.
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Affiliation(s)
- Sun-Young Jun
- Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Jae Hoon Shin
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihyun Chun
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyo Jeong Kang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Tamura S, Yamamoto Y, Sugiura T, Okamura Y, Ito T, Ashida R, Ohgi K, Sasaki K, Sugino T, Uesaka K. The evaluation of the 8th and 7th edition of the American joint committee on cancer tumor classification for distal cholangiocarcinoma: the proposal of a modified new tumor classification. HPB (Oxford) 2021; 23:1209-1216. [PMID: 33358564 DOI: 10.1016/j.hpb.2020.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 10/03/2020] [Accepted: 12/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The 7th and 8th editions of the American Joint Committee on Cancer (AJCC) tumor (T) classification of distal cholangiocarcinoma (DCC), which are based on either layer or depth, may not accurately stratify patient survival. METHODS A total of 121 patients who underwent resection for DCC between 2002 and 2016 were analyzed. The impact of the AJCC staging system on survival was examined and a new T classification was established based on independent prognostic factors. RESULTS Regarding overall survival, the optimal depth of invasion (DOI) cut-off value (8 mm) was the only independent prognostic factor. Regarding the relapse-free survival (RFS), a DOI >8 mm, portal vein (PV) invasion, and duodenal or pancreatic invasion were independent prognostic factors. A new T classification was developed as follows: T1, no invasion of adjacent organs; T2, invasion of the duodenum or pancreas; T3, invasion >8 mm into the bile duct wall; and T4, invasion of the PV or arteries. There were no significant differences in RFS according to the 8th edition of the AJCC. However, significant differences were observed in the RFS between T1 and T2 and between T2 and T3. CONCLUSION A new T classification based on the layer and depth may be more feasible.
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Affiliation(s)
- Shunsuke Tamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
| | - Keiko Sasaki
- Division of Pathology, Shizuoka Cancer Center, Japan
| | | | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan
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Oba M, Nakanishi Y, Amano T, Okamura K, Tsuchikawa T, Nakamura T, Noji T, Asano T, Tanaka K, Hirano S. Stratification of Postoperative Prognosis by Invasive Tumor Thickness in Perihilar Cholangiocarcinoma. Ann Surg Oncol 2020; 28:2001-2009. [PMID: 33040247 DOI: 10.1245/s10434-020-09135-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 08/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The pathological tumor classification of distal cholangiocarcinoma in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition is based on invasive depth, whereas that of perihilar cholangiocarcinoma (PHCC) continues to be layer-based. We aimed to clarify whether invasive depth measurement based on invasive tumor thickness (ITT) could help determine postoperative prognosis in patients with PHCC. METHODS We enrolled 184 patients with PHCC who underwent hepatectomy plus extrahepatic bile duct resection or hepatopancreatoduodenectomy with curative intent. ITT was measured using simple definitions according to the sectioning direction or gross tumor pattern. RESULTS The median ITT was 5.8 mm (range 0.7-15.5). Using the recursive partitioning technique, ITT was classified into grades A (ITT < 2 mm, n = 9), B (2 mm ≤ ITT < 5 mm, n = 68), C (5 mm ≤ ITT < 11 mm, n = 81), and D (11 mm < ITT, n = 26). The median survival times (MSTs) in patients with grade B, C, or D were 90.8, 44.6, and 21.1 months, respectively (patients with grade A did not reach the MST). There were significant differences in postoperative prognosis between ITT grades (A vs. B, p = 0.027; B vs. C, p < 0.001; C vs. D, p = 0.004). Through multivariate analysis, regional node metastasis, invasive carcinoma at the resected margin, and ITT grade were determined as independent prognostic factors. CONCLUSION ITT could be measured using simple methods and may be used to stratify postoperative prognosis in patients with PHCC.
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Affiliation(s)
- Mitsunobu Oba
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.,Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | - Yoshitsugu Nakanishi
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
| | - Toraji Amano
- Clinical Research and Medical Innovation Centre, Hokkaido University Hospital, Sapporo, Japan
| | - Keisuke Okamura
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Toshimichi Asano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
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Refining Severe Tricuspid Regurgitation Definition by Echocardiography with a New Outcomes-Based "Massive" Grade. J Am Soc Echocardiogr 2020; 33:1087-1094. [PMID: 32651124 DOI: 10.1016/j.echo.2020.05.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 05/07/2020] [Accepted: 05/07/2020] [Indexed: 11/23/2022]
Abstract
BACKGROUND Current echocardiographic guidelines recommend that tricuspid regurgitation (TR) severity be graded in three categories, following assessment of specific parameters. Findings from recent trials have shown that the severity of TR frequently far exceeds the current definition of severe. We postulated that a grading approach that emphasizes outcomes could be useful to identify patients with severe TR at increased risk of mortality. METHODS We identified 284 patients with echocardiograms demonstrating severe functional TR, defined as vena contracta (VC) ≥ 0.7 cm. Demographics and mortality data were obtained from the medical records. Patients were divided into study (n = 122 patients with three-dimensional images) and validation (n = 162) cohorts. The VC was measured in both the right ventricular (RV) inflow and apical four-chamber views and averaged. For the study cohort, tricuspid annular, RV end-diastolic (basal, mid, long axis) dimensions, tricuspid leaflet tenting height and area, RV free-wall longitudinal strain, and RV volumes were measured from two- and three-dimensional data sets. A K-partition algorithm was used in the study cohort to derive a mortality-related cutoff VC value, above which TR was termed "massive." The ability of this VC cutoff to identify patients at greater mortality risk was then tested in the validation cohort using Kaplan-Meier survival analysis. RESULTS In the study cohort, VC > 0.92 cm (massive TR) was optimally associated with worse survival. Tricuspid annular and RV size were larger in the massive group (P < .05), while there were no significant differences in demographics between the TR groups. Importantly, in the independent validation cohort, the above VC cutoff also correlated with increased mortality in the massive group (log-rank P < .05). CONCLUSIONS Among patients traditionally defined as having severe TR, a subset exists with massive TR, resulting in greater adverse RV remodeling and increased mortality. These patients may derive the greatest benefit from emerging percutaneous therapies.
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10
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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.
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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.
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Clinicopathological significance of olfactomedin-4 in extrahepatic bile duct carcinoma. Pathol Res Pract 2020; 216:152940. [PMID: 32276789 DOI: 10.1016/j.prp.2020.152940] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/01/2020] [Accepted: 03/21/2020] [Indexed: 12/28/2022]
Abstract
The clinicopathological and prognostic significance of olfactomedin-4 (OLFM4) expression has not yet been elucidated in extrahepatic bile duct carcinomas (EBDCs). Immunohistochemical analysis of OLFM4 expression in 31 normal biliary epithelia, 33 biliary intraepithelial neoplasias (BilINs), and 180 surgically resected EBDCs (54 perihilar and 126 distal) was performed and was used to analyze clinicopathological variables including patient survival. The expression of OLFM4 showed a progressive increase from normal biliary epithelia (0.2 ± 0.4) to BilINs (2.8 ± 3.2) to EBDCs (4.6 ± 4.2; P < 0.001). OLFM4 was highly expressed in 26.1% (47/180) of the EBDC cases, and high OLFM4 levels were more frequently observed in tumors with nodular growth (P = 0.029), well differentiation (P = 0.011), and lower T-category (P = 0.025) and stage grouping (P = 0.013). Patients with EBDC having high expression of OLFM4 had better survival than those with low expression of OLFM4 (median, 43.3 vs. 29.2 months; P = 0.037). OLFM4 might play an important role in carcinogenesis and in the progression from BilINs to EBDCs. High OLFM4 expression predicted less aggressive clinical behavior in patients with EBDC.
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12
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Proposed Modification of Staging for Distal Cholangiocarcinoma Based on the Lymph Node Ratio Using Korean Multicenter Database. Cancers (Basel) 2020; 12:cancers12030762. [PMID: 32213853 PMCID: PMC7140100 DOI: 10.3390/cancers12030762] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 03/17/2020] [Accepted: 03/20/2020] [Indexed: 02/07/2023] Open
Abstract
The 8th American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (DCC) included a positive lymph node count (PLNC), but a comparison of the prognostic predictive power of PLNC and lymph node ratio (LNR) is still under debate. This study aimed to compare various staging models made by combining the abovementioned factors, identify the model with the best predictive power, and propose a modified staging system. We retrospectively reviewed 251 patients who underwent surgery for DCC at four centers. To determine the superiority of various staging models for predicting overall OSR, Akaike information criterion (AIC), Bayesian information criterion (BIC), AIC correction (AICc), and Harrell’s C-statistic were calculated. In multivariate analysis, age (p = 0.003), total lymph node count (p = 0.033), and revised T(LNR)M staging (p < 0.001) were identified as independent factors for overall survival rate. The predictive performance of revised T (LNR) M staging (AIC: 1288.925, BIC: 1303.377, AICc: 1291.52, and Harrell’s C statics: 0.667) was superior to other staging system. A modified staging system consisting of revised T category and LNR predicted better overall survival of DCC than AJCC 7th and AJCC 8th editions. In the future, external validation of the proposed new system using a larger cohort will be required.
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13
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Zhao S, Qi W, Chen J. Competing risk nomogram to predict cancer-specific survival in esophageal cancer during the intensity-modulated radiation therapy era: A single institute analysis. Oncol Lett 2020; 19:3513-3521. [PMID: 32269625 PMCID: PMC7114720 DOI: 10.3892/ol.2020.11448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 01/21/2020] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to investigate the probability of cancer-associated mortality of patients with esophageal cancer undergoing intensity-modulated radiation therapy (IMRT), and to establish a competing risk nomogram to predict the esophageal cancer-specific survival (EC-SS) of these patients. A total of 213 patients with EC who underwent IMRT between January 2014 and May 2017 were selected to establish nomograms according to Fine and Gray's competing risk analysis. Predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index), calibration curves and the area under receiver operating characteristic curves. Decision tree analysis was also constructed for patient grouping. With a median follow-up of 19 months (range, 3–50), the 2-year EC-specific mortality (EC-SM) and the non-esophageal cancer specific mortality (NEC-SM) of the cohort were 35.4 and 3.51%, respectively. Furthermore, an elevated 2-year EC-SM was observed in patients with tumor length ≥4.5 cm compared with patients with tumor length <4.5 cm (45.8% vs. 21.4%; P<0.001), patients with non-squamous cell carcinoma compared with patients with squamous cell carcinoma (49.9 vs. 33.7%; P=0.025) and patients with N3 stage (43.2%; P=0.005). The 2-year NEC-SM of patients with tumor length ≥4.5 cm was 6% vs. 0% in patients with tumor length <4.5 cm (P=0.016). Three independent risk factors for survival, including tumor length, histological type and N stage, were integrated to build competing nomograms for the EC-SS model (C-index=0.72; 95% confidence interval, 0.66–0.77). In addition, the nomograms displayed better discrimination power than the 7th edition of the Tumor-Node-Metastasis staging system for predicting EC-SS (area under the curve=0.707 vs. 0.634). Furthermore, the results from the classification tree analysis demonstrated that N stage was the initial node and that primary tumor length was a determinant for EC-SM in these patients. In conclusion, NEC-SM represented a competing event for patients with EC with a tumor length ≥4.5 cm. The competing risk nomograms may therefore be considered as convenient individualized predictive tools for cancer-specific survival in patients with EC undergoing IMRT treatment.
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Affiliation(s)
- Shengguang Zhao
- Department of Radiation Oncology, Rui Jin Hospital Affiliated Medicine School of Shanghai Jiao Tong University, Shanghai 200025, P.R. China
| | - Weixiang Qi
- Department of Radiation Oncology, Rui Jin Hospital Affiliated Medicine School of Shanghai Jiao Tong University, Shanghai 200025, P.R. China
| | - Jiayi Chen
- Department of Radiation Oncology, Rui Jin Hospital Affiliated Medicine School of Shanghai Jiao Tong University, Shanghai 200025, P.R. China
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14
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Park JY, Kim SY, Shin DH, Choi KU, Kim JY, Sol MY, Lee HJ, Hwang C, Ryu JH, Yang KH, Lee TB, Lee JH. Validation of the T category for distal cholangiocarcinoma: Measuring the depth of invasion is complex but correlates with survival. Ann Diagn Pathol 2020; 46:151489. [PMID: 32169826 DOI: 10.1016/j.anndiagpath.2020.151489] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 02/25/2020] [Accepted: 02/25/2020] [Indexed: 10/24/2022]
Abstract
According to the current 8th edition of the American Joint Committee of Cancer (AJCC), the T category of distal cholangiocarcinomas is classified based on the depth of invasion (DOI) (T1, < 5 mm; T2, between 5 and 12 mm; T3, > 12 mm). In consideration of the discrepancies between previous studies about the prognostic significance, we aimed to validate the current AJCC T staging system of distal cholangiocarcinomas. DOI was measured using three different methods: DOI1, DOI2, and DOI3. DOI1 was defined and stratified according to the AJCC 8th edition. DOI2 was measured as the distance from an imaginary curved line approximated along the distorted mucosal surface to the deepest invasive tumor cells. DOI3 was defined as the total tumor thickness. DOI2 and DOI3 were also divided into three categories using the same cut-off points as in the AJCC 8th edition. We compared these three DOI methods to the AJCC 7th edition as well. In contrast with the AJCC 7th edition, all three groups showed a correlation with patients' overall survival. Above all, the DOI2 group demonstrated the best significance in multivariate analysis. However, when the C indices were compared between these groups, differential significance proved to be negligible (DOI1 vs DOI2, p = 0.915; DOI2 vs DOI3, p = 0.057). Therefore, the measurement of DOI does not need to be rigorously and stringently performed. In conclusion, we showed that the current T classification system better correlates with the overall survival of patients with distal cholangiocarcinomas than the previous system.
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Affiliation(s)
- Joon Young Park
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - So Young Kim
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Dong Hoon Shin
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Kyung Un Choi
- Department of Pathology, Pusan National University Hospital, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan-si 49241, Republic of Korea
| | - Jee Yeon Kim
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Mee Young Sol
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Hyun Jung Lee
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Chungsu Hwang
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Kwang Ho Yang
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Tae Beom Lee
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Jung Hee Lee
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea.
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15
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Ueno M, Morizane C, Ikeda M, Okusaka T, Ishii H, Furuse J. A review of changes to and clinical implications of the eighth TNM classification of hepatobiliary and pancreatic cancers. Jpn J Clin Oncol 2020; 49:1073-1082. [PMID: 31822900 DOI: 10.1093/jjco/hyz150] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 08/27/2019] [Indexed: 12/19/2022] Open
Abstract
Hepatobiliary and pancreatic cancers have poor outcomes. Clinical staging is useful for predicting survival and selecting treatment options. The 8th edition of tumor-node metastasis (TNM) was published in 2016 and came into effect from 2018. Regarding liver cancer (hepatocellular carcinoma), tumour size and vascular invasion were more emphasized adding numbers. Tumour size was included for intrahepatic cholangiocarcinoma. T2 for gallbladder cancer was divided into two categories based on the side of invasion, and lymph node metastasis was classified according to the number of lymph nodes, not the site. The N category for perihilar cholangiocarcinoma was changed to the same as that for gallbladder cancer (total number of regional lymph nodes). The depth of tumour invasion using cut-off values of 5 and 12 mm was adopted as the T category for distal cholangiocarcinoma. The N category was also changed (the total number of regional lymph nodes). Regarding cancer of the ampulla of Vater, the T category was classified in more detail and the N category was also changed to the total number of regional lymph nodes. T1 for pancreatic cancer was separated into T1 subcategories (T1a, T1b and T1c) based on cut-off values of 5 and 10 mm. T1-T3 were classified with cut-off values of ≤2 cm, >2 to 4 cm and >4 cm. Furthermore, the N category was changed to the total number of regional lymph nodes. Although there are limitations due to treatment decisions only being based on imaging interpretation, this classification predicts the prognosis of patients more accurately than the previous edition.
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Affiliation(s)
- Makoto Ueno
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Japan
| | - Hiroshi Ishii
- Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Japan
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Jun SY, An S, Sung YN, Park Y, Lee JH, Hwang DW, Hong SM. Clinicopathologic and Prognostic Significance of Gallbladder and Cystic Duct Invasion in Distal Bile Duct Carcinoma. Arch Pathol Lab Med 2019; 144:755-763. [DOI: 10.5858/arpa.2019-0218-oa] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—
The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated.
Objective.—
To define the characteristics and prognostic significance of gallbladder or CD invasions in patients with DBDC.
Design.—
Organ invasion patterns with clinicopathologic features were assessed in 258 resected DBDCs.
Results.—
CD invasions (N = 31) were associated with frequent concomitant pancreatic and/or duodenal invasions (23 of 31, 74%) and showed stromal infiltration (16 of 31, 52%) and intraductal cancerization (15 of 31, 48%) patterns. In only 2 cases, invasions with intraductal cancerization were observed in the gallbladder neck. Conversely, all pancreatic (N = 175) and duodenal (83) invasions developed through stromal infiltration. CD invasions were associated with larger tumor size (P = .001), bile duct margin positivity (P = .001), perineural invasions (P = .04), and higher N categories (P = .007). Patients with pancreatic or duodenal invasions had significantly lower survival rates than those without pancreatic (median, 31.0 versus 93.9 months) or duodenal (27.5 versus 56.8 months, P < .001, both) invasions. However, those with gallbladder or CD invasions did not have different survival times (P = .13). Patients with concomitant gallbladder/CD and pancreatic/duodenal invasions demonstrated significantly lower survival rates than those without organ invasions (P < .001).
Conclusions.—
Gallbladder invasions were rare in DBDCs as neck invasions with intraductal cancerization. CD invasions occurred by stromal infiltrations and intraductal cancerization, whereas all pancreatic and duodenal invasions had stromal infiltration patterns. Gallbladder and/or CD invasions did not affect survival rates of patients with DBDC, while pancreatic and duodenal invasions affected survival rates. Therefore, these differences in survival rates may originate from the different invasive patterns of DBDCs.
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Affiliation(s)
- Sun-Young Jun
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Soyeon An
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - You-Na Sung
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yejong Park
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Hoon Lee
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dae Wook Hwang
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung-Mo Hong
- From the Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea (Drs Jun and An); and the Departments of Pathology (Drs Sung and Hong) and Surgery (Drs Park, Lee, and Hwang), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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17
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Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth. Br J Surg 2019; 106:427-435. [DOI: 10.1002/bjs.11063] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/26/2018] [Accepted: 10/30/2018] [Indexed: 12/19/2022]
Abstract
Abstract
Background
The T system for distal cholangiocarcinoma has been revised from a layer-based to a depth-based approach in the current American Joint Committee on Cancer (AJCC) classification. In perihilar cholangiocarcinoma, tumour depth in the staging scheme has not yet been addressed. The aim of this study was to propose a new T system using measured tumour depth in perihilar cholangiocarcinoma.
Methods
Patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively. The vertical distance between the top of the tumour and deepest invasive cells was measured as invasive tumour thickness (ITT) by two independent pathologists. Log rank statistics were used to determine cut-off points, and the concordance (C) index was used to assess survival discrimination of each T system.
Results
ITT was measurable in all 440 patients, with a median value of 6·0 (range 0–45) mm. The median difference in ITT between observers was 0·6 (range 0–20) mm. Cut-off points for prognosis were 1, 5 and 8 mm. Five-year survival decreased with increasing ITT (P < 0·001): 67 per cent for ITT less than 1 mm (25 patients), 54·9 per cent for ITT 1 mm and over to less than 5 mm (138 patients), 43·4 per cent for ITT 5 mm and over to less than 8 mm (118 patients), and 32·2 per cent for ITT 8 mm and over (159 patients). The C-index of this classification was comparable to that of the current AJCC T classification (0·598 versus 0·589).
Conclusion
ITT is a reliable approach for making a depth assessment in perihilar cholangiocarcinoma. A four-tier ITT classification with cut-off points of 1, 5 and 8 mm is an adequate alternative to the current layer-based T classification.
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18
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Endobiliary radiofrequency ablation for distal extrahepatic cholangiocarcinoma: A clinicopathological study. PLoS One 2018; 13:e0206694. [PMID: 30439965 PMCID: PMC6237299 DOI: 10.1371/journal.pone.0206694] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/17/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Most patients with distal extrahepatic cholangiocarcinoma have developed jaundice or cholangitis at the time of initial diagnosis, which can delay surgery. We aim to evaluate the actual EB-RFA ablation volume and validated the clinical feasibility of preoperative endobiliary radiofrequency ablation (EB-RFA) for resectable distal extrahepatic cholangiocarcinoma. METHODS The medical records of patients who underwent EB-RFA from July 2016 to June 2017 at a single tertiary academic medical center were reviewed. Inclusion criteria were patients with resectable distal extrahepatic cholangiocarcinoma who required preoperative biliary decompression. Clinical outcomes of EB-RFA were reviewed retrospectively and the surgical specimens were reevaluated. RESULTS Of the eight patients who required a delayed operation, preoperative EB-RFA was successfully performed without serious complications including peritonitis, hemobilia, or perforation. Although curative resection was attempted in all patients, one patient underwent open and closure due to hepatic metastasis. Seven patients underwent curative surgical resection and the histology revealed that median maximal ablation depth was 4.0 mm (range, 1-6) and median effective ablation length (histological ablation length/fluorosocopic ablation length) was 72.0% (range, 42.1-95.3). CONCLUSIONS EB-RFA partially ablated human cancer tissue and preoperative EB-RFA might be a safe and feasible in patients with distal extrahepatic cholangiocarcinoma who require a delayed operation. Ablation of the target lesion longer than the estimated length by fluoroscopy may improve the efficacy of EB-RFA.
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19
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Min KW, Kim DH, Son BK, Moon KM, Kim EK, Oh YH, Kwon MJ, Choi HS. Dual-organ invasion is associated with a lower survival rate than single-organ invasion distal bile duct cancer: A multicenter study. Sci Rep 2018; 8:10826. [PMID: 30018404 PMCID: PMC6050240 DOI: 10.1038/s41598-018-29205-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 07/06/2018] [Indexed: 01/04/2023] Open
Abstract
The revised criteria of the 8th American Joint Committee on Cancer (AJCC) cancer staging system consider depth of invasion as one of the factors that determine stage in distal bile duct (DBD) cancer, but exclude adjacent organ invasion. The aims were to evaluate the association between adjacent organ invasion and relapse-free survival (RFS) and overall survival (OS) after curative surgical resection of DBD cancer and to propose optimal criteria for predicting clinical outcomes. In this retrospective cohort study, 378 patients with DBD cancer treated in multi-institutions between 1996 and 2013 were investigated. This study evaluated the relationship between clinicopathologic parameters and adjacent organ invasion and used organ invasion to compare the survival times of each group. Among 204 patients with adjacent organ invasion, 152 were in the single-organ invasion group and 52 were in the dual-organ invasion group based on a review of microscopic slides. In univariate and multivariate analyses, patients with dual-organ invasion had a shorter RFS and OS time than those with single-organ invasion. Organ invasion should be included as one of the factors that determine the AJCC stage; this might ultimately help to predict better the survival rate of patients with DBD cancer.
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Affiliation(s)
- Kyueng-Whan Min
- Department of Pathology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Dong-Hoon Kim
- Departments of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Byoung Kwan Son
- Departments of Internal Medicine Eulji Hospital, Eulji University School of medicine, Seoul, Republic of Korea.
| | - Kyoung Min Moon
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea
| | - Eun-Kyung Kim
- Departments of Pathology, Eulji Hospital, Eulji University School of medicine, Seoul, Republic of Korea
| | - Young-Ha Oh
- Department of Pathology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Mi Jung Kwon
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Ho Soon Choi
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
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20
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Abstract
This article focuses on cholangiocarcinoma, both intrahepatic and extrahepatic. The various classification schemes based on anatomic location, macroscopic growth pattern, microscopic features, and cell of origin are outlined. The clinicopathologic, immunohistochemical and molecular differences between intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, as well as differences in the 2 subtypes of intrahepatic cholangiocarcinoma, are discussed. Finally, precursor lesions, prognosis, treatment, and promising new potential targeted therapies are reviewed.
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Affiliation(s)
- Alyssa M Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University Hospital, 1364 Clifton Road Northeast, Suite H180D, Atlanta, GA 30322, USA.
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21
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Aoyama H, Ebata T, Hattori M, Takano M, Yamamoto H, Inoue M, Asaba Y, Ando M, Nagino M, Aoba T, Kaneoka Y, Arai T, Shimizu Y, Kiriyama M, Sakamoto E, Miyake H, Takara D, Shirai K, Ohira S, Kobayashi S, Kato Y, Yamaguchi R, Hayashi E, Miyake T, Mizuno S, Sato T, Suzuki K, Hashimoto M, Kawai S, Matsubara H, Kato K, Yokoyama S, Suzumura K. Reappraisal of classification of distal cholangiocarcinoma based on tumour depth. Br J Surg 2018; 105:867-875. [DOI: 10.1002/bjs.10869] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 02/22/2018] [Accepted: 03/02/2018] [Indexed: 02/02/2023]
Abstract
Abstract
Background
In the eighth edition of the AJCC cancer staging classification, the T system for distal cholangiocarcinoma (DCC) has been revised from a layer-based to a depth-based approach. The aim of this study was to propose an optimal T classification using a measured depth in resectable DCC.
Methods
Patients who underwent pancreatoduodenectomy for DCC at 32 hospitals between 2001 and 2010 were included. The distance between the level of the naive bile duct and the deepest cancer cells was measured as depth of invasion (DOI). Invasive cancer foci were measured as invasive tumour thickness (ITT). Log rank χ2 scores were used to determine the cut-off points, and concordance index (C-index) to assess the survival discrimination of each T system.
Results
Among 404 patients, DOI was measurable in 182 (45·0 per cent) and ITT was measurable in all patients, with median values of 2·3 and 5·6 mm respectively. ITT showed a positive correlation with DOI (rs = 0·854, P < 0·001), and the cut-off points for prognosis were 1, 5 and 10 mm. Median survival time was shorter with increased ITT: 12·4 years for ITT below 1 mm, 5·2 years for ITT at least 1 mm but less than 5 mm, 3·0 years for ITT at least 5 mm but less than 10 mm, and 1·5 years for ITT 10 mm or more (P < 0·001). This classification exhibited more favourable prognostic discrimination than the T systems of the seventh and eighth editions of the AJCC (C-index 0·646, 0·622 and 0·624 respectively).
Conclusion
ITT is an accurate approach for depth assessment in DCC. The four-tier ITT classification with cut-off points of 1, 5 and 10 mm seems to be a better T system than those in the seventh and eighth editions of the AJCC classification.
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Affiliation(s)
- H Aoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - T Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - M Hattori
- Department of Surgery, Nishichita General Hospital, Tokai, Japan
| | - M Takano
- Department of Surgery, Asahi Rousai Hospital, Owariasahi, Japan
| | - H Yamamoto
- Department of Surgery, Tokai Hospital, Nagoya, Japan
| | - M Inoue
- Department of Surgery, Tokoname City Hospital, Tokoname, Japan
| | - Y Asaba
- Department of Surgery, JA Shizuoka Kohseiren Enshu Hospital, Hamamatsu, Japan
| | - M Ando
- Centre for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
| | - M Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - T Aoba
- Toyohashi Municipal Hospital, Toyohashi
| | | | - T Arai
- Anjo Kosei Hospital, Anjo
| | - Y Shimizu
- Aichi Cancer Centre Hospital, Nagoya
| | | | - E Sakamoto
- Japanese Red Cross Nagoya Daini Hospital, Nagoya
| | - H Miyake
- Japanese Red Cross Nagoya Daiichi Hospital, Nagoya
| | - D Takara
- Kiryu Kosei General Hospital, Kiryu
| | | | | | | | - Y Kato
- Nagoya Ekisaikai Hospital, Nagoya
| | | | - E Hayashi
- Japan Community Health Care Organization Chukyo Hospital, Nagoya
| | | | - S Mizuno
- Shizuoka Welfare Hospital, Shizuoka
| | - T Sato
- Hekinan Municipal Hospital, Hekinan
| | - K Suzuki
- Japan Community Health Care Organization Kani Tono Hospital, Kani
| | | | - S Kawai
- Tsushima City Hospital, Tsushima
| | | | - K Kato
- Inazawa Municipal Hospital, Inazawa
| | | | - K Suzumura
- Shizuoka Saiseikai General Hospital, Shizuoka
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22
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Jun SY, Sung YN, Lee JH, Park KM, Lee YJ, Hong SM. Validation of the Eighth American Joint Committee on Cancer Staging System for Distal Bile Duct Carcinoma. Cancer Res Treat 2018; 51:98-111. [PMID: 29510611 PMCID: PMC6333967 DOI: 10.4143/crt.2017.595] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Accepted: 03/01/2018] [Indexed: 12/31/2022] Open
Abstract
PURPOSE T category of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for distal bile duct carcinoma (DBDC) was changed to include tumor invasion depth measurement, while the N category adopted a 3-tier classification system based on the number of metastatic nodes. Materials and Methods To validate cancer staging, a total of 200 surgically resected DBDCs were staged and compared according to the seventh and eighth editions. RESULTS T categories included T1 (n=37, 18.5%), T2 (n=114, 57.0%), and T3 (n=49, 24.5%). N categories included N0 (n=133, 66.5%), N1 (n=50, 25.0%), and N2 (n=17, 8.5%). Stage groupings included I (n=33, 16.5%), II (n=150, 75.0%), and III (n=17, 8.5%). The overall 5-year survival rates (5-YSRs) of T1, T2, and T3 were 59.3%, 42.4%, and 12.2%, respectively. T category could discriminate patient survival by both pairwise (T1 and T2, p=0.011; T2 and T3, p < 0.001) and overall (p < 0.001) comparisons. The overall 5-YSRs of N0, N1, and N2 were 47.3%, 17.0%, and 14.7%, respectively. N category could partly discriminate patient survival by both pairwise (N0 and N1, p < 0.001; N1 and N2, p=0.579) and overall (p < 0.001) comparisons. The overall 5-YSRs of stages I, II, and III were 59.0%, 35.4%, and 14.7%, respectively. Stages could distinguish patient survival by both pairwise (I and II, p=0.002; II and III, p=0.015) and overall (p < 0.001) comparisons. On multivariate analyses, T and N categories (p=0.014 and p=0.029) and pancreatic invasion (p=0.006) remained significant prognostic factors. CONCLUSION The T andNcategories of the eighth edition AJCC staging system for DBDC accurately predict patient prognosis.
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Affiliation(s)
- Sun-Young Jun
- Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - You-Na Sung
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kwang-Min Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Joo Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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23
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Validation of Feasibility of Magnetic Resonance Imaging for the Measurement of Depth of Tumor Invasion in Distal Bile Duct Cancer According to the New American Joint Committee on Cancer Staging System. Acad Radiol 2017; 24:1526-1534. [PMID: 28780173 DOI: 10.1016/j.acra.2017.06.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/21/2017] [Accepted: 06/12/2017] [Indexed: 12/14/2022]
Abstract
RATIONALE AND OBJECTIVES This study aimed to develop and validate a method for measuring the depth of tumor invasion (DoI) using magnetic resonance imaging (MRI) and to investigate the diagnostic performance of the measured DoI for stratifying tumor (T) classification in patients with distal bile duct cancer according to the new American Joint Committee on Cancer staging system. MATERIALS AND METHODS Fifty-four patients (30 men and 24 women; age range, 43-81 years) with distal bile duct cancer were enrolled. A study coordinator first developed a "provisional method" for measuring DoI on T2-weighted MRI. Subsequently, after compensating for defects, the "improved method" was developed. Two reviewers independently measured DoI and assessed its correlations with the histopathologic reference standard using intraclass correlation coefficient (ICC). The study population was grouped according to the DoI for T classification based on the new staging system for evaluation of diagnostic predictive values. RESULTS The ICC values between the radiologic and the histopathologic DoI were calculated. Using the "improved method," the ICC for the coordinator's DoI was very good (ICC, 0.885), which was a significantly higher value than that obtained using the "provisional method" (ICC, 0.501, P = .00000); and for two reviewers' DoIs, the ICC values were good (ICC, 0.752 and 0.784, respectively). The overall accuracy of MRI for stratifying bile duct tumors using DoI was 87.0% and 85.2%, respectively. CONCLUSIONS This newly developed method reliably measured DoI on T2-weighted MRI and can be used for preoperative T classification of patients with distal bile duct cancer according to the new staging system.
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24
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Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers. Ann Surg Oncol 2017; 25:845-847. [PMID: 28752469 DOI: 10.1245/s10434-017-6025-x] [Citation(s) in RCA: 533] [Impact Index Per Article: 66.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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25
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Gonzalez RS, Bagci P, Basturk O, Reid MD, Balci S, Knight JH, Kong SY, Memis B, Jang KT, Ohike N, Tajiri T, Bandyopadhyay S, Krasinskas AM, Kim GE, Cheng JD, Adsay NV. Intrapancreatic distal common bile duct carcinoma: Analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas. Mod Pathol 2016; 29:1358-1369. [PMID: 27469329 PMCID: PMC5598556 DOI: 10.1038/modpathol.2016.125] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 06/16/2016] [Accepted: 06/17/2016] [Indexed: 01/04/2023]
Abstract
Distal common bile duct carcinoma is a poorly characterized entity for reasons such as variable terminology and difficulty in determining site of origin of intrapancreatic lesions. We compared clinicopathologic features of pancreatobiliary-type adenocarcinomas within the pancreas, but arising from the distal common bile duct, with those of pancreatic and ampullary origin. Upon careful review of 1017 pancreatoduodenectomy specimens with primary adenocarcinoma, 52 (5%) qualified as intrapancreatic distal common bile duct carcinoma. Five associated with an intraductal papillary neoplasm were excluded; the remaining 47 were compared to 109 pancreatic ductal adenocarcinomas and 133 ampullary carcinomas. Distal common bile duct carcinoma patients had a younger median age (58 years) than pancreatic ductal adenocarcinoma patients (65 years) and ampullary carcinoma patients (68 years). Distal common bile duct carcinoma was intermediate between pancreatic ductal adenocarcinoma and ampullary carcinoma with regard to tumor size and rates of node metastases and margin positivity. Median survival was better than for pancreatic ductal adenocarcinoma (P=0.0010) but worse than for ampullary carcinoma (P=0.0006). Distal common bile duct carcinoma often formed an even band around the common bile duct and commonly showed intraglandular neutrophil-rich debris and a small tubular pattern. Poor prognostic indicators included node metastasis (P=0.0010), lymphovascular invasion (P=0.0299), and margin positivity (P=0.0069). Categorizing the tumors based on size also had prognostic relevance (P=0.0096), unlike categorization based on anatomic structures invaded. Primary distal common bile duct carcinoma is seen in younger patients than pancreatic ductal adenocarcinoma or ampullary carcinoma. Its prognosis is significantly better than pancreatic ductal adenocarcinoma and worse than ampullary carcinoma, at least partly because of differences in clinical presentation. Use of size-based criteria for staging appears to improve its prognostic relevance. Invasive pancreatobiliary-type distal common bile duct carcinomas are uncommon in the West and have substantial clinicopathologic differences from carcinomas arising from the pancreas and ampulla.
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Affiliation(s)
- Raul S. Gonzalez
- Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA
| | - Pelin Bagci
- Department of Pathology, Marmara University, Istanbul, Turkey
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Serdar Balci
- Department of Pathology, Emory University, Atlanta, GA, USA
| | | | - So Yeon Kong
- Department of Epidemiology, Emory University, Atlanta, GA, USA
| | - Bahar Memis
- Department of Pathology, Emory University, Atlanta, GA, USA
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nobuyuki Ohike
- Department of Pathology, Showa University School of Medicine, Tokyo, Japan
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachiouji Hospital, Tokyo, Japan
| | | | | | - Grace E. Kim
- Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
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Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach. World J Surg 2016; 41:232-240. [DOI: 10.1007/s00268-016-3687-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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27
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Tsukahara T, Shimoyama Y, Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, Yamaguchi J, Nakamura S, Nagino M. Cholangiocarcinoma with intraductal tubular growth pattern versus intraductal papillary growth pattern. Mod Pathol 2016; 29:293-301. [PMID: 26769137 DOI: 10.1038/modpathol.2015.152] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 11/17/2015] [Accepted: 11/20/2015] [Indexed: 02/08/2023]
Abstract
Intraductal neoplasms of the bile duct are macroscopically characterized by exophytic or polypoid growth patterns and have a favorable prognosis. Although some tumors with a predominantly tubular microscopic pattern have been reported, they have not been well characterized clinicopathologically. The purpose of the present study was to compare the newly recognized cholangiocarcinoma with an intraductal tubular growth pattern and cholangiocarcinoma with an intraductal papillary growth pattern and to investigate the pathological and prognostic significance of the former. This study analyzed 161 patients with tumors with exophytic or polypoid growth patterns from a large series of 733 cholangiocarcinoma cases surgically resected from January 1998 to May 2013. The study patients were divided into two groups: those whose tumors showed a predominantly tubular growth pattern (n=52) and those whose tumors exhibited a predominantly papillary growth pattern (n=109). Tubular growth pattern was associated with combined vascular resection and the absence of macroscopic mucin. Several histological indexes were significantly higher for the tubular growth pattern than the papillary one, including tubular adenocarcinoma, depth of invasion, microscopic lymphatic invasion, venous invasion, perineural invasion, and necrosis. Although the survival curves overlapped (P=0.693), the rate of liver metastasis was significantly higher for the tubular growth pattern than for the papillary one (P=0.012). Genomic DNA analysis focusing on somatic mutations in codons 12 and 13 of KRAS and codon 600 of BRAF revealed only one (4%) KRAS and no BRAF mutation among the 25 tubular cases examined. In conclusion, the tubular growth pattern exhibited differences in some histologic indexes, in addition to a higher hepatic metastasis rate and a lower KRAS mutation frequency, compared with the papillary growth pattern, but no difference in prognosis was observed. The distinctiveness of this tubular neoplasm should be further examined in the future.
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Affiliation(s)
- Tetsuo Tsukahara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshie Shimoyama
- Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Gen Sugawara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shigeo Nakamura
- Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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28
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Ahn KS, Kang KJ, Kang YN, Kim YH, Kim TS. Confinement to the intrapancreatic bile duct is independently associated with a better prognosis in extrahepatic cholangiocarcinoma. BMC Gastroenterol 2016; 16:21. [PMID: 26911927 PMCID: PMC4765136 DOI: 10.1186/s12876-016-0444-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Accepted: 02/18/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Actual differences of long term outcome of extrahepatic cholangiocarcinoma according to the location of the tumor have not yet been studied. The aim of this study was to evaluate the prognosis and optimal surgical procedure for middle (BD) cancer. METHODS Among 109 patients with carcinoma of the extrahepatic BD underwent surgical resection, curative resection of extrahepatic BD cancer was performed in 90 patients. They were classified into three groups according to the location of tumors: DISTAL (n = 32), tumor was confined to the intrapancreatic bile duct; MID (n = 20), tumor was located between below the confluence of the hepatic duct bifurcation and suprapancreatic portion of the BD; and DIFFUSE (n = 38), tumor was located diffusely. RESULTS Tumor involving the middle BD (MID or DIFFUSE) had a higher rate of perineural invasion as compared to the DISTAL group. The overall and disease-free survival rate for the MID or DIFFUSE group was significantly worse than that of DISTAL. In the MID/DIFFUSE group, there was no significant difference of survival according to the type of the operation (pancreaticoduodenectomy or segmental BD resection). The multivariate analysis showed that tumor involving middle BD (MID or DIFFUSE group) and node metastasis were independently poor prognostic factors for the disease free and overall survival. CONCLUSION Extrahepatic cholangiocarcinoma involving the extrapancreatic BD has a worse prognosis than those confined to the intrapancreatic BD. In patients with tumors confined to the middle BD, BD resection can be considered as an alternative surgical procedure to pancreaticoduodenectomy, if an R0 resection can be accomplished.
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Affiliation(s)
- Keun Soo Ahn
- Department of Surgery, Keimyung University School of Medicine, Dongsan Medical Center, 56 Dalsung-ro, Jung-gu, Daegu City, Republic of Korea.
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Dongsan Medical Center, 56 Dalsung-ro, Jung-gu, Daegu City, Republic of Korea.
| | - Yu Na Kang
- Department of Pathology, Keimyung University School of Medicine, Dongsan Medical Center, 56 Dalsung-ro, Jung-gu, Daegu City, Republic of Korea.
| | - Yong Hoon Kim
- Department of Surgery, Keimyung University School of Medicine, Dongsan Medical Center, 56 Dalsung-ro, Jung-gu, Daegu City, Republic of Korea.
| | - Tae-Seok Kim
- Department of Surgery, Keimyung University School of Medicine, Dongsan Medical Center, 56 Dalsung-ro, Jung-gu, Daegu City, Republic of Korea.
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29
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Moon A, Choi DW, Choi SH, Heo JS, Jang KT. Validation of T Stage According to Depth of Invasion and N Stage Subclassification Based on Number of Metastatic Lymph Nodes for Distal Extrahepatic Bile Duct (EBD) Carcinoma. Medicine (Baltimore) 2015; 94:e2064. [PMID: 26683915 PMCID: PMC5058887 DOI: 10.1097/md.0000000000002064] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1: < 5 mm, T2: 5 to 12 mm, and T3: ≥ 12 mm). Specifically, we evaluated DoI in 114 cases of distal EBD carcinoma using digital scan images to achieve more objective measurements of tumor DoI. In addition, we evaluated the effect of the number of metastatic lymph nodes (LNs) as well as the number of total examined LNs on the survival rate in the same patient group, and performed a comparative analysis of these data to assess patient survival. We also analyzed 114 cases of distal EBD carcinoma using the current T and N classification of the AJCC staging system (7th edition). The T stage of the current AJCC staging system was not associated with significant differences in patient survival, especially between T2 and T3. However, T staging by DoI was associated with statistically significant differences in patient survival (P < 0.001 in DoI-1, P = 0.002 in DoI-2). With respect to N stage, we divided patients into 3 tiers comprising class 1 (no nodal metastasis), class 2 (1-3 nodal metastases), and class 3 (4 or more nodal metastases). In 3-tier classification analysis, the median survival times for classes 1, 2, and 3 were 79.2, 28.8, and 10.9 months, respectively. The difference in survival among the 3 classes was statistically significant (P < 0.001). We found the cut-off value of 11 LNs (1 to 10 vs ≥ 11) for N0 stage showed most significant difference (P = 0.007). We think at least 11 LNs should be examined for more accurate evaluation of N stage in distal EBD carcinoma. We propose an alternative T classification using DoI and 3-tier sub-classification of N stage for distal EBD carcinoma.
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Affiliation(s)
- Ahrim Moon
- From the Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Gyeonggi-do, Korea (AM); Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (DWC, SHC, JSH); and Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (K-TJ)
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30
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Jhaveri KS, Hosseini-Nik H. MRI of cholangiocarcinoma. J Magn Reson Imaging 2014; 42:1165-79. [PMID: 25447417 DOI: 10.1002/jmri.24810] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 10/21/2014] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinomas are the second most common primary hepatobiliary tumors after hepatocellular carcinomas. They can be categorized either based on their location (intrahepatic/perihilar/extrahepatic distal) or their growth characteristics (mass-forming/periductal-infiltrating/intraductal) because they exhibit varied presentations and outcomes based on their location and or pattern of growth. The increased risk of cholangiocarcinoma in PSC necessitates close surveillance of these patients by means of imaging and laboratory measures; and because currently surgical resection is the only effective treatment for cholangiocarcinoma, the need for accurate pre-operative staging and assessment of resectability has emphasized the role of high quality imaging in management. Today magnetic resonance imaging (MRI) is the modality of choice for detection, pre-operative staging and surveillance of cholangiocarcinoma.
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Affiliation(s)
- Kartik S Jhaveri
- Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.,Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, and Women's College Hospital, Toronto, Ontario, Canada
| | - Hooman Hosseini-Nik
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, and Women's College Hospital, Toronto, Ontario, Canada
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31
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Increased number of metastatic lymph nodes in adenocarcinoma of the ampulla of Vater as a prognostic factor: A proposal of new nodal classification. Surgery 2014; 155:74-84. [DOI: 10.1016/j.surg.2013.08.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 08/12/2013] [Indexed: 12/15/2022]
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32
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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.
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Abstract
Although most tumors of the bile ducts are predominantly invasive, some have an exophytic pattern within the bile ducts; these intraductal papillary neoplasms usually have well-formed papillae at the microscopic level. In this study, however, we describe a novel type of intraductal neoplasm of the bile ducts with a predominantly tubular growth pattern and other distinctive features. Ten cases of biliary intraductal neoplasms with a predominantly tubular architecture were identified in the files of the Pathology Department at Memorial Sloan-Kettering Cancer Center from 1983 to 2006. For each of these cases we studied the clinical presentation, histologic and immunohistochemical features (9 cases only), and the clinical follow-up of the patients. Three male and 7 female patients (38 to 78 y) presented with obstructive jaundice or abdominal pain. Eight of the patients underwent a partial hepatectomy; 2 underwent a laparoscopic bile duct excision, followed by a pancreatoduodenectomy in one of them. The tumors range in size from 0.6 to 8.0 cm. The intraductal portions of the tumors (8 intrahepatic, 1 extrahepatic hilar, 1 common bile duct) were densely cellular and composed of back-to-back tubular glands and solid sheets with minimal papillary architecture. The cells were cuboidal to columnar with mild to moderate cytologic atypia. Foci of necrosis were present in the intraductal component in 6 cases. An extraductal invasive carcinoma component was present in 7 cases, composing <25% of the tumor in 4 cases, and >75% in 1 case. It was observed by immunohistochemical analysis that the tumor cells expressed CK19, CA19-9, MUC1, and MUC6 in most cases and that SMAD4 expression was retained. MUC2, MUC5AC, HepPar1, synaptophysin, chromogranin, p53, and CA125 were negative in all cases and most were negative for CEA-M and B72.3. Four patients were free of tumor recurrence after 7 to 85 months (average, 27 mo). Four patients with an invasive carcinoma component suffered metastases, 1 after local intraductal recurrence. However, the occurrence of metastasis in 3 of these patients was quite late (average, 52 mo). Intraductal tubular neoplasm of the bile ducts is a biliary intraductal neoplasm with a distinctive histologic pattern resembling the recently described intraductal tubulopapillary neoplasm of the pancreas. Immunohistochemical features are similar to those of other pancreatobiliary-type carcinomas. However, this tumor may be hard to recognize as intraductal because of its complex architecture. When the tumor is entirely intraductal, the outcome appears to be favorable, but metastases can occur when invasive carcinoma is present, even after many years.
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Adsay NV, Bagci P, Tajiri T, Oliva I, Ohike N, Balci S, Gonzalez RS, Basturk O, Jang KT, Roa JC. Pathologic staging of pancreatic, ampullary, biliary, and gallbladder cancers: pitfalls and practical limitations of the current AJCC/UICC TNM staging system and opportunities for improvement. Semin Diagn Pathol 2012; 29:127-41. [PMID: 23062420 DOI: 10.1053/j.semdp.2012.08.010] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Tumors of the ampulla-pancreatobiliary tract are encountered increasingly; however, their staging can be highly challenging due to lack of familiarity. In this review article, the various issues encountered in staging of these tumors at the pathologic level are evaluated and possible solutions for daily practice as well as potential improvements for future staging protocols are discussed. While N-stage parameters have now been well established (the number of lymph nodes required in pancreatoduodenectomies is 12), the T-staging has several issues: for the pancreas, the discovery of small cancers arising in intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) necessitates the creation of substages of T1 (as T1a, b, and c); lack of proper definition of "peripancreatic soft tissue" and "common bile duct involvement" (as to which part is meant) makes T3 highly subjective. Increasing resectability of main vessels (portal vein) brings the need to redefine a "T" for such cases. For the ampulla, due to factors like anatomic complexity of the region and the under-appreciation of three-dimensional spread of the tumors in this area (in particular, the frequent extension into periduodenal soft tissues and duodenal serosa, which are not addressed in the current system and which require specific grossing approaches to document), the current T-staging lacks reproducibility and clinical relevance, and therefore, major revisions are needed. Recently proposed refined definition and site-specific subclassification of ampullary tumors highlight the areas for improvement. For the extrahepatic bile ducts, the staging schemes that use the depth of invasion may be more practical to circumvent the inconsistencies in the histologic layering of the ducts; better definition of terms like "periductal spread" is needed. For the gallbladder, since many gallbladder cancers are "unapparent" (found in clinically and grossly unsuspected cholecystectomies), establishing proper grossing protocols and adequate sampling are crucial. Since the gallbladder does not have the distinct layering of the other gastrointestinal organs, the definitions of Tis/T1a/T1b lack practicality, and therefore, "early gallbladder carcinoma" category proposed in high-risk regions may have to be recognized instead. Involvement of the Rokitansky-Aschoff sinuses should be a part of the evaluation and management of these early gallbladder cancers; for advanced cancers, documentation of hepatic versus serosal involvement is necessary. In summary, T-staging of ampulla-pancreatobiliary tract tumors has many challenges. Proper grossing and appreciation of histo-anatomic subtleties of this region are crucial in addressing these issues and achieving more applicable and clinically relevant staging systems in the future.
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Affiliation(s)
- N Volkan Adsay
- Department of Pathology, Emory University, School of Medicine, Atlanta, Georgia, USA.
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Rocha FG, Lee H, Katabi N, DeMatteo RP, Fong Y, D'Angelica MI, Allen PJ, Klimstra DS, Jarnagin WR. Intraductal papillary neoplasm of the bile duct: a biliary equivalent to intraductal papillary mucinous neoplasm of the pancreas? Hepatology 2012; 56:1352-60. [PMID: 22504729 DOI: 10.1002/hep.25786] [Citation(s) in RCA: 179] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2012] [Accepted: 04/06/2012] [Indexed: 12/13/2022]
Abstract
UNLABELLED Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma characterized by intraductal growth and better outcome compared with the more common nodular-sclerosing type. IPNB is a recognized precursor of invasive carcinoma, but its pathogenesis and natural history are ill-defined. This study examines the clinicopathologic features and outcomes of IPNB. A consecutive cohort of patients with bile duct cancer (hilar, intrahepatic, or distal) was reviewed, and those with papillary histologic features identified. Histopathologic findings and immunohistochemical staining for tumor markers and for cytokeratin and mucin proteins were used to classify IPNB into subtypes. Survival data were analyzed and correlated with clinical and pathologic parameters. Thirty-nine IPNBs were identified in hilar (23/144), intrahepatic (4/86), and distal (12/113) bile duct specimens between 1991 and 2010. Histopathologic examination revealed 27 pancreatobiliary, four gastric, two intestinal, and six oncocytic subtypes; results of cytokeratin and mucin staining were similar to those of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Invasive carcinoma was seen in 29/39 (74%) IPNBs. Overall median survival was 62 months and was not different between IPNB locations or subtypes. Factors associated with a worse median survival included presence and depth of tumor invasion, margin-positive resection, and expression of MUC1 and CEA. CONCLUSION IPNBs are an uncommon variant of bile duct cancer, representing approximately 10% of all resectable cases. They occur throughout the biliary tract, share some histologic and clinical features with IPMNs of the pancreas, and may represent a carcinogenesis pathway different from that of conventional bile duct carcinomas arising from flat dysplasia. Given their significant risk of harboring invasive carcinoma, they should be treated with complete resection.
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Affiliation(s)
- Flavio G Rocha
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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de Jong MC, Hong SM, Augustine MM, Goggins MG, Wolfgang CL, Hirose K, Schulick RD, Choti MA, Anders RA, Pawlik TM. Hilar cholangiocarcinoma: tumor depth as a predictor of outcome. ACTA ACUST UNITED AC 2011; 146:697-703. [PMID: 21690446 DOI: 10.1001/archsurg.2011.122] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The American Joint Committee on Cancer staging system for hilar cholangiocarcinoma may be inaccurate because the bile duct lacks discrete tissue boundaries. OBJECTIVES To examine the accuracy of the American Joint Committee on Cancer staging schemes and to determine the prognostic implications of tumor depth. DESIGN, SETTING, AND PATIENTS From January 1, 1987, through December 31, 2009, there were 106 patients who underwent resection of hilar cholangiocarcinoma who had pathologic slides available for re-review. MAIN OUTCOME MEASURES Tumor depth and overall survival. RESULTS Overall median survival was 19.9 months. The 6th and 7th editions of the T-classification criteria were unable to discriminate among T1, T2, and T3 lesions (P > .05 for all). Median survival was associated with the invasion depth of the tumor (≥5 mm vs <5 mm): 18 months vs 30 months (P = .01). On multivariate analysis, tumor depth remained predictive of disease-specific death (hazard ratio, 1.70; P = .03). CONCLUSIONS The American Joint Committee on Cancer T-classification criteria did not stratify patients with regard to prognosis. Depth of tumor invasion is a better predictor of long-term outcome.
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Affiliation(s)
- Mechteld C de Jong
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Washington MK, Berlin J, Branton PA, Burgart LJ, Carter DK, Compton CC, Fitzgibbons PL, Frankel WL, Jessup JM, Kakar S, Minsky B, Nakhleh RE, Vauthey JN. Protocol for the examination of specimens from patients with carcinoma of the perihilar bile ducts. Arch Pathol Lab Med 2010; 134:e19-24. [PMID: 20367295 DOI: 10.5858/134.4.e19] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Mary Kay Washington
- Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA.
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Washington MK, Berlin J, Branton PA, Burgart LJ, Carter DK, Compton CC, Fitzgibbons PL, Frankel WL, Jessup JM, Kakar S, Minsky B, Nakhleh RE, Vauthey JN. Protocol for the examination of specimens from patients with carcinoma of the distal extrahepatic bile ducts. Arch Pathol Lab Med 2010; 134:e8-13. [PMID: 20367298 DOI: 10.5858/134.4.e8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Mary Kay Washington
- Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA.
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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.
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Affiliation(s)
- Seung-Mo Hong
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
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Chung JY, Hong SM, Choi BY, Cho H, Yu E, Hewitt SM. The expression of phospho-AKT, phospho-mTOR, and PTEN in extrahepatic cholangiocarcinoma. Clin Cancer Res 2009; 15:660-7. [PMID: 19147772 DOI: 10.1158/1078-0432.ccr-08-1084] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation, and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma. EXPERIMENTAL DESIGN Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay. RESULTS Expressions of p-AKT and p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal and dysplastic bile duct epithelium (P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion (P < 0.05), T classification (P < 0.05), and stage grouping (P < 0.05), and the presence of invasion of the pancreas (P < 0.05) and duodenum (P < 0.05). Decreased PTEN expression (P = 0.004) as well as decreased PTEN/p-AKT (P = 0.003) and PTEN/p-mTOR (P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis. CONCLUSIONS The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by univariate analysis.
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Affiliation(s)
- Joon-Yong Chung
- Tissue Array Research Program, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland, USA
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Chung YE, Kim MJ, Park YN, Lee YH, Choi JY. Staging of extrahepatic cholangiocarcinoma. Eur Radiol 2008; 18:2182-95. [PMID: 18458911 DOI: 10.1007/s00330-008-1006-x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2007] [Revised: 03/24/2008] [Accepted: 03/27/2008] [Indexed: 12/18/2022]
Abstract
Preoperative staging of extrahepatic cholangiocarcinoma is important in determining the best treatment plan. Several classification systems have been suggested to determine the operability and extent of surgery. Longitudinal tumor extent is especially important in extrahepatic cholangiocarcinoma because operative methods differ depending on the tumor extent. The Bismuth-Corlette classification system provides useful information when planning for surgery. However, this classification system is not adequate for selecting surgical candidates. Anatomic variation of the bile duct and gross morphology of the tumor must be considered simultaneously. Lateral spread of the tumor can be evaluated based on the TNM staging provided by American Joint Committee on Cancer (AJCC). However, there is a potential for ambiguity in the distinction of T1 and T2 cancer from one another. In addition, T stage does not necessarily mean invasiveness. Blumgart T staging is helpful for the assessment of resectability with the consideration of nodal status and distant metastasis as suggested by the AJCC cancer staging system. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary tools used in the assessment of longitudinal and lateral spread of a tumor when determining respectability. Diagnostic laparoscopy and positron emission tomography (PET) may play additional roles in this regard.
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Affiliation(s)
- Yong Eun Chung
- Department of Diagnostic Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seodaemun-ku Shinchon-dong 134, Seoul, 120-752, Korea
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