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Kim J, Lee YS, Lee JC, Hwang JH. Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study. BMC Gastroenterol 2025; 25:138. [PMID: 40045214 PMCID: PMC11883955 DOI: 10.1186/s12876-025-03746-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 02/28/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Choledocholithiasis has been reported to be associated with the occurrence of cholangiocarcinoma (CCA); however, the association has not yet been sufficiently demonstrated. This study aimed to evaluate the association between choledocholithiasis (common bile duct stones) and CCA. METHODS This nationwide retrospective cohort study used the Health Insurance Review and Assessment database of individuals diagnosed with choledocholithiasis between 2008 and 2009 in South Korea. Individuals were stratified by age, and CCA was categorized into extrahepatic CCA (ECA) and intrahepatic CCA (ICA). The standardized incidence ratio (SIR) was calculated to compare CCA incidence between patients with choledocholithiasis and the general population. RESULTS The study enrolled 20,808 patients with choledocholithiasis (52.35% men and 47.65% women; male-to-female ratio: 1.09:1). Over a 10-year follow-up period, CCA occurred in 548 (2.64%) patients, comprising 238 (1.14%) ECA cases and 310 (1.48%) ICA cases. The SIR was 25.23 (95% confidence interval [CI]: 21.98-28.85) for ECA and 24.64 (95% CI: 21.87-27.73) for ICA. Statistical significance persisted even after excluding cases within the first 2 years from the index date, with an SIR of 18.63 (95% CI: 16.23-21.28) for ICA and 12.73 (95% CI: 10.50-15.30) for ECA. The SIRs peaked in patients diagnosed with choledocholithiasis at the age of 70-79 years (SIR 16.61, 95% CI: 11.83-22.69) for ECA and 60-69 years (SIR 29.27, 95% CI: 23.53-36.03) for ICA. CONCLUSION Our study demonstrated a significant association between choledocholithiasis and cholangiocarcinoma, particularly those in their 70s for ECA and 60s for ICA. However, causation cannot be established due to the retrospective design.
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Affiliation(s)
- Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Yoon Suk Lee
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, 170, Juhwa-ro, Ilsanseo-gu, Goyang, South Korea.
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
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Zhang WH, Zhao Y, Zhang CR, Huang JC, Lyu SC, Lang R. Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy. World J Gastrointest Surg 2024; 16:2910-2924. [PMID: 39351557 PMCID: PMC11438816 DOI: 10.4240/wjgs.v16.i9.2910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/05/2024] [Accepted: 08/13/2024] [Indexed: 09/18/2024] Open
Abstract
BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). METHODS This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). RESULTS The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P < 0.001). CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.
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Affiliation(s)
- Wen-Hui Zhang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China
| | - Yu Zhao
- Department of Urology Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China
| | - Cheng-Run Zhang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China
| | - Jin-Can Huang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China
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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: 33] [Impact Index Per Article: 3.7] [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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Zhang JW, Chu YM, Lan ZM, Tang XL, Chen YT, Wang CF, Che X. Correlation between metastatic lymph node ratio and prognosis in patients with extrahepatic cholangiocarcinoma. World J Gastroenterol 2015; 21:4255-4260. [PMID: 25892876 PMCID: PMC4394087 DOI: 10.3748/wjg.v21.i14.4255] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 01/16/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prognostic value of metastatic lymph node ratio (MLNR) in extrahepatic cholangiocarcinoma (ECC) patients undergoing radical resection.
METHODS: Seventy-eight patients with ECC were enrolled. Associations between various clinicopathologic factors and prognosis were investigated by Kaplan-Meier analyses. The Cox proportional-hazards model was used for multivariate survival analysis.
RESULTS: The overall three- and five-year survival rates were 47.26% and 23.99%, respectively. MLNR of 0, 0-0.2, 0.2-0.5, and > 0.5 corresponded to five-year survival rates of 28.59%, 21.60%, 18.84%, and 10.03%, respectively. Univariate analysis showed that degree of tumor differentiation, lymph node metastasis, MLNR, tumor-node-metastasis (TNM) stage, and margin status were closely associated with postoperative survival in ECC patients (P < 0.05). Multivariate analysis showed that MLNR and TNM stage were independent prognostic factors after pancreaticoduodenectomy (HR = 2.13, 95%CI: 1.45-3.11; P < 0.01; and HR = 1.97, 95%CI: 1.17-3.31; P = 0.01, respectively). The median survival time for MLNR > 0.5, 0.2-0.5, 0-0.2, and 0 was 15 mo, 24 mo, 23 mo, and 35.5 mo, respectively. There were statistical differences in survival time between patients with different MLNR (χ2 = 15.38; P < 0.01).
CONCLUSION: MLNR is an independent prognostic factor for ECC patients after radical resection and is useful for predicting postoperative survival.
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Diagnosis of distal cholangiocarcinoma after the removal of choledocholithiasis. Gastroenterol Res Pract 2012; 2012:396869. [PMID: 23227039 PMCID: PMC3512266 DOI: 10.1155/2012/396869] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Revised: 10/16/2012] [Accepted: 10/18/2012] [Indexed: 01/01/2023] Open
Abstract
Background and Aim. Distal cholangiocarcinoma associated with choledocholithiasis has not been reported, and the causal relationship remains to be established. We evaluated diagnosis of distal cholangiocarcinoma diagnosed after the removal of choledocholithiasis. Patients and Methods. We assigned 9 cases of cholangiocarcinoma with choledocholithiasis to Group A. As a control group, 37 patients with cholangiocarcinoma without choledocholithiasis were assigned to Group B. Results. Abdominal pain at admission is the only significant difference between Group A and Group B (P = 0.001). All patients in Group A had gall bladder stones, compared with 7 patients (19%) in Group B (P < 0.01). Of the 9 patients in Group A, endoscopic retrade cholangiopancreatography (ERCP) detected normality in 2 patients (22%) and abnormalities in 7 patients (78%). Of the 32 patients in Group B, ERCP detected normality in 4 patients (13%) and abnormalities in 28 patients (88%) (P = 0.597). Intraductal ultrasonography (IDUS) detected a tumor in 8 patients in Group A, while in Group B, IDUS detected normality in 1 patient (3%) and tumors in 29 patients (97%) (P = 1.000). Conclusions. IDUS after stone removal may potentially help in the detection of unexpected tumors. Therefore, we believe that IDUS after stone removal will lead to improve outcome and prognosis.
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