BackgroundThe aim of the present study was to examine the outcomes and prognostic factors after surgery with curative intent for distal cholangiocarcinoma during a modern timespan, in a Swedish tertiary referral center.MethodsAll patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma between April 2008 and December 2015 were identified. Survival was estimated using the Kaplan-Meier analysis. Demographic, clinical, laboratory and histopathological data were evaluated for prognostic factors relating to mortality, using univariable and multivariable statistical analysis.ResultsFifty-four patients were included. The mean age was 68±8 years and 21 (39%) of the patients were female. Jaundice was present at diagnosis in 73% of the patients. There was no 90-day mortality. Complications graded as Clavien-Dindo ≥3 occurred in 10 (19%) of the patients. Twenty-eight (52%) received adjuvant therapy. Overall survival rates at 1, 3, and 5 years were 80%, 21%, and 9.2%, respectively. Median survival was 22.2 months. The presence of lymph node metastases was found to be the only independent predictor of survival (hazard ratio 2.88, 95% confidence interval 1.22-6.84; P=0.016). The total number of lymph node metastases, lymph node ratio or total number of resected nodes did not improve the prediction.ConclusionsWe found that the recurrence rate was higher and the survival poorer after surgery for distal cholangiocarcinoma than has previously been reported. Lymph node status at the time of resection was the most important prognostic factor for survival in the current material.

Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

Purpose Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Methods Thrombospondin-2 was measured in prospectively collected serum samples from patients who underwent surgery with a histopathological diagnosis of distal cholangiocarcinoma (N = 51), pancreatic ductal adenocarcinoma (N = 52) and benign pancreatic diseases (N = 27) as well as healthy blood donors (N = 52) using an enzyme-linked immunosorbent assay. Results Thrombospondin-2 levels (ng/ml) were similar in distal cholangiocarcinoma 55 (41–77) and pancreatic ductal adenocarcinoma 48 (35–80) (P = 0.221). Thrombospondin-2 + CA 19-9 had an area under the curve of 0.92 (95% CI 0.88–0.97) in differentiating distal cholangiocarcinoma and pancreatic ductal adenocarcinoma from healthy donors which was superior to CA 19-9 alone (P < 0.001). The diagnostic value of adding thrombospondin-2 to CA 19-9 was larger in early disease stages. Thrombospondin-2 did not provide additional value to CA 19-9 in differentiating the benign disease group; however, heterogeneity was notable in the benign cohort. Three of five patients with autoimmune pancreatitis patients had greatly elevated thrombospondin-2 levels. Thrombospondin-2 levels had no correlation with prognoses. Conclusions Serum thrombospondin-2 in combination with CA 19-9 has potential as a biomarker for distal cholangiocarcinoma and pancreatic cancer.