Impact of classical and basal-like molecular subtypes on overall survival in resected pancreatic cancer in the SPACIOUS-2 multicentre study.

BACKGROUND: The recently identified classical and basal-like molecular subtypes of pancreatic cancer impact on overall survival (OS). However, the added value of routine subtyping in both clinical practice and randomized trials is still unclear, as most studies do not consider clinicopathological parameters. This study examined the clinical prognostic value of molecular subtyping in patients with resected pancreatic cancer. METHODS: Subtypes were determined on fresh-frozen resected pancreatic cancer samples from three Dutch centres using the Purity Independent Subtyping of Tumours classification. Patient, treatment, and histopathological variables were compared between subtypes. The prognostic value of subtyping in (simulated) pre- and postoperative settings was assessed using Kaplan-Meier and Cox regression analyses. RESULTS: Of 199 patients with resected pancreatic cancer, 164 (82.4 per cent) were classified as the classical and 35 (17.6 per cent) as the basal-like subtype. Patients with a basal-like subtype had worse OS (11 versus 16 months (HR 1.49, 95 per cent c.i. 1.03 to 2.15; P = 0.035)) than patients with a classical subtype. In multivariable Cox regression analysis, including only clinical variables, the basal-like subtype was a statistically significant predictor for poor OS (HR 1.61, 95 per cent c.i. 1.11 to 2.34; P = 0.013). When histopathological variables were added to this model, the prognostic value of subtyping decreased (HR 1.49, 95 per cent c.i. 1.01 to 2.19; P = 0.045). CONCLUSION: The basal-like subtype was associated with worse OS in patients with resected pancreatic cancer. Adding molecular classification to inform on tumor biology may be used in patient stratification.

Differentiation of malignant and benign proximal bile duct strictures: the diagnostic dilemma.

AIM: To identify the criteria for the differentiation of hilar cholangiocarcinoma (HCCA) from benign strictures. METHODS: A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These findings were analyzed to obtain the final diagnosis. RESULTS: Histological examination of the resected specimens confirmed HCCA in 58 patients (85%, group I) whereas 10 patients (15%, group II) were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients (79% group I vs 60% group II, P = 0.23). Laboratory findings showed greater elevation of transaminase levels in group I compared to group II. The various imaging modalities showed vascular involvement exclusively in the malignant group (36%, P < 0.05). Brush cytology was positive for malignant cells in only 50% patients in group I whereas none in group II showed malignant cells. CONCLUSION: Despite improvements in imaging techniques, 10 patients (15%) with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.