Benefits and limitations of middle bile duct segmental resection for extrahepatic cholangiocarcinoma

Background: Pancreaticoduodenectomy (PD) is a standardized strategy for patients with middle and distal bile duct cancers. The aim of this study was to compare clinicopathological features of bile duct segmental resection (BDR) with PD in patients with extrahepatic cholangiocarcinoma. Methods: Consecutive cases with extrahepatic cholangiocarcinoma who underwent BDR (n = 21) or PD (n = 84) with achievement of R0 or R1 resection in Kobe University Hospital between January 2000 and December 2016 were enrolled in the present study. Results: Patients who underwent PD were significantly younger than those receiving BDR. The frequency of preoperative jaundice, biliary drainage and cholangitis was not significantly different between the two groups. The duration of surgery was longer and there was more intraoperative bleeding in the PD than in the BDR group (553 vs. 421 min, and 770 vs. 402 mL; both PClavien-Dindo IIIa) were observed in the PD group (46% vs. 10%, P<0.01). Postoperative hospital stay was also longer in that group (30 vs. 19 days, P = 0.02). Pathological assessment revealed that tumors were less advanced in the BDR group but the rate of lymph node metastasis was similar in both groups (33% in BDR and 48% in PD, P = 0.24). The rate of R0 resection was significantly higher in the PD group (80% vs. 38%, P<0.01). Adjuvant chemotherapy was more frequently administered to patients in the BDR group (62% vs. 38%, P = 0.04). Although 5-year overall survival rates were similar in both groups (44% for BDR and 51% for PD, P = 0.72), in patients with T1 and T2, the BDR group tended to have poorer prognosis (44% vs. 68% at 5-year, P = 0.09). Conclusions: BDR was comparable in prognosis to PD in middle bile duct cancer. Less invasiveness and lower morbidity of BDR justified this technique for selected patients in a poor general condition

Increased expression of SPRR1A is associated with a poor prognosis in pancreatic ductal adenocarcinoma.

ObjectivesSmall proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC.MethodsWe examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro.ResultsAmong the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression.ConclusionIncreased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC