Correlation of survival length after pancreaticoduodenectomy for pancreatic head adenocarcinoma depending on tumor characteristics detected by means of computed tomography and resection margins status.

Pancreatic carcinoma is an aggressive tumor with a grim prognosis. Accurate staging is essential for indicating surgery in patients with borderline resectable tumors. This paper examines the correlation between pre-operation characteristics of tumors found on CT, infiltration of individual resection margins as confirmed by a pathologist, and the survival of patients with resectable pancreatic head ductal adenocarcinoma. This prospective cohort study involved patients operated on for pancreatic head adenocarcinoma, which was clearly resectable based on the staging CT and intraoperative observation between 2011-2014. Only patients without postoperative complications who underwent adjuvant chemotherapy were analyzed. Seventy-nine patients were assessed, of which 16 (20.3%) had R0 resection and 63 (79.7%) had R1 resection. Patients with R1 results had up to 2.7 times higher risk of death than patients with R0 resection. We found a trend towards shorter survival associated with a closer relationship of the tumor to the superior mesenteric vein/portal vein (SMV/PV) wall in the pre-operation CT examination. Patients with a tumor interface between the vein wall of up to 180 ° circumference had up to 1.97 times higher risk of death than patients without (p=0.131). The results of our work confirmed that in our center, even surgically treated, clearly resectable pancreatic head tumors still have a high occurrence of positive surgical margins (R1 resection) and that tumors with R1 resection had statistically significantly reduced survival compared to R0 resection. A trend for shorter overall survival was found after tumor resection depending on the increasing interface between the tumor and the SMV/PV wall, but this result was not statistically significant.

Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216.

The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44. Mice were treated by experimental Stony Brook Taxane SB-T-1216. The transcript profile of 34 Hedgehog pathway genes in patients and xenografts was assessed using quantitative PCR. The Hedgehog pathway was strongly overexpressed in pancreatic tumors and upregulation of SHH, IHH, HHAT and PTCH1 was associated with a trend toward decreased patient survival. No association of Hedgehog pathway expression with KRAS mutation status was found in tumors. Sonic hedgehog ligand was overexpressed, but all other downstream genes were downregulated by SB-T-1216 treatment in vivo. Suppression of HH pathway expression in vivo by taxane-based chemotherapy suggests a new mechanism of action for treatment of this aggressive tumor.

[Standardization of pancreatic cancer specimen pathological examination]. / Standardizace patologického vysetrení resekátu pankreatu.

INTRODUCTION: The frequency of R1 resections for pancreatic cancer in studies where a non-standardized protocol of pathological evaluation of the specimen is used varies from 17 to 30%. The aim of our study is to apply the standardized (so-called Leeds) protocol of resected pancreatic specimen pathological examination, and to evaluate the frequency of R1 resections for pancreatic cancer using this new protocol. MATERIAL AND METHODS: Ninety-one patients who underwent pancreatoduodenectomy for pancreatic cancer were included in the study. This group was divided into two subgroups: patients examined by the Leeds protocol (n=20) and those examined by a non-standardized pathological protocol (n=71). The R1 resection rate was evaluated separately in each group. The positivity rate of every individual resection margin was specified in the Leeds protocol group. The correlation of R1 resection rate and "tumour - resection margin distance" parameter was evaluated. The tumour infiltration of peripancreatic adipose tissue was assessed in the non-standardized group. RESULTS: In the Leeds protocol subgroup, R1 and R0 resection rate was 60% (12/20) and 40% (8/20), respectively. Resection line positivity rates were as follows: dorsal 45% (9/20), ventral 35% (7/20), VMS 20% (4/20), cervical 20% (4/20), AMS 15% (3/20). The correlation between the tumour - resection line distance and R1 resection frequency was the following: direct infiltration 30% R1, tumour-resection margin border 0.5 mm 50% R1, 1mm 60%, 1.5 mm 75% R1, 2 mm 80% R1, >2 mm 80% R1. If the criterion of resection line positivity ( 1mm) was set, the R1 resection rate difference between the two groups was of statistical significance. In the subgroup where the non-standardized protocol was used (n=71), R1 resection was recorded in 25 (35.2%) patients. The main cancer-positive areas were peripancreatic adipose tissue in 26.8% (19/71) of cases, and VMS, AMS or retroperitoneal line in 8.5% (6/71), respectively. R0 resection was achieved in 46 (64.8%) patients. The statistically significant (p=0.046) difference in R0 and R1 resection rates was detected (Leeds protocol and non-standardized one: R0 40.0% vs. 64.8% and R1 60.0% vs. 35.2%, respectively) in the studied groups. CONCLUSION: The rate of R1 resections for pancreatic cancer increased in all studies, including ours, where the standardized (Leeds) protocol of pancreatic specimen pathological examination was used. The higher R1 resection rate when using the Leeds protocol is approaching to the local recurrence rate of pancreatic cancer. Therefore, the Leeds protocol can provide more realistic evaluation of local radicality of pancreatoduodenectomy and can also offer more accurate evaluation of the surgical and adjuvant therapy of pancreatic cancer.