Assessment of Telomere Length and Molecular Characterization of TERT Gene Promoter in Periampullary Carcinomas

Genetic and epigenetic alterations of the telomere maintenance machinery like telomere length and telomerase reverse transcriptase (encoded by TERT gene) are reported in several human malignancies. However, there is limited knowledge on the status of the telomere machinery in periampullary carcinomas (PAC) that are rare and heterogeneous groups of cancers arising from different anatomic sites around the ampulla of Vater. In the current study, we investigated the relative telomere length (RTL) and the most frequent genetic and epigenetic alterations in the TERT promoter in PAC (n=20) and compared with tumor-adjacent nonpathological duodenum (NDu; n=16). We found shorter RTLs (1.27 vs 1.33, P=0.01) and lower TERT protein expression (p=0.04) in PAC tissues as compared to the NDu. Although we did not find any mutation at two reactivating hotspot mutation sites of the TERT promoter, we detected polymorphism in 55% (11/20) of the cases at rs2853669 (T>C). Also, we found a hypermethylated region in the TERT promoter of PACs consisting of four CpGs (cg10896616 with ∆β 7%; cg02545192 with ∆β 9%; cg03323598 with ∆β 19%; and cg07285213 with ∆β 15%). In conclusion, we identified shorter telomeres with DNA hypermethylation in the TERT promoter region and lower TERT protein expression in PAC tissues. Further studies with a larger sample size are necessary to substantiate these results.

A CT-Based Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Periampullary Carcinomas

PurposeTo establish and validate a radiomics nomogram for preoperatively predicting lymph node (LN) metastasis in periampullary carcinomas.Materials and MethodsA total of 122 patients with periampullary carcinoma were assigned into a training set (n = 85) and a validation set (n = 37). The preoperative CT radiomics of all patients were retrospectively assessed and the radiomic features were extracted from portal venous-phase images. The one-way analysis of variance test and the least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature was constructed with logistic regression algorithm, and the radiomics score was calculated. Multivariate logistic regression model integrating independent risk factors was adopted to develop a radiomics nomogram. The performance of the radiomics nomogram was assessed by its calibration, discrimination, and clinical utility with independent validation.ResultsThe radiomics signature, constructed by seven selected features, was closely related to LN metastasis in the training set (p < 0.001) and validation set (p = 0.017). The radiomics nomogram that incorporated radiomics signature and CT-reported LN status demonstrated favorable calibration and discrimination in the training set [area under the curve (AUC), 0.853] and validation set (AUC, 0.853). The decision curve indicated the clinical utility of our nomogram.ConclusionOur CT-based radiomics nomogram, incorporating radiomics signature and CT-reported LN status, could be an individualized and non-invasive tool for preoperative prediction of LN metastasis in periampullary carcinomas, which might assist clinical decision making.

Primary Periampullary Adenocarcinoma of the Duodenum – Report of Two Cases

The duodenum is an infrequent site of neoplasms. Among the periampullary carcinomas, duodenal neoplasia is the least common type. This manuscript describes two cases of primary adenocarcinoma of the duodenum in the periampullary region, with similar clinical manifestations, both surgically treated with pacreaticoduodenectomy.

AN UNUSUALLY PROLONGED SURVIVAL IN METASTATIC PERIAMPULLARY PANCREATIC ADENOCARCINOMA

Periampullary cancer is the term used for neoplasms arising from the head of pancreas, ampulla of Vater, distal bile duct and periampullary region of duodenum. Of these, the pancreatic adenocarcinoma carries the worst prognosis with majority of mortalities within the 1st year. The overall 5-year survival is <3%. Studies have shown that pancreatic carcinoma has the shortest median survival of 17.1 months of all periampullary carcinomas. With the development of metastasis, the median survival tends to reduce to 3–6 months. We are reporting a case of metastatic periampullary pancreatic adenocarcinoma that received minimal and interrupted chemotherapy due to poor tolerance and yet managed to survive far beyond the reported median survival. Key words: Adenocarcinoma, pancreas, periampullary, prognosis