These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer.

Primary cancers of the appendix are rare and are frequently diagnosed after surgery for appendicitis, presumed ovarian primary malignancy, or other indications. Primary appendix cancers are histologically diverse, and classification of these tumors has historically been confusing because of the nonstandardized nomenclature that is used. This review aimed to describe the epidemiology, presentation, workup, staging, and management of primary appendix cancers using current, recommended nomenclature. For this purpose, tumors were broadly classified as colonic-type or mucinous adenocarcinoma, goblet cell adenocarcinoma, or neuroendocrine carcinoma. Signet ring cell carcinoma was not regarded as an individual entity. The presence of signet ring cells is a histologic feature that may or may not be present in colonic-type or mucinous adenocarcinoma. The management of primary appendix cancer is complex and is dependent on the histologic subtype and extent of disease. Randomized, prospective trials do not exist for these rare tumors and management is largely guided by retrospective data expert consensus guidelines, which are summarized here.

Preoperative factors are associated with perioperative outcomes after PD. The prediction tool estimates the probability of early morbidity and mortality for patients undergoing PD. The tool may be used to provide information for patient counseling during the informed consent process and to identify high-risk patients for the purpose of tailoring perioperative care.

Newcastle disease virus (NDV) has been previously shown to possess oncolytic activity, causing specific lysis of cancerous but not normal cells. Here we show that despite these findings, the oncolytic efficiency of naturally occurring NDV strains can still be relatively low, as many tumors exhibit strong innate immune responses that suppress viral replication and spread. To overcome this problem, we generated a recombinant fusogenic NDV expressing influenza NS1 protein, a protein exhibiting interferon (IFN)-antagonist and antiapoptotic functions in human and mouse cells. Interestingly, the resultant virus was dramatically enhanced in its ability to form syncytia, lyse a variety of human and mouse tumor cell lines, and suppressed the induction of the cellular IFN responses. Using the aggressive syngeneic murine melanoma model, we show that the NDV-NS1 virus is more effective than virus not expressing NS1 in clearing the established footpad tumors and results in higher overall long-term animal survival. In addition, mice treated with NDV-NS1 exhibited no signs of toxicity to the virus and developed tumor-specific cytotoxic T lymphocyte (CTL) responses. These findings demonstrate that modulation of innate immune responses by NDV results in enhancement of its oncolytic properties and warrant further investigation of this strategy in design of oncolytic NDV vectors against human tumors.

Introduction Data on laparoscopic gastrectomy in patients with gastric cancer in the Western hemisphere are lacking. This study aimed to compare outcomes following laparoscopic versus open gastrectomy for gastric adenocarcinoma at a Western center. Methods Eighty-seven consecutive patients who underwent laparoscopic gastrectomy from November 2005 to April 2013 were compared with 87 patients undergoing open resection during the same time period. Patients were matched for age, stage, body mass index, and procedure (distal subtotal vs. total gastrectomy). Endpoints were short- and long-term perioperative outcomes. Results Overall, 65 patients (37 %) had locally advanced disease, and 40 (23 %) had proximal tumors. The laparoscopic approach was associated with longer operative time (median 240 vs.165 min; p < 0.01), less blood loss (100 vs.150 mL; p < 0.01), higher rate of microscopic margin positivity (9 vs.1 %; p = 0.04), decreased duration of narcotic and epidural use (2 vs. 4 days, p = 0.04, and 3 vs. 4 days, p = 0.02, respectively), decreased minor complications in the early (27 vs. 16 %) and late (17 vs. 7 %) postoperative periods (p < 0.01), decreased length of stay (5 vs. 7 days; p = 0.01), and increased likelihood of receiving adjuvant therapy (82 vs. 51 %; p < 0.01). There was no difference in the number of lymph nodes retrieved (median 20 in both groups), major morbidity, or 30-day mortality. Conclusions Laparoscopic gastrectomy for gastric adenocarcinoma is safe and effective for select patients in the West.

Purpose: Esophageal, gastro-esophageal junction and gastric adenocarcinoma (herein gastroesophageal adenocarcinomas) are associated with poor prognosis and limited systemic treatment options. To further understand the genomic landscape of gastroesophageal cancers and its clinical correlations, circulating tumor DNA (ctDNA) from patients’ plasma was evaluated using next-generation sequencing (NGS). Methods: We analyzed genomic alterations of 55 patients (mostly advanced disease; nine, surgically resectable) with gastroesophageal adenocarcinomas using clinical-grade NGS performed on plasma-derived ctDNA (54-73 gene panel). The test detects single nucleotide variants, as well as copy number amplifications, fusions and indels in selected genes. Results: Seventy-six percent of patients (42/55) had ≥1 genomic alteration (including variants of unknown significance [VUSs]) and 69.1% (38/55) had ≥1 characterized alteration (excluding VUSs). The median number of alterations per patient was 2 (range, 0–15). TP53 (50.9%, 28/55), PIK3CA (16.4%, 9/55), ERBB2 (14.5%, 8/55) and KRAS (14.5%, 8/55) genes were most frequently affected characterized alterations. Thirty-one patients also had tissue NGS. Concordance between tissue and ctDNA ranged from 61.3% (TP53 alterations) to 87.1% (KRAS alterations). ERBB2 alterations were significantly associated with poor overall survival (HR: 14.06, 95% CI: 2.44 – 81.03, P=0.003 multivariate analysis). Among patients with ≥1 alteration, no two patients had identical molecular portfolios. All patients with ≥1 characterized alteration had theoretically targetable alterations by an FDA-approved agent (on- or off-label). Illustrative case treated with cognate agent is presented. Conclusions: Evaluation of ctDNA by NGS among gastroesophageal adenocarcinoma patients is feasible. Patients harbored heterogeneous patterns of genomics, with most having alterations that are potentially pharmacologically tractable.

The rate of serious complication after DP is 22%. The DP-specific preoperative risk scoring system described in this paper may be utilized for patient counseling and informed consent discussions, identifying high-risk patients who would benefit from disease optimization, and risk adjustment when comparing outcomes between institutions.

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