RADPs were equivalent to LDPs in nearly all measures of outcome and safety but significantly reduced the risk of conversion to open resection, despite a statistically greater probability of malignancy in the robotic cohort. We concluded that robotic assistance may broaden indications for minimally invasive pancreatectomy.

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

Background and Objectives Computer Assisted Robotic Surgery allows complex resections and anastomotic reconstructions to be performed with nearly identical standards to open surgery. We applied this technology to a variety of pancreatic resections to assess the safety, feasibility, versatility and reliability of this technology. Methods A retrospective review of a prospective database of robotic pancreatic resections at a single institution between August 2008 and November 2012 was performed. Peri-operative outcomes were analyzed. Results 250 consecutive robotic pancreatic resections were analyzed; pancreaticoduodenectomy (PD =132), distal pancreatectomy (DP=83), central pancreatectomy (CP=13), pancreatic enucleation (10), total pancreatectomy (TP=5), Appleby resection (4), and Frey procedure (3). Thirty day and 90 day mortality was 0.8 % and 2.0%. Rate of Clavien 3 and 4 complications was 14 and 6 %. The ISGPF grade C fistula rate was 4%. Mean operative time for the two most common procedures was 529 ± 103 mins for PD, and 257 ± 93 mins for DP. Continuous improvement in operative times was observed over the course of the experience. Conversion to open procedure was required in 16 patients (6%);(11 PD, 2 DP, 2 CP, 1 TP) for failure to progress (14) and bleeding (2). Conclusions This represents to our knowledge the largest series of robotic pancreatic resections. Safety and feasibility metrics including the low incidence of conversion support the robustness of this platform and suggest no unanticipated risks inherent to this new technology. By defining these early outcome metrics this report begins to establish a framework for comparative effectiveness studies of this platform.

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e19 (https://www. gastrojournal.org/cme/home). Learning Objective: Upon completion of this CME activity, successful leaners will be able to identify current clinically relevant genomic alterations in pancreatic ductal adenocarcinoma.

Background Trials examining FOLFIRINOX in metastatic pancreatic cancer demonstrate higher response rates compared to gemcitabine-based regimens. There is currently limited experience with neoadjuvant FOLFIRINOX in pancreatic cancer. Methods Retrospective review of outcomes of patients with borderline resectable or locally unresectable pancreatic cancer who were recommended to undergo neoadjuvant treatment with FOLFIRINOX. Results FOLFIRINOX was recommended for 25 patients with pancreatic cancer, 13 (52%) unresectable and 12 (48%) borderline resectable. Four patients (16%) refused treatment or were lost to follow up. 21 patients (84%) were treated with a median of 4.7 cycles. 6 patients (29%) required dose reductions secondary to toxicity. 2 patients (9%) were unable to tolerate treatment and 3 patients (14%) had disease progression on treatment. 7 patients (33%) underwent surgical resection following treatment with FOLFIRINOX alone, 2 (10%) of which were initially unresectable. 2 patients underwent resection following FOLFIRINOX + stereotactic body radiation therapy (SBRT). The R0 resection rate for patients treated with FOLFIRINOX +/− SBRT was 33% (55% borderline resectable, 10% unresectable). A total of 5 patients (24%) demonstrated a significant pathologic response. Conclusions FOLFIRINOX is a biologically active regimen in borderline resectable and locally unresectable pancreatic cancer with encouraging R0 resection and pathologic response rates.

Tumor infiltration with effector CD8+ T cells (Teff) predicts longer recurrence-free survival in mmany types of human cancer, illustrating the broad significance of Teff for effective immunosurveillance. Colorectal tumors with reduced accumulation of Teff express low levels of Teff-attracting chemokines such as CXCL10/IP10 and CCL5/RANTES. In this study, we investigated the feasibility of enhancing tumor production of Teff-attracting chemokines as a cancer therapeutic strategy, using a tissue explant culture system to analyze chemokine induction in intact tumor tissues. In different tumor explants, we observed highly heterogeneous responses to IFNα or poly-I:C (a TLR3 ligand) when they were applied individually. In contrast, a combination of IFNα and poly-I:C uniformly enhanced the production of CXCL10 and CCL5 in all tumor lesions. Moreover, these effects could be optimized by the further addition of COX inhibitors. Applying this triple combination also uniformly suppressed the production of CCL22/MDC, a chemokine associated with infiltration of T regulatory cells (Treg). The Teff-enhancing effects of this treatment occurred selectively in tumor tissues, as compared to tissues derived from tumor margins. These effects relied on the increased propensity of tumor-associated cells (mostly fibroblasts and infiltrating inflammatory cells) to hyper-activate NF-κB and produce Teff-attracting chemokines in response to treatment, resulting in an enhanced ability of the treated tumors to attract Teff cells and reduced ability to attract Tregs. Together, our findings suggest the feasibility of exploiting NF-κB hyper-activation in the tumor microenvironment to selectively enhance Teff entry into colon tumors.

Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear.Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst.Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92).Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.

In this experience, RDP outcomes were optimized after 40 cases. Familiarity with the platform and dedicated training are likely to contribute to significantly shorter learning curves in future adopters.