Cachexia is a debilitating condition characterized by extreme skeletal muscle wasting that contributes significantly to morbidity and mortality. Efforts to elucidate the underlying mechanisms of muscle loss have predominantly focused on events intrinsic to the myofiber. In contrast, less regard has been given to potential contributory factors outside the fiber within the muscle microenvironment. In tumor-bearing mice and patients with pancreatic cancer, we found that cachexia was associated with a type of muscle damage resulting in activation of both satellite and nonsatellite muscle progenitor cells. These muscle progenitors committed to a myogenic program, but were inhibited from completing differentiation by an event linked with persistent expression of the self-renewing factor Pax7. Overexpression of Pax7 was sufficient to induce atrophy in normal muscle, while under tumor conditions, the reduction of Pax7 or exogenous addition of its downstream target, MyoD, reversed wasting by restoring cell differentiation and fusion with injured fibers. Furthermore, Pax7 was induced by serum factors from cachectic mice and patients, in an NF-κB-dependent manner, both in vitro and in vivo. Together, these results suggest that Pax7 responds to NF-κB by impairing the regenerative capacity of myogenic cells in the muscle microenvironment to drive muscle wasting in cancer.

Cachexia contributes to nearly a third of all cancer deaths, yet the mechanisms underlying skeletal muscle wasting in this syndrome remain poorly defined. We report that tumor-induced alterations in the muscular dystrophy-associated dystrophin glycoprotein complex (DGC) represent a key early event in cachexia. Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin transgenic mice that blocked induction of muscle E3 ubiquitin ligases. Furthermore, DGC deregulation correlated positively with cachexia in patients with gastrointestinal cancers. Based on these results, we propose that, similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting.

This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

Background For patients with metastatic pancreatic cancer, FOLFIRINOX (fluorouracil [5-FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) has shown improved survival rates compared with gemcitabine but with significant toxicity, particularly in patients with a high tumor burden. Because of reported response rates exceeding 30 %, the authors began to use a modified (m) FOLFIRINOX regimen for patients with advanced nonmetastatic disease aimed at downstaging for resection. This report describes their experience with mFOLFIRINOX and aggressive surgical resection. Methods Between January 2011 and August of 2013, 43 patients with borderline resectable pancreatic cancer (BRPC, n = 18) or locally advanced pancreatic cancer (LAPC, n = 25) were treated with mFOLFIRINOX (no bolus 5-FU, no LV, and decreased IRI). Radiation was used based on response and intended surgery. Charts were retrospectively reviewed to assess response, toxicities, and extent of resection when possible. Results The most common grade 3/4 toxicity was diarrhea in six patients (14 %) with no grade 3/4 neutropenia or thrombocytopenia. Resection was attempted in 31 cases (72 %) and accomplished in 22 cases (51.1 %) including 11 of 25 LAPC cases (44 %). Vascular resection was required in 4 cases (18 %), with R0 resection in 86.4 %of the resections. Complications occurred in 6 cases (27 %), with no perioperative deaths. The median progression-free survival period was 18 months if the resection was achieved compared with 8 months if no resection was performed (p < 0.001). Conclusion Neoadjuvant mFOLFIRINOX is an effective, well-tolerated regimen for patients with advanced nonmetastatic pancreatic cancer. When mFOLFIRINOX is coupled with aggressive surgery, high resection rates are possible even when the initial imaging shows locally advanced disease. Although data are still maturing, resection appears to offer at least a progression-free survival advantage.

Transgastric diagnostic peritoneoscopy is safe and feasible. This study demonstrates the initial steps of NOTES in humans, providing a potential platform for incisionless surgery. Technical issues, including instrumentation, visualization, intra-abdominal manipulation, and gastric closure need further development.

Background-Cancers of the ampulla of Vater, distal common bile duct, and pancreas are known to have dismal prognosis. It is often reported that ampullary cancers are less aggressive relative to the other periampullary carcinomas. We sought to evaluate predictors of survival for periampullary cancers following pancreaticoduodenectomy to identify biologic behavior.

BACKGROUND The incidence of pancreatic cancer is age related; patients older than the age of 65 represent 60% of all cases. We assessed our institution’s experience and outcomes with pancreatic resection for malignancy in patients in their ninth decade. STUDY DESIGN We reviewed records of patients undergoing pancreatic resection for malignancy at our institution between 1990 and 2007. Demographics, laboratory, treatment, and outcomes data were gathered. Comparisons were made between patients older and younger than the age of 80. Survival was analyzed using the Kaplan-Meier method and comparisons between groups were performed using the log-rank test. Regression methods were used to evaluate predictors of outcomes. RESULTS There were 517 pancreatic resections for cancer reviewed. Of these, 27 patients were 80 years or older (age range 80 to 91 years), compared with 490 patients less than 80 (range 20 to 79 years). The distribution of clinical characteristics was similar between the 2 groups. The majority of patients undergoing pancreatic resection harbored a mass in the head of the pancreas, so the most common procedure was pancreaticoduodenectomy (n = 398, 78%). There were no significant differences in complication rates for younger and older groups (59% vs 52%, respectively, p = 0.4), median length of stay (11 vs 12 days, p = 0.33), or perioperative mortality rates (3.7% vs 3.7%, p = 1.0). Overall survival between the 2 groups was similar (21.9 vs 33.3 months, p = 0.18). CONCLUSIONS Pancreatectomy for malignancy is a safe option for the elderly. Patients older than age 80 achieved similar results, with similar rates of perioperative complications and mortality. Pancreatectomy for cancer offers a similar survival benefit in both groups.

BACKGROUND Intraoperative cholangiography (IOC) is the current gold standard for biliary imaging during laparoscopic cholecystectomy (LC). However, utilization of IOC remains low. Near Infrared Fluorescence Cholangiography (NIRF-C) is a novel, noninvasive method for real-time, intraoperative biliary mapping. Our aims were to assess the safety and efficacy of NIRF-C for identification of biliary anatomy during LC. METHODS Patients were administered indocyanine green (ICG) prior to surgery. NIRF-C was used to identify extrahepatic biliary structures before, and after partial and complete dissection of Calot's triangle. Routine IOC was performed in each case. Identification of biliary structures using NIRF-C and IOC, and time required to complete each procedure were collected. RESULTS Eighty-two patients underwent elective LC with NIRF-C and IOC. Mean age and BMI were 42.6±13.7 years and 31.5±8.2 kg/m2, respectively. ICG was administered 73.8±26.4 minutes prior to incision. NIRF-C was significantly faster than IOC (1.9±1.7 vs. 11.8±5.3 minutes, p<0.001). IOC was unobtainable in 20 (24.4%) patients while NIRF-C did not visualize biliary structures in 4 (4.9%) patients. After complete dissection, the rates of visualization of the cystic duct, common bile duct, and common hepatic duct using NIRF-C were 95.1%, 76.8%, and 69.5%, respectively, compared to 72.0%, 75.6%, and 74.3% for IOC. In 20 patients where IOC could not be obtained, NIRF-C successfully identified biliary structures in 80% of the cases. Higher BMI was not a deterrent to visualization of anatomy with NIRF-C. No adverse events were observed with NIRF-C. CONCLUSIONS NIRF-C is a safe and effective alternative to IOC for imaging extrahepatic biliary structures during LC. This technique should be evaluated further under a variety of acute and chronic gallbladder inflammatory conditions to determine its usefulness in biliary ductal identification.