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Mistreatment has been documented as a negative factor in the learning environment for the past 30 y but little progress has been made to determine an effective way to significantly improve these interactions. Faculty may also be victims of a hostile work environment as well, although frequency has not been well-measured or reported. In fact, it may be difficult to identify and address mistreatment and hostility in the work place within the commonly established surgical culture. Thus, efforts to define, identify, and address workplace mistreatment or hostility are crucial to the success of the academic surgical environment. This article summarizes presentations and panel discussion that took place at the 2019 Academic Surgical Congress organized by the Association for Academic Surgery and the Society of University Surgeons. Definitions of mistreatment and hostility were provided, as well as information regarding occurrence. Tools for addressing mistreatment in the work environment and tips for creating a positive environment were presented and discussed.

Recombinant methioninase (rMETase) derived from Pseudomonas putida targets the elevated methionine (MET) requirement of cancer cells (methionine dependence) and has shown efficacy against a variety of cancer types in mouse models. To enhance the efficacy of rMETase, we constructed the pLGFP-METSN retrovirus encoding the P. putida methioninase (METase) gene fused with the green fluorescent protein (GFP) gene. pLGFP-METSN or control vector pLGFPSN was introduced into the human lung cancer cell line H460. The retrovirus-mediated METase gene transfer decreased the intracellular MET level of the cancer cells and consequently enhanced the efficacy of treatment with the rMETase protein. The rMETase gene was introduced into an adenovirus. rAd-METase transduction of human OVACAR-8 ovarian cancer cells and human fibrosarcoma HT1080 cells in vitro and in vivo resulted in high levels of METase expression up to 10% or more of the total protein of the cells, depending on the multiplicity of infection. The combination of rAd-METase and rMETase was synergistic to kill these cells. Normal fibroblasts, on the other hand, appeared relatively resistant to the METase gene in the presence of rMETase. Adenoviral METase-transduced cancer cells were used in combination with selenomethionine, releasing highly toxic methylselenol, which killed both the cancer cells containing the METase gene and bystanders. Methylselenol damaged the mitochondria via oxidative stress and caused cytochrome c release into the cytosol, thereby activating the caspase cascade and cancer-cell apoptosis. Adenoviral METase-gene/SeMET treatment also inhibited tumor growth in rodents and significantly prolonged their survival. AdMETase/SeMET therapy was effective against Bcl-2-overproducing A549 lung cancer cells, which were resistant to staurosporine-induced apoptosis, with a strong bystander effect. The combination of Ad-METase/SeMET and doxorubicin (DOX) delayed the growth of the H460 human lung cancer, growing subcutaneously in nude mice. These results demonstrate the potential of methionine restriction (MR) for cancer treatment.

Our previous studies demonstrate that patients with non-pancreatic periampullary adenocarcinomas have a favorable prognosis relative to those with pancreatic adenocarcinoma. This study investigates histopathologic factors that contribute to the superior outcome of these patients.A retrospective review of all patients explored for periampullary neoplasms at a single institution over a 20-year period.291 patients with periampullary neoplasms underwent exploratory laparotomy, of which 185 had resectable tumors. Periampullary adenocarcinomas were resected in 120: pancreatic head (n=74), distal common bile duct (n=10), duodenum (n=5), and ampulla of Vater (n=31). The resection rate for non-pancreatic adenocarcinomas was 90%, while that of pancreatic cancers was 44% (p0.01). Median survival for resected non-pancreatic adenocarcinomas was 38.8 months; that of pancreatic tumors was 15.3 months (p0.01). Non-pancreatic adenocarcinomas were significantly smaller (p0.001), better differentiated (p0.001), and less likely to have involved nodes (p0.001), margins (p0.001), perineural invasion (p0.001), or vascular invasion (p0.2) than pancreatic adenocarcinomas.Histopathologic features of non-pancreatic periampullary adenocarcinomas significantly differentiate them from pancreatic adenocarcinoma and contribute to their relatively favorable long-term outcome following resection.