Preoperative risk factors for anastomotic leak after esophagectomy with gastric reconstruction: A 6-year national surgical quality improvement (NSQIP) database analysis.

BACKGROUND: Anastomotic leak is a serious complication after esophagectomy that has been associated with worse outcomes. However, identifying patients at increased risk for anastomotic leak remains challenging. METHODS: Patients were included from the 2016 to 2021 National Surgical Quality Improvement Project database who underwent elective esophagectomy with gastric reconstruction for cancer. A multivariable logistic regression model was used to identify risk factors associated with anastomotic leak. RESULTS: A total of 4,331 patients were included in the study, of whom 647 patients experienced anastomotic leak (14.9%). Multivariable logistic regression revealed higher odds of anastomotic leak with smoking (adjusted odds ratio 1.24, confidence interval 1.02-1.51, P = .031), modified frailty index-5 score of 1 (adjusted odds ratio 1.44, confidence interval 1.19-1.75, P = .002) or 2 (adjusted odds ratio 1.52, confidence interval 1.19-1.94, P = .000), and a McKeown esophagectomy (adjusted odds ratio 1.44, confidence interval 1.16-1.80, P = .001). Each 1,000/µL increase in white blood cell count was associated with a 7% increase in odds of anastomotic leak (adjusted odds ratio 1.07, confidence interval 1.03-1.10, P = .0005). Higher platelet counts were slightly protective, and each 10,000/ µL increase in platelet count was associated with 2% reduced odds of anastomotic leak (adjusted odds ratio 0.98, confidence interval 0.97-0.99, P = .001). CONCLUSION: In this study, smoking status, frailty index, white blood cell count, McKeown esophagectomy, and platelet counts were all associated with the occurrence of anastomotic leak. These results can help to inform surgeons and patients of the true risk of developing anastomotic leak and potentially improve outcomes by providing evidence to improve preoperative characteristics, such as frailty.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice.

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by periods of heavy drinking and periods of withdrawal. Chronic exposure to ethanol causes profound neuroadaptations in the extended amygdala, which cause allostatic changes promoting excessive drinking. The bed nucleus of the stria terminalis (BNST), a brain region involved in both excessive drinking and anxiety-like behavior, shows particularly high levels of pituitary adenylate cyclase-activating polypeptide (PACAP), a key mediator of the stress response. Recently, a role for PACAP in withdrawal-induced alcohol drinking and anxiety-like behavior in alcohol-dependent rats has been proposed; whether the PACAP system of the BNST is also recruited in other models of alcohol addiction and whether it is of local or nonlocal origin is currently unknown. Here, we show that PACAP immunoreactivity is increased selectively in the BNST of C57BL/6J mice exposed to a chronic, intermittent access to ethanol. While pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor-expressing cells were unchanged by chronic alcohol, the levels of a peptide closely related to PACAP, the calcitonin gene-related neuropeptide, were found to also be increased in the BNST. Finally, using a retrograde chemogenetic approach in PACAP-ires-Cre mice, we found that the inhibition of PACAP neuronal afferents to the BNST reduced heavy ethanol drinking. Our data suggest that the PACAP system of the BNST is recruited by chronic, voluntary alcohol drinking in mice and that nonlocally originating PACAP projections to the BNST regulate heavy alcohol intake, indicating that this system may represent a promising target for novel AUD therapies.