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Context:Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms.Objective:To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression.Design:These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies.Patients:Two groups, more than 5 months after RYGB for obesity (n = 7–11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies.Intervention:Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task.Main Outcome Measures:Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups.Results:Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1.Conclusions:Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Spigelian hernias are a rare abdominal wall hernia. The aim of this study was to assess the efficacy and outcomes of patients who underwent a laparoscopic spigelian hernia repair. A retrospective study was performed reviewing all patients who had a laparoscopic spigelian hernia repair. We assessed the success of the procedure including conversion rates, postoperative morbidities, and recurrence rates. Forty patents had a laparoscopic repair. Two thirds (n=25) had an intraperitoneal repair. There was no conversion to open repair. Four patients had postoperative morbidities. At 6-month follow-up all patients were pain free, with 1 recurrence. There is considerable evidence supporting the opinion that laparoscopic repair offers excellent outcomes. This report is the largest series to date, and we advocate that this approach should become the standard of care.

According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

Background & objective: Liver resection for breast cancer liver metastases is becoming a more widely accepted therapeutic option for selected groups of patients. The aim of this study was to describe the outcomes of patients undergoing liver resection for breast cancer-related liver metastases and identify any variables associated with recurrence or survival.Methods: A retrospective review of a prospectively maintained database was undertaken for the 12 year period between 2009 and 2021. Clinicopathological, treatment, intraoperative, recurrence, survival and follow-up data were collected on all patients. Kaplan-Meier methods, the log-rank test and Cox proportional hazards regression analysis were used to identify variables that were associated with recurrence and survival.Results: A total of 20 patients underwent 21 liver resections over the 12-year period. There were no deaths within 30 days of surgery and an operative morbidity occurred in 23.8% of cases. The median local recurrence free survival and disease free survival times were both 50 months, while the 5 year overall survival rate was 65%. The presence of extrahepatic metastases were associated with a decreased time to local recurrence (p < 0.01) and worse overall survival (p = 0.02).Conclusions: This study has demonstrated that liver resection for breast cancer-related liver metastases is feasible, safe and associated with prolonged disease free and overall survival in selected patients. It is likely that this option will be offered to more patients going forward, however, the difficulty lies in selecting out those who will benefit from liver resection particularly given the increasing number of systemic treatments and local ablative methods available that offer good long-term results.

The cellular mechanisms involved in mediating cytoprotection against ischemia-reperfusion (IR) injury are not well understood. In animal models, NF-E2-related factor-2 (Nrf2) protects against IR injury by transcriptional activation of phase II antioxidants. Here, we investigate how the expression of Nrf2 mRNA in human donor livers in the setting of liver transplantation (LT) correlates with the histological damage associated with IR injury and whether or not this influences the outcome of LT.

Altered nitric oxide (NO) metabolism has been shown to contribute to ischemia-reperfusion (IR) injury in animal models. However, similar studies have not been performed in human liver transplantation (LT). In this study, we examined nitrate, nitrite, and nitrosothiols (NOx), NO synthases (endothelial constitutive nitric oxide synthase eNOS and inducible nitric oxide synthase iNOS), and nitrotyrosine in early IR injury after human LT.

Prostaglandins have been shown to protect against a variety of liver insults, including ischemia-reperfusion injury. Decreased graft injury and improved survival have been demonstrated in animal studies of liver transplantation after donor pretreatment with prostaglandin before organ retrieval. This potential clinical application has not been examined in human subjects.

Geoghegan, J. G., C. A. Cheng, D. C. Lawson and T. N. Pappas. The effect of caloric load and nutrient composition on induction of small intestinal satiety in dogs. Physiol Behav 62(1) 39–42, 1997.—The influence of caloric load and nutrient composition on small intestinal satiety was investigated in six dogs with chronic esophageal fistulas. Dogs received small bowel infusion of a mixed nutrient liquid meal, a fat, carbohydrate, and a protein solution over two hours. Each infusion was given over a range of caloric densities which represented between 0 to 20% of the total 24 h caloric requirement for each animal. Satiety was measured by sham feeding at the end of the infusion. Infusion of 0.25 cal/ml (equivalent to 5% of the 24 h caloric requirement) of a liquid mixed nutrient meal (Isocal®) significantly suppressed sham feeding (volume sham fed: control 265 ± 28 ml/min; Isocal 0.25 cal/ml 218 ± 52 ml/min, p< 0.05). Oleate and dextrose polymer also significantly reduced sham feeding at a caloric concentration of 0.25 cal/ml (volume sham fed: control 265 ± 28 ml/min; oleate 112 ± 28 ml/min; oleate 112 ± 9 ml/min; dextrose polymer 190 ± 11 ml/min), whereas peptone did not significantly suppress sham feeding until a solution with 0.5 cal/ml was given. These studies demonstrate that caloric load of intestinal nutrients must reach a threshold to produce satiety in sham feeding dogs. The threshold caloric load is different for the three nutrient groups, with fats requiring the lowest caloric load to produce satiety. These provide insight into the mechanisms by which small intestinal signals might contribute to regulation of the inter-meal interval.

Background:Neuropeptide Y (NPY), a centrally located neurotransmitter, is known to increase appetite in fasted and satiated animals. In addition to evaluating NPY's effect on eating behavior, this study was intended to determine whether intracerebroventricular (ICV) NPY would have an effect on canine gastric and pancreatic secretion. Methods:Four dogs were prepared with cerebroventricular guides and gastric and pancreatic fistulas. ICV and intravenous NPY was administered during intragastric titration of a glucose and peptone meal. During this study, gastric and pancreatic secretion was measured, as well as insulin levels and pancreatic polypeptide (PP). An additional set of four dogs were prepared with esophageal fistulas and cerebroventricular guides, and the effect of ICV NPY on sham feeding was studied. Results:ICV NPY significantly increased sham feeding, meal-stimulated gastric and pancreatic secretion, basal gastric acid, pancreatic bicarbonate, insulin levels, and PP. Vagotomy blocked the effect of ICV NPY on gastric acid secretion in a urethane-anesthetized rat model with acute gastric fistula. Conclusions:ICV NPY increased sham feeding, gastric and pancreatic secretion, insulin levels, and PP in the dogs. NPY's effect on gastric secretion was blocked by vagotomy in a rat model. NPY should be considered a candidate mediator of cephalic phase secretion.

Molecular and clinical markers outperform current clinical and imaging criteria for the diagnosis and management of patients with pancreatic cysts.