Richard Babor

Randomized clinical trial of enhanced recovery versus standard care after laparoscopic sleeve gastrectomy.

Optimized perioperative care within an enhanced recovery after surgery (ERAS) protocol is designed to reduce morbidity after surgery, resulting in a shorter hospital stay. The present study evaluated this approach in the context of sleeve gastrectomy for patients with morbid obesity.

Lower Fetuin-A, Retinol Binding Protein 4 and Several Metabolites after Gastric Bypass Compared to Sleeve Gastrectomy in Patients with Type 2 Diabetes

Background Bypass of foregut secreted factors promoting insulin resistance is hypothesized to be one of the mechanisms by which resolution of type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery. Aim To identify insulin resistance-associated proteins and metabolites which decrease more after GBP than after sleeve gastrectomy (SG) prior to diabetes remission. Methods Fasting plasma from 15 subjects with T2D undergoing GBP or SG was analyzed by proteomic and metabolomic methods 3 days before and 3 days after surgery. Subjects were matched for age, BMI, metformin therapy and glycemic control. Insulin resistance was calculated using homeostasis model assessment (HOMA-IR). For proteomics, samples were depleted of abundant plasma proteins, digested with trypsin and labeled with iTRAQ isobaric tags prior to liquid chromatography-tandem mass spectrometry analysis. Metabolomic analysis was performed using gas chromatography-mass spectrometry. The effect of the respective bariatric surgery on identified proteins and metabolites was evaluated using two-way analysis of variance and appropriate post-hoc tests. Results HOMA-IR improved, albeit not significantly, in both groups after surgery. Proteomic analysis yielded seven proteins which decreased significantly after GBP only, including Fetuin-A and Retinol binding protein 4, both previously linked to insulin resistance. Significant decrease in Fetuin-A and Retinol binding protein 4 after GBP was confirmed using ELISA and immunoassay. Metabolomic analysis identified significant decrease of citrate, proline, histidine and decanoic acid specifically after GBP. Conclusion Greater early decrease was seen for Fetuin-A, Retinol binding protein 4, and several metabolites after GBP compared to SG, preceding significant weight loss. This may contribute to enhanced T2D remission observed following foregut bypass procedures.

Progression of diabetic retinopathy after bariatric surgery

To assess the impact of bariatric surgery on the progression of diabetic retinopathy in patients with Type 2 diabetes.

Single-stage laparoscopic sleeve gastrectomy: safety and efficacy in the super-obese

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is increasingly used as a single-stage bariatric procedure. However, its safety and efficacy in super-obese patients (body mass index [BMI] > 50 kg/m(2)) is less well defined. This series reports on 400 consecutive patients who underwent LSG at our institution, to evaluate safety and efficacy in the super-obese. MATERIALS AND METHODS We performed a retrospective review of prospectively collected data on 400 consecutive patients who underwent LSG at our institution. We analyzed baseline demographic data, median length of hospital stay, complications, length of follow-up, weight loss, and comorbidity resolution. We graded complications according to the Clavien-Dindo classification system. We classified patients as super-obese and non-super-obese and compared outcomes between groups. We used the two-tailed t-test and Fishers exact test as necessary. RESULTS There were 400 patients, 291 of whom were female (73%). The mean age was 44 y (standard deviation [SD] ± 9 y). The mean preoperative weight and BMI were 140 kg (SD ± 31 kg) and 49 kg/m(2) (SD ± 9 kg/m(2)), respectively. There were 67 complications (16%) in total. The major complication rate was 7.2%, with one recorded death. The median length of hospital stay was 3 d, and the mean follow-up period was 1 y. A total of 170 patients (43%) were super-obese, with a mean preoperative BMI of 56 kg/m(2) (SD ± 5 kg/m(2)). The mean absolute weight loss (59 versus 36.7 kg; P < 0.01) and percentage excess weight loss (58.9% versus 45.9%; P < 0.01) was significantly higher in the super-obese. The mean postoperative BMI for super-obese patients was 38.9 kg/m(2). There was no difference between groups in the incidence of major complications (8.2% versus 6.5%; P = 0.56). CONCLUSION Laparoscopic sleeve gastrectomy is safe and effective in the super-obese, with acceptable weight loss and no increase in the major complication rate.

Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer

Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and generally poor clinical outcome. Another ~40% of patients had pNETs that lacked this recurrent LoH pattern but had chromosome 11 LoH, bi-allelic MEN1 inactivation, and universally good clinical outcome. The somatic aneuploidy allowed pathogenic germline variants (e.g., ATM) to be expressed unopposed, with RNA expression patterns showing inactivation of downstream tumor suppressor pathways. No prognostic associations were found with tumor morphology, single gene mutation, or expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. In pNETs, single gene mutations appear to be less important than aneuploidy, with MEN1 the only statistically significant recurrently mutated driver gene. In addition, only one pNET in the series had clearly actionable single nucleotide variants (SNVs) (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two clinically relevant patterns of LoH described here define a novel oncogenic mechanism and a plausible route to genomic precision oncology for this tumor type.Cancer: Frequent chromosome loss in rare pancreatic tumorsThe loss of entire chromosomes seems to be a fundamental driver of tumors arising from the hormone-producing cells of the pancreas. A team led by Cristin Print and Ben Lawrence from the University of Auckland, New Zealand, performed genomic and pathological analysis of 57 pancreatic neuroendocrine tumors, a rare form of cancer caused by the abnormal growth of hormone-producing islet cells within the pancreas. The researchers observed two distinct patterns of chromosome loss, with 26% of the samples missing one copy of 10 specific chromosomes and another 40% lacking a copy of chromosome 11. In both groups, the abnormal chromosome count prompts abnormal gene activity patterns, with recessive mutations unleashed and expressed unopposed. Single gene mutations seem to play only a minor role, suggesting that single gene-targeted drugs will provide little benefit in this disease setting, with more nuanced approaches required.