Gastric Stasis and Gastric Ulcer after Selective Vagotomy Without a Drainage Procedure

Two independent trials of selective vagotomy without the addition of a drainage procedure in the treatment of uncomplicated duodenal ulcer have shown that gastric stasis may occur after the operation and that in some cases this may be complicated by gastric ulcer. These findings do not support the contention that selective vagotomy alone allows normal gastric emptying.     

Changes of Body Weight and Plasma Ghrelin Levels after Gastric Banding and Gastric Bypass

Objective: Ghrelin is an enteric peptide with strong orexigenic and adipogenic effects. Plasma ghrelin levels are decreased in obese subjects but increase after weight loss; this increase is not observed after Roux‐en‐Y gastric bypass (RYGB). Prospective and comparative data after adjustable silicone gastric banding (ASGB) have not been reported previously. Research Methods and Procedures: Overnight fasting plasma ghrelin concentration was measured in morbidly obese subjects at baseline and 3, 6, 12, and 24 months after ASGB (n = 8) or RYGB (n = 5) and in nonoperated controls (n = 7). Results: After RYGB, body weight (BW) decreased by 29.5 ± 5.5 kg (mean ± SE, p < 0.001), whereas plasma ghrelin failed to increase significantly (+167 ± 119 pg/mL, not significant). In contrast, after ASGB, BW decreased less (by 22.8 ± 5.9 kg; p < 0.001), and plasma ghrelin significantly increased by 377 ± 201 pg/mL (p = 0.025). Neither BW nor plasma ghrelin changed in nonoperated controls. Plasma leptin decreased in both operated groups (similarly p < 0.05) but not in nonoperated controls. Plasma growth hormone and insulin‐like growth factor 1 were not correlated with changes in plasma ghrelin concentrations. Discussion: Plasma ghrelin levels failed to increase during substantial weight loss after RYGB, but did increase in response to lesser weight loss after ASGB. These findings suggest that the plasma ghrelin response after weight loss is impaired after exclusion of major parts of the stomach and the duodenum (RYGB), and the smaller long‐term weight loss after ASGB compared with RYGB may be due, at least in part, to an absent increase in plasma ghrelin after RYGB.     

Quality of Life after Gastric Bypass Surgery: A Cross-Sectional Study

Objective: Numerous reports document significant weight loss after gastric bypass; however, there is little objective data on postsurgical changes in health-related quality of life (HRQL). Research Methods and Procedures: This study examined HRQL in four groups of patients: presurgery (T1), several weeks postsurgery (T2), 6 months postsurgery (T3), and 1 year postsurgery (T4). Subjects were given three HRQL measures: the short form 36 (SF-36), the Impact of Weight on Quality of Life-Lite Questionnaire (IWQOL-Lite), and the Bariatric Analysis and Reporting Outcome System (BAROS). Subjects also completed the Beck Depression Inventory (BDI) and the Rosenberg Self-Esteem Scale (RSE). Results: There were no significant differences among the groups on demographics or presurgical body mass index. Results showed significant differences between T1 and T2 on several SF-36 and IWQOL-Lite subscales, as well as the RSE and BDI. Significant differences were found on all measures between T2 and T3. Significant differences were found on all subscales of the IWQOL-Lite, but no subscales of the SF-36, the RSE, or the BDI between T3 and T4. Discussion: This study is the first to objectively document these differences in several objective measures of HRQL, depression, and self-esteem after gastric bypass in a large sample. It is notable that many differences are apparent within several weeks after surgery. Furthermore, results indicate that the IWQOL-Lite may be more sensitive than the SF-36 to the changes of quality of life that gastric bypass patients report.     

Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation

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Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice

MethodsTo investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.ResultsRYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.     

Development and Verification of a Mouse Model for Roux-en-Y Gastric Bypass Surgery with a Small Gastric Pouch

Existing mouse models of Roux-en-Y gastric bypass (RYGB) surgery are not comparable to human RYGB in gastric pouch volume for a large or absent gastric volume. The aim of this study was to develop and characterize a mouse RYGB model that closely replicates gastric pouch size of human RYGB surgery of about 5% of total gastric volume. We established this model in diet-induced obese (DIO) mice of C57BL/6J. This surgery resulted in a sustained 30% weight loss, entirely accounted for by decreased fat mass but not lean mass, compared to sham-operated mice on the high fat diet. Compared to sham-operated mice, energy expenditure corrected for total body weight was significantly increased by about 25%, and substrate utilization was shifted toward higher carbohydrate utilization at 8 weeks after RYGB when body weight had stabilized at the lower level. The energy expenditure persisted and carbohydrate utilization was even more pronounced when the mice were fed chow diet. Although significantly increased during daytime, overall locomotor activity was not significantly different. In response to cold exposure, RYGB mice exhibited an improved capacity to maintain the body temperature. In insulin tolerance test, exogenous insulin-induced suppression of plasma glucose levels was significantly greater in RYGB mice at 4 weeks after surgery. Paradoxically, food intake measured at 5 weeks after surgery was significantly increased, possibly in compensation for increased fecal energy loss and energy expenditure. In conclusion, this new model is a viable alternative to existing murine RYGB models and the model matches human RYGB surgery in anatomy. This model will be useful for studying molecular mechanisms involved in the beneficial effects of RYGB on body weight and glucose homeostasis.     

Hormone Substitution after Gastric Bypass Surgery in Patients with Hypopituitarism Secondary to Craniopharyngioma

Objective: Craniopharyngiomas (CPs) are benign brain tumors presenting frequently in childhood and are treated by surgery with or without radiotherapy. About 50% of cured patients suffer from eating disorders and obesity due to hypothalamic damage, as well as hypopituitarism, necessitating subsequent hormone substitution therapy. Gastric bypass surgery has been reported to be an efficient treatment strategy for morbid hypothalamic obesity. However, so far it is unknown whether oral hormone substitution is affected by impaired intestinal drug absorption, potentially leading to severe hypopituitarism or pituitary crisis.Methods: Four morbidly obese CP patients with panhypopituitarism treated by gastric bypass surgery were included in this retrospective analysis. Dosages of hormone substitution therapy, blood concentrations of hormones, potential complications of impaired drug absorption, and anthropometric characteristics were investigated pre- and postoperatively after 6 to 14 months and 13 to 65 months.Results: In all CP patients (3 female/1 male; baseline body mass index, 49 ± 7 kg/m²), gastric bypass resulted in distinct weight loss (-35 ± 27 kg). In follow-up examinations, mean daily dosage of thyroid hormone (levothyroxine_baseline 156 ± 44 μg/day versus levothyroxine_follow-up 150 ± 30 μg/day), hydrocortisone (hydrocortisone_baseline 29 ± 12 mg/day versus hydrocortisone_follow-up 26 ± 2 mg/day), growth-hormone (somatotropin_baseline 0.9 ± 0.5 mg/day versus somatotropin_follow-up 1.0 ± 0.4 mg/day), and desmopressin (desmopressin_baseline 222 ± 96 μg/day versus desmopressin_follow-up 222 ± 96 μg/day) substitution was unchanged. No patient developed adrenal insufficiency. Oral thyroid/hydrocortisone absorption testing performed in 1 patient indicated sufficient gastrointestinal drug absorption after bariatric surgery.Conclusion: Our preliminary results suggest that oral hormone substitution therapy is not impaired following gastric bypass operation in CP patients with morbid obesity, indicating that it might be a safe and effective treatment strategy.Abbreviations:BMI = body mass indexCP = craniopharyngiomafT4 = free thyroxineGH = growth hormoneIGF-1 = insulin-like growth factor 1     

Remodeling of the Residual Gastric Mucosa after Roux-En-Y Gastric Bypass or Vertical Sleeve Gastrectomy in Diet-Induced Obese Rats

Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP) after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H⁺/K⁺-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.     

Cancer Incidence and Mortality After Gastric Bypass Surgery

Despite weight loss recommendations to prevent cancer, cancer outcome studies after intentional weight loss are limited. Recently, reduced cancer mortality following bariatric surgery has been reported. This study tested whether reduced cancer mortality following gastric bypass was due to decreased incidence. Cancer incidence and mortality data through 2007 from the Utah Cancer Registry (UCR) were compared between 6,596 Utah patients who had gastric bypass (1984–2002) and 9,442 severely obese persons who had applied for Utah Driver's Licenses (1984–2002). Study outcomes included incidence, case‐fatality, and mortality for cancer by site and stage at diagnosis of all gastric bypass patients, compared to nonoperated severely obese controls. Follow‐up was over a 24‐year period (mean 12.5 years). Total cancer incidence was significantly lower in the surgical group compared to controls (hazard ratio (HR) = 0.76; confidence interval (CI) 95%, 0.65–0.89; P = 0.0006). Lower incidence in surgery patients vs. controls was primarily due to decreased incidence of cancer diagnosed at regional or distant stages. Cancer mortality was 46% lower in the surgery group compared to controls (HR = 0.54; CI 95%, 0.37–0.78; P = 0.001). Although the apparent protective effect of surgery on risk of developing cancer was limited to cancers likely known to be obesity related, the inverse association for mortality was seen for all cancers. Significant reduction in total cancer mortality in gastric bypass patients compared with severely obese controls was associated with decreased incidence, primarily among subjects with advanced cancers. These findings suggest gastric bypass results in lower cancer risk, presumably related to weight loss, supporting recommendations for reducing weight to lower cancer risk.     

Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding

Background

The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity.

Method

In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS.

Results

Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies.

Conclusions

Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term.     

Differential Pre-mRNA Splicing Regulates Nnat Isoforms in the Hypothalamus after Gastric Bypass Surgery in Mice

Background

Neuronatin (NNAT) is an endoplasmic reticulum proteolipid implicated in intracellular signalling. Nnat is highly-expressed in the hypothalamus, where it is acutely regulated by nutrients and leptin. Nnat pre-mRNA is differentially spliced to create Nnat-α and -β isoforms. Genetic variation of NNAT is associated with severe obesity. Currently, little is known about the long-term regulation of Nnat.

Methods

Expression of Nnat isoforms were examined in the hypothalamus of mice in response to acute fast/feed, chronic caloric restriction, diet-induced obesity and modified gastric bypass surgery. Nnat expression was assessed in the central nervous system and gastrointestinal tissues. RTqPCR was used to determine isoform-specific expression of Nnat mRNA.

Results

Hypothalamic expression of both Nnat isoforms was comparably decreased by overnight and 24-h fasting. Nnat expression was unaltered in diet-induced obesity, or subsequent switch to a calorie restricted diet. Nnat isoforms showed differential expression in the hypothalamus but not brainstem after bypass surgery. Hypothalamic Nnat-β expression was significantly reduced after bypass compared with sham surgery (P = 0.003), and was positively correlated with post-operative weight-loss (R² = 0.38, P = 0.01). In contrast, Nnat-α expression was not suppressed after bypass surgery (P = 0.19), and expression did not correlate with reduction in weight after surgery (R² = 0.06, P = 0.34). Hypothalamic expression of Nnat-β correlated weakly with circulating leptin, but neither isoform correlated with fasting gut hormone levels post- surgery. Nnat expression was detected in brainstem, brown-adipose tissue, stomach and small intestine.

Conclusions

Nnat expression in hypothalamus is regulated by short-term nutrient availability, but unaltered by diet-induced obesity or calorie restriction. While Nnat isoforms in the hypothalamus are co-ordinately regulated by acute nutrient supply, after modified gastric bypass surgery Nnat isoforms show differential expression. These results raise the possibility that in the radically altered nutrient and hormonal milieu created by bypass surgery, resultant differential splicing of Nnat pre-mRNA may contribute to weight-loss.     

Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β

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胃转流术后远端肠黏膜形态及生长因子表达的变化

目的：探讨胃转流术后远端肠管黏膜的适应性变化及生长因子的表达情况。方法：将8周龄的Wistar大鼠随机分为对照组、假手术组和胃转流术组,术后8周取吻合口远端肠管行常规病理切片检查,测量肠黏膜厚度和绒毛高度,采用免疫荧光法检测肠粘膜中表皮生长因子（EGF）和胰岛素样生长因子-1（IGF—1）的表达。结果：胃转流术组黏膜厚度（672±39与500±31um,P〈0．01）和绒毛高度（445±19与342±15um,P〈0．01）均显著高于假手术组（P〈0．01）,而对照组和假手术组间均无显著差异。与假手术组比较,胃转流术组肠粘膜中EGF和IGF-1的表达显著升高（P〈0．01）,而对照组和假手术组间无显著差异。结论：胃转流术后远端肠管粘膜发生适应性增生,同时伴随着EGF和IGF—1表达水平的升高。     

Binge Status and Quality of Life after Gastric Bypass Surgery: A One‐Year Study

Objective: This study evaluated gastric bypass surgery outcomes according to presurgical binge eating severity. Research Methods and Procedures: Adult patients completed assessment questionnaires including the Short Form‐36, Gormally Binge Eating Scale (BES), and Beck Depression Inventory (BDI) before and 12 months after surgery. Results: One hundred nine patients (18 men, 91 women) were recruited. Based on their baseline BES scores, patients were non‐ [n = 52 (48%)], moderate [n = 31 (28%)], or severe [n = 26 (24%)] binge eaters. Although the percentage of excess weight loss was greatest after 12 months in the severe binge eaters, the difference among groups was not significant. Severe binge eaters had higher baseline BDI scores than either non‐ or moderate binge eaters (p = 0.001). After surgery, BDI scores declined significantly in all groups from the baseline scores but remained higher postoperatively in the severe binge eaters (p = 0.018). BES scores declined significantly (p = 0.000) after surgery within all groups. There was no difference in the Short Form‐36 physical component summary scores at baseline among groups. Mental component summary scores were significantly lower in the severe binge eaters (p = 0.001). After surgery, there was no difference among groups in either physical or mental component summary scores. Discussion: In conclusion, data from the present study suggest that patients have similar outcomes in terms of improved depression scores, binge eating behavior, and health‐related quality of life regardless of their binge eating severity before surgery. Patients with the most severe binge eating behavior before surgery showed the most improvement when assessed 12 months after surgery.     

胃转流术后远端肠黏膜形态及生长因子表达的变化

目的:探讨胃转流术后远端肠管黏膜的适应性变化及生长因子的表达情况。方法:将8周龄的Wistar大鼠随机分为对照组、假手术组和胃转流术组,术后8周取吻合口远端肠管行常规病理切片检查,测量肠黏膜厚度和绒毛高度,采用免疫荧光法检测肠粘膜中表皮生长因子(EGF)和胰岛素样生长因子-1(IGF-1)的表达。结果:胃转流术组黏膜厚度(672±39与500±31μm,P<0.01)和绒毛高度(445±19与342±15μm,P<0.01)均显著高于假手术组(P<0.01),而对照组和假手术组间均无显著差异。与假手术组比较,胃转流术组肠粘膜中EGF和IGF-1的表达显著升高(P<0.01),而对照组和假手术组间无显著差异。结论:胃转流术后远端肠管粘膜发生适应性增生,同时伴随着EGF和IGF-1表达水平的升高。