Postbariatric surgery hypoglycemia: Nutritional, pharmacological and surgical perspectives.

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition.

Canagliflozin or acarbose versus placebo to ameliorate post-bariatric hypoglycaemia - The HypoBar I randomized clinical trial protocol.

INTRODUCTION: Post-bariatric hypoglycaemia (PBH) is a rare yet disabling clinical condition, mostly reported after Roux-en-Y gastric bypass (RYGB) surgery. RYGB is one of the most widely used and effective bariatric procedures. The pathophysiology of PBH remains unclear, and treatment options are limited in effectiveness and/or carry significant side effects. Acarbose slows carbohydrates digestion and absorption and is generally considered first-line pharmacological treatment for PBH but its gastrointestinal side effects limit patient compliance. Canagliflozin inhibits intestinal and renal sodium-dependent glucose absorption and reduces postprandial excursions of glucose, insulin and incretins after RYGB - effects that could be beneficial in ameliorating PBH. AIMS: The trial aims to investigate how blood glucose levels are affected during daily living in subjects with PBH during treatment with canagliflozin or acarbose compared with placebo, and to study the meal-induced entero-endocrine mechanisms implied in the treatment responses. METHODS: In a double-blinded, randomized, crossover clinical trial, HypoBar I will investigate the effectiveness in reducing the risk of PBH, safety, ambulatory glucose profile and entero-endocrine responses when PBH is treated with canagliflozin 300 mg twice daily during a 4-week intervention period, compared with acarbose 50 mg thrice daily or placebo. ETHICS AND DISSEMINATION: HypoBar I is approved by the Local regulatory entities. Results will be published in peer-reviewed journals. CONCLUSION: If effective, well-tolerated and safe, canagliflozin could be a novel treatment for people with PBH. HypoBar I might also unravel new mechanisms underlying PBH, potentially identifying new treatment targets. TRIAL REGISTRATION: EudraCT number 2022-000157-87.

Long-term results after transoral outlet reduction (TORe) of the gastrojejunal anastomosis for secondary weight regain and dumping syndrome after Roux-en-Y gastric bypass.

BACKGROUND: Bariatric surgery has been proven to be the most effective therapy for obesity and Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedure. However, weight regain and dumping syndrome occur over time. The transoral outlet reduction (TORe) procedure using an endoscopic suturing device may be an option to treat these conditions. We aimed to analyze outcome parameters and long-term results for this endoscopic technique. METHODS: A retrospective data analysis of patients who underwent TORe using an endoscopic suturing system at our institution from January 2015 to December 2020 was performed. A total of 71 subjects were included. Forty-five patients received the intervention for weight regain, 9 for dumping syndrome and 17 for both. The primary endpoint was weight stabilization or weight loss for subjects with weight regain, and resolution of symptoms for those with dumping syndrome. Secondary endpoints were intraoperative complications, procedure time, length of hospital stay and diameter of gastrojejunal anastomosis 1 year post-intervention. RESULTS: The median size of the gastrojejunal anastomosis was estimated at 30 mm before intervention, and after performing a median of 3 endoscopic sutures, the median estimated gastrojejunal anastomosis width was reduced to 9.5 mm. Eight perioperative complications occurred. Overall mean follow-up was 26.5 months. All interventions achieved weight stabilization or weight loss or resolution of dumping symptoms within the first 3 months, 98.2% at 12 months, 91.4% at 24 months and 75.0% at 48 months. In 22/26 subjects a persisting improvement of dumping syndrome was achieved. CONCLUSIONS: TORe is a safe and effective procedure in the treatment of patients with dumping syndrome after laparoscopic RYGB, the effect on weight stabilization is less significant. A prospective randomized trial should be conducted to compare the effects of TORe with other surgical methods like banding the gastrojejunal anastomosis.

Is Sigstad's score really capable of detecting post-surgical late dumping syndrome?

BACKGROUND: This clinical trial explores the Sigstad score for late dumping syndrome in postoperative patients who have undergone sleeve gastrectomy (SG) or One Anastomosis Gastric Bypass (OAGB). The aims of this study are to investigate the correlations with late dumping syndrome, to evaluate the reliability and validity of the Sigstad score and to discuss a modified scoring system. METHODS: The study was conducted at the Obesity Center of the Westküstenklinikum Heide and included 271 patients. Data collection involved conducting interviews, diet diaries and measuring blood glucose levels. Non-parametric tests, logistic regression and McDonald's Omega were the selected statistical approaches. RESULTS: Body Mass Index (BMI) decreased over time (-9.67 kg/m2 at 4 months, -15.58 kg/m2 at 12 months). Preoperatively, the Sigstad score exhibited the highest value, and no occurrences of late dumping syndrome were observed. No significant differences were found in BMI concerning late dumping syndrome or Sigstad score among postoperative patients. Postoperative patients experienced an increase in gastrointestinal symptoms. The reliability test showed a McDonald's omega value of 0.509. The analysis conducted through binary logistic regression indicated dizziness as a significant predictor of late dumping syndrome; however, this finding did not hold up after performing Bonferroni correction. CONCLUSION: The Sigstad score is not a reliable or valid method for detecting late dumping syndrome after surgery for obesity and metabolic disorders. It is necessary to have alternatives that use objective measures and assess the quality of life, and that these alternatives be validated in large patient cohorts.

Transoral gastric outlet reduction for post-prandial hypoglycemia after Roux-en-Y gastric bypass.

BACKGROUND: Post-prandial hypoglycemia is an uncommon but disabling late complication of Roux-en-Y gastric bypass (RYGB). Most patients can be treated with dietary interventions and medications; however, some patients develop refractory hypoglycemia that may lead to multiple daily episodes and seizures. While RYGB reversal surgery is an effective treatment, complication rates are high, and patients inevitably experience weight regain. Transoral gastric outlet reduction (TORe) is a minimally invasive treatment that is effective for early and late dumping syndrome. However, prior studies have not distinguished the effectiveness of TORe specifically for patients with post-prandial hypoglycemia. This study aims to describe a single institution's experience of TORe for treating post-prandial hypoglycemia. METHODS: This is a case series of patients with prior RYGB complicated by post-prandial hypoglycemia who underwent TORe from February 2020 to September 2021. Pre-procedural characteristics and post-procedural outcomes were obtained. Outcomes assessed included post-prandial hypoglycemia episodes, dumping syndrome symptoms, and weight change. RESULTS: A total of 11 patients underwent TORe from 2020 to 2021 for post-prandial hypoglycemia. Three (27%) patients had a history of seizures due to hypoglycemia. All had been advised on dietary changes, and ten patients (91%) were on medications for dumping. All patients reported a reduction in post-prandial hypoglycemic events as well as the majority of dumping syndrome symptoms during an average follow-up time of 409 ± 125 days. Ten patients (91%) had experienced weight regain from their post-RYGB nadir weight. For these patients, the average total body weight loss 12 months post-TORe was 12.4 ± 12%. There were no complications requiring hospitalization. One patient experienced post-TORe nausea and vomiting requiring dilation of the gastrojejunal anastomosis with resolution in symptoms. CONCLUSION: TORe is a safe and effective treatment for post-prandial hypoglycemia and weight regain after RYGB in patients with symptoms refractory to medications and dietary changes.

Severity of post-Roux-en-Y gastric bypass dumping syndrome and weight loss outcomes: is there any correlation?

PURPOSE: The present research was conducted to evaluate the effect of the severity of dumping syndrome (DS) on weight loss outcomes after Roux-en-Y gastric bypass (RYGB) in patients with class III obesity. METHODS: The present retrospective cohort study used the dumping symptom rating scale (DSRS) to evaluate the severity of DS and its correlation with weight loss outcomes in 207 patients 1 year after their RYGB. The patients were assigned to group A with mild-to-moderate DS or group B with severe DS. RESULTS: The mean age of the patients was 42.18 ± 10.46 years and their mean preoperative BMI 42.74 ± 5.59 kg/m2. The total weight loss percentage (%TWL) in group B was insignificantly higher than that in group A, but besides that was not significantly different in the two groups. CONCLUSION: The present findings suggested insignificant relationships between the presence and severity of DS after RYGB and adequate postoperative weight loss.

Transoral Outlet Reduction (TORe) for the Treatment of Weight Regain and Dumping Syndrome after Roux-en-Y Gastric Bypass.

Obesity is a chronic relapsing disease of global pandemic proportions. In this context, an increasing number of patients are undergoing bariatric surgery, which is considered the most effective weight loss treatment for long-term improvement in obesity-related comorbidities. One of the most popular bariatric surgeries is the Roux-en-Y gastric bypass (RYGB). Despite its proven short- and long-term efficacy, progressive weight regain and dumping symptoms remain a challenge. Revisional bariatric surgery is indicated when dietary and lifestyle modification, pharmaceutical agents and/or psychological therapy fail to arrest weight regain or control dumping. However, these re-interventions present greater technical difficulty and are accompanied by an increased risk of peri- and postoperative complications with substantial morbidity and mortality. The endoscopic approach to gastrojejunal anastomotic revision, transoral outlet reduction (TORe), is used as a minimally invasive treatment that aims to reduce the diameter of the gastrojejunal anastomosis, delaying gastric emptying and increasing satiety. With substantial published data supporting its use, TORe is an effective and safe bariatric endoscopic technique for addressing weight regain and dumping syndrome after RYGB.

Uncooked cornstarch for the prevention of hypoglycemic events.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases -i.e. glycogen storage diseases and other rare disorders - and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.

Endoscopic revision of gastrojejunal anastomosis for the treatment of dumping syndrome in patients with Roux-en-Y gastric bypass: a systematic review and meta-analysis.

BACKGROUND: Dumping syndrome is a known complication of Roux-en-Y gastric bypass (RYGB). Recently, endoscopic gastrojejunal anastomosis (GJA) revision has been employed as a treatment option. The primary aim of this study was to perform a systematic review and meta-analysis for the role of endoscopic GJA revision in patients with RYGB for the treatment of dumping syndrome. METHODS: Search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception through December 2020 in accordance with PRISMA and MOOSE guidelines. Pooled proportions with rates estimated using random effects models were used. Outcomes included pooled technical success, clinical success, adverse events, and rate of reintervention. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot using Egger and Begg tests. RESULTS: Six studies (n = 263 patients; 60.25% female) were included (1 prospective and 5 retrospective). Mean age was 46.27 ± 2.54 years. Average patient weight was 95.59 ± 4.78 kg, BMI of 41.43 ± 3.07 kg/m2, and pre-procedure GJA size of 32.23 ± 8.68 mm. Pooled technical and clinical success was 98.15% and 89.5%. Among studies reporting Sigstad scores, endoscopic GJA revision resulted in a significant improvement [mean Sigstad score difference of - 9.96 (95% CI, - 19.951 to - 0.975); P < 0.03]. Mean procedure time was 37.12 ± 10.40 min with an intra-procedural adverse event rate of 2.42%. Over a mean follow-up of 8.03 ± 6.87 months, post-procedure adverse events occurred in 2.96% of patients with a reintervention rate of 11.54%. CONCLUSION: This systematic review and meta-analysis suggests that endoscopic GJA revision appears an effective and safe treatment for dumping syndrome.

Endoscopic trans-oral outlet reduction after bariatric surgery is safe and effective for dumping syndrome.

BACKGROUND: Dumping syndrome (DS) is a common complication of bariatric surgery. Treatments include dietary and behavioral changes, as well as pharmacotherapy and revision surgery. All can be costly or hard to adhere to. In recent years, evidence accumulates in favor of endoscopic trans-oral outlet reduction (TORe) as an effective treatment for DS, targeting the pathophysiology of rapid gastric clearance. The objective of this study is to assess the safety and efficacy of TORe for DS in a single referral center. METHODS: Patients after bariatric surgery suffering DS were followed, and data were retrospectively analyzed. Diagnosis and post-procedural assessment of DS were made clinically using Sigstad score. During the procedure, the anastomotic rim was cauterized. Afterwards, 2 non-interrupted "8-figure" sutures were placed, resulting in imbrication of additional gastric tissue on top of the anastomosis and narrowing to <1 cm at the end of the procedure. Patients were instructed to keep a liquid diet for 14 days and follow-up continued for 6 months. RESULTS: Between 8/2018 and 9/2019 TORe was carried out in 13 patients (M:F = 3:10) with mean age of 45.1 (range 25-56) and BMI of 33.5 (range 28.1-40.3). Average time since recent surgery was 5.5 years (range 1-9). Mean pre-procedure anastomosis diameter was 25.2 mm (range 15-30) and was reduced to a mean of 5.6 mm (range 5-10). Three patients (23%) were admitted overnight due to inability to drink which resolved spontaneously. No major complications were reported. At 6 months, the Sigstad score was significantly reduced (19.4 ± 3.6 vs 5.2 ± 5.5, P < 0.001), and 11/13 (85%) of patients had a complete resolution of their dumping symptoms. In addition, BMI decreased by a mean of 2.3 kg/m2 (-1 to 7.5, p = 0.002). CONCLUSION: TORe is a safe and effective treatment for patients suffering dumping syndrome and should be considered early in the treatment of DS.

Functional syndromes and symptom-orientated aftercare after esophagectomy.

BACKGROUND: Surgery is the cornerstone of esophageal cancer treatment but remains burdened with significant postoperative changes of gastrointestinal function and quality of life. PURPOSE: The aim of this narrative review is to assess and summarize the current knowledge on postoperative functional syndromes and quality of life after esophagectomy for cancer, and to provide orientation for the reader in the challenging field of functional aftercare. CONCLUSIONS: Post-esophagectomy syndromes include various conditions such as dysphagia, reflux, delayed gastric emptying, dumping syndrome, weight loss, and chronic diarrhea. Clinical pictures and individual expressions are highly variable and may be extremely distressing for those affected. Therefore, in addition to a mostly well-coordinated oncological follow-up, we strongly emphasize the need for regular monitoring of physical well-being and gastrointestinal function. The prerequisite for an effective functional aftercare covering the whole spectrum of postoperative syndromes is a comprehensive knowledge of the pathophysiological background. As functional conditions often require a complex diagnostic workup and long-term therapy, close interdisciplinary cooperation with radiologists, gastroenterologists, oncologists, and specialized nutritional counseling is imperative for successful management.

Late complications of biliopancreatic diversion in an older patient: a case report.

BACKGROUND: In the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications. CASE PRESENTATION: A 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning. CONCLUSIONS: Long-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.

Risk factors of dumping syndrome after fundoplication for gastroesophageal reflux in children.

PURPOSE: In postoperative cases of fundoplication, the gastric emptying ability is promoted and sometimes exhibits dumping syndrome. Dumping syndrome often goes unrecognized in children. Furthermore, the risk factors for postoperative dumping syndrome are unknown. This study aimed to investigate the risk factors of developing dumping syndrome after fundoplication. METHODS: A retrospective chart review of all consecutive patients between January 2003 and March 2018 (190 patients) who had fundoplication at our clinic was conducted. Regarding the risk factors of dumping syndrome, gender, age and body weight at the time of surgery, neurological impairment, severe scoliosis, microgastria, chromosomal abnormalities, complex cardiac anomalies, gastrostomy, and laparoscopic surgery were retrospectively studied. RESULTS: 17 patients (9%) developed dumping syndrome post-operatively. Multivariate analysis showed that significant risk factors for dumping syndrome included: undergoing surgery within 12 months of age (adjusted OR 10.3, 95% CI 2.6-45.2), severe scoliosis (adjusted OR 19.3, 95% CI 4.4-91.1), and microgastria (adjusted OR 26.5, 95% CI 1.4-896.4). CONCLUSIONS: We identified that: age at fundoplication being within 12 months of age, severe scoliosis, and microgastria were risk factors for dumping syndrome after fundoplication, and that this information should be explaining to the family before conducting the fundoplication.

The gastro-jejunal anastomosis site influences dumping syndrome and weight regain in patients with obesity undergoing Laparoscopic Roux-en-Y Gastric Bypass.

PURPOSE: The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is an effective weight loss procedure. The gastro-jejunal (GJ) anastomosis required can be performed on the anterior or posterior gastric pouch wall. No studies have compared these variants in terms of efficacy and onset of dumping syndrome (DS) and weight regain (WR). We aimed at assessing the prevalence of DS in relation to the site of anastomosis together with identifying prognostic factors of DS and WR. METHODS: Patients who had undergone LRYGB with anterior (AGJ) or posterior (PGJ) anastomosis in 2010-2019 were retrospectively analyzed. We collected demographic data, medical history and the prevalence of DS evaluated through the Sigstad Score, together with WR data. RESULTS: 213 patients were enrolled, of which 51.6% had an AGJ and 48.4% had a PGJ. The mean follow-up time was 81 ± 18 and 27 ± 13 months in the AGJ and PGJ group, respectively (p < 0.0001). Excess weight loss was 77.59% and 94.13% in patients with AGJ and PGJ, respectively (p < 0.001). WR rate was 16% and 4% in the AGJ and PGJ population, respectively (p < 0.001). DS prevalence was 38% and 76% in the AGJ and the PGJ population, respectively (p < 0.0001). The site of anastomosis was identified as an independent predictor of DS (OR5.15; 95% CI 2.82-9.41; p < 0.0001) and WR (OR5.31; 95% CI 2.32-12.15; p < 0.0001). Obesity-related complications significantly improved after surgery independent of the anastomosis site. CONCLUSION: LRYGB is effective in determining long-term weight loss and improvement of complications. AGJ is associated with lower prevalence of DS but more frequent WR. The anastomosis site is a factor to be considered when performing LRYGB. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Diet approach before and after bariatric surgery.

Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5-10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.

Utility of continuous glucose monitoring following gastrectomy.

BACKGROUND: Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. METHODS: We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. RESULTS: We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CONCLUSIONS: CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

Gastrointestinal Motility Issues in Cancer Patients.

PURPOSE OF REVIEW: This paper seeks to highlight GI motility disorders that are frequently present in patients with a malignancy. GI dysmotility can occur due to the cancer itself or as a consequence of medical and surgical treatments. Often, symptoms are nonspecific and the diagnosis requires a high index of suspicion. The goal of the paper is to review the common motility problems seen in patients with cancer, their clinical manifestations, and options for management. RECENT FINDINGS: Studies show that newer endoscopy techniques such as endoscopic mucosal dissection can cause esophageal dysmotility. Opioid-induced constipation is frequently encountered in patients with cancer. Motility disorders in cancer patient can lead to clinical morbidity, poor quality of life, and malnutrition. Newer diagnostic tests and medical and surgical treatments may be helpful in improving the diagnosis and management of these disorders.

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 2, Systemic Miscellaneous Conditions.

Flushing disorders with involvement of the gastrointestinal tract represent a heterogeneous group of conditions. In part 1 of this review series, neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and hyperbasophilia were discussed. In this section we discuss the remaining flushing disorders which primarily or secondarily involve the gastrointestinal tract. This includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications. With the exception of paroxysmal pain disorders, panic disorders and some medications, these disorders presents with dry flushing. A detailed and comprehensive family, social, medical and surgical history, as well as recognizing the presence of other systemic symptoms are important in distinguishing the different disease that cause flushing with gastrointestinal symptoms.

Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia.

AIMS/HYPOTHESIS: Post-bariatric hypoglycaemia (PBH) is a rare, but severe, metabolic disorder arising months to years after bariatric surgery. It is characterised by symptomatic postprandial hypoglycaemia, with inappropriately elevated insulin concentrations. The relative contribution of exaggerated incretin hormone signalling to dysregulated insulin secretion and symptomatic hypoglycaemia is a subject of ongoing inquiry. This study was designed to test the hypothesis that PBH and associated symptoms are primarily mediated by glucagon-like peptide-1 (GLP-1). METHODS: We conducted a double-blinded crossover study wherein eight participants with confirmed PBH were assigned in random order to intravenous infusion of the GLP-1 receptor (GLP-1r) antagonist. Exendin (9-39) (Ex-9), or placebo during an OGTT on two separate days at the Stanford University Clinical and Translational Research Unit. Metabolic, symptomatic and pharmacokinetic variables were evaluated. Results were compared with a cohort of BMI- and glucose-matched non-surgical controls (NSCs). RESULTS: Infusion of Ex-9 decreased the time to peak glucose and rate of glucose decline during OGTT, and raised the postprandial nadir by over 70%, normalising it relative to NSCs and preventing hypoglycaemia in all PBH participants. Insulin AUC and secretion rate decreased by 57% and 71% respectively, and peak postprandial insulin was normalised relative to NSCs. Autonomic and neuroglycopenic symptoms were significantly reduced during Ex-9 infusion. CONCLUSIONS/INTERPRETATION: GLP-1r blockade prevented hypoglycaemia in 100% of individuals, normalised beta cell function and reversed neuroglycopenic symptoms, supporting the conclusion that GLP-1 plays a primary role in mediating hyperinsulinaemic hypoglycaemia in PBH. Competitive antagonism at the GLP-1r merits consideration as a therapeutic strategy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02550145.

Etiologies and management of cutaneous flushing: Nonmalignant causes.

The flushing phenomenon may represent a physiologic or a pathologic reaction. Although flushing is usually benign, it is prudent that the physician remains aware of potentially life-threatening conditions associated with cutaneous flushing. A thorough investigation should be performed if the flushing is atypical or not clearly associated with a benign underlying process. The diagnosis often relies on a pertinent history, review of systems, physical examination, and various laboratory and imaging modalities, all of which are discussed in the 2 articles in this continuing medical education series. This article reviews flushing associated with fever, hyperthermia, emotions, menopause, medications, alcohol, food, hypersensitivity reactions, rosacea, hyperthyroidism, dumping syndrome, superior vena cava syndrome, and neurologic etiologies.