Frank K. Friedenberg

Botulinum toxin A for the treatment of delayed gastric emptying.

BACKGROUNDObservational data suggest that intrapyloric injection of botulinum toxin A (BoTN/A) reduces symptoms and accelerates gastric emptying in idiopathic and diabetic gastroparesis. Our purpose was to determine whether botulinum toxin improves symptoms to a significantly greater extent than placebo. An additional objective was to determine whether there is an acceleration of gastric emptying after injection.METHODSA single-institution, randomized, double-blind, placebo-controlled trial* was done. Eligible patients had a Gastroparesis Cardinal Symptom Index score >27 with randomization to intrapyloric botulinum toxin, 200 U (units), or saline placebo. Reassessment of symptoms and repeat gastric emptying scan at 1-month follow-up were done.RESULTSThirty-two patients were randomized to botulinum toxin (N = 16) and placebo (N = 16). At 1-month follow-up, 37.5% randomized to botulinum toxin and 56.3% randomized to placebo achieved improvement as defined by this study. There were no identifiable clinical predictors of response. The botulinum toxin group demonstrated improvement in gastric emptying; however, this was not superior to placebo. No serious adverse events were attributable to botulinum toxin.CONCLUSIONSIntrapyloric injection of botulinum toxin improves gastric emptying in patients with gastroparesis, although this benefit was not superior to placebo at 1 month. Also, in comparison to placebo, symptoms do not improve significantly by 1 month after injection. Overall, we are unable to recommend botulinum toxin therapy for widespread use in the treatment of delayed gastric emptying until more data are available.

Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis

BACKGROUNDnBotulinum toxin A injected into the pyloric sphincter has been reported in small case series to treat gastroparesis. This study reviews the use of this treatment in a large number of patients with gastroparesis.nnnMETHODSnPatients who underwent pyloric botulinum injection for treatment of gastroparesis were identified. Response was defined as improvement or resolution of the patients major symptom and/or two minor symptoms for 4 weeks.nnnRESULTSnOf 115 patients treated, 63 patients met the study criteria. There were 53 women, 10 men, mean age 42 years. Most patients (56%) had idiopathic gastroparesis. Twenty-seven of 63 (43%) patients experienced a symptomatic response to treatment. By stepwise logistic regression, male gender was associated with response to treatment (OR 3.27: 95% CI[1.31, 8.13], p = 0.01). Vomiting as a major symptom was associated with a lack of response (OR 0.16: 95% CI[0.04, 0.67], p = 0.01). Despite the association of male gender with response, the mean duration of response for those patients responding, with a minimum of 3 months follow-up was 4.9 months (+/-2.7 months) for women and 3.5 months (+/-0.71 months) for men (p = 0.59). The corresponding medians and interquartile ranges (IQR) were 5 (IQR 3-6) for females and 3.5 (IQR 3-4) for males.nnnCONCLUSIONSnOf the patients, 43% had a response to botulinum toxin treatment that lasted a mean of approximately 5 months. Male gender was associated with a response to this therapy; however, durability of response was unrelated to gender. Vomiting as a major symptom predicted no response.

The association between gastroesophageal reflux disease and obesity.

Nearly all epidemiologic studies have found an association between increasing body mass index (BMI) and symptoms of gastroesophageal reflux disease (GERD). Changes in gastroesophageal anatomy and physiology caused by obesity may explain the association. These include an increased prevalence of esophageal motor disorders, diminished lower esophageal sphincter (LES) pressure, the development of a hiatal hernia, and increased intragastric pressure. Central adiposity may be the most important risk for the development of reflux and related complications such as Barretts esophagus and esophageal adenocarcinoma. Weight loss, through caloric restriction and behavioral modification, has been studied infrequently as a means of improving reflux. Bariatric surgery and its effects on a number of obesity-related disorders have been studied more extensively. Roux-en-Y gastric bypass (RYGB) has been consistently associated with improvement in the symptoms and findings of GERD. The mechanism of action through which this surgery is successful at improving GERD may be independent of weight loss and needs further examination. Current evidence suggests that laparoscopic adjusted gastric banding should be avoided in these patients as the impact on gastroesophageal reflux disease appears unfavorable.

Wireless Capsule Motility: Comparison of the SmartPill GI Monitoring System with Scintigraphy for Measuring Whole Gut Transit

IntroductionAssessment of whole gut transit, by radio-opaque markers or scintigraphy, is used to evaluate patients with constipation for slow gastrointestinal transit. Wireless capsule motility, using the SmartPill® GI monitoring system, samples and transmits intraluminal pH, pressure, and temperature data from a capsule at regular intervals as it traverses through the gastrointestinal tract; from these, gastric emptying and whole gastrointestinal tract transit can be assessed. The objective of this study was to compare the SmartPill® with whole gut transit scintigraphy to determine whether the SmartPill system could serve as a test for measurement of whole gut motility and transit.MethodsTen healthy, asymptomatic subjects underwent simultaneous whole gut scintigraphy and SmartPill® assessment of whole gut transit.ResultsAll subjects completed the study per protocol and experienced natural passage of the pill. Capsule residence time in the stomach correlated very strongly with percent gastric retention of the Tc-99 radiolabel at 120xa0min (rxa0=xa00.95) and at 240xa0min (rxa0=xa00.73). Small bowel contraction-min−1 measured by the SmartPill correlated with small bowel transit % (rxa0=xa00.69; Pxa0=xa00.05) and with isotopic colonic geometric center at 24xa0h after ingestion (rxa0=xa00.70, Pxa0=xa00.024). Capsule transit time correlated with scintigraphic assessment of whole gut transit.ConclusionsSmartPill® capsule assessment of gastric emptying and whole gut transit compares favorably with that of scintigraphy. Wireless capsule motility shows promise as a useful diagnostic test to evaluate patients for GI transit disorders and to study the effect of prokinetic agents on GI transit.

Cannabinoid Hyperemesis Syndrome

Coinciding with the increasing rates of cannabis abuse has been the recognition of a new clinical condition known as Cannabinoid Hyperemesis Syndrome. Cannabinoid Hyperemesis Syndrome is characterized by chronic cannabis use, cyclic episodes of nausea and vomiting, and frequent hot bathing. Cannabinoid Hyperemesis Syndrome occurs by an unknown mechanism. Despite the well-established anti-emetic properties of marijuana, there is increasing evidence of its paradoxical effects on the gastrointestinal tract and CNS. Tetrahydrocannabinol, cannabidiol, and cannabigerol are three cannabinoids found in the cannabis plant with opposing effects on the emesis response. The clinical course of Cannabinoid Hyperemesis Syndrome may be divided into three phases: prodromal, hyperemetic, and recovery phase. The hyperemetic phase usually ceases within 48 hours, and treatment involves supportive therapy with fluid resuscitation and anti-emetic medications. Patients often demonstrate the learned behavior of frequent hot bathing, which produces temporary cessation of nausea, vomiting, and abdominal pain. The broad differential diagnosis of nausea and vomiting often leads to delay in the diagnosis of Cannabinoid Hyperemesis Syndrome. Cyclic Vomiting Syndrome shares several similarities with CHS and the two conditions are often confused. Knowledge of the epidemiology, pathophysiology, and natural course of Cannabinoid Hyperemesis Syndrome is limited and requires further investigation.

Predictive Factors for Clinical Improvement with Enterra Gastric Electric Stimulation Treatment for Refractory Gastroparesis

The objectives of this study were to determine the clinical response to Enterra gastric electric stimulation (GES) in patients with refractory gastroparesis and to determine factors associated with a favorable response. Methods This study was conducted in patients undergoing Enterra GES for refractory gastroparesis. Symptoms were scored before and after GES implantation using the Gastroparesis Cardinal Symptom Index (GCSI) with additional questions about abdominal pain and global clinical response. Results During an 18-month period, 29 patients underwent GES implantation. Follow-up data were available for 28 patients, with average follow-up of 148xa0days. At follow-up, 14 of 28 patients felt improved, 8 remained the same, and 6 worsened. The overall GCSI significantly decreased with improvement in the nausea/vomiting subscore and the post-prandial subscore, but no improvement in the bloating subscore or abdominal pain. The decrease in GCSI was greater for diabetic patients than idiopathic patients. Patients with main symptom of nausea/vomiting had a greater improvement than patients with the main symptom of abdominal pain. Patients taking narcotic analgesics at the time of implant had a poorer response compared to patients who were not. Conclusions GES resulted in clinical improvement in 50% of patients with refractory gastroparesis. Three clinical parameters were associated with a favorable clinical response: (1) diabetic rather than idiopathic gastroparesis, (2) nausea/vomiting rather than abdominal pain as the primary symptom, and (3) independence from narcotic analgesics prior to stimulator implantation. Knowledge of these three factors may allow improved patient selection for GES.

Clostridium difficile among hospitalized patients receiving antibiotics: a case-control study.

OBJECTIVESnClostridium difficile is the most common cause of infectious nosocomial diarrhea and can be found in up to 30% of asymptomatic hospitalized patients. Our primary aim was to compare the clinical characteristics of hospitalized patients who received antibiotics and developed C. difficile-associated diarrhea (CDAD) with those of hospitalized patients who received antibiotics and did not develop the disease.nnnDESIGNnCase-control study comprising inpatients at a single institution.nnnPATIENTSnCase-patients were defined as patients who had diarrhea and tested positive for C. difficile. Control-patients (matched 4:1 to case-patients) were defined as patients who received antibiotics for at least 5 days and did not develop CDAD.nnnRESULTSnOn univariate analysis, nine variables were associated with CDAD. Only three of the variables, need for intensive care, length of stay, and macrolide antibiotic use, were found to be significant (P < .05) on logistic regression analysis. The odds ratios for status as a CDAD case were 3.68 (CI95, 1.44 to 9.40) for stay in the intensive care unit and 1.03 (CI95, 1.02 to 1.05) for each day of hospital stay. Receipt of macrolide antibiotics reduced risk significantly; the odds ratio was 0.23 (CI95, 0.19 to 0.87).nnnCONCLUSIONSnWe identified need for intensive care and length of stay as important risk factors for the development of CDAD. We also identified macrolide antibiotic use as protective against its development. Patients receiving intensive care may represent a population to study for targeted prophylaxis.

Vitamin, Mineral, and Drug Absorption Following Bariatric Surgery

UNLABELLEDnThe prevalence of obesity continues to rise throughout the world. Increasingly, bariatric surgery is used for those with morbid obesity as a pivotal approach to achieve weight loss. Along with substantial weight loss, malabsorption of essential vitamins, minerals, and drugs also occurs. Therefore, more than ever, a better understanding of the physiology and mechanisms by which these deficiencies occur is essential. We review the normal physiology of vitamin, mineral, and drug absorption. This is followed by a description of currently performed bariatric surgeries in the United States. A detailed review of specific nutrient and mineral deficiency states is presented, based on the most significant studies published in the last two decades. Of note, screening and supplementation recommendations have been included. Drug absorption data after these procedures is presented and discussed. Studies were identified by searching the Cochrane Registry and MEDLINE using relevant search terms, as well as through review of the reference section of included manuscripts.nnnCONCLUSIONSnBariatric surgery can be effectively used to achieve sustainable weight-loss in morbidly obese patients. It simultaneously brings forth important functional consequences on nutrient deficiencies and drug absorption that clinicians must be aware of. Further prospective, randomized research on specific procedures and deficiencies is required.

Gastroparesis: Approach, Diagnostic Evaluation, and Management

Gastroparesis is a chronic motility disorder of the stomach that involves delayed emptying of solids and liquids, without evidence of mechanical obstruction. Although no cause can be determined for the majority of cases, the disease often develops as a complication of abdominal surgeries or because of other underlying disorders, such as diabetes mellitus or scleroderma. The pathophysiology behind delayed gastric emptying is still not well-understood, but encompasses abnormalities at 3 levels--autonomic nervous system, smooth muscle cells, and enteric neurons. Patients will often cite nausea, vomiting, postprandial fullness, and early satiety as their most bothersome symptoms on history and physical examination. Those that present with severe disease may already have developed complications, such as the formation of bezoars or masses of undigested food. In patients suspected of gastroparesis, diagnostic evaluation requires an initial upper endoscopy to rule out mechanical causes, followed by a gastric-emptying scintigraphy for diagnosis. Other diagnostic alternatives would be wireless capsule motility, antroduodenal manometry, and breath testing. Once gastroparesis is diagnosed, dietary modifications, such as the recommendation of more frequent and more liquid-based meals, are encouraged. Promotility medications like erythromycin and antiemetics like prochlorperazine are offered for symptomatic relief. These agents may be frequently changed, as the right combination of effective medications will vary with each individual. In patients who are refractory to pharmacologic treatment, more invasive options, such as intrapyloric botulinum toxin injections, placement of a jejunostomy tube, or implantation of a gastric stimulator, are considered. Future areas of research are based on current findings from clinical studies. New medications, such as hemin therapy, are emerging because of a better understanding of the pathophysiology behind gastroparesis, and present treatment options, such as gastric electric stimulation, are evolving to be more effective. Regenerative medicine and stem cell-based therapies also hold promise for gastroparesis in the near future.

Trends in Gastroesophageal Reflux Disease as Measured by the National Ambulatory Medical Care Survey

BackgroundThe prevalence of reflux disease is increasing. Health-care utilization including physician visits for this disorder is lacking. Our purpose was to analyze the trend in physician visits for GERD from the period 1995–2006 using the National Ambulatory Medical Care Survey. We also sought to determine health-care utilization for GERD indirectly by assessing prescription trends for proton-pump inhibitors and H2 receptor blockers during the period.MethodsThe National Ambulatory Medical Care Survey is a survey of approximately 3,000 office-based physicians that uses a three-stage probability sampling procedure to allow extrapolation to the US population. All visits between 1995 and 2006 for symptoms and/or diagnoses compatible with GERD were combined into a single categorical variable. Weighted data was utilized for descriptive and inferential statistical analysis.ResultsAfter weighting, there were Nxa0=xa0321,513 adult ambulatory care encounters for all diagnoses. Visits for reflux increased throughout the examined period. Using logistic regression, visits for reflux were associated with female gender, age over 40, and calcium channel blocker use. Proton-pump inhibitor use increased substantially during the study period while H2 blocker use declined. Family practitioners and internists saw the majority of reflux patients.ConclusionsThe frequency of ambulatory visits in the United States for gastroesophageal reflux disease increased significantly between 1995 and 2006. The use of PPI therapy is increasing even more substantially. Older age, female gender, and use of calcium channel blockers were associated with a higher frequency of GERD visits. Health-care utilization for this disorder is increasing perhaps due to our ever-increasing epidemic of obesity.