Pyloric injection of botulinum toxin for treatment of diabetic gastroparesis

BACKGROUND: Diabetic gastroparesis is a common clinical problem. The pathophysiology includes prolonged pyloric contractions that may cause functional resistance to gastric outflow. Botulinum toxin was injected into the pyloric sphincter in an attempt to decrease pyloric resistance and improve gastric emptying. METHODS: Six patients with diabetic gastroparesis and an abnormal solid phase gastric emptying study underwent upper endoscopy during which 100 units of botulinum toxin were injected into the pyloric sphincter. Gastric emptying studies were obtained at 48 hours and 6 weeks after injection. Patients were questioned about symptoms of gastroparesis, and a symptom score was obtained at baseline and at 2 weeks and 6 weeks after injection. OBSERVATIONS: There was a mean improvement in the subjective symptom score at 2 weeks of 55% (range 14% to 80%). This improvement was maintained at 6 weeks. There was a 52% improvement in gastric emptying at 2 and 6 weeks. CONCLUSION: Pyloric injection of botulinum toxin can improve symptoms and gastric emptying in patients with diabetic gastroparesis. Further evaluation of pyloric injection of botulinum toxin as a treatment for diabetic gastroparesis is warranted.     

Botulinum toxin A for the treatment of delayed gastric emptying

BACKGROUND: Observational 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. METHODS: A single-institution, randomized, double-blind, placebo-controlled trial* was done. Eligible patients had a Gastroparesis Cardinal Symptom Index score > or = 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. RESULTS: Thirty-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. CONCLUSIONS: Intrapyloric 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.     

Características del esfínter pilórico utilizando EndoFLIP® en gastroparesia

Introduction and aims

Pyloric sphincter abnormalities may be detected in gastroparesis. Botulinum toxin A (BoNT/A) injection into the pylorus has been used to treat gastroparesis with varying results. The aim of the present article was to assess whether pyloric sphincter characteristics using the endoscopic functional lumen imaging probe (EndoFLIP^®) with impedance planimetry in patients with gastroparesis correlated with symptoms, gastric emptying, and therapeutic response to pyloric sphincter BoNT/A injection.

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

BACKGROUND: Botulinum 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. METHODS: Patients who underwent pyloric botulinum injection for treatment of gastroparesis were identified. Response was defined as improvement or resolution of the patient's major symptom and/or two minor symptoms for 4 weeks. RESULTS: Of 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. CONCLUSIONS: Of 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.     

Botulinum toxin for the treatment of gastroparesis: a preliminary report

Gastroparesis is a disorder of gastric motility that results in delayed gastric emptying. Common symptoms include early satiety, postprandial fullness, epigastric pain, nausea, vomiting, and weight loss. The underlying etiologies of gastroparesis are many and include diabetes, prior gastric surgery, collagen vascular disorders, and a previous viral illness. Up to one third of cases are classified as idiopathic. Treatment typically consists of a change in diet to small volume, frequent meals and the use of the prokinetic agents metoclopramide, cisapride, erythromycin, or domperidone. Botulinum toxin has recently been shown to be effective in treating disorders of smooth muscle hypertonicity in the GI tract. This case report describes three patients with severe gastroparesis whose symptoms persisted despite dietary changes and the use of high dose prokinetic agents. All three were treated with intrasphincteric injection of the pylorus with botulinum toxin and all had significant symptomatic improvement afterwards. Possible mechanisms of action of botulinum toxin on the pylorus and its effects in patients with gastroparesis are discussed.     

Factors Associated with Symptom Response to Pyloric Injection of Botulinum Toxin in a Large Series of Gastroparesis Patients

Case series report symptom reductions after pyloric botulinum toxin injection in gastroparesis, but small controlled trials show no benefit. Factors that enhance response to therapy are undefined. A retrospective analysis of 179 gastroparetics undergoing pyloric botulinum toxin injection from 2001 to 2007 assessed responses relating to drug dosing, demographic factors, comorbidities, and gastric function. Overall, there was a decrease in gastroparetic symptoms 1–4 months after pyloric botulinum toxin injection in 92 patients (51.4%). Increasing the botulinum toxin dose significantly improved clinical responses of patients who provided information on symptoms after therapy (100 units: 54.2%; 200 units: 76.7%; P = 0.02). Other factors that improved response to botulinum toxin included female gender, age <50 years, and nondiabetic nonpostsurgical etiology (all P < 0.05). Eighty-seven patients received 307 follow-up injections. A clinical response to a second injection was observed in 73.4% of evaluable patients. In conclusion, responses to pyloric botulinum toxin depended on dose and were maintained on repeat injection. Subgroup analyses defined subgroups likely to benefit. These findings provide the foundation for large, controlled trials of high-dose botulinum toxin in selected gastroparesis subsets.     

Pyloric Injection of Botulinum Toxin for the Treatment of Refractory GERD Accompanied with Gastroparesis: A Preliminary Report

Gastroesophageal reflux disease (GERD) refractory to conventional medical treatment is frequently associated with gastroparesis, a complex condition with no definitive treatment to date. We first developed a scoring system to assess the severity and frequency of both reflux- and gastroparesis-related symptoms. We then tested, for the first time, the hypothesis that endoscopic pyloric botulinum toxin injection alleviates both of these symptom types. Eleven patients (four males) with GERD (confirmed by esophageal pH monitoring) plus gastroparesis (confirmed by gastric emptying study) underwent toxin injection. Patients had no concomitant disease and were not allowed to use prokinetics before or after treatment. Injection significantly improved both gastroparesis- and reflux-related symptoms in the majority of patients but the duration of symptom relief was relatively short. Responders to treatment had significantly higher total reflux symptom scores (before injection) than nonresponders. All but one of the patients in whom gastroparesis symptoms improved also showed response in reflux symptoms, which supports our hypothesis. We believe that response to toxin injection is a reliable predictor of response to subsequent surgery following the recurrence of symptoms.     

Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management

Delayed gastric emptying can be due to muscular, neural, or humoral abnormalities. In the absence of an identified cause, gastroparesis is labelled as idiopathic. We present the case of a patient with severe idiopathic gastroparesis. Pharmacological approaches failed, as well as reduction in gastric emptying resistance with pyloric injection of botulinum toxin and pyloroplasty. Therefore, subtotal gastrectomy was performed. Histological and immunohistochemical study of the resected specimen showed hypoganglionosis, neuronal dysplasia, and a marked reduction in both myenteric and intramuscular interstitial cells of Cajal. To our knowledge, this is the first time these rare histological findings have been described in a patient with idiopathic gastroparesis.     

Endoscopic Pyloric Injection of Botulinum Toxin-A for the Treatment of Postvagotomy Gastroparesis

ObjectivesTo evaluate the efficacy of botulinum toxin-A in the treatment of postvagotomy gastroparesis.MethodsThis open-labeled trial identified and recruited 11 subjects who developed symptomatic gastroparesis after a vagotomy (9 fundoplication, 1 trauma, and 1 exploratory laparotomy). Gastroparesis was defined as an abnormal solid-phase gastric emptying test using the standardized 4-hour radionuclide eggbeater meal method and vagotomy was confirmed with a sham meal challenge test. To complete the study, subjects should have completed the 6-month follow-up visit after their pylorus was injected with botulinum toxin-A injection in a 4-quadrant manner. Patients either received 100 (n = 2) or 200 (n = 9) units of botulinum toxin. Questionnaires recorded symptom severity of gastroparesis at baseline and at monthly intervals for 6 months after the therapy was completed by the patients.ResultsOf the 11 subjects initially recruited, 10 finished the 6-month follow-up visit (7 women). Mean age was 51 years (range, 31–84 years). Mean symptom score at baseline was 16 (95% CI 13–19) and showed a numerical decline to 9 (P > 0.05) over the 6-month period after the procedure (95% CI 5–13). Seven (70%) patients observed >30% improvement in the total symptom score. No complications were recorded.ConclusionsIn conclusion, this open-label study in patients with postvagotomy gastroparesis patients reveals a reduction of gastroparetic symptoms at 1 and 3 months after treatment with pyloric injection of botulinum toxin-A, with return of symptoms by 6 months. Thus, botulinum toxin treatment does not produce a sustained reduction in gastroparetic symptoms in this clinical setting.     

Long-term follow-up of achalasia patients treated with botulinum toxin

AIMS: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated. RESULTS: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.     

The Treatment of Idiopathic and Diabetic Gastroparesis with Acute Intravenous and Chronic Oral Erythromycin

The objective of this study was to investigate the effects of intravenous erythromycin and chronic oral dosing of erythromycin on gastric emptying in patients with idiopathic or diabetic gastroparesis. Symptoms were assessed on oral dosing and during long-term follow-up in an ambulatory setting at a University referral center. Fourteen patients (10 idiopathic and four diabetic gastroparesis) were studied. Four patients left during the 4-wk study; two due to rash, one with cramps and vomiting on erythromycin, and one due to other medical problems. Ten patients completed the 4-wk study and commenced long-term therapy. Five of these patients experienced enough symptomatic relief to continue oral erythromycin long-term, being followed for an average period of 8.4 months. After initial documentation of delayed gastric emptying, patients received 6 mg/kg intravenous erythromycin lactobionate before a second gastric emptying study. Erythromycin base was then given orally at a dose of 500 mg tid-ac and qhs, with a final gastric emptying study performed after 4 wk. During long-term follow-up, erythromycin dosage was adjusted to minimize symptoms. Radionuclide-labeled gastric emptying of a solid meal was studied at baseline, following intravenous erythromycin, and after 4 wk of oral treatment with erythromycin. Symptom scores were assessed at baseline, at 4 wk, and then at 8-wk intervals. The percentage of the solid meal retained in the stomach at 2 h decreased from 85%±11% (SD) at baseline to 20%± 29% following intravenous erythromycin ( p < 0.001), and to 48%± 21% after 4 wk of oral therapy ( p < 0.01 vs. baseline). There was a reduction in total symptom scores and a significant reduction in global assessment scores ( p = 0.03). We conclude that erythromycin bas a strong gastric prokinetic effect in both idiopathic and diabetic gastroparesis, and may represent a useful new therapeutic approach to this problem.     

Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?

BACKGROUND: Idiopathic gastroparesis is a syndrome characterised by severely delayed gastric emptying of solids without an obvious underlying organic cause. Although delayed gastric emptying is traditionally considered the mechanism underlying the symptoms in these patients, poor correlations with symptom severity have been reported. AIMS: To investigate proximal stomach function and to study the correlation of delayed gastric emptying and proximal stomach dysfunction with symptom pattern and severity in idiopathic gastroparesis. METHODS: 58 consecutive patients (19 men, mean (standard deviation) age 41 (2) years) with severely delayed solid gastric emptying (gastric half-emptying time (t(1/2))>109 min) without an organic cause were recruited. They filled out a symptom-severity questionnaire and underwent a gastric barostat study for assessment of gastric sensitivity and accommodation. Correlation of these mechanisms with symptom pattern and overall symptom severity (sum of individual symptoms) was analysed. RESULTS: At two different cut-off levels for gastric emptying (upper limit of normal t(1/2) up to 1.5 and 2 times), no significant change in symptom pattern occurred. 25 (43%) patients had impaired accommodation, and this was associated with higher prevalence of early satiety (p<0.005) and weight loss (p = 0.009). 17 (29%) patients had hypersensitivity to gastric distension, and this was associated with higher prevalences of epigastric pain (p = 0.005), early satiety (p = 0.04) and weight loss (p<0.005). Overall symptom severity was not correlated with gastric emptying or accommodation, but only with sensitivity to gastric distension (R = -0.3898, p = 0.003) and body weight (R = -0.4233, p = 0.001). CONCLUSIONS: In patients with idiopathic gastroparesis, the symptom pattern is determined by proximal stomach dysfunction rather than by the severity of delayed emptying.     

Delayed gastric emptying: Whom to test, how to test, and what to do

Opinion statement Gastroparesis, or delayed gastric emptying, is a common cause of chronic nausea and vomiting as seen in a gastroenterology practice. Diabetic, postsurgical, and idiopathic causes remain the three most common forms of gastroparesis. In addition to nausea and vomiting, symptoms of gastroparesis may include early satiety, postprandial fullness, and abdominal pain. Physiologic changes that may explain symptoms in patients with gastroparesis, in addition to delayed gastric emptying, include impaired fundic accommodation, antral hypomotility, gastric dysrhythmias, pylorospasm, and perhaps visceral hypersensitivity. Diagnosis of gastroparesis is best determined using a radioisotope-labeled solid meal with scintigraphic imaging for at least 2 hours, and preferably 4 hours, postprandially. Most commonly, a 99mTc sulfur colloid-labeled egg sandwich with imaging at 0, 1, 2, and 4 hours is used. Extension of the gastric emptying test to 4 hours improves the accuracy of the test, but unfortunately, this is not commonly performed at many centers. Emptying of liquids remains normal until the late stages of gastroparesis and is less useful. The aims of treatment should be to control symptoms and maintain adequate nutrition and hydration. Patients should be advised to eat small meals and to limit their intake of fat and fiber. Additional dietary recommendations may include increasing caloric intake in the form of liquids. For diabetic patients, control of blood glucose levels is important, as symptom exacerbation is frequently associated with poor glycemic control. Specific treatment often begins with metoclopramide, 10 mg, up to four times daily, after a discussion of possible side effects with the patient. An antiemetic agent, such as prochlorperazine, 5 to 10 mg orally or 25 mg by suppository, can be added on an as-needed basis every 4 to 6 hours to control nausea. If these antiemetic medications are not effective, or if side effects develop, orally dissolving ondansetron, 8 mg every 8 to 12 hours, can be tried on an as-needed basis. If this regimen is unsuccessful, then alternative prokinetic agents—erythromycin, 125 mg, or tegaserod, 6 mg, prior to meals—can be tried. For cases refractory to these treatments, referral to a center with US Food and Drug Administration permission to use domperidone should be considered. Alternatively, symptom modulators such as low-dose tricyclic antidepressants can be tried to reduce symptoms, but these do not improve gastric emptying. In patients for whom all medical therapy fails, other options that are tried at experienced centers include the injection of botulinum toxin into the pylorus, placement of a feeding jejunostomy, and/or placement of a gastric electrical stimulator.     

Augmentation of lower esophageal sphincter pressure and gastric yield pressure after radiofrequency energy delivery to the gastroesophageal junction: a porcine model

BACKGROUND: An endoscopic technique that eliminates gastroesophageal reflux disease would be of benefit to patients. The endoscopic delivery of radiofrequency energy to the porcine gastroesophageal junction was investigated and its effect on lower esophageal sphincter pressure, gastric yield pressure, and histology was assessed. METHODS: Twenty pigs underwent esophageal manometry and endoscopic injection of botulinum toxin (100 units) into the lower esophageal sphincter. After 1 week, animals were randomized to radiofrequency energy treatment of the gastroesophageal junction with a 4- needle catheter and thermocouple-controlled generator (n = 13) or no further intervention (control, n = 7). At 9 weeks, animals underwent esophagoscopy, manometry, gastric yield pressure determination, and sacrifice for histopathologic evaluation. RESULTS: Mean lower esophageal sphincter pressure declined by 3.7 +/- 2.6 mm Hg (control, p = 0.03) vs. 0.97 +/- 5.8 mm Hg (radiofrequency, p = 0.29) after 9 weeks. Mean gastric yield pressure was 24.9 +/- 8.2 mm Hg (control), compared with 43.4 +/- 10. 7 mm Hg (radiofrequency) (p = 0.0007). Histopathologic assessment demonstrated normal mucosa, mild fibrosis, and no inflammation. CONCLUSIONS: Radiofrequency energy delivery reversed much of the lower esophageal sphincter pressure reduction achieved with botulinum toxin injection and augmented gastric yield pressure by 75% compared with controls. Given the safety of radiofrequency energy delivery in this study and in other areas of medicine, human studies to assess the effect of radiofrequency energy on gastroesophageal reflux disease are warranted.     

不同阶段糖尿病胃运动障碍诊治对策

糖尿病患者常见胃运动障碍,表现为上腹胀、早饱、上腹不适、恶心、呕吐等症状以及胃排空延迟,胃排空延迟影响降血糖药的药代动力学,造成餐后血糖升高与降血糖药或胰岛素的血浓度高峰不匹配,进而影响血糖的控制与稳定。糖尿病不同阶段胃运动障碍表现形式不同。核素法是最常用的胃排空诊断方法。糖尿病胃运动障碍的处理包括饮食调节、促动力药以减轻症状、控制血糖,针对胃轻瘫的治疗包括胃电刺激、内镜下幽门注射肉毒杆菌毒素A、内镜下放置鼻胃空肠营养管或经皮内镜下胃（空肠）造瘘、外科手术等。     

Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia

BACKGROUND & AIMS: Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported. METHODS: Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed. RESULTS: One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia. CONCLUSIONS: Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer. (Gastroenterology 1996 Dec;111(6):1418-24)     

Diagnostic and therapeutic approach to patients with gastroparesis

Gastroparesis is a chronic alteration of gastric motility characterized by symptoms suggestive of mechanical obstruction and delayed gastric emptying in the absence of obstruction. Gastroparesis can be idiopathic or attributable to neuropathy or myopathy as in diabetes mellitus and scleroderma or can occur after vagotomy. Diagnosis is based on symptoms (nausea, vomiting, abdominal distension and early satiety), physical examination (capotement) and on complementary investigations, the procedure of choice being isotope gastric emptying tests. Treatment depends on the clinical repercussions. In most patients, gastroparesis can be controlled by prokinetic drugs, dietary measures, exclusion of drugs that alter gastric emptying, and exhaustive control of blood glucose levels. In patients with severe gastroparesis, hospital nutritional measures (intravenous and/or enteral), gastric decompression and intravenous antiemetic and prokinetic agents are required. Aggressive nutritional therapies (parenteral or enteral nasojejunal nutrition), intrapyloric injection of botulinum toxin, implantation of a gastric stimulation device, or gastrectomy should only be used in patients unresponsive to conservative treatment or if there is selective alteration of gastric motility.     

Gastric emptying in patients with restricting and binge/purging subtypes of anorexia nervosa

OBJECTIVES: Gastrointestinal symptoms are common in anorexia and in bulimia nervosa, but their relationship with gastric dysmotility and their possible improvement with refeeding are still debated. METHODS: Twenty-three anorexic patients (12 with the binge/purging and 11 with the restricting subtypes) were studied using an ultrasonographic gastric-emptying test, psychopathological questionnaires, and bowel symptom questionnaires, before and after 4 and 22 wk rehabilitation. RESULTS: Gastric symptom scores were markedly higher in patients than in controls and improved significantly with treatment. On entry, compared to controls, gastric emptying was significantly delayed in restricters and purgers (357 +/- 25.3 and 360 +/- 13.0 min, respectively, mean +/- SEM; controls 207 +/- 9.1). After 4 and 22 wk of treatment, it improved in restricters (315 +/- 20.1 and 296 +/- 17.2 min, respectively), but not in purgers (337 +/- 14.3 and 335 +/- 15.9 min). No relationship was found between entry values of symptoms of gastric emptying and of psychopathological tests or between their variations over time. CONCLUSIONS: Gastric emptying derangement and dyspeptic symptoms are present in both subtypes of anorexia nervosa patients. Long-term rehabilitation improves gastrointestinal symptoms, gastric emptying, and psychopathological distress in an independent manner, whereas short-term refeeding does not.     

Oral erythromycin and symptomatic relief of gastroparesis: a systematic review

OBJECTIVE: Erythromycin is a motilin agonist that greatly increases the fractional rate of gastric emptying. Although a number of studies document the efficacy of erythromycin in improving gastric emptying, little information exists concerning symptom improvement in patients with gastroparesis. The aim of this study was to review clinical trials of erythromycin to determine the efficacy of this agent in producing symptom relief in patients with gastroparesis. METHODS: A MEDLINE search from 1966 to 2001 was performed to identify all clinical trials using erythromycin in patients with gastroparesis. The search was further limited to clinical trials using symptom assessment as an endpoint. References from index citations were reviewed to identify additional studies. The search was conducted independently by two authors, and discrepancies were resolved by consensus opinion. RESULTS: Thirty-five clinical trials were identified, and five met inclusion criteria. One study each involved gastroparesis caused by surgery and systemic sclerosis. Three studies evaluated patients with diabetic or idiopathic gastroparesis. No study used symptoms as a primary endpoint. Improvement was reported in 26 of 60 (43%) patients. Individual symptom scores were available for 23 of 60 subjects in these studies, and symptom improvement was seen in 11 of 23 (48%) patients. One study compared erythromycin and metoclopromide in an open-label, crossover fashion, and found no difference between the two agents. All studies were methodologically weak and highly subject to bias. Four of five studies were open-label trials. Sample sizes in all studies were < or =13 subjects, and treatment duration was < or =4 wk in all studies. CONCLUSIONS: Although clearly a potent prokinetic, limited data exist concerning efficacy of erythromycin in treating gastroparesis. Small sample sizes, uncontrolled designs, short duration, and inadequate symptom assessment limit available studies. Well-designed trials designed to assess symptom relief in gastroparesis are needed.     

Treatment of symptomatic nonachalasia esophageal motor disorders with botulinum toxin injection at the lower esophageal sphincter

The purpose of this study was to determine if botulinum toxin injection at the lower esophageal sphincter improves symptoms in patients with nonachalasia spastic esophageal motility disorders. Fifteen patients with nonachalasia spastic esophageal motility disorders (diffuse esophageal spasm, nonspecific esophageal motility disorders, and lower esophageal sphincter dysfunction) unresponsive to medical therapy underwent endoscopic injection of botulinum toxin at the level of the gastroesophageal junction. Symptoms were scored (0=no symptoms, 1=mild, 2=moderate, 3=severe and 4=very severe) before treatment, at seven days and every 30 days after treatment. There was significant improvement in chest pain, dysphagia, and regurgitation at 7, 30, 60 and 90 days after treatment. At one month after treatment, 11 of 15 (73%) patients had a good or excellent response to treatment. At the last patient interview (mean follow-up of 10.6 months), five (33%) patients continued to have a good to excellent response, whereas 10 (67%) underwent subsequent treatment with repeat botulinum toxin, pneumatic dilation, or bougienage. We conclude that botulinum toxin injection at the gastroesophageal junction leads to significant symptom improvement in patients with nonachalasia esophageal motility disorders. These results suggest that botulinum toxin may be an effective treatment option in some of these patients not responsive to conventional medical therapy.