Stanley B. Benjamin

Imipramine in patients with chest pain despite normal coronary angiograms

BACKGROUND Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients. METHODS Sixty consecutive patients underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then participated in a randomized, double-blind, placebo-controlled three-week trial of clonidine at a dose of 0.1 mg twice daily (20 patients), imipramine at a dose of 50 mg nightly with a morning placebo (20 patients), or placebo twice daily (20 patients); this treatment phase was compared with an identical period of twice-daily placebo for all patients (placebo phase). RESULTS Thirteen (22 percent) of the 60 patients had ischemic-appearing electrocardiographic responses to exercise, 22 of the 54 tested (41 percent) had abnormal esophageal motility, 38 of 60 (63 percent) had one or more psychiatric disorders, and 52 of 60 (87 percent) had their characteristic chest pain provoked by right ventricular electrical stimulation or intracoronary infusion of adenosine. During the treatment phase, the imipramine group had a mean (+/- SD) reduction of 52 +/- 25 percent in episodes of chest pain, the clonidine group had a reduction of 39 +/- 51 percent, and the placebo group a reduction of 1 +/- 86 percent, all as compared with the placebo phase of the trial. Only the improvement with imipramine was statistically significant (P = 0.03). Repeat assessment of sensitivity to cardiac pain while the patients were receiving treatment showed significant improvement only in the imipramine group (P = 0.01). The response to imipramine did not depend on the results of cardiac, esophageal, or psychiatric testing at base line, or on the change in the psychiatric profile during the course of the study, which generally improved in all three study groups. CONCLUSIONS Imipramine improved the symptoms of patients with chest pain and normal coronary angiograms, possibly through a visceral analgesic effect.

Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome.

OBJECTIVE To determine the relative abilities of somatostatin receptor scintigraphy (SRS) and conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) to localize gastrinomas before surgery in patients with Zollinger-Ellison syndrome (ZES) subsequently found at surgery, and to determine the effect of SRS on the disease-free rate. SUMMARY BACKGROUND DATA Recent studies demonstrate that SRS is the most sensitive imaging modality for localizing neuroendocrine tumors such as gastrinomas. Because of conflicting results in small series, it is unclear in ZES whether SRS will alter the disease-free rate, which gastrinomas are not detected, what factors contribute to failure to detect a gastrinoma, or whether the SRS result should be used to determine operability in patients without hepatic metastases, as recently recommended by some investigators. METHODS Thirty-five consecutive patients with ZES undergoing 37 exploratory laparotomies for possible cure were prospectively studied. All had SRS and conventional imaging studies before surgery. Imaging results were determined by an independent investigator depending on surgical findings. All patients underwent an identical surgical protocol (palpation after an extensive Kocher maneuver, ultrasound during surgery, duodenal transillumination, and 3 cm duodenotomy) and postoperative assessment of disease status (fasting gastrin, secretin test imaging within 2 weeks, at 3 to 6 months, and yearly), as used in pre-SRS studies previously. RESULTS Gastrinomas were detected in all patients at each surgery. Seventy-four gastrinomas were found: 22 duodenal, 8 pancreatic, 3 primaries in other sites, and 41 lymph node metastases. The relative detection order on a per-patient or per-lesion basis was SRS > angiography, magnetic resonance imaging, computed tomography > ultrasound. On a per-lesion basis, SRS had greater sensitivity than all conventional studies combined. SRS missed one third of all lesions found at surgery. SRS detected 30% of gastrinomas < or =1.1 cm, 64% of those 1.1 to 2 cm, and 96% of those >2 cm and missed primarily small duodenal tumors. Tumor size correlated closely with SRS rate of detection. SRS did not increase the disease-free rate immediately after surgery or at 2 years mean follow-up. CONCLUSIONS SRS is the most sensitive preoperative imaging study for extrahepatic gastrinomas in patients with ZES and should replace conventional imaging studies as the preoperative study of choice. Negative results of SRS for localizing extrahepatic gastrinomas should not be used to decide operability, because a surgical procedure will detect 33% more gastrinomas than SRS. SRS does not increase the disease-free rate. In the future, more sensitive methods to detect small gastrinomas, especially in the duodenum and in periduodenal lymph nodes, or more extensive surgery will be needed to improve the postoperative disease-free rate in ZES.

Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety

OBJECTIVE:Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis.METHODS:A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial.RESULTS:After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4–99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4–99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2–69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7–40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free.CONCLUSIONS:Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.

Nonmalignant obstruction is a common problem with metal stents in the treatment of esophageal cancer.

BACKGROUND The use of metal stents for the treatment of dysphagia due to esophageal malignancy is an important advance because of ease of delivery and their self-expandable property. Obstruction due to tumor overgrowth is a recognized complication, but nonmalignant obstruction in patients with metal stents is rarely reported. METHODS Database records of patients who had esophageal cancer and underwent metal stent insertion were reviewed. RESULTS A total of 116 patients were seen between October 1993 and October 1997. Four types of metal stents had been used (Ultraflex, Z Stent, Wallstent, and Esophacoil). Detailed follow-up information was available for 81 patients, who constitute the study sample. Forty-nine (60%) stent obstructions were reported, 26 of the 49 (53%) were due to tumor overgrowth and 23 (47%) were not associated with malignancy. Histologic analysis of the nonmalignant obstructing tissue showed granulation tissue (56%), reactive hyperplasia (22%) and fibrosis (22%). CONCLUSIONS Nonmalignant obstruction is a common although infrequently reported complication after placement of metal stents for esophageal cancer. The tissue response of the esophageal mucosa occurred with all 4 types of stents used. No specific characteristic of the stent or prior treatment seems to be related to obstruction of the stent in patients with either nonmalignant obstruction or tumor overgrowth.

Coronary flow reserve, esophageal motility, and chest pain in patients with angiographically normal coronary arteries

PURPOSE AND METHODS To ascertain the relative prevalence of abnormalities of coronary flow reserve and esophageal function in patients with chest pain despite angiographically normal coronary arteries, 87 patients underwent invasive study of coronary flow reserve and, during the same week, esophageal testing. RESULTS Sixty-three of the 87 patients (72%) demonstrated abnormalities of coronary flow reserve, as evidenced by an increase in coronary resistance during the stress of rapid atrial pacing after administration of ergonovine 0.15 mg intravenously (1.33 +/- 0.36 mm Hg.minute/mL), compared with pacing at the same heart rate before ergonovine administration (1.10 +/- 0.33 mm Hg.minute/mL). This higher coronary vascular resistance occurred in the absence of significant epicardial coronary artery luminal narrowing. Fifty-seven of these 63 patients (90%) with a coronary vasoconstrictor response to ergonovine described their typical chest pain during pacing stress, compared with only six of 24 patients (25%) who demonstrated no coronary flow abnormality (p less than 0.001). After administration of dipyridamole 0.5 to 0.75 mg/kg intravenously to 65 patients, the 48 patients with ergonovine-induced vasoconstriction had a significantly higher minimum coronary resistance, compared with the 17 patients without a coronary vasoconstrictor response to ergonovine (0.65 +/- 0.21 versus 0.47 +/- 0.13 mm Hg.minute/mL, p less than 0.03). Twenty of 87 patients (23%) had abnormal esophageal motility [nutcracker esophagus (11), nonspecific motility disorder (seven), and diffuse esophageal spasm (two)], including 16 of the 63 patients (25%) with abnormal coronary flow reserve. Twenty-four (28%) patients experienced their typical chest pain during motility testing, but only five of these patients met criteria for abnormal esophageal motility. Nine of 75 patients tested (12%) had their typical chest pain during Bernstein testing, and 18 of 38 patients (47%) tested had their typical chest pain provoked by intraesophageal balloon distention. CONCLUSIONS Seventy-one of 87 patients (82%) with anginal-like chest pain and normal epicardial vessels in our series had a disorder of either coronary flow reserve, esophageal motility, and/or reproduction of typical chest pain during acid infusion. Of interest, chest pain was commonly encountered during cardiac and esophageal testing (85% of patients), regardless of the ability to demonstrate an abnormality of coronary flow reserve or abnormal esophageal function. This suggests that pain experienced by these patients may be a consequence of myocardial ischemia, esophageal dysfunction, abnormal visceral nociception, or a combination of any or all of these entities.

Double-blind controlled trial of the Garren-Edwards gastric bubble: An adjunctive treatment for exogenous obesity

Since its approval by the Food and Drug Administration in September 1985, the Garren-Edwards gastric bubble has been extensively used as an adjunct to diet and behavioral modification in the treatment of exogenous obesity. In an attempt to evaluate the efficacy of the Garren-Edwards gastric bubble, a double-blind crossover study was undertaken. Ninety patients were randomized into three groups: bubble-sham, sham-bubble, and bubble-bubble in two successive 12-wk periods. Sixty-one patients completed the entire 24-wk study. All groups participated in ongoing diet and behavioral modification therapy in a free-standing obesity program, the members of which were blinded to randomization arms. All patient groups lost weight during this study. The mean cumulative weight loss in pounds at 12 wk was as follows: bubble-sham = 19, sham-bubble = 12, and bubble-bubble = 8; and at 24 wk: bubble-sham = 23, sham-bubble = 16, and bubble-bubble = 18. The mean cumulative change in body mass index (kg/m2) at 12 wk was as follows: bubble-sham = -3.1, sham-bubble = -2.3, and bubble-bubble = -2.9; and at 24 wk: bubble-sham = -3.1, sham-bubble = -3.0, and bubble-bubble = -3.3. Although weight loss occurred more consistently in patients with a Garren-Edwards gastric bubble, there were no significant differences between any of the three groups at 12 or 24 wk with respect to weight loss or change in body mass index. The major part of the weight loss noted during this study occurred during the first 12-wk period, irrespective of therapy (bubble or sham). Side effects observed during this study included gastric erosions (26%), gastric ulcers (14%), small bowel obstruction (2%), Mallory-Weiss tears (11%), and esophageal laceration (1%). We conclude that, in this study, the use of a Garren-Edwards gastric bubble did not result in significantly more weight loss than diet and behavioral modification alone in the management of exogenous obesity, and it may result in significant morbidity.

Endoscopic ultrasound for staging esophageal cancer, with or without dilation, is clinically important and safe

BACKGROUND To fully evaluate patients with esophageal cancer by endoscopic ultrasonography (EUS), the transducer must pass through the entire tumor to the cardia to scan the celiac axis. Dilation may be necessary. Published information suggests that dilation with EUS carries a sizeable risk. METHODS In order to assess the complication rate associated with dilation prior to EUS in patients with esophageal cancer and the clinical significance of dilation for complete EUS staging, we reviewed the records of all patients who had undergone EUS for esophageal cancer. RESULTS Sixty-three patients underwent EUS staging of esophageal cancer. Thirty-nine (62%) had lesions through which the EUS scope was passable (Group I). Ten (16%) patients (Group II) had lesions through which an EUS scope (diameter 13 mm) was unable to pass even after dilation. Fourteen patients (22%) had lesions that were dilated to allow passage of the EUS scope (Group III). All patients in Groups II and III had confirmation of EUS staging by CT and/or surgery. In Group II, five patients had tumors defined as T4 (50%) and five as T3 (50%). In Group III, nine (64%) had T4 tumors, four (29%) had T3, and one (7.7%) had T2. No complications were encountered in any group. CONCLUSION EUS, either alone or after dilation, is a safe procedure and the complete EUS examination with celiac node visualization adds prognostically significant information.

Silicone-covered wallstent prototypes for palliation of Malignant esophageal obstruction and digestive-respiratory fistulas

BACKGROUND Endoscopic palliation of malignant esophageal obstruction with uncovered self-expanding metal stents has been shown to have fewer complications than with conventional plastic stents. The addition of a membrane might prevent tumor ingrowth and allow treatment of digestive-respiratory fistulas. We report the clinical experience with a prototype silicone membrane-covered self-expanding metal stent. METHODS Twenty-three silicone membrane-covered Wallstent prototypes were used in 21 patients with dysphagia due to inoperable malignant tumors involving the esophagus and cardia. RESULTS Stent implantation was technically successful in all patients. There were no procedure-related perforations or deaths. The prototype stent was successful in sealing seven of the eight (87.5%) digestive-respiratory fistulas. As a group, the mean dysphagia grade improved significantly after stent placement (4.8 +/- 0.9 vs 3.4 +/- 1.6, p < 0.0005). However, 9 of 21 (42.9%) patients experienced no improvement in their dysphagia. Complications occurred in 13 of 21 (61.9%) patients. Tumor ingrowth was not observed in any patient. CONCLUSIONS The prototype covered self-expanding metal stent was effective in sealing digestive-respiratory fistulas and provided palliation of dysphagia in slightly more than one half of the patients studied. A great deal has been learned from the preliminary experience, which has led to design modifications. The utility of the commercially available device should be evaluated in further prospective clinical trials.

Utility of upper endoscopy in the evaluation of noncardiac chest pain

The diagnostic yield of esophagogastroduodenoscopy, esophageal manometry, and Bernstein testing was assessed in 100 consecutive patients being evaluated for non-cardiac chest pain. Manometric studies revealed the nutcracker esophagus in 21 patients; non-specific esophageal motility disorders in 19 patients; a hypertensive lower esophageal sphincter in 4 patients; diffuse esophageal spasm in 2 patients; and normal motility in 54 patients. Endoscopy was normal in 38 patients; but revealed grades II to IV esophagitis in 24 patients; gastritis and/or duodenitis in 18 patients; a sliding hiatal hernia without evidence of esophagitis in 14 patients; and gastric or duodenal ulcers in 6 patients. Twenty-five individuals were found to have normal manometric studies in combination with a negative Bernstein test. Among these 25 patients, however, 7 patients had esophagitis (grade II or higher); 6 patients had gastritis and/or duodenitis; five patients had a sliding hiatal hernia without esophagitis; 1 patient had peptic ulcer disease; and only 6 patients had a normal endoscopic exam. Our results indicate that endoscopy can identify a significant number of patients with acid-peptic disease who present with non-cardiac chest pain, that would not have been otherwise diagnosed by esophageal manometry or Bernstein testing alone or in combination.

Prospective analysis of complications 30 days after outpatient upper endoscopy

Abstract OBJECTIVE: The aim of this study was to compare complication rates reported by patients 30 days after outpatient upper endoscopy with those discussed at our monthly morbidity and mortality conference. We also intended to establish which complications were reported most frequently 30 days after upper endoscopy, and which patients or procedures involved the highest risk. METHODS: Trained interviewers performed standardized telephone interviews on consecutive outpatients undergoing upper endoscopy over a 1-yr period. Patients were queried regarding potential events related to their upper endoscopy in the 30 days subsequent, including symptoms, emergency room (ER) and/or physician visits, and hospitalizations. The indications, findings, and therapies were reviewed from endoscopic reports. RESULTS: A total of 473 patients were contacted 30 days after outpatient upper endoscopy and agreed to participate in our study. The most common complications reported by patients at 30 days were sore throat (9.5%) and abdominal discomfort (5.3%). Twelve patients (2.5%) required an ER/physician visit and five patients (1.1%) required hospitalization. The minority of both ER/physician visits (16.7%) and hospitalizations (40%) were discussed at our monthly morbidity and mortality conferences. CONCLUSIONS: More complications were reported by patients 30 days after outpatient upper endoscopy than were discussed at our monthly morbidity and mortality conferences. The most frequent complications reported by patients were sore throat and abdominal pain. The minority of ER/physician visits and hospitalizations were discussed at our morbidity and mortality conferences.