Acquired segmental megacolon in an adult patient with cystic fibrosis.

Cystic fibrosis (CF) is characterized by symptoms related to pulmonary dysfunction and pancreatic insufficiency. Constipation, though a frequent complaint of patients with CF, receives less attention. We report a case of acquired segmental megacolon and constipation necessitating surgical colonic resection in an adult patient with CF. The differential diagnosis and possible causes of megacolon in this setting are discussed.

Prevalence of gastroesophageal reflux after laparoscopic Heller myotomy.

BACKGROUND: There is still some controversy over the need for antireflux procedures with Heller myotomy in the treatment of achalasia. This study was undertaken in an effort to clarify this question. METHODS: To determine whether Heller myotomy alone would cause significant gastroesophageal reflux (GER), we studied 16 patients who had undergone laparoscopic Heller myotomy without concomitant antireflux procedures. Patients were asked to return for esophageal manometry and 24-h pH studies after giving informed consent for the Institutional Review Board (IRB)-approved study at a median follow-up time of 8.3 months (range, 3-51). Results are expressed as the mean +/- SEM. RESULTS: Fourteen of the 16 patients reported good to excellent relief of dysphagia after myotomy. They were subsequently studied with a 24-h pH probe and esophageal manometry. These 14 patients had a significant fall in lower esophageal sphincter (LES) pressure from 41.4 +/- 4.2 mmHg to 14.2 +/- 1.3 mmHg, after the myotomy (p < 0.01, Student's t-test). The two patients who reported more dysphagia postoperatively had LES pressures of 20 and 25 mmHg, respectively. Two of 14 patients had DeMeester scores of >22 (scores = 61.8, 29.4), while only one patient had a pathologic total time of reflux (percent time of reflux, 8%). The mean percent time of reflux in the other 13 patients was 1.9 +/- 0.6% (range, 0.1-4%), and the mean DeMeester score was 11.7 +/- 4.6 (range, 0.48-19.7). CONCLUSIONS: Laparoscopic Heller myotomy is effective for the relief of dysphagia in achalasia if the myotomy lowers the LES pressure to <17 mmHg. If performed without dissection of the entire esophagus, the laparoscopic Heller myotomy does not create significant GER in the postoperative period. Clearance of acid refluxate from the aperistaltic esophagus is an important component of the pathologic gastroesophageal reflux disease (GERD) seen after Heller myotomy for achalasia. Furthermore, GERD symptoms do not correlate with objective measurement of GE reflux in patients with achalasia. Objective measurement of GERD with 24 h pH probes may be indicated to identify those patients with pathologic acid reflux who need additional medical treatment.

The role of elective operation in the treatment of portal hypertension.

Variceal bleeding is associated with a high rate of rebleeding and death if left untreated. Operative therapy is an important modality for managing portal hypertension in patients unsuitable for, or who fail, sclerotherapy. Review of 41 patients undergoing 42 surgical procedures for portal hypertension since 1988 revealed 22 elective procedures with a 4.5 per cent operative mortality. Ten emergent procedures were undertaken for patients actively bleeding, resulting in a 40 per cent mortality rate. Minor rebleeding not related to portal hypertension occurred in 2 of the 35 patients who survived long term, and long-term shunt patency was 97 per cent. These 41 patients were compared with 35 patients undergoing transjugular intrahepatic portosystemic shunts (TIPS) at Vanderbilt University Medical Center, whom we have previously reported. Five patients underwent shunt procedures after TIPS failure. Attempts to decompress portal hypertension using TIPS placement have met with limited success because of early thrombosis (12%), stenosis (41%), and a high rebleeding rate. Our data suggest that elective operative shunting procedures for the treatment of portal hypertension in Child's class A or B patients are associated with low rates of mortality, encephalopathy, and rebleeding. Moreover, the encephalopathy rate that occurred after TIPS or operative total shunt was higher than that observed in patients undergoing selective distal splenorenal shunt. Therefore, we advocate the elective operation rather than TIPS in the management of portal hypertension in patients with good liver reserve. TIPS is better suited for the patient with active bleeding, poor liver reserve, transplant candidates, or in patients with prohibitive operative risk.

Incidence of shunt occlusion or stenosis following transjugular intrahepatic portosystemic shunt placement.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) placement has been used for the treatment of recurrent variceal hemorrhage. The 1-year incidence of shunt stenosis or occlusion after TIPS placement was prospectively assessed, and the accuracy of Doppler ultrasonography to predict TIPS stenosis was evaluated. METHODS: Twenty-two patients with recurrent variceal hemorrhage were selected for TIPS placement between April 1991 and May 1992. Preoperative and postoperative evaluation included clinical assessment, upper gastrointestinal endoscopy, portal angiography with pressure measurements, and Doppler ultrasonography. Follow-up was performed at 3 and 12 months post-TIPS and when patients developed recurrent bleeding. RESULTS: Twenty-one of 22 patients (Child-Pugh class A-1, B-11, C-9) had successful TIPS placement. Seventeen of 21 patients have completed follow-up for at least 12 months. Of these 17 patients, 2 of 17 (12%) developed TIPS occlusion, 7 of 17 (41%) developed shunt stenosis, and 8 of 17 (47%) showed no stenosis on follow-up angiography. Doppler ultrasonographic assessment of the TIPS predicted shunt stenosis or occlusion with 100% sensitivity, 98% specificity, and 90% positive predictive value. CONCLUSIONS: Shunt occlusion or stenosis develops frequently within 12 months after TIPS placement, and Doppler ultrasonography is accurate in the noninvasive assessment of shunt stenosis. TIPS placement without careful follow-up and shunt revision cannot be considered a long-term treatment of variceal hemorrhage.

Transjugular intrahepatic portosystemic shunt: US assessment with maximum flow velocity.

PURPOSE: To evaluate the ability of Doppler ultrasonography (US) to depict the patency of a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: Twenty-eight patients were followed up after creation of TIPS with US, angiography, and endoscopy performed at regular intervals. Magnetic resonance (MR) angiography was performed in four patients. US was performed first, and the results were correlated with those at angiography. Measurements of maximum flow velocity (Vmax) were taken from the proximal part of the shunt. RESULTS: In normal shunts, mean Vmax was 95 cm/sec. Shunt obstruction was seen in 12 cases: occlusion in four and stenosis in eight. All cases of occlusion were detected with US and appeared as absent flow within the shunt. There was one false-positive diagnosis of occlusion. All cases of stenosis resulted in reduced Vmax (mean, 32 cm/sec; P < .001). After successful revision in seven patients, Vmax rose to a mean of 122 cm/sec. Artifact from the metal stent prevented flow assessment with MR imaging. CONCLUSION: US can be performed to evaluate shunt status, and Vmax is an accurate noninvasive parameter for assessing shunt patency.

Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo.

Approximately 50 to 60% of Helicobacter pylori isolates produce a vacuolating cytotoxin in vitro. To assess cytotoxin production in vivo, we sought to determine whether infection with a Tox+ H. pylori strain is associated with the presence of serum antitoxin antibodies. H. pylori isolates and serum samples were obtained from 30 patients, and serum samples were obtained from 20 uninfected patients as controls. Sera were tested by enzyme-linked immunosorbent assay for reactivity with the purified 87-kDa vacuolating cytotoxin, and the 30 H. pylori isolates were tested for vacuolating cytotoxin production. Supernatants from 14 (47%) of the 30 H. pylori isolates induced vacuolation of HeLa cells. Sera from the 30 H. pylori-infected patients reacted with the purified 87-kDa cytotoxin to a greater extent than sera from the uninfected controls for both immunoglobulin G (IgG) and IgA classes (P = 0.0004 and P < 0.0001, respectively). Serum IgG and IgA responses to the purified 87-kDa cytotoxin were higher among the 14 patients infected with Tox+ strains than among the 16 patients infected with Tox- strains (mean optical densities +/- standard errors of the means of 0.603 +/- 0.11 versus 0.234 +/- 0.07 [P = 0.005] and 0.644 +/- 0.12 versus 0.341 +/- 0.08 [P = 0.04] for IgG and IgA, respectively). Infection with a Tox+ strain compared with a Tox- strain was associated with increased antral polymorphonuclear leukocyte inflammation scores (P = 0.04). These data indicate that cytotoxin production by H. pylori isolates in vitro correlates with cytotoxin production in vivo and that infection with Tox+ H. pylori isolates may be associated with increased antral mucosal polymorphonuclear leukocyte infiltration.

Possible role of transforming growth factor alpha in the pathogenesis of Ménétrier's disease: supportive evidence form humans and transgenic mice.

Ménétrier's disease is an uncommon disorder of unknown etiology characterized by enlarged gastric folds with foveolar hyperplasia and cystic dilatation of gastric glands. Biochemical features that are seen frequently include hypoproteinemia, hypochlorhydria, and increased gastric mucus. Because transforming growth factor alpha (TGF alpha) is an epithelial cell mitogen that inhibits gastric acid secretion and increases gastric mucin content, we hypothesized that its altered expression might be involved in the pathogenesis of this disease. Therefore, we characterized TGF alpha immunoreactivity in the gastric mucosa of 4 patients with Ménétrier's disease. In contrast to the normal pattern of TGF alpha immunostaining in which TGF alpha appears most concentrated in parietal cells, there was intense staining in the majority of mucous cells in the gastric mucosa of patients with Ménétrier's disease. In one patient from whom sufficient fresh tissue was obtained to isolate RNA, expression of TGF alpha and the epidermal growth factor receptor was higher in the gastric mucosa relative to a normal control. In addition, metallothionein-TGF alpha transgenic mice, which overexpress TGF alpha in gastric mucosa, show a number of features characteristic of Ménétrier's disease. These include foveolar hyperplasia and glandular cystic dilatation, increased gastric neutral mucin staining, and reduced basal and histamine-stimulated rates of acid production. Taken together, observations derived from the human material and correlation with data from a transgenic mouse model support an important role for TGF alpha in the pathogenesis of Ménétrier's disease.

Acceleration of gastric emptying with electrical stimulation in a canine model of gastroparesis.

We investigated the effects of electrical stimulation of the stomach on gastric emptying and the electrical activity of the stomach in 10 dogs. A model of gastroparesis was developed in five dogs using truncal vagotomy combined with injections of glucagon. Glucagon also induced electrical dysrhythmias. Bipolar electrodes were implanted in the stomach and the duodenum for electrical stimulation and for recording electrogastrograms. Gastric emptying of an isotope-labeled solid meal was assessed for 2 h. External electrical stimulation was delivered to the corpus of the stomach at its own physiological frequency to investigate whether it could restore normal gastric emptying. Such stimulation had no significant effect on gastric emptying in intact animals (45 vs. 43%: retention of isotope after 2 h) or when only vagotomy was performed (78 vs. 66%), but it significantly accelerated gastric emptying in animals with vagotomy and glucagon (from 86 to 68%). From this model of delayed gastric emptying, we suggest that electrical stimulation of the stomach at its own intrinsic frequency may recoordinate uncoupled slow wave activity induced by glucagon after vagotomy thus improving the rate of gastric emptying.

Variation in the size and number of stone fragments after gallbladder lithotripsy.

Ninety-four gallbladder ultrasound examinations were carried out in 11 patients at intervals for the first 40 days after lithotripsy. No dissolution or other active therapy was carried out during this time. Fragment size and number were measured to determine the postlithotripsy variability. Analysis of variance (ANOVA) showed no significant changes in fragment size or number over time. The changes in fragment size and number compared to the previous measurements were then evaluated. Again, ANOVA showed no significant changes between times. The average change in absolute size was 3.1 +/- 0.6 mm, and the average change in absolute number was 1.4 +/- 0.5. We conclude that fragment size and number as determined by ultrasound do not vary significantly with time during the first 40 days. The absolute size change measured to the nearest millimeter should be at least 4 mm to surpass the 95% confidence interval. Similarly, the absolute change in number should be at least 2 to be regarded as significant.

Purified choleragenoid does not induce migrating action potential complex activity in rabbit ileum in vivo.

The migrating action potential complex (MAPC), a single ring contraction that propels luminal contents abroad, is elicited by Vibrio cholerae and its enterotoxin, choleragen (A1A2B5), in rabbit ileal loops in vivo. Choleragenoid (B5; the binding subunit) was shown previously to induce MAPCs without activating the adenylate cyclase system and without stimulating fluid output. We restudied purified B5 (extracted by high-performance liquid chromatography) to assess its effects on the myoelectric activity of rabbit ileum: can MAPC activity can be induced without associated fluid production? Four different B5 preparations and two controls, V. cholerae and sterile saline, were used. MAPC activity and ileal fluid output were significantly increased in animals inoculated with A1A2B5 (V. cholerae-El Tor) compared with all other preparations and controls. Importantly, MAPC activity and fluid output in all B5 groups did not differ from those in saline controls, demonstrating that purified B5 does not induce MAPC activity in rabbit ilium in vivo. The previous study showing B5-induced MAPCs may have resulted from A1A2B5 contamination. These results suggest A1A2B5-induced adenylate cyclase activation; myoelectric activity may be interrelated with holotoxin binding that causes a neural response.

Effects of Vibrio cholerae recombinant strains on rabbit ileum in vivo. Enterotoxin production and myoelectric activity.

Previous studies have identified the effects of Vibrio cholerae and its enterotoxin, choleragen (CT A+B+), on the myoelectric activity of rabbit ileal loops in vivo. The response was defined as the migrating action potential complex, the single ring contraction that propels luminal contents aborad. In this study the same rabbit model is used to assess whether migrating action potential complex activity or fluid output is induced by recombinant strains of V. cholerae that produce no subunit of cholera toxin (CT A-B-) or only by the inactive binding subunit (CT A-B+). Three live strains were studied: El Tor wild-type N16961 (CT A+B+) and recombinant strains CVD106 (CT A-B+) and JBK70 (CT A-B-). Controls received sterile culture broth. Migrating action potential complex frequency in animals inoculated with CT A+B+ was significantly increased compared with that in all other experimental groups (P less than 0.01). Fluid output was also increased in animals inoculated with CT A+B+ compared with fluid output in all other groups (P less than 0.05). Migrating action potential complex frequency and fluid output in rabbits given CT A-B+ or CT A-B- did not differ from activity in controls. How these recombinant strains induce diarrhea is unknown, but the mechanism may involve bacterial colonization or production of an unknown toxin.

Motility disorders in the irritable bowel syndrome.

Specific abnormalities of colonic and small bowel motility are identifiable and associated with symptoms in IBS. Characteristic abnormalities in colonic motility include a prolonged increase in 3-cycles/min colonic motor activity after a meal, an exaggerated increase in 3-cycles/min motor activity in response to stressors and CCK, and increased visceral sensitivity and motor activity in response to balloon distention. Symptoms in patients with IBS correlate in some cases with the abnormal gastrocolonic response and with pain induced by distention at various sites in the colon. Small bowel motility abnormalities identified reproducibly in IBS include an increase in daytime jejunal DCCs, an increase in daytime ileal PPCs, and more frequent cycling of daytime MMCs (in diarrhea-predominant IBS only). DCCs and PPCs are strongly associated with symptoms in IBS, and PPCs associated with altered ileocecal transit may be an important mechanism of symptoms in some patients with IBS. Esophageal and gastroduodenal motility abnormalities are inconsistently identified in IBS, and most symptoms in IBS appear to be secondary to small bowel or colonic dysfunction. Because of the paroxysmal nature of these motor abnormalities in IBS, prolonged motility recordings are required to better understand the pathophysiology of this syndrome. Patients with IBS may have altered visceral sensation and changes in afferent reflex mechanisms that modulate GI motility. These patients do not have a generalized increase in pain perception, but may have a distinct sensitivity to visceral afferent stimulation in both gastrointestinal and other viscera. Whether the altered "setpoint" to visceral afferent stimulation in IBS is intrinsic to the smooth muscle of viscera or secondary to CNS and ANS modulation is not known. Many of the symptoms and abnormalities of small bowel and colonic motility in IBS probably result from these changes in afferent sensation and reflex mechanisms. These findings support the concept that IBS is an abnormality of intestinal motility in conjunction with a "sensitive" gut.