William C. Santangelo

Prophylactic sclerotherapy of large esophageal varices.

We randomly assigned 95 patients with large esophageal varices (Grade 3 or 4) who had not previously had upper gastrointestinal tract bleeding to two groups: 49 received intravariceal sclerotherapy, and 46 were followed as controls. Over a mean follow-up of 13 months there was no difference between the sclerotherapy group and the control group in mortality (24.4 percent) or any significant difference in average hospital stay per month (3.0 vs. 2.6 days). Sclerotherapy was associated with significantly more episodes of upper gastrointestinal bleeding (26 vs. 10 episodes, P less than 0.05); 75 percent of deaths in the sclerotherapy group were related to bleeding, as compared with 18 percent in the control group. An additional 54 patients with cirrhosis who did not qualify for the study were also followed--20 with small varices and 34 with none. Mortality was 20 and 15 percent, respectively; no deaths were due to bleeding. We conclude that prophylactic sclerotherapy does not provide clinical benefit to patients with large esophageal varices.

α1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders

Fecal clearance of plasma alpha 1-antitrypsin is used as a measure of protein leakage into the intestinal tract. In this study, the alpha 1-antitrypsin concentration in stool and the plasma clearance of alpha 1-antitrypsin in normal subjects and in a consecutive series of patients with chronic diarrhea, malabsorption, or unexplained hypoalbuminemia was determined. The normal subjects were studied in their usual state and also when they had diarrhea secondary to ingestion of lactulose, sorbitol, sodium sulfate, or phenolphthalein. The study first concluded that induced diarrhea can cause an increase in alpha 1-antitrypsin clearance; if this is not considered in establishing normal values, there may be an overdiagnosis of excess protein leakage in patients with diarrhea. Second, there is a highly significant statistical correlation (P less than 0.001) between alpha 1-antitrypsin clearance and serum albumin concentration. On average, the serum albumin falls below 3.0 g/dL (30 g/L) when the alpha 1-antitrypsin clearance exceeds 180 mL/day, a value that is about threefold higher than the upper limit of normal. Third, three of nine patients with microscopic/collagenous colitis had elevated clearance of alpha 1-antitrypsin; by contrast, abnormal alpha 1-antitrypsin clearance was not found in 23 patients with idiopathic secretory diarrhea. Fourth, fecal alpha 1-antitrypsin concentration is not a reliable index of abnormal alpha 1-antitrypsin clearance.

Pancreatic Cholera Syndrome: Effect of a Synthetic Somatostatin Analog on Intestinal Water and Ion Transport

The effect of a synthetic somatostatin analog was studied in a patient with severe secretory diarrhea due to pancreatic cholera syndrome. Basal intestinal perfusion studies indicated an absence of water and sodium absorption, and active chloride secretion in the small bowel. Intravenous administration of the somatostatin analog (1 microgram/kg.h) changed zero net water movement to absorption (122 mL/30 cm of the jejunum per hour). Chloride secretion changed to absorption (5.0 to 7.9 meq/30 cm.h), and plasma vasoactive intestinal polypeptide concentration was reduced from 330 to 45 pmol/L (normal, less than 51). When the analog was given subcutaneously, 100 micrograms twice daily, stool weight decreased, and plasma vasoactive intestinal polypeptide concentration fell toward the normal range (67 pmol/L). Plasma concentration of pancreatic polypeptide was initially elevated and dropped during intravenous infusion of somatostatin analog but returned to baseline on maintenance therapy with the analog delivered subcutaneously. The patient has not had further diarrhea during 9 months of therapy.

The Self-Limited Nature of Chronic Idiopathic Diarrhea

BACKGROUND Little is known about the clinical presentation and natural history of previously healthy patients in whom chronic idiopathic diarrhea develops. METHODS We reviewed the case records of 152 patients with chronic diarrhea who had no history of gastrointestinal surgery and who were evaluated in detail as part of a chronic-diarrhea protocol from 1985 to 1990. Patients were considered to have chronic idiopathic diarrhea if they had persistently loose stools for more than four weeks, no systemic illness, and no identifiable cause of diarrhea. RESULTS Seventeen patients (10 men and 7 women) ranging in age from 33 to 72 years met the criteria for chronic idiopathic diarrhea. Each patient had a history of a relatively abrupt onset of symptoms, often soon after returning home from a trip, starting two to seven months before evaluation. Their diarrhea did not occur during a local outbreak of diarrhea, and other family members did not become ill. Stool frequency ranged from 5 to 25 movements per day, stool weights ranged from 417 to 1480 g per day, and fecal electrolyte and osmolality values were consistent with a diagnosis of secretory diarrhea. The results of biopsies of the small intestine and colon were normal, as were small-bowel roentgenograms. Extensive studies for infectious causes of diarrhea were negative, and no patient responded to antibiotic therapy. In every patient the diarrhea stopped without specific therapy after 7 to 31 months (mean, 15) and did not recur during a follow-up period averaging 38 months. CONCLUSIONS Sporadic idiopathic chronic diarrhea is a recognizable syndrome that can last many months, but is self-limited.

Effect of Somatostatin Analog on Water and Electrolyte Transport and Transit Time in Human Small Bowel

The present study was undertaken to investigate how a somatostatin analog (201–995 Sandoz), which is now commonly used for treatment of patients with gut hormone-producing tumors, affects water and ion absorption and transit time in the normal jejunum. Six healthy volunteers were given somatostatin analog intravenously at a dose of 1 μg/kg/hr. At the same time, jejunal water and ion movement and transit time were measured using the triple-lumen tube technique [perfusion of a plasma-like electrolyte solution with PEG as a nonabsorbable marker at a rate of 15 ml/min; dye dilution curves ([3H]mannitol, [14C]PEG, BSP) for determination of jejunal transit time]. During somatostatin analog administration, transit time through a 30-cm segment of perfused jejunum increased from 4.0 min to 17.0 min. While the somatostatin analog increased jejunal transit time, it had no effect on net water and electrolyte absorption under steady-state conditions. The effect of somatostatin analog on the proximal small bowel is similar to the action of an eight-times higher dose of intravenous native somatostatin previously studied. The effect of the analog on transit time suggests a potentially beneficial effect in patients with large-volume diarrhea in which no tumor or circulating secretagogue can be identified, such as in pseudopancreatic cholera syndrome.

Sevelamer crystals in the gastrointestinal tract (GIT): A new entity associated with mucosal injury

We report the first description of sevelamer crystals (Renagel and Renvela, Genzyme; phosphate-lowering agents) in the gastrointestinal tract. We prospectively collected cases with novel, histologically identical crystals from 4 major academic centers over a 1-year period and studied pertinent clinicopathologic features. Sevelamer usage in the setting of chronic kidney disease was demonstrated in all cases (n=15 total cases, 7 patients). Sites of involvement included the esophagus (n=2), small bowel (n=2), and colon (n=11). The background mucosa was normal in only 1 case. Notable mucosal abnormality included chronic mucosal damage (n=5), acute inflammation (n=4), inflammatory polyp (n=2), extensive ulceration (n=2), ischemia (n=1), and necrosis (n=1). In general, sevelamer crystals displayed broad, curved, and irregularly spaced “fish scales” with a variably eosinophilic to rusty brown color on hematoxylin and eosin (H&E) staining and violet color on periodic acid-Schiff-alcian special staining with diastase (PAS/D). To validate these findings, sevelamer tablets (Renvela) were crushed and submitted for histologic processing; the findings were identical to those in the patient specimens. The possibility of Kayexalate (sodium polystyrene sulfonate) and cholestyramine had been raised in error. However, Kayexalate has narrow, rectangular “fish scales” and is violet on H&E and magenta on PAS/D; cholestyramine lacks internal “fish scales,” is bright orange on H&E, variably gray or hot pink on PAS/D, and is unassociated with mucosal injury. Further study is required to determine whether sevelamer plays a causal role in these injuries; however, its crystal is an important mimic of both Kayexalate and choleystyramine. As the history of sevelamer administration was not documented in any pathology requisition, awareness of sevelamer’s characteristic morphology is crucial to avoid the diagnostic pitfalls of its mimics.

Diagnostic value of fasting plasma peptide concentrations in patients with chronic diarrhea.

To evaluate the utility of screening for multiple gastrointestinal peptides in the evaluation of patients with chronic diarrhea, we studied 193 patients referred for evaluation of chronic diarrhea and eight patients with known peptide-secreting tumors as a reference group. Fasting plasma samples were assayed for motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, vasoactive intestinal polypeptide, gastrin-releasing peptide, and calcitonin during a protocol evaluation for causes of chronic diarrhea. Although none of the referred patients were found to have tumors, abnormal levels of one or more peptides were found in 86 of 193 patients (45%). Abnormal plasma peptide levels were sometimes as high in these patients as in patients with known peptide-secreting tumors and would have led to mistaken diagnoses of tumors much more often than they would have led to correct diagnoses. The positive predictive value of elevation of any assayed peptide was<2% at realistic prevalence rates for peptide-secreting tumors; the negative predictive value of a series of normal results was>99%, but much of this was due to the rarity of these tumors. Patients with chronic diarrhea should not be screened routinely with a panel of plasma peptide assays in an effort to detect tumors; instead, peptide levels should be ordered selectively. Elevated fasting concentrations of the plasma peptides measured in this study are most likely epiphenomena due to diarrhea and should not be the sole basis for invasive diagnostic or surgical management of these patients.

Loss of absorptive capacity for sodium chloride as a cause of diarrhea following partial ileal and right colon resection

Previous studies have emphasized the role of bile acid and fat malabsorption as the cause of the diarrhea that may follow ileal and right colon resection; unabsorbed bile acids and fat are believed to reduce sodium chloride and water absorption in the remaining colon. In this paper we report studies in eight patients with severe postresection diarrhea, in search of a more basic defect in sodium chloride absorption, ie, a loss of sodium chloride absorptive capacity as a direct consequence of resection of sodium chloride absorption sites. First, we determined whether or not diarrhea persisted during a 48-hr fast; in all patients diarrhea and large fecal electrolyte losses continued during a fast. Second, we measured sodium chloride and water absorption rates during total gut perfusion with a balanced electrolyte solution; compared to normal controls, the patients absorbed 23–31% less water, sodium, and chloride. In three patients who could be studied further, the absorptive defect was markedly accentuated when the perfusing solution was such that sodium chloride absorption had to take place against a concentration gradient. These observations indicate that postresection diarrhea patients have a reduced capacity to absorb sodium chloride, particularly when there is a concentration gradient between lumen and plasma. Although all of these patients had malabsorption of radiolabeled taurocholic acid, there was only a modest and statistically insignificant reduction in daily stool weight during treatment with large doses of cholestyramine, suggesting that bile acid malabsorption was not responsible for a major part of their diarrhea. We postulate that a loss of ileal and colonic absorptive capacity for sodium chloride rather than a cathartic effect of unabsorbed bile acids or fat is the major cause of diarrhea in these patients.

Somatostatin analog-induced remission of necrolytic migratory erythema without changes in plasma glucagon concentration.

A 41-year-old woman with metastatic glucagonoma and the characteristic disabling rash, necrolytic migratory erythema, was treated with a synthetic somatostatin analog while waiting to undergo curative surgical resection. Plasma glucagon concentration (1,500-3,300 pg/ml, normal <200) remained elevated during analog therapy as the rash cleared. Only with surgical resection (partial pancreatectomy and partial hepatectomy) did glucagon levels return to normal. The therapeutic benefit caused by the analog in this syndrome differs from that in other endocrine tumor syndromes such as pancreatic cholera, carcinoid, or gastrinoma where circulating levels of tumor-produced agents are suppressed in conjunction with control of symptoms.

Surreptitious Ipecac Administration Simulating Intestinal Pseudo-Obstruction

Excerpt Surreptitious administration of ipecac, presumably by a mother to her mentally retarded son, caused an illness that resembled intestinal pseudo-obstruction. Case Report An 18-year-old white...