Epidemiologic pattern of esophageal cancer at an inner-city university hospital.

The incidence of esophageal adenocarcinoma has increased significantly during the past 25 years in the United States and Europe. This increase has occurred predominantly among white men. To determine the effect of ethnicity and selected clinical features on the type of esophageal cancer in an urban, minority population, we retrospectively reviewed esophageal cancer at our institution. All patients with esophageal cancer from 1980 to 1995 were identified using the tumor registry data base and patient medical records at UMDNJ-University Hospital. Inclusion criteria were self-reported ethnicity and a confirmed pathologic diagnosis of either esophageal adenocarcinoma (ADENO) or squamous cell carcinoma (SCCA). Data abstracted from the record included age and year of diagnosis, weeks of survival, and risk factors, such as Barrett's esophagus and tobacco and alcohol abuse. Of 150 cases of esophageal cancer, 139 (93%) were SCCA and 11 (7%) were ADENO; the male:female ratio was 11:4. African and Latino Americans comprised 87% and white Americans 13% of the group. The incidence of ADENO increased during the study period: 1980-1984, 1 case; 1985-1989, 3 cases; and 1990-1995, 7 cases (P = .022); whereas the incidence of SCCA remained constant during the same intervals: 51, 52, and 36 cases, respectively (P > .05). By ethnicity, ADENO occurred more frequently among whites (7/19, 37%) than among African and Latino Americans (4/131, 3%); SCCA was more common among African and Latino Americans (127/131, 97%) than among whites (12/19, 63%) (P < .001). Other risk factors did not influence the type of esophageal cancer. The study concluded that the incidence of ADENO increased, primarily among white men, from 1980 to 1995 at UMDNJ-University Hospital. In contrast, the incidence of SCCA remained constant and was the primary type of esophageal cancer in African and Latino Americans. This study supports previous reports that ethnicity influences the histology of esophageal cancer.

Immunoproliferative small intestinal disease: case report and literature review.

Immunoproliferative small intestinal disease (IPSID) is a subtype of lymphoma of mucosa-associated lymphoid tissue. Notable for a high production of alpha-heavy chains, it is designated alpha-heavy-chain disease. IPSID is a debilitating disease that has a predilection for impoverished populations of developing countries. It has been documented primarily in subjects of Middle Eastern countries and thus was previously referred to as Mediterranean lymphoma. We report the case of a 42-year-old man from Senegal who presented with chronic diarrhea, dehydration, and weight loss. The endoscopic, pathologic, and serologic findings before, during, and after treatment with fludarabine phosphate are presented. We review the literature concerning current concepts on the etiology, pathogenesis, and management of IPSID.

Idiopathic esophageal ulceration in acquired immunodeficiency syndrome: successful treatment with misoprostol and viscous lidocaine.

OBJECTIVE: Esophageal ulceration is a common and important cause of morbidity in patients with acquired immunodeficiency syndrome (AIDS). After known causes are excluded, a subgroup remains with unexplained esophageal ulceration, known as idiopathic esophageal ulceration (IEU). The current therapy of IEU includes corticosteroids or, less frequently, thalidomide, although no placebo-controlled trials have been reported. The aim of this retrospective study was to determine the outcome of treating IEU with misoprostol and viscous lidocaine. METHODS: A retrospective review of esophageal ulceration in AIDS identified seven subjects with IEU at our institution. IEU in these subjects was treated successfully with misoprostol, 200 microg, crushed and suspended in 2% viscous lidocaine, 15 ml, given orally a.c. and h.s. for 4 wk. RESULTS: All patients reported symptomatic improvement within 2-3 days and complete resolution of their symptoms within 15 days. Healing of esophageal ulcerations was confirmed in five of seven subjects at a repeat endoscopy 8-12 wk later. CONCLUSIONS: Misoprostol, an antiulcer drug, has GI cytoprotective properties, and viscous lidocaine, a topical anesthetic, coats mucosal surfaces. We speculate that misoprostol when delivered topically is 3-6 times more effective than when delivered systemically. Considering the rapid resolution of symptoms, healing of ulcers, and lack of side effects, we believe that misoprostol crushed and suspended in viscous lidocaine should be considered for further evaluation in prospective, placebo-controlled trials of IEU.

Noncirrhotic portal hypertension in the adult: case report and review of the literature.

Noncirrhotic portal hypertension results from thrombosis of the extrahepatic portal vein that subsequently is recanalized. Liver function is preserved. In the adult, esophageal variceal hemorrhage is the most common presentation and may occur years after the portal vein thrombosis. We report the case of a 34-year-old man who presented with recurrent esophageal variceal hemorrhage. After ultrasonographic and angiographic evaluation, a diagnosis of idiopathic noncirrhotic portal hypertension was made. Due to recurrent esophageal variceal bleeding, the patient required surgical intervention to control bleeding. The incidence of noncirrhotic portal hypertension is unknown. Multiple etiologies may cause the disorder, although nearly half are idiopathic. The pathogenesis, clinical manifestations, diagnostic evaluation, natural history, prognosis, and management of noncirrhotic portal hypertension are discussed. Endoscopic management of esophageal variceal bleeding is the preferred therapy. However, when endoscopic treatment fails to control variceal hemorrhage, a distal splenorenal shunt is likely to be the most successful operation.

Use and safety of aspirin in the chemoprevention of colorectal cancer.

Colorectal cancer is the third leading cause of cancer-related mortality and a significant public health problem in the United States. Aspirin and other nonsteroidal anti-inflammatory drugs reduced the incidence of colorectal cancers and related mortality by 30% to 60% as well as the incidence of colonic adenomas. This effect is presumably due to an inhibition of cyclooxygenase 2, an inducible enzyme involved in the synthesis of prostaglandins. Prostaglandins are increased in colorectal neoplasms. Aspirin's effect appears to be dose related and enhanced by long-term exposure. Two prospective studies, however, failed to show a protective benefit of aspirin in colorectal cancer. When used long term, aspirin has significant adverse effects and is poorly tolerated. The gastrointestinal toxicity of aspirin is dose related, but even low doses of aspirin (75 mg per day) when used regularly result in significantly higher gastrointestinal toxicity, manifested by melena, hematemesis, and peptic ulcer disease, in aspirin users compared with nonusers. Furthermore, some studies indicate an increased risk of hemorrhagic strokes in aspirin users. Presently, aspirin should not be recommended for the primary chemoprevention of colorectal cancer in the general population due to significant risks of serious cerebrovascular and gastrointestinal adverse effects associated with long-term aspirin use.

Esophageal candidoma in a patient with acquired immunodeficiency syndrome.

Oral thrush and esophagitis caused by Candida are common in patients infected with the human immunodeficiency virus. We present the case of a 33-year-old man with acquired immunodeficiency syndrome who developed dysphagia during a hospitalization for pneumonia. Signs and symptoms were consistent with Candida esophagitis. Despite therapy with fluconazole, the patient's symptoms persisted. At upper endoscopy, a 1-cm, polypoid esophageal mass at 30 cm from the incisors and several other nodular lesions were observed; white plaques were noted throughout the esophagus. Biopsy specimens of the mass contained hyphal forms consistent with Candida species. Therapy with amphotericin B improved the patient's symptoms, and resolution of the mass was confirmed by repeat upper endoscopy. We believe this is the first case in the medical literature of a Candida mass (candidoma) causing dysphagia in a patient with acquired immunodeficiency syndrome. Candidoma should be considered in the differential diagnosis of dysphagia in patients with human immunodeficiency virus infection or immunosuppression due to other causes.

Gastrointestinal angiodysplasia.

Angiodysplasia of the gastrointestinal tract is common in the population 60 years of age and older and may be the cause of acute and/or chronic bleeding. Colonic angiodysplastic lesions are presumed to be degenerative in nature, secondary to either intermittent obstruction of the submucosal veins or hypoxemia. The pathogenesis of upper intestinal angiodysplasia is most likely related to a degenerative process. The clinical presentation varies from an incidental finding in an otherwise asymptomatic person to occult bleeding or an acute massive hemorrhage. Endoscopy and angiography are useful diagnostic modalities. Management options include surgery, endoscopic obliteration, or angiographic embolization of an identified bleeding angiodysplastic lesion(s). In a subset of patients who have angiodysplasia associated with Osler-Rendu-Weber disease or chronic renal failure, hormonal therapy with estrogen-progesterone may be efficacious.

Palliation of esophageal cancer with a self-expanding, silicone-covered stent and a technique for stent retrieval.

Most patients with carcinoma of the esophagus present with progressive, unrelenting dysphagia, malnutrition, and weight loss. Palliation is the primary treatment, since these patients are not candidates for curative surgical resection. Surgery, radiotherapy, and endoscopic modalities have been used for palliation. Recently, self-expanding, metallic stents have been used with considerable success. This type of stent can dislodge into the stomach during or after deployment. We report an approach to retrieve an expandable, silicone-coated stent using a double-channel endoscope, an esophageal dilating balloon, and a polypectomy snare.

Idiopathic esophageal ulceration in patients infected with human immunodeficiency virus.

Esophageal disease is a common and important cause of morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. The etiology of HIV-related esophageal ulceration varies. After all known etiologies are excluded, a subgroup of patients remains with esophageal ulceration known as idiopathic esophageal ulceration (IEU). Establishing a diagnosis of IEU is critical and precludes unnecessary treatment with antiviral, antifungal, or antibiotic agents. A review of the current literature indicates that there are no prospective, placebo-controlled, randomized, double-blind trials on the specific treatment of IEU. Several preliminary reports suggest that corticosteroids and thalidomide may be effective. The incidence and natural history of IEU are incompletely known. It is important to establish that any potential therapeutic agents employed to treat IEU do not increase viral replication or provide viral protection. There is a need for well-designed, placebo-controlled, prospective studies to assess the risks and benefits of corticosteroids, thalidomide, and other agents in the treatment of idiopathic esophageal ulceration.

Nasopancreatic drainage: a novel approach for treating internal pancreatic fistulas and pseudocysts.

Internal pancreatic fistulas are rare but debilitating complications of chronic pancreatitis. Fistulous tracts from the pancreatic duct to the peritoneal or pleural cavities have been treated by medical therapy and surgical management, with success rates of 41% and 89%, respectively. Endoscopic stent placement for internal and external pancreatic fistulas has also been shown effective. We report on three patients with histories of chronic alcohol abuse and pancreatitis. Two patients presented with dyspnea and pleuritic chest pain. Imaging studies revealed pleural effusions, and endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a patent fistulous tract from the pancreatic duct to the pleural cavity in each patient. Chemical analysis of the pleural fluid indicated pancreatic origin. The third patient, who had left-upper-quadrant abdominal pain and a small pleural effusion, had a large noncommunicating pseudocyst adjacent to the stomach. Nasopancreatic drains, along with chest tube drainage, were placed in the patients with pancreatic pleural fistulas. The patient with the pseudocyst received nasocystic drainage via the stomach. Drainage was measured until closure of the fistulas or cyst. Additionally, simply by injecting contrast medium, we were able to monitor the closure of fistulas without ERCP. The fistulas closed within 7 days, and the pseudocyst resolved within 14 days. Following discharge, all three patients were pain free, without evidence of recurrent fistulas or pseudocyst. In conclusion, the use of nasopancreatic/cyst drainage is an effective and convenient way to treat internal, communicating collections and pseudocysts of pancreatic origin. Furthermore, this method provides a simple means of assessing closure of fistulas and pseudocysts.

Drugs for treatment of peptic ulcers.

Pharmacologic management of peptic ulcer disease continues to evolve with the introduction of diverse types of new therapeutic agents. The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer, and delay ulcer recurrence. This article provides a broad perspective on the pharmacology and therapeutic actions of antiulcer drugs. To date, no drug meets all goals of therapy. Drug treatment of peptic ulcers is targeted at either counteracting aggressive factors or stimulating the mucosal defense. Drugs that inhibit or neutralize gastric acid secretion include histamine H2-receptor antagonists, proton pump inhibitors, anticholinergics, prostaglandins, and antacids. H2-receptor antagonists have become first-line drugs for treatment of uncomplicated duodenal ulcers, gastric ulcers, prevention of ulcer relapse, and mild esophagitis. However, H2-receptor antagonists, like other gastric antisecretory/antiulcer drugs, have high rates of ulcer recurrence following discontinuation of therapy. They therefore need to be administered continuously in patients prone to such recurrences. Omeprazole has emerged as a major drug for the treatment of severe erosive esophagitis, refractory ulcers, and Zollinger-Ellison syndrome. The major disadvantage of proton pump inhibitors is the concern for their long-term safety. The roles of M1-antimuscarinic agents and antacids have not been fully defined. Misoprostol, effective for the treatment of gastric and duodenal ulcers, is now the only drug that prevents ulcers induced by nonsteroidal anti-inflammatory drugs. Mucosal protective drugs that do not inhibit gastric acid secretion include sucralfate and organic bismuth salts. Sucralfate is a nonsystemic, well-tolerated, effective drug for treatment of duodenal ulcers and prevention of duodenal ulcer relapse. The organic bismuth salt bismuth subcitrate is efficacious in the treatment of duodenal and gastric ulcers. Furthermore, it has also been established that it alters the course of ulcer recurrence. However, bismuth encephalopathy is a major toxicity concern that needs to be addressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pigment gallstone disease.

Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease. The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates. At the pH of bile, this results in two monohydrogenated bilirubin anions that precipitate with calcium ions. Bilirubin monoconjugates that are increased in several conditions, such as Gilbert's syndrome and chronic hemolysis, may play a pivotal role in black stone formation as a source of unconjugated monohydrogenated bilirubin and as a possible co-precipitant with calcium. The precipitation of calcium carbonate and phosphate is influenced by local gallbladder factors. Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts. We used nb/nb mice with a chronic hemolytic anemia as a model of hemolysis-induced black stone disease. The presence of 40% bilirubin monoconjugates in mouse gallstones indicated the importance of this moiety in the pathogenesis of black stones. Other data obtained by marrow transplantation experiments in mice revealed the relative importance of genotype versus the hemolytic anemia on determinants such as biliary bile acid composition and mucin secretory glands in the mouse gallbladder neck. Additional physical chemical studies of the interaction of unconjugated bilirubin in model bile solutions will be helpful in further delineating the pathogenesis of both black and brown pigment gallstones.

Hepatitis and glomerulonephritis in secondary syphilis.

In early secondary syphilis, predominant features of spirochetal infection may include hepatitis and glomerulonephritis. We report a 27-year-old woman with characteristic physical, laboratory, and microscopic findings of syphilitic hepatitis and glomerulonephritis; she responded to penicillin therapy and recovered completely. The importance of clinically and pathologically recognizing this treatable disease is emphasized.

The apparent association constant of calcium and bilirubinate ions in Triton X-100 micelles.

Calcium bilirubinate [Ca(HB)2], a major component of pigment gallstones, rapidly precipitates from aqueous solutions, thereby precluding an accurate determination of the apparent association constant (K') of calcium (Ca2+ and monohydrogenated bilirubinate (HB) ions. In this study, we determine the K' in solutions of Triton X-100, a nonionic detergent with a critical micellar concentration of 0.01 g/dL, by analysis of spectral shifts, using a Hewlett-Packard diode array spectrophotometer. In the absence of Ca2+, 10 microM sodium bilirubinate (NaHB) solutions were incorporated into Triton X-100 micelles in 0.15 M NaCl, 0.10 M Tris Cl, pH 8, as evidenced by a progressive shift in the wavelength maximum (lambda max) of 10 microM HB from 438 to 458 nm in 0-0.1 g/dL (0-10 microM of micelles/L) Triton. Thus the lambda max plateau occurred with 1 mole of HB per micelle of Triton. As Ca2+, 0-90 microM, was added to 100 microM NaHB in 0.5 g/dL Triton X-100, there was a progressive downward shift in the lambda max of HB from 458 to 434 nm; an isosbestic point was present at 448 nm. A calibration curve using ratios of absorbance (Abs) 420/470 for known concentrations of Ca(HB)2 or NaHB was used to determine the mole fraction of Ca(HB)2. The spectral data were consistent with the equilibrium equation: Ca2+ + 2 HB = Ca(HB)2.(ABSTRACT TRUNCATED AT 250 WORDS)

Monoconjugated bilirubin is a major component of hemolysis-induced gallstones in mice.

The role of bilirubin conjugates in the formation of pigment gallstones is not known. In this study, we completely solubilized and then analyzed by high-performance liquid chromatography specimens of black pigment gallstones from eight nb/nb mice with hereditary hemolytic anemia. Each dried gallstone specimen of about 200 micrograms was dissolved in 5 ml of dimethyl sulfoxide/0.15 M HCI/50 mM disodium-EDTA (8:1:1 by volume) at room temperature. Stone dissolution was complete by 30 min as monitored by the A456 and direct observation, and no oxidative products of bilirubin were observed in the visible spectrum, 350 to 750 nm. By high-performance liquid chromatography, the intact tetrapyrroles were separated as diconjugated and monoconjugated bilirubins; unconjugated bilirubin was resolved as XIII, IX and III alpha-isomers. The isocratic solvent system used was 0.1 M di-n-dodecylamine acetate/0.1 M di-n-octylamine acetate (4:1, v/v) in methanol, pH 7.4, at a flow of 1 ml per min. Diconjugated bilirubin accounted for 6.0 +/- 2.4 molar % (mean +/- S.E.), monoconjugated bilirubin for 37.4 +/- 8.4% and unconjugated bilirubin for 56.3 +/- 8.9% of the solubilized pigments. The IX alpha-isomer represented 96 +/- 1.9% of the unconjugated bilirubin. The presence of bilirubin conjugates in gallstones was confirmed by ethylanthranilate diazotization: the conjugated azodipyrrole in stone had the same retention time as that of conjugated azodipyrrole from rat and mouse bile. A majority of the bilirubin conjugates was sensitive to beta-glucuronidase of liver origin, indicating that the C-1 glucuronide ester was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Milk of calcium bile. Evidence that gallbladder stasis is a key factor.

Milk of calcium bile is a rare disorder in which the gallbladder lumen is filled with a semisolid radiopaque material composed primarily of calcium carbonate. The etiology is unknown, although gallbladder stasis is believed to be a prerequisite. We report a case of milk of calcium bile in which preexisting gallbladder stasis was retrospectively evaluated by reviewing plain abdominal films and by using iodide as a marker for retained contrast. This latter approach was validated by demonstrating that obstructed gallbladders do not physiologically sequester iodide and that following oral cholecystography functioning gallbladders do not retain significant iodide for prolonged periods. In the case described, we propose that gallbladder stasis was present as long as 2 1/2 years prior to the diagnosis of milk of calcium bile.

The calcium ionophore A23187 stimulates glycoprotein secretion by the guinea pig gallbladder.

The purpose of this study was to examine the role of calcium ions in gallbladder glycoprotein secretion in cultured guinea pig gallbladder explants. The calcium ionophore A23187 showed a threshold of 2 micrograms per ml medium for stimulation of secretion of [3H]glucosamine-labeled glycoproteins over a 30 min incubation period. The ionophore at 3 and 5 micrograms per ml medium resulted in a 3- to 4-fold increase in secretion of [3H]glucosamine-labeled glycoproteins. Ionophore-induced stimulation of glycoprotein secretion was abolished by the addition of 0.01 mM verapamil to the medium. To study the effect of changes in extracellular calcium on basal glycoprotein secretion, explants were cultured for 24 hr in media with 0.007, 0.5 or 2.0 mM calcium; no differences in basal glycoprotein secretion were observed. When cultured in medium with 1.0 mM EGTA, basal secretion decreased significantly vs. controls in 0.007 mM total calcium medium. Total [3H]glucosamine incorporation by explants in medium with EGTA was unaltered, however, suggesting that the low level of calcium in the medium was selectively impairing the secretory process. These findings indicate that calcium ions are important in the regulation of gallbladder glycoprotein secretion.