Long-term follow-up of complete Barrett's eradication endoscopic mucosal resection (CBE-EMR) for the treatment of high grade dysplasia and intramucosal carcinoma.

BACKGROUND AND STUDY AIMS: In patients with Barrett's esophagus (BE), targeted endoscopic mucosal resection (EMR) of visible lesions of high grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) is effective, but carries the risk of leaving in place synchronous lesions and Barrett's epithelium with the potential for recurrent disease. We evaluated the safety and long-term efficacy of complete Barrett's eradication EMR (CBE-EMR) for the treatment of patients with HGD or IMC, independently of the presence of macroscopically visible lesions or surgical risk. PATIENTS AND METHODS: 26 consecutive patients with BE and HGD or IMC underwent CBE-EMRs, which were performed with the endoscopic cap suction method and/or a 2.3-mm monofilament mucosectomy snare. Endoscopic follow up after completion of resection was carried out to assess the rate of residual or recurrent BE with or without HGD or IMC. RESULTS: 24 patients completed the study. They underwent a total of 44 EMR sessions with a median of 3 pieces (range 1-8) removed per session. Two patients with immediate bleeding were successfully managed endoscopically. Three patients developed an early esophageal stricture that was completely resolved with a single endoscopic dilation. After a median follow-up of 28 months (range 15-51 months), persistent endoscopic and histologic eradication of BE was demonstrated in 21 patients (87.5 %). In two patients, Barrett's epithelium was detected beneath the neosquamous epithelium 3 months after completion of the resection. In the remaining patient, IMC was found in a nodule seen and removed by EMR at 12-month surveillance endoscopy. CONCLUSIONS: CBE-EMR is a safe and highly effective long-term treatment that should be offered to all patients with Barrett's esophagus with HGD and IMC.

Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia.

BACKGROUND: Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades. To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study. METHODS: The study included 554 subjects newly diagnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric adenocarcinomas, and 695 control subjects. Estimates of risk (odds ratios [ORs] and corresponding 95% confidence intervals [CIs]) were calculated for the four tumor types separately and for esophageal and gastric cardia adenocarcinomas combined. RESULTS: Risk of esophageal and gastric cardia adenocarcinomas combined was increased among current cigarette smokers (OR = 2.4; 95% = 1.7-3.4), with little reduction observed until 30 years after smoking cessation; this risk rose with increasing intensity and duration of smoking. Risk of these tumors was not related to beer (OR = 0.8; 95% CI = 0.6-1.1) or liquor (OR = 1.1; 95% CI = 0.8-1.4) consumption, but it was reduced for drinking wine (OR = 0.6; 95% CI = 0.5-0.8). Similar ORs were obtained for the development of noncardia gastric adenocarcinomas in relation to tobacco and alcohol use, but higher ORs were obtained for the development of esophageal squamous cell carcinomas. For all four tumor types, risks were higher among those with low income or education. CONCLUSIONS: Smoking is a major risk factor for esophageal and gastric cardia adenocarcinomas, accounting for approximately 40% of cases. IMPLICATIONS: Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.

Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia.

BACKGROUND: Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. METHODS: Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. RESULTS: The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. CONCLUSIONS: Increasing prevalence of obesity in the United States population may have contributed to the upward trends in esophageal and gastric cardia adenocarcinomas.

Localization and expression of p27KIP1 in multistage colorectal carcinogenesis.

The cyclin-dependent kinase inhibitor p27Kip1 can inhibit the G1 to S transition of the cell cycle and is a putative tumor suppressor. However, our laboratory found that a variety of human cancer cell lines express relatively high levels of this protein and that this is often associated with increased expression of cyclin D1 or cyclin E. Therefore, in the present study we analyzed by immunohistochemistry the expression of p27Kip1 in a series of human tissue samples representing various stages of colon carcinogenesis, using 20 samples of normal colon mucosa, 20 hyperplastic polyps, 19 samples of adenomatous polyps, and 40 samples of various types of colorectal carcinomas. Parallel immunostaining was done for cyclin D1 and also for Ki67 to evaluate cell proliferation. An additional 17 human colon carcinoma samples, together with paired adjacent normal mucosa samples, were analyzed for levels of expression of the p27Kip1 protein by Western blot analysis, and 7 of these pairs of samples were examined by Northern blot analysis for levels of p27Kip1 mRNA. We did not find a positive or negative correlation between p27Kip1 expression and cell proliferation in the normal mucosa and tumor samples. There was, however, an inverse correlation between p27Kip1 and Ki67 expression in the lymphoid follicles present in the colonic mucosa. There was no evidence for a consistent increase or decrease in p27Kip1 expression in the mucosal cells during colon carcinogenesis, because the mean values for percentage p27Kip1-positive cells were similar in the normal mucosa, adenomatous polyps, and carcinoma samples. This is in contrast to Ki67 and cyclin D1 expression, which did show significant increases in mean values with tumor development. A subset (35%) of the carcinomas displayed diffuse cytoplasmic staining, in addition to nuclear staining, for p27Kip1, and in these cases the percentage of cells that were positive for p27Kip1 was higher than in cases that had only nuclear staining. There was a significant correlation between p27Kip1 expression and tumor grade; ie., well and moderately differentiated carcinomas had high p27Kip1 expression, whereas poorly differentiated carcinomas had lower expression. The Western blot analysis data on p27Kip1 expression confirmed this correlation. Comparisons of Northern and Western blots did not show a correlation between the level of p27Kip1 mRNA and the corresponding protein, a finding consistent with evidence that the p27Kip1 protein is regulated mainly via a posttranscriptional mechanism. The immunostaining studies revealed a significant correlation between high p27Kip1 protein expression and high cyclin D1 expression in the adenomatous polyps and in the subset of carcinomas that had only nuclear p27Kip1 expression. This may reflect the existence of a homeostatic feedback mechanism that is lost in the high-grade carcinomas that express low levels of p27Kip1.

An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma.

Gastric colonization with Helicobacter pylori, especially cagA+ strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA+ strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA- strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA+ strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries.

Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings.

Although the small intestine contains 75% of the mucosal surface of the gastrointestinal tract, it is the site of only 2% as many malignancies as the large bowel. The association of Crohn's disease with small intestine adenocarcinoma is well known, but the analytic epidemiology of small intestine malignancies has not received much attention. We reviewed the medical records of 19 patients with adenocarcinoma and 17 with malignant carcinoids identified from the Columbia-Presbyterian Medical Center Tumor Registry in the years 1980-1987. These were compared with 52 controls with nonmalignant conditions from the same time period. Three adenocarcinoma patients but no carcinoid patients or controls had previous Crohn's disease (P < 0.004). Three adenocarcinomas and three carcinoids, but no controls, had previous cholecystectomy (P < 0.004). Previous peptic ulcer disease was recorded for two patients with adenocarcinoma and three with carcinoid but no controls (P < 0.02, P < 0.0002). The age and sex adjusted odds ratio for cigarette smoking was 4.6 (95% confidence interval, 1.0-20.7) for adenocarcinomas and 4.2 (0.8-22.4) for carcinoids. The adjusted odds ratio for alcohol consumption was 4.0 (1.0-15.9) for adenocarcinomas and 3.1 (0.7-13.9) for carcinoids. Further studies are warranted to confirm these associations and to identify potential protective factors in the small intestine.

Increased expression of the cyclin D1 gene in Barrett's esophagus.

Previous studies have found a 3-10-fold amplification and overexpression of the cyclin D1 gene in about 32% of human esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of increased expression of the cyclin D1 protein in Barrett's esophagus. Using 69 formalin-fixed and paraffin-embedded human esophageal specimens, which had been removed endoscopically or obtained at surgery during 1993 and 1994, all immunohistochemical analyses were performed using an avidin-biotin complex immunoperoxidase technique. Increased nuclear expression of the cyclin D1 protein was noted in 32 of 69 samples (46%; 44% of the samples from males and 50% of the samples from females). Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women. Nuclear accumulation of the cyclin D1 protein was also found in both dysplastic and nondysplastic lesions, and it was not associated with sex, age, or cigarette or alcohol consumption. Samples from patients taking proton pump inhibitors tended to be less frequently positive (32%) for cyclin D1 nuclear staining when compared to patients taking H2 antagonists (45%) or antacids (55%). These studies suggest that increased expression of cyclin D1 is an early event in the tumorigenic process of esophageal adenocarcinomas and that the increased expression of this gene might predispose the epithelium to malignant transformation.

Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.

Regular users of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are at reduced risk of colon cancer, but the evidence for protective effects of NSAIDs elsewhere in the digestive tract is scant. We investigated the association between the use of NSAIDs and risk of esophageal and gastric cancer, using data from a large population-based, case-control study. Cases were individuals, ages 30-79 years, diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or noncardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were selected by random digit dialing and through the rosters of the Health Care Financing Administration. After controlling for the major risk factors, we found that current users of aspirin were at decreased risk of esophageal adenocarcinoma [odds ratio (OR), 0.37; 95% confidence interval (CI), 0.24-0.58], esophageal squamous cell carcinoma (OR, 0.49; 95% CI, 0.28-0.87), and noncardia gastric adenocarcinoma (OR, 0.46; 95% CI, 0.31-0.68), but not of gastric cardia adenocarcinoma (OR, 0.80; 95% CI, 0.54-1.19), when compared to never users. Risk was similarly reduced among current users of nonaspirin NSAIDs. The associations with current NSAID use persisted when we excluded use within 2 or 5 years of reference date, which might have been affected by preclinical disease in cases, and when we restricted analyses to subjects reporting no history of chronic gastrointestinal symptoms. Our findings add to the growing evidence that the risk of cancers of the esophagus and stomach is reduced in users of NSAIDs, although whether the association is causal in nature is not clear.

Risk of esophageal and gastric adenocarcinomas in relation to use of calcium channel blockers, asthma drugs, and other medications that promote gastroesophageal reflux.

Incidence of adenocarcinomas of the esophagus and gastric cardia has risen dramatically over the past 2 decades in the U. S., for reasons that are not yet clear. A number of common medications (e.g., calcium channel blockers, tricyclic antidepressants, and certain asthma medications) promote gastroesophageal reflux by relaxing the lower esophageal sphincter (LES). Reflux is thought to increase cancer risk by promoting cellular proliferation, and by exposing the esophageal epithelium to potentially genotoxic gastric and intestinal contents. Recent studies have suggested that calcium channel blockers may also increase cancer risk by inhibiting apoptosis. Using personal interview data from a multicenter, population-based case-control study conducted between 1993 and 1995 in three areas of the U. S., we evaluated whether the use of LES-relaxing drugs was associated with increased risk of adenocarcinomas of the esophagus and gastric cardia. Cases of esophageal adenocarcinoma (n = 293) and gastric cardia adenocarcinoma (n = 261) were compared with general population controls (n = 695). Information on additional case groups of esophageal squamous cell carcinoma (n = 221) and noncardia gastric cancer (n = 368) were also available for comparison. Overall, 27.4% of controls had used one or more of these drugs for at least 6 months, compared with 30.2% of esophageal adenocarcinoma and 23.8% of gastric cardia adenocarcinoma cases. The adjusted odds ratios (ORs) for ever use were 1.0 [95% confidence interval (CI) = 0.7-1.5] and 0.8 (95% CI = 0.5-1.1), respectively. There was little evidence of increasing risk with increasing duration of use of all LES-relaxing drugs together. We found an increased risk of esophageal adenocarcinoma among persons reporting use of asthma drugs containing theophylline (OR = 2.5; 95% CI = 1.1-5.6) or beta agonists (OR = 1.7; 95% CI = 0.8-3.8). Risks were higher among long-term users (>5 years) of these drugs (OR = 3.1; 95% CI = 0.9-10.3 and OR = 2.3; 95% CI = 0.8-7.0, respectively). In contrast, there was no evidence that the use of calcium channel blockers or other specific groups of drugs increased the risk of any of the cancers studied. These results provide reassuring evidence that the increases in incidence of adenocarcinomas of the esophagus and gastric cardia are not likely to be related to the use of LES-relaxing drugs as a group, or calcium channel blockers in particular, but they do suggest that persons treated for long-standing asthma may be at increased risk of esophageal adenocarcinoma.

Nutrient intake and risk of subtypes of esophageal and gastric cancer.

Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and noncardia gastric adenocarcinoma (n = 352), along with population controls (n = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk.

Tissue diagnosis of selected AIDS-related opportunistic infections.

Opportunistic infections are the most common initial manifestations of AIDS and, in many instances, are first encountered in surgical specimens. Pneumocystis carinii pneumonitis is by far the most frequent infection seen in biopsy specimens of AIDS patients. Most pathologists are familiar with its histopathologic presentations from previous experience. By contrast, many other opportunistic infections are either new or present clinically and pathologically in unfamiliar ways. Cytomegalovirus affects primarily the alimentary tract and lung. Colitis is the most common presentation. Penetrating ulcers may perforate. Most often, mesenchymal cells, endothelium in particular, show the typical intranuclear and intracytoplasmic inclusion bodies. The greater the number of inclusion bodies in tissues the shorter is the survival of the patient. Mycobacterium avium-intracellulare affects mainly small intestine and lymph nodes and produces a clinical and histologic picture similar to that of Whipple's disease. Diffuse infiltrates of histiocytes stuffed with acid-fast bacilli are characteristic. Cryptosporidiosis is the most ominous enteric opportunistic infection. Protozoa attach themselves to the epithelial surface and produce severe profuse, watery diarrhea. Cryptococcosis is seen in lung, lymph node, and brain biopsy specimens. Large numbers of organisms, sometimes with deficient mucinous capsules, and little or no inflammatory reaction, are notable. Toxoplasmosis is the most common cause of neurological complications in AIDS. Brain biopsy specimens show necrosis, microglial nodules, perivascular lymphocytic infiltrates, and, in 50% of cases, trophozoites.

Biopsy diagnosis of colitis: possibilities and pitfalls.

The histopathologic diagnosis of inflammation is common in colorectal biopsies but is of limited value, if not further specified. We reviewed 280 endoscopic colorectal biopsy specimens for nonneoplastic disease from 100 consecutive patients in order to assess (a) the frequency of inflammation in excess of the physiologic infiltrate, (b) the frequency with which the cause of the inflammation could be specified, and (c) the interobserver variability in diagnosing inflammation. Based on the reviewers' impression, each case was classified into one of three categories: (I) normal or nonspecific change, (II) nonspecific inflammation, and (III) inflammation suggestive or diagnostic of specific cause. Inflammation was diagnosed in 68% of cases. The majority of these cases (75%) showed features typically associated with specific types of colitis, including Crohn's disease (n = 16), ulcerative colitis (n = 13), inflammatory bowel disease not otherwise specified (n = 5), infectious colitis (n = 6), ischemic colitis (n = 4), solitary rectal ulcer syndrome (n = 3), radiation colitis (n = 2), and lymphocytic colitis (n = 2). Interobserver variability was greatest in biopsy specimens interpreted by the reviewers as normal or showing nonspecific changes, most of which had been diagnosed as mild inflammation by the original pathologists. Etiologic classification of colitis was lacking in 59% of the cases interpreted by the reviewers as suggestive or diagnostic of a specific cause. We conclude that (a) the majority of colorectal biopsy specimens from patients with nonneoplastic disease in this series show inflammation, (b) the majority of such cases allow a specific cause of colitis to be suggested or firmly diagnosed, and (c) pathologists tend to overdiagnose the physiologic inflammatory infiltrate as evidence of colitis and underdiagnose specific etiologic types of colitis.

Mixed (composite) glandular-endocrine cell carcinoma of the stomach. Report of a case and review of literature.

A case of mixed (composite) glandular-endocrine cell carcinoma of the stomach is presented. Whereas the admixture of rare endocrine cells in ordinary adenocarcinoma of the stomach is a rather frequent occurrence, gastric tumors with an approximately equal proportion of glandular and endocrine cells are rare, and only 20 well-documented cases have been reported. Our case is unique in its range of histopathologic patterns, including well-differentiated and poorly differentiated adenoendocrine carcinoma as well as amphicrine differentiation. Immunohistochemical and electron microscopic findings are documented and the clinical characteristics of all reported cases tabulated. From the limited experience of these 21 cases, glandular-endocrine carcinoma of the stomach is found to have the following clinicopathologic features: It affects adults aged 32 to 74 years, (mean, 52.5 years) and has a male:female ratio of 1.3:1. It is located with almost equal frequency in the gastric body and antrum and has a poor prognosis, similar to that of advanced ordinary gastric carcinoma.

Cytomegaloviral and cryptosporidial cholecystitis in two patients with AIDS.

We report two cases of acalculous cholecystitis due to infection with cytomegalovirus (CMV) and cryptosporidium. Both involved homosexual men who presented with right upper quadrant pain and elevations of serum alkaline phosphatase and bilirubin. Cholecystectomy specimens showed a thickened gallbladder wall and ulcerated mucosa. There were no stones. CMV inclusion bodies were found in granulation tissue at the base of ulcers and intact mucosa surrounding ulcers. Cryptosporidia were aligned along the luminal surface of intact mucosal epithelial cells. Both organisms have a patchy distribution; hence the diagnosis requires a high degree of suspicion. The prognosis is poor. Following cholecystectomy, both patients pursued a downhill course with development of pancreatitis and cholangitis. Both patients are now dead.

Transluminal laser catheter angioplasty.

The first transluminal laser angioplasty in animals is reported herein. An Argon laser and a specialized coronary arterial catheter with a fiberoptic wave guide were used. Immediate histologic changes consisted of a moderate degree of intimal necrosis and some loss of elastic tissue. At 5 days the intima was repaired, but focal elastic tissue loss persisted.

Laser coronary angioplasty: experience with 9 cadaver hearts.

Experience with laser angioplasty in 16 coronary arteries in 9 cadaver hearts is presented. Coronary obstructions were due to experimentally created thrombi as well as to naturally occurring calcified plaques. Successful laser angioplasty was achieved in 14 of 15 arteries. One artery was sacrificed to determine factors necessary for deliberate perforation of the arterial wall. This procedure required more than 30 seconds of laser energy at 3.0 W with the catheter tip almost perpendicular to the wall. Penetration of the arterial wall occurred only in the second left anterior descending artery which was plaque-occluded because of operator inexperience.

Gastrointestinal disease in the immunocompromised patient.

Gastrointestinal (GI) disease is frequent in all types of immunocompromised patients but occurs with greatest frequency in patients with acquired immunodeficiency syndrome (AIDS). Thus, much of this review deals with human immunodeficiency virus (HIV)-related GI diseases. Gastrointestinal diseases in other immunocompromised patients are compared with those in patients with AIDS. Conditions unique to transplant recipients, such as graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLDs), are discussed separately. We have divided these GI diseases into four main categories: (1) HIV-related inflammatory conditions other than opportunistic infections (HIV-related enteropathy, proctocolitis, and CD8 lymphocytosis); (2) inflammatory conditions unrelated to HIV or opportunistic infections (neutropenic enterocolitis, regional enteritislike enteropathy, and GVHD); (3) opportunistic infections (illnesses caused by herpesvirus, cytomegalovirus, and miscellaneous other viruses; Mycobacterium, Candida, Histoplasma, Cryptococcus, Cryptosporidium, Microsporida, Isospora, Leishmania, Toxoplasma and Strongyloides organisms as well as Pneumocystitis carinii; and (4) neoplasias (Kaposi's sarcoma [KS], AIDS-related non-Hodgkin's lymphoma [NHL], HIV-related Hodgkin's disease [HD], PTLDs, and miscellaneous neoplasms). The prevalence, pathogenesis, clinical manifestations, gross pathological findings, and microscopic features of each disease entity are discussed.

Intestinal microsporidiosis as a cause of diarrhea in human immunodeficiency virus-infected patients: a report of 20 cases.

Chronic diarrhea accompanied by weight loss is a common and often debilitating problem associated with human immunodeficiency virus (HIV) infection. Enterocytozoon bieneusi, a newly identified species of the phylum of protozoa, Microspora, has been reported associated with chronic diarrhea and wasting in 11 acquired immunodeficiency syndrome (AIDS) patients in the United States, Europe, and Africa. Diagnosis has been based solely on the ultrastructural identification of this small, intracellular parasite in bowel biopsies. Seventy-one small bowel biopsies from 67 homosexual AIDS and AIDS-related complex patients with chronic diarrhea and with no pathogens identified by light microscopy on paraffin sections, were embedded in plastic and studied by light and transmission electron microscopy. Enterocytozoon bieneusi microsporidiosis was diagnosed by electron microscopy in 20 (22 biopsies) of the patients. More jejunal biopsies (16 of 36) were positive than duodenal biopsies (six of 35). Parasites and spores were clearly visible at the light microscopic level in the semi-thin plastic sections from 17 and 21 of the biopsies, respectively. In retrospect, parasites could be identified by light microscopy in standard hematoxylin and eosin-stained paraffin sections. Infection was confined to enterocytes covering the villi, especially the tips, and was associated with villous atrophy and cell degeneration, necrosis, and sloughing. Release of spores into the bowel lumen was evident. Colorectal biopsies from two of the patients with small bowel microsporidiosis were negative for microsporidia. Enterocytozoon bieneusi infection of the small bowel may be an important cause of diarrhea in HIV-infected persons.

Solitary splenic metastasis of an adenocarcinoma of the lung.

Splenic metastasis of solid tumors is a rare event, most often diagnosed at the time of autopsy. Whereas in cases of widely disseminated cancer, splenic involvement may be fairly common, solitary splenic metastasis in the absence of other metastases is exceedingly rare. The authors report a case of a 63-year-old woman in whom the sole detectable distant metastasis of a lung carcinoma was a splenic mass. The splenic lesion was detected before the resection of the primary lung lesion during a complete metastatic work-up. At that time, however, it was considered unlikely that the mass in the spleen represented a metastasis because of the lack of metastatic disease elsewhere.

Microgranulomas in grossly normal rectal mucosa in Crohn's disease.

Rectal biopsies of sigmoidoscopically normal mucosa from 99 patients with Crohn's disease of the ileum, colon, or both were studied histologically, with particular reference to the presence of granulomas. Among the 14 cases of granulomas, some were of the usual sarcoid type and could easily be detected. Other microgranulomas were less well defined and were found only by mid- or high-power microscopic screening of serial sections. The morphologic characteristics, the relationship to ordinary Crohn's-disease granulomas and the possible significance of microgranulomas are discussed.