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Biomedical subjects

K J Lewin

Publications and source records attributed to K J Lewin.

At least 37 records · Page 2Linked to original sources

Studies of esophageal balloon cytology in Linxian, China.

Esophageal cancer is the second leading cause of cancer death in China. Esophageal cancer has a very poor prognosis, principally because most tumors are asymptomatic until they are unresectable. Esophageal balloon cytology is an early detection method developed by Chinese scientists to identify resectable early cancers and precursor lesions. Previous studies have reported high sensitivities for detecting esophageal cancer in symptomatic patients. The current report describes several studies evaluating this diagnostic technique in asymptomatic individuals. A comparison of Chinese and U. S. cytological diagnoses of the same esophageal samples showed that the Chinese categories of precancerous neoplasia were more inclusive than the corresponding U. S. categories. Comparisons of both Chinese and U. S. cytological diagnoses with concurrent histological findings showed low (14-36%) sensitivities for the cytological detection of biopsy-proven cancers. Prospective follow-up studies of several screened cohorts showed a consistent progression of risk for developing esophageal cancer with increasing severity of initial cytological diagnosis. These preliminary studies suggest that esophageal balloon cytology is a useful technique that can benefit from additional research to improve its optimal performance.

Adult↗

Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation.

OBJECTIVE: To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR). METHODS: We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries. RESULTS: Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long-term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients. CONCLUSIONS: Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.

Acute Disease↗

Clear cell carcinoid tumor of stomach. A variant mimicking gastric xanthelasma.

We report a rare case of gastric carcinoid composed entirely of clear cells with foamy cytoplasm. The patient was a 75-year-old Hispanic woman with atrophic fundic (oxyntic) gland gastritis leading to hypochlorhydria, secondary hypergastrinemia, endocrine cell hyperplasia, and multiple gastric carcinoids. Grossly, the lesion was yellow and distinct from other carcinoids in the gastric mucosa, mimicking gastric xanthelasma. Histologically, the tumor consisted of uniform clusters of polygonal cells with foamy cytoplasm. The formation of cell packets and abundant vascular stroma provided clues to its neuroendocrine nature. This was confirmed by immunoreactivity for chromogranin A and the demonstration of dense core granules ultrastructurally.

Aged↗

Metaplastic columnar cells in Barrett's esophagus: a common and neglected cell type.

Goblet cells are considered by most to be a prerequisite for the diagnosis of Barrett's esophagus. Columnar cells that are alcian blue (AB) positive (as are goblet cells) are commonly observed in the surface epithelium of Barrett's esophagus, but their distribution in relation to goblet cells has not previously been defined. The authors analyzed the prevalence and distribution of these cell types in the surface but not pit epithelium (where they may sometimes be present in normal gastric mucosa). The distribution of the AB-positive columnar cells was mapped out in the entire mucosa of nine esophagectomy specimens, resected for Barrett's-associated high-grade dysplasia or carcinoma, and compared with other cell types, especially goblet cells. AB-positive goblet and columnar cells were present in 87.1% +/- 5.6% and 85.7% +/- 5.9%, respectively, of the evaluated sections of Barrett's mucosa, whereas gastric-type, AB-negative cells were observed in 46.3% +/- 8.7% of the sections. In 53% of the sections, the surface epithelium contained more than 25% AB-positive cells, and in more than three quarters of these sections, AB-positive columnar cells were the dominant AB-positive cell type. No difference in the distribution of the AB-positive epithelial cells was noticed between the proximal and distal halves of the Barrett's mucosae. In the cardia region, seven of nine cases showed a few scattered AB-positive columnar cells, and five of nine cases showed a few scattered goblet cells. No AB-positive cells were found in fundic gland mucosa. These findings indicate that the metaplastic AB-positive columnar cells are more prevalent than goblet cells. They may be analogous to incomplete metaplastic cells of the stomach, and, therefore, their role in the development of neoplasia needs further study.

Aged↗

Veno-occlusive disease of the small bowel. An entity in search of identity.

Veno-occlusive disease of the bowel is a rare entity, and, to our knowledge, only two studies have been reported in the literature; these reports describe 11 patients with veno-occlusive disease of the small and large bowels. We describe a patient who developed veno-occlusive disease of the small bowel, whose histologic findings were somewhat different from those previously reported.

Adult↗

Pancreatic polypeptide immunoreactivity in sporadic gastrinoma: relationship to intraabdominal location.

Sporadic gastrinoma is a pancreatic endocrine tumor whose ontogeny is unknown. The anatomic area where the vast majority of sporadic gastrinomas is found (pancreatic head region) corresponds topographically to the area traversed embryologically by the ventral pancreatic bud. Pancreatic polypeptide (PP), a 36-amino acid hormone, is secreted by pancreatic endocrine cells derived almost exclusively from the ventral pancreatic bud and is proposed as a marker for ventral bud derivation. Based on these observations we postulate that sporadic gastrinomas, found around the head of the pancreas, are derived from ventral bud tissue and should display a high incidence of PP immunoreactivity. Overall, we found PP immunoreactivity in 7 of 14 (50%) gastrinomas. Of those tumors located to the right of the superior mesenteric artery (SMA) (around the head of the pancreas), seven of nine (78%) contained PP, whereas no gastrinoma to the left of the SMA (n = 5) contained PP (p = 0.021; Fisher exact test). Only one other pancreatic endocrine or exocrine tumor, a glucagonoma located to the left of the SMA, stained positively for PP. We conclude that sporadic gastrinomas found around the head of the pancreas (to the right of the SMA) have a high incidence of PP immunoreactivity. These findings are consistent with our hypothesis that sporadic gastrinomas are derived from the ventral pancreatic bud.

Gastrinoma↗

Pathologist-gastroenterologist interaction. The changing role of the pathologist.

The importance of interaction between clinicians and pathologists is examined in the setting of gastroenterology and gastrointestinal disease, and the importance of communication is emphasized. The endoscopist must provide the pathologist with information about the patient, including results of the gross examination, biopsy location, relevant clinical history, bowel preparation, and current medications. The pathologist must provide a reproducible and useful report that answers the clinical questions posed by the endoscopist. This consultation between the gastroenterologist and pathologist provides the framework for proper patient care.

Gastroenterology↗

Squamous esophageal histology and subsequent risk of squamous cell carcinoma of the esophagus. A prospective follow-up study from Linxian, China.

BACKGROUND: Linxian, China, has some of the highest rates of esophageal cancer in the world. Previous authors have proposed that esophagitis, atrophy, and dysplasia may be precursor lesions of esophageal cancer in such high risk populations. METHODS: To examine the relationship between squamous esophageal histology and subsequent esophageal cancer in Linxian, the authors prospectively followed 682 participants of a 1987 endoscopic survey for 3.5 years and compared their initial biopsy diagnoses with the occurrence of squamous cell carcinoma during this follow-up period. RESULTS: Squamous cell carcinoma of the esophagus was identified in 52 (7.6%) of the participants during the follow-up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for squamous cell carcinoma incidence by initial histologic diagnoses were as follows: normal, 1.0 (reference); basal cell hyperplasia, 2.1 (0.4-9.8); mild dysplasia, 2.2 (0.7-7.5); moderate dysplasia, 15.8 (5.9-42.2); severe dysplasia, 72.6 (29.8-176.9); dysplasia not otherwise specified, 22.9 (6.7-78.0); and carcinoma in situ, 62.5 (24.1-161.9). CONCLUSION: In this study, moderate dysplasia, severe dysplasia, and carcinoma in situ were the only histologic lesions associated with a significantly increased risk of developing squamous cell carcinoma of the esophagus within 3.5 years after endoscopy. Increasing grades of dysplasia were associated with increasing risk, but severe dysplasia were associated with increasing risk, but severe dysplasia and carcinoma in situ had similar degrees of risk, findings that suggest a continuous spectrum of esophageal intraepithelial neoplasia, without morphologically distinguishable dysplasia and in situ carcinoma. A longer follow-up will be necessary to fully evaluate the less severe diagnostic categories, which may take more than 3.5 years to affect the occurrence of squamous cell carcinoma in this high risk population.

Adult↗

Esophageal morphology from Linxian, China. Squamous histologic findings in 754 patients.

BACKGROUND: Linxian, China, has one of the highest rates of esophageal cancer in the world. Other authors have described high prevalences of histologic esophagitis, atrophy, and dysplasia in Linxian and have suggested that these findings may represent precancerous lesions in this population. In 1987, a new endoscopic survey allowed the authors to make an independent study of esophageal histology in Linxian. METHODS: There were 1567 satisfactory squamous esophageal biopsies available from 754 patients. These biopsies were classified as normal, atrophy, acanthosis, esophagitis, squamous dysplasia, or squamous cancer. RESULTS: Classified by their worst diagnosis, 56.5% of the 754 patients had normal mucosa, 0.0% atrophy, 11.5% acanthosis, 4.6% esophagitis, 22.7% squamous dysplasia, and 4.6% squamous cancer. CONCLUSIONS: The results show a different distribution of esophageal squamous diagnoses than has been reported previously from this population. The authors believe that the major reason for this discrepancy was differences in histologic criteria. In this survey, seemingly small differences in criteria could cause large differences in apparent disease prevalence; this was especially true for esophagitis. By the criteria used in this study, histologic esophagitis and atrophy are uncommon findings in Linxian, raising questions about their significance as precursor lesions of esophageal cancer in this population.

Biopsy↗

Gastric heterotopia in the upper esophagus (inlet patch) in endoscopic surveys in northern China.

Upper esophageal gastric heterotopia (inlet patch) has not been reported in endoscopic series from China. We describe the occurrence of endoscopically and histologically typical inlet patches in two endoscopic surveys of asymptomatic adults in northern China. Because rapid endoscopic protocols were used, the 0.3-0.4% prevalence of inlet patch in these surveys probably represents a minimum figure for adults in this population.

Adult↗

Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the General Population Trial in Linxian, China.

A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.

Adenocarcinoma↗

Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the Dysplasia Trial in Linxian, China.

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Liver allograft pathology.

Complications following orthotopic liver transplantation are often difficult to differentiate from each other. Based on their experience with more than 1,800 transplantations, the authors strive to describe the varied histologic appearances of allograft injuries and how they differ.

Graft Rejection↗

Correlation of epithelial proliferation and squamous esophageal histology in 1185 biopsies from Linxian, China.

Epithelial proliferation is an active area of research in gastrointestinal cancer, but only a few studies have examined the relationship of esophageal epithelial proliferation and squamous histologic findings in populations with high rates of squamous esophageal cancer. In order to study this correlation, tritiated thymidine labeling was performed on 1185 esophageal biopsies from 745 residents of Linxian, China, a county with some of the highest esophageal-cancer rates in the world. Total labeling index (TLI = total labeled cells/total cells counted) was used to measure the amount of proliferation, and the proportion of labeled cells found in cell layers 4 to 10 (labeled cell fraction 4 plus, LF4+ = labeled cells in layers 4-10/total labeled cells) was used to measure the vertical distribution of proliferation. Of the biopsies, 979 were histologically normal, 51 showed acanthosis, 35 showed esophagitis, 116 showed squamous dysplasia, and 6 showed invasive squamous cancer. The mean values of both proliferation variables, stratified by histologic diagnosis, showed the following relationships: normal = acanthosis < esophagitis = dysplasia < cancer. The ranges of proliferation values overlapped extensively in all biopsy categories, so that measuring proliferation could not substitute for histologic diagnosis. It remains to be seen whether proliferation values, histologic diagnoses, or some combination of these methods is most predictive of subsequent esophageal cancer.

Adult↗

Effect of long-term colchicine therapy on jejunal mucosa.

Colchicine is recommended as daily prophylactic therapy in patients with familial Mediterranean fever (FMF) to prevent febrile paroxysms. The drug is known to be a potent inhibitor of mitotic activity and might therefore be expected to have a significant adverse effect on tissues that undergo rapid turnover. We studied small bowel biopsies from nine patients with FMF who were receiving daily low-dose oral colchicine therapy. In each patient the lengths of 20 crypts and villi were measured and the number of mitotic figures in 20 crypts were counted. The data were compared with similar measurements from histologically normal-appearing biopsies obtained from 14 patients with a variety of mild gastrointestinal complaints. The mean crypt length was found to be significantly greater (0.197 mm vs 0.186 mm, P < 0.0001) and the mean villous length significantly smaller (0.369 mm vs. 0.442 mm, P < 0.0001) in the FMF patients than in the control population. In addition, the mean number of mitotic figures per crypt was significantly higher in the FMF patients (2.58 vs 1.00, P < 0.001). The data reveal a pattern of mucosal injury in the colchicine-treated FMF patients characterized by a hyperplastic crypt-villous atrophy pattern with increased mitotic rate, which is indicative of an increase in cell turnover and opposite to what we anticipated based on colchicine's known effect on mitotic activity.

Adult↗

Squamous dysplasia and early esophageal cancer in the Linxian region of China: distinctive endoscopic lesions.

BACKGROUND: Linxian, China, has one of the highest rates of esophageal cancer in the world. To design a logical biopsy strategy for large-scale endoscopic surveys in Linxian, the aim of this study was to determine whether squamous dysplasia and early squamous cancer are associated with visible lesions that can be targeted for biopsy. METHODS: Sixty-three Linxian patients with balloon cytological evidence of squamous dysplasia or early cancer of the esophagus had biopsy specimens taken every 4 cm and additional specimens taken from all visually abnormal areas. The appearance of the 398 biopsy sites was described, and abnormal-appearing areas were photographed. The endoscopic descriptions were then compared with the biopsy diagnoses. RESULTS: Twenty-five of 31 (81%) moderately dysplastic or worse specimens (including all nine specimens of invasive cancer) came from visually abnormal sites classified as friability, focal red area, erosion, plaque, or nodule. Fifteen of 16 (94%) patients with moderate dysplasia or worse biopsy diagnoses would have been identified if only these visible target lesions had been sampled. CONCLUSIONS: For surveillance in this high-risk population, random biopsy specimens may be unnecessary; sampling the target lesions described appears sufficient to detect nearly all invasive cancer and most dysplasia. Awareness of these lesion appearances may also aid in earlier detection of squamous cancers of the esophagus in lower-risk populations such as those in Europe and North America.

Biopsy↗