Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) has a very poor prognosis, which is largely due to late diagnosis. Successful early detection strategies will require identification of clinically relevant precursor lesions that can be targets for screening and treatment. AIMS: To identify the clinically relevant histological precursors of OSCC. SUBJECTS: A cohort of 682 endoscoped patients from a high risk rural population in Linxian, China. METHODS: Subjects were endoscoped and biopsied at baseline and followed for 13.5 years. We estimated the relative risk of developing OSCC for each of the initial histological diagnoses using Cox proportional hazards regression models. RESULTS: A total of 114 (16.7%) patients developed OSCC during the follow up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for incidence of this tumour, by initial histological diagnosis, were: normal 1.0 (reference), oesophagitis 0.8 (0.2-3.2), basal cell hyperplasia 1.9 (0.8-4.5), mild dysplasia 2.9 (1.6-5.2), moderate dysplasia 9.8 (5.3-18.3), severe dysplasia 28.3 (15.3-52.3), and carcinoma in situ 34.4 (16.6-71.4). CONCLUSIONS: In this study, squamous dysplasia and carcinoma in situ were the only histological lesions associated with a significantly increased risk of developing OSCC within 13.5 years after endoscopy. There was no evidence that oesophagitis predisposed to this tumour. Increasing grades of dysplasia were strongly associated with increasing risk, indicating that the histological grading was clinically meaningful. The follow up experience of severe dysplasia and carcinoma in situ was equivalent, suggesting that this distinction is not clinically relevant. Documenting these precursor lesions of OSCC should assist in the development of effective prevention, early detection, and treatment strategies for this disease.

Women's knowledge of and attitudes towards hormone replacement therapy.

BACKGROUND: Hormone replacement therapy (HRT) could benefit women who have reached the natural menopause, have had a hysterectomy or have a family history of osteoporosis. OBJECTIVE: Our aim was to monitor changes in women's knowledge of, and attitudes towards, HRT since 1991. METHODS: The study was a repeat of a postal survey conducted in 1991 in the Grampian region in the North East of Scotland. Six hundred women, aged 20-69 years, were selected randomly from the eight Local Health Care Co-operatives in Grampian, Scotland. The main outcome measures were women's knowledge of HRT, their attitudes towards it and the percentage of users, past users and never users within the sample. RESULTS: A 79% response rate was achieved. Overall, 17% of post-menopausal women were current takers (increased from 9% in 1991), 22% were previous takers (increased from 7%) and 61% were never takers (decreased from 84%). This increase in ever use of HRT was more pronounced in the less educated women (increase of 24% since 1991) compared with the more educated (increase of 13%). Almost half (48%) of post-menopausal women had considered taking HRT (25% increase). However, of never users, the majority (86%) had never considered HRT and had not discussed it with a doctor. Attitudes towards the menopause remained positive, although knowledge of the effects of HRT and of risk factors for osteoporosis had decreased. Forty-two per cent of never users would be persuaded to take HRT if they knew it would not cause any problems, and 52% would be persuaded to take HRT on the recommendation of a doctor. CONCLUSIONS: Since 1991, HRT use increased overall; this increase was greater in the less educated women. However, the majority of post-menopausal women remain never users, and many were unaware of HRT. Conflicting research evidence since 1991 on the risks and benefits of HRT may account for the decrease in the women's knowledge of the effects of HRT.

Peculiar artifacts mimicking carcinoma.

Artifacts that mimic malignancy may lead to diagnostic difficulty and can cause serious consequences. We present 2 cases received in consultation which demonstrated peculiar artifacts that closely mimicked carcinoma. In case 1, contaminating products of conception were confused with squamous cell carcinoma. In case 2, artifactual signet ring cells induced by procedural trauma were suspicious for signet ring cell carcinoma. In both cases, clinical correlation failed to completely exclude carcinoma, and limited tissue prevented use of ancillary studies. Our final resolution of these artifacts required lengthy and detailed morphologic analysis.

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Differences in diagnostic criteria for esophageal squamous cell carcinoma between Japanese and Western pathologists.

BACKGROUND: Large discrepancies have been found between Western and Japanese pathologists in the diagnosis of adenoma/dysplasia versus carcinoma for gastric and colorectal glandular lesions. It is important to determine whether similar differences exist in the diagnosis of esophageal squamous lesions. METHODS: Eleven expert gastrointestinal pathologists from Japan, North America, and Europe individually reviewed a set of microscopic slides containing 21 sections of biopsies and corresponding endoscopic mucosal resection specimens from Japanese patients with superficial esophageal squamous neoplastic lesions. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS: Invasion was the most important diagnostic criterion of carcinoma for the Western pathologists whereas nuclear and structural features were more important for the Japanese pathologists. For two sections showing low grade dysplasia according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in the other. For nine sections with high grade dysplasia according to the Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in two cases and definite carcinoma in seven cases. For six sections with suspected carcinoma according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in five cases. Four sections showed definite carcinoma according to both the Western and Japanese pathologists. Thus, there was agreement among the Western and Japanese pathologists for only 5 of the 21 sections (kappa value, 0.04). However, when high grade dysplasia, noninvasive carcinoma, and suspected carcinoma were grouped together, the agreement was excellent (19 of the 21 sections; kappa value, 0.75). CONCLUSIONS: In Japan, esophageal squamous cell carcinoma is diagnosed mainly based on nuclear criteria, even in cases judged to be noninvasive low grade dysplasia in the West. This difference in diagnostic practice may contribute to the relatively high incidence rate and good prognosis of superficial esophageal carcinoma in Japan. To improve the comparability of research data, the authors recommend that high grade dysplasia, noninvasive carcinoma, and suspected carcinoma be grouped together into one category of "noninvasive high grade neoplasia." [See editorial on pages 969-70, this issue.]

Adenocarcinoma of the colon with neuroendocrine features and secretory diarrhea.

We report the case of a 63-yr-old man who had severe secretory diarrhea associated with colonic adenocarcinoma, with a prominent signet ring cell component and numerous endocrine cells as demonstrated by positive chromogranin-A staining. Improvement in the secretory diarrhea by the somatostatin analog Sandostatin suggested that the diarrhea was related to a functional neuroendocrine tumor within the colonic tumor, the first case to be reported in the literature.

Evaluation of gastric biopsies for neoplasia: differences between Japanese and Western pathologists.

Cited variations in the evaluation of gastric endoscopic biopsies for neoplasms between pathologists in Japan and those in the United States and Europe (the West) may have stemmed from several causes. The five-tiered group classification of the Japanese Research Society for Gastric Cancer (JRSGC) for interpretation of biopsies is not used in the West. Some differences may also exist in the morphologic criteria to reach a diagnosis of dysplasia or carcinoma. The goals of this study were to test the Western and Japanese classifications of gastric dysplasia and adenocarcinoma and to assess the differences between four Japanese and seven Western pathologists. One hundred biopsies, 20 from each of the five categories of the JRSGC scheme as determined by one observer, were collected. The Japanese observers used the JRSGC system, expressed in Roman numerals, whereas Western pathologists used a five- or six-tiered scheme expressed in diagnostic terms. Pairwise agreement was evaluated using k statistics within both groups. Consensus diagnosis on each biopsy was accepted as the opinion of the majority. The sensitivity and specificity of each reviewer for a certain diagnosis were also assessed. The intragroup agreements were moderate for both the Japanese (mean k = 0.663) and the Westerners (mean k = 0.652). The pairwise agreements between Japanese and Western observers were low (mean k = 0.542). Overall, the sensitivity was low for all Japanese observers for the diagnosis of dysplasia (38.7% vs 92.5%), and the sensitivity for the diagnosis of adenocarcinoma was high in both groups but higher among the Japanese observers (93.9% and 85.2%, respectively). Overall, the Japanese-Western interobserver agreement was moderate. The JRSCG scheme did not translate into higher interobserver agreement among Japanese observers. The sensitivity for the diagnosis of gastric adenocarcinoma was high for both groups, but the specificity was low among the Japanese. The cause seemed to be centered around the diagnosis of dysplasia in the Western system, which was a lesion frequently interpreted as carcinoma in Japan because of the different definitions of carcinoma in each system. Such a discrepancy might be important because it may explain some of the differences in the prevalence and prognosis of early gastric cancer between Japan and the West. An international effort is needed to harmonize morphologic criteria and analyze whether therapeutic consequences may stem from such discrepancies.

Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.

In collagenous colitis, the literature is conflicting concerning where in the colon the lesions are most likely to be present and most severe. Conflicting data furthermore shed doubt on the sensitivity of the histological detection of the morphological abnormalities and the threshold criteria for diagnosis. We addressed these questions in 56 patients with collagenous colitis. Two hundred ninety-one coded biopsy specimens were analyzed according to six standardized sites from cecum to rectum. Subepithelial collagen deposits were subjectively graded in hematoxylin and eosin (H&E) sections and quantitatively measured in trichrome-stained sections, respectively. Semiquantitative grading was also done for inflammatory changes of the lamina propria and abnormalities of the surface and crypt epithelium. The transverse colon yielded the largest percentage of biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also had the largest percentage of biopsy specimens with inflammatory changes (98%). Biopsy specimens from both the rectosigmoid and the right colon (ascending and cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of specimens obtained from the rectosigmoid were diagnostic, and 18% of these were interpreted as normal. Subepithelial collagen deposits proved to be significantly thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm; range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had collagen deposits thicker than 10 microm. However, the subjective interpretation "diagnostic of collagenous colitis" proved to be most consistent with a threshold of 30 microm. Our results indicate that biopsy specimens from at least as proximal as the transverse colon should be obtained to definitely rule out collagenous colitis. Furthermore, it is evident that in a given biopsy specimen, markedly abnormal subepithelial collagen deposition had to be present for an unequivocal histological diagnosis of collagenous colitis.

Adult polycystic liver disease with cutaneous involvement: a brief report.

This case report documents the largest example of adult polycystic liver disease reported to date. In addition, the patient was found to have numerous subcutaneous cysts, an association with polycystic disease, which, as far as we could determine from the literature, has not previously been reported.

Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: potential clues to an etiologic exposure?

Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? The Polyp Prevention Trial.

BACKGROUND & AIMS: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas. METHODS: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. RESULTS: Four hundred sixty patients (46.9%) had >/=1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or >/=1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas. CONCLUSIONS: Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma. Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable.

Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China.

BACKGROUND: In previous studies in the high risk population of Linxian, China, the majority of foci of high grade (moderate and severe) squamous dysplasia (HGD) and invasive squamous carcinoma (CA) of the esophagus were associated with endoscopically visible lesions that could be targeted for biopsy, but some foci of HGD were missed by routine endoscopic examination. This study examined whether spraying the mucosa with Lugol's iodine solution, which stains normal epithelium brown but leaves dysplasia and carcinoma unstained, could improve endoscopic detection and delineation of these lesions. METHODS: Two hundred twenty-five Linxian adults with balloon cytologic evidence of dysplasia or carcinoma underwent endoscopy. All visible lesions were described and photographed before and after staining with 1.2% Lugol's iodine solution. Biopsies were taken from all lesions visible before staining, from all unstained lesions (USLs) after applying the stain, and from representative control areas of stained mucosa. RESULTS: Two hundred fifty-three USLs and 255 control sites were biopsied. No complications occurred. Ninety-four biopsy sites contained HGD and 20 contained CA. Before staining, the sensitivity of visible lesions for identifying HGD or CA was 62%, and the specificity was 79%. After staining, the sensitivity of USLs for identifying HGD or CA was 96%, and the specificity was 63%. Eighty-eight percent of the HGD and CA lesions were larger or more clearly defined after staining. The diagnostic lesions in 17 of 31 patients with moderate dysplasia (55%), 8 of 35 patients with severe dysplasia (23%), and none of the 19 patients with invasive carcinoma (0%) were identified only after staining. CONCLUSIONS: Mucosal iodine staining improved endoscopic detection and delineation of HGD and CA in these patients. This simple technique is highly sensitive for identifying these precursor and invasive squamous lesions, and it should be used whenever optimal visualization of squamous mucosal abnormalities is required.

Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma.

BACKGROUND: In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries. METHODS: Eight expert pathologists from Japan (4), North America (2), and Europe (2) individually reviewed microscope slides of 20 colorectal lesions from Japanese patients who had undergone endoscopic mucosal resection or surgery because early stage carcinoma and/or adenoma was suspected. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS: For 11 slides that showed adenoma according to the Western pathologists with low grade dysplasia according to at least half of them, the Japanese diagnosed definite carcinoma with or without adenoma in 4 cases and adenoma in 5, and in 2 cases they were equally divided between a diagnosis of adenoma and carcinoma. For five slides showing adenoma with high grade dysplasia according to the Western pathologists, the Japanese diagnosed definite carcinoma with adenoma in three cases and adenoma in one, and in one case they were equally divided between a diagnosis of adenoma and carcinoma. For one case in which the Western pathologists were equally divided between a diagnosis of carcinoma and adenoma with high grade dysplasia, all the Japanese pathologists diagnosed definite carcinoma with or without adenoma. Three slides showed definite carcinoma with or without adenoma, according to both the Western and the Japanese pathologists. The presence of invasion was the most important diagnostic criterion of colorectal carcinoma for the Western pathologists, whereas for the Japanese the nuclear features and glandular structures were more important. CONCLUSIONS: In Japan, colorectal carcinoma is diagnosed on the basis of nuclear and structural criteria, even in cases considered by Western pathologists to be noninvasive lesions with low grade dysplasia. This diagnostic practice may contribute to the relatively high incidence of early stage colorectal carcinoma reported in Japan as compared with Western countries.

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.

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.

Differences in diagnostic criteria for gastric carcinoma between Japanese and western pathologists.

BACKGROUND: There have been many studies on gastric carcinoma in populations with contrasting cancer risks. We aimed to find out whether the criteria for the histological diagnosis of early gastric carcinoma were comparable in Western countries and Japan. METHODS: Eight pathologists from Japan, North America, and Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and 18 endoscopic mucosal resections taken from 17 Japanese patients with lesions ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The pathologists were given a list of pathological criteria and a form on which they were asked to indicate the criteria on which they based each diagnosis. FINDINGS: For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia, whereas the Japanese diagnosed definite carcinoma in four slides, suspected carcinoma in one, and adenoma in only two. Of 12 slides with high-grade adenoma/dysplasia according to most Western pathologists the Japanese gave the diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing high-grade adenoma/dysplasia with suspected carcinoma according to most Western pathologists the Japanese diagnosed definite carcinoma in all. There were no major differences in the diagnoses of three slides showing reactive epithelium and seven slides with clearly invasive carcinoma. When the opinion of the majority of the pathologists was taken as the final diagnosis there was agreement between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95% CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion for most Western pathologists whereas for the Japanese nuclear features and glandular structures were more important. INTERPRETATION: In Japan, gastric carcinoma is diagnosed on nuclear and structural criteria even when invasion is absent according to the Western viewpoint. This diagnostic practice results in almost no discrepancy between the diagnosis of a superficial biopsy sample and that of the final resection specimen. This may also contribute to the relatively high incidence and good prognosis of gastric carcinoma in Japan when compared with Western countries.

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.