Lymphocytic oesophagitis, eosinophilic oesophagitis and compound lymphocytic-eosinophilic oesophagitis I: histological and immunohistochemical findings.

AIMS: To report four histological-immunohistochemical oesophagitis phenotypes. METHODS: Oesophageal biopsies from 311 patients were stained with H&E and with CD3, a T cell marker. Additional immunohistochemical stains (n=413) were performed in 77 cases. RESULTS: Four histological-immunohistochemical oesophagitis phenotypes were recorded: lymphocytic oesophagitis (LyE, ≥40 CD3+ lymphocytes/HPF in CD3 immunostain), eosinophilic oesophagitis (EoE, ≥15 eosinophils/HPF in H&E stain), lymphocytic infiltration (≤39 CD3+/HPF) and compound lymphocytic oesophagitis-eosinophilic oesophagitis (Co LyE-EoE). At index biopsy, 28.3% (n=88) had LyE, 21.2% (n=66) EoE, 10.6% (n=33) Co LyE-EoE and 39.9% (n=124) lymphocytic infiltration. A persistent oesophagitis phenotype was found in 42.5% (37/87) in the first follow-up biopsy, in 34.4% (21/61) in the second follow-up biopsy and in 48.1% (26/54) in the third follow-up biopsy. Using ßF1 immunostain, two different surface T cell receptors were detected in LyE and Co Lye-EoE: one having ≥40 ßF1+/HPF (ßF1+ high) and the other having <39 ßF1+/HPF (ßF1+ low). CONCLUSIONS: Based on the literature regarding the significance of intraepithelial lymphocytes (IELs) in the initiation of EoE, we submit that the IEL phenotypes in LyE might differ from those found in EoE as they were unable to elicit the same eosinophilic response. Recent studies disclosed that group 2 innate lymphocytes (ILC2s), enriched in EoE, remain undetected in CD3 immunostain as they lack surface markers for T, B, natural killer (NK) or NK T cells. If ILC2s also participate in the lymphocytic infiltration of EoE, then the frequency of cases with Co LyE-EoE here reported might have been much higher. The four oesophagitis phenotypes described are easy to recognise, provided that the dual staining procedure (H&E-CD3) is implemented.

Traditional serrated adenomas of the upper digestive tract.

For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma-carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract.

Automated analysis of respiratory behavior in extremely preterm infants and extubation readiness.

BACKGROUND: Rates of extubation failure of extremely preterm infants remain high. Analysis of breathing patterns variability during spontaneous breathing under endotracheal tube continuous positive airway pressure (ETT-CPAP) is a potential tool to predict extubation readiness. OBJECTIVE: To investigate if automated analysis of respiratory signals would reveal differences in respiratory behavior between infants that were successfully extubated or not. METHODS: Respiratory Inductive Plethysmography (RIP) signals were recorded during ETT-CPAP just prior to extubation. Signals were digitized, and analyzed using an Automated Unsupervised Respiratory Event Analysis (AUREA). Extubation failure was defined as reintubation within 72 hr. Statistical differences between infants who were successfully extubated or failed were calculated. RESULTS: A total of 56 infants were enrolled and one was excluded due to instability during the ETT-CPAP; 11 out of 55 infants studied failed extubation (20%). No differences in demographics were observed between the success and failure groups. Significant differences on the variability of some respiratory parameters or 'metrics' estimated by AUREA were observed between the 2 groups. Indeed, a simple classification using the variability of two metrics of respiratory behavior predicted extubation failure with high accuracy. CONCLUSION: Automated analysis of respiratory behavior during a short ETT-CPAP period may help in the prediction of extubation readiness in extremely preterm infants.

European consensus on the histopathology of inflammatory bowel disease.

The histologic examination of endoscopic biopsies or resection specimens remains a key step in the work-up of affected inflammatory bowel disease (IBD) patients and can be used for diagnosis and differential diagnosis, particularly in the differentiation of UC from CD and other non-IBD related colitides. The introduction of new treatment strategies in inflammatory bowel disease (IBD) interfering with the patients' immune system may result in mucosal healing, making the pathologists aware of the impact of treatment upon diagnostic features. The European Crohn's and Colitis Organisation (ECCO) and the European Society of Pathology (ESP) jointly elaborated a consensus to establish standards for histopathology diagnosis in IBD. The consensus endeavors to address: (i) procedures required for a proper diagnosis, (ii) features which can be used for the analysis of endoscopic biopsies, (iii) features which can be used for the analysis of surgical samples, (iv) criteria for diagnosis and differential diagnosis, and (v) special situations including those inherent to therapy. Questions that were addressed include: how many features should be present for a firm diagnosis? What is the role of histology in patient management, including search for dysplasia? Which features if any, can be used for assessment of disease activity? The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas.

The frequency of advanced adenoma in consulting patients: a nationwide survey in Iceland (2003-2006).

AIM: To assess the frequency of advanced colorectal adenomas in consulting patients in Iceland. METHOD: The histological configuration of colorectal adenomas (CRA) found in 3603 patients was classified into tubular (TA), villous (VA) and serrated (SA) and the degree of neoplastic severity into low-grade dysplasia (LGD), high-grade dysplasia (HGD), carcinoma in situ (CIS), intramucosal carcinoma (IMC) and submucosal carcinoma (SMC). Advanced CRA were those showing HGD, CIS, IMC and/or SMCs. In patients with two or more adenomas, the adenoma with the highest degree of epithelial neoplasia was selected to record cases. RESULTS: Between 2003 and 2006 a total of 19424 endoscopic examinations (13572 colonoscopies and 5852 sigmoidoscopies) were performed in Iceland (mean, 4856 endoscopies per year). At histology a mean of 759.3 CRA per year were found. Thus, CRA were found in 15.6% of the colorectal endoscopies performed per year. Out of the 3037 CRA studied, 67% were TA, 29% VA and the remaining 4% SA. LGD was present in 79%, HGD in 15%, CIS in 2.4%, IMC in 1.9% and SMC in 1.9%. Consequently, out of 3037 CRA investigated, 652 (21.5%) were advanced CRA; 71% of these showed HGD, 11% CIS, 9% IMC and 9% SMC. Two-thirds of the 652 advanced CRA were advanced VA, and more than three-quarters of 58 advanced CRA with SMC, were advanced VA. CONCLUSION: Advanced VA displaying intraepithelial neoplasia (HGD and CIS) showed a propensity to evolve into invasive carcinoma. Accordingly, VA displaying HGD and CIS might be regarded as biological markers for predicting colorectal cancer risk. This is the first study in which the frequency of CRA and advanced CRA detected in consulting patients is reported on a nationwide basis.

Usefulness of colonoscopic examination with indigo carmine in diagnosing microscopic colitis.

Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is epitomized by chronic watery diarrhea, endoscopically normal colonic mucosa, and characteristic histopathological features. Reports on chromoendoscopic findings in microscopic colitis are scarce and in this paper we describe such findings. We have examined 13 patients with microscopic colitis by means of chromoendoscopy with indigo carmine 0.2 % - 0.5 %. In all 13 cases continuous mucosal changes were seen, with disappearance of innominate grooves or with irregularity of grooves. The segmental distribution of abnormal chromoendoscopic findings corresponded almost completely with the microscopic features. A diffuse mosaic pattern was found in five of 10 cases of collagenous colitis and in all three cases of lymphocytic colitis. Uneven surface was seen in four cases of collagenous colitis, one of collagenous colitis in remission, and one of lymphocytic colitis, and a nodular surface was recorded in five cases of collagenous colitis but in none of the lymphocytic colitis cases. If these findings can be reproduced in larger series of microscopic colitis cases, the need for biopsies as a diagnostic tool might be restricted to patients where chromoendoscopy shows clear mucosal changes, thereby saving costs and limiting possible complications associated with multiple biopsies.

Tumour budding correlates with local recurrence of rectal cancer.

AIM: Predictive tools for local recurrence (LR) of rectal cancer are needed. This study assessed the predictive value of tumour budding detected by MNF-116 and laminin-5 γ2 chain (Ln-5 γ2). METHOD: In a case-control study, the surgical specimens of 48 patients with LR after from primary resection of rectal carcinoma and 82 control patients matched for gender and preoperative radiation from a population of 1180 patients operated with total mesorectal excision were studied. The presence of budding was examined using immunohistochemistry with Ln-5 γ2 and pan-cytokeratin staining with MNF-116. RESULTS: Tumour budding counts ranged from 0 to 106 buds (mean 43, median 38) for all patients. Significantly more tumours with more than 35 buds were seen in the LR than in the control group (67 vs 44%; P = 0.02). The spread of budding was also more extensive in the LR than in the control group (63 vs 49%, P = 0.03). In a multivariate analysis with tumour, node, metastasis stage, MNF-116-stained budding was an independent predictor of local failure (P = 0.02). The budding frequency was higher in irradiated tumours in comparison with tumours that had not received irradiation (mean 53 vs 38, P = 0.03). For Ln-5 γ2, more tumours with ≥ 10 buds were seen in the group with LR than among the control patients, but this difference was not statistically significant (73 vs 57%; P = 0.09). No additive value was found in the multivariate logistic regression model when Ln-5 γ2-stained budding frequency was added to MNF-116 and tumour, node, metastasis stage. The agreement between budding frequency determined by MNF-116 and Ln-5 γ2 was moderate, with a κ-coefficient of 0.34 (0.16-0.51). CONCLUSION: Tumour budding determined by MNF-116 staining may serve as a predictive marker for LR in rectal cancer.

Further studies on the frequency and length of the glandulo-metaplastic esophageal mucosa in baboons.

BACKGROUND: In previous studies, the length of the glandulo-metaplastic esophageal mucosa (GMEM) at the gastroesophageal junction was assessed in a selected group of baboons. In this study, the length of the GMEM was measured in the entire esophagus in a cohort of unselected adult baboons. MATERIALS AND METHODS: In 15 female baboons, the entire esophagus was removed en bloc at autopsy, from the tongue to the angle of His. No part of the stomach was included. The length of GMEM was measured using a calibrated ocular microscale. RESULTS: GMEM was found in 11 out of the 15 esophagi. The total length of GMEM recorded in the 11 cases was 115 mm (mean 10.5 mm, range 1-45 mm). The mean age for animals with GMEM was 15.5 years (range 7-32 years) and for animals without GMEM was 14.0 years (range 7-20 years); the difference was non-significant (p<0.6). No significant association was found between the length of the GMEM and the age of the animals (p<0.6). CONCLUSION: This study substantiates the notion that GMEM in baboons is a postnatal physiological adaptative process of the esophageal mucosa to daily regurgitation with rumination of gastric juices of low pH. The GMEM apparently progresses upwards, along the esophageal mucosa. The baboon might be an excellent animal model to study the series of histological events that take place in the distal esophagus under the influence of protracted gastroesophageal reflux.

Qualitative DNA differences between two structurally different lesions: high-grade dysplasia and carcinoma in situ in colorectal adenomas.

BACKGROUND: Despite the fact that the Vienna classification of neoplasias in the gastrointestinal (GI) tract acknowledged low-grade dysplasia (LGD), high-grade dysplasia (HGD) and carcinoma in situ (CIS) and that most Western pathologists recognize CIS in many organs, both CIS and HGD are still used synonymously in colorectal adenomas. Differences between CIS and HGD in colorectal adenomas are reported. MATERIALS AND METHODS: Five large colorectal adenomas (measuring >20 mm) having areas of both HGD and CIS were stained with hematoxylin and eosin (H&E) and with Feulgen stains. RESULTS: The HGD areas showed tightly packed, spindle shaped, hyperchromatic cells with slight to moderate pleomorphic nuclei having coarse chromatin. In contrast, the CIS cells displayed marked pleomorphism, large vesicular nuclei and a prominent nucleolus. In H&E stain the hyperchromasia found in HGD nuclei was much less evident in CIS nuclei. The HGD nuclei were intensively stained (+++) with the DNA-specific Feulgen reaction but the CIS nuclei were not. CONCLUSION: It would appear that following the completion of chromosomal mutations in the nuclei of HGD-cells, their DNA, carrying the new genetic information, is transcribed into RNA in the nuclei of CIS. Thus, through messenger-RNA, the production of mutated cytoplasmic proteins, required for the ultimate invasion of the lamina propria mucosa (and beyond), would be triggered.

Frequency of epithelioid granulomas in colonoscopic biopsy specimens from paediatric and adult patients with Crohn's colitis.

AIMS: To test the assumption that epithelioid granulomas found in colonoscopic biopsy specimens in patients with Crohn's colitis are markers of a different clinical behaviour. METHODS: Sections from colonoscopic biopsy specimens from 352 consecutive patients (119 children and 233 adults) were investigated. RESULTS: A total of 1117 colonoscopies were performed: 293 in children (mean 2.46 per patient) and 824 in adults (mean 3.53 per patient) (p<0.05). Granulomas at initial colonoscopy were recorded in 67.2% (43/64) of children and 65.9% (27/41) of adults (p>0.6), and at subsequent colonoscopies in 53.8% (64/119) of children and 17.6% (41/233) of adults (p<0.05). Surgical intervention was required in 6.3% (4/64) of the children having previous granuloma, but also in 14.5% (8/55) of those without previous granuloma, the rate for operated adults being 26.8% (11/41) and 24.5% (47/192), respectively (p>0.6). CONCLUSIONS: Granulomas in entry and/or in subsequent colonoscopic biopsy specimens in patients with Crohn's colitis did not predict the need for subsequent surgical intervention. The fact that the frequency of granulomas was significantly higher in children than in adults with Crohn's colitis (despite a higher mean number of colonoscopic biopsies in adults), and that granulomas were present in colonoscopic biopsy specimens but not in the subsequent surgical specimens from 50% of the paediatric and 36% of the adult patients strengthen the conviction that granulomas in Crohn's colitis might evolve or regress at different time intervals during the course of the disease. This behaviour would reflect a particular immunological reaction, an epiphenomenon from immature tissues-as in children-when challenged by the so far elusive aetiological agent responsible for Crohn's disease.

Gastric duodenal metaplasia in duodenal adenomas.

BACKGROUND: In cases of known aetiology, gastric duodenal metaplasia (GMD) is a reversible lesion. In cases of unknown aetiology, the fate of GMD remains elusive. GMD was recently found in a duodenal adenoma. AIM: To audit the frequency of GMD occurring in a cohort of duodenal adenomas. METHODS: Filed H&E-stained sections from 306 consecutive duodenal adenomas were investigated for the presence of GMD. RESULTS: 68% of the adenomas (n = 208) were from patients with familial adenomatous polyposis (FAP), and the remaining 32% (n = 98) were sporadic. GMD was found in 31.7% (66/208) of the duodenal FAP adenomas and in 59.2% (58/98) of the duodenal sporadic adenomas (p<0.05). The causes for this difference are elusive. CONCLUSIONS: As for other metaplasias of the gastrointestinal tract (intestinal metaplasia of the oesophagus and of the stomach, and metaplastic-hyperplastic polyposis of the colon, known to antedate neoplastic transformation), a subset of GMDs of unknown cause might be present in the duodenal mucosa before adenomatous changes ensue. That subset of GMD might have neoplastic proclivity similar to the metaplastic epithelium in other organs of the gastrointestinal tract. The known carcinogenic effect of high concentrations of bile acids and pancreatic juices bathing the duodenal mucosa carrying an irreversible subset of GDM might set aflame the adenomatous neoplastic transformation in these patients.

Difference in cell proliferation between two structurally different lesions in colorectal adenomas: high-grade dysplasia and carcinoma in situ.

BACKGROUND: Despite the fact that most Western pathologists diagnose carcinoma in situ (CIS) in many organs the same pathologists generally diagnose similar histological aberrations in colorectal adenomas, as high-grade dysplasia (HGD). MATERIALS AND METHODS: Five large colorectal adenomas (measuring > or =20 mm) having areas of both HGD and CIS on staining with hematoxylin and eosin (H&E) were assessed with the proliferation antibody Ki-67 (clone MIB1). RESULTS: HGD is built of tightly packed, spindle shaped, hyperchromatic cells with moderate pleomorphic nuclei having coarse chromatin and CIS of marked pleomorphic, vesicular, hypochromatic nuclei with a prominent nucleolus. Ki-67 was expressed in 96% of the HGD cells but only in 3.5% of the CIS cells (p<0.05). CONCLUSION: The results of this and of previous investigations using the DNA-specific Feulgen stain, suggest that HGD and CIS in colorectal adenomas are two dissimilar morphological entities with dissimilar molecular behaviour. HGD cells in colorectal adenomas seem to be proliferating at any given time, whereas the majority of the CIS cells are not.

An improved method to visualize eosinophils in eosinophilic esophagitis.

We previously found in Giemsa-stained colorectal sections from IBD patients that eosinophilic granulocytes turned fluorescent when excited with indirect fluorescent light, while other inflammatory cells were non-fluorescent. We now studied with that method, the frequency of eosinophilic granulocytes in sections from patients with eosinophilic esophagitis (EE). Cell counting was done in consecutive sections stained with Giemsa stain using indirect fluorescence light (G-IFL setting) and with hematoxylin-eosin using transmitted light (HE-TL setting) in 5 cases of EE and in 10 consecutive cases of reflux esophagitis (RE) grade 2. In EE 45.0 eosinophils/case (range 39-51) were recorded with the G-IFL setting but only 33.4 eosinophils/case (range 28-39) with the HE-TL setting (p < 0.05). In RE cases, 3 eosinophils/case (range 2-4) were found with the G-IFL setting and 2 eosinophil/case (range 1-3) with the HE-TL setting. The G-IFL method is not only more sensitive in detecting eosinophils than the conventional HE-TL method but also quicker, since a differential cell counting is not necessary.

Cell proliferation at the leading invasive front of colonic carcinomas. Preliminary observations.

Dilated neoplastic glands, some with a layer of flat tumour cells and others lacking a group of consecutive lining tumour cells (i.e., glandular gaps called pores), were previously found at the leading invading tumour edge of colorectal carcinomas. Through the glandular pores, the retained intraglandular material was siphoned off directly into the juxtaposed extracellular matrix (ECM). The tumour cell fabricates, rich in proteolytic enzymes, disrupted the paratumoral anatomy of the ECM and encouraged further tumour penetration. In this work, cell proliferation in the neoplastic glands of the outermost advancing front of seven colonic carcinomas was studied with the proliferation marker Ki67. A total of 105 neoplastic glands were investigated in the seven tumours. In 33 of the 35 neoplastic glands with flat tumour cells, no Ki67 expression could be recorded in the flat cells. In the other two neoplastic glands, only occasional flat tumour cells showed Ki67 expression. The remaining (non-flat) neoplastic cells in the lateral and proximal aspects in the same 35 glands showed Ki67 expression. In 19 out of the 35 neoplastic glands with pores, the tumour cells at the tip of the pores (non-flat) showed Ki67 expression. In the remaining 16 neoplastic glands with pores, the tumour cells at the tip of the pores showed no Ki67 expression. In 15 out of the 35 neoplastic complete glands (i.e., having neither flat tumour cells nor epithelial pores) variable amounts of tumour cells lacking Ki67 expression were seen at the leading invading front. In the remaining 20 complete glands, all tumour cells showed Ki67 expression at the leading invading front. These preliminary results showed, for the first time, that human colonic flat neoplastic cells arrest their proliferation at the invading tumour front. The possibility that these Ki67-negative tumour cells were arrested in G1-phase was entertained. It is not inconceivable that this unexpected paradoxical biological behaviour of flat tumour cells might be connected with the formation of glandular pores at the level of advancing invasion in colonic carcinomas.

Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden.

In a population-based cohort study of all women aged over 50 years with breast cancer in the Swedish Cancer Register in 1961-2003, those diagnosed before 31 December 1987 were regarded as unexposed to tamoxifen, whereas those diagnosed after that date were considered potentially exposed. Crosslinkages within the Cancer Register and the Registers of Death and Emigration enabled follow-up. Standardised incidence ratios (SIRs) of oesophageal and gastric cancer represented relative risks. Among 138 885 cohort members contributing with 1 075 724 person-years of follow-up, we found a nonsignificantly increased risk of oesophageal adenocarcinoma during the potential tamoxifen exposure period (SIR 1.60, 95% confidence interval (CI) 0.83-3.08), but the risk estimates decreased with increasing latency interval. No association was observed during the unexposed period. No increased risk of cardia adenocarcinoma was identified in either period. The risk of non-cardia gastric adenocarcinoma was increased in the potential tamoxifen period (SIR 1.27, 1.03-1.57), and almost doubled (SIR 1.86, 95% CI 1.10-3.14) in the period of longest latency (10-14 years). The corresponding overall SIR was increased in the unexposed group also, but here SIR did not increase with longer latency intervals. An increased risk of tobacco-related tumours, that is, oesophageal squamous-cell carcinoma and lung cancer, was limited to the unexposed cohort, indicating that confounding by smoking might explain the increased SIR during the unexposed period. We concluded that there might be a link between tamoxifen and risk of non-cardia gastric adenocarcinoma.

Hyperplastic polyposis coli syndrome and colorectal carcinoma.

BACKGROUND: Patients with hyperplastic polyposis coli syndrome (HPCS) have a propensity to develop colorectal carcinoma (CRC). PATIENTS AND METHODS: Details were retrieved from the files of patients attending our hospital between 1988 and 2004 who fulfilled the World Health Organization criteria for HPCS. RESULTS: Over a period of 16 years, 10 cases of HPCS were identified at our hospital (0.625 cases/year or one case every 1.6 years). A mean of 40.3 hyperplastic polyps per patient were found (range 6-159). Other colorectal lesions were found as follows: two patients each had one mixed polyp; there were 15 serrated adenomas in eight patients; and there were 30 tubular, tubulovillous, or villous adenomas in eight patients. Among the 10 patients with HPCS, seven developed a CRC. Of the four villous adenomas, three were associated with a CRC, but only one of the 15 serrated adenomas was associated with a CRC. The pathway of cancer evolution in HPCS patients remains unresolved. CONCLUSIONS: Similarly to our results, a review of the literature indicates a high incidence of CRCs in HPCS patients. These patients are at a high risk of developing a CRC and should therefore receive regular colonoscopic surveillance.

Apoptosis versus polemosis. Different mechanisms leading to non-necrotic cell death.

Apoptosis is a physiological auto-suicidal, genetically-induced cell deletion process of senescent effete normal cells. Apoptosis guarantees genetic fidelity, minimizes phenotypic variation and eliminates genotypic alteration. The auto-destruction-induced by a cascade of caspases--results in the breakdown of normal cells and the formation of apoptotic bodies. Those bodies are rapidly phagocytized by macrophages and internalized by cells of the same type. On the other hand, polemosis (from Greek polemos: war) is a more dynamic mechanism of cell destruction between two different cell systems. Polemosis is focal, haphazardly distributed at the time of observation, probably erratic and influenced by the chemotactical attraction of committed lymphocytes by neoplastic cells. Polemosis is implemented by the interaction of the Fas-Fas ligand compulsory cellular system of self-defence. The end result of that struggle is manifested by the destruction of committed lymphocytes and the appearance of polemotic bodies (nuclear fragmentation with or without cytoplasmic remnants). The question arises as to whether polemotic bodies are also engulfed by macrophages, as is the case with apoptotic granules. In this work, the possible association between CD68-positive macrophages and intraepithelial polemotic bodies was investigated in sections from 50 colorectal adenomas. Polemotic bodies were found in groups of dysplastic cells in 84% (n=42) of the 50 adenomas, but none of them showed an accumulation of CD68 macrophages around the polemotic bodies. As polemotic bodies (autologous T-cells DNA) are not engulfed by macrophages it is hypothesized that the DNA of these bodies might be incorporated into the nuclei of dysplastic cells. This would satisfy the avidity of the DNA of rapidly proliferating dysplastic cells, a process that takes place, unremittingly, at any given time.

Neoplasias of the colorectal crypts.

Colorectal cancers are often preceded by noninvasive neoplasias arising in the surface epithelium, namely tubular, tubulovillous and villous adenomas. That neoplasias may also arise in the colorectal crypts is less well known. Between 1998 and 2002, colonoscopies, rectoscopies and colorectal surgical specimens from 8647 patients were received at this Department for histological diagnosis. The material included 502 adenomas, 865 invasive tumours and 221 cases of ulcerative colitis (UC). The following cryptal lesions were investigated: (a) neoplasias arising in the crypts, (b) neoplasias possibly arising in the crypts and (c) cryptal lesions alleged to be premalignant. Over the 5-year period, the most frequent phenotype encountered was single crypt dysplasia (in all 5 colectomies from familial adenomatous polyposis patients), followed by serrated adenomas (11.2%), hyperplastic polyps (8.4%), dysplasia in UC (6.3%), pure carcinoid tumours (1.7%), signet ring cell carcinoma (1.1%), adenocarcinoid tumours (0.2%) and de novo carcinomas (0.1%). In this survey, no case of Paneth cell adenoma or of cryptal neoplasia in lymphoid-associated mucosa (also known to originate from the crypts) was found. Hence, it was demonstrated that several neoplasia phenotypes actually arise in the colorectal crypts. The awareness that colorectal neoplasias may evolve from that particular cellular domain may cast more light on the understanding of the complex mechanisms of colorectal carcinogenesis.

Extensive intestinal metaplasia in gastric carcinoma and in other lesions requiring surgery: a study of 3,421 gastrectomy specimens from dwellers of the Atlantic and Pacific basins.

BACKGROUND: Extensive intestinal metaplasia (EIM) has been reported in gastrectomies from patients dwelling in the Pacific and Atlantic basins. AIMS: To compare all the results in an attempt to explain the findings. METHOD: All sections from 3,421 gastrectomies were reviewed at various hospitals: 1946 in the Atlantic and 1475 in the Pacific basin. Sections with EIM showed IM encompassing one or more entire low power field (>or=5 mm in length/section) in one or more section. RESULTS: In the Atlantic basin, EIM was present in 18.8% (153 of 814) of specimens with intestinal carcinoma (IC) and in 10.3% (65 of 630) of those with diffuse carcinoma (DC). In the Pacific basin, EIM was found in 62.9% (412 of 655) of gastrectomies with IC and in 33.3% (160 of 481) of those with DC. The numbers of specimens with EIM were significantly higher in the Pacific than in the Atlantic basin for both carcinoma phenotypes, particularly among elderly patients (>or=60 years). CONCLUSIONS: The proportion of gastrectomies with EIM was higher among populations at a higher gastric cancer risk than in those with a lower cancer risk. EIM was mostly associated with IC rather than DC or with miscellaneous gastric diseases (841 control gastrectomies) in both basins. The proportion of gastrectomies with EIM was significantly higher in Vancouver than in New York and in Santiago de Chile than in Buenos Aires, even though these populations reside at approximately the same geographical latitude, but in different basins. Environmental factors seem to accelerate the evolution of EIM.

Mott cell (Russell bodies) Barrett's oesophagitis.

The first case of Barrett's oesophagus with chronic inflammation having predominantly (> 50%) Mott cells, i.e. plasma cells with stored immunoglobulins, known as Russell bodies, is reported. Biopsies from two oesophagoscopies revealed similar changes, suggesting that the predominance of Mott cells is not a fortuitous event but a more long-lasting microscopic process. Periodic acid-Schiff (PAS) stain ruled out Candida albicans and immunostains, plasma cell neoplasia. Mott cells were not present in biopsies from the gastric mucosa or the urinary bladder, suggesting that this phenomenon was not widespread but localized to the Barrett's mucosa. The retention of immunoglobulins (Russell bodies) suggests that the mechanism of protein transport in those plasma cells is incompetent, and that the proteins are neither degraded nor secreted, but remain stored in dilated cisternae. Increased awareness of the existence of this subgroup of Barrett's oesophagitis may result in similar cases being reported in the future.