Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation

Restorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long-term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety. Ileoanal pouch biopsies from a cohort of patients and normal ileal and colonic controls were subjected to histological, biochemical, histochemical, and immunohistochemical mucin analysis. Mucin sulphation and sialic acid O-acetylation were studied as parameters of colonic phenotypic change. Fifty-one patients, 16 ileal, and 22 colonic controls were studied. Seventy per cent of biopsies retained villous mucosal architecture, with no cases of dysplasia detected. Ileoanal pouch mucosal sulphation and sialic acid O-acetylation did not reach colonic levels, thus indicating limited evidence for a more colonic phenotype. The data from this study suggest that colonic phenotypic change within the ileoanal reservoir is incomplete, with no cases of dysplasia detected. The degree of phenotypic change is less than in previous studies, which may support, but not prove, our hypothesis that there may be a process of reversion to an ileal type mucosa in the ileoanal reservoir with time.     

Galectin-3 expression in pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA)

Galectin-3, an endogenous pleiotropic beta-galactoside-binding protein, which is expressed by various malignant and normal cells, regulates many biological and pathological processes, including inflammation. In the present study, we tested a possible correlation between the severity of pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA) and the presence of galectin-3⁺ macrophages in pouch mucosa.     

Precancer and cancer in inflammatory bowel disease

The risk of cancer in inflammatory bowel disease (IBD) is increased although it remains low. A clinical subgroup of patients with extensive or total ulcerative colitis and a history of symptoms for more than 10 yr is at greatest risk. In these patients biopsy evidence of epithelial dysplasia has successfully been used as a marker for increased cancer risk. A classification system for dysplasia has recently been devised, consisting of 3 categories: negative, indefinite and positive for dysplasia. The criteria for each category are discussed. For patients at high risk who decline prophylactic colectomy, a cancer surveillance programme involving periodic clinical assessment, sigmoidoscopy, colonoscopy and rectal and colonic biopsies has provided a reasonable alternative.     

Altered expression of CK7 and CK20 in preneoplastic and neoplastic lesions in ulcerative colitis

This study is based on all patients with ulcerative colitis from a defined catchment area in Northern Sweden in a still ongoing colonoscopy surveillance programme, which started in 1977. From this material we selected tissue from eight groups of patients consisting of normal control biopsies (5), inactive colitis (10), active colitis (10), findings of low-grade dysplasia (10), high-grade dysplasia (6), aneuploidy (without dysplasia and with subsequent dysplasia) (10), and ulcerative colitis-associated cancers (5). The samples were evaluated according to immunohistochemical expression of CK7 and CK20. Colonic mucosa from normal controls and inactive colitis was found to be completely negative for CK7. In 9 out of 10 patients with active colitis, CK7 was sparsely expressed in a patchy manner and connected with active epithelial inflammatory areas. 7 out of 10 patients with low-grade dysplasia and 3 out of 6 with high-grade dysplasia were positive for CK7. Samples with aneuploidy without dysplasia were completely negative, while 2 out of 6 showing subsequent dysplasia were positive. Of the five cancers, two were positive for CK7. CK20 was expressed in nearly all samples but relatively more in the lower part of the crypts in neoplasia-associated lesions. Our results indicate a possible relationship between expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. Further studies are needed to elucidate whether these findings have clinical significance.     

Sialomucins in the assessment of dysplasia and cancer-risk patients with ulcerative colitis treated with colectomy and ileo-rectal anastomosis

The clinical notes and histology of 374 patients treated by colectomy and ileo-rectal anastomosis for ulcerative colitis were reviewed. Only those with definite diagnosis of ulcerative colitis and follow-up rectal biopsies were included (171 cases). Morphology and patterns of mucin secretion were investigated to assess whether abnormal mucin with predominance of sialomucins is a useful indicator of malignancy-risk. Carcinoma has developed in six patients and 'precancer' in seven. The results show coexistence of dysplasia and sialomucin even in the absence of inflammation in all but three biopsies; in contrast the presence of both dysplasia and normal mucin profile was found in less than 1%. A significant correlation was noted between an inflamed mucosa and the development of cancer or precancer, the presence of sialomucins and the appearance of dysplasia. Sialomucins showed a greater sensitivity in detecting cancer than dysplasia (75% versus 30%). However, dysplasia was notably more specific (94% compared with 50%), hence its greater predictive value as indicator of malignancy (50% as against 15% for a positive sialomucin result). Mucin stains on routine fixed paraffin-embedded tissue provide a simple screening method to sharpen the assessment of dysplasia and cancer-risk in patients with ulcerative colitis despite the limitations referred to above. The lack of definite evidence of dysplasia in four patients who developed malignancy without premalignant changes in the rectal biopsies emphasises the need for frequent multiple biopsies in patients with an ileo-rectal anastomosis for ulcerative colitis.     

Evidence for Immunosurveillance in Intestinal Premalignant Lesions

The immunosurveillance theory argues that the immune system recognizes tumour‐specific antigens expressed by transformed cells, which results in the destruction of cancer precursors before they become clinically manifest. As a model for the development of cancer, we set out to study premalignant lesions and immune responses in sentinel lymph nodes from patients with long‐standing ulcerative colitis and progression of mucosal dysplasia. Mesenteric lymph nodes draining dysplastic and normal intestinal segments were identified by sentinel node technique during surgery in 13 patients with ulcerative colitis who were subjected to colectomy because of intestinal dysplasia. T cells were extracted from the lymph nodes and analysed by flow cytometry, and lymphocyte proliferation assays were set up in the presence of extracts from dysplastic and normal intestinal mucosa. Increase in CD4/CD8 ratio was observed in sentinel lymph nodes draining dysplastic epithelium compared to normal mucosa. The increase in CD4⁺ T cells in relation to CD8⁺ T cells correlated with the degree of dysplasia reflected by a significant increase in the ratio against low‐grade dysplasia compared to indefinite dysplastic lesions. The T‐cell response was specific to antigens from dysplastic epithelial lining as seen in proliferation assays. The observation suggests an important surveillance role for the immune system against premalignant intestinal lesions in patients with long‐standing ulcerative colitis.     

Large bowel mucosal dysplasia and carcinoma in ulcerative colitis

The clinicopathological details of eight cases of ulcerative colitis complicated by carcinoma of the colon are described. There was a total of 14 primary colonic cancers, six of which were not detected before pathological examination of the resection specimens. The reason for this may be related to atypical tumour growth patterns. Three occurred in flat mucosa, one in a mucosal plaque lesion, and another in polypoidal mucosa. The occurrence, distribution, and morphology of mucosal dysplasia were noted in both resection specimens and biopsies taken at varying stages before resection. Tumour was associated with normal and adjacent dysplastic mucosa of varying grades. The extent and grade of dysplasia were not reliable indicators of tumour differentiation or subsequent clinical outcome. Only two cancers were poorly differentiated. In five cases a total of 23 mucosal biopsies were taken, all less than 12 months before resection. Three rectal biopsies were graded positive for dysplasia and three colonic biopsies indefinite for dysplasia. The subsequent resection specimens showed both dysplastic and carcinomatous changes. Three rectal and 14 colonic biopsies were graded negative for dysplasia despite positive findings in the subsequent resection specimens. This anomaly is partly attributed to the patchy nature of dysplasia in colitic mucosa. Two cases illustrate the possibility of dysplasia pursuing a rapidly progressive course. The mucosal changes of ulcerative colitis were assessed using a recently introduced and standardised international classification.     

Intestinal mucin antigens in ulcerative colitis and their relationship with malignancy

The expression of two intestinal mucin-associated antigens large intestine mucin antigen (LIMA) and small intestine mucin antigen (SIMA) were investigated by indirect immunoperoxidase staining of rectal mucosa from patients suffering from ulcerative colitis with (n = 6) and without (n = 31) associated carcinoma and in noncolitic controls (n = 40). The aim was to assess the relationship between antigen patterns and malignant change. SIMA, which is localised predominantly in the small intestine, is virtually undetectable in the normal adult colonic mucosa. However, this antigen is present in the foetal colon and colonic carcinoma. LIMA is expressed in normal colonic mucosa, but absent from the small intestine. LIMA staining patterns were not significantly different among the three groups. In contrast, expression of SIMA was significantly higher in the patients who had developed carcinoma (6/6) than in the noncancer group (7/71) (P less than 0.001). The presence of SIMA was also significantly related to areas of dysplasia compared to normal (P = .03) or inflammation (P less than .05), but it did not differ from mucosa showing "indefinite" atypia. The finding of 31% SIMA-positive biopsies associated with severe inflammation in colitis with active disease, but no evidence of malignancy, is difficult to explain at the present stage. A followup study would be necessary to determine its significance. Perhaps the most important finding is the increased frequency of SIMA-positive foci in histologically normal mucosa in carcinoma patients compared with the noncancer group (P less than .001), suggesting a field change. These observations may be prove useful for the identification of patients who may be at risk of developing carcinoma.     

p53 immunohistochemistry of ulcerative colitis-associated with dysplasia and carcinoma

In order to evaluate the usefulness of p53 immunohistochemistry (IHC) in the diagnosis of ulcerative colitis-associated colorectal carcinoma (UCACRC), ordinary paraffin sections were examined in 61 cases with ulcerative colitis (UC) and 29 control cases without UC. Among the 61 cases with UC, 11 were complicated by carcinoma coexisting with dysplasia, three with dysplasia, and two cases with adenoma. There were a total of 38 dysplasias, including 33 low grade dysplasias (LGD) and five mixed low and high grade dysplasias (LGD + HGD). The results of p53 IHC were divided into diffuse, nested, scattered and sporadic patterns for 29 control cases. Diffuse and nested patterns were presumed to reflect mutant forms of p53 protein and were defined as overexpression of p53 protein. In non-neoplastic mucosa of UC, the frequency of p53 positive tubules was significantly higher in active phase (13.5-17.9%) than in resolving phase (3.9-6.5%) and in remission (0.7-2.4%), regardless of association with neoplasia. Eight of the 37 lesions of dysplasia (21. 6%) showed p53 overexpression: 12.5% in LGD and 80.0% in LGD + HGD. The rate of p53 overexpression was significantly higher in UCACRC (90.9%) than in non-neoplastic mucosa of UC (0%), LGD and sporadic colorectal carcinoma (54.5%), but it did not differ between UCACRC and LGD + HGD. Interestingly, the mucosa without dysplasia showed p53 overexpression in one case of UCACRC. The biopsy specimen taken 4 years before the diagnosis of carcinoma revealed p53 overexpression in another case with UCACRC. These results suggest that p53 abnormalities play an important role in UC-associated tumorigenesis in its relatively early phase. For the diagnosis of dysplasia and carcinoma in UC, p53 IHC seems to be useful.     

PrÄcanceröse Epitheldysplasien bei Colitis ulcerosa

Summary Patients with total ulcerative colitis have a greater risk of development of carcinoma in the large bowel than the general population. Precancerous changes in rectal and colonoscopic biopsies are useful in detecting early cancer in colitis.In this study 20 patients with longstanding colitis have been examined by rectal and colonoscopic biopsies. The microscopic appearances of precancerous epithelial lesions are atypical basal cell proliferation, clear cell dysplasia, adenomatous and villous crypt proliferation and epidermoid metaplasia with epithelial atypia.We have found premalignant changes in 12 rectal and 14 colonic biopsies from 20 patients. Five of these had carcinomas in the resected specimens. One patient had two carcinomas: one was in the sigmoid and the other in the splenic flexure. Two tumours were small and inconspicuous, being confined to the bowel wall (DUKES A), three were larger, with extension beyond the bowel wall, but no nodal involvement (DUKES B). Another patient had a basaloid carcinoma of the anal glands.The extent of dysplasia was variable, ranging from small patches to large areas of involved mucosa. The precancerous lesions were sometimes in direct continuity with the carcinomas, but many showed no such connection.Four of the five patients with carcinomas had a history of colitis exceeding over 10 years, in the remaining case the history was in excess of four years duration.In a retrospective study of 39 colectomy specimens for total ulcerative colitis we have found only three patients with precancerous lesions.The early diagnosis of the carcinoma associated with colitis can be improved by systematic colonoscopic and histological examination. Precancerous epithelial dysplasia, which occurs at a high frequency, often with carcinoma, is found in the rectum and other parts of the colon. Multiple biopsies from different parts of the colon and rectum would thus seem to be desirable if mucosal sampling is to be employed as a screening test.

Für die technische Assistenz bei der Aufarbeitung der Biopsie- und OperationsprÄparate danken wir FrÄulein C. Schürmann, für die klinischen Daten Herrn Prof. Dr. K. Müller-Wieland, I. Medizinische Klinik der UniversitÄt Hamburg, und Herrn Priv.-Doz. Dr. N. Soehendra, Abteilung für Allgemeinchirurgie der Chirurgischen UniversitÄts-Klinik Hamburg.     

Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease

Identification of dysplasia in inflammatory bowel disease represents a major challenge for both clinicians and pathologists. Clear diagnosis of dysplasia in inflammatory bowel disease is sometimes not possible with biopsies remaining "indefinite for dysplasia." Recent studies have identified molecular alterations in colitis-associated cancers, including increased protein levels of alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2. In order to analyze the potential diagnostic use of these parameters in biopsies from inflammatory bowel disease, a tissue microarray was manufactured from colons of 54 patients with inflammatory bowel disease composed of 622 samples with normal mucosa, 78 samples with inflammatory activity, 6 samples with low-grade dysplasia, 12 samples with high-grade dysplasia, and 66 samples with carcinoma. In addition, 69 colonoscopic biopsies from 36 patients with inflammatory bowel disease (28 low-grade dysplasia, 8 high-grade dysplasia, and 33 indefinite for dysplasia) were included in this study. Immunohistochemistry for alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2 was performed on both tissue microarray and biopsies. p53 and alpha-methylacyl coenzyme A racemase showed the most discriminating results, being positive in most cancers (77.3% and 80.3%) and dysplasias (94.4% and 94.4%) but only rarely in nonneoplastic epithelium (1.6% and 9.4%; P < .001). Through combining the best discriminators, p53 and alpha-methylacyl coenzyme A racemase, a stronger distinction between neoplastic tissues was possible. Of all neoplastic lesions, 75.8% showed a coexpression of alpha-methylacyl coenzyme A racemase and p53, whereas this was found in only 4 of 700 nonneoplastic samples (0.6%). alpha-methylacyl coenzyme A racemase/p53 coexpression was also found in 10 of 33 indefinite for dysplasia biopsies (30.3 %), suggesting a possible neoplastic transformation in these cases. Progression to dysplasia or carcinoma was observed in 3 of 10 p53/alpha-methylacyl coenzyme A racemase-positive, indefinite-for-dysplasia cases, including 1 of 7 cases without and 2 of 3 cases with p53 mutation. It is concluded that combined alpha-methylacyl coenzyme A racemase/p53 analysis may represent a helpful tool to confirm dysplasia in inflammatory bowel disease.     

Dysplasia in inflammatory bowel disease

The risk of neoplasia in ulcerative colitis and Crohns colitis increases with both the duration and the extent of disease. In patients with extensive or pancolitis, the cancer risk increases dramatically 8 to 10 years after the first onset of disease. Childhood onset of colitis and primary sclerosing cholangitis further increase the risk of developing colorectal carcinoma. The performance of surveillance endoscopy to identify dysplastic precursor lesions via endoscopic biopsy specimens has become the main management strategy to combat this risk. Biopsies should be classified as negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, or high-grade dysplasia according to standard criteria. A prophylactic colectomy is the procedure of choice when high-grade dysplasia or low-grade dysplasia associated with a lesion or mass is present. Some centers also recommend a colectomy for the presence of low-grade dysplasia in flat mucosa. Given these management recommendations, care should be taken not to overcall reactive epithelial changes in the face of active colitis. All diagnoses of dysplasia should be confirmed, preferably by a pathologist experienced in interpreting gastrointestinal biopsies.     

Adenocarcinoma in Ileal Pouch after Proctocolectomy for Familial Adenomatous Polyposis: Report of A Case

Restorative proctocolectomy with ileal pouch-anal anastomosis is one of the surgical treatments of choice for patients with familial adenomatous polyposis. Although the risk of cancer developing in an ileal pouch is not yet clear, a few cases of adenocarcinoma arising in an ileal pouch have been reported. We report a case of adenocarcinoma in ileal pouch after proctocolectomy with ileal pouch-anal anastomosis. A 56-yr-old woman was diagnosed as having familial adenomatous polyposis. Total colectomy with ileorectal anastomosis was performed. Six years later, she underwent completion-proctectomy with ileal J pouch-anal anastomosis including anorectal mucosectomy for rectal cancer. After 7 yr, she presented with anal spotting. Endoscopic biopsies revealed adenocarcinoma at the ileal pouch. Resection of the ileal pouch and permanent ileostomy were performed. The risk of cancer in an ileal pouch and its prevention with regular surveillance must be emphasized.     

DNA fingerprinting abnormalities can distinguish ulcerative colitis patients with dysplasia and cancer from those who are dysplasia/cancer-free

Patients with extensive ulcerative colitis (UC) of longer than 8 years duration are at high risk for the development of colorectal cancer. The cancers in these patients appear to develop in a stepwise manner with progressive histological changes from negative for dysplasia --> indefinite for dysplasia --> dysplasia --> cancer. The aim of this study was to determine the timing and extent of genomic instability in the progression of UC dysplasia and cancer. Using two polymerase chain reaction (PCR)-based DNA fingerprinting methods, arbitrarily primed PCR and intersimple sequence repeat PCR, we assessed DNA sequence variation in biopsies across the spectrum of cancerous, dysplastic, and nondysplastic mucosa. UC patients with dysplasia/cancer had substantial genomic instability in both their dysplastic and nondysplastic colonic mucosa, whereas instability was not present in the majority of UC patients without dysplasia/cancer. The degree of instability in nondysplastic tissue was similar to that of dysplastic/cancerous mucosa from the same patient, suggesting that this instability was widespread and reached the maximum level early in neoplastic progression. These results suggest that UC patients who develop dysplasia or cancer have an underlying process of genomic instability in their colonic mucosa whereas UC patients who are dysplasia-free do not.     

Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens.

Mucosal biopsy specimens from the ileal reservoirs of 92 patients who had undergone restorative proctocolectomy (12 with familial adenomatous polyposis, 78 with ulcerative colitis, and two with functional bowel disease) were studied. Chronic inflammation was found in almost all, as was villous atrophy of varying severity. Other changes included pyloric metaplasia and mucosal prolapse. Acute inflammatory changes and ulceration were less common but, when present, corresponded to the clinical condition of "pouchitis". A grading system was devised to score acute and chronic inflammatory changes. There was a significant increase in acute inflammatory scores in ulcerative colitis compared with those in familial adenomatous polyposis, and pouchitis was present only in patients who had had ulcerative colitis; the morphological features of pouchitis are similar to those seen in the colorectal mucosa in ulcerative colitis. Histochemical studies of mucin in the reservoirs of mucosa showed that there may have been a change from small intestinal mucin to colonic mucin.     

Ki-67: a useful marker for the evaluation of dysplasia in ulcerative colitis.

AIMS: Evaluation of dysplasia in long standing ulcerative colitis is a difficult and often subjective task. Therefore, the aim of this study was to search for a more objective parameter to help distinguish regenerative changes from epithelial dysplasia. METHODS: A total of 97 sections from colectomy specimens from 12 patients with ulcerative colitis of more than 10 years duration were stained immunohistochemically with MIB 1 to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki-67. All patients had epithelial dysplasia in one or more areas (high grade dysplasia, n = 16; low grade dysplasia, n = 15; indefinite for dysplasia, n = 16), and three patients had additional adenocarcinoma (one Dukes's C multifocal, mucinous carcinoma; one Dukes's C adenocarcinoma in the sigmoid; and one Dukes's A adenocarcinoma in the caecum). Two patients had adenomas--one had an 8 cm villous adenoma with intramucosal carcinoma, and the other had a 4 cm tubulovillous adenoma with high grade dysplasia. RESULTS: There were highly significant differences between the percentages of Ki-67 immunopositive cells in low grade and high grade dysplasia and carcinoma compared with regenerative epithelium. In high grade dysplasia and carcinoma, the distribution of Ki-67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone. CONCLUSIONS: Assessment of the number of Ki-67 immunostained cells is of additional value in deciding whether the mucosa is regenerative or dysplastic, and the MIB 1 staining pattern is characteristic for most lesions with high grade dysplasia and carcinoma. Therefore, this technique could be combined with routine histological evaluation of colorectal epithelium being examined for dysplasia.     

Ki-67: a useful marker for the evaluation of dysplasia in ulcerative colitis.

AIMS: Evaluation of dysplasia in long standing ulcerative colitis is a difficult and often subjective task. Therefore, the aim of this study was to search for a more objective parameter to help distinguish regenerative changes from epithelial dysplasia. METHODS: A total of 97 sections from colectomy specimens from 12 patients with ulcerative colitis of more than 10 years duration were stained immunohistochemically with MIB 1 to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki-67. All patients had epithelial dysplasia in one or more areas (high grade dysplasia, n = 16; low grade dysplasia, n = 15; indefinite for dysplasia, n = 16), and three patients had additional adenocarcinoma (one Dukes's C multifocal, mucinous carcinoma; one Dukes's C adenocarcinoma in the sigmoid; and one Dukes's A adenocarcinoma in the caecum). Two patients had adenomas--one had an 8 cm villous adenoma with intramucosal carcinoma, and the other had a 4 cm tubulovillous adenoma with high grade dysplasia. RESULTS: There were highly significant differences between the percentages of Ki-67 immunopositive cells in low grade and high grade dysplasia and carcinoma compared with regenerative epithelium. In high grade dysplasia and carcinoma, the distribution of Ki-67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone. CONCLUSIONS: Assessment of the number of Ki-67 immunostained cells is of additional value in deciding whether the mucosa is regenerative or dysplastic, and the MIB 1 staining pattern is characteristic for most lesions with high grade dysplasia and carcinoma. Therefore, this technique could be combined with routine histological evaluation of colorectal epithelium being examined for dysplasia.     

The start of a programme for measuring diamine oxidase activity in biopsy specimens of human rectal mucosa

In human subjects, apart from in the kidney, diamine oxidase occurs mainly in the gut. Therefore this enzyme can be used as an indicator of intestinal integrity.In biopsies of rectal mucosa the diamine oxidase activity was assayed in 55 patients, 41 having a histologically normal mucosa and 14 being diseased. The determinations of the enzymic activity were supervised by statistical quality control.In the unchanged rectal mucosa the diamine oxidase activity was 40 nmol/min×g on average. In 7 patients with rectal polyps the enzymic activity was significantly diminished in these benign tumours (x=7.7 nmol/min×g) apart from one, where it was elevated. A decrease in diamine oxidase activity was further observed in rectal carcinoma and ulcerative colitis.Whether the reduction of intestinal diamine oxidase activity accompanies premalignant or malignant states or whether it is a general sign of a disturbance of intestinal integrity remains questionable.Supported by a grant from Deutsche Forschungsgemeinschaft (Ku 464/1).     

Barrett's oesophagus--a pathologist's view

Barrett's oesophagus, a precancerous condition for oesophageal adenocarcinoma, detected on endoscopy and confirmed on histology, shows intestinal metaplasia of the lower oesophagus. The significance of microscopic foci of intestinal metaplasia at the gastro-oesophageal junction, corresponding either to so-called 'ultrashort' segment Barrett's oesophagus, or to carditis with intestinal metaplasia, is still a matter of debate. The surveillance of patients with Barrett's oesophagus is still based on systematic biopsy sampling of Barrett's mucosa on endoscopy, looking for dysplasia. Although well-established classifications of dysplasia are now used by most pathologists, there remain numerous problems with this subjective marker (sampling, diagnostic reproducibility, natural history, etc). Therefore, many alternative biomarkers have been proposed, but only DNA aneuploidy, proliferation markers and p53 loss of heterozygosity/overexpression have been shown to be of some use at the present time. Some endoscopic improvements already allow a better selection of biopsies, and it may be that in future new technologies will allow 'virtual biopsies'. On the other hand, the role of pathologists now extends to the evaluation of new therapeutic modalities of early neoplastic lesions in Barrett's oesophagus, especially endoscopic mucosal resection.     

Qualitative assessment and morphometry in the study of the ileal reservoir after restorative proctocolectomy

Little is known about the long-term effects on the reservoir mucosa in patients with ulcerative colitis and familial polyposis coli who undergo proctocolectomy with subsequent construction of ileal reservoir/pouch and ileoanal anastomosis. In these patients, questions regarding adaptation towards a more colon-like mucosa and/or development of (pre)malignant changes are of particular importance. With the aim of designing a method for reliable evaluation of the mucosa in the ileal pouch, biopsies from 10 patients were studied by semiquantitative assessment and morphometry. The findings were compared with those obtained from normal jejunum, ileum, and colon. The following parameters were found to be important: Villous surface density, quantity of goblet cells, number of mitoses, and the presence/absence of predominantly sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The villous surface density was determined by a cycloid test system applied to vertical sections. Semiquantitative assessment was a sufficiently precise method for the evaluation of the quantity of goblet cells. The counting of sulphated mucin+ goblet cells was not reproducible, instead a simple statement about the presence or absence of these cells was judged to be adequate. The number of mitoses and of Paneth cells were counted directly. During the first year of function the ileal pouch showed signs of adaptation towards a colon-like mucosa: Reduction of villous surface density, increased mitotic activity, and appearance of sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The amount of goblet cells was generally not increased, rather reduced in some patients.