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Notes: Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only ‘fair’ or ‘moderate’. As expected, agreement over the two categories ‘dysplasia’vs‘no dysplasia’ was better, ranging from 68% to 84%, and for ‘atypia present’ (reactive atypia, low- and high-grade dysplasia) vs‘no atypia’ two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia was examined. Given that a first observer allocates a case as high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of ‘atypia, significance uncertain’, so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Notes: Histopathological material from operation specimens of rectal adenocarcinoma was reviewed and invasion of veins identified in 51.9% of 703 cases. The extent of venous invasion, thickness of the walls of invaded veins and various other histological features were examined in detail. By follow-up studies recurrence rates, incidence of distant metastases and corrected 5-year survival rates were obtained; correlation with the histopathological results showed that invasion of extramural and thick-walled veins is associated with a poor prognosis independent of the degree of differentiation of the adenocarcinoma. Prognosis is not significantly related to the presence of necrosis of intravenous growth. Aneurysmal distension and inflammatory damage of the walls of invaded veins, a thrombus cap or endothelial cell mantle covering intravenous tumour and a clearly defined stroma in the intravenous growth all appear to exert a protective influence on patient survival, whereas permeation of capillaries in vein walls, the presence of loose clumps of tumour cells in veins and direct contact between tumour cells and venous blood appear to adversely affect survival. Venous invasion is shown to be related to local invasiveness of rectal carcinoma. Suggested modes of venous spread and interaction with host tissues are proposed, with implications for general attitudes to the spread of cancer and metastasis.

Notes: Clinicopathological significance of the `keloid-like' collagen and myxoid stroma in advanced rectal cancer Aim: To establish the histological categorization of fibrotic stroma which reflects the biological behaviour of advanced rectal cancer. Methods and results: Six hundred and twenty-seven surgically resected cases of advanced rectal carcinoma were examined. We histologically categorized fibrotic stroma in the invasive frontal region into three groups: type A, multiple fine and mature fibres were stratified into layers; type B, broad bands of eosinophilic hyalinized collagen (`keloid-like' collagen) were intermingled; type C, myxoid stroma. Type A stroma was observed in 63% of patients, type B stroma in 25%, type C stroma in 12%. The incidence of type A stroma decreased in accordance with Dukes stage (98% in Dukes A; 73% in B; 41% in C1; 29% in C2) and conversely, there was an increase of C type (0% in Dukes A; 4% in B; 20% in C1; 54% in C2). Stroma type had a significant correlation with long-term survival (80% of 5-year survival in type A stroma; 54% in type B; 26% in type C). Based on multivariate analysis, it was found that the stromal pattern had independent prognostic value, together with nodal involvement, growth pattern, and lymphocyte infiltration. Conclusions: Tumour fibrotic stroma may play an important role as a regulator of neoplastic behaviour. Pathological categorization of the fibrotic stroma is helpful for predicting the prognostic outcome of patients with rectal carcinoma.

Notes: Tumour `budding' as an index to estimate the potential of aggressiveness in rectal cancer Aims: Although the characteristic of invasive pattern which contributes to Jass's classification is a sensitive prognostic marker in rectal cancer, reproducibility of its assessment has been shown to be problematic. As another histological parameter of invasive margin, we examined the prognostic significance of tumour ‘budding’ and attempted to establish its appropriate criteria. Methods and results: A total of 638 rectal cancer specimens was examined. We defined tumour `budding' as an isolated single cancer cell or a cluster composed of fewer than five cancer cells. We divided these into two groups by their intensity, i.e. the number of `budding' foci within a microscopic field of × 250. Rectal cancer with high-grade `budding' (≥ 10 foci in a field) was observed in 30.1% of patients, and was associated with lower 5-year survival rates (40.7%) than patients with low-grade `budding' (84.0%) (P 〈 0.0001). Based on multivariate analysis, tumour `budding' was selected as the significant independent variable, together with the number of nodes involved, extramural spread, lymphocytic infiltration, apical nodal involvement and tumour differentiation. Kappa coefficient of two-graded tumour `budding' in the intraobserver study was 0.84. Conclusions: Because of its value as a prognostic indicator and its reproducibility, tumour `budding' would be a good index to estimate the aggressiveness of rectal cancer.

Notes: Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0–18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:02692813:APT1203:les" location="les.gif"/〉 2, endoscopic score of 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:02692813:APT1203:les" location="les.gif"/〉 1 and total score of 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:02692813:APT1203:les" location="les.gif"/〉 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best=32–224).〈section xml:id="abs1-4"〉〈title type="main"〉Results:Forty-four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment. Thirty-six (82%) went into remission. The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8–17) and 3 (range, 1–10), respectively (P 〈 0.0001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74–183) to 175 (range, 76–215) with this therapy (P 〈 0.0001). The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs. 35 years; P=0.007), had a longer history of pouchitis (95.5 vs. 26 months; P=0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing: 6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1.0–2.4) and tended to have a higher Pouchitis Disease Activity Index score before treatment (median 14.5 vs. 12; P=0.13) than those who went into remission. Even in these eight patients, the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8–16) to 9.5 (range, 7–10) (P=0.0078), as did the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74–134) to 127 (range, 76–187) (P=0.039). The Inflammatory Bowel Disease Questionnaire score strongly correlated with the Pouchitis Disease Activity Index score (r=0.79, P 〈 0.0001), and was significantly related to the patients' overall assessment of satisfaction (P 〈 0.0001). No serious side-effects were noted.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Four-week treatment with a combination of metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively improving the inflammation and quality of life. The Inflammatory Bowel Disease Questionnaire is a sensitive tool for evaluating patients with pouchitis, and correlates well with disease activity.

Notes: Background : Food antigens may contribute to gut inflammation in Crohn's disease.Aim : To assess in vivo sensitization to food antigens, ascertain whether sensitivity is gut specific, assess food sensitization in vitro, and correlate in vivo changes with histological and blood changes.Methods : Skin testing and rectal exposure to six food antigens (cereal, cabbage, citrus, milk, yeast and peanut) and control saline were assessed double-blind by immediate and 3.5-h laser Doppler blood flowmetry, and rectal biopsies were taken. Peripheral blood lymphocyte proliferation was measured in response to the same antigens.Results : Ten patients with Crohn's disease and 10 healthy controls were studied. Blood flow increased in 24 of 60 antigen sites in Crohn's disease patients and six of 60 antigen sites in controls (P 〈 0.0001) after 3.5 h. The Crohn's disease group demonstrated higher rectal blood flow than controls in response to all food antigens, and this was significantly different for the responses to yeast (P = 0.036) and citrus fruits (P = 0.038). Lymphocyte proliferation occurred in 32 of 60 tests in Crohn's disease patients and eight of 60 tests in controls (P 〈 0.0001). There were no skin responses. Submucosal oedema corresponded to increased mucosal flow.Conclusions : Crohn's disease patients demonstrate in vivo and in vitro sensitization to food antigens, which is gut specific. Mucosal flowmetry allows the identification of sensitization to gut antigens.

Notes: Abstract PURPOSE: This study was designed to investigate neural and muscular features of the colonic wall in patients with severe idiopathic constipation. METHODS: By using quantitative immunohistochemistry, resected specimens from 14 patients with idiopathic chronic constipation and 17 nonobstructed cancer controls were studied. RESULTS: Routine histology revealed no significant histologic abnormality throughout the colon apart from four cases of melanosis coli. Ratio of the thickness of circular to longitudinal muscle was significantly lower in the left colon in constipated subjects. The myenteric plexus appeared morphologically normal in all subjects. S-100 protein, which stains neuronal supporting tissues, demonstrated an increase in the proportion of neural tissue in the myenteric plexus. There was an increased number of PGP-9.5 immunoreactive nerve fibers in the muscularis propria in constipated patients, and this was significantly higher in the ascending and descending colon. CONCLUSION: Intractably constipated patients have alterations in the neural composition of the colonic myenteric plexus and innervation of the circular muscle.

Notes: Abstract. Pneumatosis coli is a rare condition characterised by multiple gas-filled cysts within the bowel wall. We present 25 cases treated over the past 30 years. The patients' mean age was 59 years: 15 were female. Presenting symptoms included diarrhoea (n = 17), mucus discharge (n = 17), rectal bleeding (n = 15) and constipation (n = 12). Pneumatosis usually affected the left colon (96%), and diagnosis was by sigmoidoscopy and biopsy in 18 cases (72%). Pneumatosis coli was associated with psychiatric disorders (36%), chronic lung disease (20%) and colitis (12%). A redundant sigmoid colon was observed in 80% of cases on contrast radiology. Five patients had mucosal pseudolipomatosis on histological examination. Histological and immunohistochemical review indicated that the cysts were lined by cells of macrophage/monocyte phenotype and that many similar mononuclear cells were present in the adjacent submucosa and overlying mucosa. Treatment with antidiarrhoeals and anti-inflammatory drugs in 14 patients resulted in improvement in 9 cases (64%). Oxygen therapy (n = 9) always alleviated symptoms. There was a high recurrence rate (50–78%), but with further courses of therapy lasting remission was achieved in five patients. Two patients underwent colectomy. The associations of pneumatosis coli with psychiatric disorders and mucosal pseudolipomatosis are new and of possible pathogenetic significance. A novel pathogenetic mechanism is suggested to explain the association of pneumatosis coli and chronic respiratory disorders. A model of pneumatosis coli linking some of the apparently disparate pathogenetic theories is proposed.

Notes: Abstract  To evaluate the relationship between cell proliferation and apoptosis in sporadic colorectal carcinogenesis, immunohistochemistry for proliferation-associated antigen Ki-67 and in situ end labelling for identifying apoptotic bodies were performed on paraffin sections from 59 adenomas and 22 carcinomas. These results were correlated with the expression of the proliferation and apoptosis modulators Bcl-2 and p53. Carcinomas showed increased proliferation and apoptosis compared with adenomas (P〈0.0001, P〈0.001, respectively). There were positive linear correlations between proliferation and apoptosis in adenomas and carcinomas (P〈0.02, P〈0.05, respectively). The proliferative rate increased significantly from mild to moderate, and from moderate to severe dysplasia (P〈0.002, P〈0.001, respectively). Apoptotic rate also increased in this sequence, but the increases did not reach statistical significance (both P〉0.05). Expression of Bcl-2 was associated with lower apoptotic rate in adenomas (P〈0.025) but not in carcinomas (P〉0.25), whereas p53 expression was correlated with higher proliferative rate in both adenomas and carcinomas (P〈0.01, P〈0.05, respectively). An inverse relationship between Bcl-2 and p53 expression was seen in both adenomas and carcinomas (P〈0.05, P〈0.005, respectively). These data suggest that the normal balance between proliferation and apoptosis is disturbed in colorectal carcinogenesis, both being increased, but proliferation occurs in excess. Bcl-2 and p53 may each play a role in modulating cell apoptosis or proliferation during the development of colorectal carcinoma.