Bleeding due to colorectal atheroembolism. Diagnosis by biopsy of adenomatous polyps or of ischemic ulcer.

Atheroembolism, although not infrequent at autopsy, is seldom identified in life, when it may present as a multisystem disease involving lower limbs, kidney, and gastrointestinal (GI) tract. Diagnosis of isolated GI involvement usually requires examination of surgically resected tissue, because recognition by endoscopic GI biopsy is exceptional. We diagnosed colorectal atheroembolism by biopsy in four patients. All were elderly (68-80 years old) and had generalized atheroma, including aortic aneurysms. Three patients had sudden onset of frank rectal bleeding with clots or bloody diarrhea, lower abdominal discomfort, and tenderness. Biopsy revealed atheroemboli in a rectal ischemic ulcer and in colorectal adenomatous polyps. In all three, disease resolved on conservative management and did not recur during the period of follow-up. In the fourth patient, asymptomatic atheroembolism was identified in an adenomatous polyp at the splenic flexure. Extraintestinal disease attributable to atheroembolism was not present in any of the patients. Atheroembolism with manifestations confined to the colon may sometimes be diagnosed by biopsy, appears to be more frequent than currently recognized, and may present a diagnostic challenge as a self-limited episode of rectal bleeding.

Infected infarcts of the testis: a study of 18 cases preceded by pyogenic epididymoorchitis.

Eighteen cases of infected infarcts of the testis are presented, and evidence is put forward that these result from venous occlusions in the epididymis and cord. The venous lesions probably result from thrombosis during the course of an attack of epididymoorchitis. Granulomatous orchitis was present in some part of half of the orchidectomy specimens, and the clinical histories, bacteriological findings, and histological data all suggest that this form of inflammation results from pyogenic infection of the testicle. What the factor is which determines whether the inflammation is granulomatous or not is unknown.

Coeliac disease with histological features of peptic duodenitis: value of assessment of intraepithelial lymphocytes.

AIMS: To determine if a clinically important polymorphonuclear leucocyte infiltrate and surface gastric epithelial metaplasia occur in the second part of the duodenum in coeliac disease; to evaluate the utility of these morphological criteria in the differential diagnosis of coeliac disease and peptic duodenitis. METHODS: 49 mucosal biopsy specimens of the second part of the duodenum reported as showing inflammation were reviewed. Sections were prepared with haematoxylin and eosin, periodic acid Schiff, and Warthin-Starry stains. Clinical presentation, outcome, and immunological investigations were assessed. RESULTS: Four cases confirmed as coeliac disease on clinical and immunological grounds showed acute inflammation and surface epithelial gastric metaplasia. Increased intraepithelial lymphocytes (IELs) were found in each of the four. CONCLUSIONS: Clinically important polymorphonuclear leucocyte infiltration and surface epithelial gastric metaplasia may occur in the duodenal mucosa in coeliac disease and should not be used as diagnostic features to exclude the diagnosis of coeliac disease in the absence of confirmatory clinical and immunological information.

Fatal non-malignant ulceration in the gastric tube after oesophagectomy.

The clinical, histological, and necropsy findings of three cases of fatal, nonmalignant ulceration in the gastric tube after oesophageal resection for oesophageal malignancy are presented. The deaths occurred three, 30, and 42 months, respectively, after initial surgery. Two of the patients had received chemoradiotherapy, one at initial presentation, and one for a recurrence 18 months after surgery. In two patients death was due to an aspiration pneumonia, consequent on the development of a gastrobronchial fistula. The third patient died after a massive haematemesis. In none of the cases was there any evidence of residual or recurrent malignancy at necropsy, although in the two cases where radiological and endoscopic assessment was performed before death, recurrent tumour had been clinically diagnosed. As improved surgical techniques reduce the incidence of death due to anastomotic leakage and combined modality treatment regimens offer improved prospects of tumour remission, deaths from other causes will assume a greater importance. As such, the possibility that ulceration in the gastric tube may be due to causes other than tumour recurrence deserves greater recognition.

Quality assurance programme for necropsies.

One hundred and eight consecutive necropsies were entered into a quality assessment of the necropsy service in this hospital using a previously published American protocol. Our results were similar to those of the American series, with confirmation of the major clinical diagnosis in 75%, but a higher rate of unsuspected diagnosis (44%). Necropsy was helpful in 58% of cases. The presentation of selected cases at a monthly conference on causes of death was valuable in correlating clinical and pathological findings, and in helping integrate both services.

Ischaemic lesions of the alimentary tract.

The clinical and pathological findings in 23 patients with ischaemic lesions of the alimentary tract (ischaemic enterocolitis) are described. These are compared with findings in 13 patients with occlusive thrombosis of the superior mesenteric artery. The pathological features distinguishing the two conditions are discussed. Ischaemic enterocolitis was found to be a relatively common condition (0.6% of necropsies). The occurrence of mucosal fibrosis (a hitherto undescribed feature) has been of help in the biopsy diagnosis of ischaemic lesions of the gut.

Relation of granulomas to lymphatic vessels in Crohn's disease.

AIMS: To examine the relation between granulomas and lymphatic vessels in Crohn's disease. METHODS: Formalin fixed, paraffin wax embedded sections were selected from surgical resection specimens from 10 cases diagnosed as Crohn's disease. The block that showed the most granulomas was selected from each case. Sections 5 microns thick were immunostained with antibodies directed against the endothelial markers factor VIII related antigen and Ulex europaeus lectin, and against the vascular wall components collagen IV and laminin. Granulomas were counted on each slide in the serosa, muscularis propria, submucosa, and mucosa. In each area granulomas were classified according to their relation to lymphatic or blood vessels. RESULTS: Overall, an average of 46.1% of granulomas (range 15.3-90.4%) was related to lymphatic vessels, with the majority of these being adjacent to the vessel, rather than in the lumen or distorting the wall. A smaller percentage (10.1%, range 2.4-25.8%) was related to blood vessels. CONCLUSIONS: A significant proportion of granulomas in Crohn's disease is associated with lymphatic vessels. Blood vessel involvement may be a secondary phenomenon, rather than the primary event.

Peptic duodenitis--does it exist in the second part of the duodenum?

AIM: To re-evaluate all patients diagnosed histologically as having peptic duodenitis who had known endomysial antibody (EMA) test results to find out whether they would still be classified as peptic duodenitis on histological analysis and to review their subsequent clinical course. METHODS: All mucosal biopsy specimens of the second part of the duodenum which were reported as showing features of peptic duodenitis and on which a serum EMA test had been done between January 1990 and January 1995 were reviewed. The number of intraepithelial lymphocytes (IELs) per 500 epithelial cells was also counted. The cases were re-assigned to one of three clinical categories: normal, coeliac disease or peptic duodenitis. Clinical details were reviewed for any cases where the re-assigned diagnosis and the EMA test result did not correlate. RESULTS: Of the 24 cases, 21 showed a correlation between morphology and immunology-that is, if the biopsy specimen was characteristic of coeliac disease, the EMA was positive and if the biopsy specimen was normal or characteristic of peptic duodenitis, the EMA was negative. Three cases had a negative correlation: two had a positive EMA test but a biopsy diagnosis of peptic duodenitis and one had a normal duodenal biopsy specimen with a positive EMA test. On review of their clinical details, two of the three patients were diagnosed with coeliac disease and the other with silent coeliac disease. EMA test results and IEL counts correlated with the final diagnosis in all cases. CONCLUSIONS: The diagnosis of peptic duodenitis on biopsy specimens of the second part of the duodenum was not substantiated in 92% of cases. On review of 24 cases, a histological diagnosis of peptic duodenitis was reached in four. In difficult cases, the histological appearances should be correlated with the EMA test result and the IEL count. Correlation of this kind should leave no cases of coeliac disease undiagnosed.

Histological changes associated with wheat protein antibodies in the absence of villous atrophy.

A retrospective study was conducted to assess the association of alpha-gliadin antibodies with intraepithelial lymphocyte counts. Twelve subjects with apparently normal small intestinal histology and raised alpha-gliadin antibody titres had significantly increased intraepithelial lymphocyte counts (42 (SEM) 5.9) when compared with 16 subjects with normal alpha-gliadin antibody titres (17 (3.2); p less than 0.001). These findings show that in the absence of gross pathology raised alpha-gliadin antibody titres are associated with increased numbers of intraepithelial lymphocytes and may reflect continuous immunological processes in the small intestine.

Duodeno-jejunal adenocarcinoma as a first presentation of coeliac disease.

Long standing coeliac disease is associated with an increased risk of malignancy, not only of intestinal lymphoma but also small intestinal adenocarcinoma. Two patients whose initial presentation was adenocarcinoma of the small bowel, but who were subsequently found to have coeliac disease after Whipple's resection, are described. The diagnosis was made early in the postoperative period in the first patient after close histological examination of the tumour-free mucosal margins. This patient was placed on a gluten-free diet and had an uncomplicated postoperative recovery with rapid weight gain. Diagnosis and dietary intervention in the second patient was very delayed and resulted in the development of severe malabsorption and weight loss. This illustrates the importance of ruling out coeliac disease prior to surgery in patients with small intestinal malignancies.

DNA ploidy in squamous oesophageal carcinoma.

The role of DNA ploidy in the management of oesophageal carcinoma is unclear. Most studies have employed flow cytometry (FC) for DNA analysis but some have used image analysis (IA) of tissue sections. In this study aneuploidy rates in stage IIa squamous tumours were determined by both FC and IA of cell suspensions and results were compared with outcome in two patient subgroups. Group 1 (n = 15) were patients who died from tumour recurrence within 1 year of surgery while Group 2 (n = 21) were patients who survived tumour free for at least 1 year. Aneuploidy rates differed significantly between techniques; 29 of 36 tumours (81%) were aneuploid by IA compared with 19 of 34 (56%) by FC (P < 0.05). Aneuploidy rates differed significantly between groups 1 and 2 as determined by FC (79%) versus 40%) (P < 0.05) but not by IA (93% versus 71%) (P = ns). Euploid status was a good prognostic indicator; 6 of 7 (86%) patients with euploid tumours by IA and 12 of 15 (80%) by FC (P < 0.05) survived more than 1 year. The sensitivity and specificity of euploidy was 93% and 28.6% for IA compared with 78.6% and 60% for FC. Since 33 (92%) of these tumours exhibited a marked peritumoral desmoplastic or chronic inflammatory reaction IA, being more sensitive to subtle nuclear change, may be a more appropriate technique than FC for evaluation of the role of ploidy in such tumours.

Colo-rectal carcinoma 1975 and 1990: no improvement in the stage of disease at resection.

There is no overall consensus as to what screening patterns should be adopted for individuals of average risk for colo-rectal carcinoma. The single most important prognostic factor in survival is the stage of the colo-rectal neoplasm at the time of resection. Consequently significant resources have been directed to early detection while the disease is at a curative stage. To assess the impact of widespread availability of faecal occult blood testing and large bowel endoscopy we prospectively examined all large intestine specimens resected for carcinoma in 1990 and compared them with specimens resected for colonic carcinoma in 1975. We excluded adenomatous polyps with malignant change which had been treated by snaring at colonoscopy, without subsequent colectomy, as their precise Duke's staging was so difficult. In any event, their numbers were small (> 5 in 1990). Our study shows that despite the resources targeted at early diagnosis of colo-rectal carcinoma resection of tumours at a prognostically favourable stage has not been improved in the 25 years since 1975.

Helicobacter pylori infection increases following cholecystectomy.

Cholecystectomy is frequently linked with duodenogastric reflux and gastritis but its effect on Helicobacter Pylori (H pylori) infection has not been examined. In a prospective study, twenty two patients with documented cholelithiasis underwent upper gastrointestinal endoscopy and biopsy and 24hr dual channel pH monitoring prior to cholecystectomy and again at 3-6 months post-operatively. The antral biopsies were histologically assessed for H pylori and gastritis and awarded an alkaline reflux score. The number of patients with H pylori infection increased from 7 (32%) preoperatively to 15 (68%) post-cholecystectomy (p < 0.05). Cholecystectomy was also associated with an increase in the incidence of gastritis from 7 to 15 (p < 0.05). The increase in H pylori infection rate occurred in association with an increase in the percentage time gastric pH > 4 in the supine position, from 9.6 (2.2) to 22.2 (4.8) percent, (p < 0.01). The median chemical gastritis score, however, did not change significantly following surgery [8(3-11) vs 7(3-11)]. Seven patients remained symptomatic following cholecystectomy all of whom were H pylori positive and had gastritis. H pylori can survive in the alkaline environment which follows cholecystectomy and may contribute to the post-cholecystectomy syndrome.

Coeliac disease during the teenage period: the value of serial serum folate estimations.

A group of teenage coeliac patients has been followed at three monthly intervals in the Outpatient Department to assess their progress and also to monitor their ability to maintain a gluten-free diet. After a follow-up period of four to six years a detailed reassessment was carried out in hospital on 10 patients, only five of whom had persevered with a gluten-free diet. The jejunal mucosal histology of those patients who did not persist with a gluten-free diet remained ;flat' although these patients appeared to have remitted clinically. Those subjects who did persist with a gluten-free regime had a normal or near normal mucosal histology. It was difficult on the basis of clinical, haematological, or biochemical criteria to separate the two groups. The best single assessment of whether these patients were maintaining a gluten-free diet was serial serum folate estimations. It is often extremely difficult to say whether teenage coeliac patients are keeping to their diet unless repeated jejunal biopsies are obtained, and this study suggests that serial serum folate estimations can act as a reasonable criterion of whether subjects are maintaining a gluten-free regime.