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Biomedical subjects

B F Warren

Publications and source records attributed to B F Warren.

At least 19 recordsLinked to original sources

The relationship between inflammatory and serosal connective tissue changes in ileal Crohn's disease: evidence for a possible causative link.

The relationship between the gross connective tissue and inflammatory changes in ileal Crohn's disease remains unclear. This study investigated 20 patients undergoing ileal resection for Crohn's disease and 20 normal controls. The specimens were blocked in 1 cm serial sections and fully examined, including fresh morphometry and documentation of a range of pathological features. Pathological features of disease showed uniform distributions within affected segments, although specimens showed different patterns and severity of affliction. Serosal fat wrapping (FW) was present in all cases and was significantly greater than normals [mean 63.5% (SD 27. 8) vs. 21.0% (6.4), p<0.001], as was mesenteric thickening (MTh) [mean 18.0 mm (SD 11.1) vs. 5.9 mm (2.2), p<0.001]. The extent of FW correlated significantly with the degree of acute and chronic inflammation (r()=0.32 and 0.23 respectively, p<0.01), particularly the extent of transmural inflammation in the form of lymphoid aggregates (r()=0.35, p<0.01). MTh did not correlate with any features studied. These findings support the hypothesis that serosal connective tissue changes in Crohn's disease are related to the local effects of underlying chronic inflammatory infiltrates. Full thickness, radial samples from a grossly affected area are representative of the histopathological features present in a diseased segment as a whole.

Acute Disease↗

Aneuploidy and columnar cuff surveillance after stapled ileal pouch-anal anastomosis in ulcerative colitis.

PURPOSE: A stapled pouch-anal anastomosis without mucosectomy is widely used in restorative proctocolectomy. Uncertainty exists about the longer-term outcome of retaining a columnar cuff of epithelium in the anal canal and about the need for surveillance of the columnar cuff. The aim of this article was to assess the ability to obtain biopsies of the columnar cuff, to assess the risk of dysplasia, and to search for the presence of aneuploidy as an early of marker of dysplasia in nondysplastic epithelium. METHOD: A total of 457 biopsy specimens were taken during 203 examinations of 113 patients. All biopsy specimens were stained with hematoxylin and eosin and examined by microscopy. One hundred thirty-two of these biopsy specimens from 67 patients were frozen and analyzed by flow cytometry for aneuploidy. RESULTS: Mean follow-up after pouch formation was 2.5 years, and the time after diagnosis of ulcerative colitis was 10.1 years. Successful columnar cuff biopsies were done on 93 percent of patients. There was no dysplasia. Two biopsy specimens from one patient had aneuploidy. CONCLUSION: To date, neoplastic change in the columnar cuff is rare. A selective policy of surveillance biopsies is recommended that includes patients greater than ten years after the diagnosis of ulcerative colitis and patients with dysplasia or cancer in their proctocolectomy specimen, but long-term follow-up data are needed.

Anal Canal↗

Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas.

BACKGROUND: MUC5AC is a secreted mucin aberrantly expressed by polypoid colorectal adenomas. It has been hypothesised that the "normal" surrounding colorectal mucosa expresses MUC5AC as a field change phenomenon that can be used to predict adenoma recurrence following resection. AIM: To determine if there is a field change of de novo MUC5AC expression in histologically normal rectal mucosa adjacent to villous and tubulovillous adenomas, and thus whether MUC5AC expression can be used as a marker of early tumour recurrence. METHODS: In a prospective cohort study paired mucosal biopsies of adenomatous and macroscopically "normal" mucosa were obtained from 11 patients with villous and 11 patients with tubulovillous adenomas who underwent primary resection for purpose of cure. The tissues were studied to determine MUC5AC gene expression by immunohistochemistry and in situ hybridisation. Patients were followed up by flexible sigmoidoscopy to detect the presence of early local recurrence. RESULTS: 10 villous adenomas showed mature MUC5AC glycoprotein and all 11 expressed MUC5AC mRNA. Five tubulovillous adenomas showed mature MUC5AC glycoprotein and 10 expressed MUC5AC mRNA. Neoexpression of the MUC5AC mucin gene was not detected in any of the mucosal biopsies taken adjacent to either villous or tubulovillous adenomas, even in three patients with early, locally recurrent disease. CONCLUSIONS: Aberrant MUC5AC gene expression is not a "field change" in the colorectal mucosa in patients with rectal adenomas and therefore cannot be used to predict local recurrence of villous and tubulovillous adenomas.

Adenoma, Villous↗

"Cuffitis" and inflammatory changes in the columnar cuff, anal transitional zone, and ileal reservoir after stapled pouch-anal anastomosis.

PURPOSE: During the past eight to ten years most surgeons have adopted the double-stapled technique to accomplish the pouch-anal anastomosis in restorative proctocolectomy for ulcerative colitis. Little attention has been focused on the functional implications of retaining a segment of diseased columnar mucosa in the upper anal canal. The aim of this study was to investigate clinically significant inflammation in the columnar cuff. METHOD: In all, 113 patients were studied and 715 biopsies were performed during a 2.5-year period. Biopsy specimens were taken from two or three sites, including the columnar cuff, ileal pouch, and anal transitional zone. Acute and chronic inflammation was scored for biopsy specimens from all three sites and compared with endoscopic assessment and pouch function. RESULTS: In the columnar cuff acute histologic inflammation was found in 13 percent of patients, and in 9 percent this was symptomatic during follow-up and was accompanied by evidence of endoscopic inflammation. Most patients had mild inflammation in the cuff that persisted over time. Inflammation in the pouch, pouch frequency, and anastomotic height were not related to columnar cuff inflammation. CONCLUSIONS: Cuffitis is a cause of pouch dysfunction after a double-stapled restorative proctocolectomy. We propose a triad of diagnostic criteria, including symptoms and endoscopic and histologic inflammation.

Anal Canal↗

Reduction of sialic acid O-acetylation in human colonic mucins in the adenoma-carcinoma sequence.

The oligo-O-acetylation of sialic acids found in normal colonic mucins is greatly reduced in colorectal cancer. Mucins prepared from cancer tissue in adenocarcinoma showed this reduction, while normal O-acetylation was detected in resection margin and control cases and total mucin sialic acid content was significantly decreased in cancer vs. control samples. A reduction of the O-acetyl transferase activity catalysing the O-acetylation reaction was also found. A series of cultured human colorectal cell lines derived from the same premalignant adenomatous line, and representative of the adenoma-carcinoma sequence were examined and revealed a depletion of oligo-O-acetylation in the original diploid premalignant line, re-expression in a further premalignant line and reduction in malignant mucinous and adenocarcinoma cell lines. Reduction of sialic acid O-acetylation appears as an early event in the process of malignant transformation in human colorectal cancer.

Acetylation↗

Comparison of two closure techniques for the repair of experimental colonic perforations.

BACKGROUND: Primary repair of penetrating wounds of the colon is gaining increasing acceptance in surgical practice. This study compared two techniques for the repair of experimental colonic perforations in the presence of peritonitis. METHODS: Multiple colonic perforations were created in the colon of 24 pigs. Following a 6-h delay the perforations were closed either by local excision and suture or by skin staples applied to the seromuscular layers of the colon. The repairs were assessed biomechanically and histologically for up to 14 days after surgery. RESULTS: All animals had diffuse peritonitis at the time of colonic repair. Stapled repairs were completed significantly faster than sutured repairs (mean(s.d.) 4.8(1.6) versus 30.7(4.0) min, P < 0.001). Bio- mechanical evaluation of repairs revealed no significant differences between the two techniques. Histological examination of repairs closed by staples demonstrated more advanced healing compared with suture closure, on the basis of tissue apposition and inflammatory changes. CONCLUSION: Experimental colonic injuries may be treated successfully by primary repair in the presence of peritonitis. The use of skin staples for repair does not appear to prejudice colonic wound healing.

Animals↗

Preoperative radiotherapy for rectal cancer: implications for surgeons, pathologists and radiologists.

BACKGROUND: Over 10,000 new cases of rectal cancer are reported in the UK each year and adjuvant treatments, such as preoperative radiotherapy, are now being used almost routinely. METHODS: A literature review was performed on the Medline database for English language publications on preoperative radiotherapy and rectal cancer. The radioresponsiveness of rectal cancer, tumour downstaging, radiological staging of irradiated rectal cancer, effects of radiotherapy on anastomotic integrity, anorectal and genitourinary function, the role of preoperative radiotherapy in local excision of rectal cancer, and the histological changes peculiar to radiotherapy were evaluated. RESULTS AND CONCLUSION: Following preoperative radiotherapy, rectal cancer may be downstaged or, occasionally, eradicated histologically. Rectal cancer can now be staged accurately before operation, but this is significantly less reliable following irradiation. The pathological specimen must be examined thoroughly before a tumour can be reported to have been eradicated, especially as unique histological changes are produced by radiotherapy. There is no evidence to suggest that preoperative radiotherapy adversely affects anastomotic integrity. It appears that preoperative radiotherapy has some adverse affects on long-term anorectal dysfunction, but this must not distract from its main objectives in rectal cancer, namely reduced local recurrence rates and improved overall survival.

Colorectal Neoplasms↗

Polymerase chain reaction based human leucocyte antigen genotyping for the investigation of suspected gastrointestinal biopsy contamination.

BACKGROUND: Mislabelling or contamination of surgical specimens may lead to diagnostic inaccuracy, particularly within gastrointestinal pathology when multiple small mucosal biopsy specimens are commonly taken, and where a tiny fragment of foreign tissue may be indistinguishable from true biopsy material using histological assessment alone. AIMS: To assess the utility of polymerase chain reaction (PCR) based human leucocyte antigen (HLA) genotyping techniques for the investigation of potentially mislabelled or contaminated gastrointestinal biopsy specimens. PATIENTS: Ten cases (28 samples) in which mislabelling or contamination was suspected, comprising four upper gastrointestinal tract biopsies and six colonoscopic biopsy series. METHODS: Direct and nested PCR-sequence specific primer (SSP) based HLA class II genotyping was performed on DNA extracted from formalin fixed and paraffin wax embedded tissue (23 samples) or peripheral blood leucocytes (five samples). RESULTS: A full HLA-DRB1 genotype was determined in all 28 samples. In seven cases the HLA-DRB1 genotype of the putative contaminant was different to that of the corresponding reference tissue, confirming different individual origins for the contaminant and reference material. In one case the contaminant tissue was shown to possess the same HLA-DRB1 alleles as a second patient (probable source). In the remaining three cases the same HLA-DRB1 alleles were detected within the potential contaminant and reference tissues. CONCLUSIONS: PCR based HLA class II genotyping is a valuable tool for investigating potential contamination or mislabelling within gastrointestinal biopsy specimens and this report has confirmed contamination in seven of ten cases studied.

Adult↗

Interpreting the 13C-urea breath test among a large population of young children from a developing country.

The 13C-urea breath test is a noninvasive tool for the diagnosis of gastric Helicobacter pylori infection. However, it has not been validated in young children from the developing world, where infection is very common. 13C urea breath tests were performed on 1532 occasions on 247 Gambian infants and children aged from 3 to 48 mo. The means and variances of the separate sub-populations of 13C enrichment results contained within the overall dataset were estimated by a Genstat procedure using the EM algorithm, thereby identifying a cut-off value to discriminate positive from negative results. To illustrate the appropriateness of this calculated cut-off value, 13C urea breath tests were performed upon a small group of 14 patients aged 6 to 28 mo undergoing diagnostic upper endoscopy. Fixed gastric antral biopsies were examined to identify H. pylori. Two subpopulations were identified within the large dataset. A cut-off value of 5.47 delta per thousand relative to Pee Dee Belemnite limestone above baseline at 30 min identified 95% of the normally distributed negative sub-population and 99.4% of the log normal distributed positive sub-population. Comparison with endoscopic data confirmed that this cut-off value was appropriate for this population, as 7/7 children without H. pylori on their gastric biopsies had negative urea breath tests, and 6/7 children with gastric H. pylori colonization had positive urea breath tests. These findings confirm the value of the urea breath test as a diagnostic tool in young children from developing countries. They also offer a way to calculate the most appropriate cut-off value for use in different populations and the likelihood that it will correctly assign any value into the appropriate sub-population, without the need for endoscopy.

Breath Tests↗

Early colorectal cancer: recognition, classification and treatment.

BACKGROUND: With the introduction of colorectal cancer screening and improvements in endoscopic technology, the recognition and management of early colorectal cancer assumes increasing importance. METHODS: A literature review was undertaken using Medline (National Library of Medicine, Washington DC, USA) searches of the headings early colonic, colorectal and rectal cancer, carcinoma and adenocarcinoma up to and including 1997. All relevant references were examined. RESULTS AND CONCLUSION: The diagnosis, classification and treatment options are described. Accurate diagnosis, preoperative and histopathological staging is crucial in the management of early colorectal cancer.

Colorectal Neoplasms↗

A new look at the anal transitional zone with reference to restorative proctocolectomy and the columnar cuff.

BACKGROUND: The anal transitional zone (ATZ) is of interest in relation to anorectal function and its fate during the operation of restorative proctocolectomy. There are only a few studies describing the anatomy of this structure. This study applied new techniques to quantify the ATZ in normal and inflammatory bowel disease states. METHODS: The epithelial linings of 28 anal canals were analysed by two techniques: whole-mount Alcian blue staining and a new method of creating a computer map of the histological findings based on longitudinal sections taken every 3 mm. The Alcian blue pictures and the histology maps were measured and compared using image analysis software. RESULTS: The ATZ usually commences just above the dentate line, which is situated a median of 1.05 cm above the lower border of the internal sphincter. The median length of the ATZ measured from computer maps of the histology was 0.45 cm. This was significantly smaller than the 0.73 cm obtained by the Alcian blue technique, which overestimates the length of the ATZ. The amount of columnar epithelium in the ATZ is very small. The median lowest point of columnar epithelium in the anal canal was 1.1 cm above the lower border of the internal sphincter. CONCLUSION: The ATZ is only half the length described previously. After double-stapled restorative proctocolectomy there is a 1.5-2.0-cm cuff of diseased columnar epithelium remaining in the upper anal canal above the ATZ. This is suitably termed the 'columnar cuff' and is an important consideration in long-term follow-up.

Anal Canal↗

Apparent deficiency of mucosal vascular collagen type IV associated with angiodysplasia of the colon.

AIMS: To investigate the presence and distribution of vascular collagen type IV in colonic tissue in cases of angiodysplasia and age and sex matched controls. METHODS: Sections of colon from seven cases of colonic angiodysplasia and eight age and sex matched controls were examined for the presence of collagen type IV in vessels of the mucosa and submucosa. Immunohistochemical staining was performed on paraffin wax embedded sections, and the degree of vascular staining for each marker compared between mucosa and submucosa and between cases and controls. Staining for endothelial markers P-selection and factor VIII was used to control for non-specific differences in immunostaining. RESULTS: In both the angiodysplastic tissues and approximately half the control tissues, staining for collagen type IV was considerably weaker in vessels in the mucosa than in the submucosa. In angiodysplasia, ectatic vessels in the mucosa appeared to contain less collagen type IV than similarly sized vessels in the submucosa, and perforating vessels appeared in many cases to lose staining at the level of the muscularis mucosae. No differences were found in staining intensity for the control endothelial markers between cases and controls. CONCLUSIONS: The apparent relative deficiency of collagen type IV in the mucosal vessels in angiodysplasia may be related to their susceptibility to ectasia and haemorrhage. The finding of a similar deficiency in half of the control cases may reflect a population at risk of this relatively common condition.

Aged↗

How many lymph nodes to stage colorectal carcinoma?

This study aimed to establish the number of cassettes that should be filled with lymph nodes to stage a colorectal carcinoma as Dukes's stage C. The records from the Oxford Colorectal Cancer database of all patients diagnosed with Dukes's stage C cancer from late 1988 to early 1993 were reviewed. Each slide of lymph nodes was examined to determine how many slides needed to be looked at to find the first positive lymph node. The resected specimens were not fat cleared but dissected manually in a routine fashion. One hundred and eight slides were retrieved. The mean total lymph node harvest was 8.44 for each patient. Ninety eight patients (90.7%) had positive lymph nodes on the first slide with an average of 3.42 lymph nodes on each slide, of which a mean of 1.82 were positive. For nine patients, two slides were required to make a diagnosis of lymph node involvement, and for one patient the first three slides needed inspection to establish Dukes's stage C. In conclusion, using a routine technique to obtain lymph nodes from colorectal cancer specimens 99% of Dukes's stage C colorectal carcinoma can be found by filling two cassettes with lymph nodes.

Adenocarcinoma↗

Unacceptably high site variability in postmortem blood alcohol analysis.

Blood alcohol concentration is a frequently requested test in forensic pathology. The variability of this value was studied by measuring the blood alcohol concentration from six sites in nine subjects at necropsy in whom alcohol was the implicated cause of death. There were small consistent differences in the blood alcohol concentrations between the sites in the nine subjects (p < 0.04). Calculation of the mean blood:vitreous humour alcohol concentration ratio (B:V ratio) showed that vitreous humour alcohol concentration most closely reflected the concentration at the femoral vein (B:V ratio = 0.94, r = 0.98), which is considered the optimal site for blood alcohol measurement. The correlation of left heart blood with femoral blood was lower compared with the other sites. There is a potential for an unacceptably large variation in the postmortem measurement of blood alcohol within each subject.

Accidents, Traffic↗