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Biomedical subjects

B F Warren

Publications and source records attributed to B F Warren.

At least 37 records · Page 2Linked to original sources
PubMed2002

Histopathology of stapled haemorrhoidectomy specimens: a cautionary note.

OBJECTIVE: Stapled haemorrhoidectomy is a new technique with encouraging early results. The aim of this study was to examine the tissue removed during stapled haemorrhoidectomy, in particular to check on the presence or absence of transitional or squamous anal canal mucosa and internal anal sphincter muscle. METHODS: Twenty-six consecutive patients undergoing stapled haemorrhoidectomy were studied. Resected tissue was examined histologically according to a standardized histological protocol. RESULTS: All 26 specimens contained columnar mucosa. Twelve specimens also contained anal transitional and stratified squamous epithelium. Two specimens contained columnar and transitional mucosa. Twenty-two of 26 specimens contained smooth muscle as well as mucosa (median maximum diameter 7.5 mm, range 2-20 mm). In 11 specimens this was circular muscle only; in 11 circular and longitudinal smooth muscle were present. In 10 specimens smooth muscle was seen to be lying beneath stratified squamous or transitional epithelium, suggesting that it was from the internal anal sphincter. CONCLUSIONS: Stapled haemorrhoidectomy results in resection of stratified squamous mucosa or part of the internal anal sphincter in a significant proportion of patients. Surgeons should be aware that this technique may result in damage to the internal anal sphincter.

Journal Article↗
PubMed2002

Histological changes associated with the use of intravenous cyclosporin in the treatment of severe ulcerative colitis may mimic dysplasia.

BACKGROUND: During six years experience of intravenous cyclosporin (i.v. Cy) for severe ulcerative colitis we have noted that changes of villous architecture and epithelial regeneration occur even when the disease fails to enter clinical remission and colectomy is required. OBJECTIVE: To describe the histological changes in patients who received i.v. Cy and steroids compared with those treated with i.v. steroids alone. PATIENTS AND METHODS: Two groups of histological sections were reviewed. The first group was of 23 colectomy specimens from patients who had been treated with i.v. Cy and steroids. For 11 patients pre-Cy histological sections were available. The second group was of 10 colectomy specimens from patients who had received i.v. steroids alone. Biopsies were scored for their histological disease activity (HDAI), villous architecture and epithelial regeneration. The HDAI assesses the degree of acute and chronic inflammation. RESULTS: The post-Cy group had higher median scores for villous architecture and epithelial regeneration compared to the pre-Cy and poststeroid groups. For the patients where both pre- and post-Cy histological sections were available 63% increased their villous score post-Cy and 82% increased their epithelial regeneration score post-Cy. CONCLUSION: Although villous transformation and epithelial regeneration may be seen in UC they are more frequent and more severe in those patients who received i.v. Cy and i.v. steroids, compared to controls who received i.v. steroids alone. These histological changes may mimic dysplasia. Increased awareness of this potential mimic of dysplasia is crucial for patient management.

Journal Article↗
PubMed2002

An insight into the genetic pathway of adenocarcinoma of the small intestine.

BACKGROUND: Although the adenoma to carcinoma pathway in colorectal cancer is well described, the mechanisms of carcinogenesis in the small intestine remain unclear. AIMS: The aim of this study was to investigate candidate genes in the genetic pathway of adenocarcinoma of the small intestine. SUBJECTS AND METHODS: A total of 21 non-familial, non-ampullary adenocarcinomas of the small intestine were analysed. DNA was extracted from formalin fixed paraffin wax embedded tissue using standard techniques. The replication error (RER) status was determined by amplification of BAT26. The mutation cluster region (MCR) of the adenomatous polyposis coli (APC) gene was screened using polymerase chain reaction single strand conformational polymorphism and direct sequencing. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for hMLH1, hMSH2, beta-catenin, E-cadherin, and p53. RESULTS: Fourteen male and seven female patients with a median age of 64 years (range 21-85) presented with adenocarcinoma of the duodenum (10), jejunum (7), and ileum (4). One cancer (5%) was found to be RER+, and all tumours stained positive for hMLH1 and hMSH2. No mutations were detected in the MCR of the APC gene. beta-Catenin showed increased nuclear expression with loss of membranous staining in 10 cancers (48%). Absent or decreased membrane expression of E-cadherin was found in eight cancers (38%). Strong staining of p53 was found in the nucleus of five cancers (24%). CONCLUSION: We did not detect mutations in the MCR of the APC gene, and this suggests that adenocarcinoma of the small intestine may follow a different genetic pathway to colorectal cancer. Abnormal expression of E-cadherin and beta-catenin was common and reflects an early alternative to APC in this pathway in which mutations may be found in adenocarcinoma of the small intestine.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Mucin gene expression in the ileoanal reservoir is altered and may be relevant to the risk of inflammation and dysplasia.

BACKGROUND: Adaptive colonic phenotypic change of the ileal mucosa is a feature of the ileoanal reservoir (IAR) with time, as described by mucin glycoprotein and histological analysis. Mucin gene expression is altered in colorectal neoplasia and inflammatory bowel disease but little is known of its expression in the IAR. AIMS: To examine the changes in mucin gene expression contributing to mucosal protection of the IAR against a background of known changes occurring in inflammatory disease and colorectal neoplasia. PATIENTS: Paraffin embedded specimens from 29 "W" and 11 "J" ileoanal reservoirs were studied. Colonic and ileal control tissue was obtained from normal resection margins. METHODS: Mucin mRNA was detected by in situ hybridisation using [(35)S]dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry. RESULTS: There was no change in mRNA expression of MUC1-4 in the IAR compared with ileal controls but there was a decrease in the protein product of MUC1 and MUC3. No mRNA transcripts of MUC5AC, 5B, or 6 were detected but protein product of MUC5AC and MUC6 was detected. Both cases of MUC6 positivity and 1/5 cases of MUC5AC positivity were confined to the ulcer associated cell lineage. No dysplasia was detected. CONCLUSIONS: There is a change in the pattern of the membrane associated mucins MUC1 and MUC3, part of which is in keeping with changes described in colorectal neoplasia. A small number of cases demonstrated mucin gene changes (MUC5AC) which are seen in early neoplasia and this may provide a valuable monitor for such changes in IAR surveillance.

Child↗
PubMed2002

Reduplication cyst of appendix with mucinous carcinoma and Müllerian metaplasia: a case report.

This report describes a case of mucinous carcinoma and Müllerian metaplasia arising within an appendiceal duplication cyst found incidentally during an emergency Caesarian section. Intestinal duplication cysts are rare and although there are occasional reports of malignant transformation, this is the first case where Müllerian metaplasia was found concurrently with a malignancy. There was no previous history of endometriosis and no other abnormalities were found at surgery. Treatment included surgical excision. The patient is alive and well two years after removal of the cyst.

Adenocarcinoma, Mucinous↗
PubMed2002

Dukes' staging is poorly understood by doctors managing colorectal cancer.

OBJECTIVE: This study set out to investigate the current understanding of Dukes' staging for colorectal cancer. DESIGN: A questionnaire was distributed to surgeons and general practitioners attending colorectal meetings asking for a definition of Dukes' stages A, B and C. Results were analysed blind by two authors jointly to assess accuracy as correct, within definition, or incorrect. Within definition was defined as a description fitting within but not covering all tumours within that stage. RESULTS: 128 answers were received from 48 GPs, 7 final year medical students, 38 house officers and SHOs, 19 higher surgical trainees and 16 consultants. Overall, 3.9% defined all three stages correctly and 13.3% got all three definitions incorrect. Correct stages were Dukes' A 7.8%, Dukes' B 16.4% and Dukes' C 29.7%. Two consultants (12.5%) achieved three correct definitions, as did two HSTs (10.5%). No GPs had all three stages correct and 10 (20.8%) were wrong in all three. If those said to be within definition were considered right, 35.1% were correct for all three stages with 76.6% getting Dukes' A correct, 46.9% Dukes' B and 56.6% Dukes' C. CONCLUSIONS: Dukes' staging is, therefore, still poorly understood by doctors managing patients with colorectal cancer. The introduction of proformas will reduce the reliability upon memory for this and more complex staging classifications.

Clinical Competence↗
PubMed2001

Differential expression of the chromosome 11 mucin genes in colorectal cancer.

The four secretory mucin genes clustered on chromosome 11, MUC2, MUC5AC, MUC5B and MUC6, were screened in 37 patients with cancers in the left hemi-colon or rectum and 10 normal rectal controls. The mucin genes were detected by in situ hybridization using oligonucleotide probes to the variable number tandem repeat (VNTR) sequences, while the proteins were stained with non-VNTR (MUC2, MUC5AC and MUC5B) or VNTR (MUC6) antibodies. Low levels of MUC2 mRNA were detected in non-mucinous adenocarcinomas (5/27) while a higher proportion of mucinous carcinomas (4/9) was positive. All 25 cases of adjacent normal tissue expressed MUC2 mRNA. No transcripts for MUC5AC, MUC5B or MUC 6 were detected in any of these specimens. MUC2 protein product was detected immunohistochemically in 34/36 carcinoma specimens, with no change from normal controls. There was de novo expression of MUC5AC in 23/36 carcinomas. No MUC5B or MUC6 protein was detected. No difference in MUC2 and MUC5AC protein was found between mucinous and non-mucinous carcinomas. The level of MUC2 was increased in moderately differentiated cancers compared with normal controls and decreased in the poorly differentiated group. Decreased MUC2 was found in poorly differentiated compared with moderately differentiated tumours. More MUC5AC protein was detected in well and moderately differentiated tumours than in poorly differentiated tumours and in all tumours relative to controls. The pattern of MUC2 staining in cancers was different from control tissue, with strong staining in the perinuclear region and none in goblet cell vesicles. MUC5AC staining was mainly detected in the cytoplasm. Poor detection of MUC2 and MUC5AC mRNA and associated strong staining for the total protein suggests altered biosynthesis and processing, leading to the characteristic subcellular distribution. Hence, change in the synthesis of MUC2 and the de novo appearance of MUC5AC in colorectal carcinomas may be significant events in the adenoma-carcinoma sequence, with possible implications for tumour prognosis.

Adenocarcinoma↗
PubMed2001

Connective tissue changes in ileal Crohn's disease: relationship to disease phenotype and ulcer-associated cell lineage.

PURPOSE: Abnormalities of enteric collagen and smooth-muscle cell content have been documented in Crohn's disease. We studied the relationships among connective tissue changes, disease "type," and other disease features using immunohistochemistry and image analysis. METHODS: Twenty consecutive ileal resections for Crohn's disease and ten normal terminal ileal specimens were evaluated using conventional histopathologic examination. Monoclonal antibodies to smooth-muscle actin and Type III collagen fibers were used to determine the percentage area of the submucosa occupied by these constituents using image analysis. RESULTS: There were no significant differences in smooth-muscle content among stenosed, perforated, and ulcerated specimens. There was a significantly increased submucosal Type III collagen content in stenosed vs. other types. The only factor that correlated with smooth-muscle cell content was the amount of ulcer-associated cell lineage present. CONCLUSIONS: Increased deposition of Type III collagen fibers rather than smooth-muscle proliferation is associated with a stenotic phenotype. Loss of Type III collagen fibers may play a role in the development of perforating complications. We have found no evidence that smooth-muscle cells are the source of Type III collagen fiber production although there is evidence that ulcer-associated cell lineage may be related to the stimulus leading to submucosal neomuscularization.

Cell Division↗
PubMed2001

The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo.

Fractalkine (CX3CL1) is synthesized as a type I transmembrane protein. Its unique CX(3)C chemokine domain is attached to a 241-amino acid mucin stalk, a 19-amino acid transmembrane domain, and a 37-amino acid intracellular domain of unknown function. A soluble form of fractalkine can be generated by proteolytic cleavage at the base of the mucin stalk. Novel monoclonal and polyclonal antibodies that specifically recognize only the amino- or carboxyl-terminal ends of the human fractalkine molecule have revealed that epithelial cells are the predominant cell type expressing transmembrane forms of fractalkine in human skin, the tonsil, and the large intestine. Using these specific anti-fractalkine reagents we do not detect high-level expression of fractalkine on endothelial cells in normal or inflamed colon samples obtained from patients with Crohn's disease or ulcerative colitis. In contrast to previous reports we do not detect fractalkine expression by Langerhans cells or immature dendritic cells in mucosal-associated lymphoid tissues in vivo. We show that the reagent used in previous studies, an anti-fractalkine N-terminal peptide antisera, cross-reacts with human CD84. Finally we discuss potential roles for fractalkine in constitutive leukocyte trafficking based on its observed pattern of expression in epithelia.

Adenocarcinoma↗
PubMed2001

The African enigma: low prevalence of gastric atrophy, high prevalence of chronic inflammation in West African adults and children.

BACKGROUND: Helicobacter pylori infection is very common in Africa, yet peptic ulcer disease and gastric malignancy are rare. AIM: The aim of this study was to quantify mucosal responses to H. pylori in Gambian adults and children and to estimate the prevalence of antibodies to bacterial virulence factors (cagA and vacA) in a symptomatic population. PATIENTS AND METHODS: Adults (mean 36 SD 12 years) with dyspepsia and children (mean 1.4 years SD 0.4 years) with malnutrition underwent gastroscopy with biopsy. Blood was simultaneously drawn for cagA and vacA antibody status. Histopathological scoring used the modified Sydney classification. RESULTS: Both adults (n = 45) and children (n = 37) mainly demonstrated chronic mild antral inflammation. Only 2/83 cases of focal atrophy (GA) and 4/83 cases of intestinal metaplasia (IM) were observed. Adults tended to demonstrate more frequent acute (AI) and chronic inflammation (CI) (38% compared with 18% and 85% compared with 72%, respectively). Sixty-seven percent of children were cagA IgG+ and 21% vacA IgG+ and 93% of adults were IgG cagA+ and 86% vacA+. There were no differences in mucosal responses between those who were cagA or vacA positive compared with those who were negative. CONCLUSION: Gambian adults and children mount a CI response to H. pylori but GA, IM and AI are uncommon. cagA and vacA are commonly expressed in Gambian strains of H. pylori. Further studies are needed in order to confirm that GA and IM are not late findings in old age.

Adolescent↗
PubMed2001

Adult small bowel Dieulafoy lesion.

A 47 year old woman presented with melaena and haemodynamic instability. Preliminary investigations failed to locate the source of bleeding. At laparotomy an arteriovenous malformation was identified in the distal ileum. Histology revealed this to be of the Dieulafoy type. This is the first published case of a histologically proved ileal Dieulafoy lesion in an adult.

Arteriovenous Malformations↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Role of a defunctioning stoma in the management of large bowel Crohn's disease.

BACKGROUND: The faecal stream plays a significant role in the pathogenesis of Crohn's disease. This retrospective study aimed to assess the effect of faecal diversion on the natural history of refractory Crohn's colitis (RCC) and severe perianal disease (PAD). METHODS: All patients undergoing a defunctioning stoma without resection for RCC or PAD between 1970 and 1997 were studied. Indications for surgery, acute clinical response, subsequent outcome and stoma rates were recorded. RESULTS: Some 73 patients underwent a defunctioning stoma (55 RCC and 18 PAD). Acute remission was achieved in 63 patients (48 RCC, 15 PAD). Twenty-nine patients had subsequent closure of the defunctioning stoma (25 of 48 acute responders with RCC and four of 15 acute responders with PAD). Eleven patients with RCC and two with PAD achieved good long-term function without disease relapse (median follow-up 36 months). Overall 52 patients have undergone proctocolectomy or remain with a defunctioning stoma (37 with RCC and 15 with PAD). CONCLUSION: Faecal diversion is associated with acute clinical remission in the majority of patients with RCC and PAD, but sustained benefit occurs less often. For selected patients, diversionary surgery alone offers a realistic alternative to major bowel resection.

Adult↗
PubMed2000

Anatomy of Denonvilliers' fascia and pelvic nerves, impotence, and implications for the colorectal surgeon.

BACKGROUND: The development and anatomy of Denonvilliers' fascia have been controversial for many years and confusion exists about its operative appearance. Better appreciation of this poorly understood anatomy, and its significance for impotence after rectal dissection, may lead to further functional improvements in pelvic surgery. METHOD: A literature review of the embryology and anatomy of Denonvilliers' fascia and impotence after pelvic rectal surgery was undertaken. RESULTS: Denonvilliers' fascia has no macroscopically discernible layers. The so-called posterior layer refers to the fascia propria of the rectum. The incidence of erectile and ejaculatory dysfunction after rectal excision is high in older patients, and when performed for rectal cancer. There is no consensus about the relationship of Denonvilliers' fascia to the plane of anterior dissection for rectal cancer. CONCLUSION: Colorectal surgeons should focus on the important anatomy between the rectum and the prostate to improve functional outcomes after rectal excision. A classification of the available anterior dissection planes is proposed. Surgeons should be encouraged to document the plane used as well as outcome in terms of sexual function.

Autonomic Nervous System↗