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Biomedical subjects

J M Northover

Publications and source records attributed to J M Northover.

At least 19 recordsLinked to original sources

Peri-operative management of patients having external anal sphincter repairs: temporary prevention of defaecation does not improve outcomes.

OBJECTIVE: To determine whether there was any detectable difference in outcomes of external anal sphincter repair depending on whether patients were managed routinely with a covering stoma, a constipating dietary regimen or a laxative dietary regimen in the early postoperative period. PATIENTS AND METHODS: A consecutive retrospective series of 299 anal sphincter repairs undertaken on 286 patients within a single institution was studied. Patients were divided into three groups depending on the peri-operative regimen followed: routine use of a covering stoma (group 1), routine use of a postoperative constipating dietary regimen (group 2) and routine use of a laxative dietary regimen (group 3). Choice of peri-operative regimen depended on surgeon preference alone. Short-term outcomes (length of stay, complications) and long-term outcomes (functional reported degree of continence, anal ultrasound and physiology test results) were assessed in relation to peri-operative group as well as aetiology of sphincter damage. RESULTS: Short-term results (complications of surgery) were obtainable in all patients; long-term results were available for 89% of patients. Length of stay was similar for all 3 groups (excluding re-admission for stoma closure). Complication rates were not significantly different between the three groups. Functional improvement in continence was reported by 68% of group 1, 69% of group 2 and 79% of group 3 (differences not statistically significant). An anatomical sphincter defect was detected postoperatively in 8% of patients in group 1, 9% in group 2 and 7% of group 3. Poorer outcomes were achieved in older patients and in patients with previous ileo-anal pouch formation. Early faecal impaction and repair breakdown were independently associated with poor long-term outcomes. CONCLUSIONS: Neither routine use of a covering stoma nor a postoperative constipating regimen produced better results following external anal sphincter repair than did the use of a postoperative laxative regimen which encouraged early passage of loose stool without the need for straining.

Journal Article↗

Design of a multicentre randomised trial to evaluate flexible sigmoidoscopy in colorectal cancer screening.

A randomised, controlled trial in progress in 14 United Kingdom and six Italian centres is evaluating screening for colorectal cancer using a single flexible sigmoidoscopy (FS) at around the age of 60 with removal during FS of all small adenomas, and colonoscopy for "high risk" polyps. The regimen aims to ensure that 95% of people (with either no polyps or only low risk polyps) complete the entire screening process in a single visit. This paper describes the rationale and design of the trial. Participants were patients aged between 55 and 64 on the lists of designated general practitioners (GPs) who were not excluded by their GP. A two stage recruitment procedure was employed to raise compliance rates in the intervention group. Potentially eligible persons were sent an "interest in screening" questionnaire; those who responded positively were randomised to the intervention or control groups. The trial is sufficiently large to estimate within narrow confidence intervals the magnitude of benefit and the duration of effect and optimum age for a single screen. It also examines the feasibility and acceptability of the screening regimen, and will identify training and quality assurance issues. Recruitment and screening are now complete and all baseline data have been collected. The first analysis of the effect on colorectal cancer incidence and mortality rates and suitability for a national screening programme can be expected in 2004.

Age Factors↗

Single blind, randomised trial of efficacy and acceptability of oral picolax versus self administered phosphate enema in bowel preparation for flexible sigmoidoscopy screening.

OBJECTIVE: To compare the acceptability and efficacy of two methods of self administered bowel preparation for flexible sigmoidoscopy screening: a single phosphate enema and a single sachet of Picolax. DESIGN: Single blind, randomised trial. SETTING: Endoscopy units of two general hospitals. PARTICIPANTS: 1442 men and women aged 55-64 years who had agreed to be screened by flexible sigmoidoscopy. MAIN OUTCOME MESURESs: Attendance rates, compliance with allocated preparations, adverse effects, quality of bowel preparation, procedure time, and yield of neoplasia. RESULTS: Compliance with the enema was higher than with the Picolax (608 (84%) v 566 (79%); difference 6%, 95% confidence interval 2% to 10%). Almost half of those who refused Picolax used an enema at home. Wind, incontinence, and sleep disturbance were more frequent in the Picolax group than the enema group; bottom soreness was more frequent in the enema group. Around 30% (187) found the diet restriction required by Picolax difficult; 78% (471) found the enema easy to administer. The quality of preparation was better with the enema; the proportion of procedures complete to the descending colon was greater and the mean duration of the procedure was shorter. There was no significant difference in polyp detection rates. CONCLUSION: A single phosphate enema self administered around one hour before leaving home is a more acceptable and effective method of preparing the distal bowel for flexible sigmoidoscopy than Picolax.

Administration, Oral↗

Effect of radioimmunoscintigraphy on the management of recurrent colorectal cancer.

BACKGROUND: Radioimmunoscintigraphy (RIS) is being used increasingly as a new investigation in the diagnosis of recurrent colorectal cancer. This study assessed the efficacy of 99mTc-radiolabelled PR1A3 scanning in a cohort of patients with possible recurrent colorectal cancer and the effects of scan interpretation on subsequent clinical management. METHODS: The scans and case notes of patients scanned over a 3-year period were reviewed. RESULTS: Forty-seven scans in 40 patients were available for analysis. In 39 instances in which scan interpretation could be verified accurately, sensitivity for recurrent colorectal cancer was 22 of 23 (96 per cent), specificity for recurrent colorectal cancer was eight of 16 (50 per cent), positive predictive value for recurrence was 22 of 30 (73 per cent) and negative predictive value for recurrence was eight of nine (89 per cent). In 16 of the 40 patients, scan interpretation strengthened a management decision or altered management. This was beneficial to ten patients and possibly detrimental to six. CONCLUSION: This study demonstrated that RIS is sensitive in the detection of recurrent colorectal cancer and benefited the patient in one-quarter of cases. For the majority of patients, accurate detection of recurrent disease cannot be followed by curative therapy, but there is an important subgroup of patients in whom RIS alters management beneficially. However, a randomized prospective study is needed to confirm this.

Adult↗

Adenocarcinoma within a rectal duplication cyst: case report and literature review.

Intestinal duplications are uncommon but recognised developmental anomalies. Duplications of the rectum are the most uncommon of these anomalies. They may present with perianal fistulae, bleeding, a pelvic mass or symptoms produced by a mass, or, rarely, malignant change. We present a case of an adenocarcinoma within a rectal duplication cyst which was initially thought to be inoperable but was treated by radical surgery.

Adenocarcinoma↗

Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing.

OBJECTIVES: To compare the feasibility of mass screening by flexible sigmoidoscopy with screening by faecal occult blood testing (Haemoccult) and both tests combined. DESIGN: Patients were randomised to screening by flexible sigmoidoscopy, faecal blood testing, or both tests. The flexible sigmoidoscopy examinations were performed by a general practitioner. SETTING: General practice. SUBJECTS: 3744 patients aged 50-75 years. MAIN OUTCOME MEASURES: Uptake, positive results, detection of neoplasia, complications, and recall for diagnostic colonoscopy. RESULTS: Uptake was significantly higher in the flexible sigmoidoscopy group (46.6%) than in the faecal blood test group (31.6%; P<0.001) or than in the group having both tests (30.1%; P<0.001). Telephone reminders increased uptake of sigmoidoscopy to 61.8%. In total, 1116 sigmoidoscopy examinations were performed without major complication. Polyps were found in 19. 3% (95% confidence interval 17.0% to 21.6%) but only 6.8% (5.3% to 8. 3%) had adenomas and 2.4% (1.5% to 3.3%) "high risk" adenomas. Cancer was detected in four subjects. The faecal blood test yielded positive results in 0.8% (0.2% to 1.4%) but missed at least one cancer and 30 cases of adenoma which were found by sigmoidoscopy in the combined group. Use of histological criteria-shown elsewhere to correlate with future risk of colorectal cancer-to select "positive" patients could reduce recall for diagnostic colonoscopy from about 20% to less than 5%. CONCLUSIONS: Some of the predicted obstacles to screening with flexible sigmoidoscopy are surmountable. Clear evidence relating to efficacy will be obtained only from a randomised controlled trial.

Aged↗

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system.

A total of 301 colorectal carcinoma (CRC) archival samples were analysed using the amplification-refractory mutation system (ARMS). Each sample was examined to determine the mutation status of codons 12 and 13 of the K-ras oncogene. The results from direct DNA sequence analysis carried out on 30 of the samples differed from the ARMS result in almost 50% of the cases as a result of the relative excess of wild-type to mutated DNA sequences. To assess the validity of the ARMS data, the polymerase chain reaction (PCR) was used to generate an amplicon from K-ras exon 1 from 23 of the samples. The PCR amplicons were cloned and sequenced, and the DNA sequence analysis of the cloned material was in agreement with the ARMS results in all but one case. This case represented a tumour that exhibited a five-nucleotide reversed inversion. The cloned sequence data confirm the sensitivity and specificity of the individual ARMS reactions and that it is possible in certain cases to detect additional, more complex, sequence variations.

Adenoma↗

Anovestibular fistula to Bartholin's gland.

BACKGROUND: Acquired fistulation from the anal canal to Bartholin's gland has not been reported before. This fistula has been identified in 11 women treated between 1991 and 1995. METHODS: All discharge diagnoses during this period were searched. The clinical records of patients managed for this diagnosis were reviewed. RESULTS: Eleven women aged 24-49 years were identified. Seven of 11 fistulas arose in association with inflammatory bowel disease (five Crohn's disease, two ulcerative colitis). Patients typically presented with the vulval passage of flatus and faeces or acute sepsis of Bartholin's gland. Time to diagnosis of the fistula ranged from 1 to 15 (median 8) months after the onset of symptoms. Anatomically, all fistulas were high trans-sphincteric or suprasphincteric. All eight fistulas for which repair was attempted (five in the presence of inflammatory bowel disease) remain healed at short-term follow-up. Proctocolectomy was undertaken in two patients with severe Crohn's colitis. CONCLUSION: Ano-Bartholin's fistulas, although rare in general surgical practice, present with troublesome symptoms and may be repaired successfully. Gynaecologists and surgeons should be aware of this clinical entity to avoid unnecessary delays in treatment.

Adult↗

Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening.

BACKGROUND: A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. AIMS: To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. SUBJECTS: A total of 3540 subjects aged 55-64 years in Welwyn Garden City (WGC) and 19,706 in Leicester (LE). METHODS: Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. RESULTS: In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. CONCLUSIONS: Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention.

Adenoma↗

Staging and management of colorectal cancer.

The management of colorectal cancer becomes ever more complex. Rational decision-making depends on knowledge of the apparent stage of the disease in the individual patient. Many decisions require input from the patient, who therefore must be party to all relevant information, including any that is predictive of the likely outcome of the disease and the effects of treatment. The process of staging once required only pathologic information gleaned from the surgical specimen. Later clinical information was often added to produce a more practically useful prediction of outcome; necessarily, the staging process, whether pathologic or clinicopathologic, could only be completed postoperatively. Today there is a momentum toward preempting this process through the use of scanning and other modalities, so "staging" information can be used when planning primary treatment, including neoadjuvant therapy and surgery. The ultimate staging system would comprise just two reliably predictive patient categories: those expected to survive and those destined to die. So far no system has approached that "ideal." Given such a system, therapeutic and research efforts could be concentrated on reversing the outcome for those predicted to die.

Biomarkers, Tumor↗

Clinical and molecular features of the hereditary mixed polyposis syndrome.

BACKGROUND & AIMS: Various inherited syndromes predispose to the development of colonic juvenile polyps and colorectal cancer, with potential importance for sporadic tumorigenesis. This study describes features of a possibly new syndrome of atypical juvenile polyps and other colonic tumors and compares these features with those of known gastrointestinal tumor syndromes. METHODS: A large family, St. Mark's family 96, with a tendency to develop colonic polyps of mixed histological types is described. Genetic linkage to known polyposis syndromes has been tested. RESULTS: Adenomatous and hyperplastic polyps occur in affected members of the family, although the characteristic lesion is an atypical juvenile polyp. Some affected individuals have developed polyps of more than one type, and individual polyps may contain features of more than one histological type. Polyps can undergo malignant change. Typically, fewer than 15 polyps are found at colonoscopy and there is no extracolonic disease associated with the development of polyps. The family's polyps seem to be inherited in an autosomal-dominant fashion, but the disease is probably unlinked to candidate loci with importance in colorectal tumorigenesis, such as APC, hMSH2, and hMLH1. CONCLUSIONS: We term this family's disease hereditary mixed polyposis syndrome (HMPS). Although mutations in the putative HMPS gene may be responsible for syndromes such as juvenile and Peutz-Jeghers polyposes, HMPS may also be a distinct disease.

Adenomatous Polyposis Coli↗

Properties of HPV-positive and HPV-negative anal carcinomas.

Evidence of human papillomavirus (HPV) can be found in up to 85 per cent of anal carcinomas. In the vulva, a discrete subset of HPV-positive carcinomas which show koilocytic morphology and distinct clinical features has recently been identified (warty carcinoma). The morphological and prognostic features of HPV-positive and HPV-negative anal carcinomas were compared in this study of the tumour distribution of HPV DNA. Vulval and anal neoplasia are similar in many ways and we have also looked to see if their similarity extends to 'warty' morphology in relation to HPV status. Thirty-five resection specimens of anal carcinoma were examined with biotin-labelled probes for HPV 6, 11, 16, and 18 DNA, using a non-isotopic in situ hybridization (ISH) technique. No tumour was found to contain HPV 6, 11, or 18. Twenty-four (72 per cent) showed positivity for HPV 16 DNA. Staining was homogeneous and independent of local squamous, basaloid, or ductal differentiation. The majority of tumours showed staining suggestive of episomal, non-productive HPV infection. HPV-positive tumours were more likely to occur in the anal canal than perianally and to show a mixed squamous and basaloid appearance. No difference between the two groups was found in patient age, presence of adjacent dysplasia, ductal differentiation, or prognosis. There was no correlation between condylomatous tumour morphology and HPV 16 DNA positivity; thus, a subset equivalent to vulval warty carcinoma could not be identified.

Anus Neoplasms↗

Evaluation of surgery for perianal Crohn's fistulas.

PURPOSE: This study was designed to evaluate the operative treatments performed on patients with perianal Crohn's disease at a tertiary referral colorectal university hospital and to determine the efficacy of management by assessing patient satisfaction. METHODS: A retrospective survey included 59 patients with perianal Crohn's disease who had undergone surgery during the period of 1991 to 1993, inclusive. RESULTS: Twenty-seven patients were treated by laying the fistula open (81 percent successful), and another 27 cases were treated with a loose seton (85 percent successful). Five cases were complicated fistulas and underwent diversionary stomas as part of a primary procedure. Overall success rate, as judged by patient satisfaction, was 83 percent. CONCLUSION: Conservative surgery has a role in management of perianal Crohn's disease. Patient satisfaction can be achieved without complete healing. Better preoperative assessment may improve results further.

Adolescent↗

Attitudes to predictive DNA testing in familial adenomatous polyposis.

Attitudes to predictive DNA testing for familial adenomatous polyposis were documented in 62 affected adults. Patient views on prenatal testing and termination of pregnancy for this disorder were sought, as were opinions on the most suitable age to offer predictive testing for at risk children and the most appropriate age to begin screening. While 15 (24%) of those questioned stated that they would proceed to termination of pregnancy if a prenatal test indicated that the unborn baby was affected, in clinical practice no one has yet requested this option. Six (10%) people who had refrained from having children for fear of passing on the polyposis gene felt that the arrival of prenatal testing would enable them to consider planning a family. The majority of patients (93%) said they would like their children tested by DNA analysis at birth or in infancy, but felt that 10 to 12 years was the most appropriate time to discuss the diagnosis with the child.

Abortion, Spontaneous↗

Genetic mapping of hereditary mixed polyposis syndrome to chromosome 6q.

Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. HMPS appears to be inherited in an autosomal dominant manner. Genetic linkage analysis has been performed on a large family with HMPS. Data did not support linkage to the APC locus or to any of the loci for hereditary nonpolyposis colorectal cancer. Evidence that the HMPS locus lies on chromosome 6q was, however, provided by significant two-point LOD scores for linkage between HMPS and the D6S283 locus. Analysis of recombinants and multipoint linkage analysis suggested that the HMPS locus lies in a 4-cM interval containing the D6S283 locus and flanked by markers D6S468 and D6S301.

Adenoma↗

Human immunodeficiency virus infection and genital warts as risk factors for anal intraepithelial neoplasia in homosexual men.

The incidence of anal intraepithelial neoplasia (AIN) was studied in a group of 210 homosexual and bisexual men. The presence of genital warts and human immunodeficiency virus (HIV) infection was assessed as risk factors for the development of AIN. In all, 74 (35 per cent) of the group had histological evidence of AIN. The relative risk of being positive for HIV on AIN (relative to being negative for HIV) was 1.58 (95 per cent confidence interval (c.i.) 1.01-2.48). The relative risk of anal warts on AIN (relative to absence of anal warts) was 4.70 (95 per cent c.i. 1.81-12.20). Logistic regression analysis showed no significant interactive effect between HIV and anal warts on the risk of AIN. It is concluded from the results of a Mantel-Haenzel analysis that the presence of anal warts and HIV infection are independent risk factors for the development of AIN in homosexual and bisexual men.

Anus Diseases↗