Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.

A prospective audit of fistula-in-ano at St. Mark's hospital.

OBJECTIVE: To conduct a prospective audit of all patients presenting with anal fistula at St. Mark's Hospital during one calendar year and to compare the presentation and outcome of this cohort with previous reports from this institution. PATIENTS AND METHODS: All patients undergoing examination under anaesthetic (EUA) for anal fistula during 1997 were studied. All fistulae were anatomically classified and operative procedures recorded. During a mean follow-up period of 14 months details of healing, recurrence and function were gathered. RESULTS: 98 patients with a mean age of 43.7 years were assessed. 86 (88%) patients had fistulae of cryptoglandular (idiopathic) origin. Fistulae were superficial in 11 (11%) patients, intersphincteric in 30 (31%) patients, trans-sphincteric in 52 (53%) patients, suprasphincteric in 3 (3%) patients and extra-sphincteric in 2 (2%) patients. 49 (50%) fistulae were classified as complex. Eradication of fistulae with preservation of function was achieved in 89 (91%) patients. Fistula recurrence occurred in 4 (4%) cases. Ten (10%) patients had some degree of incontinence, 9 (9%) of whom had undergone previous fistula surgery. Nine (9%) patients still had setons in situ at the end of the follow-up period. CONCLUSIONS: A greater proportion of difficult fistulae was seen during the year compared with previous studies from St. Mark's. Despite this a satisfactory outcome was achieved in the vast majority with a relatively low rate of disturbed function. Previous fistula surgery is a risk factor for incontinence, which can usually be managed conservatively.

Overlap repair of damaged anal sphincter. A single surgeon's series.

PURPOSE: This study was undertaken to review consecutive cases of anal sphincter repair performed by a single surgeon with respect to outcome as measured by continence grade using the Parks-Browning scale. Other parameters such as manometry, pudendal nerve function, and morbidity are also reviewed with respect to outcome. METHODS: Thirty-one of 52 patients identified by computer were available for analysis. Case notes were retrieved, and information was transferred into a standard proforma. Minimum follow-up was one month, and continence grade was documented from clinical notes recorded at follow-up. Statistical analysis was performed using Instat computer package. RESULTS: Four patients were male, 27 were female. Average age was 41.9 years. There was no postoperative mortality; postoperative morbidity was 32 percent in total, but morbidity per procedure was 19.6 percent. Most (20 of 31) patients had a clear obstetric-related cause of their anal sphincter injury. Successful outcome was achieved in 74.2 percent of patients. Postoperative anal manometry was not discriminatory between successful and failed groups. Anal ultrasound appeared accurate in documenting residual anal sphincter defects in the poor outcome group in the small number of patients in whom it was done. Use of a stoma in covering the anal wound while it healed was associated with less infection of the wound, but there was no statistical difference in success rate between those covered by a stoma and those not covered. CONCLUSIONS: Overlap repair of the damaged anal sphincter continues to give good results. Routine use of covering stomas is not supported in this small study; however, it should still be considered in difficult cases. Endoanal ultrasound may have the ability to identify those patients with poor results from an initial repair who may benefit from repeat repair.

Trephine colostomy: a warning.

A case of trephine colostomy is presented in which air insufflation incorrectly identified the distal limb. Disaster was averted by correct identification at laparotomy. The probable cause of the error and methods of avoidance are discussed.

Persistence of idiopathic anal fistula may be related to epithelialization.

Anal fistulas may fail to heal because of continuing disease within the intersphincteric anal glands. Histological studies of the intersphincteric component of 18 consecutive idiopathic anal fistulas show that fistula persistence may be caused by epithelialization of the fistula track from internal or external openings. Some fistulas are lined by epithelium similar to that of anal gland ducts, but this may also represent epithelium derived from the transitional zone of the anal canal. Persistence may be related more to non-specific epithelialization of the track than to a chronically infected anal gland.

CT appearances of desmoid tumours in familial adenomatous polyposis: further observations.

Intra-abdominal desmoid tumours represent a major cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP), and such patients are also liable to develop musculoskeletal desmoids. We have reviewed the CT appearances of 44 desmoid lesions (28 intra-abdominal and 16 musculoskeletal) in 20 patients with FAP. We found a considerable heterogeneity in the CT appearance of musculoskeletal and intraabdominal desmoids, with respect to their density, definition and change in size or density on follow-up, not only between different patients but also in patients with multiple lesions, who rarely showed identical appearances of all lesions. In some cases, mesenteric tumours may initially present as ill-defined soft tissue infiltration of mesenteric fat, becoming larger and more mass-like with time. On medical treatment, shrinkage was seen infrequently in musculoskeletal desmoids, and not at all with mesenteric lesions. CT evidence of bowel involvement by intra-abdominal lesions was frequent, most commonly appearing as 'tethering' or encasement of bowel loops. The presence of a large mesenteric mass (> 10 cm diam.), multiple mesenteric masses, extensive small bowel involvement and/or bilateral hydronephrosis were associated with ultimate death.

Overlapping anal sphincter repair for faecal incontinence due to sphincter trauma: five year follow-up functional results.

Disruption of the anal sphincter results from obstetric injury, ano-rectal operations or external trauma. Obstetric or surgical division of the sphincteric mechanism may not be immediately apparent and the clinical presentation of incontinence may occur several years later [1, 2]. Reconstruction of the sphincter using a fascial sling or direct end-to-end repair of the disrupted sphincter result in a high failure rate. Failure after direct end-to-end repair is usually caused by break down of the suture line owing to retraction of the muscle ends [3]. Parks advocated an overlapping repair [4] in which the disrupted ends of the sphincter were mobilised and wrapped around each other. This paper reports the results of overlapping sphincter repair for faecal incontinence resulting from trauma, after a 5 year follow-up period.

Results of Delorme's procedure for rectal prolapse.

PURPOSE: This study was designed to examine the results of Delorme's procedure. METHODS: Thirty-two patients (24 males and 8 females, mean age, 70 years) underwent Delorme's procedure between 1978 and 1990 following symptoms lasting between two weeks and ten years. Thirteen patients had had 21 previous operations for prolapse. RESULTS: The mean operation time was 65 minutes. No blood transfusions were needed, there was no operative mortality, and only two patients had complications (one chest infection and one anastomotic dehiscence). No patients were lost to follow-up. Over a mean follow-up of 24 months (4 months to 4 years), 9 patients died of unrelated conditions. There were four recurrences (12.5 percent), two in patients who had each had two previous procedures. Incontinence improved in 46 percent. No patient became constipated and 50 percent of those constipated preoperatively improved. CONCLUSION: Although abdominal rectopexy is safe and has a low recurrence rate (< 5 percent), it involves the hazards of a laparotomy. In addition, up to 40 percent of patients become constipated after rectopexy which may be debilitating. Delorme's procedure has a low morbidity, results in good bowel function, and has a low recurrence rate. It can be performed on unfit patients with possible advantages over rectopexy and perhaps should be used more readily.

Oral calcium inhibits rectal epithelial proliferation in familial adenomatous polyposis.

Calcium reduces colorectal cell turnover and might therefore protect against neoplasia. The inhibitory effects of dietary calcium were tested in a double-blind controlled trial in patients with familial adenomatous polyposis who had undergone previous abdominal colectomy and ileorectal anastomosis. Patients received supplemental calcium carbonate (1500 mg/day) or placebo tablets for 6 months; sigmoidoscopy was performed before and after treatment. Rectal biopsies were maintained in short-term organ culture, and crypt cell production rate (CCPR) was measured stathmokinetically. A total of 25 patients completed the trial; polyp counts were obtained before and after treatment in all and CCPR values in 16. Calcium treatment reduced the mean (s.e.m.) CCPR from 4.72 (0.48) to 2.42 (0.48) cells per crypt per h (P < 0.05), while values for placebo were unchanged (5.46 (1.21) versus 5.08 (1.17) cells per crypt per h). Calcium had no demonstrable effect on the number, size or distribution of rectal polyps. The ability of oral calcium supplementation to suppress rectal epithelial proliferation supports its potential to prevent development of colorectal carcinoma in high-risk individuals.

Management of familial adenomatous polyposis.

The management of FAP involves treatment of affected individuals and their families. Such an approach is best coordinated by registrars working in dedicated registries, in close collaboration with nurses, physicians, surgeons, clinical geneticists and others who become involved in the care of these patients. The large bowel of patients with FAP should be removed (totally or subtotally) by the third decade of life. Screening of other areas at risk is recommended to document the natural history of extracolonic manifestations and to allow study of the effects of intervention. Despite these other, sometimes life-threatening manifestations, a near to normal life span is possible in the majority of patients with FAP. The aims of management of the individual and of the family are to ensure that their quality of life is optimal, that support is provided in times of emotional need, that anxiety is minimized and that relatives are adequately screened and treated.

An evaluation of the penetration of cefuroxime axetil into human paranasal sinus tissue.

Nineteen patients presenting for sinus surgery were studied to evaluate the percentage penetration from serum to paranasal sinus tissue of a single orally administered dose of cefuroxime axetil. The methods and results are presented. Cefuroxime penetrates well into human sinus mucosa following oral administration and the concentrations obtained exceed minimum inhibitory concentrations of cefuroxime for the most common pathogens in sinusitis.

Clinical and functional results of abdominal rectopexy for complete rectal prolapse.

Between 1977 and 1987, 53 patients underwent polyvinyl alcohol sponge rectopexy for complete rectal prolapse. The mean follow-up period was 36.7 months. Full thickness prolapse recurred in two patients (3.8 per cent). Infection around the prosthesis and faecal impaction developed in two patients each. Continence improved significantly after operation, particularly in those under 70 years of age (P = 0.028, chi 2 test) and nulliparous women (P = 0.026, chi 2 test). Bowel function was generally unchanged after rectopexy; in particular only eight patients (15 per cent) had significant postoperative constipation.

Comparison of morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis.

Restorative proctocolectomy with an ileal reservoir (RPC) should prevent colorectal cancer in patients with familial adenomatous polyposis. Until this is confirmed its role compared with total colectomy and ileorectal anastomosis (IRA) will depend on the relative morbidity and postoperative bowel function after the two procedures. This was analysed in 99 patients (37 RPC, 62 IRA) operated on between 1977 and 1989. Morbidity was greater after RPC with subsequent ileostomy closure (median hospital stay, 24 versus 11 days; complications, 60 versus 21 per cent; reoperation, 29 versus 3 per cent; return to normal activity; 31 versus 14 weeks). There was little difference in bowel function; after IRA median frequency was 3/24 h and urgency (unable to wait 15 min) occurred in 50 per cent, compared with 4.5/24h and 17 per cent after RPC. Night evacuation occurred in 10 and 43 per cent respectively. IRA was performed in younger patients (median 19 versus 31 years) who had fewer bowel motions before operation (2 versus 5/24 h). The greater morbidity of RPC suggests that it should be restricted to patients at higher risk of developing later rectal cancer, including those unavailable for follow-up and those with large or confluent rectal polyps or with curable colon cancer at the initial colectomy.

A review of physical abnormalities in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition wherein multiple polyps may be found in the gastrointestinal tract. Initially referred to as familial polyposis coli, it has become evident that virtually all patients with FAP develop adenomas in the upper gastrointestinal tract and thus the syndrome is now termed familial adenomatous polyposis. The number of associated conditions both malignant and benign has been increasingly recognized. Some of these lesions cause morbidity and mortality in affected individuals whilst others act as important clinical markers for identifying patients not yet expressing the phenotype. These abnormalities can arise from tissues of all three primary embryonic layers and are described in this paper.

Rectopexy for internal rectal intussusception.

Twelve patients presented with symptomatic internal intussusception of the rectum between 1979 and 1987. All were women with a mean age of 55.5 years. Ten patients had symptoms of obstructed defaecation and only three were completely continent. Polyvinyl alcohol sponge abdominal rectopexy was performed in each patient. Over a mean follow-up period of 26.9 months there was no recurrence of internal intussusception. The functional results, however, were mixed but only one patient remained incontinent for solid stool. Rectal discomfort and defaecatory difficulties persisted; six patients continued to strain at stool and in three this was worsened by the operation. Abdominal rectopexy can be recommended for those with associated incontinence, significant rectal bleeding or solitary rectal ulcer but may not benefit those who have obstructed defaecation.