Robin S. McLeod

Results of the pelvic-pouch procedure in patients with Crohn's disease

The pelvic-pouch procedure has become a standard operation for selected patients with ulcerative colitis, but is contraindicated in patients with Crohns disease at our institution. However, the distinction between ulcerative colitis and Crohns colitis can sometimes be difficult, if not impossible. Between January 1982, and March 1989, 272 patients with ulcerative colitis underwent pelvic-pouch procedures at our institution. Nine (35 percent) of these patients eventually were found to have Crohns disease. The records of these patients were examined to assess their clinical outcome and complication rate. There were five females and four males with a mean age of 28.8 years. In five patients (Group I) the diagnosis of Crohns disease was made postoperatively on histologic examination of the rectum. The ileostomy was closed in all patients. Two developed complications necessitating excision of the pouch. Three patients are well. In the other four cases (Group II) the mean time to diagnosis was 2.5 years after the pouch procedure. Three patients developed pouch-vaginal fistula, and one multiple anal fissures and stenosis. Two required excision of the pouch whereas two have a functioning pouch but with a persistent pouch-vaginal fistula (n=1) or anal fissures (n=1). Overall, four patients have had their pouches removed, and five patients have functioning pouches: three with no complications and two with persistent perianal disease. Thus, we would conclude that the pelvic-pouch procedure should not knowingly be performed in patients with Crohns disease because of the high associated complication rate.

Quality of life, nutritional status, and gastrointestinal hormone profile following the Whipple procedure.

Pancreatic cancer is the second commonest gastrointestinal cancer, after colorectal cancer, in Canada, and most other European and North American countries. Unfortunately, most patients present with advanced locoregional or metastatic disease. For the 10-20% of patients who have localized disease, pancreatic resection is generally the preferred treatment option. Because pancreaticoduodenectomy can be performed safely in expert hands, it has become a more accepted procedure for patients with pancreatic cancer. Furthermore, it has also meant that there is increasing scrutiny of the longterm outcome of patients, especially their nutritional status and quality of life. In a study of 25 unselected patients who had a Whipple procedure at least 6 months previously and were not known to have residual or recurrent disease, patients appeared to have few gastrointestinal symptoms compared to control patients. However, none of the subjects appeared to be clinically malnourished. Dietary intake and lean body mass were comparable to that of the control group. Quality of life was excellent in these patients. The mean utilities were 0.98 and 1.0 suggesting near normal wellbeing. Similarly, results using the SIP and GIQLI suggested no/minimal impairment in general wellbeing and gastrointestinal function. Two other studies suggest that median survival and performance status are improved in patients having a resection, but it may be due to their disease being more favorable rather than the treatment being beneficial. Further studies objectively assessing the quality of life of all patients undergoing treatment for pancreatic cancer at the various disease stages are required.

The ileal reservoir and ileoanal anastomosis procedure

A retrospective review was undertaken to determine factors important in predicting functional results following the ileal reservoir and ileoanal anastomosis procedure. One hundred seventy-nine patients underwent ileal reservoir and ileoanal anastomosis at the University of Toronto between December 1981 and January 1987. One hundred sixty-three patients had ulcerative colitis, 11 had familial adenomatous polyposis, and five had Crohns disease. A J-reservoir was constructed in 72 patients and an S-reservoir in 107 patients. Functional results were assessed in 102 patients who had had their loop ileostomies closed for more than one year. The most significant technical complications were anal anastomotic leaks (10 percent), reservoir anastomotic leaks (3.9 percent), anal anastomotic stricture (7.8 percent), late fistula-inano (2.8 percent), small-bowel obstruction (19 percent), and loop ileostomy complications (23 percent). Overweight males and patients with operative blood loss greater than 1000 cc developed anal stricture more frequently (P<.005). Patients who had a stapled J-reservoir had a higher rate of reservoir leak. The average number of bowel movements reported by patients for 24 hours was 6.2±3.1. Only ten (9.8 percent) patients had to intubate their reservoir to empty it. Urgency was experienced by 24 patients and soilage at night by 23 (22.5 percent) and during the day by 18 (17.6 percent). Seven patients (6.8 percent) were incontinent during the night and only one during the day. Pouchitis was reported in 16 patients (15.7 percent). Patients with anal anastomotic stricture had more urgency and pouchitis, and had to intubate their reservoir more frequently (P<.05). No other factors analyzed affected technical or functional results.

Ultrastructural Evidence for Piecemeal and Anaphylactic Degranulation of Human Gut Mucosal Mast Cells in vivo

One hundred and seventeen coded intestinal biopsies were examined by electron microscopy and evaluated for morphological evidence of mast cell and basophil secretion in situ. Sixty percent of the biopsies had evidence of secretion. Mast cell secretion was evident in control biopsies, many of which were obtained from uninvolved tissues of patients with inflammatory bowel disease. Biopsies of inflamed continent pouches from ulcerative colitis (UC) patients showed more mast cell secretion than noninflamed UC pouch biopsies. This evidence of mast cell secretion supports recent work that documents high constitutive levels of histamine in jejunal fluids of Crohns disease patients and suggests a proinflammatory role for mast cells in inflammation associated with pouchitis.

Dietary fibre for the prevention of colorectal adenomas and carcinomas

BACKGROUNDnColorectal cancer (CRC) is a major cause of morbidity and mortality in industrialized countries. Experimental evidence has supported the hypothesis that dietary fibre may be protective for the development of CRC, although epidemiologic data have been inconclusive.nnnOBJECTIVESnWe have conducted a systematic review and meta-analysis to assess the effect of dietary fibre on the incidence or recurrence of colorectal adenomas, the incidence of CRC, and the development of adverse events.nnnSEARCH STRATEGYnWe identified randomized controlled trials from Medline, Embase, and the Cochrane Controlled Trials Register up to Oct 2001nnnSELECTION CRITERIAnRandomized or quasi-randomized controlled trials were assessed. The population included all subjects that had adenomatous polyps but no previous history of colorectal cancer (CRC), a documented clean colon at baseline and repeated visualization of the colon/rectum after at least two years of follow-up. Dietary fibre was the intervention. The primary outcomes were the number of subjects with: a) at least one adenoma, b) more than one adenoma, c) at least one adenoma greater than or equal to 1 cm or d) a new diagnosis of CRC. The secondary outcome was the number of adverse events.nnnDATA COLLECTION AND ANALYSISnTwo reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as relative risks (RR) and risk difference (RD) with 95% confidence intervals (CI). If statistical significance was reached, the number need to treat (NNTT) or harm (NNTH) was reported. The study data were combined with the fixed effects model if it was clinically, methodologically, and statistically reasonable.nnnMAIN RESULTSnFive studies with 4349 subjects met the inclusion criteria. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. When the data were combined there was no difference between the intervention and control groups for the number of subjects with at least one adenoma [RR 1.04 (95% CI 0.95,1.13); RD 0.01 (95% CI 0.02,0.04)]. As well, the combined results for the number of subjects with more than one adenoma [RR 1.02 (95% CI 0.89,1.17), RD 0.00 (-0.02,0.03)] or at least one adenoma 1 cm or greater [RR 0.94 (95% CI 0.77,1.15), RD -0.01 (-0.02,0.01)] were not statistically significant. Other primary and secondary outcomes and subanalyses by type of fibre intervention were not statistically or clinically significant.nnnREVIEWERS CONCLUSIONSnThere is currently no evidence from RCTs to suggest that increased dietary fibre intake will reduce the incidence or recurrence of adenomatous polyps within a two to four year period.

Reconstructive Techniques After Rectal Resection for Rectal Cancer

BACKGROUNDnTotal mesorectal resection (TME) has led to improved survival and reduced local recurrence in patients with rectal cancer. Straight coloanal anastomosis after TME can lead to problems with frequent bowel movements, fecal urgency and incontinence. The colonic J pouch, side-to-end anastomosis and transverse coloplasty have been developed as alternative surgical strategies in order to improve bowel function.nnnOBJECTIVESnThe purpose of this study is to determine which rectal reconstructive technique results in the best postoperative bowel function.nnnSEARCH STRATEGYnA systematic search of the literature (MEDLINE, Cancerlit, Embase and Cochrane Databases) was conducted from inception to Feb 14, 2006 by two independent investigators.nnnSELECTION CRITERIAnRandomized controlled trials in which patients with rectal cancer undergoing low rectal resection and coloanal anastomosis were randomized to at least two different anastomotic techniques. Furthermore, a measure of postoperative bowel function was necessary for inclusion.nnnDATA COLLECTION AND ANALYSISnStudies identified for potential inclusion were independently assessed for eligibility by at least two reviewers. Data from included trials was collected using a standardized data collection form. Data was collated and qualitatively summarized for bowel function outcomes and meta-analysis statistical techniques were used to pool data on postoperative complications.nnnMAIN RESULTSnOf 2609 relevant studies, 16 randomized controlled trials (RCTs) met our inclusion criteria. Nine RCTs (n=473) compared straight coloanal anastomosis (SCA) to the colonic J pouch (CJP). Up to 18 months postoperatively, the CJP was superior to SCA in most studies in bowel frequency, urgency, fecal incontinence and use of antidiarrheal medication. There were too few patients with long-term bowel function outcomes to determine if this advantage continued after 18 months postop. Four RCTs (n=215) compared the side-to-end anastomosis (STE) to the CJP. These studies showed no difference in bowel function outcomes between these two techniques. Similarly, three RCTs (n=158) compared transverse coloplasty (TC) to CJP. Similarly, there were no differences in bowel function outcomes in these small studies. Overall, there were no significant differences in postoperative complications with any of the anastomotic strategies.nnnAUTHORS CONCLUSIONSnIn several randomized controlled trials, the CJP has been shown to be superior to the SCA in bowel function outcomes in patients with rectal cancer for at least 18 months after gastrointestinal continuity is re-established. The TC and STE anastomoses have been shown to have similar bowel function outcomes when compared to the CJP in small randomized controlled trials; further study is necessary to determine the role of these alternative coloanal anastomotic strategies.

A population‐ and family‐based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease

The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population- and family-based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB1*0103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case–control analysis of non-Jewish IBD-affected individuals. This association was apparent among both Crohns disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non-Jewish IBD population by results of family-based association analysis using the transmission disequilibrium test. HLA DQB1*0501 was also associated with IBD (OR = 1.64, p = 0.02) in the non-Jewish population, but statistically significant association of this allele with disease was not detected for Crohns disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non-Jewish IBD families, IBD was as strongly associated with the DRB1*0103 DQB1*0501 haplotype as with the DRB1*0103 allele alone. The carrier frequency of the DRB1*0103 allele was found to be 10-fold higher in Crohns disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB1*0103 allele with both Crohns disease and ulcerative colitis and with large intestine–restricted disease in non-Jewish IBD patients and therefore identify HLA DRB1*0103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.

[Crohn's disease and pregnancy].

Seventy-eight pregnancies in 50 patients were reviewed to evaluate the effects of Crohns disease on the outcome of pregnancy and the influence of the pregnancy on the course of Crohns disease. Overall, 21 pregnancies (27 percent) had abnormal outcomes including spontaneous abortions (9), infants small for gestational age (6), premature infants (5), and infants who developed respiratory distress (1). Eight (50 percent) patients with active disease compared with 13 (21 percent) patients with inactive disease at conception had abnormal outcomes (P<0.05). During pregnancy 15 (55 percent) with active disease and 6 (12 percent) with inactive disease had an abnormal outcome (P<0.001). Neither medical nor surgical treatment, independent of disease activity, appeared to affect the outcome adversely. Eighteen of 73 (25 percent) patients with quiescent or mild disease relapsed, and seven of 16 patients with some disease activity improved (44 percent). Of 34 patients on medication, nine relapsed (27 percent), and of 39 patients not on medication, nine relapsed (24 percent) (P=N.S.). These results suggest that the outcome of pregnancy is not adversely affected by Crohns disease. However, patients with active disease at conception and/or during the pregnancy have poorer outcomes independent of the use of medication or requirement of surgery. Neither pregnancy nor medications taken affect the course of the disease.

Subtotal colectomy for ulcerative colitis: Complications related to the rectal remnant

Complications related to the retained rectal remnant were reviewed in 136 patients undergoing subtotal colectomy for acute ulcerative colitis. Fifty-five patients (Group 1) had a closed rectal stump brought up into the subcutaneous tissue, and 30 (Group 2) had an open mucous fistula. These were compared with an intrapelvic Hartmanns pouch performed in 51 patients (Group 3). All patients eventually had a pelvic pouch procedure. Age, duration and activity of disease, and preoperative steroid use were similar in all groups. There was no mortality. The rectal stump in 19 Group 1 patients (35 percent) spontaneously opened, and seven (13 percent) developed local left lower quadrant wound infections. Two Group 1 patients (4 percent) developed pelvic septic complications, as compared with two Group 2 patients (7 percent) and six Group 3 patients (12 percent). Subsequent pelvic dissection was difficult in 20 percent of Group 3 patients,vs.4 percent and 0 percent of Group 1 and Group 2 patients, respectively (P<0.05). Persistent rectal disease activity was present in 41 percent of Group 3,vs.27 percent of Groups 1 and 2. Our study suggests that exteriorization of the closed rectal stump following subtotal colectomy is associated with fewer pelvic septic complications and minimal local morbidity, facilitates subsequent pelvic dissection, and is not associated with increased disease activity in the retained rectum.

Congenital hypertrophy of the retinal pigment epithelium as a marker for familial adenomatous polyposis.

Fifty patients were assessed for congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a potential phenotypic marker for familial adenomatous polyposis (FAP), with and without other extracolonic manifestations (ECM). The ocular anomaly, which characteristically is multiple, benign, and congenital, was studied in three groups. Group 1 contained eight patients with nonpolyposis colon cancer as disease controls. All had negative eye findings. Group 2 included 40 patients with FAP, 35 (87.5 percent) of whom had retinal lesions. Twenty-two of 25 patients with FAP alone had retinal lesions while 13 of 15 patients with FAP and extracolonic manifestations were similarly affected. Group 3 included 11 offspring at risk for FAP. Eight (72.7 percent) offspring had retinal lesions. One of the eight subjects with the ocular trait was subsequently diagnosed with FAP. Two of the eight patients also had other ECM but have not been sigmoidoscoped for FAP. Seven of 11 offspring (mean age, 12.5 years) have had negative flexible sigmoidoscopy. Specificity of the retinal lesions in FAP cannot be ascertained until subsequent adenomas are identified on follow-up of the group at risk. The gene responsible for CHRPE appears to be transmitted from one generation to another, demonstrated by the high sensitivity of the retinal lesions in patients with FAP alone and with other ECM.