Bruce G. Wolff

Natural history of untreated colonic polyps

The natural history of untreated colonic polyps is uncertain. A retrospective review of Mayo Clinic records from a 6-yr period just before the advent of colonoscopy identified 226 patients with colonic polyps greater than or equal to 10 mm in diameter in whom periodic radiographic examination of the colon was elected over excisional therapy. In all patients, follow-up of polyps spanned at least 12 mo (mean, 68 mo; range, 12-229 mo) and included at least two barium enema examinations (mean, 5.2; range, 2-17). During the follow-up period, 83 polyps (37%) enlarged. Twenty-one invasive carcinomas were identified at the site of the index polyp at a mean follow-up of 108 mo (range, 24-225 mo). Actuarial analysis revealed that the cumulative risk of diagnosis of cancer at the polyp site at 5, 10, and 20 yr was 2.5%, 8%, and 24%, respectively. In addition, 11 invasive cancers were found at a site remote from the index polyp during the same follow-up period. These data further support the recommendation for excision of all colonic polyps greater than or equal to 10 mm in diameter. Periodic examination of the entire colon is recommended in this group of patients to identify neoplasms arising at a site remote from the index polyp. Although this study has limitations inherent to any retrospective analysis, comparable prospective data are unlikely to be available in the future because of the current widespread availability of colonoscopy.

Simplified assessment of segmental colonic transit.

Transit times of radiopaque markers through the human gut were measured by published techniques and compared with a simplified method. Three sets of distinctive markers were ingested by 24 healthy persons on 3 successive days. In the first part of the study, daily abdominal x-rays were taken and individual stools were collected for radiography. Mouth-to-anus transits were assessed from the fecal output of markers and mean colonic and segmental colonic transits were calculated from the daily radiographs. These established methods were then compared with estimates of total colonic and segmental transits based on a single abdominal film, taken on the fourth day. The single-film technique correlated well with values obtained from the previous, but more inconvenient, methods. Using the simpler approach, colonic transit was assessed in 49 additional healthy subjects, for a total group of 73. Total colonic transit was 35.0 +/- 2.1 h (mean +/- SE); segmental transits was 11.3 +/- 1.1 h for the right colon, 11.4 +/- 1.4 h for the left colon, and 12.4 +/- 1.1 h for the rectosigmoid. Men had significantly shorter transits for the whole colon than did women (p less than 0.05), and this difference was apparent to some extent in the right (p = 0.06) and left colon (p = 0.07) but not in the rectosigmoid. Age did not influence transit significantly nor did a small dose of supplemental fiber. The technique is simple, convenient for clinical usage, and reduces the exposure to radiation to acceptable levels. There should be a role for this approach in the evaluation of colonic transit in selected patients.

Ileal pouch-anal anastomosis for chronic ulcerative colitis. Long-term results.

The aim of this study was to determine the long-term outcome among 390 patients with ulcerative colitis who underwent ileal J pouch-anal anastomosis and whether patient or operative factors influenced results. The combined operative morbidity rate for the pouch-anal anastomosis and the subsequent closure of the temporary ileostomy was 29% (bowel obstruction, 22%; pelvic sepsis, 5%), with one death due to pulmonary embolus. The probability of a successful outcome at 5 years was 94%. Of the 24 patients who failed (6% of total), 18 did so within 1 year (4%), three during year 2 (1%), three during year 3 (1%), and none thereafter. Stool frequency (7 stools/24 h), the occurrence of pouchitis (14%), and satisfactory daytime continence (94% of patients) remained stable over 4 years after operation, whereas nocturnal fecal spotting decreased (51% of patients to 20%). Women had more spotting than men, whereas patients over 50 years old had more stools per day than those 50 years or younger. In conclusion, ileal pouch-anal anastomosis achieved a reasonable stool frequency and satisfactory continence in patients with ulcerative colitis over the long-term. These results support the ileal pouch-anal anastomosis as a safe, satisfactory alternative to permanent ileostomy.

Reduction in adhesive small-bowel obstruction by Seprafilm adhesion barrier after intestinal resection.

IntroductionAlthough Seprafilm® has been demonstrated to reduce adhesion formation, it is not known whether its usage would translate into a reduction in adhesive small-bowel obstruction.MethodsThis was a prospective, randomized, multicenter, multinational, single-blind, controlled study. This report focuses on those patients who underwent intestinal resection (n = 1,701). Before closure of the abdomen, patients were randomized to receive Seprafilm® or no treatment. Seprafilm® was applied to adhesiogenic tissues throughout the abdomen. The incidence and type of bowel obstruction was compared between the two groups. Time to first adhesive small-bowel obstruction was compared during the course of the study by using survival analysis methods. The mean follow-up time for the occurrence of adhesive small-bowel obstruction was 3.5 years.ResultsThere was no difference between the treatment and control group in overall rate of bowel obstruction. The incidence of adhesive small-bowel obstruction requiring reoperation was significantly lower for Seprafilm® patients compared with no-treatment patients: 1.8 vs. 3.4 percent (P < 0.05). This finding represents an absolute reduction in adhesive small-bowel obstruction requiring reoperation of 1.6 percent and a relative reduction of 47 percent. In addition, a stepwise multivariate analysis indicated that the use of Seprafilm® was the only predictive factor for reducing adhesive small-bowel obstruction requiring reoperation. In both groups, 50 percent of first adhesive small-bowel obstruction episodes occurred within 6 months after the initial surgery with nearly 30 percent occurring within the first 30 days. Additionally no first adhesive small-bowel obstruction events were reported in Years 4 and 5 of follow-up.ConclusionsThe overall bowel obstruction rate was unchanged; however, adhesive small-bowel obstruction requiring reoperation was significantly reduced by the use of Seprafilm®, which was the only factor that predicted this outcome.

Early Postoperative Complications are not Increased in Patients with Crohn's Disease Treated Perioperatively with Infliximab or Immunosuppressive Therapy

AIM:The aim was to determine whether the use of steroids, immunosuppressive agents, or infliximab prior to abdominal surgery for Crohns disease is associated with an increased rate of early postoperative complications.METHODS:All patients who underwent abdominal surgery for Crohns disease between October 1998 and December 2001 were identified. Medical records were abstracted for demographics, location and duration of disease, use of infliximab within 8 wk before and 4 wk after surgery, and dose and duration of corticosteroids, azathioprine/6-mercaptopurine, and methotrexate. Steroid use was defined as: high (intravenous or oral ≥40 mg/day), moderate (oral ≥20 mg/day for at least 2 months), low (oral <20 mg/day or oral >20 mg/day for <2 months), or none. Early (within 30 days postinfliximab) septic and nonseptic complications were identified. Septic complications included wound sepsis, intraabdominal, and extraabdominal infections. Nonseptic complications included Crohns disease recurrence, small bowel obstruction, gastrointestinal bleeding, and thromboembolism. A logistic regression analysis assessed the association between perioperative therapy with infliximab, corticosteroids, or immunosuppressive therapy and subsequent occurrence of septic complications and separately overall complications.RESULTS:Two hundred and seventy patients were operated upon including 107 patients who received steroids (34 low dose, 34 moderate dose, 43 high dose), 105 patients who received immunosuppressives (64 azathioprine, 38 6-mercaptopurine, 4 methotrexate), and 52 who received infliximab. Forty-eight patients underwent urgent or emergent surgery and 222 underwent elective surgery. Septic complications occurred in 52 of 270 (19%) patients including wound sepsis in 28 (10%), anastomotic leak in 9 (3%), intraabdominal abscess in 5 (2%), and extraabdominal infections in 19 (7%). Nonseptic complications occurred in 18 of 270 (7%) patients. Preoperative use of high- or moderate-dose steroids, immunosuppressives, or infliximab was not associated with greater complication rates. No deaths occurred.CONCLUSION:Early complications after elective abdominal surgery for CD are not associated with steroid dose, immunosuppressive therapy, or infliximab use.

Meckel Diverticulum: The Mayo Clinic Experience With 1476 Patients (1950–2002)

Objective:Through a comprehensive review of the Mayo Clinic experience with patients who had Meckel diverticulum, we sought to determine which diverticula should be removed when discovered incidentally during abdominal surgery. Summary Background Data:Meckel diverticula occur so infrequently that most articles have reported either small series or isolated cases. From these limited series, various conclusions have been reported without clearly indicating which incidental diverticula should be removed. Methods:Medical records were reviewed of 1476 patients found to have a Meckel diverticulum during surgery from 1950 to 2002. Preoperative diagnosis; age; sex; date of surgery; and intraoperative, macroscopic, and microscopic findings from operative and pathology reports were recorded. Logistic regression analysis was used to determine which clinical or histologic features were associated with symptomatic Meckel diverticulum. The features analyzed were age; sex; length, base width, and ratio of length to base width of the diverticulum; and the presence of ectopic tissue or abnormal tissue (inflammation or enteroliths). Results:Among the 1476 patients, 16% of the Meckel diverticula were symptomatic. The most common clinical presentation in adults was bleeding; in children, obstruction. Among patients with a symptomatic Meckel diverticulum, the male-female ratio was approximately 3:1. Clinical or histologic features most commonly associated with symptomatic Meckel diverticula were patient age younger than 50 years (odds ratio [OR], 3.5; 95% confidence interval [CI], 2.6–4.8; P < 0.001), male sex (OR, 1.8; 95% CI, 1.3–2.4; P < 0.001); diverticulum length greater than 2 cm (OR, 2.2; 95% CI, 1.1–4.4; P = 0.02), and the presence of histologically abnormal tissue (OR, 13.9; 95% CI, 9.9–19.6; P < 0.001). Conclusions:After analyzing our data, we neither support nor reject the recommendation that all Meckel diverticula found incidentally should be removed, although the procedure today has little risk. If a selective approach is taken, we recommend removing all incidental Meckel diverticula that have any of the 4 features most commonly associated with symptomatic Meckel diverticulum.

Alvimopan, a novel, peripherally acting μ opioid antagonist: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus

Objective:To demonstrate that alvimopan (6 or 12 mg) accelerates recovery of gastrointestinal (GI) function in patients undergoing laparotomy for bowel resection or radical hysterectomy. Summary Background Data:Postoperative ileus (POI) following laparotomy may increase morbidity and extend hospitalization. Opioids can contribute to the duration of POI. Alvimopan is a novel opioid receptor antagonist in development for the management of POI. Methods:A total of 510 patients scheduled for bowel resection or radical hysterectomy were randomized (1:1:1) to receive alvimopan 6 mg, alvimopan 12 mg, or placebo orally ≥2 hours before surgery, then twice a day (b.i.d.) until hospital discharge or for up to 7 days. The primary efficacy end point was a composite of time to recovery of upper and lower GI function. An associated secondary end point was time to hospital discharge order written. Results:The modified intent-to-treat population included 469 patients (451 bowel resection and 18 radical hysterectomy patients). Time to recovery of GI function was accelerated for the alvimopan 6 mg (hazard ratio [HR] = 1.28; P < 0.05) and 12 mg (HR = 1.54; P < 0.001) groups with a mean difference of 15 and 22 hours, respectively, compared with placebo. The time to hospital discharge order written was also accelerated in the alvimopan 12 mg group (HR = 1.42; P = 0.003) with a mean difference of 20 hours compared with placebo. The incidence of adverse events was similar among treatment groups. Conclusions:Alvimopan accelerated GI recovery and time to hospital discharge order written compared with placebo in patients undergoing laparotomy and was well tolerated.

Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease☆☆☆

BACKGROUND & AIMS Recurrence of Crohns disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohns disease after surgical resection is performed. METHODS One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months. RESULTS The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group. CONCLUSIONS Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohns disease after surgical resection is performed.

Functional Outcomes After Ileal Pouch-Anal Anastomosis for Chronic Ulcerative Colitis

OBJECTIVE To assess long-term outcomes after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (CUC) with specific emphasis on patient sex, childbirth, and age. SUMMARY BACKGROUND DATA Childbirth and the process of aging affect pelvic floor and anal sphincter function independently. Early function after IPAA is good for most patients. Nonetheless, there are concerns about the impact of the aging process as well as pregnancy on long-term functional outcomes after IPAA. METHODS Functional outcomes using a standardized questionnaire were prospectively assessed for each patient on an annual basis. RESULTS Of the 1,454 patients who underwent IPAA for CUC between 1981 and 1994, 1,386 were part of this study. Median age was 32 years. Median length of follow-up was 8 years. Pelvic sepsis was the primary cause of pouch failure irrespective of sex or age. Functional outcomes were comparable between men and women. Eighty-five women who became pregnant after IPAA had pouch function, which was comparable with women who did not have a child. Daytime and nocturnal incontinence affected older patients more frequently than younger ones. Incontinence became more common the longer the follow-up in older patients, but this was not found in younger patients. Poor anal function led to pouch excision in only 3 of 204 older patients. CONCLUSIONS Incontinence rates were significantly higher in older patients after IPAA for CUC compared with younger patients. However, this did not contribute to a greater risk of pouch failure in these older patients. Patient sex and uncomplicated childbirth did not affect long-term functional outcomes.

Long-term results of ileal pouch-anal anastomosis in patients with Crohn's disease

PURPOSE: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for most patients with chronic ulcerative colitis. Crohns disease is, however, a contraindication. Because distinction between UC and Crohns disease can be difficult, some patients with Crohns disease inadvertently undergo IPAA. The aim of this study was to determine the long-term outcome of patients with Crohns disease who have undergone IPAA. METHODS: A total of 37 patients (20 men) were studied. Each had undergone mucosectomy with handsewn IPAA (J-pouch, n=35; S-pouch, n=1; W-pouch, n=1). Histologic examination of the resected specimen at time of IPAA showed features of ulcerative colitis (n=22), indeterminate colitis (n=9), or Crohns disease (n=6). The stoma was closed in all patients. RESULTS: A total of 11 of 37 patients developed complex fistulas (pouch-cutaneous (n=6), pouch-vaginal (n=4), or pouch-vesical (n=1). Crohns disease has recurred in the pouch (n=20), anal canal (n=4), pouch and anal canal (n=10), and elsewhere (n=3). After ten years (range, 3–14), the pouch remainsin situin 20 patients in whom frequency of bowel movement is seven times (3–10)/24 hours,in situbut defunctioned in seven patients, and excised in ten patients (failure rate, 45 percent). CONCLUSIONS: Inadvertent IPAA for Crohns disease is associated with a high rate of failure (45 percent) but an acceptable long-term functional result if the pouch can be keptin situ.