Joel J. Bauer

Cyclosporine in severe ulcerative colitis refractory to steroid therapy.

BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago. In an uncontrolled study, 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. METHODS We conducted a randomized, double-blind, controlled trial in which cyclosporine (4 mg per kilogram of body weight per day) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy. A response to therapy was defined as an improvement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatment with oral medications. Failure to respond to therapy resulted in colectomy, but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine. RESULTS Nine of 11 patients (82 percent) treated with cyclosporine had a response within a mean of seven days, as compared with 0 of 9 patients who received placebo (P < 0.001). The mean clinical-activity score fell from 13 to 6 in the cyclosporine group, as compared with a decrease from 14 to 13 in the placebo group. All five patients in the placebo group who later received cyclosporine therapy had a response. CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis.

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.

Repair of large abdominal wall defects with expanded polytetrafluoroethylene (PTFE).

Most abdominal wall incisional hernias can be repaired by primary closure. However, where the defect is large or there is tension on the closure, the use of a prosthetic material is indicated. Expanded polytetrafluoroethylene (PTFE) patches were used to repair incisional hernias in 28 patients between November 1983 and December 1986. Twelve of these patients (43%) had a prior failure of a primary repair. Reherniation occurred in three patients (10.7%). Wound infections developed in two patients (7.1%), both of whom had existing intestinal stomas, one with an intercurrent pelvic abscess. The prosthetic patch was removed in the patient with the abscess, but the infection was resolved in the other without sequelae. Septic complications did not occur after any operations performed in uncontaminated fields. None of the patients exhibited any undue discomfort, wound pain, erythema, or induration. Complications related to adhesions, erosion of the patch material into the viscera, bowel obstruction, or fistula formation did not occur. Based on this clinical experience, the authors believe that the PTFE patch appears to represent an advance in synthetic abdominal wall substitutes.

Phase III Trial of Alvimopan, a Novel, Peripherally Acting, Mu Opioid Antagonist, for Postoperative Ileus After Major Abdominal Surgery

PURPOSEPostoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus.METHODSPatients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study.RESULTSMean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group.CONCLUSIONSIn patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.

Restorative proctocolectomy without diverting ileostomy

PURPOSE: Restorative proctocolectomy (RPC) by abdominal colectomy and ileal pouch-anal anastomosis (IPAA) in the setting of chronic ulcerative colitis (CUC) and familial adenomatous polyposis (FAP) has gained widespread popularity among surgeons and patients. Traditionally, temporary loop ileostomy has been established proximal to the ileal pouch in an effort to mitigate the effects of any suture line complications that may occur. This study compares functional results and complications encountered after RPC with mucosectomy with and without temporary ileostomy. METHODS: One hundred forty-three consecutive patients with either CUC or FAP underwent RPC including mucosectomy and ileal “J” reservoir. Proximal loop ileostomy was performed in 69 patients, and ileostomy was omitted in 74. Ileostomy was omitted if the patient was taking no immunosuppressives and less than 20 mg of prednisone daily in the month preceding surgery, the anastomosis was absolutely tension-free, and blood supply to the pouch was excellent. RESULTS: There were no perioperative deaths. There were two instances of pelvic abscess, one in the diverted group and one in the nondiverted group. Occurrence of IPAA suture line dehiscence was not significantly different between the two groups (ileostomy, 4/69 (6 percent),vs.no ileostomy, 6/74 (8 percent);P>0.05). Comparison of 129 patients with colitis with and without diversion also failed to demonstrate a significant difference with regard to IPAA suture line dehiscence (ileostomy, 4/69 (6 percent)vs.4/60 (7 percent);P>0.05). Frequency of bowel movements and continence were the same in both groups and were comparable with results obtained without mucosectomy. Mean hospital stay at the time of RPC for the nondiverted group was significantly longer (12 daysvs.10 days;P=0.0004). Significantly fewer patients without an ileostomy were hospitalized for partial intestinal obstruction (ileostomy, 13/69 (19 percent),vs.no ileostomy, 3/74 (4 percent);P=0.02), and significantly fewer required enterolysis (ileostomy, 7/69 (10 percent),vs.no ileostomy, 1/74 (1 percent);P=0.04). On average, patients without an ileostomy spent significantly fewer total days in the hospital (17vs.24;P=0.002). CONCLUSION: Restorative proctocolectomy with mucosectomy and without ileostomy is the procedure of choice for selected patients with FAP and CUC. Septic complications and functional results are similar to those seen in patients managed with a stoma. Anastomotic leakage, when it occurs, can be safely managed in most cases without surgery. RPC without ileostomy results in significantly fewer episodes of intestinal obstruction, fewer instances of re-exploration, and fewer total days in the hospital.

Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose-based bioresorbable membrane: A prospective, randomized, evaluator-blinded multicenter study

INTRODUCTIONPostoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients.METHODSTwelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no antiadhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.RESULTSData were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose.CONCLUSIONSGlycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.

Laparoscopic-assisted intestinal resection for Crohn's disease

PURPOSE: The inflammatory process associated with Crohns disease often makes dissection difficult, even in “open” surgery. This study was undertaken to determine if dissection and resection could be performed laparoscopically and whether it would benefit this group of patients. METHODS: Between November 1992 and November 1994, laparoscopic-assisted intestinal resection was attempted in 18 patients with Crohns disease and was successfully completed in 14. One patient had ileal disease, requiring ileal resection with ileoileal anastomosis. The remainder had disease requiring ileocolic resections. Muscle-splitting incisions averaging 5 cm in length were made to facilitate removal of specimens. RESULTS: Commencement of oral alimentation was possible at an average of 3.6 (range, 1–7) days postoperatively. Discharge occurred at an average of 6.6 (range, 4–9) postoperative days. In comparison, 14 patients operated on by the authors for the same disease in the open manner during the past six months stayed an average of 8.5 (range, 5–14) postoperative days. Postoperative complications were minimal. CONCLUSIONS: On the basis of this initial study, it appears that laparoscopic-assisted intestinal resection can be readily performed in patients with Crohns disease. In our early experience, we have found that laparoscopic mobilization and resection may be difficult or impossible in patients with large fixed masses, multiple complex fistulas, or recurrent Crohns disease. Extraction incisions are frequently so large in these patients that they do not derive the same benefits from laparoscopic surgery that are enjoyed by patients without these findings. Most patients having laparoscopic resections eat earlier, may require fewer narcotics, and are able to be discharged from the hospital an average of two days earlier than patients operated on in an open manner. In addition, it appears that laparoscopic-assisted intestinal resection results in a shorter, easier convalescence and an earlier return to full activity.

Is routine postoperative nasogastric decompression really necessary

Controversy exists regarding the need for nasogastric tube decompression and the incidence of complications resulting from its use following major intra-abdominal surgery. To determine the value of such tubes, 100 patients were managed after surgery with a nasogastric tube in situ until the passage of flatus per rectum (Group I). In a second group of 100 patients, no nasogastric tube was placed after surgery unless vomiting, gross distention, or overt obstruction occurred (Group II). In Group I, the nasogastric tube remained in place an average of 6 days and five patients required replacement of the tube after its initial removal. In Group II, nasogastric intubation was required at some point after surgery in six patients. No aspiration pneumonia, nasal septum necrosis, anastomotic leak, or wound dehiscence was seen in either group. There were three wound infections in Group I and two in Group II. The most obvious difference was the increased comfort and mobility of the group of patients treated without routine nasogastric decompression (Group II). Routine use of the nasogastric tube adjunct to patient care following gastrointestinal tract surgery may be safely eliminated.

Surgical repair of rectovaginal fistulas in patients with Crohn's disease : transvaginal approach

The surgical management of rectovaginal fistulas complicating Crohns disease has been associated with unacceptably high failure rates. We sought to modify the available surgical techniques to provide a solution to this challenging problem. Between December 1983 and January 1990, 14 patients with Crohns disease underwent repair of a rectovaginal fistula. A modified transvaginal approach was employed by the authors. A diverting loop ileostomy was performed on all patients, either as the initial step in the staged management of intractable perianal disease or concurrent with the repair of the rectovaginal fistula. The fistula was completely eradicated in 13 of the 14 women and did not recur during the mean follow-up period of 55.0 months (range, 3–77 months). Intestinal continuity was reestablished in these 13 patients within 6 months after the initial fistula repair. One patient with a very low-lying fistula constituted our only failure. We have found the transvaginal method preferable to the transanal approach because of the relative ease in raising the vaginal flap as compared with a flap of fibrotic and inflamed anorectal mucosa. On the basis of this study, we conclude that a modified transvaginal approach is an effective method for repair of rectovaginal fistulas secondary to Crohns disease.

Dysplasia complicating chronic ulcerative colitis: Is immediate colectomy warranted?

PURPOSE: Inflammatory bowel disease surveillance strategies are designed to identify patients at greater than average risk for the development of invasive colonic carcinoma. Colonoscopic detection of mucosal dysplasia is considered the best available surveillance tool. However, the usefulness of dysplasia as a marker for cancer is uncertain. Furthermore, when dysplasia is found some suggest immediate colectomy, whereas others opt for continued surveillance. The aim of this study is to determine whether an association between dysplasia grade and cancer exists in patients with chronic ulcerative colitis, to ascertain the sensitivity, specificity, and positive predictive value of dysplasia as a cancer marker, and to clarify what action to take once dysplasia is discovered. METHODS: The pathology reports of 590 patients who underwent total proctocolectomy or restorative proctocolectomy for chronic ulcerative colitis were reviewed for dysplasia, grade of dysplasia, presence of carcinoma, and tumor stage. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery. Findings from these studies were also reviewed. RESULTS: Seventy-seven specimens (13.1 percent) contained at least one focus of dysplasia. Invasive cancers were found in 38 specimens (6.4 percent). Cancers were significantly more common among specimens with dysplastic changes (33/77vs. 5/513;P<0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III disease was found in association with indefinite or low-grade dysplasia in 5 of 26 (19.2 percent) of cases. Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 (69.5 percent) cases. Dysplasia, cancer or both were missed in 25 cases. Lesions were correctly identified in only 31 (39.7 percent) of cases. Colonoscopically diagnosed dysplasia as a marker for synchronous cancer had a sensitivity of 81 percent and a specificity of 79 percent. The positive predictive value of a finding of preoperative dysplasia of any grade was 50 percent. The positive predictive value of a finding of low-grade dysplasia was 70 percent. CONCLUSIONS: Dysplasia is an unreliable marker for the detection of synchronous carcinoma. However, when dysplasia of any grade is discovered at colonoscopy, the probability of a coexistent carcinoma is relatively high. Colonoscopic evidence of low-grade dysplasia has a higher positive predictive value than either dysplasia associated mass or lesion or high-grade dysplasia. Dysplasia grade does not predict tumor stage. Because advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade is an indication for colectomy.