Fabrizio Michelassi

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.

Survival in 1001 Patients with Carcinoma of the Pancreas

Among 1001 patients with carcinoma of the pancreas, 23 of 912 patients with exocrine carcinomas, 10 of 46 with ampullary carcinomas, and 21 of 43 with malignant islet cell tumors survived 3 years. Of the survivors with exocrine cancers, there were nine of 97 patients who had curative operation, two had had palliative resections only, and one was an incidental microfocal carcinoma; in the remaining 11 patients a histologic origin in the pancreas was not established. Preoperatively suspected and histologically proven 3-year survivors included six patients with ductal adenocarcinomas, three patients with mucinous cystadenocarcinomas, one patient with acinic cell carcinoma, and one patient with microadenocarcinoma. Only two patients can be considered cured. Tumor size and lymph node status did not correlate with survival. Cystadenocarcinomas comprised 1% of cases but one third of 3-year survivors. Long-term survival in histologically confirmed pancreatic carcinoma is a rare event that cannot be predicted in the individual case.

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.

Primary and recurrent Crohn's disease. Experience with 1379 patients.

Between 1970 and 1988, 1379 patients with Crohns disease were treated at the University of Chicago. Of these, 639 (mean age, 32.5 years; 322 men, 317 women) required at least one surgical procedure. The most common indications for operation were failure of medical treatment (n = 215, 33%), presence of a fistula (n = 154, 24%), and bowel obstruction (n = 141, 22%). A fistula was the most common intraoperative Crohns-related complication. In 582 patients (92%), a resection was necessary, with primary anastomosis in 416 (65%), a temporary stoma in 124 (20%), and a permanent stoma in 42 (7%). The remaining 57 patients underwent diverse procedures (stricturoplasty, bypass, and so on). Two patients (0.3%) died. Follow-up data was obtained in 95%. One hundred eighteen patients developed recurrence requiring reoperation. The recurrence rate was 20% at 5 years and 34% at 10 years. The recurrence involved a permanent stoma or a previous anastomosis in 62 patients (afferent limb in 46, efferent in 16). In the 391 patients without previous surgery for Crohns disease, a covariate analysis was performed to determine those variables significantly associated with recurrence. Variables included demographic data, findings at operation, surgical procedures, and histopathologic characteristics. The analysis revealed that the number of sites involved was the only variable that was significantly associated with the intra-abdominal recurrence rate (p less than 0.001). The annualized risk of recurrence was 1.6% for patients with single-site involvement and 4% for those with multiple-site involvement. Perineal disease was associated with a significantly higher risk of local recurrence than any other site (p less than 0.02). A subanalysis of 236 patients with single-site involvement but no previous operation allowed us to study the influence of site on indications for surgery and type of operative procedure. Failure of medical treatment was the most common indication for all sites. In contrast the site involved influenced the procedure: resection and primary anastomosis was feasible in 88% of jejunoileal and terminal ileal cases and a temporary ileostomy was necessary in only 12%. No patients with small bowel localization required a permanent stoma. A resection with primary anastomosis was feasible in only 32% of patients with colonic disease. The remaining two thirds of patients required either a temporary or a permanent stoma. It is concluded that multisite involvement is associated with 2.5 times the rate of recurrence of single-site disease, while the presence of perineal disease has a significantly higher incidence of local recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-term Functional Results After Ileal Pouch Anal Restorative Proctocolectomy for Ulcerative Colitis: A Prospective Observational Study

Objective To document functional results in patients treated with an ileal pouch anal anastomosis (IPAA). Summary Background Data The restorative proctocolectomy with IPAA has become the procedure of choice for patients with ulcerative colitis, yet the long-term functional results are not well known. Methods We performed this prospective observational study in 391 consecutive patients (56% male; mean age, 33.7 ± 10.8 years; range, 12–66 years) who underwent an IPAA between 1987 and 2002 (mean follow-up, 33.6 months; range, 0 to 180 months). Results The majority of patients underwent the procedure under elective circumstances with a hand-sewn ileal pouch anal anastomosis and a protective ileostomy. In 25 patients (6.4%), the procedure was performed under urgent conditions; in 137 patients (35%), the temporary ileostomy was omitted; in 117 patients (29.9%), the ileal pouch anal anastomosis was stapled. There was 1 hospital mortality (0.25%) and 1 30-day mortality. Mean length of stay was 9.2 ± 5.6 days (3–68 days; median, 8 days) and was increased by the occurrence of septic complications (8.9 versus 13.6 days; P < 0.02) and by the omission of a temporary ileostomy (8.3 versus 10.4 days; P = 0.005). Complications included pelvic abscess (1.3%), anastomotic dehiscence (6.4%), bowel obstruction (11.7%), and anastomotic stenosis in need of mechanical dilatation (10.7%). Patients were asked to record their functional results on a questionnaire for 1 week at 3, 6, 9, 12, 18, and 24 months after the IPAA and yearly thereafter. Our data to 10 years show that median number of bowel movements (bms) was 6 bm/24 hours at all time intervals. The average number of bms increased by 0.3 bm/decade of life (P < 0.001). Throughout the entire follow-up, more than 75% of patients had at least 1 bm most nights, although fewer than 40% found it necessary to alter the time of their meals to avoid bms at inappropriate times. Depending on the time interval, between 57% and 78% of patients were always able to postpone a bm until convenient, and this ability was similar in patients with a stapled or hand-sewn ileoanal anastomosis; only up to 18% were able to always distinguish between flatus and stools, and this ability was similar in patients with a stapled or hand-sewn ileoanal anastomosis. Complete daytime and nighttime continence was achieved by 53–76% of patients depending on the time interval. The percentage of fully continent patients was higher following the stapled rather than the hand-sewn technique (P < 0.001), and this difference persisted over time. When patients experienced incontinence, its occurrence ameliorated over time (P < 0.001), and the occurrence of perianal rash and itching as well as the use of protective pads decreased over time (P < 0.008). At 5 years, patients judged quality of life as much better or better in 81.4% and overall satisfaction and overall adjustment as excellent or good in 96.3% and 97.5%, respectively. Conclusions We conclude that the IPAA confers a good quality of life. The majority of patients are fully continent, have 6 bms/d on average, and can defer a bm until convenient. When present, incontinence improves over time.

Experience with 647 consecutive tumors of the duodenum, ampulla, head of the pancreas, and distal common bile duct.

Between 1946 and 1987, 647 patients with periampullary tumors were diagnosed at the University of Chicago Medical Center. These included 549 tumors located in the head of the pancreas, 40 in the distal common bile duct, 29 in the duodenum, and 29 at the ampulla of Vater. Ninety-eight per cent of all tumors were adenocarcinoma, with 93% of the remaining being duodenal carcinoid or sarcoma. Operability rate ranged from 81% to 97%, according to the tumor location and histologic type. A combination of laparotomy, biopsy, and bypass was performed in 433 patients and only one survived 5 years (0.2%). Resectability rate ranged from 16.5% for pancreatic adenocarcinoma to 89.3% for ampullary tumors. Of the 133 resections, 80 were pancreatoduodenectomies, 29 total pancreatectomies, 7 duodenectomies, 2 gastrectomies, 8 common bile duct resections, and 7 local excisions. Overall 19% of patients who underwent radical resection died in the immediate postoperative period, although mortality has decreased to 5% since 1981. Mortality was 20% after a standard pancreatoduodenectomy and 24.1% after a total pancreatectomy. Five-year actuarial survival rates, including perioperative deaths, were 8.8%, 20%, and 32% for pancreatic, duodenal, and ampullary adenocarcinoma, respectively. One half of patients with sarcoma and two-thirds with carcinoid of the duodenum survived 5 years. No patient with distal common bile duct adenocarcinoma achieved a 5-year survival rate. Multivariate analysis on all patients operated on (n = 566) revealed that the 5-year survival rate was significantly related to intent of operation (palliative 0.2%, curative 12%; p less than 0.001), histologic type (adenocarcinoma 2%, carcinoid and sarcoma 31%; p less than 0.0001), and site (ampullary and duodenal 21%, biliary and pancreatic 0.9%; p less than 0.001). A second multivariate analysis, evaluating only those patients with adenocarcinoma who survived the perioperative period of the radical resection (n = 97) analyzed the influence of tumor size and differentiation, lymphatic, capillary, and perineural microinvasion, lymph node status, and type of procedure (pancreatoduodenectomy vs. total pancreatectomy) on 5-year survival. None of these additional variables was significantly associated with long-term survival rates. In addition we evaluated the presence of local or distant recurrence after resection by analyzing the findings from all autopsies performed on these patients (n = 49): 29.4% of patients died with local recurrence alone, 23.5% with distant recurrence alone, and 47.1% had both local and distant recurrences.(ABSTRACT TRUNCATED AT 400 WORDS)

Identifying important predictors for anastomotic leak after colon and rectal resection: prospective study on 616 patients.

Objective:The purpose of this study was to identify patient, clinical, and surgical factors that may predispose patients to anastomotic leak (AL) after large bowel surgery. Background:Anastomotic leak is still one of the most devastating complications following colorectal surgery. Knowledge about factors predisposing patients to AL is vital to its early detection, decision making for surgical time, managing preoperative risk factors, and postoperative complications. Methods:This was a prospective observational, quality improvement study in a cohort of 616 patients undergoing colorectal resection in a single institution with the main outcome being AL within 30 days postoperatively. Some of the predictor variables were age, sex, Charlson Comorbidity Index (CCI), radiation and chemotherapy, immunomodulator medications, albumin, preoperative diagnoses, surgical procedure(s), surgical technique (laparoscopic vs open), anastomotic technique (staple vs handsewn), number of major arteries ligated at surgery, surgeons experience, presence of infectious condition at surgery, intraoperative adverse events, and functional status using 36-Item Short Form General Health Survey. Results:Of the 616 patients, 53.4% were female. The median age of the patients was 63 years and the mean body mass index was 25.9 kg/m2. Of them, 80.3% patients had laparoscopic surgery and 19.5% had open surgery. AL occurred in 5.7% (35) patients. In multivariate analysis, significant independent predictors for leak were anastomoses less than 10 cm from the anal verge, CCI of 3 or more, high inferior mesenteric artery ligation (above left colic artery), intraoperative complications, and being of the male sex. Conclusions:Multiple risk factors exist that predispose patients to ALs. These risk factors should be considered before and during the surgical care of colorectal patients.

Side-to-side isoperistaltic strictureplasty for multiple Crohn's strictures

BACKGROUND: Strictureplasties are being used with increased frequency in the surgical treatment of severe and extensive Crohns disease of the small bowel; concerns regarding their use have been raised in the presence of long and rigid strictures or when strictures are located in close proximity to each other. METHODS: A new surgical technique, a side-to-side isoperistaltic strictureplasty, has been used in three patients with severe Crohns disease of the small bowel extending up to three feet in length. RESULTS: Three patients (3 males; mean age, 42 years) had recurrent Crohns jejunoileitis extending over the length of 22, 37, and 14 inches. This represented 19, 16, and 24 percent, respectively, of the entire length of their small bowel. In the first two patients, resection of 5 and 7 inches, respectively, from the middle third of the diseased segment facilitated performance of the side-to-side isoperistaltic strictureplasty; in the last patient, the procedure was performed after resection of a 57-inch bypassed loop. All patients had an uncomplicated postoperative course and, at a recent follow-up visit between 4 and 24 months, they continue to be asymptomatic and do not require steroid medications. CONCLUSIONS: We believe that the side-to-side isoperistaltic strictureplasty is a useful adjunct to the armamentarium of the surgeon dealing with patients affected by inflammatory bowel disease. With this technique, bowel is not resected, blind or bypassed loops are avoided, and stenoses are palliated.

Prospective study of the features, indications, and surgical treatment in 513 consecutive patients affected by Crohn's disease☆

BACKGROUND The aim of this prospective study was to elucidate the features, indications, and surgical treatment in patients affected by complications of Crohns disease. METHODS Between January 1985 and July 1996, 513 consecutive patients (248 male, 265 female; mean age, 38 years) were operated on for 542 occurrences of Crohns disease. Data were collected prospectively. RESULTS Indications for abdominal surgery were often multiple but included failure of medical management (n = 220), obstruction (n = 94), intestinal fistula (n = 68), mass (n = 56), abdominal abscess (n = 33), hemorrhage (n = 7), and peritonitis (n = 9). Four hundred sixty-four abdominal procedures were performed, necessitating 425 intestinal resections and 97 stricture plasties. The use of stricture plasty was more common in the second half of the study (16.0% versus 7.3%, second half versus first half; p < 0.01). Perioperative complications occurred in 75 of the 464 abdominal operations (16%). There were no deaths. One hundred thirty patients (25%) required operation for perineal complications of Crohns disease. The presence of Crohns disease in the rectal mucosa was associated with a higher risk for permanent stomas in patients requiring operation for treatment of perianal Crohns disease (67% versus 11%; p < 0.001). CONCLUSIONS Patterns of surgical treatment in Crohns disease are changing, with more emphasis on nonresectional options. The presence of rectal involvement significantly increases the need for a permanent stoma in patients with perianal Crohns disease.

Incidence, diagnosis, and treatment of enteric and colorectal fistulae in patients with Crohn's disease

OBJECTIVE The authors review their experience, evaluating the incidence and examining the various modalities employed in the diagnosis and treatment of patients with Crohns disease complicated by fistulae. SUMMARY BACKGROUND DATA Although common, internal and external fistulae in Crohns disease may pose challenging problems to the surgeon. METHODS Of 639 patients who underwent surgical treatment at the University of Chicago between 1970 and 1988 for complications of Crohns disease, 222 patients (34.7%) were found to have 290 intra-abdominal fistulae. RESULTS A fistula was diagnosed preoperatively in 154 patients (69.4%), intraoperatively in 60 (27%), and only after examination of the specimen in 8 (3.6%). The fistula represented the primary or single indication for surgical treatment in 14 patients (6.3%) and one of several indications in the remaining patients. Of 165 patients with an abdominal mass or abscess, 69 (41.8%) had a fistula. All patients underwent resection of the diseased intestinal segment; 160 (73.1%) with primary anastomosis and the remaining 62 with a temporary or permanent stoma. The fistula was directly responsible for a stoma in only 16 patients (7.2%) and was never responsible for a permanent stoma. Resection of the diseased bowel achieved en bloc removal of the fistula in 145 cases. Removal of 93 additional fistulae required resection of the diseased bowel segment along with closure of a fistulous opening on the stomach or duodenum (n = 14), bladder (n = 35), or rectosigmoid (n = 44). When the fistula drained through a vaginal cuff (n = 4), the opening was left to close by secondary intention; when the fistula opened through the abdominal wall (n = 46), the fistulous tract was debrided. In the remaining two entero-salpingeal fistulae, en bloc resection of the involved salpinx accomplished complete removal of the fistula. There was a dehiscence of one duodenal and one bladder repair; 14 patients (6%) experienced postoperative septic complications and one patient died. CONCLUSIONS Fistulae are diagnosed preoperatively in 69% of cases and can be suspected in as many as 42% of patients with an abdominal mass. Fistulae are the primary or single indication for surgical treatment and are directly responsible for a stoma only in a few patients. Treatment, based on resection of the diseased bowel and extirpation of the fistula, can be accomplished with minimal morbidity and mortality.