Subclinical time span of inflammatory bowel disease in patients with primary sclerosing cholangitis

PURPOSE: This study is designed to describe colonic histology in patients with primary sclerosing cholangitis (PSC) without clinical symptoms of inflammatory bowel disease (IBD) and to do a follow-up study of these patients to find the time span from first detection of histologic signs until development of clinical symptoms of IBD. METHODS: In a cohort of 76 patients with PSC treated at Huddinge University Hospital, 11 patients did not have any clinical symptoms of IBD at the time of PSC diagnosis. Nine of these patients underwent diagnostic colonoscopy with multiple biopsies. RESULTS: In the group of nine PSC patients, without clinical signs of IBD undergoing colonoscopy, histologic signs of IBD were found in seven patients (6 ulcerative colitis and 1 Crohn's disease). Among them one had dysplasia, and another had epithelial changes probably positive for dysplasia. Two other patients had histologic signs of inflammation, however, not fully compatible with IBD. Three of 11 patients developed clinical symptoms of IBD after one, three, and seven years of follow-up since diagnostic colonoscopy. CONCLUSIONS: In patients with PSC, histologic signs of IBD, including premalignant changes, may precede development of clinical symptoms of IBD by as much as seven years. This indicates that IBD onset may have a substantial subclinical phase of IBD far longer than previously appreciated. This finding may be of clinical importance because underestimation of disease duration may delay inclusion of PSC patients with extensive colitis in colonoscopic surveillance programs. The subclinical phase may also allow the studies of early pathogenesis in vivo.Supported by grants from the Nanna Svartz Scholarship.     

Substance P containing nerve fibers in rectal mucosa of ulcerative colitis

BACKGROUND AND PURPOSE: The intestine is rich in peptidergic innervation, which modulates mucosal immune responses. Among neuropeptides, substance P (SubP) has received considerable attention for stimulatory effects on various immunocytes in inflammatory diseases. In our prior study, we demonstrated increased innervation of SubP containing nerve fibers (SubP fibers) in ulcerative colitis (UC) surgically resected colonic specimens. In the present study, we examined the alterations of SubP fibers among various subgroups of UC, divided according to clinicopathologic features. METHODS: Distribution of SubP fibers were examined immunohistochemically in the rectal biopsy specimens of UC. The UC group was further divided into subgroups according to six clinicopathologic parameters. The linear density of SubP fibers was measured by digitalized morphometry for quantitative analysis. RESULTS: Multivariate analysis revealed significant correlations between linear density of SubP fibers vs.activity of diseases and total dose of prednisolone. Linear density was significantly increased in active cases of UC (active UC, 22.6±1.6 μm/1,000 μm ²;vs.inactive UC, 12.2±0.8 μm/1,000 μm ²;P<0.01). Furthermore, the increase was pronounced in cases that showed persistent inflammation and, accordingly, needed a high dose or continuous administration of prednisolone. CONCLUSION: Alterations in SubP fibers appear to play an important role in the pathogenesis of UC.     

Colorectal adenocarcinoma in Crohn's disease

PURPOSE: The aim of this study was to review all histopathologic sections from surgical specimens with inflammatory bowel disease and colorectal carcinoma filed at this hospital between 1951 and 1996. METHOD: A total of 40 surgical (n=39) or autopsy (n=1) colon or colorectal specimens were reviewed. Internationally accepted histologic criteria were strictly applied to differentiate Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC). RESULTS: Of the 40 specimens with inflammatory bowel disease and carcinoma, 22 (55 percent) had CD, 16 (40 percent) had UC, and the remaining 2 (5 percent) had IC. Males accounted for 72.7 percent or 16 of the 22 patients with colorectal carcinoma in CD and for 68.7 percent or 11 of the 16 patients with carcinoma in UC. Both patients with IC and carcinoma were males. The median age of patients at diagnosis was as follows: CD, 20 (range, 7–68) years; UC, 23 (range, 5–21) years. In IC, the age was 61 and 81 years, respectively. The median disease duration (before detection of colorectal cancer) was as follows: CD, 18.5 (range, 1–45) years; UC, 19 (range, 6–38) years. For cases with IC, it was 13 and 19 years, respectively. Median age of patients at cancer diagnosis was as follows: CD, 48 (range, 21–78) years; UC, 49 (range, 21–81) years. Ages at cancer diagnosis in IC were 68 and 81 years. Colorectal carcinoma tend to develop among relatively young patients with CD and UC. Mucinous adenocarcinomas accounted for approximately one-third of the carcinomas affecting CD. Thirty percent of old specimens (before the end of 1982) had in fact carcinoma complicating CD and not UC (the latter being the diagnosis appearing in old pathologic reports). During a time lapse of 38 years (i.e.,between 1951 and 1989), only 11 cases of colorectal CD with carcinoma (i.e.,0.2 cases/year) were found, but as many as 11 during the past 6.5 years (i.e.,1.7 cases/year) have been diagnosed. Only 42.3 percent (11/26) of cases with colorectal inflammatory bowel disease and carcinoma operated on between 1951 and the end of 1989 had Crohn's colitis but as many as 78.6 percent (11/14) of those operated on between 1990 and May 1996 had Crohn's colitis. Review of the literature indicated that 64.8 percent or 191 of the 295 cases of colorectal carcinomas in CD so far reported occurred in the past 6.5 years. It would seem as if the risk of colorectal carcinoma in Crohn's colitis has increased in later years. CONCLUSIONS: 1) Reports on cancer frequency in UC based on old histopathologic records should be subjected to critical histologic re-evaluation; 2) carcinoma in Crohn's colitis has increased at this hospital, particularly since 1990; 3) the surveillance program strategy used in patients with long-standing UC at this hospital should also embrace patients with Crohn's colitis.Supported by the Cancer Society and the Karolinska Institute, Stockholm, Sweden.     

Safety of urgent restorative proctocolectomy with ileal pouch-anal anastomosis for fulminant colitis

PURPOSE: Subtotal colectomy with ileostomy is the operation of choice for patients with fulminant colitis. Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is preferred for patients who undergo elective surgery for ulcerative colitis. We retrospectively evaluated the safety of RPC with IPAA in patients with a moderate form of fulminant colitis. METHODS: A chart review of 737 patients who underwent RPC with IPAA for ulcerative and indeterminate colitis from 1983 through 1992 was performed. Moderate fulminant colitis was defined as acute disease requiring hospitalization and parenteral steroid therapy, but without hypotension (systolic blood pressure, <100 mmHg), tachycardia (>120 beats/min), or megacolon. RESULTS: Twelve patients with moderate fulminant colitis underwent urgent surgery (1.6 percent). They had been treated preoperatively for 5.1±2.3 days with intravenous high-dose steroids, total parenteral nutrition, and antibiotics. These patients had a shorter length of disease ( P =0.01), lower hemoglobin, hematocrit, and albumin (P=0.001), and higher temperature (P=0.002) and leukocyte count (P=0.007) than patients undergoing elective surgery. No early septic complications occurred, although perianal abscess occurred in one patient and pouch-anal fistula in another patient, 13 and 14 months after surgery, respectively. CONCLUSION: In carefully selected, hemodynamically stable patients with fulminant colitis and without megacolon, RPC with IPAA can be safely performed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Clinical course of ulcerative colitis in patients with and without primary sclerosing cholangitis

BACKGROUND AND AIM: We noticed in our practice that patients with ulcerative colitis (UC) who have developed primary sclerosing cholangitis (PSC) experience a milder course of colonic disease. Our objective in this study was to define whether or not there is any difference between UC activity and its course in patients with and without PSC. METHODS: Nineteen patients with UC and PSC (eight male, mean age 25 years) were enrolled. To every patient with UC and PSC, three patients with UC alone (total of 57 patients, 28 male, mean age 24 years) matched for age at onset, duration of the disease and extension of colonic disease were selected as the control group. We used number of hospitalizations due to activity of UC and number of short corticosteroid administrations in various years of follow-up as variables indicating course and severity of the colonic disease in this period. For comparing trends of UC activity between two groups, we used repeated measures two-way analysis of variances. RESULTS: Mean duration of follow up in case and control groups was 12.2 +/- 5.7 and 11.4 +/- 4.9 years, respectively. Two groups had no significant difference in use of sulfasalzine or aminosalicylates. Number of hospitalizations and courses of steroid therapy because of UC activity decreased significantly over time (P < 0.000) in both groups, and it was significantly higher in controls than in cases (P = 0.045 and 0.032, respectively). CONCLUSIONS: Development of PSC in patients with UC might have a positive effect on colonic disease. Further investigations to evaluate the basis of this improvement are warranted.     

SevereClostridium difficile colitis

PURPOSE: Reports of fatality related to Clostridium difficile colitis and a sharp increase in prevalence of this infection prompted a study of patients who develop a more aggressive form of this disease. METHODS: Over 38 months, 710 patients at our institution developed C. difficile colitis. Twenty-one (3 percent) of these patients either required intensive care unit admission or died as a result of their infection. A retrospective, case-controlled study was undertaken to compare these patients, who were considered to have severe C. difficile colitis, with the remaining patients with milder disease. RESULTS: Factors that predisposed to the development of severe C. difficile colitis included intercurrent malignancy, chronic obstructive pulmonary disease, immunosuppressive and antiperistaltic medications, renal failure, and administration of clindamycin (P<0.05 for all). Patients with severe C. difficile colitis were more likely to have abdominal pain, tenderness and distention, peritonitis, hemoconcentration (>5 points), hypoalbuminemia (<3 mg/dl), and elevated or suppressed white blood cell count (>25,000; <1,500;P<0.05 for all). These factors were used to create a scoring system that could distinguish between patients with severe C. difficile colitis and those with mild disease. Thirteen patients in the late stages of terminal illness with metastatic malignancy or age >90 were considered poor or inappropriate surgical candidates. Only the remaining eight patients could have potentially recovered from operation with hope for long-term survival. Of these, seven were treated without colonic resection, and six of the seven survived, whereas one patient underwent colectomy and did not survive. CONCLUSIONS: Patients with severe C. difficile colitis can be readily identified. Often they have coexisting illness that precludes operation. In this series, only 1 of 21 patients with severe C. difficile might have benefited from an aggressive surgical approach.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Instant technetium 99m hexamethyl propylenamine oxime-labeled leukocyte scan compared with colonoscopy in early assessment of disease extent and activity in acute colitis

AIM: This study was undertaken to evaluate technetium 99m (Tc 99m) hexamethyl propylenamine oxime (HMPAO)-labeled leukocyte scintigraphy for assessment of disease extent and activity in acute colitis. PATIENTS AND METHODS: Twenty-seven patients, hospitalized because of acute watery and/or bloody diarrhea, were investigated using both total colonoscopy and Tc 99m HMPAO-labeled leukocyte scintigraphy within 48 hours after admittance. RESULTS: Final diagnoses were ulcerative colitis in 14 patients, Crohn's disease in 7 patients, and infectious colitis in 6 patients. Using colonoscopy as the reference method, the maximum extent of colitis was correctly assessed by the leukocyte scan in 18 patients (67 percent), although rectal engagement was not visualized in 5 (19 percent). In six additional patients, there was almost complete agreement between the two methods. One other patient, with left-sided ulcerative colitis, was erroneously assessed as having total extent. Two other patients (one with Crohn's colitis and one with infectious colitis) had different segments incorrectly assessed. Sensitivity, specificity, and diagnostic accuracy of scintigraphy in detecting active inflammatory segments were 0.85, 0.83, and 0.85, respectively. Intensity of inflammatory activity assessed by the leukocyte scan correlated significantly with colonoscopic assessment (r=0.719;P <0.0001). CONCLUSION: Information regarding extent, localization, and disease activity in patients with acute colitis of inflammatory or infectious origin may be satisfactorily obtained using Tc 99m HMPAO-labeled leukocyte scanning. The noninvasive nature of the method makes it an attractive early alternative to other investigational procedures such as total colonoscopy or barium examination, particularly in cases with an established diagnosis of inflammatory bowel disease.Supported by grants from the Karolinska Institute.     

Colonic subepithelial collagenous thickening in diabetic patients

PURPOSE: This study was designed to investigate the effect of intestinal subepithelial collagenous thickening on diabetic diarrhea because one of the seven patients diagnosed with collagenous colitis was diabetic. METHODS: Rectosigmoidoscopic rectal biopsies were taken from 50 diabetic patients (8 with and 42 without diarrhea), 20 nondiabetic patients with diarrhea, and 10 healthy patients. Histopathologic examinations and measurements of subepithelial collagen layers were performed on these biopsies. RESULTS: In diabetic patients who had diarrhea, the subepithelial collagen layer (SCL) was thicker than it was in diabetics without diarrhea (P<0.05). In diabetic groups, the SCL was thicker than it was in both nondiabetics with diarrhea and those without diarrhea (P<0.05). There was no statistical difference between nondiabetics with diarrhea and those without (P>0.05). There was no correlation between collagen thickness, age, and diabetes duration (P>0.05). CONCLUSION: It was concluded that there was a thickening of the colonic SCL in diabetic patients.     

Variable expression of P-glycoprotein in normal,inflamed, and dysplastic areas in ulcerative colitis

Screening programs for the detection of cancer in ulcerative colitis are inexact and not always successful in finding early, curable cancers. P-glycoprotein is a membrane-based, energy-dependent protein found in varying degrees within normal human tissue. P-glycoprotein is overexpressed in malignant tumors, particularly colorectal cancer, and is known to convey resistance to certain anticancer drugs by acting as a membrane pump. The purpose of this study was to determine the expression of this protein in inflamed and premalignant colonic epithelium, compare its expression with normal controls, and assess its potential use as a screening tool for high-risk patients with ulcerative colitis. Using immunohistochemical techniques, the colons of 21 patients (10 with dysplasia) with ulcerative colitis were stained with monoclonal antibody C-219 (MAbC219) specific for P-glycoprotein. P-glycoprotein was expressed in 38 percent of normal areas, 71 percent of inflamed areas (P =0.0156), and 70 percent of dysplastic areas. Comparing the level of expression when progressing from normal to inflamed areas within a given patient, 11 patients (52 percent) showed increased expression, 8 (38 percent) showed equal expression, and only 2 (10 percent) showed decreased expression (P =0.0225). Comparing expression when progressing from inflamed to dysplastic areas (10 patients), 7 showed equal expression and 3 showed increased expression (P =0.25). Increasing duration of disease was associated with a significant increase in P-glycoprotein expression, but only in histologically normal areas. Duration of disease had no effect on P-glycoprotein expression in inflamed or dysplastic areas. Similarly, when surgery was performed for elective reasons, there was a significant overexpression of P-glycoprotein, but only in histologically normal areas. Our findings suggest that the increase in P-glycoprotein expression from normal to inflamed and dysplastic areas reflects the premalignant nature of ulcerative colitis and occurs early in the course of the disease. Further research needs to be done to determine its role in cancer surveillance.Presented at the meeting of the American College of Gastroenterology, Boston, Massachusetts, October 14, 1991.This work was supported in part by the Bowman Research Fund.     

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. Crohn's disease is, however, a contraindication. Because distinction between UC and Crohn's disease can be difficult, some patients with Crohn's disease inadvertently undergo IPAA. The aim of this study was to determine the long-term outcome of patients with Crohn's 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 Crohn's 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). Crohn's 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 remains in situ in 20 patients in whom frequency of bowel movement is seven times (3–10)/24 hours,in situ but defunctioned in seven patients, and excised in ten patients (failure rate, 45 percent). CONCLUSIONS: Inadvertent IPAA for Crohn's disease is associated with a high rate of failure (45 percent) but an acceptable long-term functional result if the pouch can be kept in situ.Read at the meeting of the Association of Surgeons of Great Britain and Ireland, Glasgow, United Kingdom, May 22 to 24, 1996.     

Patterns and prognosis ofClostridium difficile colitis

The incidence of Clostridium difficile colitis has increased during recent years, presumably because of liberal use of broad-spectrum antibiotic regimens. METHODS: A retrospective review to determine patterns of C. difficile colitis development, morbidity, and treatment results was undertaken. During an 18-month period, 90 patients were diagnosed with C. difficile colitis by fecal toxin assays. Patient demographics, symptoms, previously administered antibiotic regimens, diagnostic evaluations, treatment modalities, morbidity, and mortality were identified, entered into a computer data base, and analyzed. RESULTS: The mean age was 58 years; males outnumbered females 1.21. Among 90 patients, 41 (46 percent) developed C. difficile colitis after surgical procedures. Eighty (89 percent) patients received antibiotic therapy before developing C. difficile colitis: 35 (44 percent) for documented infections and 45 (56 percent) as empiric or prophylactic therapy. Cephalosporins, penicillins, quinolones, vancomycin, and aminoglycosides were the most frequently administered antibiotic classes prior to C. difficile colitis diagnosis. Ten (11 percent) patients developed C. difficile colitis without previous antibiotic therapy. Eighty-two (91 percent) patients presented with diarrhea, while eight (9 percent) had fever only. Primary C. difficile colitis treatment for both groups included vancomycin (66 percent), metronidazole (24 percent), or both drugs (10 percent). Ten (11 percent) patients received no treatment. No patient developed toxic colitis or megacolon. Colonoscopy was performed in four (4 percent) patients; pseudomembranes were identified in one (25 percent) patient. There was one C. difficile colitis recurrence after treatment, but no C. difficile colitis-associated morbidity. Mortality (14 patients, 16 percent) was not related to C. difficile colitis, but to underlying illness. No difference in patient age, sex, previous antibiotic administration, serum albumin, total days hospitalized, duration of C. difficile colitis antibiotic therapy,C. difficile colitis treatment regimens, or mortality was identified between nonsurgical and surgical patients. The white blood cell count was significantly lower in the nonsurgical group however.Clostridium difficile colitis developed most commonly after antibiotic administration with symptoms of diarrhea, but did occur without previous antibiotic administration or diarrhea. CONCLUSION: Despite the clinical setting,C. difficile colitis had no associated morbidity and treatment was highly effective. Mortality was related to underlying medical illness, not C. difficile colitis.Read at the meeting of The American Society of Colon and Rectal Surgery, Chicago, Illinois, May 2 to 7, 1993.     

Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis

PURPOSE: The aim of this study was to compare the efficacy of intermittent therapy with mesalazine enemas and continuous oral mesalazine to maintain remission of distal ulcerative colitis or proctitis. METHODS: Thirt-yeight patients with distal ulcerative colitis (n=17) or ulcerative proctitis (n=21) in clinical, endoscopic, and histologic remission were randomly assigned to receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n=19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid enema every third night, n=19). Both groups were comparable in regard to sex, age, age at disease onset, extent and duration of disease, number and mode of treatment of previous attacks, and time in remission. Patients were reviewed at the beginning of the study and, subsequently, at two-month intervals for 24 months or until a relapse occurred. At each visit, diaries were reviewed and clinical and laboratory assessments were performed. Sigmoidoscopy was carried out and biopsies were obtained by a blinded observer. Histology was assessed without knowledge of the patient's clinical state or treatment category. RESULTS: At the end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19 patients on mesalazine enemas (74 percent) were still in full remission (log rank test: 15.280,P <0.001). Differences in relapse rates between groups were significant even when data were stratified by extent of disease (P <0.01). In the oral group, six and seven patients relapsed at 12 and 24 months, respectively. In the enema group, three and two relapses occurred in the first and second year of the study, respectively. All patients complied with the treatment satisfactorily and there were no dropouts. CONCLUSION: These results suggest that intermittent therapy with mesalazine enemas is more effective than continuous oral mesalazine in maintaining remission in patients with distal ulcerative colitis and proctitis.Read at the meeting of the First United European Gastroenterology Week, Athens, Greece, September 25 to 30, 1992.     

Quality of life after restorative proctocolectomy with a pelvic ileal reservoir compares favorably with that of patients with medically treated colitis

There remains some reluctance among physicians to refer patients for restorative proctocolectomy (RP). They argue that their patients would be worse off with a pouch because of the attendant problems of urgency and frequent bowel actions. The aim of this study was to compare quality of life in patients who had undergone RP with that of patients with ulcerative colitis on long-term medical treatment. A detailed questionnaire and the Hospital Anxiety and Depression (HAD) test were completed by 103 patients who had undergone RP and by 95 patients with ulcerative colitis on medical treatment and in remission attending a gastroenterology clinic. Patients with a pouch had a greater frequency of bowel action [five times per 24 hours (range, 4–7) vs.two times per 24 hours (range, 1–3);P <0.001] but less urgency of defecation [12/103 (11.7 percent) vs.69/95 (72.6 percent);P <0.001] than patients with medically treated colitis. Efficiency of evacuation, discrimination between flatus and feces, use of perianal pads, and perianal soreness were similar. Use of antidiarrheal medication was more common in the pouch group [53 of 103 patients (51.5 percent) vs.3 of 95 patients (3.2 percent);P < 0.05], whereas use of topical steroids was more common in medically treated patients [40 of 95 patients (47.1 percent) vs.9 of 103 patients (8.7 percent);P <0.05]. Limitation of social activity and HAD scores were significantly higher in medically treated patients. Quality of life for patients with a pouch appears to be as good as that for patients with medically treated colitis.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.     

Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model

Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n=33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P<0.05). Gross inspection showed severe colonie inflammation through the first week (mean score =4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonie inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans.     

Cyclosporine for the treatment of fulminant ulcerative colitis in children

PURPOSE: Emergency surgery for fulminant colitis is often complicated by high-dose steroid therapy, poor nutrition, and psychologic maladjustment. Cyclosporine is effective for fulminant ulcerative colitis in adults, resulting in avoidance of immediate surgery in 75 percent of patients and a 55 percent long-term remission rate. Over the last five years, we studied the effectiveness of cyclosporine in children with fulminant colitis. METHODS: Fourteen patients with ulcerative colitis (age, 7–20 years) received cyclosporine after satisfying the following criteria: 1) greater than five bloody diarrheal stools per day; 2) severe abdominal pain; 3) no improvement after ten days of bowel rest, 4) intravenous methylprednisolone (1–2 mg/kg/day); and 5) parenteral nutrition. Treatment was begun with oral cyclosporine (4.6–9.6 mg/kg/day), and the dose was adjusted to achieve whole blood trough levels measured with a monoclonal radioimmunoassay between 150 and 300 ng/ml. If improved, patients were discharged on oral cyclosporine, prednisone, and a regular diet. RESULTS: Eleven of 14 patients (78 percent) responded within two to nine days and were able to consume a normal diet, had three or less soft stools per day, and had no pain. One did not respond after ten days and underwent an ileal pouch-anal anastomosis procedure. Two patients elected surgery after 20 days of therapy and a partial response. Of 11 patients who left the hospital, 4 had recurrent symptoms after 2 to 11 months of taking therapeutic doses of cyclosporine and 3 flare ups while weaning from cyclosporine after 4 to 8 months. Three patients have been weaned from cyclosporine after 8 to 13 months and have remained in remission from six months to five years. One patient is about to complete a six-month course of cyclosporine. Overall ten (72 percent) have undergone surgery, including 7 of 11 who responded initially to cyclosporine and left the hospital. Weight (P<0.001), albumin (P <0.01), erythrocyte sedimentation rate (P>0.05), and prednisone dose (P<0.001) improved significantly in the seven patients on cyclosporine who responded initially, left the hospital, and subsequently underwent surgery. CONCLUSIONS: Cyclosporine is effective in achieving clinical remission in 80 percent of children with refractory fulminant colitis; however, within one year, most initial responders will require colectomy because of a flare up of the disease. In a majority of patients, the role of cyclosporine therapy is to rapidly ameliorate symptoms and prevent precipitous colectomy, improve nutrition and psychologic adaptation, and reduce the steroid dose leading to surgery in a well-prepared patient.Read in part at the meeting of the American Society of Gastrointestinal Endoscopy, New Orleans, Louisiana, May 15 to 18, 1994. Winner of the Midwest Society of Colon and Rectal Surgeons William C. Bernstein, M.D. Award.     

Total abdominal colectomy and ileorectal anastomosis for inflammatory bowel disease

PURPOSE: This retrospective study assesses the results of total colectomy and ileorectostomy for inflammatory bowel disease. METHODS: Between January 1974 and December 1990, 90 patients underwent total colectomy and ileorectal anastomosis for chronic ulcerative colitis (n=48) or Crohn's colitis (n=42) at the Mayo Clinic. Patients' records were reviewed retrospectively. Long-term results were assessed by chart reviews and postal questionnaires. Conversion to a permanent ileostomy, with or without proctectomy, was considered a failure of the procedure. The Kaplan-Meier method was used to estimate survivorship free of failure. The log-rank test was used to compare survivorship curves. Ninety-five percent confidence intervals were calculated at selected time points.P values<0.05 were considered to be statistically significant. RESULTS: The main indication for surgery was refractory chronic disease. There were no immediate postoperative deaths. The anastomotic leakage rate was 4.4 percent, and small-bowel obstruction occurred in 15.6 percent. At the time of follow-up (mean, 6.5±4.8 years), 46 patients (58.9 percent) had recurrence or exacerbation of the disease. This was the most common indication for subsequent proctectomy/permanent ileostomy in the follow-up period. There were 8 failures in 48 patients with ulcerative colitis (16.7 percent) and 11 failures in 42 patients with Crohn's disease (26.2 percent), although this difference was not statistically significant. Cumulative probability of having a functioning ileorectal anastomosis at five years was 84.2 percent (95 percent confidence interval, 71–95.9 percent) for ulcerative colitis and 73.8 percent (95 percent confidence interval, 58.6–88.6 percent) for Crohn's disease. In the latter group, females showed a significantly lower cumulative probability of having a functioning ileorectal anastomosis (females, 634 percent; males, 92.3 percent;P =0.04). Crohn's patients 36 years of age or younger also showed a lower probability of success (patients 36 years, 57 percent; patients >36 years, 93.8 percent;P =0.03). In the group with chronic ulcerative colitis, younger patients also seemed to require additional surgery more frequently; however, this difference was not statistically significant. Previous duration of symptoms, with mild or moderate disease in a distensible rectum, had no effect on results in either disease group. Functional results were acceptable in 63.6 and 87.5 percent of patients with Crohn's and ulcerative colitis, respectively. Eighty-four percent of ulcerative colitis patients and 91 percent of Crohn's disease patients reported an improvement in their quality of life, and overall, more than 90 percent considered their health status to be better than before surgery. One patient with ulcerative colitis developed carcinoma of the rectal stump 11.5 years after the colectomy and ileorectal anastomosis (cumulative probability of remaining free of cancer, 85.7 percent at 12 years; 95 percent confidence interval, 57.7–100 percent). CONCLUSIONS: These results demonstrate that, in selected patients with a relatively spared rectum and without severe perineal disease, total colectomy and ileorectal anastomosis still remains a viable option to total proctocolectomy with extensive Crohn's colitis. In addition, ileorectal anastomosis, as a sphincter-saving procedure, continues to have a place in the surgical treatment of chronic ulcerative colitis for high-risk or older patients who are not good candidates for ileal pouch-anal anastomosis, when the latter procedure cannot be done because of technical reasons and in the presence of advanced carcinoma concomitant with colitis, when life expectancy is limited.     

Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease

Objective: The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province.

Methods: Data of 678 incident IBD patients (Crohn’s disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21–40 years, disease duration: 6, IQR: 2–9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26–50 years, duration: 7, IQR: 4–10 years).

Results: EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p?=?0.02) need for steroid (p ?p?=?0.02), while in UC, young age at onset (p?=?0.03), extensive disease (p?=?0.003), female gender (p?=?0.07), need for steroids (p?p?=?0.004) and need for IBD-related hospitalization (p?=?0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (p_CD?=?0.001, p_UC?=?0.04), disease location/extent (p_CD?=?0.02, p_UC?p_CD,UC?p_CD?p_UC?=?0.002) and hospitalization (p_CD?=?0.004, p_UC?p?=?0.002).

Conclusions: The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.     

One-stage restorative proctocolectomy without temporary ileostomy for ulcerative colitis

PURPOSE: This study was designed to determine the safety of omitting a temporary defunctioning ileostomy in restorative proctocolectomy for ulcerative colitis. METHOD: One hundred consecutive patients with ulcerative colitis were treated electively by restorative proctocolectomy and pouch-anal anastomosis, without mucosal stripping; 50 had a defunctioning ileostomy added, and 50 underwent a one-stage procedure without ileostomy. RESULTS: There was no operative mortality. The incidence of postoperative complications was similar in the two groups of patients. Lifethreatening complications, however, were more common among patients who did not have a defunctioning ileostomy, of whom 11 developed pelvic sepsis and 7 required reoperation. Among patients with an ileostomy, seven developed pelvic sepsis but none required reoperation (P <0.02). Emergency reoperations were required in 11 patients without an ileostomy but in only 1 patient with an ileostomy (P <0.01). CONCLUSION: One-stage restorative proctocolectomy without a defunctioning ileostomy is associated with increased risk to life. Its routine use cannot be recommended.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Quantitative appraisal of Picolax (sodium picosulfate/magnesium citrate) in the preparation of the large bowel for elective surgery

The authors have investigated the metabolic sequelae Picolax bowel preparation in a group receiving their preparation either 24 hours (n=17) or 48 hours (n=18) before elective colonic resection. No significant changes in any metabolic parameter were found in the 24-hour group. In the 48-hour group, there was a significant decrease in serum sodium ( P <0.005), serum chloride ( P <0.005), pH ( P <0.005), HCO ₃ (P <0.005), and base excess ( P <0.005). Only 16 of 35 cases (46 percent) had an acceptable bowel preparation: 11 of 17 (65 percent) in the 24-hour group and 5 of 18 (28 percent) in the 48-hour group. Marker studies did not correlate with the quality of bowel preparation. The risk of potentially explosive intraluminal gas was increased if the bowel preparation was poor: 12 of 19 patients (63 percent) with a poor bowel preparation compared with 3 of 16 patients (19 percent) of those with an acceptable preparation ( P <0.005). Picolax is a poor mechanical bowel preparation and is associated with unacceptable physiologic disturbance if given two days before surgery.Reprints will not be available.     

Effects of short chain fatty acids on mucosal proliferation and inflammation of ileal pouches in patients with ulcerative colitis and familial polyposis

PURPOSE: To verify whether short chain fatty acids (SCFA) alter the proliferative and endoscopic pattern of the mucosa in ileal pouches of ulcerative colitis (UC) or familial adenomatous polyposis (FAP) patients. METHODS: We studied patients after proctocolectomy carrying a pelvic ileal pouch for FAP or UC (noncanalized pouches in 10 UC and 4 FAP patients and canalized pouches in 6 UC and 5 FAP patients). Patients with noncanalized pouches were treated twice daily for one week with 30 ml of a SCFA solution (60 mM sodium acetate, 30 mM sodium propionate, 40 mM sodium butyrate, and 22 mM sodium chloride, pH 7); patients with canalized pouches were treated with the same solution twice daily for two weeks. Pouch mucosal biopsies were collected before and after SCFA. Mucosal proliferation was assessed by incorporation of [³ H]thymidine in vitro and autoradiography. RESULTS: In UC patients proliferation did not vary in noncanalized pouches but was significantly reduced in canalized pouches after SCFA. In FAP patients SCFA did not alter proliferation. No significant effects of SCFA were observed on daily defecation frequency, endoscopic appearance, or histopathology of the pouches. CONCLUSIONS: SCFA do not control inflammation and clinical functions but reduce cell proliferation in UC patients. On the contrary, FAP patients are refractory to SCFA.Supported by grants of Progetto finalizzato ACRO of CNR, Progetto finalizzato FATMA, of EEC program AIR 2 CT940933, and MURST (40 percent).