Blood and Urinary Changes in Patients with Ileostomies and Ileorectal Anastomoses

Biochemical investigations done on the blood and urine of currently healthy, uncomplicated patients previously treated by either proctocolectomy and ileostomy or colectomy and ileorectal anastomosis for ulcerative colitis were compared with estimations on matched controls. The most striking finding was the reduced urine volume, and to a lesser extent its sodium content, in patients with ileostomies. The urinary pH indicated persistent acidity in postoperative patients but this was also a remarkably constant feature in control subjects. These findings are in agreement with other studies related to the occurrence of urinary calculi after colectomy and ileostomy, and are consistent with the contention that there is a lower incidence of calculi after ileorectal anastomosis.     

Chronic Ulcerative Colitis Before and After Colectomy

There is a proper time to advise removal of the colon and creation of a permanent ileostomy in the course of progressive toxic ulcerative colitis. When a thorough trial of medical therapy, including corticosteroids, has failed to halt progression of the disease, a properly timed colectomy may give the patient a new lease on life and enable him to maintain himself socially and economically.The development of ileostomy (Q-T) clubs has been an important factor in preparing them for and sustaining these young patients through the psychological trauma of an ileostomy. Two patients are described who illustrate the value of properly timed surgery and the contribution that ileostomy clubs can make.     

Visceral and skin granuloma annulare,diabetes, and polyendocrine disease.

A middle aged man suffered with insulin dependent diabetes, autoimmune Addison''s disease, myxoedema, and severe ulcerative colitis, for which he had undergone subtotal colectomy with formation of an ileostomy. Granuloma annulare confined to the anterior abdominal wall was diagnosed in 1981. In 1983 an episode of severe colicky pain and excessive working of the ileostomy occurred associated with severe hyperglycaemia and increased irritation of the granuloma annulare. Laparotomy disclosed adhesions and numerous white nodules over bowel, mesentery, and peritoneum histologically identical with the skin lesions. Two further episodes of subacute small bowel obstruction occurred, and a repeat laparotomy showed widespread intra-abdominal granuloma annulare. Visceral granuloma annulare appears not to have been reported before, and in this patient exacerbation of the skin lesion was associated with poor diabetic control.     

Pouchitis.

Pouchitis is a major long-term complication of the continent ileostomy as well as the ileoanal pouch anastomosis. When diagnosed on the basis of clinical, endoscopic and histologic features, this syndrome has been demonstrated almost exclusively in patients with ulcerative colitis. The clinical course, the endoscopic findings and the histologic abnormalities resemble those of ulcerative colitis. The association with extra-intestinal manifestations further supports the hypothesis that pouchitis represents ulcerative colitis in the small bowel. All ileal reservoirs show bacterial overgrowth, especially of anaerobes. As a response to this altered intraluminal environment chronic inflammation and incomplete colonic metaplasia occur. The efficiency of metronidazole does suggest that bacteriological factors play an important role in the pathogenesis of pouchitis.     

Cancer and Ulcerative Colitis

Ulcerative colitis is a potential precursor of cancer of the colon or rectum. In a series of patients with ulcerative colitis operated on between 1952 and 1968 seven developed carcinoma in the residual rectal stump after total colectomy and ileorectal anastomis. After assessment of the risks of the other available forms of treatment, I believe that ileorectal anastomosis is the best operation in the majority of cases.     

Immunoresponsiveness in Ulcerative Colitis and Crohn's Disease—Effect of Colectomy and Suppression of Disease Activity

We evaluated the effect of medically induced symptomatic disease improvement on in vitro tests of cell-mediated immune responses in 33 patients with Crohn''s disease. When results obtained in 17 patients with ulcerative colitis were compared with those of 10 patients with ulcerative colitis who had undergone a colectomy, no significant correlation was detected between individual clinical and laboratory variables or the Crohn''s disease activity index and in vitro tests of cell-mediated immunity. A different pattern emerged from the longitudinal tests of cell-mediated immunity: when these test results were initially abnormal in patients with Crohn''s disease, clinical improvement as assessed by the Crohn''s disease activity index was associated with normalizing cell-mediated immunity. In contrast, when the test results were initially normal, clinical improvement was not associated with any change in the immune response. Following colectomy in patients with ulcerative colitis, some abnormalities of suppressed immune responses remained, although patients were cured of their disease. Factors other than clinical disease activity may be responsible for the suppressed immunoresponsiveness in some patients with inflammatory bowel disease, and variable changes in cell-mediated immunity occur after both surgical and medical treatment.     

Surgical Treatment of Severe Attacks of Ulcerative Colitis,with Special Reference to the Advantages of Early Operation

The management and outcome of 258 severe attacks of ulcerative colitis from 1952 to 1969 has been reviewed. If remission did not occur during an initial course of intensive medical treatment, including administration of corticosteroids, operation (generally ileostomy with proctocolectomy or subtotal colectomy) was performed. This took place some 12 to 17 days after admission as a rule during the years 1952-63, but usually within five to seven days from 1964 to 1969.Roughly half the attacks underwent spontaneous remission during the two periods, but the medical mortality was 4·8% in the former and 0·7% in the latter, the operative mortality 20·0 and 7·0%, and the overall mortality 11·3 and 4.5% respectively. The lowering of the mortality was particularly striking in severe first attacks and in severe attacks in patients over 60 years of age.Perforation of the colon was found in 21 cases, or nearly 20% of 112 patients coming to operation during attacks, being commoner in the first period (32·5%) than in the second (11·1%). The immediate mortality of all such operations was 11·6%; in cases with perforation it was 28·6%.Acute colonic dilatation was observed in 28 cases. All but one were treated by emergency colectomy, at which the colon was noted to be perforated in 11. The mortality of these operations was 18·5%.Follow-up of the 140 patients who survived without coming to operation during their attacks shows that 52 (37·1%) subsequently underwent surgical treatment either during further attacks or electively.Though all 258 attacks were thought at the time to be due to ordinary ulcerative colitis, subsequent pathological examination of operative specimens derived from 98 patients who came to urgent or subsequent operation during the 1964-9 period revealed that the lesion in the large bowel was Crohn''s disease in 17 instances.     

Social prognosis in patients with ulcerative colitis.

One hundred and twenty-two randomly selected patients with ulcerative colitis (28 of whom had undergone colectomy) were interviewed to obtain data on the quality of their family, emotional, social, and professional lives. They were compared with an age- and sex-matched group of patients with acute conditions from the same area. The two groups were similar in marital status, the frequency of severe family or sexual problems, leisure activities, physical and earning capacity, the incidence of mental disorders before the interview, and intake of alcohol and psychopharmacological drugs. A higher proportion of the patients with colitis had had a higher education and belonged to higher socioeconomic groups than the controls, and this difference had been present at the time of diagnosis. These results show that patients with ulcerative colitis seem to adapt themselves well to their condition and suffer few social or professional disabilities.     

Colorectal cytology in chronic ulcerative colitis

During a period of ten years, 109 colorectal cytology specimens were obtained from 41 patients with chronic ulcerative colitis. There were 28 male and 13 female patients, whose average age was 45 years. All patients were symptomatic and had ulcerative colitis with repeated attacks of profuse diarrhea on the average for 12 years prior to their first cytologic examination. Eight cytology specimens were positive for malignant cells, 35 had atypia, 58 were negative and 8 were unsatisfactory. The malignant cells showed marked anisocytosis, pleomorphism and nuclear hyperchromasia and appeared in loosely cohesive clusters or in single forms in an inflammatory and necrotic background. Subsequent colectomy revealed invasive carcinoma in five patients and carcinoma in situ in two. Smears that were negative or showed atypia contained abundant chronic inflammatory cells. The atypical colonic epithelial cells contained prominent nuclei and formed cohesive clusters. Surgical biopsy and/or segmental resection revealed the presence of polyps, pseudopolyps, polypoid hyperplasia, mucosal atypia and crypt abscesses in patients with atypical and negative cytologic findings. It is concluded that cytologic examination of the colon can play an important role in the examination of patients with ulcerative colitis and allows for the detection of malignant transformation of the colonic mucosa.     

In-vitro Inhibition of Leucocyte Migration in Crohn's Disease by a Sarcoid Spleen Suspension

A Kveim suspension has been shown to inhibit the migration of leucocytes in vitro from 12 out of 18 patients with Crohn''s disease but to have no comparable effect on leucocytes from patients with ulcerative colitis or from a group of patients with other diseases. These findings provide further evidence of cross-reactivity or of a possible aetiological link between Crohn''s disease and sarcoidosis and suggest a further immunological distinction between Crohn''s disease and ulcerative colitis.     

Tumor Necrosis Factor Alpha Blocking Agents as Treatment for Ulcerative Colitis Intolerant or Refractory to Conventional Medical Therapy: A Meta-Analysis

Background

Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results.

Aim

To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy.

Methods

Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects.

Results

Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23).

Conclusion

TNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.     

Managers for Medicine

For many years patients with chronic ulcerative colitis were subjected to operation as a last resort, but now, owing to improved surgical techniques and adequate preoperative preparation of the patient, mortality associated with operation has decreased and better-risk patients are being operated upon electively. The experience of the University of Alberta Hospital during the past 10 years in respect of the surgical management of chronic ulcerative colitis is reviewed, on the basis of 105 patients, 36 of whom underwent operation. The indications for surgery include obstruction, suspected carcinoma, hemorrhage, perforation, acute fulminating disease with toxic megacolon, and intractability. A variety of surgical procedures were used during this period, reflecting changing views in surgical management. Surgical complications include wound infections, bowel obstruction with ileostomy malfunction, skin excoriation, and electrolyte imbalance. In this series three of the 36 died, a mortality rate of 8%. One death was from liver failure and two were from peritonitis.     

Toxic Megacolon in Ulcerative Colitis

Toxic dilatation of the colon is now a well-recognized complication of ulcerative colitis. Our experience with four cases is presented. The clinical picture was characterized by severe ulcerative colitis with increasing abdominal distension, high swinging temperatures, obvious toxicity, and a moderate to high leukocytosis with a pronounced shift to younger forms. Accurate history and physical examination, plain radiographs of the abdomen, sigmoidoscopy and, most important of all, awareness of the condition facilitate diagnosis in most cases. The main indications for surgical intervention are progressive abdominal distension and impending or actual perforation. Ileostomy and subtotal or total colectomy are the surgical procedures of choice. We feel that steroids play little part in the early management, but are of value in the early postoperative period. The three patients in our series treated surgically survived. One treated by medical means alone died of peritonitis.     

Cytomegalovirus infection masquerading as an ulcerative colitis flare-up: case report and review of the literature.

We report the case of a patient with a case of cytomegalovirus (CMV) colitis, which presented as a flare-up of her ulcerative colitis. Standard treatment for the flare-up, which included intravenous corticosteroids, bowel rest, topical salicylates and ultimately colectomy were not effective. The patient did not improve until therapy with intravenous ganciclovir was initiated. There have been 26 previous reports of CMV colitis complicating inflammatory bowel disease (IBD). The diagnosis is not frequently entertained and, if not made, leads to a high rate of colectomy (67 percent) and mortality (33 percent). Appropriate antiviral therapy appears to eliminate these complications, thus a high index of suspicion for CMV superinfection in cases of IBD refractory to traditional therapy is warranted.     

Proctocolectomy without ileostomy for ulcerative colitis.

An operation has been developed that permits total removal of all disease-prone mucosa in ulcerative colitis but avoids the need for a permanent ileostomy. The colon and upper half of the rectum are excised and the remaining inflamed mucosa is stripped from the rectal stump down to the dentate line of the anal canal. A pouch is fashioned from a triplicated loop of terminal ileum. This is drawn down through the denuded rectum and an anastomosis created, via the per-anal approach, between the ileum just distal to the pouch and the mid-anal canal. A temporary ileostomy is made. Out of eight patients so treated, five were available for assessment, and four of them were highly satisfied with the result in improved health and function. The remaining three were awaiting closure of their ileostomies.     

Inflammatory bowel disease and serum beta-N-acetylhexosaminidase

Serum beta-N-acetylhexosaminidase levels in 49 patients with inflammatory bowel disease (IBD; 23 patients with ulcerative colitis, 10 with Crohn's disease, and 16 with ileostomy after total proctocolectomy) as well as in healthy normal controls were determined. They were found to be significantly elevated in 91% of all patients, disregarding the state of activity of the disease. It seems most likely that activated macrophages are the source of this lysosomal hydrolase in the serum of IBD patients since other theoretical possibilities, like damaged hepatocytes or elevated serum bile acid levels, are not relevant for these patients.     

Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis.

OBJECTIVE--To investigate the mode of inheritance of ulcerative colitis and Crohn''s disease by complex segregation analysis. DESIGN--Cross sectional population based survey of familial occurrence of chronic inflammatory bowel disease. SETTING--Population of the Copenhagen county in 1987. SUBJECTS--662 patients in whom inflammatory bowel disease had been diagnosed before 1979, of whom 637 (96%) provided adequate information. Of 504 patients with ulcerative colitis, 54 had 77 relatives with ulcerative colitis and of 133 patients with Crohn''s disease, five had seven relatives with Crohn''s disease. MAIN OUTCOME MEASURES--Patterns of segregation of either disease as assessed by complex segregation analysis performed with the computer program POINTER. RESULTS--The analysis suggested that a major dominant gene with a penetrance of 0.20-0.26 is present in 9-13% of adult patients with ulcerative colitis. The analysis did not allow for other components in the familial aggregation. For Crohn''s disease the best fitting model included a major recessive gene with complete penetrance, for which 7% of the patients are homozygous. However, this model was not significantly different from a multifactorial model. CONCLUSIONS--The segregation pattern indicates that a major dominant gene has a role in ulcerative colitis, and suggests that a major recessive gene has a role in Crohn''s disease.     

Mortality in patients with and without colectomy admitted to hospital for ulcerative colitis and Crohn's disease: record linkage studies

Objective To compare mortality outcomes in the three years after elective colectomy, no colectomy, and emergency colectomy among people admitted to hospital for inflammatory bowel disease, to inform whether the threshold for elective colectomy in clinical practice is appropriate.Design Record linkage studies.Setting Oxford region (1968-99) and England (1998-2003).Participants 23 464 people with hospital stay for more than three days for inflammatory bowel disease, including 5480 who had colectomy.Main outcome measures Case fatality, relative survival, and standardised mortality ratios.Results In the Oxford region, three year mortality was lower after elective colectomy than after either no colectomy or emergency colectomy, although this was not significant. For England, mortality three years after elective colectomy for ulcerative colitis (3.7%) and Crohn''s disease (3.3%) was significantly lower than that after either admission without colectomy (13.6% and 10.1%; both P<0.001) or emergency colectomy (13.2% and 9.9%; P<0.001 for colitis and P<0.01 for Crohn''s disease). Three or more months after elective colectomy, mortality was similar to that in the general population. Adjustment for comorbidity did not affect the findings.Conclusions In England, the clinical threshold for elective colectomy in people with inflammatory bowel disease may be too high. Further research is now required to establish the threshold criteria and optimal timing of elective surgery for people with poorly controlled inflammatory bowel disease.     

5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis

Background

Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis.

Methods

Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed.

Results

Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89].

Conclusion

Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.     

Controlled trial of azathioprine in chronic ulcerative colitis.

A double-blind controlled trial of azathioprine in a dose of 2-2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis. Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed. Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo; the reduction was greater among those who took azathioprine (p less than 0.001). Activity of the disease apparently improved in both treatment groups but a significant (p less than 0.001) trend was observed only in those patients treated with azathioprine. No serious side effects from azathioprine occurred during the trial but seven of 24 patients had to stop the drug because of nausea. Azathioprine may have a role in the treatment of a few patients wih troublesome chronic colitis for whom conventional drug treatment is ineffectual, or for whom continuous systemic corticosteroid treatment is needed to control symptoms, and for whom surgical treatment is inappropriate.