Gynaecological state of health of 2 654 women in Nurmes 1970-71. A clinical outpatient study

Eighty-one patients who had had colectomy and ileorectal anastomosis for ulcerative colitis or Crohn's disease of the colon from 1 to 13 years previously were interviewed and examined by a surgeon with whom they had had no previous contact. Sixty-four patients (79 per cent) had a satisfactory result. In 12 patients the operation had failed and an ileostomy had been established, and in a further 5 patients the result was considered unsatisfactory. Despite a high incidence of frequent loose stools and minor anorectal complications, most of the patients were satisfied with the result and would not contemplate the alternative of an ileostomy. No patient had developed rectal cancer. Provided that the rectum is examined regularly for pre-malignant or malignant change, colectomy and ileorectal anastomosis offer a satisfactory alternative to proctocolectomy and ileostomy for many patients with ulcerative colitis or Crohn's disease.     

A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis

OBJECTIVES: The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis. METHODS: Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit. RESULTS: At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated. CONCLUSIONS: The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone.     

Assessment of dysplasia, mucosal mucins, p53 protein expression, and DNA content in ulcerative colitis patients with colectomy and ileorectal anastomosis

BACKGROUND: Patients with ileorectal anastomosis after colectomy for ulcerative colitis remain at risk of developing rectal malignancy. Detection of mucosal dysplasia has been used for regular screening but is difficult in inflammatory mucosa, prompting the search for complementary markers. METHODS: This prospective study aimed to assess the prevalence of dysplasia, the predominance of sialomucin, DNA aneuploidy, and p53 overexpression as possible predictors of colorectal tumourigenesis, in the rectal mucosa of an unselected group of 27 patients with ileorectal anastomosis performed for ulcerative colitis. Patients had neither neoplastic nor dysplastic lesions on the colectomy specimen and the retained rectum at the time of surgery. One biopsy specimen of each lateral rectal wall was studied, using routine histology, mucin histochemistry, DNA flow cytometry, and the streptavidin-biotin complex method with D07 monoclonal antibodies directed towards the p53 protein. RESULTS: Seventeen, seven, and three patients showed inflammatory lesions of inactive, moderate, and severe active colitis, respectively. Dysplasia, sialomucin predominance, DNA aneuploidy, and p53 overexpression were not detected. CONCLUSIONS: The risk of malignant transformation of the rectal mucosa after ileorectal anastomosis seemed to be low in this ulcerative colitis group without high-grade dysplasia or carcinoma in the previous colectomy specimen, carefully followed up endoscopically and histologically. It remains to be evaluated which of the methods studied above will optimize the histopathologic surveillance of the rectal mucosa of ulcerative colitis patients with ileorectal anastomosis.     

Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel disease

BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors in inflammatory bowel disease, particularly Crohn's disease. The aim of our study was to assess rectal blood flow in patients with active inflammatory bowel disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood flow was performed by laser Doppler flowmetry in 45 subjects divided into three groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS: Rectal perfusion was found to be significantly impaired in patients with ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our results confirm the role of local ischemia in ulcerative colitis, but do not support the theory that vascular factors play a key role in the pathogenesis of Crohn's disease.     

Assessment and management of ulcerative colitis in children

The incidence of ulcerative colitis in school-age children in most parts of Europe has been steady at 1.5-2.0 per 100,000 children per year for the last 20-30 years. In comparison to adults, abdominal pain is a relatively frequent presenting symptom in children in addition to rectal bleeding, bloody diarrhoea or diarrhoea. Distribution of disease in children is generally more extensive (ratio rectal:left sided:extensive 25:30:45). There are remarkably few clinical trials of therapy in children and reasons for this are discussed. Subjective indices of disease severity and activity are unreliable in children. Objective measures such as endoscopy are of value to define the extent of ulceration and histopathological features; a test of gut protein loss using whole gut lavage gives an objective index of disease activity. Principles of medical management in children are generally the same as in adults with the additional need for scrupulous attention to nutrition and growth, and psychological factors. Reassuring results of a review of the health status of young adults who had developed ulcerative colitis in childhood are presented. Twenty-four of 27 considered themselves fully fit although nine of the patients had a permanent ileostomy.     

Transformations of ileo-rectal anastomosis into ileo-anal anastomosis in hemorrhagic rectocolitis. Indications and results

In order to precise the indications and results of this procedure, we assessed 11 cases of transformation of ileorectal anastomosis (IRA) to ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). These 5 men and 6 women had undergone IRA at a mean age of 31 years, 33 months after the diagnosis of UC (range 3-120). Four of these IRA, excluded by an ileostomy, had never been in function: the cause was severe persistent proctitis in 2 cases and anastomotic leakage and peritonitis in 2 cases. The other 7 IRA had been in function during a mean period of 25 months (range 6-45) and were reoperated because of anal sepsis (1 case), low rectal stenosis (1 case), disabling proctitis (4 cases) and rectal dysplasia (1 case). No patient had specific pathologic signs of Crohn's disease. The 11 IPAA were complicated by pelvic sepsis in 3 cases; surgical drainage succeeded in 1 case, but the 2 others needed pouch excision and terminal ileostomy. The diagnosis of Crohn's disease was eventually made in these 2 patients. The 9 patients with functioning IPAA, at a mean follow-up of 40 months (range 12-60), had 5.2 stools per 24 h (range 2-12), 5 patients had no nocturnal stooling, and 6 had a perfect continence. One patient had disabling chronic pouchitis. In conclusion, proctectomy with IPAA is always feasible when a previous IRA for UC had failed or offers poor results, but should be rejected in case of anal involvement, as that may suggest Crohn's disease. This procedure is followed by similar functional results than after primary IPAA.     

Per anal suturing of a bleeding ulcer to achieve successful hemostasis of massive hemorrhage associated with ulcerative colitis: report of two cases

We report herein the cases of two patients with ulcerative colitis complicated by massive hemorrhage who were successfully treated by per anal suturing of a bleeding ulcer. A 40-year-old woman and a 22-year-old man had suffered from extensive colitis for 8 and 2 years, respectively, and both followed a similar clinical course. They were admitted under emergency conditions and, despite treatment with intravenous high-dose prednisolone and thereafter with intraarterial injections of prednisolone, suffered several attacks of massive hemorrhage with hypovolemic shock. Emergency subtotal colectomy with ileostomy and rectal mucous fistula were performed, but recurrent massive hemorrhage occurred during the early postoperative period. Bleeding from a discrete ulcer in the rectum was subsequently located, and both patients underwent per anal suturing of the ulcer. No recurrent bleeding occurred thereafter, and an ileoanal anastomosis was performed several months later. Massive hemorrhage is a rare complication of ulcerative colitis which is most often resolved by subtotal colectomy without proctectomy. Although bleeding associated with ulcerative colitis usually occurs diffusely, these case reports serve to demonstrate that massive bleeding can also result from a discrete ulcer. We advocate that this condition be treated by an endoscopic or local hemostatic procedure.     

Conservative management of small adenomata in ulcerative colitis

OBJECTIVE AND METHODS: Patients with chronic ulcerative colitis may develop colitis-related dysplasia and/or sporadic adenomata. Differentiating between these two processes is important because they may dictate different therapeutic approaches. Although distinguishing features of sporadic adenomata versus colitis-related dysplasia have been suggested previously on an a priori basis, they have never been verified by follow-up analysis. We have identified six chronic ulcerative colitis patients whose discrete adenomata were managed conservatively, with subsequent continuation in their surveillance programs. RESULTS: Mean patient age was 69 yr with a mean 21.3 yr of ulcerative colitis. Surveillance endoscopy of 63 patient-yr duration yielded 24 adenomata. A mean follow-up after the initial adenoma diagnosis was 7.2 yr with no carcinoma identified (including the examination of one prophylactic colectomy specimen). One patient, with a 34-yr history of ulcerative colitis and a single sporadic adenoma subsequently developed dysplasia of flat mucosa 14 months later. CONCLUSIONS: Our findings concur with previous reports and indicate that small, discrete adenomata with morphology identical to those seen in the general population occur in patients with ulcerative colitis. Such lesions in patients older than 45 yr, with tubular or tubulovillous architecture and low-grade dysplasia, are effectively treated by polypectomy only and are not necessarily an indication for colectomy. However, sporadic adenomata and colitis-related dysplasia can develop metachronously. It is suggested that subsequent to a diagnosis of sporadic adenoma in a patient with chronic ulcerative colitis, surveillance should increase to colonoscopic examination every 6 to 12 months.     

Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis

OBJECTIVES: In adults, the premalignant nature of ulcerative colitis (UC) has long been accepted. Currently there is increasing concern that Crohn's disease (CD) may be equally premalignant. As a consequence, most adults with long-standing UC and many with chronic CD are enrolled in ongoing endoscopic cancer surveillance programs. In contrast, the risk of colonic cancer in adolescents and young adults with either form of colitis is less well recognized, and the need for dysplasia and cancer screening in this population has not been systematically evaluated. We therefore report the prospective results of colonoscopic cancer screening in such a young population. METHODS: Thirty-five adolescents and young adults with long-standing colitis (18 UC, 17 CD; 21 +/- 3 yr old, 11 +/- 3 yr colitis duration) underwent colonoscopic cancer screening. All had multiple biopsies for flow cytometry and light microscopy. RESULTS: Seven subjects had aneuploidy (3/18 UC, 4/17 CD). Of these seven, only two had dysplasia [one high grade (UC), one low grade (CD)]. One additional subject had indefinite dysplasia with normal flow cytometry. The remaining 27 subjects had both normal flow cytometry and light microscopy. Five of the seven aneuploid subjects underwent surgery within 1 yr of screening. Four, including both subjects with dysplasia, had no evidence of colon cancer at surgery. However, a 24-yr-old female with a 14-yr history of UC and no evidence of dysplasia or cancer at screening had a Dukes C adenocarcinoma. CONCLUSIONS: Adolescents and young adults with childhood onset UC or CD are at risk for aneuploidy, dysplasia, and colon cancer. Aneuploidy can be evident 10 yr after the onset of colitis and in patients as young as 16 yr of age. Therefore, the risk for colon cancer in patients with childhood onset colitis must be based on the duration of the illness, not on their chronological age. Incorporation of flow cytometry into an endoscopic screening protocol appears to enhance the ability to identify individuals at highest risk for colon cancer.     

Nephrotic syndrome in ulcerative colitis

Complicating disorders in various organs outside the intestinal tract are common in ulcerative colitis. This report deals with the occurrence of nephrotic syndrome in two patients with long-standing ulcerative colitis. In the patient studied in most detail, 2 episodes have taken place, the first developing into uremia. After colectomy had been performed, rapid improvement of renal function took place. The morphological changes in kidney biopsies were compatible with the presence of focal glomerular sclerosis. Activity in the complement system and a favorable response to steroid treatment indicate that humoral immune mechanisms are of pathogenetic importance with regard to the renal disease in these two patients. To our knowledge nephrotic syndrome has not previously been described as a complication to ulcerative colitis.     

Growth suppression mediated by transfection of wild-type hMLH1 in human cancer cells expressing endogenous truncated hMLH1 protein

Eosinophils contribute to the inflammatory process in a variety of chronic inflammatory bowel diseases. Ketotifen is beneficial in experimental models of colitis and in patients with eosinophilic gastroenteritis. Therefore, we investigated the efficacy of ketotifen therapy for the treatment of active ulcerative colitis. Children with newly or previously diagnosed ulcerative colitis with mild-moderate disease activity were treated with ketotifen at a dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician disease severity index and by endoscopic and histologic examinations. Ten patients were enrolled. Symptoms improved in four patients and resolved completely in one patient. There was endoscopic improvement in three patients and histologic improvement in one. Increased eosinophils on rectal biopsy at entry were present in two of the responders. Five patients withdrew due to a lack of symptomatic improvement. No adverse events were identified. Low-dose ketotifen offers a limited therapeutic advantage in active ulcerative colitis that may be enhanced in the subgroup of patients with a high eosinophil count in the colonic mucosa. Further study of therapeutic efficacy with increased dosages of the mast cell stabilizer for acute and maintenance therapy is warranted.     

Elevated serum lipoprotein (a) levels associated with ulcerative colitis in a young Japanese patient

Thromboembolism has been shown to play a role in the pathogenesis of inflammatory bowel disease (IBD). A possibility exists that lipoprotein (a) [Lp(a)], a newly-discovered prothrombotic factor, also participates in the development of at least some cases of IBD. Marked elevation of serum Lp(a) levels was observed in a young patient with ulcerative colitis. A biopsy specimen of the rectal mucosa showed findings compatible with ulcerative colitis, as well as small vessel thrombus occurring within the muscularis mucosa in the rectum. Serum Lp(a) levels were markedly elevated on admission (71 mg/dl), with a gradual decrease to 46 mg/dl on discharge. Moreover, serum Lp(a) levels decreased in parallel with clinical improvement. In the quiescent clinical stage, no small vessel thrombus was observed in the mucosa on follow-up colonoscopy. The association between IBD and hyper-Lp(a)-emia would be presumable but it has been, to our knowledge, previously unreported. The case reported here would be the first young patient, suggesting the presence of hyper-Lp(a)-emia and small vessel thrombus formation occurring in association with the development of ulcerative colitis.     

Ulcerative colitis associated with Weber-Christian panniculitis and musculitis: a case report

A case of 22-year-old man suffering from ulcerative colitis, in whom Weber-Christian panniculitis and musculitis occurred simultaneously, is reported. He had suffered from ulcerative colitis for 7 years and he again had bloody stools 1 month before being admitted. Two weeks before admission, large (2-4 cm) subcutaneous tumors appeared. Weber-Christian panniculitis, musculitis, and active stage ulcerative colitis were diagnosed. All the symptoms went into remission after steroid therapy. The possibility of the existence of a common antigen in enterobacterial wall, colonic epithelium, and adipose tissue was suggested.     

The possibility of resuscitating livers after warm ischemic injury

The onset and course of ulcerative colitis diagnosed in 38 children at or before 10 years of age were reviewed. The mean age at onset was 5.9 years. A family history of inflammatory bowel disease was present in 24% of patients, and 13% had a history of cow milk allergy in infancy. Initially, by radiologic or colonoscopic studies, 71% had total colonic disease, 13% had left-sided colitis, and 6% had proctitis; extensive examination was not performed in 4 patients. Four patients (11%) presented with severe colitis, 14 (37%) with moderate colitis, and 20 (53%) with mild colitis. The most frequent symptoms were abdominal pain (94%), diarrhea (84%), and rectal bleeding (84%). Between 2 and 10 years after diagnosis, 89% of children had total colonic disease and 11% had left-sided disease. All four patients with severe disease at onset responded to medical therapy with one having a colectomy 15 years later with pathology consistent with Crohn's disease. Of those with moderate disease, half had infrequent moderate recurrences and half had intermittent mild disease. One patient had colectomy at 21 years for intractable disease. Of the 20 with mild disease, 16 continued to have intermittent mild recurrences, 1 had chronic mild disease, 2 had moderate recurrent disease, and 1 has remained asymptomatic for 5 years. Psychiatric disturbances requiring therapy were identified in 5 (13%) children. Results are encouraging: after the first 2 years of illness, two thirds of the children have had subsequent mild colitis with infrequent relapses and three quarters consider their life to be of good quality.     

Guidelines for the treatment of ulcerative colitis in remission

The role is reviewed of sulphasalazine, 5-aminosalicylic acid (5-ASA), immunosuppressive agents and corticosteroids in the maintenance treatment of ulcerative colitis in remission. Sulphasalazine and oral 5-ASA are the drugs of first choice in preventing relapses for patients suffering from intermittent chronic ulcerative colitis. Rectally administered 5-ASA may be a valid alternative for treating patients with proctitis and left-sided ulcerative colitis. The optimal dosage of oral 5-ASA in the maintenance therapy of ulcerative colitis in remission is not clear. However, there is evidence that a higher dose of 5-ASA is more effective than low dosage in preventing relapses in patients in remission. For patients with chronically active or steroid-dependent ulcerative colitis who have achieved remission while taking immunosuppressants, continuing azathioprine or 6-mercaptopurine is indicated. Existing data cast doubts as to whether or not continuous maintenance is still necessary in patients suffering from intermittent chronic ulcerative colitis with prolonged endoscopic, clinical and histological remission.     

Ulcerative colitis and total alopecia in a mother and her son

Extraintestinal autoimmune disorders are associated with ulcerative colitis in selected patients and lend support to the theory of immune-mediated injury in inflammatory bowel disease. Rarely, alopecia areata has been associated with ulcerative colitis, and familial aggregation and an HLA association have been reported for both disorders. The occurrence of both alopecia and ulcerative colitis in a mother and son are reported with a detailed investigation of antineutrophil cytoplasmic antibodies and HLA alleles in this family. Treatment with the immunosuppressive agent cyclosporine proved beneficial in the child leading to remission of the ulcerative colitis and nascent growth of scalp and body hair.     

Treatment of ulcerative colitis with an engineered human anti-TNFalpha antibody CDP571

BACKGROUND: Tumour Necrosis Factor-alpha (TNFalpha) is a pro-inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFalpha antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis. METHODS: Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGgamma4 antibody CDP571 and monitored for 8 weeks. RESULTS: Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left-sided disease, four extensive disease and six patients were steroid-unresponsive. The treatment was well tolerated and plasma half-life of CDP571 was approximately 7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell-Tuck score by 1 week post-infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin-6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance. CONCLUSION: A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

Proctocolectomy with ileal W pouch anal anastomosis for ulcerative colitis

Restorative proctocolectomy with ileal pouch anal anastomosis, which is a relatively new procedure, has become a standard procedure for ulcerative colitis (UC) requiring surgical management. The main impact of this procedure is to cure patients of disease and to avoid permanent ileostomy, preserving better defecatory function and acceptable QOL. Some key aspects of our surgical procedure are as follows: 1) two or three separate staged operation, 2) W-shaped reservoir, 3) distal rectal mucosectomy and handsewn ileo-anal anastomosis, 4) short muscular cuff, and 5) temporary diverting ileostomy. Staged operation and diverting ileostomy are helpful to decrease risk of pelvic infection. Total removal of the rectal mucosa is necessary to cure the disease, and shorter muscular cuff decreases operating time and bleeding and thus the risk of pelvic sepsis. The W-shaped reservoir described by Nicholls brings both spontaneous defecation and improved function. We have adopted ileal W-pouch among several types of reservoir to 58 patients with UC since 1984, and found that a large and wide reservoir might allow better defecatory function. There were no cases of serious complications and no needs to remove the reservoir. Mean daily stool frequency was gradually decreased with time, and 4.9 stools per 24 hours at present day, and clinical score of neorectal function also gradually improved according to reduction of stool frequency. Seventy three percent of patients felt their defecatory function satisfactory and 89% of the patients recovered acceptable QOL no less than that obtained during the medically treated period.     

Failure of colonoscopic surveillance in ulcerative colitis

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.