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R Löfberg

Publications and source records attributed to R Löfberg.

70 records · Page 4Linked to original sources
PubMed1992

DNA aneuploidy in ulcerative colitis: reproducibility, topographic distribution, and relation to dysplasia.

Fifty-nine patients with longstanding, total ulcerative colitis were followed up in a prospective colonoscopic surveillance program. Biopsy specimens were sampled from predetermined locations of the colon and rectum at regular intervals. All specimens were assessed for histological dysplasia and, by flow cytometry, for detection of DNA aneuploidy during 8 years of follow-up. Special emphasis was made to correlate the findings of DNA aneuploidy with findings of dysplasia at colonoscopy or, in case proctocolectomy was performed, in the surgical specimen. Fifteen patients (25.4%) had DNA aneuploidy detected at least once during the follow-up. Eight of 10 patients with repeated findings had consistent ploidy level of the aneuploid peaks from one examination to another. Ten patients had multiple peaks. DNA aneuploidy tended to become more widespread in the bowel during the follow-up but persisted in the same part(s) of the colon and rectum. DNA aneuploidy occurred before development of definite dysplasia in 6 patients, simultaneously with development of dysplasia in 6 patients, and after the development of dysplasia in 1 patient only. In 2 patients, single aneuploid peaks were detected once but could not be found again at subsequent examinations. Dysplasia correlated closely topographically to DNA aneuploidy, but the latter finding was more common without concomitant dysplasia. Only in 1 patient, and at one examination, definite dysplasia was recorded without findings of DNA aneuploidy. Detection of DNA aneuploidy in patients with ulcerative colitis is persistent and reproducible and closely correlated to dysplasia. Widespread changes indicate that the entire colorectal mucosa is at increased risk of malignant transformation. Changes in nuclear DNA content appear to be an earlier phenomenon than dysplasia in the malignant transformation of the colorectal mucosa in ulcerative colitis, and the use of flow cytometry in surveillance programs may be of value for selection of patients at high risk of developing colorectal carcinoma.

Aneuploidy↗
PubMed1991

Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a defined patient group.

In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955-1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n = 22, one postoperative death) or owing to dysplasia (n = 3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low.

Anastomosis, Surgical↗
PubMed1991

Dysplasia and DNA aneuploidy in a pelvic pouch. Report of a case.

A patient with an 18-year history of ulcerative colitis was operated on with colectomy, mucosal proctectomy, ileoanal anastomosis, and an S-type pelvic pouch due to intractable chronic continuous disease. The patient was followed by endoscopic controls and biopsy sampling from the pouch at regular intervals. A gradual development of severe atrophy in the ileal mucosa was followed by the development of low grade dysplasia. At the most recent endoscopic control, 4 years after the construction of the pouch, biopsies were sampled also for flow cytometric DNA analyses. DNA aneuploidy was detected in a biopsy from the center of the pouch, and a biopsy taken immediately adjacent showed low grade dysplasia. These findings underline the importance of endoscopic follow-up after construction of a pelvic pouch and focus attention to the potential of malignant transformation of the mucosa.

Adult↗
PubMed1991

Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study.

Twenty four patients with longstanding colonic Crohn's disease were examined prospectively with colonoscopy and multiple biopsy sampling in order to detect histological dysplasia or abnormal aneuploid DNA content, or both. Biopsy specimens were taken from 10 predetermined locations in the colon and rectum. No patient had definite dysplasia but three displayed DNA aneuploidy (12.5%), and one of these subsequently developed a carcinoma (Dukes' C at operation) in the ascending colon. No concomitant dysplasia was detected but the carcinoma as well as other parts of the mucosa were DNA aneuploid. It is concluded that dysplasia is rare in patients with Crohn's colitis, but findings of DNA aneuploidy warrant vigilance in follow up as this may indicate impending carcinoma. Further prospective studies are needed before the predictive value of DNA aneuploidy can be determined and before general recommendations of colonoscopic surveillance, as in longstanding ulcerative colitis, can be made.

Adult↗
PubMed1990

Long-term results of ileorectal anastomosis in ulcerative colitis in Stockholm County.

The long-term results of ileorectal anastomosis in patients with ulcerative colitis in Stockholm County over a 30-year period, 1955 to 1984, were investigated. During this time, 486 patients underwent colectomy and ileorectal anastomosis was performed in 60 of those patients (12 percent). A retrospective histologic examination of the slides of the operative specimens in the latter group revealed that nine patients had Crohn's disease. Of the 51 remaining patients with ulcerative colitis, the colectomy and ileorectal anastomosis was performed as an elective procedure in 44 cases (86 percent) and as a one-stage procedure in 48 patients (94 percent). Complications occurred in 7 of 43 patients (16 percent) undergoing an elective, one-stage procedure. There were two postoperative deaths (4 percent). There were 22 patients (43 percent) who had their ileorectal anastomosis in function at the time of follow-up, with a mean time of observation of 13 years. The cumulative probability of having the ileorectal anastomosis in function at 10 years was 51 percent. The causes of total excision were recurrent inflammation in the retained rectum (N = 23), dysplasia (N = 3), and postoperative complications (N = 3). No rectal carcinoma occurred. Patients with preoperative mild rectal disease had a better outcome (ileorectal anastomosis in function at time of follow-up) compared with patients with moderate rectal disease (P less than 0.001). The functional outcome of ileorectal anastomosis was, if anything, better than what is stated in the literature following pelvic pouch procedure.

Adolescent↗
PubMed1990

Colonoscopic surveillance in long-standing total ulcerative colitis--a 15-year follow-up study.

In a 15-year surveillance program composed of 72 patients with total ulcerative colitis, 12 patients developed definite dysplasia. At endoscopy, low-grade dysplasia was detected in seven patients, high-grade in four, and a carcinoma (Dukes' stage A at operation) in one. One of the patients with high-grade dysplasia and macroscopical lesions at colonoscopy had a carcinoma (Dukes' A) detected at operation. A sequential development of dysplasia was found in seven patients. The cumulative risk of developing at least low-grade dysplasia was 14% after 25 years of disease duration. Using flow cytometric analyses, abnormal, aneuploid DNA content was detected in biopsies of 12 of 59 patients (20.3%); this correlated significantly with low-grade and high-grade dysplasia. Aneuploidy preceded dysplasia in two patients and was also detected in two dysplasia-free patients. The long-term use of colonoscopic surveillance in ulcerative colitis is a reliable way to select patients, in whom dysplasia is developing, for prophylactic surgery. Additionally, flow cytometric DNA analyses may help in the selection. The risk of missing a carcinoma until it becomes incurable appears to be low.

Adolescent↗
PubMed1989

Unsatisfactory effect of cyclosporin A treatment in Crohn's disease: a report of five cases.

Five patients with chronic continuous Crohn's colitis were treated with peroral Cyclosporin A (CyA) for 3 months in an open, uncontrolled pilot trial. The CyA dose was 10 mg kg-1 d-1 the first month of study, and thereafter 5 mg kg-1 d-1. Three of the patients initially showed some response to the treatment with decreases in the Crohn's disease activity index, but subsequently deteriorated. In one patient the condition was unchanged and another clearly worsened. Increases in serum creatinine levels were noted in three patients, and all of these also had decreased 51Cr-EDTA clearance indicating impaired renal function. Hypertrichosis and hyperaesthesia were also noted as side-effects. This study does not support the use of CyA in the short-term treatment of Crohn's disease in the colon.

Adult↗
PubMed1989

Comparative DNA analyses in longstanding ulcerative colitis with aneuploidy.

In seven patients with longstanding ulcerative colitis, multiple mucosal biopsies taken at colonoscopy were assessed for DNA content and histological dysplasia. DNA analyses were performed using flow cytometric analyses in biopsies and microspectrophotometry in imprint slides prepared from the biopsies. Abnormal aneuploid DNA content was detected in five of the patients in eight separate locations in the colon. There was good conformity between the two methods in the detection of aneuploidy. Both methods of DNA analysis are considered to be applicable in mucosal biopsies from patients with ulcerative colitis. In two patients with significant low grade dysplasia in association with macroscopical lesions (DALMs), there was a relationship with aneuploid DNA pattern found by flow cytometric or microspectrophotometric analyses. Indefinite changes, probably dysplastic were found in three other patients and two of those also displayed aneuploidy, although only once in the same biopsy location. In five locations aneuploidy was detected without concomitant dysplasia. DNA-aneuploidy seems therefore to appear earlier than dysplasia and may be an early marker of malignant transformation of the mucosa in ulcerative colitis. Prospective trials are needed before the clinical significance of early findings of aneuploidy can be determined.

Aneuploidy↗
PubMed1989

Studies in longstanding ulcerative colitis with special reference to malignant transformation of the colorectal mucosa.

The risk of colorectal carcinoma was estimated retrospectively in a cohort of patients with ulcerative colitis from three defined geographical areas (West Midlands and Oxford regions, England and Stockholm County, Sweden). The cohort consisted of 824 primary referral patients with a diagnosis of ulcerative colitis established within five years from onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset and they were followed for a minimum of 17 years and a maximum of 38 years. There was an eight-fold risk of developing colorectal cancer in the series as a whole, relative to that of the general population. In extensive colitis the risk was nineteen-fold. The cumulative risk of developing cancer in extensive colitis was 12% after 25 years of disease duration. No significant effects of the cancer risk for age at onset, sex or referral centre were detected. Abnormal, aneuploid DNA-content of cell nuclei in colorectal mucosal biopsies was found in five out of 53 patients with longstanding, total ulcerative colitis in a prospective study using flow cytometric DNA-analyses. Findings of DNA-aneuploidy were found at repeated examinations in four of these patients and there was a correlation with precancerous, mucosal changes (dysplasia) found at histological examination. In one patient DNA-aneuploidy preceded the finding of a carcinoma (Dukes' A) in the colon. Microspectrophotometry of imprint preparations from mucosal biopsies was compared to flow cytometry for detection of nuclear DNA-aneuploidy in seven patients with ulcerative colitis in a prospective study. DNA-aneuploidy was detected in five patients in eight separate locations of the colon and rectum. There was a good conformity between the two methods in the detection of DNA-aneuploidy, which was detected in non-dysplastic mucosa as well as in association with dysplasia. In a fifteen year follow-up surveillance program, comprising 72 patients with total ulcerative colitis, colonoscopy was performed at fixed intervals and biopsies sampled from ten predetermined locations in the colon and rectum. Definite dysplasia developed in 12 patients, two of which had carcinoma (Dukes' A). Nine patients were selected for prophylactic colectomy due to findings of dysplasia. A sequential development of dysplasia was found in seven patients. The cumulative risk of developing at least low grade dysplasia was 14% after 25 years of disease duration. Using flow cytometry, DNA-aneuploidy was detected in 12 out of 59 patients, significantly correlating with low and high grade dysplasia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Flow cytometric DNA analysis in longstanding ulcerative colitis: a method of prediction of dysplasia and carcinoma development?

During a prospective study lasting 3.5 years flow cytometric DNA analysis was evaluated as a possible predictor of dysplastic and malignant lesions in longstanding ulcerative colitis. Fifty three patients with total ulcerative colitis (mean disease duration of 22 years) were regularly colonoscoped. Biopsies of colonic mucosa were analysed by flow cytometric technique and were also assessed histologically. Findings of abnormal DNA pattern (aneuploidy) were compared with findings of dysplasia. Five patients (9%) had aneuploidy, four of those at repeated colonoscopies. Four of those patients also had various degrees of dysplasia. In one patient aneuploidy preceded the finding of dysplasia and in another aneuploidy preceded a well differentiated adenocarcinoma, grade Dukes' A subsequently found at surgery. Four additional patients had dysplasia, all in connection with macroscopic lesions, but were diploid. It is suggested that flow cytometric DNA analysis in long standing ulcerative colitis may be helpful in addition to histopathology in the detection of potential malignancy in ulcerative colitis.

Adult↗
PubMed1987

A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis.

Sixty-four patients with active distal ulcerative colitis participated in a multicentre, randomized, investigator-blind trial to compare the effect of budesonide enema, 2 mg/100 ml, with prednisolone disodium phosphate enema, 31.25 mg/100 ml. Budesonide is a new potent corticosteroid with a rapid first-pass elimination. The patients were treated for 4 weeks, and the efficacy of the drugs were evaluated by sigmoidoscopy, histology, and subjective symptoms after 2 and 4 weeks. After 4 weeks of treatment 16 of 31 patients (52%) receiving budesonide enema had healed endoscopically, compared with 8 of 33 (24%) (p = 0.045) receiving prednisolone enema. Budesonide was superior to prednisolone in terms of both significantly improved sigmoidoscopic and histologic scores and subjective symptoms evaluated by visual analogue scales. The patients receiving prednisolone had a significant depression of endogenous cortisol levels during the treatment period, but not the patients receiving budesonide. Budesonide enema seems to be a promising therapy for active distal ulcerative colitis and causes no adverse reactions.

Adolescent↗
PubMed1987

The risk of colorectal cancer in ulcerative colitis. An epidemiologic study.

Patients with a definite diagnosis of ulcerative colitis in Stockholm County during the 35-year period 1945-79 were identified and followed up with regard to the development of cancer of the colon. We found 25 patients who had developed 31 cancers. In 24 of 25 cases this occurred in patients with total colitis. The cumulative risk of developing cancer for patients with total colitis at follow-up study was calculated by means of life-table methods. It was 13% at 25 years (SD +/- 4.2%) among patients diagnosed in 1945-79, compared with the 1.9% expected in a population matched for age and sex. Among patients diagnosed in 1955-79 the risk was approximately 5% at 20 years (SD +/- 3.0%), compared with 1.4% for the background population. The cancer risk for all patients with colitis was higher but not significantly higher than that of the general population. The outcome of patients who developed cancer was dependent on histologic staging (Dukes's) at surgery but not on age at cancer diagnosis.

Adult↗
PubMed1986

Cancer surveillance of patients with longstanding ulcerative colitis: a clinical, endoscopical, and histological study.

An eight year endoscopical and histological cancer surveillance programme comprising 71 patients with ulcerative colitis is presented. Forty one patients had total colitis and 30 substantial colitis. Mean duration of the disease was 19.7 years (range 9-46 years). An average of 2.6 colonoscopies per patient in the total colitis group were carried out, and at least two biopsies were taken at 10 locations in the colon. In the total colitis group, seven had either low (four), or high grade dysplasia (two), or Dukes' A cancer (one). In the group with substantial colitis two patients with low grade dysplasia were found. Dysplasia or cancer leading to operation was found above the rectum in four of five operated patients, all having had total colitis for 25 to 44 years. The dysplasia and cancer findings at the colonoscopy preceding surgery corresponded well with the surgical specimens. In three operated patients a sequence of dysplasia development was recorded. With the exception of long duration and dysplasia, nothing in the clinical course distinguished the operated cases. Using this surveillance programme prophylactic colectomy can be limited to patients in a high risk group developing dysplasia. The risk of missing a cancer before it becomes incurable seems to be low.

Adult↗
PubMedDate not supplied

Age- and site-dependent cell cycle composition of the normal human colonic mucosa.

BACKGROUND AND AIM: As a reference to studies of DNA-ploidy and S- and G2/M-phase fractions in patients with inflammatory bowel diseases, we describe the mucosa of normal individuals with respect to age and localization in the colon. MATERIALS AND METHODS: One hundred and sixty-five biopsies from the right, transverse and left colon from 44 subjects (20 men, 24 females, median age 55 years (range 21-80)) who were referred for colonoscopy due to rectal bleeding, diarrhoea or suspicion of neoplasia, but with normal macroscopic and microscopic findings, were analysed by DNA-flow cytometry for ploidy and cell cycle composition. The biopsies were immediately fixed in buffered formalin and then analysed by a method for high quality preparations of cell nuclei without any centrifugation steps, resulting in minimal cell damage and low frequencies of aggregates, making the background levels low in the DNA-histograms. RESULTS: The median S-phase fraction of the biopsies, all diploid, was 2.35% (0.1-8.3). The S-phase fraction increased linearly with age (p = 0.001) and decreased from the right colon (median 2.75% (0.5-8.3)) over the transverse colon (median 2.3% (0.1-6.2)) to the left colon (median 1.9% (0.8-6.5), p < 0.02). The fraction of G2-cells (median 1.1%, range 0.2-5.1) increased significantly with increased S-phase fraction (p < 0.0001). CONCLUSION: DNA-FCM analyses of normal colonic tissue demonstrate an age- and site-dependent variation with regard to cell proliferation. This variation has to be taken into consideration when biopsy specimens from chronic colitis mucosa are evaluated.

Adult↗
PubMedDate not supplied

Colorectal cancer in colonic Crohn's disease--high frequency of DNA-aneuploidy.

BACKGROUND: The risk of colorectal cancer (CRC) in colonic Crohn's disease (CCD) seems to be of the same magnitude as in extensive, longstanding ulcerative colitis (UC) and colonoscopic surveillance has been advocated. Mucosal dysplasia and DNA-aneuploidy are early warning markers of malignant transformation in UC. Data concerning the occurrence of such premalignant lesions in CCD are scarce. AIMS: The objective of this study was to investigate the DNA ploidy pattern in CCD-patients with manifest CRC, both in the tumour, as well as in the adjacent and distant colorectal mucosa. The results from DNA-flow cytometry analyses (FCM) prior to the development of a CRC in CCD were also investigated. MATERIALS AND METHODS: Biopsies obtained at colonoscopy and surgical specimens from 43 patients with colonic or ileocolonic CD developing CRC between 1988 and 1998 were reviewed. The CRC histological phenotype, and the occurrence of dysplasia were registered. CRC-tissue and tissue from areas with dysplasia adjacent to and/or distant from the tumour were obtained from paraffin-embedded blocks and were analysed by FCM after preparation. RESULTS: Twenty-four CRCs in 21 patients (14 men) were suitable for FCM-analyses. The median age at CRC-diagnosis was 53 years (21-73) and the median CCD-duration was 14.5 years (1-50). A predominance of CRC was found either in the cecum (9124) or in the rectum (7/24). DNA-aneuploidy was found in 62.5% (15/24) of the tumours, in 25% (2/8) in adjacent and/or distant mucosa, and in 50% (2/4) of the patients that had been subjected to colonoscopic surveillance prior to the CRC-diagnosis. In 7patients (29%), definite dysplasia was detected adjacent to andlor distant from the tumour. Of the 6 patients undergoing colonoscopic surveillance, 3 (50%) displayed definite dysplasia prior to the colectomy. CONCLUSION: Since DNA- aneuploidy is a' common feature in CRCs in CCD and precede the development of invasive carcinoma, inclusion of FCM-analyses of colorectal biopsies may enhance the sensitivity of identifying high-risk CCD-patients prone to develop CRC within the frame of colonoscopic surveillance programs.

Adult↗