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We report a patient with ulcerative colitis who underwent colectomy when aged 25 years for multifocal high grade dysplasia which had developed within 2 years of diagnosis, and only 5 1/2 years after his first symptoms. The implications of this case for the management of ulcerative colitis are discussed.
One hundred and seven patients (57 patients with ulcerative colitis and 50 controls) were investigated for in vitro tetraploidy (IVT) in dermal fibroblast monolayer cultures. There was no difference in incidence of IVT between patients with ulcerative colitis and controls. We advance the hypothesis that the genetic background of the colorectal cancer type found in ulcerative colitis differs from that found in the colon cancer syndromes and in non-hereditary colorectal cancers. Colorectal cancer in ulcerative colitis is probably only dependent on the degree of inflammatory lesions of the colonic mucosa.
In the colon of ulcerative colitis (UC) patients, apoptotic bodies have been recognized in routine histopathological preparations. To investigate the extent of the apoptosis, colonic biopsies were examined from involved and uninvolved areas of untreated active UC and from normal areas in patients with colonic polyps, utilizing various markers of apoptosis. The markers included DNA breaks detected by TUNEL, Fas (CD95/APO-1) and Fas ligand (Fas-L) localized by immunohistochemistry, electron microscopic features of apoptosis, and laddering of extracted DNA. Apoptosis marker positive cells were found mainly on the luminal epithelium of the normal colon and were present in active UC in crypts of involved and uninvolved areas of the colon, in addition to the luminal epithelium. The DNA extracted from active UC colon electrophoresed as a ladder. These findings suggest that the loss of epithelial cells in active UC occurs mainly by apoptosis in crypts of involved and adjacent uninvolved areas and that the Fas/Fas-L interaction is a mediator of the apoptosis.
Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse.
Inflammatory cell infiltrates in ulcerative colitis have been investigated by means of the immunoperoxidase method and by electronmicroscopy. Considerable morphological and functional changes of the local plasma cell population have been found. The absolute number of plasma cells is raised with a marked increase of IgG-cells and a relative decrease of IgA-cells. In particular complement (C3) has been demonstrated at the basement membrane of the surface epithelium and between epithelial cells. The significance of these findings, as a local humoral immune response, is briefly considered, with regard to their possible pathogenetic importance in aggravating and perpetuating the disease.
Three patients suffering from ulcerative colitis, who had previously undergone a colectomy and temporary Brooke ileostomy and who were under treatment with methylprednisolone and 5-aminosalicylic acid per the rectum, were readmitted to the hospital, presenting with profuse rectal hemorrhage with six to nine blood losses per day. An adrenaline chloride solution washout of the rectum was given in an attempt to avoid surgery. In the two to six hours after treatment, hemorrhage was considerably reduced, the hemoglobin levels were stationary, and no further transfusions were necessary.
Total proctocolectomy following surgery for ulcerative colitis and carcinoma may be associated with difficulty in healing of the perineal wound. The presentation of delayed abscesses may be insidious in nature and present a diagnostic dilemma. We present a patient with delayed abscess eight years following total proctocolectomy for ulcerative colitis. Early use of computerized tomography is helpful in evaluating the late occurrence of pain in these patients.
Ulcerative colitis (UC) and Crohn's disease (CD), the major forms of inflammatory bowel diseases (IBDs). are multifactorial disorders of unknown etiology. We reported a possible association of rare variable number of tandem repeat (VNTR) alleles of the "MUC3" gene with a susceptibility to UC. However, an entire structure of "MUC3" is still unknown because the long stretches of tandem repeats in this "gene" make its cloning extraordinarily difficult. In this study, we report evidence that "MUC3" consists of two genes, MUC3A and MUC3B, both of which encode membrane-bound mucins with two epidermal growth factor-like motifs, and we describe the complete 3'-terminal structures of these two genes. We have also analyzed the single nucleotide polymorphisms (SNPs) in the exonic sequences of the 3' portions of these two genes to investigate whether sequence variations in these regions can cause person-to-person differences in the susceptibility to IBDs, and report here that non-synonymous SNPs of MUC3A, involving a tyrosine residue with a proposed role in cell signaling, may confer genetic predisposition to CD (P = 0.0132). Our findings suggest that variants of MUC3A may be involved in the occurrence of UC and CD in distinct manners.
An important hallmark of ulcerative colitis (UC) is mucosal neutrophil (PMN) infiltration associated with mucosal damage. This suggests that colonic chemoattractants such as bacterial products (e.g., N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS)) reach systemic circulation and attract PMNs to the colon. PMNs are then activated in the colonic mucosa and release their toxic oxidative metabolites. However, bacterial products are also present in the systemic circulation of healthy subjects. Thus we hypothesized that PMNs develop tolerance to colonic factors in the normal state and that this tolerance is absent in UC. We evaluated the PMN respiratory burst in response to stimulation with fMLP, LPS, or phorbol 12-myristate 13-acetate (PMA) by measuring the production of reactive oxygen species (ROS) with both luminol-enhanced chemiluminescence and a cytochrome C reduction assay. PMNs were obtained from control subjects, inactive UC patients, patients with UC who had undergone colectomies, and non-UC patients with colectomies. All three stimuli induced a significant rise in ROS. PMNs from non-UC colectomy subjects produced significantly higher ROS than PMNs from control subjects with intact colons in response to both fMLP and LPS. In contrast, PMNs from UC colectomy patients produced levels of ROS similar to those produced by PMNs from UC patients with intact colons in response to fMLP and LPS. Colectomy had no effect on PMA-induced ROS production in controls. The observed difference in fMLP-induced ROS production in control subjects with intact colons was not due to fMLP receptor down-regulation because a competition assay performed with the fMLP blocker BMLP showed a similar receptor apparent affinity in all four groups. We conclude the following: (1) the normal colonic milieu modulates the PMN respiratory burst, resulting in hyporesponsiveness of PMNs to "physiologic" but not "pharmacologic" stimulation. This effect is not due to receptor down-regulation. (2) UC colonic milieu does not appear to modulate PMN respiratory burst. This loss of PMN "tolerance" to colonic factors may have a pathogenic role in the sustained inflammation and tissue damage in UC.
Ulcerative colitis and Crohn's Disease can be cured if they are treated as autoimmune diseases with a special understanding of the personality conflicts in the patient. The author hypothesizes that all autoimmune diseases are characterized by a high normal amount of the aggressive instinctual drives and ambivalence about their realization. Each patient's personality causes the ambivalence to be somaticized into specific autoimmune bodies that aggressively are overproduced and then attack specific tissues. Hypnosis helps in gaining insight, reinforcing interpretations, handling stress, visualizing normal intestinal areas, and controlling of the autoimmune antibodies to the normal level. This paper deals specifically with these 2 diseases.
Ulcerative colitis is a surgically curable mucosal disease of the colon and rectum. Optimal management of this chronic condition requires close coordination between the patient, surgeon, and primary care provider or gastroenterologist. Knowledge of surgical indications and the operative alternatives available helps to individualize therapy. Acute and chronic indications for surgery and the five surgical methods currently in use are described.
Women with ulcerative colitis (UC) are usually young and thus likely to undergo pregnancy. They should be advised to conceive when the disease is quiescent. Steroids and salicylates may be used normally during pregnancy, possibly without exceeding a dose of 2g/day for mesalazine. Azathioprine can be maintained if its indication is clear cut. Cyclosporin seems to be without additional risk in the pregnant woman, its use being limited to acute steroid-refractory disease, as an alternative to surgery.
BACKGROUND: Ulcerative colitis associated colorectal cancer (UCACRC) has several distinctive clinicopathological and genetic features which differ from sporadic colorectal cancer (SCRC). Hypermethylation of the E-cadherin gene (CDH1) has not been described previously in colorectal cancer. AIMS: A panel of SCRC and UCACRC were investigated for mutations in CDH1, and for hypermethylation of the promoter region of CDH1. SUBJECTS AND METHODS: DNA was available from 14 patients with UCACRC and from 14 with SCRC. All exons of CDH1 were amplified with the polymerase chain reaction (PCR) and screened using single strand conformational polymorphism and direct sequencing. Hypermethylation of the CDH1 promoter region was determined by methylation specific PCR following bisulphite modification, and compared with E-cadherin protein expression from a previous immunohistochemistry study. RESULTS: Thirteen of 28 cancers (46%) were hypermethylated in the CDH1 promoter region-eight cancers (57%) in the UCACRC group and five cancers (36%) in the SCRC group (NS)-and this correlated with reduced E-cadherin expression (p<0.05). There was a trend for methylation to be associated with a more advanced stage of cancer although this did not reach statistical significance. There were no mutations in CDH1 in either group although there were several polymorphisms. CONCLUSION: We have demonstrated hypermethylation of the promoter region in CDH1 in 46% of colorectal cancers studied. There was no difference between the UCACRC and SCRC groups. Just as there are specific differences in the genetic changes between UCACRC and SCRC, there is also likely to be a large degree of overlap among the genetic pathways of these cancers.
A young woman with ulcerative colitis developed pneumonia, which responded to corticosteroids. Histological examination showed this to be bronchiolitis obliterans organising pneumonia.
AIM: Ulcerative colitis (UC) primarily affects young adults, but the proportion of elderly patients with UC seems to be increasing. It is important that the clinical characteristics of elderly patients be analyzed. METHODS: In the older group consisted of 32 outpatients (23 aged 50-64 years old, 9 aged 65 or over) in our hospital, we evaluated disease duration, severity, therapeutic efficacy and other clinical problems. RESULTS: The age distributions of the disease onset showed a peak at early age and decreased with aging. The degree of severity was mainly mild, and left-sided or pancolitis were more frequent than expected in the older group. Most elderly patients suffered other diseases, and care was required in the administration of steroids. CONCLUSION: The clinical features of elderly patients with UC were similar to those of younger patients. However, It should be considered that elderly patients often have complications requiring care in the use of steroids.
AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRalpha and GRbeta) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRalpha and GRbeta expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRalpha and GRbeta expression. Both positive association between GRalpha expression and the response of UC to GC and strong negative association between GRbeta expression and the response of UC to GC were identified. There was no significant association between GRalpha/GRbeta expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRalpha and GRbeta may play an important role in the action of GC, and that GRbeta functions as a dominant negative inhibitor of GRalpha. Expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.
Selection of treatment for ulcerative colitis is based on the definition of clinical severity. In those medication is a main course. Mild and moderate cases are treated mainly with salicylazosulfapyridine or mesalazine. Patients with proctitis-type are added betamethazone suppositories and those with left-sided and total colitis-type predonisolone enema therapy simultaneously. If there is no response, they are given additional oral predonisolone. Even after remission, patients should be carefully observed. A good patient-physician relationship, continuation of maintenance therapy, and periodic follow-up examinations using colonoscopy or barium enema are essential to successful long-term management of this disease. Patients who have repeated relapsing should receive the stronger treatment, according to the endoscopic findings and clinical course in addition to the clinical severity.
BACKGROUND: Patients with idiopathic ulcerative colitis (IUC) may suffer from one or more extraintestinal manifestations. We decided to prospectively study the prevalence of extraintestinal manifestations among patients with IUC, with special reference to pulmonary and hematological alterations. METHODS: Fifty-one consecutive patients with IUC attending the gastroenterology services of our tertiary-care referral center were evaluated prospectively. A detailed clinical evaluation of the musculoskeletal system, eye and skin, X-ray examination of the sacroiliac joints and chest, liver function tests, coagulation profile, hemogram, pulmonary function tests (PFT) and diffusion capacity for carbon monoxide (DLCO) were done in all patients. ERCP, liver biopsy and high-resolution computerized tomography (HRCT) of the chest were performed whenever indicated. RESULTS: Nearly half (24/51; 47%) the patients had one or more extraintestinal manifestations; these included pulmonary function abnormalities (14 patients; 27%), sacroiliitis (8; 16%), arthritis (5; 10%), ocular complications (4; 8%), and pyoderma gangrenosum and Budd-Chiari syndrome (one patient each). Of the 14 (27%) patients who had abnormal pulmonary function, isolated PFT abnormalities were seen in 8 (restrictive pattern in 7, obstructive pattern in 1), decreased DLCO in four, and both of the above in two. All patients with decreased DLCO (n=6) were asymptomatic and had normal chest X-ray and HRCT chest. Thirteen (25%) patients had thrombocytosis, 19 (37%) had increased fibrinogen level, and one patient had decreased antithrombin level. Disease activity had significant association with decreased DLCO (p=0.008), increased platelet count (p<0.0001), increased fibrinogen level (p=0.016), low antithrombin levels (p=0.046) and arthritis (p=0.002). CONCLUSION: Extraintestinal manifestations of IUC were seen in 47% of patients. Asymptomatic pulmonary interstitial involvement was seen in 12%, more often among patients with active disease.