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.     

Clinical and anti-aging effect of mud-bathing therapy for patients with fibromyalgia

This study focuses on two inflammatory diseases, viz., “diabetes mellitus (DM)” that causes serious complications such as retinopathy, nephropathy, and neuropathy, and “ischemic colitis” which is evoked by DM. Ischemic colitis originates from the reduction in mesenteric blood flow to the colon with existence of the occlusive or non-occlusive reasons. Our study objective was to provide early diagnostic approach for ischemic colitis in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into four groups: (i) control use of 0.1 M citrate buffer, the solvent of streptozotocin (C), (ii). induced ischemia (I), (iii) rats subjected to 60 mg/kg STZ intraperitoneally to induce type 1 diabetes (D) (48 h after STZ injection, blood glucose levels >200 mg/dl were considered as diabetic), and (iv) diabetic rats subjected to intestinal ischemia (D+I). The third diabetic group (D) was not operated. At the end of the experimental period, rats were sacrificed, C-reactive protein (CRP) and calprotectin levels were measured in the serum and colon tissue specimens. Tissue specimens were also analyzed histologically. We found that serum and colon calprotectin levels were elevated in the D+I group compared to the D and/or I group alone, but relatively calprotectin levels increased in I as compared to C group in colon tissues. CRP levels were significantly increased with ischemic colitis in diabetes, while colon CRP levels were decreased. These results provide evidence for the existence of inflammation in the STZ-induced diabetic rats with ischemic colitis. In conclusion, our measurements of serum calprotectin levels of STZ-induced diabetic rats with ischemic colitis provide a practical approach for an early diagnosis of ischemic colitis. Furthermore, these biochemical analyses correlate well with the histopathologic findings of STZ-induced diabetic rats with ischemic colitis. Future studies would be desirable to further strengthen the role of calprotectin in the early diagnosis of ischemic colitis in diabetics clinical settings.     

Retrograde spread of hydrocortisone containing foam given intrarectally in ulcerative colitis.

A method is described of estimating retrograde spread through the colon of a 10% hydrocortisone acetate foam by labelling the foam with technetium-99m sulphur colloid and observing spread after intrarectal administration by serial gamma-camera pictures. The recommended 51 ml dose of foam reached the mid-sigmoid colon in all of the nine patients who had active ulcerative colitis. Furthermore, in seven the foam reached the proximal sigmoid colon. Foam spread less extensively in five patients with quiescent disease than in those with active disease. Increasing the volume of enema to 50 ml did not improve retrograde spread through the colon. These results suggest that 10% hydrocortisone foam may be useful in treating patients with distal ulcerative colitis that is not necessarily limited to the rectum.     

溃疡性结肠炎与缺血性结肠炎临床特征内镜特点相关分析

目的：提高缺血性结肠炎（IC）和与溃疡性结肠炎（UC）诊断的正确率。方法：选择2008年1月至2011年6月的住院患者,确诊IC 43例,UC 36例,对其临床特征、内镜特点进行回顾性比较分析。结果：组间性别、年龄、病程和基础疾病比较差异有统计学意义（P〈0.05）,而主要临床表现比较,差异无统计学意义。IC组以老年女性多见,病程短,多伴发心脑血管等基础疾病（29/43,67.0%）。IC组C反应蛋白高于UC组,血小板低于UC组（P〈0.05）。IC多累及乙状结肠,直肠少见;病变为区域局限性,溃疡为纵形或不规则形,病灶愈合迅速,病理以黏膜炎症为主。UC组病变多起源于直肠,一般累及肠壁全周,病变为倒灌连续性,以散在针尖样地图状溃疡为主,病理表现为隐窝炎和脓肿。结论：年龄、病程、基础疾病、C反应蛋白、内镜及病理特征是鉴别诊断的要点。     

Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn's disease

Summary. Nitric oxide synthase (NOS) activities are responsible for the enzymatic conversion of L-arginine into NO and L-citrulline. Relatively low amounts of NO are produced in intestinal epithelial cells or are released from nerve endings. The effects of NO production are related to the maintenance of epithelial integrity and permeability. A pathological role of an increased NO production has been suggested to play a role in models of experimental colitis. In humans, NOS activity in colon mucosa from patients with ulcerative colitis is clearly increased when compared with the activity of the control group. In contrast, an increase of NOS activity in the colon mucosa from patients with Crohn's disease remains controversial. In the present work, we have measured NOS activity in colon biopsies originating from the control group (n = 16), from patients with ulcerative colitis (n = 23) and Crohn's disease (n = 17) using the radiochemical method of the conversion of L-[guanido-¹⁴C] arginine into radioactive L-citrulline. In the control group, NOS activity was mainly of the inducible type (88% of total NOS activity) since it was characterised by its insensibility to the absence of calcium in the assay medium. In colon biopsies originating from patients with ulcerative colitis, inducible NOS activity was increased 3 fold (p < 0.005) and in patients with Crohn's disease, inducible NOS activity was increased 5 fold (p < 0.005). Correlations between NOS activity in colon biopsies and the intensity parameters of the disease i.e. Truelove index, endoscopic score and histo-logical parameters were evidenced in patients with ulcerative colitis. In contrast, in patients with Crohn's disease, the high inducible NOS activity was not correlated with any intensity parameters of the disease. From these data, we concluded that although inducible NOS activity was increased several fold in colon biopsies originating from patients with both ulcerative colitis and Crohn's disease, a correlation between this activity and the severity of bowel inflammation was not found in either cases. Received August 7, 1999     

Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis.

Finger clubbing, measured objectively by using the hyponychial angle, was present in 75 out of 200 (38%) patients with Crohn''s disease, 15 out of 103 (15%) with ulcerative colitis, and two out of 24 (8%) with proctitis. In Crohn''s disease and ulcerative colitis the hyponychial angle was significantly correlated with both disease activity and the extent of fibrosis in the resected specimens from 47 surgically treated patients. The prevalence of finger clubbing in patients with macroscopic disease within the area of the gut innervated by the vagus nerve was significantly higher than that in patients in whom the disease was confined to the distal colon and rectum. Finger clubbing in patients with Crohn''s disease tended to regress after resection of macroscopic disease. It is concluded that finger clubbing is significantly commoner in Crohn''s disease than ulcerative colitis. The focal stimuli for finger clubbing include mucosal inflammatory change and fibrosis mediated by the vagus and possibly other autonomic pathways acting as the afferent arc of a finger-clubbing reflex.     

Multiple displacement amplification of DNA from human colon and rectum biopsies: bacterial profiling and identification of Helicobacter pylori-DNA by means of 16S rDNA-based TTGE and pyrosequencing analysis

Amplifying bacterial DNA by PCR from human biopsy specimens has sometimes proved to be difficult, mainly due to the low amount of bacterial DNA present. Therefore, nested or semi-nested 16S rDNA PCR amplification has been the method of choice. In this study, we evaluate the potential use of whole genome amplification of total DNA isolated from human colon and rectum biopsy specimens, followed by 16S rDNA PCR amplification of multiple displacement amplified (MDA)-DNA. Subsequently, a H. pylori-specific 16S rDNA variable V3 region PCR assay was applied directly on MDA-DNA and, combined with pyrosequencing analysis; the presence of H. pylori in some biopsies from colon in patients with microscopic colitis was confirmed. Furthermore, temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA amplicons using primers flanking variable regions V3, V4, and V9, was used to establish bacterial profiles from individual biopsies. A variation of the bacterial profiles in the colonic mucosa in microscopic colitis and in normal rectal mucosa was observed. In conclusion we find the MDA technique to be a useful method to overcome the problem of insufficient bacterial DNA in human biopsy specimens.     

Localized colonic inflammation increases cytokine levels in distant small intestinal segments in the rat

Local inflammation in the colon has been associated with nutrient malabsorption and altered motility in the small bowel. These remote effects suggest the release of mediators which can act (or alter) the function of intestinal segments located far from the primary area of inflammation. This study describes the changes in the expression of pro-inflammatory cytokines in the colon and in various segments of the small intestine in two rat models of experimental colitis. Colitis was induced by the intracolonic administration of 100 microL of 6% iodoacetamide or 250 microL of 2, 4, 6-trinitrobenzene sulfonic acid. Levels of interleukin one beta, interleukin 6, and tumor necrosis factor alpha were measured by ELISA in tissue homogenate sampled from duodenum, jejunum, ileum and colon at different time intervals. In homogenates of strips isolated from duodenum, jejunum and ileum, tumor necrosis alpha and interleukin-6, increased significantly 3-6 h after iodoacetamide or TNBS administration and remained elevated until the colonic inflammation subsided. Interleukin one beta showed comparable but delayed increase. Similar, but more pronounced increase of the three cytokines was noticed in areas of the colon adjacent to the ulcer. Histologic examinations revealed important inflammatory changes in the colon; however, examination of sections from the small intestines did not reveal significant differences between controls and rats with colitis. In conclusion, expression of pro-inflammatory cytokines is increased in remote segments of the small intestines during colitis. The findings may provide a partial explanation or a molecular substrate for the associated small bowel dysfunction.     

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.     

Potentialities of modern clinical X-ray radiology in the differential diagnosis of tumor and other obstructive diseases of the large bowel

The misdiagnosis rate in defining the cause of obstructive colonic disease is 8.2-24.4%. This is consistent with the fact that every 5 patients with colonic obstruction present difficulties in establishing the nature of a pathological process. The paper provides the results of analysis of clinical and X-ray symptoms in 350 patients with difficult differentially diagnosed cases of narrowing of the rectum and colon. Based on the analysis, the authors identified the basically important X-ray signs that might differentiate tumor stenoses from other obstructive diseases. They also defined the specific X-ray signs of such diseases as infiltrative cancer; extraintestinal cancer involved in the large bowel; inflammatory strictures in ulcerative colitis, diverticulosis, actinomycosis, tuberculosis, intestinal endometriosis, invagination, and other obstructive diseases. The developed differentiated diagnostic criteria could enhance the overall accuracy of X-ray study in this difficult group of patients from 72.7-80% to 93%.     

Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production

Interleukin (IL)-18, initially described as interferon (IFN)-gamma-inducing factor, is expressed in the inflamed mucosa of patients with Crohn's disease. To investigate the role of IL-18 in intestinal inflammation, the effect of neutralizing antimurine IL-18 antiserum in dextran sulfate sodium (DSS)-induced colitis in BALB/c and C57BL/6 mice was examined. During a dose response of DSS, levels of colonic IL-18 increased parallel with clinical worsening. With the use of confocal laser microscopy, the increased IL-18 was localized to the intestinal epithelial layer. Anti-IL-18 treatment resulted in a dose-dependent reduction of the severity of colitis in both BALB/c and C57BL/6 mice. Colon shortening following DSS-induced colitis was partially prevented in the treatment groups. In the colon tissue homogenates, IFN-gamma concentrations were lower in the anti-IL-18-treated DSS-fed mice compared with untreated DSS-fed mice. This suppressive effect of anti-IL-18 administered in vivo was also observed on spontaneous tumor necrosis factor-alpha, IL-18, and IFN-gamma production from ex vivo colon organ cultures. The stimulation of lamina propria mononuclear cells by IL-18 and IL-12 resulted in a synergistic increase in IFN-gamma synthesis. These findings suggest that IL-18 is a pivotal mediator in experimental colitis.     

Expression of Toll-like receptor 2 (TLR2), TLR4, and CD14 in biopsy samples of patients with inflammatory bowel diseases: upregulated expression of TLR2 in terminal ileum of patients with ulcerative colitis.

Dysregulation of innate and adaptive intestinal immune responses to bacterial microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2), TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon samples were obtained by colonoscopy from patients with Crohn's disease (CD), ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and CD14 showed a significant increase in TLR2 expression in the terminal ileum of patients with inactive and active UC against controls. Significant upregulation of TLR4 expression relative to controls was found in the terminal ileum and rectum of UC patients in remission and in the terminal ileum of CD patients with active disease. CD14 expression was upregulated in the terminal ileum of CD patients in remission and with active disease, in the cecum of UC patients in remission and with active disease, and in rectum of UC patients with active disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.     

Hyperbaric oxygenation and drug therapy in treatment of nonspecific ulcerative colitis and Crohn's disease]

Patients with nonspecific ulcerative colitis and Crohn's disease were treated with drug therapy (prednisolone, sulphasalazine, metronidazole per os and hydrocortisone per rectum) and subjected to 12 sessions of HBO. Every 10-14 months the HBO course was repeated. After 7 years of such a treatment a gradual partial recovery of large intestine mucosa and in some cases even its absolute recovery were observed. It was most difficult to get good results when treating lesion of distal colon segments. HBO produced a good effect when the disease was diagnosed at the early stage, when the intestine injury was accompanied by hepatobiliary system disease and in teenagers.     

Expression of the histone H3 gene in the evaluation of cellular proliferation in colitis ulcerosa

A comparison of the number of mRNA molecules of histone H3 in 1 microg total RNA extracted from colon sections sampled during colonoscopy was used to evaluate cellular proliferation activity in the rectum and sigmoid, in normal tissue and in colitis ulcerosa. Samples with similar intensity of the disease were selected for the study. Statistically significant differences between both groups of rectal sections were found in the expression of histone H3 encoding genes. The statistically significant result (p = 0.0485) indicates a more active division of cells in the healthy rectum, with no statistically significant differences in the sigmoid (p=0.9575).     

War injuries of colon and rectum--results after 10 years

The aim of our study is to evaluate results of treating war injuries of colon and rectum, after 10 years. During the war in Croatia, 21 wounded, with colon (19) and rectum (2) injuries, were treated in the Department of Surgery at Nova Gradiska General Hospital from August 1991 to April 1992. Bullet wounds accounted for 57% of the injuries. All patients had other associated injuries. Primary repair and proximal derivation was possible in 2 cases (9.5%), while primary resection with intraperitoneal anastomosis was performed in 3 (14.3%) patients. In 2 (9.5%) patients sustained intraperitoneal and extraperitoneal rectal penetrating injury rectum was resected and closed performing temporary sigmoidostomy. When multiple perforations or crush injury of the colon were found, in 8 (38.1%) injured persons resection of the involved segment was combined with proximal end colostomy and aboral mucous fistula. Exteriorization of injured segment of the colon and creating colostomy incorporating the injured colon as the stoma was performed in 6 (28.5%) wounded patients. Four of the wounded (19.0%) died two of them during the operative procedure due to hemorrhagic shock. One injured died after eight days due to pulmonary embolism, and one patient died after thirty days due to sepsis. Reoperation was necessary in two (9.5%) injured due to bowel obstruction four days following initial surgery because of adhesions. Three (14.3%) of the injured had wound infection, one of them died 30 days after injury due to sepsis, and two (9.5%) consequently developed ventral hernia that was operated after 4 and 5 years respectively. Four (19.0%) of the injured are still occasionally experiencing occasional abdominal pain.     

Mortality of captive tortoises due to viviparous nematodes of the genus Proatractis (Family Atractidae)

Between September 1982 and January 1984, verminous colitis was diagnosed post mortem in eight red-footed tortoises (Geochelone carbonaria) and three leopard tortoises (Geochelone pardalis) from the reptile collection of the National Zoological Park. This represented 69% of 16 tortoise necropsy accessions for that period. Etiology was determined to be a viviparous pinworm-like nematode of the genus Proatractis (Family Atractidae). Clinical signs were either nonspecific, consisting of anorexia, lethargy, and depression, or were absent. Limited trials with piperazine citrate and fenbendazole appeared to be ineffectual against the parasite and supportive therapy was unsuccessful. Post mortem examination revealed roughening and thickening of the mucosa of the cecum and colon, and in severe cases myriads of tiny (0.5-1.0 cm) nematodes were evident on the mucosal surface. In six tortoises, worms were found also in the small intestine. Histopathologic features in severe cases included mucosal necrosis with parasites and mixed inflammatory cells extending into the tunica muscularis. Focal to diffuse lymphoplasmacytic infiltrates were present consistently in the submucosa of the cecum and colon, and similar but milder lesions occasionally occurred in the small intestine.     

Evidence of 1,25-dihydroxyvitamin D3-receptors in human digestive mucosa and carcinoma tissue biopsies taken at different levels of the digestive tract, in 152 patients

Epidemiological and experimental data suggest that dietary calcium and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) are protective against colorectal cancers, while their activity on colon mucosa still remains unknown. Since the presence of receptors is required for steroid action, specific 1,25-(OH)2D3 receptors were investigated in biopsies taken at different levels of the digestive tract from the oesophagus to the rectum and in pancreas. The total study involved biopsies from 152 patients. In 82% of the cases they were paired biopsies in adenocarcinoma tissue and in adjacent normal mucosa (NM). There were 120 operated on for colorectal adenocarcinoma (HCRA). 1,25-(OH)2D3 receptor was assayed in tissue extract by the dextran-coated charcoal (DCC) technique and also characterised by sucrose density gradient centrifugation. Scatchard analyses showed a single class of specific high affinity-low capacity sites binding for 1,25-(OH)2D3 with a Kd = 1.48 +/- 0.8 x 10(-10) M (n = 119). The sedimentation coefficient of the steroid receptor complex was approximately 3.2 S. The incidence of 1,25-(OH)2D3 receptors was significantly higher in NM (82.5%) than in HCRA (34.5%). In HCRA this incidence decreased from right colon (64.7%) to left colon (27.7%) and rectum (15%). All positive HCRA in left colon and rectum (16/76) were histologically well differentiated. The receptor content in NM and HCRA was in the same range: (median) 10-314 (58) and 13-175 (64) fmol/mg protein. These data suggest that 1,25-(OH)2D3 may modulate calcium transport in colon, as in the intestine. Also, loss of receptivity to 1,25-(OH)2D3 is observed as associated with malignant transformation of the human colorectal mucosa.     

A protective effect of the synthetic coumarine derivative Cloricromene against DNB-colitis in the rat

Biologic therapies, namely antibodies against tumor necrosis factor-alpha (TNF- alpha) or its receptors, have been recently introduced for the treatment of patients with inflammatory bowel disease (IBD). In the present study the effects of cloricromene, an agent with known antithrombotic actions and with demonstrated anti-TNF- alpha activity were investigated in a rat model of experimental colitis induced with dinitrobenzenesulphonic acid (DNB)/ethanol. We investigated three experimental groups: (i) sham-colitis with vehicle-treatment (controls, n = 6), (ii) colitis with vehicle-treatment (saline, 0.1 ml s.c., daily) (DNB-V, n = 7), (iii) colitis with cloricromene-treatment (10 mg/kg/day s.c.; DNB-C, n = 8). After 7 days, the weight gain, colon wet weight, macroscopic damage score, coagulation parameters, colon mucosal myeloperoxidase activity (MPO), and tissue concentrations of TNF- alpha and of macrophage inhibitory peptide-2 (MIP-2) were assessed. The macroscopic damage scores, colon wet weights, and tissue MIP-2 levels were significantly increased in untreated and in cloricromene-treated rats compared with controls. Cloricromene treatment was associated with a minor body weight loss (p < 0.025) and significantly reduced tissue concentrations of MPO and TNF-alpha (p < 0.02, both). Blood coagulation parameters were not affected by treatment. In the DNB-model treatment with cloricromene effectively reduces tissue levels of TNF- alpha and of myeloperoxidase, whereas MIP-2 concentrations were not influenced. Blood coagulation parameters remained unchanged indicating safety of treatment. Since biological therapies frequently fail to improve disease course of IBD, other therapies with similar targets should be further investigated.     

South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin--peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their α-2,6 or α-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy