Increased risk of breast cancer in first-degree relatives of Crohn's disease patients. An IG-IBD study.

BACKGROUND: Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. AIM: To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. PATIENTS AND METHODS: A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3,292 first-degree relatives of Crohn's disease patients and in 3,303 first-degree relatives of controls. RESULTS: Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls (p=0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio=2.16; 95% confidence interval=1.14-4.08; p=0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. CONCLUSIONS: These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.

Assessment of small intestinal damage in patients treated with pelvic radiotherapy.

Pelvic radiotherapy almost always induces intestinal symptoms. We investigated the radiation-induced damage to the small intestinal mucosa and evaluated its relationship with symptoms, using cellobiose/mannitol permeability test (CE/MA) and plasma postheparin diamine oxidase test (PHD) in 20 patients treated with pelvic radiotherapy. The symptoms developed during radiotherapy were noted. Intestinal permeability significantly (p=0.013) increased from 0.021 +/- 0.026 to 0.047 +/- 0.055 (mean +/- SD) after 15 days of radiotherapy, while it returned to normal values (0.010 0.015) at the end of radiotherapy. PHD values did not change. All patients developed intestinal symptoms. These findings indicate that pelvic radiotherapy induces an early small bowel mucosa damage followed by mucosal adaptation. Acute intestinal symptoms during pelvic radiotherapy may not depend only on small intestinal mucosal damage.

Intestinal permeability in Crohn's disease patients and their first degree relatives.

BACKGROUND: Family studies suggested that an altered intestinal permeability plays a role in the genesis of Crohn's disease. AIM: Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohn's disease. SUBJECTS: 16 Crohn's disease patients and 26 of their cohabiting first degree relatives were studied. METHODS: To investigate intestinal permeability, Cellobiose/Mannitol test was administered to both groups. RESULTS: In the two groups, we found that the median intestinal permeability values were higher and statistically different from those obtained in 32 healthy control subjects as well as in five healthy control families. Six (37.5%) Crohn's disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohn's disease patients was unrelated to sex, age, disease activity, localisation, duration, treatment schedule, as well as to serum anti-Saccharomyces cervisiae antibody positivity in a pilot study conducted in 7 Crohn's disease patients; anti-Saccharomyces cervisiae antibody values were negative in all 10 first degree relatives investigated. CONCLUSIONS: These findings demonstrate the increase in IP in 37% of the patients and in 11% of their relatives. More extensive investigation of the correlation between ASCA alterations and IP will be needed in both patients with Crohn's disease and their relatives.

Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients.

BACKGROUND: Increased intestinal permeability was described in several intestinal auto-immune conditions. There are very few and contradictory reports about type I diabetes mellitus, an auto-immune condition sometimes associated with celiac disease. AIMS: To investigate intestinal permeability in type I diabetes mellitus patients with no concomitant celiac disease, with a comparison to ultra-structural aspects of duodenal mucosa. PATIENTS: 46 insulin dependent diabetes mellitus, non-celiac, patients (18 females and 28 males, mean age 15.8 +/- 5.3 [S.D.] years) were enrolled. The mean duration of the disease was 5.7 years. METHODS: The morphological aspect of the small bowel mucosa, at standard light microscopy and electron transmission microscopy, along with intestinal permeability (by lactulose/mannitol test) were studied. Lactulose and mannitol urinary excretion were determined by means of high performance anion exchange chromatography-pulsed amperometric detection. RESULTS: The lactulose/mannitol ratio was 0.038 [0.005-0.176] (median and range) in 46 patients compared to 0.014 [0.004-0.027] in 23 controls: insulin dependent diabetes mellitus group values being significantly higher than those of the controls (P < 0.0001, Mann-Whitney test). Eight insulin dependent diabetes mellitus patients underwent endoscopy and biopsies were analysed by means of light microscopy and transmission electron microscopy. At the light microscopy level, none of the biopsy samples showed any sign of atrophy nor inflammation, whereas transmission electron microscopy analysis showed remarkable ultra-structural changes in six out of the eight patients. Four parameters were evaluated: height and thickness of microvilli, space between microvilli and thickness of tight junctions. CONCLUSIONS: This alteration of intestinal barrier function in non-celiac type I diabetes mellitus, frequently associated with mucosal ultra-structural alterations, could suggest that a loss of intestinal barrier function can be a pathogenetic factor in a subset of insulin dependent diabetes mellitus patients.

Ranitidine vs cimetidine: short-term treatment of gastric ulcer.

We compared the clinical effectiveness and endoscopic results of ranitidine and cimetidine treatment; 71 outpatients, all affected with benign gastric ulcer, were selected for the study (43 type I, 7 type II and 21 type III, according to Johnson's classification). The patients were treated randomly for 4 weeks with ranitidine (300 mg daily) or cimetidine (1 g daily). An endoscopic examination was repeated within 3 days after the end of the treatment. Clinical checks were performed weekly in order to monitor the clinical course of pain and antacid consumption, according to the patient's needs. The patients who did not demonstrate complete healing on endoscopic examination were treated for an additional 4 week period. At the end of this 4 week period, another endoscopic examination was done. Thirty-six patients treated with ranitidine and 33 with cimetidine completed the first period of therapy. The two groups were homogeneous with regard to sex, age, duration of disease, smoking habits, alcohol consumption, and type and size of ulcer. Ranitidine and cimetidine treatments did not demonstrate any significant difference with regard to ulcer healing after the 4th or the 8th week of therapy. Both ranitidine and cimetidine were less effective in healing type I than type II and III G.U., at the 4th week of treatment. No significant differences between the two groups were noted with regard to pain or weekly antacid consumption. No significant side effects were reported.

Intestinal permeability and diabetes mellitus type 2.

BACKGROUND: Intestinal permeability can be investigated by means of molecular probes which are able to cross the intestinal wall through tight junctions of villi (smaller probes) and/or of crypts (larger probes). Intestinal permeability is altered in the majority of uncomplicated diabetes mellitus type 1 patients, due to the augmented absorption of the smaller probe. The aim of this work was to investigate if any similar alteration of intestinal permeability is present in diabetes mellitus type 2. METHODS: Intestinal permeability was studied by means of the Cellobiose/Mannitol test (CE/MA). The first and larger probe (Cellobiose) crosses tight junctions of crypts, the smaller (Mannitol) crosses those of villi. The CE/MA test was administered to 18 patients affected by diabetes mellitus type 2, with length of disease = 4.5+/-1.9 years (mean+/-SD) with no relevant intestinal pathologies. Results obtained in these 18 patients were compared with those of 25 healthy volunteers. RESULTS: Intestinal permeability to the CE/MA test was normal in all patients. All the investigated permeability parameters (%CE, %MA, CE/MA) overlapped, as a mean, with those of control subjects and were not statistically different. CONCLUSIONS: The present data confirm that diabetes mellitus type 2 has not pathophysiological components at intestinal level. This is different from what was demonstrated in diabetes mellitus type 1, the last being very well known to be associated with autoimmune diseases and celiac disease.

[Hereditary non polyposis colon cancer (NHP CC) prevalence in South Italy (Campania). Report on a preliminary retrospective study]. / Prevalenza di cancro ereditario del colon non su poliposi (HNPCC) nel sud Italia (Campania). Studio retrospettivo pilota.

The aim of this study was to determine a prevalence of Hereditary Non Polyposis Colo-rectal Cancer (HNPCC) in consecutive one hundred twenty-eight patients living in Campania district and affected by first diagnosed colorectal cancer. Data on 128 patients and their relatives was collected and available for analysys. Our preliminary results seem to demonstrate a low prevalence of HNPCC in Campania and will be verified with a prospective multicentric study in the same area.

[Ulcerative rectocolitis diagnosed in the elderly. Case studies]. / La rettocolite ulcerosa diagnosticata nell'anziano. Contributo casistico.

Fourteen patients with idiopathic ulcerative colitis (UC) diagnosis made over 60 years of age have been extrapolated from 255 (5.49%) consecutive. Some clinical parameters (sex; symptoms of onset; delay in diagnosis; extension of disease; density of relapses; therapy with cortisone) have been compared between the 14 patients with ultra sixtieth year of age diagnosis (A group) and the 241 patients with a diagnosis made previously (B group). There were no significant differences concerning the symptoms at onset and the delay in diagnosis. In group A a larger prevalence of the male (M/F 3.66 against 1.46) and distal localization (64% against 53%) have been reported. The density of relapse and therapy with cortisone (p < 0.025) prevailed in B group. In conclusion, limited to our experience, the UC in A group is less severe than in B group.

Intestinal permeability assessment before and after ileal pouch-anal anastomosis.

AIM: Intestinal permeability is considered an index of anatomic and functional integrity of the small intestine mucosa. Altered intestinal permeability has been suggested to be a possible cause of pouchitis. Aim of this paper was to assess variations in intestinal permeability during the first year of a pouch reconstruction. METHODS: Intestinal permeability (IP) was investigated in 8 ulcerative colitis patients before and after total proctocolectomy, with ileal pouch-anal anastomosis (IPAA), by means of the cellobiose/mannitol test. To each patient a basal test (before surgery) and 3 more tests during a 1 year follow-up were administered. RESULTS: Individual data were altered despite clinical findings in 9 of 30 IP measured values. An overall pattern of unaffected permeability was however shown and none of our patients, during the first year follow-up, has developed pouchitis. CONCLUSIONS: Six of the 8 investigated patients presented at least 1 altered IP value. A longer follow-up aimed to further investigate patients beyond the first year after IPAA confection as to the occurrence of pouchitis and its possible correlation with a previous permeability alteration of the pouch mucosa is in progress.

Segmental ischemic colitis associated with nonsteroidal antiinflammatory drugs.

We have seen two cases of a segmental ischemic colitis develop during nonsteroidal antiinflammatory drug (NSAID) treatment. No other possible etiologic factors were shown. The short-term clinical course and the follow-up were uneventful. NSAIDs have been reported to cause different lesions in the large bowel, either by worsening preexisting colonic diseases or by inducing a primary pathology. We suggest that ischemia should be considered a possible mechanism of NSAID-associated colitis. Such ischemic colitis, not triggered by severe cardiovascular disease or operation, may be related to NSAIDs more often than currently recognized.

Double-blind comparison of the effectiveness of azathioprine and sulfasalazine in idiopathic proctocolitis. Preliminary report.

A double-blind therapeutic trial of azathioprine in 20 patients with acute proctocolitis was performed over a 3-month period. Azathioprine was compared with sulfasalazine in patients paired and treated in a sequential order. Clinical, laboratory, endoscopic, biopsy, and radiologic data were assessed by semiquantitative criteria. No significant difference in the effect of the drugs was observed. Both azathioprine and sulfasalazine produce significant improvement in clinical symptoms, some laboratory findings (ESR, serum iron), and endoscopic and biopsy findings (P smaller than 0.05). Radiologic improvement was less evident (P smaller than 0.10). On the overall final evaluation of the trial, 14 patients were improved, and 6 remained stationary or worsened (P smaller than 0.10). This short-term trial confirms previous uncontrolled experiences of one of the authors on larger series of patients.

Change in the extent of idiopathic ulcerative proctocolitis.

Two complete colonoscopic examinations, up to the ileocecal valve, were performed in 51 patients with idiopathic ulcerative proctocolitis. The extent of the disease was assessed as prevalent in the endoscopic and histological observations on biopsy tissue. The mean interval between the two endoscopies was 36 months (minimum interval 3 months). In 58.8% of cases, a variation of extent was observed: in 33.3% with an upward diffusion, in 25.5% with a reduction. In a larger group (51 vs 31) of patients observed for a longer period of time (36 vs 17 months), the findings of Niv et al. were confirmed. No correlation between epidemiological and clinical data and changes in the anatomical extent of colitis was shown. Disease extent does not, therefore, appear to contribute to the prognosis, in particular to the more severe attacks and cancer.

[Clinical-therapeutic considerations in the treatment of aspecific abdominal disturbances in patients with ulcerative colitis in remission: preliminary note on therapy with rifaximin]. / Considerazioni clinico-terapeutiche sul trattamento di disturbi addominali aspecifici in pazienti affetti da rettocolite ulcerosa in fase di quiescenza: note preliminari della terapia con Rifaximina.

In this study the efficacy of a topic intestinal antibiotic, Rifaximine, on quiescent ulcerative colitis has been evaluated. Twelve patients, aged 20-45 years, affected by ulcerative colitis, with an endoscopic evidence of remission and abdominal symptoms referable to microflora alteration have been admitted. All patients have been treated with Rifaximine 800 mg p.o. three times a day for 10 consecutive days. Meteorism, abdominal pain, and the stool number have been evaluated at admission and on the 2nd, 4th, 6th, 8th and 10th days of therapy. All symptoms and clinical parameters showed a mean significant early reduction on Rifaximine treatment. Only one patient failed to show a substantial improvement. In no case side effects appeared.

Acute liver disorders in left-sided heart failure.

A case of apparent acute hepatitis developed during a mild attack of left-sided heart failure is reported. No shock or significant systemic hypotension was observed which are usually reported in such patients. The signs of the liver impairment were transient, subsiding with the successful treatment of the heart failure.

Clinical evolution in an outpatient series with indeterminate colitis.

PURPOSE: Diagnosis of indeterminate colitis, which is mainly based on histologic criteria, could represent either an interlocutory or a definite classification within inflammatory bowel diseases. A later evaluation could allow elimination of cases with transient attacks of colitis and the eventual change of diagnosis to that of ulcerative colitis (UC) or Crohn's disease of the colon in some other patients. METHODS: A clinical follow-up study for a mean of 64 months was performed in 37 patients with inflammatory bowel disease with an initial diagnosis of indeterminate colitis. RESULTS: At the end of the follow-up period, 21 patients complained of persistent symptoms, and in 13 of these patients, endoscopic and histologic evolution of colitis was controlled. In four patients with initially a normal endoscopy, the pattern of normality was confirmed also on a histologic basis at the end of the follow-up. In seven of the remaining nine patients with an initial UC-like endoscopic picture, the UC diagnosis was made eventually also on a histologic basis. CONCLUSIONS: A closer monitoring, as with UC patients, could be recommended only in moderate patients with indeterminate colitis, with an initial UC-like endoscopic picture.

Incompletely and completely healed duodenal ulcers' outcome in maintenance treatment: a double blind controlled study.

A six month, double blind, controlled study was performed in 107 asymptomatic duodenal ulcer patients who, after short term cimetidine treatment, showed complete or incomplete endoscopic healing. Patients were stratified according to the type of healing and randomly allocated to cimetidine (200 mg at lunch, 400 mg at bedtime) or placebo. Endoscopic examinations were carried out after six months or when symptoms recurred. Eighty seven patients completed the maintenance trial. Of the 56 patients admitted to the study with complete healing, 30 were placed on cimetidine and 26 on placebo. Of the 31 patients admitted with incomplete healing, 15 were placed on cimetidine, and 16 on placebo. Results showed that, regardless of maintenance treatment, patients with incompletely healed ulcers had a higher ulcer crater recurrence rate, than patients with complete healing (71% vs 34%; p less than 0.005). A significantly higher ulcer crater recurrence was observed in incompletely healed ulcer patients, even when cimetidine or placebo treatment groups were considered separately. Irrespective of the type of healing, ulcer crater recurrence was more frequent in placebo treated patients than in those treated with cimetidine (67% vs 29%; p less than 0.001). We conclude that, in order to prevent a high ulcer recurrence rate, maintenance treatment should start only after the assessment of a complete endoscopic healing of duodenal ulcers.

Outcome of ulcer-associated duodenitis after short-term medical treatment.

The relationship between duodenitis and the outcome of duodenal ulcers was prospectively investigated by evaluating the frequency and extent of bulbar duodenitis before and after short-term medical treatment of the ulcer. Duodenitis appeared to be more frequent and more severe in the bulbar area close to the ulcer and was more widespread in the bulb of patients whose ulcer did not respond to treatment. After medical treatment, duodenitis improved only in the ulcer area and only in patients with complete ulcer healing. While confirming that, in some patients, duodenitis may well be an inflammatory reaction to the presence of the ulcer, data from the present study indicate that, in other patients, duodenitis, throughout the bulb, does not seem to be influenced by the outcome of the ulcer or the treatment. These findings suggest that there are subpopulations of duodenal ulcer patients who differ according to the pattern of bulbar duodenitis.