Cameron lesions: A still overlooked diagnosis. Case report and systematic review of literature.

Cameron lesions are erosive-ulcerative alterations of gastric mucosa occurring in patients with large hiatal hernia, potentially causing gastrointestinal bleeding and iron deficiency anaemia. Diagnosis may be challenging, and not infrequently erosions are overlooked at endoscopy, so that repeated and unnecessary diagnostic procedures are performed, particularly in those patients with chronic anaemia. We described two peculiar cases of patients with iron deficiency anaemia in whom Cameron lesions were either overlooked or misinterpreted. By reviewing data of 22publications reporting endoscopic and clinical data of 140patients, we noted a large prevalence of females (75%). The most frequent presenting symptoms were anaemia (62%) and overt gastrointestinal bleeding (36%). Noteworthy, as many as 69% of patients underwent one or more previous upper endoscopy before diagnosis of Cameron lesion was achieved. Patients were mainly treated with proton pump inhibitor (PPI) therapy and iron supplementation. Moreover, endoscopic haemostasis was performed in 10% of case, blood transfusion was required in one third of cases, and a similar quote of patients underwent a surgical approach for hiatal hernia repair. The observation that as many as 60% patients were already receiving standard PPI therapy when diagnosis was performed would suggest that either long-term treatment with adequate dose PPI or surgical approach for hiatal hernia repair is required. In conclusion, Cameron lesion is still an overlooked diagnosis in patients with iron deficiency anaemia in whom a 5-9.2% prevalence has been reported.

Segmental colitis associated with diverticula: a rare clinical entity and a new challenge for the gastroenterologist.

BACKGROUND AND AIM: Segmental colitis associated with diverticula (SCAD) has recently drawn a particular attention in the field of rare forms of colitis because of some peculiarities suggesting both its autonomy as a clinical entity and a resemblance with the most relevant forms of inflammatory bowel diseases (IBD). Aim of this review was to report the state of art on this topic. METHODS: Epidemiological, clinical, endoscopic/histological and diagnostic features are described. Moreover, from both the pathogenetic and therapeutic point of view, new relevant information is highlighted regarding the possible role of tumour necrosis factor alpha (TNF-alpha) in mucosal inflammation. RESULTS: SCAD would appear as a rare autonomous clinical entity distinctive of old age, although it is still not well defined. It is likely that prevalence of SCAD could have been underestimated in the past since its main clinical presentation (namely bleeding without pain) is often found in elderly patients with diverticula. Endoscopy and histology could be helpful to discriminate it from infectious diverticulitis. Increasing evidence encourages the concept that SCAD includes pathogenetic and therapeutic aspects peculiar of IBD. This could be relevant for clinical management of SCAD. Indeed, the resolution of a severe, refractory case of SCAD has been recently reported with biological drugs used for IBD therapy. This observation could encourage, in the near future, the use of biological therapy in severe forms of SCAD as an alternative to surgery.

Systematic review: Endoscopic dilatation in Crohn's disease.

BACKGROUND: Endoscopic dilatation for Crohn's disease has been evaluated only in some small and heterogeneous studies. AIM: To evaluate any association between the main clinical variables and endoscopic variables and the efficacy and safety of endoscopic dilatation in Crohn's disease. METHODS: A Medline search regarding pneumatic dilatation in Crohn's disease was performed. Several technical and clinical variables were extracted from each study to build up a descriptive, pool-data analysis. Data on individual patients were extracted from suitable studies to create a simulated population upon which a multivariate statistical analysis was performed. RESULTS: Thirteen studies enrolling 347 Crohn's disease patients were reviewed. Endoscopic dilatation was mainly applied to postsurgical strictures, being technically successful in 86% of the cases. Long-term clinical efficacy was achieved in 58% of the patients. Mean follow-up was as long as 33 months, corresponding to 800 patient years of follow-up. Major complication rate was 2%, being higher than 10% in two series. At multivariate analysis, a stricture length < or = 4 cm was associated with a surgery-free outcome (OR: 4.01; 95% CI: 1.16-13.8; P < 0.028). CONCLUSIONS: Endoscopic dilatation is an effective and safe treatment for short strictures caused by Crohn's disease, impacting substantially on the natural history of these patients.

Tumor necrosis factor alpha in ulcerative colitis and diverticular disease associated colitis.

Conventional treatment of moderate-severe ulcerative colitis (UC) has resulted in only a limited therapeutic benefit. Advancing knowledge of UC pathogenesis and recent advances in biotechnology have led to the development of biological agents that selectively target individual inflammatory pathways. In particular, the role of tumor necrosis factor alpha (TNF-alpha) in UC pathogenesis has been clarified by serological and immunohistochemical studies in humans and by experimental models. Clinical efficacy of anti-TNF-alpha therapy with infliximab has been assessed in two large controlled trials, showing a good compromise between therapeutic gain and safety. The aim of this review is to provide an insight into the role of TNF-alpha and anti-TNF-alpha therapy in patients with UC and diverticular disease associated colitis.

Tumour necrosis factor alpha down-regulation parallels inflammatory regression in ulcerative colitis patients treated with infliximab.

BACKGROUND: Treatment with the anti-tumour necrosis factor alpha monoclonal antibody infliximab has been shown to be effective in moderate-to-severe ulcerative colitis. However, its effect on the mucosal histopathological abnormalities of this disease is largely unknown. This study aimed to assess the immunohistological effect of infliximab in ulcerative colitis. METHODS: Nine patients with moderate-to-severe ulcerative colitis received infliximab (5mg/kg) at weeks 0, 2 and 6, respectively. Colonic biopsies were collected before therapy and at week 10, when the Mayo score (including the endoscopic subscore) was also assessed. Severity of inflammation was evaluated by histologic score and histomorphometry. Immunohistochemical staining with antibody against tumour necrosis factor alpha was performed on all biopsies and expressed as percentage of positive stromal cells/1000 counted (tumour necrosis factor alpha score). RESULTS: A profound down-regulation of mucosal tumour necrosis factor alpha occurred in all the six patients who achieved a clinical response, but not in the three who did not respond. Median tumour necrosis factor alpha score dropped from 44.8 (range 35-58.3) to 12.8 (range 5.3-15.3) in the responders (p=0.03), whilst it remained unchanged in the non-responders. Such effect was related with a dramatic regression of the median histologic score, which dropped from 2.7 (range 2-3) to 0.5 (range 0.0-1.5) in responder patients (p=0.002). This was related to a virtual disappearance of neutrophils in responders (r=0.72; p=0.002; Spearman's test), but not in those who did not improve. Tumour necrosis factor alpha score appeared to be correlated with the histologic, endoscopic and clinical activity. CONCLUSIONS: A profound tumour necrosis factor alpha down-regulation appears to be strictly associated with a dramatic regression of the inflammation in patients with moderate-to-severe ulcerative colitis treated with infliximab. Such immunohistochemical effect seems to be critical for a clinical and endoscopic response to therapy.

Epithelial cell proliferation of the colonic mucosa in diverticular disease: a case-control study.

BACKGROUND: A higher risk of both advanced adenoma and carcinoma occurs in the sigmoid colon of patients with diverticular disease, for which bacterial carcinogens have been claimed to play a role. AIM: To assess epithelial cell proliferation in colonic mucosa of diverticular disease patients before and after rifaximin treatment. METHODS: Twelve consecutive patients with a new endoscopic diagnosis of left-sided diverticular disease and 12 matched controls were enrolled. Epithelial cell proliferation in the sigmoid mucosa was assessed by using proliferating cell nuclear antigen. The proliferating cell nuclear antigen index of the whole crypt and of the upper third was separately evaluated before and after 10-day rifaximin (400 mg b.d.) therapy. RESULTS: Proliferating cell nuclear antigen index in the upper third of the crypt was significantly higher in the diverticular patients (median: 25, range: 14-32) as compared with controls (median: 15, range: 5-20) (P = 0.038), and it was not reverted by rifaximin therapy. No difference of the proliferating cell nuclear antigen index of the whole crypt was detected between cases (median: 27, range: 23-44) and controls (median: 25, range: 18-42) (P = 0.6). CONCLUSIONS: Our data showed an upward shifting of cellular proliferation in the sigmoid mucosa of patients with diverticular disease. Because of rifaximin failure in reversing this alteration, factors other than the bacterial load should probably be investigated.

The prolongation of triple therapy for Helicobacter pylori does not allow reaching therapeutic outcome of sequential scheme: a prospective, randomised study.

BACKGROUND AND AIM: One-week triple therapy for Helicobacter pylori revealed, during these last few years, a decrease in the eradication rate, so that the prolongation of its duration has been proposed. A sequential scheme recently showed very satisfactory results. We performed a prospective randomised study with the aim of either evaluating whether the triple therapy prolongation may improve its effectiveness and comparing its outcome with that of sequential regimen. PATIENTS AND METHODS: Three hundred and forty-two H. pylori positive patients completed the study. They were randomised to receive one of the following treatments: (i) a 7-day triple therapy comprising of rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and amoxycillin (1 g, b.i.d.); (ii) a 10-day triple therapy comprising the same scheme; (iii) a 10-day sequential regimen comprising of rabeprazole (20 mg, b.i.d.) plus amoxycillin (1 g, b.i.d.) for 5 days followed by rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and tinidazole (500 mg, b.i.d.) for the next 5 days. Therapeutic results were expressed using both intention-to-treat and per protocol analyses with 95% confidence intervals. A model of multivariate logistic regression analysis was performed using therapeutic outcome as a dependent variable and including endoscopic finding, smoking habit, age and sex as candidates for the model. RESULTS: Sequential regimen showed a significant gain in the eradication rate as compared to the 7-day (P < 0.0001) and the 10-day (P < 0.01) triple therapies, respectively. Overall eradication was lower in smokers than in non-smokers, but the difference remained significant only in the 7-day triple therapy (P < 0.01). Additionally, the overall eradication was higher in peptic ulcer than dyspepsia (P < 0.01), even if this difference was significant only for both triple therapies. CONCLUSIONS: Seven-day triple therapy achieves disappointing eradication rates in dyspeptics and smokers. Prolonging triple therapy to 10 days does not significantly improve the eradication rate. The novel 10-day sequential regimen is more effective and equally tolerated than the 10-day triple therapy.

Sequential treatment for Helicobacter pylori does not share the risk factors of triple therapy failure.

BACKGROUND: Predicting factors for the outcome of conventional Helicobacter pylori triple therapy have been identified. Of these, the presence of the CagA gene is a strong predictor of successful treatment. Our preliminary data show that this factor becomes irrelevant when sequential therapy is used. AIM: To identify predicting factors for the outcome of H. pylori eradication using two therapeutic schemes (triple and sequential) of equal duration (10 days). METHODS: Ninety-six patients with H. pylori infection were randomly assigned to receive one of the following therapeutic schemes: group A: rabeprazole (20 mg b.d.) plus amoxicillin (1 g b.d.) for 5 days, followed by rabeprazole (20 mg b.d.) plus tinidazole (500 mg b.d.) and clarithromycin (500 mg b.d.) for a further 5 days; group B: rabeprazole (20 mg b.d.) plus amoxicillin (1 g b.d.) and clarithromycin (500 mg b.d.) for 10 days. Age, sex, smoking, endoscopic and histological findings, and CagA and VacA status were considered as candidates for a model of multivariate analysis which used therapeutic outcome as the dependent variable. CagA and VacA status were assessed by polymerase chain reaction on DNA isolated from gastric antral specimens. RESULTS: The sequential scheme was significantly more effective than prolonged triple therapy (P < 0.05). Smoking (P < 0.001) and the absence of the CagA gene (P < 0.05) were significantly associated with the failure of triple therapy, but the effectiveness of sequential treatment was not predicted by these factors. CONCLUSION: Our data suggest that sequential therapy is not affected by bacterial and host factors which have, until now, predicted the outcome of conventional eradication treatments.

A third-line levofloxacin-based rescue therapy for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori infection persists in a considerable proportion of patients after both first- and second-line current treatments. A standard therapy for re-treatment in such refractory patients is still lacking. This study aimed to evaluate the efficacy of a levofloxacin-amoxycillin combination in patients who previously failed two or more therapeutic attempts. PATIENTS AND METHODS: Consecutive patients with persistent Helicobacter pylori infection were enrolled. Bacterial infection was assessed by rapid urease test and histology on gastric biopsies at endoscopy. Patients were assigned to receive a 10-day triple therapy, comprising rabeprazole 20 mg b.d., levofloxacin 250 mg b.d., and amoxycillin 1 g b.d. Four to 6 weeks after therapy, Helicobacter pylori eradication was assessed by a further endoscopy or 13C urea breath test. RESULTS: Overall, 36 patients were enrolled, but two patients were lost to follow-up. Helicobacter pylori was successfully cured in 30 patients, giving an 83.3% (95% CI=71.2-95.5) and 88.2% (95% CI=77.4-99) eradication rate at intention-to-treat and per protocol analysis, respectively. Compliance was good in all but two patients, who discontinued the treatment at 8 and 6 days, respectively, on account of glossitis. No major side-effects were reported, whilst 7 (20.1%) patients complained of mild side-effects. CONCLUSIONS: This study demonstrates that a 10-day levofloxacin-amoxycillin triple therapy is a safe and successful third-line therapeutic approach for Helicobacter pylori eradication.

Helicobacter pylori strains and histologically-related lesions affect the outcome of triple eradication therapy: a study from southern Italy.

BACKGROUND: Certain evidence suggests that Helicobacter pylori strains expressing genes for cytotoxin production show a higher sensitivity than non-cytotoxic organisms to eradication treatment. No data are available on the involvement of bacterium-related lesions in different therapeutic outcomes. AIMS: (i) To investigate whether differences in eradication rates may be related to the different expression of virulent strains (cagA, vacA, iceA) in patients undergoing proton pump inhibitor-based triple therapy, and (ii) to evaluate whether therapeutic outcome may be affected by bacterium-induced gastric lesions. METHODS: One hundred and ten H. pylori-positive subjects were enrolled. H. pylori was genotyped by polymerase chain reaction. Treatment consisted of lansoprazole-amoxicillin-clarithromycin, twice daily for 1 week. Eradication was checked by urea breath test. RESULTS: The eradication rate was 70%, and the absence of cagA was associated with unsuccessful treatment. No difference between the groups with successful and unsuccessful eradication was found with regard to vacA and iceA. Lympho-epithelial lesions and fibrosis were associated with unsuccessful treatment. CONCLUSIONS: The present data confirm the importance of cagA (but not vacA and iceA) as a predictor of successful eradication. When fibrosis and lympho-epithelial lesions are present, therapy appears to be less effective. Therefore, these histological features may be involved in an unsuccessful therapeutic outcome.

Second harmonic imaging improves trans-abdominal ultrasound detection of biliary sludge in 'idiopathic' pancreatitis.

BACKGROUND: Recently, biliary sludge has been strongly correlated with 'idiopathic pancreatitis'. It is often diagnosed by trans-abdominal ultrasonography, despite the low sensitivity of this investigation. New scanners, using second harmonic imaging, may improve the quality of the echographic picture. AIM: To verify the impact of this methodology on the detection of biliary sludge in patients with 'idiopathic' pancreatitis. METHODS: Fifty patients with 'idiopathic' pancreatitis observed over a 18-month period entered the study. Exclusion criteria were gall-bladder stones, polyps, clinical conditions related to biliary sludge development and haemolytic disorders. Patients were assessed blind by two operators using either conventional ultrasonography or second harmonic imaging. The parameters of diagnostic quality of both examinations were evaluated using, as the gold standard, microscopic examination of the gall-bladder content collected at endoscopy after cholecystokinin infusion. RESULTS: An improvement in sensitivity, specificity, efficiency and negative predictive value was obtained by second harmonic imaging compared with conventional ultrasonography. CONCLUSIONS: Second harmonic imaging, in our experience, is a reliable non-invasive tool for the diagnosis and follow-up of biliary sludge in the course of 'idiopathic' pancreatitis.

Endoscopic ultrasound localization of a solitary insulinoma of pancreatic tail misdiagnosed as epilepsy: case report.

A 17-year-old female patient with features of epilepsy was treated with valproic acid. Two years later, hypoglycemia and hyperinsulinemia appeared. Transabdominal ultrasonography, spiral computed tomography, and indium-111 Octreoscan were performed without positive results. Endoscopic ultrasonography identified an oval tumor in the pancreatic tail with a color Doppler hypervascular pattern. Surgical enucleation decreased levels of insulin and C-peptide within 20 min, and the patient became free of symptoms and medications.

Diverticular disease as a risk factor for sigmoid colon adenomas.

BACKGROUND: Diverticular disease and colorectal neoplasia share similar epidemiological features and risk factors. AIM: To evaluate a possible association between diverticular disease and both adenomas and colorectal cancer in patients undergoing total colonoscopy. METHODS: Overall, 630 consecutive patients were recruited from the 3 Units. Inclusion criteria were age over 45 years and the performance of total colonoscopy. Demographic and clinical data were recorded. Adenomas were defined as advanced when their size was >1 cm in diameter, and/or the percentage of the villous component was >30% and/or high grade dysplasia was present. RESULTS: At endoscopy, 291 (47%) out of 630 patients presented evidence of diverticular disease. Adenomas were found in 92 (31.9%) patients with diverticular disease and in 98 (28.9%) patients without [p=ns]. The prevalence of adenomas located in the sigmoid colon was significantly higher in patients with diverticula than in controls (64.1% vs 41.8%; p<0.05). Similarly, the detection of advanced adenomas located in the sigmoid colon was more likely in patients with diverticula than in controls (59.6% vs 37.5%; p<0.05). Colorectal cancer prevalence was similar in patients with and without diverticula (8.3% vs 7.1%; p=ns), and no difference was detected regarding site, between the two groups. CONCLUSIONS: Patients with diverticular disease have a higher risk of harbouring adenomas and advanced adenomas in the sigmoid colon. This observation should be taken into account in screening and surveillance programmes for colorectal neoplasia.

Relationship between antral lymphocyte density and basal gastrin levels in patients with Helicobacter pylori infection.

BACKGROUND: The mechanism by which Helicobacter pylori causes hypergastrinaemia is not completely understood. AIM: To evaluate whether antral lymphocyte density could play a role in this alteration. METHODS: A total of 12 patients with active duodenal ulcer and 10 with non-ulcer dyspepsia were enrolled upon detection of Helicobacter pylori infection at endoscopy Enrolled as controls were 7 matched dyspeptic patients without Helicobacter pylori infection. Biopsy specimens were collected for Helicobacter pylori and histological assessments, and for antral lymphocyte density assessment by a histomorphometric method. A blood sample was obtained from each patient to determine basal gastrin levels. All patients were controlled by a further endoscopy 4 weeks after the end of Helicobacter pylori treatment. RESULTS: Antral lymphocyte density (5,464 +/- 1,328 and 5,635 +/- 1,186 vs 2,267 +/- 557 lymphocytes/mm2; p<0.001 and p<0.001, respectively) and gastrin levels (66.7 +/- 14.1 and 60.4 +/- 21.7 vs 40.7 +/- 7.8 pg/dl; p=0.004 and p=0.02, respectively) were higher in duodenal ulcer and non-ulcer dyspepsia patients than in controls, while no significant differences emerged between duodenal ulcer and non-ulcer dyspepsia patients. There was a significant direct correlation between antral lymphocyte density and gastrin levels both in duodenal ulcer (r=0.77; p=0.003) and in non-ulcer dyspepsia (r=0.75; p=0.03) patients, while no correlation was found in controls [r=0.12; p=0.8). After treatment, this correlation persisted in 10 eradication failure patients (r=0.68; p=0.027), but disappeared in those successfully cured. CONCLUSIONS: These data suggest that lymphocyte density in the antral mucosa could play a role in the impaired gastrin production occurring in patients with Helicobacter pylori infection.

Measurement variability and diagnostic sensitivity of gastric mucosal inflammatory cell morphometry.

OBJECTIVE: To assess the variability and sensitivity of morphometric measures of gastric mucosal lymphocyte and plasma cells to determine a systematic procedure for evaluating the density of these mononuclear inflammatory cells (MNC). STUDY DESIGN: Gastric biopsies of antrum (n = 3), incisura angularis (n = 2) and corpus (n = 3) from two controls and three patients with Helicobacter pylori-related gastritis (antral, diffuse or multifocal gastritis) were considered. In each biopsy, three fields from each of three sections were selected. In each field, stromal area was obtained by subtracting gland area (GA) from total area, and MNC were counted. Results were expressed as MNC/total mm2 and MNC/stromal mm2. Correlations with GA, coefficients of variation (CV), discriminant power analysis and analysis of variance were performed. RESULTS: Correlations always existed between GA and MNC/total mm2 and rarely between GA and MNC/stromal mm2. CV of MNC/stromal mm2 were lower (18%) than those of MNC/total mm2 (30%). High sensitivity (95.4%) and specificity (95.8%) were found for MNC/stromal mm2 but not for MNC/total mm2. Differences in MNC/stromal mm2 existed in all subjects (P < .0001). Highly significant differences in MNC/stromal mm2 were also found between normal and inflammatory states, gastric sites and sections. CONCLUSION: In contrast to MNC/total mm2, MNC/stromal mm2 is an unbiased estimate of MNC density. The following sampling procedure is proposed: two biopsies from each gastric site, two sections from each biopsy and two microscopic fields from each section.