Human cytomegalovirus induced pseudotumor of upper gastrointestinal tract mucosa: effects of long-term chronic disease?

Human cytomegalovirus-induced lesions resembling malignancies have been described in the gastrointestinal tract and include ulcerated or exophytic large masses. The aim of this study was to review the cases registered in the databases of two academic hospitals and formulate a hypothesis concerning the pathogenic mechanisms responsible for cytomegalovirus-induced pseudotumor development. All the diagnoses of human cytomegalovirus infections of the upper gastrointestinal tract recorded from 1991 to 2013 were reviewed. Cases of mucosal alterations misdiagnosed endoscopically as malignancies were selected. Large ulcers occurring in the stomach (three cases) and an irregular exophytic mass at the gastro-jejunal anastomosis were misdiagnosed endoscopically as malignancies (4 cases out of 53). Histologically, all lesions reflected hyperplastic mucosal changes with a prevalence of epithelial and stroma infected cells, without signs of cell atypia. The hypothesis presented is that the development of human cytomegalovirus-induced pseudotumors may be the morphological expression of chronic mucosa damage underlying long-term infection.

Functional magnetic resonance imaging study reveals differences in the habituation to psychological stress in patients with Crohn's disease versus healthy controls.

In patients with Crohn's disease (CD) stress is believed to increase the incidence of disease relapse. The brain processes stressful stimuli and triggers the stress-evoked responses. Habituation to stress is an adaptive process that allows minimizing these responses. We hypothesized inadequate habituation to stress in CD patients. The aim of this study was to compare the neural habituation between CD patients and controls. Twenty CD patients and eighteen controls underwent a functional magnetic resonance imaging while performing two repeated runs of a stress-evoking task. The task elicited different neural activity between the groups across runs in (1) amygdala, hippocampus, (2) insula, putamen (3) cerebellar regions, suggesting altered habituation to stress in patients. These structures regulate the neuroendocrine and autonomic stress-evoked responses that control the proinflammatory responses. The inadequate habituation to stress that we found in patients could play a role in the relationship between stress and inflammatory exacerbations in CD.

Cytomegalovirus infection of the upper gastrointestinal tract: a clinical and pathological study of 30 cases.

OBJECTIVE: The study reviews the endoscopic and histological features of human cytomegalovirus (HCMV) infections of the upper gastrointestinal (UGI) tract. MATERIALS AND METHODS: Clinical histories, endoscopic findings and bioptic specimens of 30 cases of HCMV infection of the UGI tract, diagnosed in a University Hospital in a 10-year period, were reviewed. In all cases, viral inclusion bodies were detected in routine histopathological sections and the diagnosis was confirmed with immunohistochemistry. RESULTS: Six patients were HIV+, whereas four had received organ transplantations, one was affected by common variable immunodeficiency and four had a recent history of malignancy. No other pathologic condition was evidenced in the remaining 15 cases. Mucosal alterations were endoscopically observed in the stomach (19 cases), esophagus (9), cardias (6) and duodenum (1), and multiple organs being synchronously affected in five patients (3 HIV+, 2 with history of malignancy). The antropyloric area was the most frequently affected site. Single ulcers were detected in 11 cases and multiple ulcers in 8, whereas mucosal thickenings (in the form of localized thickenings, polyps or rugal hypertrophy) were present in 13 patients. Thickenings of the mucosa were detected only in the stomach. At histology, necrotic material and granulation tissue were associated with moderate or marked lympho-plasmacytic infiltrate and foveolar hyperplasia in ulcerative lesions, whereas lesions labeled as mucosal thickenings showed mild or moderate chronic inflammatory infiltrate and foveolar hyperplasia. CONCLUSIONS: Endoscopic manifestations of UGI tract involvement in HCMV infection are not specific, varying from erythematous mucosa to ulcers to mucosal thickenings.

Ultrasonographic and clinical assessment of peripheral enthesitis and arthritis in an Italian cohort of inflammatory bowel disease patients.

AIMS: To evaluate the prevalence of clinical and ultrasonographic musculoskeletal involvement in Italian patients with inflammatory bowel disease (IBD). METHODS: In this cross-sectional multicenter study, 148 consecutive patients with IBD were evaluated by a gastroenterologist and a rheumatologist. All patients underwent a B-mode and power Doppler ultrasonographic examination of 6 pairs of entheses and of knee and ankle joints. RESULTS: A positive history for at least one musculoskeletal manifestation was reported by 40.5% of patients, more frequently in ulcerative colitis (UC) (p = 0.033). Inflammatory back pain was reported by 13.5% of patients, and a past history of peripheral arthritis by 14.9%, entheseal inflammation by 14.2% and dactylitis by 2.7%. At clinical examination, arthritis was observed in 19.6% of patients and enthesitis in 33%. Oligoarthritis and enthesitis at clinical examination were more frequently observed in UC than in Crohn disease (CD). 37.8% of total IBD patients fulfilled ASAS classification criteria for axial and/or peripheral spondyloarthritis, 8.1% ASAS classification criteria for axial spondyloarthritis, and 29.7% ASAS classification criteria for peripheral spondyloarthritis. With ultrasonographic examination, signs of entheseal involvement were observed in 87.8% of patients, while at power Doppler, ≥1 abnormality was observed in 27.1%. ASAS+ patients compared to those ASAS- had a significantly higher frequency at ultrasonography of acute entheseal abnormalities, power Doppler entheseal positivity and joint involvement. These abnormalities at ultrasonography were also observed in 34%, 13% and 12% of ASAS- patients. CONCLUSIONS: Musculoskeletal manifestations occur frequently in patients with IBD. Ultrasonographic entheseal and joint involvement were also observed in asymptomatic patients.

Activities related to inflammatory bowel disease management during and after the coronavirus disease 2019 lockdown in Italy: How to maintain standards of care.

BACKGROUND AND AIMS: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities. METHODS: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase. RESULTS: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future. CONCLUSION: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.

Myeloperoxidase-positive cell infiltration in colorectal carcinogenesis as indicator of colorectal cancer risk.

Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in x100 optical fields under a light microscope. Patients with colorectal tumors had a higher mean number of MPO-positive cells in normal mucosa than controls (mean +/- SD, 2.7 +/- 2.0 versus 1.4 +/- 1.4; P = 0.017). MPO-positive cell number was tightly linked to dysplasia in aberrant crypt foci and adenomas, and it was higher in carcinomas microsatellite unstable than those microsatellite stable (21.6 +/- 15.5 versus 11.9 +/- 8.0; P < 0.01). MPO immunohistochemistry is a simple and reliable technique for the quantification of inflammation in colorectal mucosa., and it may be a potential marker of colorectal cancer risk. Microsatellite instability seems to influence host immune responses to colorectal carcinoma. These observations strongly support a key role of inflammation in colorectal carcinogenesis.

Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease.

Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6-84), surgery for IBD (OR 15.1, 95% CI 3.1-73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4-110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0-0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.

Efficacy of a Novel Granulocyte Monocyte Apheresis Adsorber Device in the Treatment of Inflammatory Bowel Diseases: A Pilot Study.

Granulocyte monocyte apheresis (GMA) is a non-pharmacological treatment for inflammatory bowel disease. In our study, we tested a novel GMA adsorber device in terms of clinical efficacy and safety in patients' non-response to pharmacological therapy. Secondary outcomes were the evaluation of adsorber's technical performance, the reduction of inflammatory markers and the improvement of patients' life quality. The prospective study included 18 patients enrolled from 2011 to 2012 with a monitoring of 48 weeks. All patients with Crohn's disease achieved a clinical remission after GMA treatments, sustained until the end of follow up, while 80% of ulcerative colitis patients obtained a clinical benefit, maintained after 48 weeks of monitoring. Leukocytes, neutrophils, monocytes and platelets, compared to erythrocytes and lymphocytes, were effectively removed from peripheral blood. There was no statistically significant result about serological markers of inflammation. A consistent improvement of the patients' quality of life was observed up to the end of follow up. No significant side-effects were recorded. Our study underlines the efficacy and the safety of this novel GMA adsorber device; a prospective randomized clinical trial with adequate sample size should be performed.

Absence of change in the gray matter volume of patients with ulcerative colitis in remission: a voxel based morphometry study.

BACKGROUND: Recent neuroimaging studies have investigated the brain involvement in patients with Crohn's disease (CD) and Ulcerative Colitis (UC). Functional studies found abnormalities in cognitive and emotional functions in CD and UC, while a voxel based morphometry (VBM) study found morphological changes in CD. We conducted a VBM study to compare the gray matter (GM) volume of UC patients and controls. METHODS: Eighteen UC patients in remission and eighteen healthy controls underwent structural MRI. VBM is a fully automated technique allowing identification of regional differences in the amount of GM, which enables an objective analysis of the whole brain. VBM was used for comparisons between patients and controls. RESULTS: UC patients were all in remission and had a mild clinical course. There were no differences between patients and controls in GM volume. CONCLUSION: The brain morphology of patients with UC in remission is similar to controls. The lack of GM abnormalities in UC patients might reflect the mild clinical course of the inflammatory bowel disorder. Further research involving patients with different degrees of disease severity or during flares could shed more light on potential brain structural changes in UC.

Proposal of a new clinical index predictive of endoscopic severity in ulcerative colitis.

Assessment of disease activity by clinical parameters in ulcerative colitis is still controversial. Different clinical indexes have been proposed. Colonoscopy provides detailed information on mucosal damage. The aim of this study was to identify, among 21 clinical and laboratory parameters, which were predictive of endoscopic activity. We included 137 consecutive patients with ulcerative colitis who underwent colonoscopy, clinical examination, and blood tests within 4 weeks. Endoscopic severity was recorded using a simple score (range, 0-30). The multiple stepwise regression coefficient of each significant variable predictive of mucosal damage was used to develop a new activity index predictive of endoscopic appearance (Endoscopic-Clinical Correlation Index; ECCI). We tested the ability of our score to discriminate patients with severe endoscopic disease, calculating the area under the receiver operator characteristic curve, and we compared it to activity indexes proposed by other authors. Endoscopic severity was significantly influenced by four parameters: bloody stool, nocturnal bowel movements, body temperature >37.5 degrees C, and serum albumin. The new scoring system was calculated as ECCI = {[serum albumin x (-26)] + (bloody stool x 17) + (nocturnal bowel movements x 16) + [fever (0 or 1) x 39]} + 107. The ECCI accurately identified patients with severe endoscopic disease in our sample (sensitivity = 81%, specificity = 95%). In conclusion, the ECCI should be useful in clinical practice because it is simple and strongly related to endoscopic activity.