Cristian Gheorghe

Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.

Aim The Romanian Society of Gastrointestinal Endoscopy developed a multicentre, prospective study to evaluate the frequency and epidemiological features of inflammatory bowel disease (IBD) in an adult population that refers to gastroenterology centres in Romania. Material and methods Eighteen centres with adequate diagnostic and therapeutic facilities uniformly distributed across Romania reported through a proforma the new and old IBD cases between 1 June 2002 and 1 June 2003. The rates of incidence and prevalence of ulcerative colitis (UC) and Crohns disease (CD) have been reported per 100 000 inhabitants. Epidemiological features and disease characteristics were analysed. Results During the study, 407 cases of UC (163 incident cases) and 254 cases of CD (85 incident cases) were identified. The incidence in the referral population was 0.97/100 000 and 0.50/100 000 for UC and CD, respectively, whereas the prevalences was 2.42/100 000 and 1.51/100 000 for UC and CD, respectively. A slight male predominance, wider age distribution and predominant urban residence were the main demographic features of incident cases; smoking and appendectomy/appendicitis were infrequent in UC, while a higher proportion of CD patients were smokers. Lower rates of severe, extensive or complicated IBD were noted as compared with the literature. Conclusion Incidence and prevalence rates of IBD in Romania are low. Predominant male involvement and a wider distribution of incident cases were the main demographic features in our population. IBD in our patients had a more ‘benign’ course as compared with the literature, with lower rates of severe, extensive or complicated disease and a small proportion of patients who need surgery.

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease.

Objectives To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. Methods Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). Results From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10–15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. Conclusion Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(−) profile, and probable diagnosis according with the scoring system for AIH.

Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery

BACKGROUND The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. METHODS A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohns disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. RESULTS The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. CONCLUSIONS A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery.

The prevalence and risk factors of hepatitis B virus infection in an adult population in Romania: a nationwide survey.

Aim The prevalence and risk factors of hepatitis B virus (HBV) infection in the general population in Romania are still largely unknown. Methods A nationwide cross-sectional survey among a Romanian adult population (18–69 years) was conducted during 2006–2008 using a stratified, multistage sampling design. A total of 17 600 individuals were enrolled randomly into the study; the prevalence of chronic HBV infection (HBsAg-positive and anti-HBcAb-positive samples) was assessed on 13 127 individuals (74.6%) and a history of previous HBV infection (anti-HBcAb-positive, but HBsAg-negative samples) was assessed on 12 470 individuals (70.5%). A questionnaire was used to collect information on the sociodemographic characteristics of the participants and the potential risk factors for HBV transmission. Results The overall prevalence rate of HBV chronic infection among all the participants tested was 4.4% (confidence interval: 4.0–4.8%), with significant differences (P=0.0001) between participants from the main geographical regions of residence (Moldavia 4.5%, Muntenia and Dobrogea 5.4%, and Transylvania and Banat 3.1%). The total prevalence of previous HBV infection of all participants was 27.0% (confidence interval: 26.2–27.8%). The proportion of individuals with previous HBV infection, as well as with chronic HBV infection, showed a statistically significant increasing trend with age. The personal history of blood or blood product transfusion, surgical interventions, tattooing, and alcohol consumption greater than 60 g/day were risk factors associated with both anti-HBcAb and HBsAg seropositivity. Conclusion A prevalence rate of 4.4 and 27.0% for HBsAg and anti-HBcAb, respectively, represents a high figure within the European Union and a strong motivation for developing adequate strategies for prevention, active detection, and treatment of HBV infection in Romania.

Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: A comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol

BACKGROUND AND AIMS Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohns disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. METHODS Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. RESULTS In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. CONCLUSIONS RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy

Pegylated interferon‐alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug‐induced Sweets syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweets syndrome in association with pegylated interferon‐alpha therapy.

Predictors of short term treatment outcome in patients with achalasia following endoscopic or surgical therapy

BACKGROUND/AIMS Pneumatic balloon dilation and surgical myotomy are the most effective treatments for achalasia. While there is controversy which method is best, the aim of the current study was to identify predictors of symptom recurrence after endoscopic or surgical therapy. METHODOLOGY Patients undergoing pneumatic balloon dilatation (30mm) or laparoscopic Heller myotomy with Dor fundoplication were included in the study. Analyzed parameters include total symptom score (sum of 0-5 point intensity for dysphagia, regurgitation and chest pain), width and height of esophageal column at 2 and 5 minutes after oral barium ingestion, lower esophageal sphincter (LES) length, resting (LESP) and residual pressure (LESRP) before and 3 months after intervention. Patients with symptoms score <3 at the 3-month follow-up visit were considered asymptomatic. RESULTS Twenty-one patients underwent pneumatic dilation (14) or laparoscopic myotomy (7). Total symptom score improved (p<0.01) from pre- (7.2±2.7) to post-intervention (1.7±2.6). Eleven (85.8%) patients in the endoscopic group vs. 7 (100%) patients in the surgical group were symptom-free 3 months after intervention. Therapies improved LESP (24.4±8.2mmHg pre- vs. 15.4±10.3mmHg post-therapy; p=0.003) and mean LESRP (7.9±4.3mmHg pre- vs. 5.3±6.7mmHg post-therapy; p=0.03). Univariate linear regression analysis identified barium contrast column width >5cm at 2 minutes (p=0.04), LES length <2cm (p=0.003) and LESRP >10mmHg (p=0.02) as predictors for persistent symptoms. CONCLUSIONS While >85% of achalasia patients responded well to 30mm pneumatic balloon dilation, patients with elevated LES pressure, short LES and wide esophagus should be considered as primary surgical candidates.

Modeling the Vortical Structures in Hemodynamics of Small Vessels and Capillaries

The paper is dedicated to the flow modeling in micro‐bifurcations, with application in hemodynamics of vessels and capillaries located in the endothelial wall. In particular, the present study is focused to the experimental and numerical simulations of the vortical patterns in micro‐junctions for Newtonian and Carreau—Yasuda models at Re≪1.

High Resolution Manometry - A Mandatory Examination in the Pre and Postoperative Assessment of Patients with Achalasia

High resolution manometry (HRM) is currently the gold standard for the diagnosis of achalasia and other functional esophageal disorders. All patients accusing dysphagia should be endoscopically evaluated prior to manometric investigations in order to rule out pseudoachalasia. The Chicago HRM classification has led to a subclassification of three manometric types of achalasia that seem to have different results to treatment. None of the actual achalasia treatment options are curative. Type II achalasia patients respond best to all treatment options compared to those with types I and III. Pneumatic dilation (PD) or Heller miotomy (LHM) can be both chosen as initial therapy in type I and II as they have good outcome , while type III achalasia patients respond better to LHM as a first therapeutic option. Peroral endoscopic myotomy (POEM) is a promising new technique but long-term follow-up studies for its safety and efficacy must be performed. This article reviews the current therapeutic options in achalasia and other functional esophageal disorders, based on the differences in safety and efficacy between approaches, highlighting the impact of HRM to predict the outcome but also the role of the techinque in guiding antireflux surgery.

Very Early Onset Pancreatic Adenocarcinoma - Clinical Presentation, Risk Factors and Therapeutic Options

Background: Pancreatic cancer (PC) is usually diagnosed in the 7th decade, but cases diagnosed in younger patients are associated with a greater disease burden, through the potential years of life lost. The aim of our study was to compare the differences in risk factors, clinical presentation and treatment options between patients diagnosed with pancreatic adenocarcinoma below 45 years of age (very early onset pancreatic adenocarcinoma - VEOPC), and those diagnosed over 45 years. Methods: A retrospective study has been conducted by registering in standardized Excel Worksheets all PC cases diagnosed in our tertiary referral center between 01.01.2015 and 31.12.2017. Only patients with a documented diagnosis of pancreatic adenocarcinoma (PDAC) were included in the statistical analysis that has been conducted using the NCSS v9 Statistical Software package. Categorical data have been compared using Chi2 test or Fisher Exact as appropriate, with a statistical significance p value 0.05. Results: There were 296 patients diagnosed with pancreatic solid tumors during the study period, 183 cases with documented histology: 80.87% PDAC, 17.5% neuroendocrine tumors, 2 cases of LMNH and 1 MANEC tumor. In our study group there were 24 patients (16.22%) with VEOPC. Family history of pancreatic neoplasia (33.3% vs 1.03%, p=0.0004) and alcohol consumption (42.86% vs 5.41%, p=0.01) were significantly more prevalent in young patients. Pain, as primary symptom, was reported at higher rates in patients with VEOPC (60% vs 22.94%, p=0.006). Tumors were more frequently located in the head of the pancreas in younger patients (56.52%) and in the body of the pancreas in older patients (52.07%, p=0.02). There was no significant difference in therapy or death rate during follow-up period between the two study groups, although patients diagnosed under 45 years were more frequently subjected to a radical resection (33.3% vs 22.69%). Conclusions: Our study has identified alcohol consumption and family history of pancreatic neoplasia as risk factors for VEOPC. Pain is the primary symptom at diagnosis in young patients with PDAC. In our cohort, therapeutic options do not differ significantly in PDAC patients with age of onset.