1,2Elena-Gabriela Buleteanu, 3Alina Tantau, 4Simona Valean, 3Lorena Ciumarnean, 5Marcel Tantau 1 Department of Internal Medicine “Regina Maria” Cluj-Napoca, Romania; 2”Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Department of Gastroenterology of “CFR” Hospital Cluj-Napoca, ”Iuliu Hatieganu” University of Medicine and Pharmacy, Romania; 4Department of Gastroenterology County Hospital Cluj-Napoca, Romania; 5Institute of Gastroenterology and Hepatology “O. Fodor” Cluj-Napoca, Romania;

Background and aims. Liver cancer is one of the most common cause of deaths from cancer. Hepatocellular carcinoma (HCC) was reported at a frequency of 7% of patients with autoimmune hepatitis (AIH) - related cirrhosis in 1988. We aimed to provide a systematic literature review on the frequency of HCC in patients with AIH, after the discovery of hepatitis C virus (HCV), in order to avoid any possible confounding etiology. Methods. A literature search of the PubMed database between 1989-2016 was performed, using the relevant keywords “hepatocellular carcinoma” and “autoimmune hepatitis”. We followed the PRISMA statement guidelines during the preparation of this review. Results. Eleven studies (n=8,460 patients with AIH) were retained for the final analysis. HCC was diagnosed in 0-12.3% of the AIH patients included in these studies. The overall occurrence of HCC in patients with AIH was estimated in two studies, at 5.1% and 6.2%, respectively. In patients with AIH and cirrhosis, the percentage of HCC varied between 0.2%-12.3%. The proportion of HCC in patients with AIH without cirrhosis was estimated at 1.03%. The percentage of cirrhosis in AIH patients varied from 18.7% to 83.3% in Japan, and from 12% to 50.2% in the other areas. The mean follow-up of the patients with AIH was of 10 years. Conclusions. The development of HCC in patients with AIH appeared to be similar before and after the discovery of HCV, and it was mainly associated to cirrhosis. The number of patients developing cirrhosis in relation with AIH was impressive. The long evolution of AIH to cirrhosis and, eventually, to HCC, has been be suggested.

Cancer has emerged as the leading cause of death in human populations, according to recent estimations. Epidemiological studies emphasized the role of life style and of environmental factors in promoting the risk for digestive cancers. The contribution of alcohol was highly suspected. Even for digestive cancers with dominant infection etiology, like liver cancer and gastric cancer, the contribution of alcohol should be assessed. At population level there is therefore a need to compare trends in epidemiological data of gastrointestinal cancers and data on alcohol consumption, in order to extrapolate any causative relationship. The purpose of this review was to analyze the time trend of digestive cancers in Romania, in terms of mortality rates (between 1955-2012), and incidence rates (between 2008-2012), in males and females, and to analyze the alcohol consumption data, aiming to find out if there is any association.

Management of patients undergoing endoscopy and under treatment with the newer direct oral anticoagulants (DOACs) is a common and a complex clinical issue that gastroenterologists have to face more and more often these days. The increasing use of DOACs in patients requiring both short- and long-term anticoagulation is mostly due to the advantages these agents offer, among which the lack of monitoring requirements and the reduced need of dose adjustments are perhaps the most important ones. Managing these patients in the peri-endoscopic period implies balancing the risk for thrombosis that a certain patient carries and the bleeding risk associated with the endoscopic procedure itself. The Romanian Society of Gastroenterology and Hepatology decided to create a consensus paper to serve to practitioners and teachers. After reviewing the available published data and existing recommendations, a Delphi consensus process was carried out involving the leaders of opinion in this field. After reaching expert consensus, we provide herein guidance for a practical approach of DOACs therapy management in patients with endoscopic interventions.

BACKGROUND AND AIMS:Cancer has emerged as the leading cause of death in human populations. The contribution of alcohol has been highly suspected. The purpose of this paper was to analyze the time trend of digestive cancers in Romania, in terms of mortality rates (1955-2012), and incidence rates (2008-2012), and the alcohol consumption data (1961-2010), aiming to find out if there is any association. METHODS:The data on six more common digestive cancers mortality rates (1955-2012) and incidence rates (2008-2012) were obtained from the historical and recent country statistics and publications of International Agency for Research on Cancer (IARC)/World Health Organisation (WHO), as age-standardized rate expressed per 100,000 population (ASRw). Data on alcohol consumption were obtained from the statistics and publications of WHO and United European Gastroenterology (UEG), as liters of pure alcohol/year. RESULTS:Between 1955-2012, the ASRw of mortality registered an increase of the cancers of the esophagus in M (from 2.03 to 3.90), and of colorectal cancer in both sexes (from 4.65 to 18.20 in M, and from 4.57 to 9.70 in F). Between 1980-2012, an increasing trend of mortality was registered, in both sexes, for the cancers of the pancreas (from 5.50 to 9.30 in M and from 2.92 to 5.10 in F) and liver (from 1.77 to 11.00, in M, and from 0.83 to 4.20 in F). In terms of incidence, between 2008-20012, an increasing trend of ASRw was registered for the cancers of the esophagus in M (from 3.90 to 4.30), gastric cancer in M (from 15.90 to 16.30), colorectal cancer in both sexes (from 27.60 to 34.50 in M and from 19.00 to 20.20 in F), pancreatic cancer in F (form 5.20 to 5.90), and liver cancer in M (from 8.10 to 9.20). Alcohol consumption per capita (liters pure alcohol/year) increased in the same period, from an average of 5 in 1961, to 12.8 in 2003-2005, and to 14.4 in 2008-2010. CONCLUSIONS:Given the parallel increase of some digestive cancers and alcohol consumption registered in our area, alcohol could represent more than a coincidence.

Aims: The purpose of this study was to analyze the diagnostic yield and accuracy of the ultrasound (US) guided core biopsy in a population of patients with osteolytic metastasis. Materials and methods: We performed a retrospective analysis of 16 consecutive cases of US-guided core biopsies of osteolytic lesions performed in our Ultrasound Unit, from January 2006 to May 2017. We used 18G or 16G Tru-cut needles coupled with automated biopsy guns. We procured a maximum number of two tissue specimens per patient. Results: We obtained a diagnostic yield and accuracy of 93.75% (15 of 16 patients) for US-guided core biopsy of osteolytic metastasis. Most of our cases were metastasis of adenocarcinomas (8 patients), squamous cell carcinomas (3 patients) followed by multiple myelomas (2 patients). Other pathologic lesions recorded were undifferentiated carcinoma (1 patient) and mesenchimal undifferentiated tumor (1 patient). The pathologic result was inconclusive in one patient. Conclusions: Our study supports the important diagnostic role of US-guided core biopsy for osteolytic bone metastasis. Two US-guided passages may be sufficient to procure a diagnostic tissue samples from osteolytic bone metastasis, if their length is at least 10 mm.

Congenital extrahepatic portosystemic shunt (Abernethy malformation) is a rare condition characterized by developmental abnormalities of the portal venous system resulting in the diversion of the portal blood from the liver to the systemic venous system through a complete or partial shunt of the portomesenteric blood. We report the case of an 18 year-old female examined for abdominal pain, presenting cholestasis syndrome and an elevated serum aspartate aminotransferase level. Liver ultrasound examination revealed the absence of the portal vein with a complete extrahepatic shunt of the portal blood, multiple focal liver lesions, and multiple associated vascular anomalies. A surgical portosystemic shunt and a secondary portosystemic shunt due to portal vein thrombosis were excluded, enabling the diagnosis of a congenital portosystemic shunt. A complex investigation also discovered bone anomalies, and the liver biopsy of the dominant focal lesion revealed adenoma. On a short-term follow-up under hepatoprotective medication, the biochemical parameters improved mildly; however, the size of the main focal lesion increased. Congenital absence of the portal vein often remains an incidental diagnosis. In experienced hands, ultrasonography can diagnose it, but a comprehensive thoraco-abdominal evaluation is compulsory, considering the many potential associated anomalies. In these patients, development of adenomatous liver lesions secondary to Abernethy type Ib malformation represents an indication for liver transplantation.

Mediastinal masses are usually assessed by computer tomography (CT) and magnetic resonance imaging (MRI). Transthoracic ultrasonography (TUS) can also provide useful information concerning prevascular and posterior mediastinal masses abutting the thoracic wall, but is underused for mediastinal pathology. Moreover, it provides a valuable and safe method for guiding interventional procedures in those areas, even in cases when other approaches are difficult or impossible. Considering TUS a very useful imagistic method for diagnosing mediastinal masses, we present a pictorial essay of various mediastinal diseases which can be assessed by this method.

Adrenal gland ultrasonography is one of the corner stones of the abdominal ultrasonography examination for many medical specialties. The adrenal areas can be easily overlooked though adrenal gland pathology is diverse. We present the normal aspects and various transabdominal ultrasonography findings of the adrenal glands, both common and rare. Even though ultrasound examination is operator and patient dependent, we consider the examination of the adrenal glands very important, due to relatively frequent incidental detection of an adrenal mass.

AIMS Ultrasound (US) is a highly valuable imagistic tool used to guide numerous interventional procedures. The US guided bone lesions biopsy has not yet received a consensus or a guideline. We aimed to evaluate the evidence to support the US role in guiding bone lesions biopsies. MATERIAL AND METHODS A computer literature search of PubMed was conducted using the keywords "ultrasound" and "bone biopsy", in order to detect relevant studies regarding the aim of our analysis. Records were screened for eligible studies and data were extracted and analyzed. RESULTS We included 23 studies (n=610 patients) in the final analysis. The specificity and diagnostic yield of US guided biopsy were very good (between 78-100%), depending on the type and dimensions of the bone lesions. The type of the biopsy - aspiration or cutting - influenced theresults. The studies which included larger groups showed a better  performance for cutting needles (83.3-100% vs 50-80.5% for aspiration). The size of the bone lesion influences the diagnostic yield of the US guided bone biopsy. Most of the studies reported nil post-procedural complications. CONCLUSION Core needle biopsy provided better diagnostic yield compared to fine needle aspiration. The number of the passages of the cutting needle biopsies in order to achieve the best diagnostic yield wasthree. Further studies are needed in order to standardize US-guided bone lesions biopsy and increase its role in the diagnosis algorithm of the bone lesions.

Case report: A 42-year-old female patient was admitted for diarrhea, abdominal pain and weight loss. Upper digestive endoscopy was performed and identified an infiltrative-eritematous lesion, of about 12mm in diameter, located in the vertical segment of the duodenum. Blood tests showed marked hypereosinophilia and colonoscopy revealed another 10mm lesion situated in the descending segment. After treatment with 5-amynosalicilates and budesonide, the patient became asymptomatic. Results of the histopathological examination of duodenum and descending colon confirmed the eosinophilic enterocolitis. After the disappearance of duodenal lesion - three months later - the treatment was discontinued, and patient remained symptom-free.Conclusion: Eosinophilic colitis is still very rare, either isolated or accompanying eosinophilic infiltration of other segments of the digestive tract. Our case underlines the need of a complete and careful endoscopic assessment combined with accurate histopathological examination in patients with peripheral hypereosinophilia.

A 28-year-old patient, who had underwent surgery 10 years before for a liver hydatid cyst, located in the segments VII, VIII and I (partial pericystectomy with total vascular exclusion) presented in our department for mild pain in the right upper quadrant, during moderate effort or quick walking. Physical examination and laboratory analysis were unremarkable. The first abdominal ultrasonography (US) and Doppler ultrasound revealed multiple calcifications and scars located anterior and lateral from the inferior vena cava (IVC). Liver vasculature presented significant alterations of the veins: absence of right hepatic vein, interruption of middle hepatic vein (Fig. 1) with multiple tortuous veins, and two important veno-venous collaterals transporting the blood from the right liver lobe to the left liver vein (Fig. 2). The diameter of the left hepatic vein was increased, as well as the velocity of the flow – above 110 cm/sec. Considering a Budd-Chiari syndrome (BCS), an abdominal CT-angiography with reconstruction of the liver veins was performed (Fig. 3). It confirmed the US findings. The development of BCS in this patient might be related to the surgical intervention and, possibly, to the previous liver hydatid disease. This type of Budd-Chiari syndrome occurs rarely. It was diagnosed in a paucisymptomatic stage of the disease, due to an accurate US examination, and was confirmed thereafter by CT angiography. The patient is being followed-up by imaging and liver function evaluation. The incidence of BCS is relatively rare, 0.13-0.36 cases annually per million population [1, 2]. Primary BCS has been IMAGE OF THE ISSUE

OBJECTIVE:This study assessed the protective potential of rifaximin in 5-fluorouracil (5-FU) induced intestinal mucositis in the Wistar rats'.MATERIALS AND METHODS:Twenty-nine Wistar rats were divided into 4 interventional groups of 6 animals (A, B, C and F) and one control group (M) of 5 animals. Groups A, B and C received for three days consecutively rifaximin orally: 50 mg/kg (group A), 100 mg/kg (group B) and 200 mg/kg (group C). In the fourth day, 500 mg/kg of 5-FU was administered intraperitoneally to the groups A, B, C and F. A semi-quantitative histological assessment for duodenum, jejunum and colon were obtained by rating 11 histological characteristics of mucositis from 0 (normal) to 3 (severe). Semi-quantitative grades were a measure for TLR4 immunopositive cells. Statistical comparisons used - U Test, with a Bonferroni correction for alpha (p ≤ 0.016).RESULTS:In the group F the most affected areas were the jejunum (median histological score 25) and the duodenum (median histological score 22). The assessment of duodenum histological lesions depicted significant difference between F and B groups (U = 1.5, p = 0.007) and between F and C groups (U = 0, p = 0.003). Graded microscopic degenerative lesions on jejunum were significantly different between F and C groups (U = 0, p = 0.004). Graded TLR4 immunopositive cells in the jejunum surface epithelium was significantly different between groups F and C (U = 2.5, p = 0.006). In the colonic mucosa, significantly differences were noted on microscopic degenerative lesions between F and A groups (U = 0, p = 0.004) and between F and C groups (U = 0, p = 0.004).CONCLUSIONS:Pretreatment with 200 mg/kg of rifaximin for 3 consecutive days proved efficient in preventing intestinal mucosal degenerative lesions induced by 5-FU.

PURPOSEThe aim of this study was to evaluate whether there is a correlation between peripheral blood expression of angiogenic transcriptional factors/receptors and colorectal cancer (CRC).METHODSEighty six blood samples collected from patients with CRC (N=42), adenomas and/or hyperplastic polyps(AP, N=30) and individuals without colon pathology (control group/CTR, N=14) were used for this study. Twelve transcription factors and receptors were assessed by qRT-PCR in a case-control study. The molecules with a minimum of 30% differences in gene expression for CRC and AP compared to CTR were then analyzed separately for each sample. Gene expression was evaluated relatively to the CTR after normalization to the large ribosomal protein PO (RPLPO) housekeeping gene, and the differential expression between studied groups was assessed by ANOVA.RESULTSSeven out of 12 genes presented differences in expression between 10-29% in CRC and/or AP compared to CTR. Considering the selection criteria, we further individually evaluated the levels of expression of 5 genes that had a minimum of 30% expression in the case-control study. Our data showed a significant up-regulation of platelet derived growth factor (PDGF) C in the blood of the patients with CRC compared to CTR (p=0.007). Likewise, clusterin (CLU) was significantly up-regulated both in CRC and AP groups compared to healthy subjects (p=0.01). For VEGFR1, PDGFRA and TGFB1 we didn't find significantly differential expression between any of the studied groups, even if increased levels were observed in both CRC and AP vs CTR.CONCLUSIONSThe results of our study indicated that increased blood level of PDGFC mRNA was associated with the presence of CRC (p=0.007). Additionally, high levels of circulating CLU mRNA were observed in both malignant and benign colorectal pathologies.

Background: Hepatic steatosis (HS) observed in chronic viral hepatitis B (VHB) and C (genotype 1)(VHC) was correlated with the presence of metabolic syndrome. In Romania, HCV genotype 1 has a prevalence of more than 90%.Aim: to quantify steatosis in liver histology specimens in patients with VHB and VHC; to correlate the Brunt score of liver steatosis with some parameters of metabolic syndrome (BMI, DMT2, impaired glucose tolerance (IGT), triglycerides (TGL), cholesterol (Chol), hypertension (HTA), and with the age of the patients.Methods: Patients (pts): 19 pts with VHB and 83 pts with VHC with liver histology, observed between 2007-2008. The quantification of hepatic steatosis was assessed using Brunt histologic score: S0: steatosis absent; S1: mild steatosis (< 33%); S2: moderate steatosis (> 33% and < 66%); S3: severe steatosis (> 66%).Results: Steatosis was recorded in 52.7% of pts with VHB and was predominantly mild (S1: 42.1%, S2: 5.3%, S3: 5.3%). VHC steatosis was recorded in 67.5% of pts, with more frequent cases of moderate and severe scores (S1: 39.7%; S2: 15.7%, S3: 12.0%). A number of 12 pts from the VHB group cumulated 2 or more metabolic risk factors. A number of 30 pts from the VHC group cumulated 3 or more metabolic risk factors. A statistically significant correlation was found for steatosis with HTA in VHB and with BMI in VHC.Conclusion: Hepatis steatosis was recorded more in hepatitis C (67.5%) than in hepatitis B (52.7%), at similar ages, and more frequently than cited in literature (51% and 27% respectively). This aspect could result from an individual cluster of metabolic risk factors, even if only two of them reached statistical significance.

AIMSNon-invasive methods are required to diagnose presence and grading of esophageal varices in patients with hepatic cirrhosis and in this respect we have evaluated the role of transient elastography and abdominal ultrasound parameters.MATERIAL AND METHODSCirrhotic patients were prospectively evaluated by transient elastography and Doppler ultrasound for diagnosis of presence and grading of esophageal varices, the results being compared with the findings of the esophagogastroduodenoscopy.RESULTSSixty patients with hepatic cirrhosis were analysed. The parameters that reached statistical significance for diagnosis of esophageal varices were: liver stiffness (LSM) > 15 kPa, hemodynamic liver index (PVr1) >/= 0.66, portal vascular resistance (PVR) > 17.66 and splenoportal index (SPI) > 4.77. The only parameter that reached statistical power for the diagnosis of large esophageal varices was LSM at a cut-off value of 28.8 kPa.CONCLUSIONSAssessment of LSM in patients with liver cirrhosis can predict both the presence of esophageal varices and of large esophageal varices. The PVr1, PVR and SPI Doppler indexes can be used to diagnose the presence of esophageal varices but have no role in the prediction of large esophageal varices. Further studies are required to confirm these results and offer a stronger clinical significance.

We aimed to compare the difference in case fatality rate between more developed and very high Human Development Index (HDI) regions, less developed and low HDI regions, and Romania. The incidence and mortality rates for digestive cancers were obtained from the IARC/WHO 2012 database. World mean mortality-to-incidence ratios registered the highest values in pancreatic cancer (0.97/0.94), and liver cancer (0.93/0.96) in males/females, respectively. The lowest values were recorded in colorectal cancer (0.48 in both sexes). Mortality-to-incidence ratios were generally higher in less developed areas, low HDI populations, and in Romania. The difference in case fatality rate between different areas showed higher variations for colorectal, gastric and gallbladder cancers, and smaller variations for esophageal, liver, and pancreatic cancers. In summary, mortality-to-incidence ratios of digestive cancers were high in 2012; higher values were registered in less developed and low HDI regions, and in Romania. Mortality-to-incidence ratios were similar in both sexes, even though the incidence was generally higher in men. Digestive cancer mortality variation suggests the necessity of finding better strategies for prevention, early diagnosis and treatment of digestive cancers.

The recent and historical publications of IARC/OMS/GLOBOCAN allowed us to compose a picture of incidence and of mortality of primitive liver cancer in Romania and to compare them with the data from the other countries. In 2012, the incidence rates were 9.2/100 000 in males and of 3/100 000 in females and the mortality rates were 11/100 000 in males and of 4.2/100 000 in females. The primitive liver cancer represented 2.8% of cancers and 5.9% of the mortality by cancer. It was situated in the 4 th rank of the digestive cancers in terms of frequency and in the 3 rd rank of the digestive cancers in terms of mortality. The incidence was one of higher registered in Europe. The mortality rate, upper to that of the incidence and in constant increase since 1980, is compatible with a late diagnosis of this cancer in Romania. This important problem of public health requires, as in the other countries, the implementation of specialized indicators and especially the launch of actions aiming at the improvement of the precocity of the diagnosis.

Les publications récentes et historiques du projet IARC/WHO/GLOBOCAN ont permis de réaliser une synthèse de données concernant l’incidence, et la mortalité du cancer primitif du foie en Roumanie et de les comparer aux données d’autres pays. En 2012, les taux d’incidence ont été de 9,2/100 000 chez l’homme et de 3/100 000 chez la femme et les taux de mortalité ont été de 11/100 000 chez l’homme et de 4,2/100 000 chez la femme. Le cancer primitif du foie représentait 2,8 % des cancers et 5,9 % de la mortalité par cancer. Il était situé au 4 e rang des cancers digestifs en termes de fréquence et au 3 e rang des cancers digestifs en termes de mortalité. L’incidence était une des plus élevées constatées en Europe. Le taux de mortalité, supérieur à celui de l’incidence et en constante augmentation depuis 1980, est compatible avec un diagnostic tardif en Roumanie. Cet important problème de santé publique nécessite, comme dans les autres pays, la mise en place d’indicateurs spécialisés et surtout le lancement d’actions visant à l’amélioration de la précocité du diagnostic.

UNLABELLED:The aim of the paper was to evaluate the national availability of colonoscopy and the quality parameters of this procedure in our country.MATERIAL AND METHOD:During a 6 months period (01.07- 31.12.2009), we performed a prospective multicenter study in which 76 centers were invited to respond to a questionnaire regarding colonoscopy, 39 centers agreeing to participate. We assessed: the number of colonoscopies, the number of total colonoscopies and the causes of incomplete colonoscopies.RESULTS:During the study period, 16,083 colonoscopies were performed, 12,294 (76.4%) of them total colonoscopies. In 1,191 cases, stenosis was the cause of incomplete colonoscopy. If we consider this an objective reason for an incomplete colonoscopy, there were 12,294 total colonoscopies (82.4%). Comparing university centers with non-university ones, the proportion of total colonoscopies was 10,400/12,475 (83.4%) vs. 1,894/2,417 (78.4%) (p less then 0.0001). However, comparing the present study with previous ones, performed in 2003 and 2007, the proportion of total colonoscopies increased from 70.5% to 76.9% and 82.4% respectively (2003 vs. 2007 p less then 0.0001; 2007 vs. 2009 p less then 0.0001), while the quality difference between university and non-university hospitals persisted.CONCLUSIONS:the quality of colonoscopy in Romania increased in the last 5 years, while the quality difference between university and non-university hospitals persisted.