Prospective study of hepatitis B and D epidemiology and risk factors in Romania:A 10-year update

BACKGROUND The global burden of hepatitis D virus(HDV)infection represents a major medical challenge and a public health crisis worldwide.However,there is a lack of accurate data on the epidemiology and risk factors for HDV.Hepatitis B virus(HBV)and HDV coinfection causes the most severe form of viral hepatitis,leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection,including the need for liver transplantation and death.AIM To investigate the epidemiology,natural history,risk factors and clinical management of HBV and HDV coinfection in Romanian patients.METHODS This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania.All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled.Patients with acute hepatitis or incomplete data were excluded.Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period,963 met the inclusion criteria.Testing for anti-HDV antibodies and HDV RNA was performed for all participants.Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires.All data were stored in an anonymized online database during the study.RESULTS The prevalence of HBV was 3.8%;among these patients,the prevalence of HBV/HDV coinfection was 33.1%.The median age of the study population was 54.0 years,and it consisted of 55.1%men.A higher prevalence of HBV/HDV coinfection was observed in patients 50–69 years old.Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection(P=0.03).Multivariate multiple regression analysis identified female gender(P=0.0006),imprisonment(P<0.0001),older age at diagnosis(P=0.01)and sexual contact with persons with known viral hepatitis(P=0.0003)as significant risk factors for HDV.CONCLUSION This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors.It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Advances in endoscopic ultrasound imaging of colorectaldiseases

The development of endoscopic ultrasound(EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal(GI) and pancreaticobiliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate indepth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn's disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS-guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations.

Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors

AIM:To study the role of time-intensity curve(TIC) analysis parameters in a complex system of neural networks designed to classify liver tumors.METHODS:We prospectively included 112 patients with hepatocellular carcinoma(HCC)(n = 41),hypervascular(n = 20) and hypovascular(n = 12) liver metastases,hepatic hemangiomas(n = 16) or focal fatty changes(n = 23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology,Craiova,Romania.We recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest(one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC analysis.The difference in maximum intensities,the time to reaching them and the aspect of the late/portal phase,as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes,corresponding to each type of liver lesion.RESULTS:The neural network had 94.45% training accuracy(95% CI:89.31%-97.21%) and 87.12% testing accuracy(95% CI:86.83%-93.17%).The automatic classification process registered 93.2% sensitivity,89.7% specificity,94.42% positive predictive value and 87.57% negative predictive value.The artificial neural networks(ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases,while in turn misclassifying four liver hemangyomas as HCC(one case) and hypervascular metastases(three cases).Comparatively,human interpretation of TICs showed 94.1% sensitivity,90.7% specificity,95.11% positive predictive value and 88.89% negative predictive value.The accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs(P = 0.225 and P = 0.451,respectively).Hepatocellular carcinoma cases showed contrast uptake during the arterial phase followed by wash-out in the portal and first seconds of the late phases.For the hypovascular metastases did not show significant contrast uptake during the arterial phase,which resulted in negative differences between the maximum intensities.We registered wash-out in the late phase for most of the hypervascular metastases.Liver hemangiomas had contrast uptake in the arterial phase without agent wash-out in the portallate phases.The focal fatty changes did not show any differences from surrounding liver parenchyma,resulting in similar TIC patterns and extracted parameters.CONCLUSION:Neural network analysis of contrastenhanced ultrasonography-obtained TICs seems a promising field of development for future techniques,providing fast and reliable diagnostic aid for the clinician.

Imaging tests for accurate diagnosis of acute biliary pancreatitis

Gallstones represent the most frequent aetiology of acute pancreatitis in many statistics all over the world, estimated between 40%-60%. Accurate diagnosis of acute biliary pancreatitis(ABP) is of outmost importance because clearance of lithiasis [gallbladder and common bile duct(CBD)] rules out recurrences. Confirmation of biliary lithiasis is done by imaging. The sensitivity of the ultrasonography(US) in the detection of gallstones is over 95% in uncomplicated cases, but in ABP, sensitivity for gallstone detection is lower, being less than 80% due to the ileus and bowel distension. Sensitivity of transabdominal ultrasonography(TUS) for choledocolithiasis varies between 50%-80%, but the specificity is high, reaching 95%. Diameter of the bile duct may be orientative for diagnosis. Endoscopic ultrasonography(EUS) seems to be a more effectivetool to diagnose ABP rather than endoscopic retrograde cholangiopancreatography(ERCP),which should be performed only for therapeutic purposes.As the sensitivity and specificity of computerized tomography are lower as compared to state-of-the-art magnetic resonance cholangiopancreatography(MRCP)or EUS,especially for small stones and small diameter of CBD,the later techniques are nowadays preferred for the evaluation of ABP patients.ERCP has the highest accuracy for the diagnosis of choledocholithiasis and is used as a reference standard in many studies,especially after sphincterotomy and balloon extraction of CBD stones.Laparoscopic ultrasonography is a useful tool for the intraoperative diagnosis of choledocholithiasis.Routine exploration of the CBD in cases of patients scheduled for cholecystectomy after an attack of ABP was not proven useful.A significant rate of the so-called idiopathic pancreatitis is actually caused by microlithiasis and/or biliary sludge.In conclusion,the general algorithm for CBD stone detection starts with anamnesis,serum biochemistry and then TUS,followed by EUS or MRCP.In the end,bile duct microscopic analysis may be performed by bile harvested during ERCP in case of recurrent attacks of ABP and these should be followed by laparoscopic cholecystectomy.

Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps

AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of mucin [HPs,21.7%(5/23):TSAs,17.9%(7/39):SSA/Ps,72.0%(36/50),P < 0.001].In magnified colonoscopic findings,17 lesions showed either type Ⅱ pit pattern alone or partial type Ⅱ pit pattern as the basic architecture,with 14 HPs(14/17,70.0%) and 3 SSA/Ps.Magnified colonoscopy showed the type Ⅱ-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7%(41/49),specificity 85.7%(54/63)].Cancer was also present in three lesions,in all of which a type Ⅵ pit pattern was also present within the same lesion.There were four HPs and four TSAs each.The type Ⅳ-S pit pattern was characteristic of TSAs [sensitivity 96.7%(30/31),specificity 89.9%(72/81)].Cancer was present in one lesion,in which a type Ⅵ pit pattern was also present within the same lesion.In our study,serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings.The pit pattern diagnosis using magnifying colonoscopy,particularly magnified colonoscopic findings using subclassifications of surface architecture,reflected the pathological characteristics of SSA/Ps and TSAs,and will be useful for colonoscopic diagnosis.CONCLUSION:We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.

State-of-the-art imaging techniques in endoscopic ultrasound

Endoscopic ultrasound (EUS) has recently evolved through technological improvement of equipment,with a major clinical impact in digestive and mediastinal diseases.State-of-the-art EUS equipment now includes real-time sono-elastography,which might be useful for a better characterization of lesions and increased accuracy of differential diagnosis (for e.g.lymph nodes or focal pancreatic lesions).Contrast-enhanced EUS imaging is also available,and is already being used for the differential diagnosis of focal pancreatic masses.The recent development of low mechanical index contrast harmonic EUS imaging offers hope for improved diagnosis,staging and monitoring of anti-angiogenic treatment.Tridimensional EUS (3D-EUS) techniques can be applied to enhance the spatial understanding of EUS anatomy,especially for improved staging of tumors,obtained through a better assessment of the relationship with major surrounding vessels.Despite the progress gained through all these imaging techniques,they cannot replace cytological or histological diagnosis.However,real-time optical histological diagnosis can be achieved through the use of single-fiber confocal laser endomicroscopy techniques placed under real-time EUS-guidance through a 22G needle.Last,but not least,EUS-assisted natural orifice transluminal endoscopic surgery (NOTES) procedures offer a whole new area of imaging applications,used either for combination of NOTES peritoneoscopy and intraperitoneal EUS,but also for access of retroperitoneal organs through posterior EUS guidance.

Autofluorescence imaging and magnification endoscopy

It is well known that angiogenesis is critical in the transition from premalignant to malignant lesions.Consequently,early detection and diagnosis based on morphological changes to the microvessels are crucial.In the last few years,new imaging techniques which utilize the properties of light-tissue interaction have been developed to increase early diagnosis of gastrointestinal(GI) tract neoplasia.We analyzed several "red-flag" endoscopic techniques used to enhance visualization of the vascular pattern of preneoplastic and neoplastic lesions(e.g.trimodal imaging including autofluorescence imaging,magnifying endoscopy and narrow band imaging).These new endoscopic techniques provide better visualization of mucosal microsurface structure and microvascular architecture and may enhance the diagnosis and characterization of mucosal lesions in the GI tract.In the near future,it is expected that trimodal imaging endoscopy will be practiced as a standard endoscopy technique as it is quick,safe and accurate for making a precise diagnosis of gastrointestinal pathology,with an emphasis on the diagnosis of early GI tract cancers.Further large-scale randomized controlled trials comparing these modalities in different patient subpopulations are warranted before their endorsement in the routine practice of GI endoscopy.

Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

AIM: To evaluate the preventive effect of Ginkgo bilobaextract (GbE) on ethanol-induced gastric mucosal injuries in rats.METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gaveGbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers,gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1)GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH oontents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanolproduced an increase in JNK activity in gastric mucosawhich also significantly inhibited by pretreatment with GbE;and (4) GbE alone had no inhibitory effect on gastric secretionin pylorus-ligated rats.CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation;(2) preservation of gastric mucus and NP-SH; and (3)blockade of cell apoptosis.

Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies

Gastrointestinal cancers represent a major cause of morbidity and mortality,with incomplete response to chemotherapy in the advanced stages and poor prognosis.Angiogenesis plays a crucial part in tumor growth and metastasis,with most gastrointestinal cancers depending strictly on the development of a new and devoted capillary network.Confocal laser endomicroscopy is a new technology which allows in vivo microscopic analysis of the gastrointestinal mucosa and its microvascularization during ongoing endoscopy by using topically or systemically administered contrast agents.Targeting markers of angiogenesis in association with confocal laser endomicroscopic examination(immunoendoscopy),as a future challenge,will add functional analysis to the morphological aspect of the neoplastic process.This review describes previous experience in endomicroscopic examination of the upper and lower digestive tract with emphasis on vascularization,resulting in a broad spectrum of potential clinical applications,and also preclinical research that could be translated to human studies.

Analysis of colonoscopic perforations at a local clinic and a tertiary hospital

AIM:To define the clinical characteristics,and to assess the management of colonoscopic complications at a local clinic.METHODS:A retrospective review of the medical records was performed for the patients with iatrogenic colon perforations after endoscopy at a local clinic between April 2006 and December 2010.Data obtained from a tertiary hospital in the same region were also analyzed.The underlying conditions,clinical presentations,perforation locations,treatment types(operative or conservative) and outcome data for patients at the local clinic and the tertiary hospital were compared.RESULTS:A total of 10 826 colonoscopies,and 2625 therapeutic procedures were performed at a local clinic and 32 148 colonoscopies,and 7787 therapeutic procedures were performed at the tertiary hospital.The clinic had no perforations during diagnostic colonoscopy and 8(0.3%) perforations were determined to be related to therapeutic procedures.The perforation rates in each therapeutic procedure were 0.06%(1/1609) in polypectomy,0.2%(2/885) in endoscopic mucosal resection(EMR),and 3.8%(5/131) in endoscopic submucosal dissection(ESD).Perforation rates for ESD were significantly higher than those for polypectomy or EMR(P < 0.01).All of these patients were treated conservatively.On the other hand,three(0.01%) perforation cases were observed among the 24 361 diagnostic procedures performed,and these cases were treated with surgery in a tertiary hospital.Six perforations occurred with therapeutic endoscopy(perforation rate,0.08%;1 per 1298 procedures).Perforation rates for specific procedure types were 0.02%(1 per 5500) for polypectomy,0.17%(1 per 561) for EMR,2.3%(1 per 43) for ESD in the tertiary hospital.There were no differences in the perforation rates for each therapeutic procedure between the clinic and the tertiary hospital.The incidence of iatrogenic perforation requiring surgical treatment was quite low in both the clinic and the tertiary hospital.No procedure-related mortalities occurred.Performing closure with endoscopic clipping reduced the C-reactive protein(CRP) titers.The mean maximum CRP titer was 2.9 ± 1.6 mg/dL with clipping and 9.7 ± 6.2 mg/dL without clipping,respectively(P < 0.05).An operation is indicated in the presence of a large perforation,and in the setting of generalized peritonitis or ongoing sepsis.Although we did not experience such case in the clinic,patients with large perforations should be immediately transferred to a tertiary hospital.Good relationships between local clinics and nearby tertiary hospitals should therefore be maintained.CONCLUSION:It was therefore found to be possible to perform endoscopic treatment at a local clinic when sufficient back up was available at a nearby tertiary hospital.

Molecular confocal laser endomicroscopy:A novel technique for in vivo cellular characterization of gastrointestinal lesions

While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently available,one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound.The second system has a confocal microscope integrated into the distal part of an endoscope.By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure(either topically or systemically administered during on-going endoscopy),a novel world of molecular evaluation opens up.The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas,subsequently resulting in immediate individualization of treatment regimens,but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions.Furthermore,studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ,which probably can be correlated to the efficacy of the drug.However,several of the studies in this research field have been conducted in animal facilities or in vitro,while only a limited number of trials have actually been carried out in vivo.Therefore,safety issues still needs further evaluations.This review will present an overview of the implications and pitfalls,as well as future challenges of molecular CLE in gastrointestinal diseases.

Real-time sono-elastography in the diagnosis of diffuse liver diseases

AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis. METHODS: The study design was prospective. A total of 132 consecutive patients with chronic liver diseases and healthy volunteers were examined by transabdominal ultrasound elastography. All examinations were done by two doctors.RESULTS: Due to the limitations of the method, we obtained high-quality elastography information in only 73.48% of the patients. The κ-means clustering method was applied to assess the inter-observer diagnosis varia- bility, which showed good variability values in accordance with the experience of ultrasound examination of every observer. Cohen’sκ test indicated a moderate agreement between the study observers (κ = 0.4728). Furthermore, we compared the way the two observers clustered the patients, using the test for comparing two proportions (t value, two-sided test). There was no statistically significant difference between the two physicians, regardless of the patients’ real status. CONCLUSION: Transabdominal real-time elastography is certainly a very useful method in depicting liver hard- ness, although it is incompletely tested in large multicenter studies.

Contrast-enhanced ultrasound of histologically proven hepatic epithelioid hemangioendothelioma

AIM: To analyze contrast-enhanced ultrasound(CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma(HEHE) in comparison to other multilocular benign focal liver lesions(FLL).METHODS: Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus.RESULTS: HEHE manifested as a single(n = 3) or multinodular(n = 22) FLL. On CEUS, HEHE showed rim-like(18/25, 72%) or heterogeneous hyperenhancement(7/25, 28%) in the arterial phase and hypoenhancement(25/25, 100%) in the portal venous and late phases(PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas(18/25, 72%); in seven patients(7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature(P < 0.01).CONCLUSION: CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE.

Frequent loss of heterozygosity at 8p22 chromosomal region in diffuse type of gastric cancer

AIM: To study the loss of heterozygosity (LOH) at 8p21-23 locus in diffuse gastric cancer.METHODS: To evaluate the involvement of this region in gastric cancer, we used eight microsatellite markers covering two Mb of mentioned region, to perform a high-resolution analysis of allele loss in 42 cases of late diffuse gastric adenocarcinoma.RESULTS: Six of these STS makers: D8S1149, D8S1645, D8S1643, D8S1508, D8S1591, and D8S1145 showed 36%, 28%, 37%, 41%, 44% and 53% LOH, respectively.CONCLUSION: A critical region of loss, close to the NAT2 locus and relatively far from FEZ1 gene currently postulated as tumor suppressor gene in this region.

Inoperable esophageal cancer and outcome of palliative care

AIM:To determine the outcome of esophageal cancer patients referred for palliative care,in Gorgan and Gonbad gastrointestinal clinics,northeast of Iran. METHODS:This cross-sectional study was done on inoperable esophageal cancer cases referred to gastrointestinal clinics in Gorgan and Gonbad city(2005-2006) . Demographic data were collected during the procedure and cases were followed up every one month. Improvement proportion was calculated with 95% confidence interval,to determine the rate of improvement. Survival analysis and Kaplan-Meier methods were used to estimate the duration of palliative care effectiveness. RESULTS:We recruited 39 cases into the study. Squamous cell carcinoma was the most prevalent(92.3%) . The middle third of the esophagus was involved predominantly(51.3%) . Dilation was the most preferred method(89.7%) and stenting was done in 4 cases. Decreasing dysphagia score was not related to palliation method or pathology type of carcinoma. Age of the patients was significantly related to the improvement of dysphagia score. Mean survival time was 137.6 d and median was 103 d. CONCLUSION:Results of this study showed a low survival rate after palliative care in esophageal cancer cases despite dysphagia scores' improvement after dilating or stenting.

Current role of non-anesthesiologist administered propofol sedation in advanced interventional endoscopy

Complex and lengthy endoscopic examinations like endoscopic ultrasonography and/or endoscopic retrograde cholangiopancreatography benefit from deep sedation, due to an enhanced quality of examinations, reduced discomfort and anxiety of patients, as well as increased satisfaction for both the patients and medical personnel. Current guidelines support the use of propofol sedation, which has the same rate of adverse effects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recovery time. Non-anesthesiologist administered propofol sedation has become an option in most of the countries, due to limited anesthesiology resources and the increasing evidence from prospective studies and metaanalyses that the procedure is safe with a similar rate of adverse events with traditional sedation. The advantages include a high quality of endoscopic examination, improved satisfaction for patients and doctors, as well as decreased recovery and discharge time. Despite the advantages of non-anesthesiologist administered propofol, there is still a continuous debate related to the successful generalization of the procedures.

Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions

AIM To investigate daclatasvir(DCV) and asunaprevir(ASV) efficacy in hepatitis C(HCV) patients, with respect to resistance-associated substitutions(RASs).METHODS A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses(SVR) according to pretreatment factors(gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion(SVR12).RESULTS The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/m L was significantly lower than those with viral loads of < 6.0 log IU/m L(P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative(P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure.CONCLUSION Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.

Role of silis in esophageal cancer

Association of silica with diseases like cancers has been determined previously. This study was designed to determine the quantity of silis in flour produced in Golestan Province, and its relation to esophageal cancer (EC). We took flour samples from all flour millings in Golestan Province. Base-melting method in nickel cruise was used at 550℃. The extract was reduced with acids. Different silis concentrations in various regions were compared. P < 0.05 was considered statistically significant. The median silis concentration was 0.0030 g, the mean silis concentration was 0.008760 ± 0.004265 g in each 100 g flour. The difference of mean silis concentrations in various regions was not significant. No high level of silica was found in the flour of Golestan Province. We could not find any significant difference in various areas between silica contaminations. Studies on the consumed bread and rice in various regions of Golestan Province can be helpful.

Endoscopic treatment of non-variceal gastrointestinal bleeding:hemoclips and other hemostatic techniques

Although the number of hospitalizations for non-variceal gastrointestinal bleeding has decreased inrecent years,acute upper gastrointestinalhemorrhage continues to be a common reason forhospital admission,and peptic ulcers account for atleast fifty percent of all cases.Despite the fact thatbleeding from ulcers ceases spontaneously inapproximately 80% of patients,it is still a