Seyed Amir Mirbagheri

Prospective evaluation of endoscopic ultrasonography in the diagnosis of biliary microlithiasis in patients with normal transabdominal ultrasonography

Prior investigators have proposed microlithiasis as a causative factor for occult gallbladder diseases. Endoscopic ultrasonography (EUS) is potentially far more sensitive than transabdominal ultrasonography (TUS) in visualizing small stones. The aim of this study was to investigate the role of endoscopic ultrasonography (EUS) in the diagnosis of microlithiasis in patients with upper abdominal pain and normal TUS. Thirty-five patients with biliary-type abdominal pain and normal TUS results were prospectively studied. All patients underwent radial EUS by means of a GF UM-20 echoendoscope (Olympus Optical, Tokyo, Japan). Of 35 patients, 33 were revealed to have gallbladder sludge or small stones, and 21 had CBD sludge or microlithiasis. Nine patients were not available for follow-up; of the remaining patients, 13 underwent combined endoscopic biliary sphincterotomy and cholecystectomy, 10 underwent cholecystectomy, and 3 underwent biliary sphincterotomy alone. In a postoperative follow-up at 9.2 months, 25 patients (96.2%) were symptom free. EUS is an important diagnostic tool in patients with unexplained biliary colic. Cholecystectomy with or without EUS is an effective treatment modality in these settings.

Pyloric injection of botulinum toxin for the treatment of refractory GERD accompanied with gastroparesis: a preliminary report.

Gastroesophageal reflux disease (GERD) refractory to conventional medical treatment is frequently associated with gastroparesis, a complex condition with no definitive treatment to date. We first developed a scoring system to assess the severity and frequency of both reflux- and gastroparesis-related symptoms. We then tested, for the first time, the hypothesis that endoscopic pyloric botulinum toxin injection alleviates both of these symptom types. Eleven patients (four males) with GERD (confirmed by esophageal pH monitoring) plus gastroparesis (confirmed by gastric emptying study) underwent toxin injection. Patients had no concomitant disease and were not allowed to use prokinetics before or after treatment. Injection significantly improved both gastroparesis- and reflux-related symptoms in the majority of patients but the duration of symptom relief was relatively short. Responders to treatment had significantly higher total reflux symptom scores (before injection) than nonresponders. All but one of the patients in whom gastroparesis symptoms improved also showed response in reflux symptoms, which supports our hypothesis. We believe that response to toxin injection is a reliable predictor of response to subsequent surgery following the recurrence of symptoms.

Tissue hypoxia in pathogenesis of ulcerative colitis: should we change all our beliefs?

Many studies have focused on the role of irregular mucosal immune response, but there are noteworthy evidences regarding the role of ischemia in pathogenesis of ulcerative colitis (UC). Hypoxia-inducible factor-1 alpha (HIF1a) is an intranuclear protein which is produced by decreased level of intracellular oxygen level. Increased levels of HIF1a in tissue specimens and high levels of vascular endothelial growth factor (VEGF) in serum samples of UC patients are novel findings, strongly congruent with the role of ischemia in UC pathogenesis. The aim of this study is to evaluate the value of tissue hypoxia in cellular level in pathogenesis of UC [1–3]. Forty subjects in four groups were enrolled in our case control study as follows: 1) ten patients with left UC (to obtain biopsy specimens from sparing parts of the colon); 2) ten healthy individuals (referred due to screening purposes); 3) ten formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with mesenteric ischemia; and 4) ten FFPE samples from patients with infectious colitis. Subjects in group 1 and 2 underwent colonoscopy. In group 1, two biopsy samples were taken, one from ulcerative tissue, and the other from spared intestinal tissue. In group 2, biopsy specimens were obtained from the left colon. All subjects were evaluated for tissue hypoxia by a single expert pathologist utilizing HIF1a immunohistochemical staining (Novus Biologicals Company, Clone ESEE122). Systemic and perirectal arteriolar oxygen saturation was then evaluated in groups 1 and 2. Systemic oxygen saturation was measured by radial artery blood sampling. Endoscopic ultrasound was used for arteriolar blood sampling in perirectal level. The venules and arterioles were distinguished according to wall thickness (Figure 1). Oxygen saturation was quantified within one minute of blood sampling. Nine (90%) of the biopsy specimens of patients with ulcerative colitis (ulcerative parts) as well as 8 (80%) of the specimens of the subjects with mesenteric ischemia showed tissue hypoxia in HIF-1a staining. By contrast, only 1 (10%) of the biopsy samples from subjects with infectious colitis and none of the samples from healthy individuals and samples from sparing parts of the colon of patients with UC had tissue hypoxia. There were no significant differences between systemic saturation in groups 1 and 2 (94.4 vs. 94.3%, p = 0.8), but pericapillary saturation was significantly higher in ulcerative colitis patients (96.4 vs. 94.3%, p = 0.001). Our data suggest that ischemia is the main pathology in a majority of UC patients. In support of our conclusion, previous studies have shown that HIF1a is involved in triggering cell immune response [4] and

Pancreatic Tuberculosis in an Immunocompetent Patient: A Case Report and Review of the Literature

There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection.

Sa1817 Tissue Hypoxia in Pathogenesis of Ulcerative Colitis; Should We Change All Our Beliefs?

Department of Surgery, University of Minnesota, Minneapolis, USAMany studies have focused on the role of irregularmucosal immune response, but there are noteworthyevidences regarding the role of ischemia in pathogen-esis of ulcerative colitis (UC). Hypoxia-induciblefactor-1 alpha (HIF1a) is an intranuclear proteinwhich is produced by decreased level of intracellularoxygen level. Increased levels of HIF1a in tissuespecimens and high levels of vascular endothelialgrowth factor (VEGF) in serum samples of UCpatients are novel findings, strongly congruent withthe role of ischemia in UC pathogenesis. The aim ofthis study is to evaluate the value of tissue hypoxia incellular level in pathogenesis of UC [1–3].Forty subjects in four groups were enrolled inour case control study as follows: 1) ten patientswithleftUC(toobtainbiopsyspecimensfromsparingpartsofthecolon);2)tenhealthyindividuals(referreddue to screening purposes); 3) ten formalin-fixedparaffin-embedded (FFPE) tissue samples frompatients with mesenteric ischemia; and 4) ten FFPEsamples from patients with infectious colitis. Subjectsin group 1 and 2 underwent colonoscopy. In group 1,two biopsy samples were taken, one from ulcerativetissue, and the other from spared intestinal tissue.In group 2, biopsy specimens were obtained from theleft colon. All subjects were evaluated for tissue hyp-oxia by a single expert pathologist utilizing HIF1aimmunohistochemical staining (Novus BiologicalsCompany, Clone ESEE122). Systemic and perirectalarteriolar oxygen saturation was then evaluated ingroups 1 and 2. Systemic oxygen saturation was mea-sured by radial artery blood sampling. Endoscopicultrasound was used for arteriolar blood sampling inperirectal level. The venules and arterioles were dis-tinguished according to wall thickness (Figure 1).Oxygen saturation was quantified within one minuteof blood sampling.Nine (90%) of the biopsy specimens of patientswith ulcerative colitis (ulcerative parts) as well as8 (80%) of the specimens of the subjects with mesen-teric ischemia showedtissue hypoxia in HIF-1a stain-ing. By contrast, only 1 (10%) of the biopsy samplesfrom subjects with infectious colitis and none of thesamples from healthy individuals and samples fromsparing parts of the colon of patients with UChad tissue hypoxia. There were no significant differ-ences between systemic saturation in groups 1 and2 (94.4 vs. 94.3%, p = 0.8), but pericapillary satura-tion was significantly higher in ulcerative colitispatients (96.4 vs. 94.3%, p = 0.001).Our data suggest that ischemia is the main pathol-ogy in a majority of UC patients. In support of ourconclusion, previous studies have shown that HIF1ais involved in triggering cell immune response [4] and

Reply:: Liver: an alarm for the heart?

We thank Dr Alavian for his thoughtful comments on our paper (1). This study was conducted in a setting with limited facilities and we fully agree that it had a number of limitations, including lack of data on the following: (i) family history of premature coronary artery disease (CAD), (ii) 2-h post-prandial glucose, to avoid under-estimation of the frequency of diabetes (DM), (iii) insulin levels which could provide a measure to evaluate insulin resistance (IR) by use of homeostasis model assessment (HOMA)-IR and (iv) liver enzymes, which could help discriminate between fatty liver (FL) and steatohepatitis. Insulin resistance accompanies microscopic CAD (2). This is true but does not introduce a flaw in our analysis. We classified the subjects according to their coronary angiography (CAG) results. Analysis was performed and results were interpreted accordingly. We concluded that FL alarms for the presence of clinically significant CAD. The group with normal or mildly abnormal CAG almost surely included some individuals with angiographically undetectable microscopic CAD (possibly accompanying IR), but the association between FL and microscopic CAD (due to IR as a potential cause of both) cannot be investigated by our methodology. Liver biopsy, which could not be performed on our patients for obvious reasons, is the only definitive way to discriminate steatohepatitis from fatty liver and to determine the histopathological severity of the condition. Studies on alternative (noninvasive) methods have shown that the differences between nonalcoholic steatohepatitis and simple liver steatosis (FL) are not apparent with any radiological modalities (3–5). Specifically, only the severity of steatosis is reflected in ultrasonography and magnetic resonance imaging (4). Attenuation of the liver seems to be correlated with histopathological grade but not with histopathological stage (3). While the manuscript was under review we recruited 103 more individuals and achieved a sample size of 420 (normal or mildly abnormal CAG: 302; clinically relevant CAD: 118). The analysis of the new dataset robustly reproduced the results we had originally obtained on 317 subjects with gender, fasting blood sugar (FBS), low-density lipoproteins (LDL), DM, hypertension and FL being the variables with statistically significant difference between the groups. We evaluated all subjects for the presence of metabolic syndrome (MS) based on the adult treatment panel III (ATPIII) criteria (6). Because FBS and blood pressure are elements of the ATP criteria, we did not include them in multivariate analysis. Therefore, binary logistic regression was performed with CAD as the dependent variable and gender, LDL, FL and MS as covariates (Table 1). As predicted by Dr Alavian, MS turned out to be a statistically significant correlate of CAD [P = 0.023, odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.10–3.43] and this association was not confounded by other variables. Interestingly, the odds ratio for FL was much larger than the one we had obtained previously (OR = 14.47, 95% CI = 7.89–26.54 vs. OR = 8.48, 95% CI = 4.39–16.40 respectively). However, there existed a considerable overlap between the corresponding 95% CIs. Despite limitations, our study sheds more light on the complex pathophysiology of MS. According to results, both FL and MS are strong independent correlates of significant CAD. This is consistent with the syndromic trend to consider nonalcoholic fatty liver disease as an additional feature of MS with specific hepatic IR and then use MS as a risk factor for CAD (7).