Digestive Diseases and Sciences (DIGEST DIS SCI)

Publications in this journal

• Article: GRG Update: DDW 2009 and Upcoming GRG-Sponsored Meetings

  Jonathan D. Kaunitz
  Digestive Diseases and Sciences 05/2012; 54(11):2301-2302.
• Article: Radiofrequency Ablation for Dysplasia in Barrett’s Esophagus Restores β-Catenin Activation Within Esophageal Progenitor Cells

  K. Krishnan, S. Komanduri, J. Cluley, R. Dirisina, P. Sinh, Jeff Z. Ko, L. Li, R. B. Katzman, T. A. Barrett
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  ABSTRACT: Background and AimsEndoscopic therapies for Barrett’s esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of β-Catenin occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of RFA in restoring AKT-mediated β-Catenin signaling in regenerative epithelium. MethodsBiopsies were taken from squamous, non-dysplastic BE, dysplastic BE and esophageal adenocarcinoma (EAC). Also, post-RFA, biopsies of endoscopically normal appearing neosquamous epithelium were taken at 3, 6, and 12months after successful RFA. Immunohistochemistry and Western blot analysis was performed for Pβ-Catenin552 (Akt-mediated phosphorylation of β-Catenin), Ki-67 and p53. ResultsThere was no difference in Pβ-Catenin552 in squamous, GERD, small bowel and non-dysplastic BE. There was a fivefold increase in Pβ-Catenin552 in dysplasia and EAC compared to non-dysplastic BE (P<0.05). Also, there was a persistent threefold increase in Pβ-Catenin552 in neosquamous epithelium 3months after RFA compared to native squamous epithelium (P<0.05) that correlated with increased Ki-67. Six months after RFA, Pβ-Catenin552 and Ki-67 are similar to native squamous epithelium. ConclusionsEnhanced AKT-mediated β-Catenin activation is seen in BE-associated carcinogenesis. Three months after RFA, squamous epithelial growth from SPC populations exhibited increased levels of Pβ-Catenin552. This epithelial response becomes quiescent at 6months after RFA. These data suggest that elevated Pβ-Catenin552 after RFA denotes a repair response in the neosquamous epithelium 3months post-RFA. KeywordsBarrett’s esophagus–Radiofrequency ablation–β-Catenin–AKT–Stem/progenitor cell–Dysplasia–Squamous epithelialium
  Digestive Diseases and Sciences 04/2012; 57(2):294-302.
• Article: Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial

  Jaya Benjamin, Govind Makharia, Vineet Ahuja, K. D. Anand Rajan, Mani Kalaivani, Siddhartha Datta Gupta, Yogendra Kumar Joshi
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  ABSTRACT: BackgroundIncreased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn’s disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP. AimWe evaluated the effect of oral glutamine on IP and intestinal morphology in patients with CD. MethodsIn a randomized controlled trial, consecutive patients with CD in remission phase with an abnormal IP were randomized to a glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively, as 0.5g/kg ideal body weight/day for 2months. IP was assessed by the lactulose mannitol excretion ratio (LMR) in urine, and morphometry was performed by computerized image analysis system. ResultsPatients (age 34.5±10.5years; 20 males) were assigned to the GG (n=15) or ACG (n=15). Fourteen patients in each group completed the trial. The LMR [median (range)] in GG and ACG at 2months was 0.029 (0.006–0.090) and 0.033 (0.009–0.077), respectively, with P=0.6133. IP normalized in 8 (57.1%) patients in each group (P=1.000). The villous crypt ratio (VCR) [mean (SD)] in GG and ACG at 2months was 2.68 (1.02) and 2.49 (0.67), respectively, (P=0.347). At the end of 2months LMR improved significantly in GG from 0.071 (0.041–0.254) to 0.029 (0.006–0.090) (P=0.0012) and in ACG from 0.067 (0.040–0.136) to 0.033 (0.009–0.077) (P=0.0063). VCR improved in the GG from 2.33 (0.77) to 2.68 (1.02) (P=0.001), and in ACG from 2.26 (0.57) to 2.49 (0.67) (P=0.009). ConclusionsIntestinal permeability and morphology improved significantly in both glutamine and ACG. KeywordsCrohn’s disease–Glutamine–Intestinal morphology–Intestinal permeability–Lactulose mannitol ratio–Villous crypt ratio
  Digestive Diseases and Sciences 04/2012; 57(4):1000-1012.
• Article: High Dose Lamivudine in HBV-Related Cirrhotic Patients with Unsatisfactory Response After Adefovir Add-On

  Marco Montagnani, Marina Giandinoto, Andrea Lisotti, Silvia Galli, Francesco Azzaroli, Federica Buonfiglioli, Laura Turco, Rita Aldini, Giuseppe Mazzella
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  ABSTRACT: BackgroundBefore tenofovir approval for chronic hepatitis B therapy, the clinical management of patients with suboptimal response or virological breakthrough during combination treatment with lamivudine and adefovir dipivoxil was a difficult clinical challenge. AimsIn order to improve virologic response and reduce the risk of decompensation, we evaluate the efficacy of a high dose of lamivudine on chronic HBV patients who have previously presented an unsatisfactory response during treatment with lamivudine 100mg/day and adefovir 10mg/day. MethodsSix patients with HBV-related liver cirrhosis were prospectively enrolled. All were HBeAg-negative and presented a suboptimal response or virological breakthrough after "adefovir add-on" because of development of clinical breakthrough during Lamivudine treatment. Lamivudine dose was increased to 200 or 300mg, depending on viral load. After 12 months of follow-up, virological and biochemical response were evaluated. ResultsAfter 12 months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant decrease of serum HBV DNA (mean reduction 2,62 ± 1,15 Log10 UI/ml, P= 0.03) and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable within 6 months. No patient developed liver decompensation and no significant changes occurred in serum creatinine, serum and urinary electrolytes. No adverse events were registered. ConclusionsIn our experience, rescue strategy with high-dose lamivudine inhibited viral replication leading to undetectability of serum HBVDNA. This rescue treatment presented a good safety profile, without adverse events during the study period. Customized increase of nucleos(t)ide analogues dose in difficult-to-treat patients may be a proficient approach in challenging clinical setting. KeywordsCirrhosis–Lamivudine–NUC–Rescue therapy–Resistance–Tenofovir
  Digestive Diseases and Sciences 04/2012; 57(2):561-567.
• Article: Diagnostic Role and Clinical Association of ASCA and ANCA in Brazilian Patients with Inflammatory Bowel Disease

  Renato Mitsunori Nisihara, Wilson Beleski de Carvalho, Shirley Ramos da Rosa Utiyama, Heda Amarante, Márcia Luiza Baptista
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  ABSTRACT: BackgroundAnti-Saccharomyces cerevisae antibody (ASCA) and perinuclear anti-neutrophil cytoplasmatic antibody (pANCA) remain the most well-established markers in inflammatory bowel disease (IBD), and both may be associated with disease phenotype. AimTo determine the utility of ASCA and pANCA as markers in a Brazilian cohort of IBD patients. Materials And MethodsA total of 90 patients with ulcerative colitis (UC), 77 patients with Crohn’s disease (CD), and 57 healthy individuals were included in the study. ASCA was determined by enzyme-linked immunosorbent assay (ELISA) and pANCA by immunofluorescence assay. ResultsIn support of diagnosis of UC, the sensitivity and specificity of pANCA were 51% and 100%, respectively. ASCA (IgA or IgG isotypes) presented sensitivity of 62% and specificity of 93% for CD. The combination of ASCA negativity and pANCA positivity (ASCA−/pANCA+) displayed sensitivity of 43% and specificity of 100% for diagnosis to UC. In CD patients, ASCA+/pANCA− presented sensitivity and specificity of 57% and 93%, respectively. Additionally, ASCA positivity correlated with early age at disease onset and ileal location in CD patients. In UC patients, pANCA positivity was correlated with pancolitis or left colitis. ConclusionsThe results evidenced that low sensitivity of ASCA and pANCA markers limits their use in IBD screening in the general population; however, their specificity may contribute to differentiation between CD and UC in IBD patients. Our study lends further support to the suggestion that serologic assessment identifies different subtypes of IBD. KeywordsInflammatory bowel disease-Ulcerative colitis-Crohn’s disease-ASCA-ANCA-Disease phenotype
  Digestive Diseases and Sciences 04/2012; 55(8):2309-2315.
• Article: Correlation of MMP-3 and MMP-9 with Crohn’s Disease Activity in Children

  Anna Kofla-Dlubacz, Malgorzata Matusiewicz, Malgorzata Krzystek-Korpacka, Barbara Iwanczak
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  ABSTRACT: BackgroundRecently published data indicate that the inflammation in Crohn’s disease (CD) may be accompanied by elevated levels of matrix metalloproteinases. AimsThe goals of the present study were the estimation of MMP-3 and -9 concentrations in sera of children with Crohn’s disease, the examination of correlation between the concentrations of MMP-3 and -9 and clinical activity of the disease in the relation to the control group and the evaluation of the utility of MMP-3 and -9 concentration measurements as markers of disease activity. MethodsSerum concentrations of MMP-3 and -9 were estimated in 82 children (45 CD patients divided into severe, moderate and mild subgroups; 37 controls) and correlated with disease activity estimated by the Pediatric Crohn’s Disease Activity Index (PCDAI), CRP, seromucoid and ESR. ResultsMean MMP-3 concentrations were: 2.49ng/ml (95% CI: 1.76–3.52) for mild, 16.44ng/ml (95% CI: 10.34–26.15) for moderate, 5.25ng/ml (95% CI: 2.73–10.11) for severe CD and 1.95ng/ml (95% CI: 1.53–2.48) for the control group (differences between all three groups were statistically significant; P<0.001). Median MMP-9 concentrations were: 2.14ng/ml (95% CI: 0–8.9) for mild, 14.21ng/ml (95% CI: 4.53–21.48) for moderate, 42.2ng/ml (95% CI: 5.74–61.27) for severe CD and 1.3ng/ml (95% CI: 0.7–2.18) for the control group. MMP-9 concentrations in moderate and severe CD differed from the concentrations in mild CD (P=0.002) and control group (P=0.0001). MMP-3 concentration significantly correlated with MMP-9, PCDAI and ESR, while MMP-9 concentration significantly positively correlated with MMP-3, PCDAI, and CRP. Diagnostic utilities of the tests were: MMP-3 accuracy 75%, positive likelihood ratio (LR+)=4.11 and negative likelihood ratio (LR−)=0.51, sensitivity 56%, specificity 87%, Youden index 0.43; for MMP-9, accuracy 73%, LR+=5.14 and LR−=0.50, sensitivity 56%, specificity 89%, Youden index 0.45; and for CRP, accuracy 74%, LR+=8.56 and LR−=0.54, sensitivity 49%, specificity 94%, Youden index 0.43. ConclusionsMMP-9 serum concentration increasing along with the activity of the disease, exhibiting high specificity and correlating well with the indices of inflammation might be of better usefulness in the prediction of CD activity status in children than MMP-3. KeywordsInflammatory bowel disease–Crohn’s disease–Children–Metalloproteinases–PCDAI
  Digestive Diseases and Sciences 04/2012; 57(3):706-712.
• Article: African Americans with Barrett’s Esophagus Are Less Likely to Have Dysplasia at Biopsy

  Joe E. Khoury, Sian Chisholm, M. Mazen Jamal, Carlos Palacio, Sunitha Pudhota, Kenneth J. Vega
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  ABSTRACT: BackgroundBarrett’s Esophagus (BE) is a pre-malignant condition. Limited data on BE dysplasia prevalence exists among United States ethnic groups. AimThe purpose of this study was to determine if the frequency of BE with dysplasia varies among the major ethnic groups presenting to our institution. MethodsThe University of Florida-Jacksonville endoscopy database was searched for all cases of endoscopic BE from September 2002 to August 2007. Histologic BE was diagnosed if salmon colored esophageal mucosa was endoscopically seen at least 1cm above the top of the gastric folds and biopsy revealed intestinal metaplasia with Alcian blue-containing goblet cells. Demographic data collected for all included: age at diagnosis, ethnicity, sex, previous history of esophageal reflux, atypical manifestations (chronic cough, aspiration), endoscopic length of BE, presence or absence of hiatal hernia, esophageal stricture or ulcer, and presence or absence of dysplasia. ResultsSalmon colored esophageal mucosa was observed in 405 of 7,308 patients (5.5%) and histologically confirmed in 115 of 405 patients (28%) reflecting an overall prevalence of BE of 115/7308 (1.6%) in this cohort. Ethnic distribution of histologic BE patients was as follows: 95 (83%) non-Hispanic white (nHw), 16 (14%) African American (AA) and 4 (3%) other. Long segment BE (LSBE) and any form of dysplasia was observed less frequently in AA than nHw (LSBE: 12% vs. 26% and dysplasia: 0% vs. 7%). ConclusionsLSBE and dysplasia are less frequent in AA than nHw. Studies in AA with BE may illustrate factors limiting dysplasia and LSBE risk. KeywordsBarrett’s esophagus–Dysplasia–Demographics–Ethnicity–African American
  Digestive Diseases and Sciences 04/2012; 57(2):419-423.
• Article: Relapse Rate Following Azathioprine Withdrawal in Maintaining Remission for Crohn’s Disease: A Meta-Analysis

  Helen French, A. Mark Dalzell, Ramesh Srinivasan, Wael El-Matary
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  ABSTRACT: BackgroundThe duration of use of azathioprine (Aza) and 6-mercaptopurine (6-MP) for maintaining remission for Crohn’s disease is debatable. AimTo examine whether Aza/6-MP can be safely withdrawn in patients with Crohn’s disease who have been in remission. MethodsThe following databases were searched: MEDLINE (1950–September 2010), EMBASE (1980–September 2010), CINHAL (1981–September 2010), PubMed (1950–September 2010), and the Cochrane Central Register of Controlled Trials (CENTRAL). Randomised controlled and cohort studies comparing azathioprine continuation versus placebo or no treatment were eligible for inclusion. Primary outcomes were relapse rate after discontinuation of Aza/6-MP at 6, 12, and 18months, and 5 and 10years. ResultsFive studies, with 256 patients and 168 controls, met the inclusion criteria. Stopping azathioprine/6-MP was found to significantly increase the risk of relapse at 6, 12, and 18months with pooled odds ratios of 0.22 (95% CI 0.09–0.53), 0.25 (95% CI 0.11–0.56), and 0.35 (95% CI 0.21–0.6), respectively. Two trials examined relapse rate at 5years with pooled OR 0.53 (95% CI 0.13–2.21). No trials looking at relapse rates beyond 5years were identified. ConclusionsThere is a clear benefit of continuing Aza/6-MP for at least 18months to maintain remission for Crohn’s disease patients who established remission. There is not enough evidence to provide clear guidance on whether or not to continue Aza/6-MP treatment beyond 18months. Well-designed randomised controlled trials addressing this issue are needed. KeywordsCrohn–Colitis–IBD–Azathioprine–6-MP
  Digestive Diseases and Sciences 04/2012; 56(7):1929-1936.
• Article: Outcome of patients with nonstenotic, nonfistulizing Crohn's disease.

  Pilar Nos, Vicente Garrigues, Guillermo Bastida, Nuria Maroto, Marta Ponce, Julio Ponce
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  ABSTRACT: The nonstenotic, nonfistulizing (or inflammatory) pattern of Crohn's disease appears to be unstable in time and may evolve toward either the stenotic or the fistulizing pattern. We aimed to assess the course of the inflammatory disease and its relation to certain clinical characteristics. After a mean follow-up of 93 months, we evaluated 73 patients with an inflammatory pattern. The behavior trend and its relation to disease location, initial treatment, and need for corticosteroids, immunosuppressors, and surgical resection were analyzed. In 64% of the patients the inflammatory pattern did not change, while in 14 and 22% it evolved toward a stenotic and a fistulizing pattern, respectively. This change was mainly determined by the appearance of perianal disease (75%). The mean time to behavior evolution was 67 months. Most patients required corticosteroids (92%). Need for immunosuppressors (48%) and surgical resection (30%) was significantly greater (P < 0.05) among patients with a change in pattern than in those with persistent inflammatory disease. The inflammatory pattern of CD remains stable in about half of patients. The course of this pattern is not indolent, however, since the needs for immunosuppression and surgical resection during follow-up are considerable.
  Digestive Diseases and Sciences 04/2012; 49(11-12):1771-6.
• Article: Alpha-Defensin DEFA1A3 Gene Copy Number Elevation in Danish Crohn’s Disease Patients

  Cathrine Jespersgaard, Peder Fode, Marianne Dybdahl, Ida Vind, Ole Haagen Nielsen, Claudio Csillag, Pia Munkholm, Ben Vainer, Lene Riis, Margarita Elkjaer, Natalia Pedersen, Elisabeth Knudsen, Paal Skytt Andersen
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  ABSTRACT: Background and Purpose of StudyExtensive copy number variation is observed for the DEFA1A3 gene encoding alpha-defensins 1–3. The objective of this study was to determine the involvement of alpha-defensins in colonic tissue from Crohn’s disease (CD) patients and the possible genetic association of DEFA1A3 with CD. MethodsTwo-hundred and forty ethnic Danish CD patients were included in the study. Reverse transcriptase PCR assays determined DEFA1A3 expression in colonic tissue from a subset of patients. Immunohistochemical analysis identified alpha-defensin peptides in colonic tissue. Copy number of DEFA1A3 and individual alleles, DEFA1 and DEFA3, were compared with those for controls, by use of combined real-time quantitative PCR and pyrosequencing, and correlated with disease location. ResultsInflammatory-dependent mRNA expression of DEFA1A3 (P<0.001), and the presence of alpha-defensin peptides, were observed in colonic tissue samples. Higher DEFA1A3 gene copy number (CD: mean copy number, 7.2 vs. controls 6.7; P<0.001) and individual DEFA1 alleles (CD mean copy number 5.6 vs. controls 5.1; P<0.01) were associated with CD, with strong association with colonic location (P<0.001). ConclusionsAlpha-defensins are involved in the inflammation of CD, with local mRNA and peptide expression. In combination with the findings that a high DEFA1A3 copy number is significantly linked to CD, these results suggest that a high DEFA1A3 copy number might be important in hindering the normal inflammatory response in CD, particularly colonic CD. KeywordsCrohn’s disease–Colonic tissue–Copy number variation–Defensin–Genetic association–Real-time PCR
  Digestive Diseases and Sciences 04/2012; 56(12):3517-3524.
• Article: Magnification Endoscopy and Chromoendoscopy in Evaluation of Specialized Intestinal Metaplasia in Barrett’s Esophagus

  Justyna Wasielica-Berger, Andrzej Baniukiewicz, Eugeniusz Wroblewski, Adam Chwiesko, Andrzej Dabrowski
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  ABSTRACT: BackgroundSpecialized intestinal metaplasia (SIM) in Barrett’s esophagus is a risk factor of esophageal adenocarcinoma. It often occurs focally and cannot be distinguished from surrounding columnar epithelium with conventional endoscopy. AimsThe purpose of this study was evaluation of methylene blue (MB) staining and magnification endoscopy with comparison of pit-pattern classifications according to Endo and Guelrud, in detection of SIM in Barrett’s esophagus. MethodsTwenty-five patients, aged 33–77years (average 57years), with displacement of Z line were prospectively enrolled and underwent gastroscopy with the use of magnification up to 115 times (Olympus GIF Q160Z). Biopsy for histopathologic examination was taken from sites stained with MB and/or places with particular pit patterns. A control group consisted of ten patients with normal gastro-esophageal junction. ResultsSIM was proved in nine patients, and significantly more frequently in patients with hiatal hernia and Barrett’s segment longer than 3cm. Round or thin linear pit patterns according to Guelrud’s and small round and straight pit patterns according to Endo’s classification were coupled with columnar epithelium. SIM was associated with deep linear and foveolar pit patterns in Guelrud’s classification. Other pit patterns were less characteristic. Both classifications had high sensitivity (Endo’s 85.7%, Guelrud’s 92.8%) but poor specificity (respectively, 21.15 and 28.4%) in detection of SIM. Sensitivity and specificity of MB staining were, respectively, 71.4 and 40.6%. ConclusionsDespite existing association between mucosal surface structure and histology, we find no convincing data indicating that pit-pattern evaluation may replacemultiple biopsies taken according to recommendations from Seattle for detection of SIM in Barrett’s esophagus. KeywordsMagnification endoscopy–Barrett’s esophagus–Pit pattern–Methylene blue–Intestinal metaplasia
  Digestive Diseases and Sciences 04/2012; 56(7):1987-1995.
• Article: Is Obesity a Risk Factor for Crohn’s Disease?

  Michael A. Mendall, A. Viran Gunasekera, B. Joseph John, Devinder Kumar
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  ABSTRACT: BackgroundObesity is associated with a proinflammatory state. AimTo determine whether obesity at diagnosis is a risk factor for Crohn’s disease vs. ulcerative colitis and also vs. community controls and whether there is a U-shaped relationship between body mass index at diagnosis and risk of Crohn’s disease versus ulcerative colitis. MethodsA total of 524 consecutive inflammatory bowel disease patients attending gastroenterology clinics were administered a questionnaire inquiring about weight at diagnosis and height as well as other risk factors for inflammatory bowel disease. An opportunistic control group of 480 community controls aged 50–70 were randomly selected from the registers of four local general practices as part of another study. ResultsObesity at diagnosis was more common in subjects with Crohn’s disease versus ulcerative colitis odds ratio 2.02 (1.18–3.43) p=0.0096 and also Crohn’s disease versus community controls in the 50–70year age group (odds ratio 3.22 (1.59–6.52) p=0.001). There was evidence of a ‘dose response’ with increasing degrees of obesity associated with increased risk. Low BMI at diagnosis was also associated with risk of Crohn’s disease versus ulcerative colitis. A U-shaped relationship between BMI and risk of Crohn’s was supported by the strong inverse association of BMI at diagnosis (p=0.0001) and positive association of BMI at diagnosis squared (p=0.0002) when they were fitted together into the model. ConclusionsObesity may play a role in the pathogenesis of Crohn’s disease and it may be that obesity-related enteropathy is a distinct entity or a sub-type of Crohn’s disease. KeywordsCrohn’s disease–Ulcerative colitis–Obesity–Environmental risk factors–Mesenteric fat
  Digestive Diseases and Sciences 04/2012; 56(3):837-844.
• Article: Predictors of Clinical and Endoscopic Findings in Differentiating Crohn’s Disease from Intestinal Tuberculosis

  Xuefeng Li, Xiaowei Liu, Yiyou Zou, Chunhui Ouyang, Xiaoping Wu, Minghuan Zhou, Linlin Chen, Lingjuan Ye, Fanggen Lu
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  ABSTRACT: BackgroundThere are many similarities and overlaps in clinical manifestations and ileocolonoscopic features between Crohn’s disease (CD) and intestinal tuberculosis (ITB). Differentiation between CD and ITB is of great importance. AimTo investigate the values of clinical and endoscopic findings in differential diagnosis between CD and ITB. MethodsClinical and endoscopic features of a cohort of 130 cases of CD and 122 cases of ITB from June 2003 to February 2009 were retrospectively reviewed following predetermined criteria. Parameters were screened by logistic regression analysis. Furthermore, the diagnostic efficacy of screened parameters was analyzed by regression equation (mathematical model) and receiver operating characteristic curve (ROC curve). ResultsThe clinical features helpful in differentiating CD from ITB are hematochezia, intestinal surgery, perianal diseases, pulmonary tuberculosis, ascites, and positive of PPD skin test; the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of regression mathematical model established by clinical features were 90.3, 76.8, 83.8, 80.7, and 88.0%, respectively. The endoscopic features helpful in differentiating CD from ITB were rectum involved lesions, longitudinal ulcer, cobblestone appearance, fixed-open ileocecal valve, transverse ulcer, and rodent ulcer; the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of regression mathematical model established by endoscopic features were 82.9, 82.0, 82.5, 82.9, and 82.0%, respectively. ConclusionsIt was proposed that a diagnostic algorithm based on available clinical and endoscopic regression equation could improve the current sensitivity, specificity, and accuracy in differentiating between CD from ITB. KeywordsCrohn’s disease–Intestinal tuberculosis–Differential diagnosis–Clinical features–Endoscopic features–Regression equation
  Digestive Diseases and Sciences 04/2012; 56(1):188-196.
• Article: Rapunzel’s Syndrome

  A. Kansagra, N. Nagaria, S. Ahlawat
  Digestive Diseases and Sciences 04/2012; 55(11):3284-3285.
• Article: Can an Immunohistochemistry Method Differentiate Intestinal Tuberculosis from Crohn’s Disease in Biopsy Specimens?

  Ali Tüzün İnce, Pembegül Güneş, Ebubekir Şenateş, Mesut Sezikli, Arzu Tiftikçi, Oya Övünç
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  ABSTRACT: BackgroundIt is sometimes difficult to diagnose whether a patient has intestinal tuberculosis or Crohn’s disease because both have similar clinical, pathologic, and endoscopic features. However, their therapies are completely different and a mistake in diagnosis can result with deterioration. Many laboratory methods for the diagnosis of tuberculosis require considerable time to receive a diagnostic result. We wanted to evaluate whether an immunohistochemical tuberculosis staining method can be helpful for faster differentiation of biopsy materials. MethodsWe used formalin-fixed paraffin-embedded histologically diagnosed small intestine (n=1), colon (n=7), skin (n=8), lung (n=5), lymph node (n=24) tuberculosis and Crohn’s disease (n=28) biopsy materials only with granulomas. Demographic characteristics like age and gender were also obtained. Pathology specimens were stained immunohistochemically with an antibody to VP-M660, targeting the 38-kDa antigen of Mycobacterium tuberculosis. ResultsIn the M. tuberculosis group, 33/45 of patients have positive immunohistochemistry (IHC) staining (73% sensitivity, 93% specifity), whereas only two of 28 patients have positive staining in the Crohn’s group (p<0.001). The positive staining with IHC was detected as 85.7, 75, 75, and 60% in colon, lymph node, skin, and lung granulomas, respectively, in M. tuberculosis patients. ConclusionsImmunohistochemical staining of biopsy specimens with anti-VP-M660 seems to be a simple and fast technique with 73% sensitivity and 93% specificity for establishing an earlier differentiation of M. tuberculosis from Crohn’s disease. KeywordsImmunohistochemistry– Mycobacterium tuberculosis –Crohn’s disease–Differential diagnosis
  Digestive Diseases and Sciences 04/2012; 56(4):1165-1170.
• Article: A Functional SNP of the Interleukin-18 Gene Is Associated with the Presence of Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients

  Yong Seok Kim, Jae Youn Cheong, Sung Won Cho, Kee Myung Lee, Jae Chul Hwang, Bermseok Oh, Kuchan Kimm, Jung A. Lee, Byung Lae Park, Hyun Sub Cheong, Hyoung Doo Shin, Jin Hong Kim
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  ABSTRACT: Background/AimThe natural course of hepatitisB virus (HBV) infection is likely related to host immune factors. Interleukin-18 (IL-18) plays a significant role in immune defense. This study was undertaken to determine the association between the presence of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in the IL-18 gene in HBV-infected patients. MethodsBetween March 2002 and December 2004, 730 Korean subjects were enrolled in two different groups: (1) chronic carrier without HCC (n=637) and (2) HCC (n=93). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions −667G>T, −148G>C, +8925C>G, and +13925A>C in the study subjects. To evaluate the functional significance of SNPs in the IL-18 gene promoter region, we performed a reporter gene assay in HepG2 and Hep3B cells transfected with different alleles. ResultsThe IL-18 −148C allele, +8925G allele, +13925C allele, and haplotype3 (TCGC) were associated with the presence of HCC in codominant and dominant models. Furthermore, functional analyses using the reporter gene assay revealed that the −148C allele conferred significantly lower promoter activity. ConclusionsThis study indicates that the −148C, +8925G, and +13925C alleles of the IL-18 gene are associated with the presence of HCC and the 148G>C SNP is functionally important in determining disease outcome.
  Digestive Diseases and Sciences 04/2012; 54(12):2722-2728.
• Article: Characterization of the Gastric Cardia in Volunteers from the General Population

  Fredrik Petersson, Lennart E. Franzén, Kurt Borch
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  ABSTRACT: The aim of this research was to characterize the mucosa of the gastric cardia in relation to infection with Helicobacter pylori and the occurrence of chronic gastritis in other parts of the stomach in a sample of the general population. In this study, 80 adult volunteers underwent esophagogastroscopy with biopsies from the gastric cardia, corpus, and antrum. Gastritis was classified according to the Sydney system. Chronic gastritis (cardia excepted) was diagnosed in 35 subjects, 30 with H.pylori infection. Epithelial proliferative activity (Ki-67), p53- and p21 expression were examined quantitatively with cell counting after immunohistochemical stainings. Esophagitis was diagnosed macroscopically. Fourty eight subjects had cardia-type and 32 corpus-type mucosa in the anatomical cardia. The prevalence of esophagitis (nine cases) did not differ between these groups. Carditis was more prevalent among subjects with cardia-type mucosa (73 vs. 28%, P<0.0001). H.pylori was present in 48% of those with cardia-type and 25% of those with corpus-type mucosa (P=0.06). Of the 44 subjects with carditis, 31 had H.pylori in this location. The group with H.pylori infection had significantly higher mucosal proliferative activity when compared to uninfected subjects. Among the subjects with H. pylori-associated carditis, more p53-positive epithelial cells were detected compared to both the non-infected group (P=0.0004) and to subjects with non-H.pylori-associated carditis (P=0.03). In subjects with cardia-type mucosa, and both carditis and gastritis, the degree of chronic inflammation was higher in the cardia compared to the corpus and antrum and the p53 expression was significantly higher in the cardia compared to the corpus, but similar to that in the antrum. The proliferative activity was significantly higher in the antrum compared to the cardia and corpus, respectively. In conclusion, H. pylori infection, carditis, and increased p53 expression are more common in subjects with cardia- than corpus-type mucosa in the gastric cardia. Carditis is mainly related to H.pylori infection. There are some differences regarding inflammation, proliferative activity, and p53 expression between the cardia and other regions of the stomach, yet the significance of these differences remains to be clarified.
  Digestive Diseases and Sciences 04/2012; 55(1):46-53.
• Article: Crohn’s Colitis Complicated by Cytomegalovirus Infection

  Barrett G. Levesque, Reetesh Pai, Christine A. Cartwright
  Digestive Diseases and Sciences 04/2012; 54(9):1864-1867.
• Article: Meckel’s Diverticulum with Gastrointestinal Bleeding: Role of Computed Tomography in Diagnosis

  Craig A. Munroe, Andrew Copland, Reetesh Pai, Shai Friedland, George Triadafilopoulos
  Digestive Diseases and Sciences 04/2012; 55(2):242-244.