Goktug Sirin

Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers.

AIM To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESD had premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.

Differential diagnosis of Crohn’s disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae

BACKGROUND/AIMS Glycoprotein 2 (GP2), the major autoantigen of Crohns disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. MATERIALS AND METHODS A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. RESULTS Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. CONCLUSION The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

ESD for Laterally Spreading Tumors in Colon: Experience for a Tertiary Unit

G A A b st ra ct s However the relations between chemoresistance, cytoskeleton and EMT are inevitable. In the present study, we investigated the effect of chemoresistance on cell motility, cytoskeleton, and EMT. METHODS: HT-29, a human colon cancer cell, was exposed to increasing doses of 5FU or oxaliplatin for 6 months to achieve resistance at clinically relevant doses. cDNA microarray analysis was performed for parent and resistant cells. Rates of proliferation and sensitivity to drugs were assessed using WST-1 Assay. Cell movement was analyzed by Timelapse imaging; the images were captured under an Axiovert 200M microscope (CarlZeiss) for eight hours at intervals of 15 min. For cytoskeleton study, morphologic and molecular changes investigated by immunofluorescence staining and PCR analyses. RESULTS; HT29 cells were finally resistant to 5FU (2μg/mL) and oxaliplatin (2μmol/L). cDNA microarray studies showed alteration of cytoskeletal gene expression (actin related genes including caldesmon were upregulated) and EMT-related genes (TGF-beta1, ZEB2, and Vimentin were upregulated and E-cadherin was downregulated) in both 5FU resistant cells and oxaliplatin resistant cells. The both resistant cells exhibited a decrease in cellular proliferation and EMTlike morphologic changes; spindle-cell shape, loss of polarity, intercellular separation, and pseudopodia formation. Time-lapse imaging showed random and accelerated cell motility. Immunofluorescence staining revealed that E-cadherin expression was decreased and caldesmon expression was enhanced. Caldesmon is reported to act as a potent repressor of cancer cell invasion, however in both resistant cells of this study, overexpressed caldesmon was not associated with F-actin and stress fiber was not developed, which was not typical EMT phenotype. Depletion of caldesmon with siRNA restored the chemoresistant cells to parental cell-like adherent epithelial shape. CONCLUSIONS: These results indicate that chemoresistant CRC developed altered cytoskeleton, accelerated cell motility and atypical EMT phenotype, and that caldesmon is involved in chemoresistance-related phenotypical changes, suggesting that the cytoskeleton related genes are potent molecular targets to chemoresistance and tumor invasion/metastasis.