Sumer Yamaner

Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population

Abstract Background: There is growing evidence describing DNA repair genes polymorphisms are related to increased cancer risk including colorectal cancer (CRC). The aim of this study was to investigate the associations between the APE1 Asp148Glu, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His polymorphisms and CRC risk in Turkish population. Patients and methods: Polymorphisms of APE1 Asp148Glu (rs3136820), hOGG1 Ser326Cys (rs1052133), XRCC1 Arg399Gln(rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and XPG Asp1104His (rs17655) were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods in blood samples of 79 CRC patients at their initial staging and 247 healthy controls. Of the CRC patients, 26 out of 40 were diagnosed with rectal cancer and received neoadjuvant chemoradiotherapy following diagnosis; 39 others were diagnosed as colon cancer. Results: Our preliminary results showed that frequencies of Glu allele of APE1 Asp148Glu and Cys allele of hOGG1 Ser326Cys were higher in CRC patients than in controls (p = 0.006, OR: 3.43; 95% CI: 1.76–6.70; p = 0.000, OR: 2.77; 95% CI: 1.40–5.48, respectively). Higher frequency of Met allele of XRCC3 Thr241Met was detected in patients treated with neoadjuvant chemoradiotherapy (p = 0.024, OR: 5.25; 95% CI: 1.23–23.39) and with proximal colon tumors (p = 0.04, OR: 2; 95% CI: 1.18–3.34). Increased frequency of Ser/Ser genotype of hOGG1 Ser326Cys was found to be associated both with higher grade (p = 0.001, OR: 6.4; 95% CI: 2.69–62.69) and liver metastasis (p = 0.005, OR: 7.5; 95% CI: 0.7–68.36). Conclusion: APE1 Asp148Glu and hOGG1 Ser326Cys polymorphisms might be associated with increasing risk of CRC in a Turkish population. Future studies with larger-sized samples, as well as detecting the association of DNA repair genes with other confounding factors will help elucidate the exact roles of DNA repair genes polymorphisms in development and progression of CRC.

Mitochondrial Lipid Peroxides and Antioxidant Enzymes in Colorectal Adenocarcinoma Tissues

Lipid peroxide levels and superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and glutathione transferase (GST) activities were investigated in mitochondrial fractions obtained from tumorous and nontumorous colorectal tissues of fourteen patients with colon and rectum cancer. Histopathological evaluations, including type, stage, necrosis and lymphocyte infiltration were also performed for each patient. The activities of SOD, GSH‐Px and GST were increased significantly, but lipid peroxide levels remained unchanged in mitochondria obtained from tumors compared to adjacent normal tissues of subjects with colorectal cancer. When the patients were grouped according to their histopathological evaluation, such as type, stage, necrosis and lymphocyte infiltration, no relationship was observed between the histopathological results and the mitochondrial lipid peroxidation or antioxidant enzyme activities.

Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0+ rectal cancer: Istanbul R-01 study

BACKGROUND AND PURPOSE The optimum duration between neoadjuvant radiochemotherapy and transmesorectal excision in locally advanced rectal cancer has not been defined yet. This randomized study was designed to compare the efficacy of four-week versus eight-week delay before surgery. METHODS One-hundred and fifty-three patients with locally advanced low- or mid-rectum rectal adenocarcinoma were included in this single center prospective randomized trial. Patients were assigned to receive surgical treatment after either four weeks or eight weeks of delay after chemoradiotherapy. Patients were followed for local recurrence and survival, and surgical specimens were examined for pathological staging and circumferential margin positivity. RESULTS 4-week and 8-week groups did not differ with regard to lateral surgical margin positivity (9.2% vs. 5.1%, P=0.33, respectively), pathological tumor regression rate (P=0.90), overall survival (5-year, 76.5% vs. 74.2%, P=0.60) and local recurrence rate (11.8% vs. 10.3%, 0.77). Overall survival was better in patients with negative surgical margins (78.8% vs. 53.0%, P=0.04). Local recurrence rate was significantly higher among patients with positive surgical margin (28.5% vs. 9.3%, P=0.02). CONCLUSIONS Intentional prolongation of the chemoradiotherapy-surgery interval does not seem to improve clinical outcomes of patients with locally advanced rectal cancer. Surgical margin positivity seems to be more important with this regard.

Effects of surgical laparoscopic experience on the short-term postoperative outcome of rectal cancer: results of a high volume single center institution.

Purpose The purpose of the study was to assess the effects of the surgeons learning curve on the short-term outcome of laparoscopic resections performed for rectal cancer. Methods A total of 284 patients who underwent laparoscopic resection for rectal cancer performed by 3 different surgical teams between 2005 and 2008 were included in the study. The operative experience was represented by the teams previous surgical case numbers (frequency). Four skill levels were categorized as follows: Level 1: the first 60 cases, Level 2: 61 to 120 cases, Level 3: 121 to 180 cases, and Level 4:>180 cases. Characteristics of the patients, perioperative variables, and the experience levels of the surgeons were analyzed and compared. To investigate the learning curve, we used the following parameters: duration of operative time, conversion rates, general complications, anastomotic leak rates, and oncologic parameters. Results Operative time gradually decreased with increasing experience. The mean operative times for Level 1, Level 2, and Level 3 were 195.0±46.7, 181.7±34.2, and 172.3±33.0 minutes, respectively, whereas the mean operative time for Level 4 was 151.3±27.7 minutes (P<0.05). With increased experience, conversion rates, complication rates, anastomotic leak rates, and hospitalization durations decreased (P<0.05). The resected specimen length was found to be longer with increased surgical experience (P<0.05). There were no significant differences among the groups with regard to tumor size, T stage, harvested lymph node count, lateral margin involvement, and R0 resections. Conclusions The operative time is inversely proportional to the level of skill. Laparoscopic surgical procedures do not have any negative effects on short-term surgical outcome. With the strict application of surgical principles, the oncologic quality of the specimen is not influenced by the experience period. With increased experience, the surgeon feels more confident and performs more difficult and complex laparoscopic surgical interventions for rectal cancer.

Endoscopic diagnosis and management of complications following surgery for gallstones.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is increasingly being performed for therapeutic purposes. This report reviews our experience in an attempt to determine the role and efficacy of ERCP in the management of postoperative complications following surgery for gallstones. Methods: This study analyzes ERCP records of 418 patients performed in a single referral center after a surgery for gallstones, in the period from December 1991 to June 2000. Results: A total of 451 endoscopic procedures were performed for 418 patients. The primary operations which required ERCP and were included in the study were laparoscopic cholecystectomy (n = 161, 38.5%), choledocholithotomy and T-tube drainage (n = 157, 37.5%), open cholecystectomy (n = 82, 19.6%), choledochoduodenostomy (n = 14, 3.3%), and cholecystostomy (n = 4, 1%). Procedure was carried out successfully in 403 patients (96.4%), whereas a proper endoscopic diagnosis was not achieved in 15 (3.5%). Retained biliary stones (without any associated abnormality) were found in 163 (38.9%), ductal injuries in 44 (10.5%), biliary strictures in 21 (5.0%), papillary stenosis in 36 (8.6%), cystic stump leak (with or without retained stones) in 30 (7.1%), leak from T-tube tract (with/or without retained stones) in 20 (4.8%), and unsuspected malignancies in 18 (4.3%). A sole diagnostic cholangiography was obtained in 63 patients (15.0%). Patients were managed by debris or stone extraction in 169 (40.4%), endoscopic sphincterotomy (ES) in 145 patients (34.6%), stent insertion in 19 (4.5%), or dilatation in 2 (0.4%). Overall successful stone removal rate was 97.4%. Thirty-nine patients with normal cholangiographic findings underwent ES for the relief of presenting signs and symptoms. ERCP-related morbidity was 13.6%. Conclusions: The need for ERCP is rising, especially for stones retained after cholecystectomies. Endoscopy offers safe and effective methods in the treatment of bile leaks, unless associated with major ductal injuries. ES is a reasonable method for treating papillary stenosis and some post-cholecystectomy pain or symptoms.

Effects of octreotide on healing of intestinal anastomosis following small bowel obstruction in rats

PURPOSE: Octreotide is an analog of somatostatin, with the same biologic effects but a longer half-life than somatostatin. The purpose of this experimental study was to search the effects of octreotide on the healing of bowel anastomosis and to observe the anatomic and physiologic changes in the obstructed bowel. METHODS: Two groups of ten male Wistar albino rats (average weight, 250 grams) were used in this study. One group was the octreotide group, and the other was the control group. In both groups, the basal diameters of jejunum were measured before ligation of the bowel 20 cm from the duodenum. Octreotide was administered subcutaneously (7 μg/kg/day, in two equal doses) in the first group, and the same volume of saline was used in the control group. Diameters of the obstructed segments were measured, and sodium and potassium levels, obtained from the luminal fluid of the obstructed bowel, were recorded 48 hours following the first operation. Dilated segments were resected, and end-to-end intestinal anastomoses were performed. In rats sacrificed on the fourth and seventh days following the second operation, bursting pressures of the anastomotic and hydroxyproline levels in tissue samples taken from the anastomosis were measured. RESULTS: The diameter of the obstructed bowel increased significantly in the control group (P<0.05). Sodium and potassium losses were significantly less in the octreotide group (P<0.001 for sodium;P<0.01 for potassium). In histopathologic examination, ischemic changes were more evident in the control group (P<0.05). Anastomotic bursting pressure differences were not significant on the fourth postoperative day (P>0.05), but differences were significant on the seventh postoperative day (P<0.05). Anastomotic tissue hydroxproline synthesis on the fourth and seventh postoperative days of the octreotide and control groups did not show significant difference (P>0.05). CONCLUSION: In this experimental model, it appears that octreotide attenuates the ischemic changes and electrolyte losses in the obstructed bowel.

MR Colonography after Oral Administration of Polyethylene Glycol–Electrolyte Solution

This prospective study was approved by the local institutional ethics committee, and written informed consent was obtained from all patients. The aim of this study was to determine whether the oral administration of a polyethylene glycol (PEG)-electrolyte solution induces adequate luminal distention for magnetic resonance (MR) colonography to be performed and to assess patient acceptance of this procedure. Fifty-five patients (26 women, 29 men; mean age, 60.5 years +/- 14 [standard deviation]; age range, 40-75 years) who were referred for optical colonoscopy (OC) owing to symptoms and findings that included rectal bleeding, altered bowel habits, and positive fecal occult blood test results participated in this study. Standard bowel preparation was performed 1 day before the procedure. MR colonography was performed and followed by OC on the same day. Before undergoing MR colonography, the patients received 2.0-2.5 L of the PEG-electrolyte solution orally. Adequate distention of all colonic segments was achieved in 50-53 (91%-96%) of patients imaged in the supine position and in 51-53 (93%-96%) of patients imaged in the prone position. Oral administration of the solution yielded uniform luminal darkening and sufficient colonic distention for MR colonography in 91%-96% of patients.

Association between PTEN IVS4 polymorphism and development of colorectal cancer in a Turkish population.

Background: Phosphatase and tensin homolog (PTEN) is one of the most frequently mutated suppressor genes in human cancers. However, there are no data about the role of PTEN IVS4 polymorphism in development of colorectal cancer (CRC). The authors aimed to determine the role of PTEN IVS4 variants in the etiology of CRC. Patients and methods: A hospital-based case–control study was conducted in 203 patients with CRC (127 colon, 76 rectum) and 245 healthy controls. The frequencies of PTEN IVS4 (rs 3830675) genotypes were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The (-/-) genotype of PTEN IVS4 that absence of ATCTT insertion at downstream of exon 4 in intron 4 of PTEN gene was found to be associated with 1.55-fold increased risk of colon cancer (p < 0.005; OR: 1.55, 95% CI: 1.24 – 1.94) and 1.4-fold increased risk of rectum cancer (p < 0.005; OR: 1.4, 95% CI: 1.08 – 1.82). Subgroup analyses showed that PTEN IVS4 genotypes were not associated with any clinicopathological characteristics of patients with CRC (p > 0.05). Conclusion: The (-/-) genotype of PTEN IVS4 gene might be associated with increased risk for development of CRC in a Turkish population. Further studies will clarify the exact role of PTEN IVS4 polymorphism in the etiology of CRC.

COMPARISON OF SODIUM PHOSPHATE, POLYETHYLENE GLYCOL AND SENNA SOLUTIONS IN BOWEL PREPARATION: A PROSPECTIVE, RANDOMIZED CONTROLLED CLINICAL STUDY

Background:  Low volume oral solutions for colon cleansing before colonoscopy are gaining popularity over large volume oral lavage solutions. Therefore, we aimed to compare three oral solutions for colonoscopy to determine any changes in either patient compliance or cleansing ability.

The Effects of Beta-Aminopropionitrile on Colonic Anastomosis in Rats

Wound contraction is a clinically important biological process because it frequently results in contractures, strictures, and stenosis. If collagen synthesis could be altered to minimize the contracture, then the outcome could be improved. Lathyrism produces poorly cross-linked collagen in healing anastomosis, keeping a larger portion of the synthesized collagen soluble. Ultimately, the amount of contracting collagen is reduced, lowering the bulk and lessening the contracture. The aim of this study was to observe the effects of a lathyrogen, beta-aminopropionitrile (BAPN), on the healing of colonic anastomosis. Thirty rats were divided into three groups. Colostomy and anastomosis were performed on all rats. Intraperitoneal saline solution (control) and either intraperitoneal (ip) or oral (po) BAPN were administered. The rats were killed 1 week later. Anastomotic healing was assessed by bursting pressure and the hydroxyproline content of the anastomotic tissues. Granulation tissue thickness, number of fibroblasts, inflammatory cells, and growing capillaries in granulation tissue per unit area were determined. Collagen fibril diameters were estimated, and spatial arrangements of fibrils were examined by an electron microscope. All results were evaluated by Mann–Whitney U-test. The analyses of anastomotic tissues from BAPN-treated rats showed a significantly reduced mean bursting pressure (158.9 ± 12.3, 171.3 ± 13.9, ip and po, respectively), hydroxyproline content (8.9 ± 2.6, 10.1 ± 2.7), granulation tissue thickness (24.3 ± 2.6, 16.1 ± 5.2), number of inflammatory cells (37.8 ± 4.3, 25 ± 4.3), fibroblasts (3.2 ± 1.1, 2.8 ± 0.7), and a significantly reduced collagen fiber diameter (15 ± 2, 20 ± 3) compared with those of control group (236.9 ± 9, 14 ± 4.4, 26.8 ± 4.8, 39 ± 2.6, 6.9 ± 1.1, and 35 ± 5, respectively). As a result, collagen fibers were flimsy, and lost their regular parallel alignment in the BAPN groups. On the other hand, a number of growing capillaries were found to be significantly increased in these groups (16.5 ± 1.1, 18.2 ± 0.7) compared to the control (6.7 ± 1.3). Thus, it is suggested that BAPN may be useful in the prevention of gastrointestinal stricture formation.