Emre Balik

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.

A surgical approach to anogenital Buschke Loewenstein tumours (giant condyloma acuminata).

Abstract Background: Condyloma acuminata are anogenital warts caused by human papillomavirus (HPV). Neglected giant peri-anal condyloma acuminata (Buschke Loewenstein Tumours) require major surgical procedures. This report reflects our experience concerning the aggressive surgical approach to this rarely presented type of condyloma acuminata. Methods: The medical records of five patients, who had been surgically treated following the diagnosis of giant perianal condyloma acuminata between April, 1996 and September, 2003 were reviewed and evaluated retrospectively. Full thickness tumour and skin excisions were performed followed by delayed split thickness skin graftings in all patients. Results: Five patients (3 men, 2 women) who suffered from giant condyloma acuminata lesions obliterating the anal canal were evaluated. The mean age was 36.5 years (range: 24–52). All patients underwent total surgical excisions. The wounds were left open for secondary healing, and following a mean time period of 35 days, split thickness skin graftings were performed. The histopathologic examinations of the specimens of these five patients did not reveal any malignant transformations. No recurrences were detected at the end of a mean follow-up period of 22 months and all patients were considered to be disease-free at the end of their long-term 5-year follow-up periods. Conclusions: Peri-anal condyloma acuminatum is usually a benign disease, but may grow locally to an excessive extent, developing into a Buschke Loewenstein Tumour, and may cause serious peri-anal hygiene problems. Even though the incidence of malignant transformation is rare, there is always a risk of this complication occurring. Transmission of the disease to other sexual partners is another point of concern. Therefore, this disease must be treated aggressively with total surgical excision. The results of our surgical treatment methods are satisfactory.

Oxidative Damage in an Experimentally Induced Gastric and Gastroduodenal Reflux Model

The exact pathophysiologic mechanisms of esophageal cell damage and carcinogenesis by gastroesophageal reflux are not clearly understood. The aim of this study was to evaluate the damage to the esophageal epithelium that occurs after acid reflex and mixed acid and bile reflux by assessing histopathology, reactive oxygen species, and DNA damage. Eighty 10-week-old male Sprague-Dawley rats were divided into two groups, an acid reflux group and a mixed (acid/bile) reflux group. Acid reflux was achieved by esophagogastroplasty in which mixed reflux was encouraged via esophagoduodenal anastomosis. Each group contained a control subgroup that underwent sham laparotomy alone. The rats were killed 3, 6, 9, and 12 months after surgery. Malondialdehyde, protein carbonyl content, and DNA damage were determined in lymphocytes. Histopathologic analysis was performed according to the histologic activity index. Inflammation, ulcer, and regeneration in both reflux groups were significantly increased in the esophagus at 3, 6, 9, and 12 months compared with the control group. Mucosal damage was greater in the mixed reflux group compared with the gastric reflux group. Malondialdehyde and carbonyl content in the serum, and DNA damage in lymphocytes, were significantly increased in both reflux groups. At 9 and 12 months, oxidative damage was increased in the mixed reflux group compared with the acid reflux group. Oxygen-derived free radicals seem to be one of the important mediators in the evaluation and generation of reflux esophagitis. The impact of oxygen free radicals, as demonstrated in this study, can be evaluated by assessing the damage that they incur to lipid membranes, serum proteins, and circulating lymphocyte DNA. Serum malondialdehyde and carbonyl content as well as lymphocyte DNA damage were significantly increased in the setting of acid and mixed acid/bile reflux in these rodent models. Further, these serum and lymphocytic changes were associated with esophageal ulceration, inflammation, and regeneration. Evaluation of such markers as serum malondialdehyde and carbonyl content as well as evaluation of lymphocyte DNA might prove to be useful investigations in patients with precancerous and cancerous conditions in addition to conventional methods of diagnosis. Further studies, both animal and human are warranted.

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.

Dual Inhibition of Wound Healing and Oxidative Process by Montelukast in Experimental Colon Anastomoses

Background. The authors aimed to investigate the effects of montelukast (ML) on the experimental rat colon anastomosis. Methods. A total of 80 Wistar albino rats were divided into 4 groups: sham-operated, colon anastomosis, and colon anastomosis with oral administration (OAML) and rectal administration of 10 mg/kg/d ML (RAML). Anastomotic bursting pressure, anastomotic hydroxyproline contents, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPX), and superoxide dismutase (SOD) levels, and the expressions of Ki-67, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) with immunohistochemistry were assessed on postoperative day 5. Results . Anastomotic bursting pressures and bFGF expressions were not changed, whereas tissue hydroxyproline concentrations and MDA levels and the expressions of Ki-67 and VEGF were significantly decreased, and GSH, GPX, and SOD levels were significantly increased in the OAML and RAML groups. Conclusion. ML causes impairment of wound healing without altering the anastomosis bursting pressure and reverses the oxidative damage of the colon anastomoses in rats.

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.

Do different abdominal incision techniques play a role in wound complications in patients operated on for gastrointestinal malignancies ? "Scalpel vs. electrocautery".

Abstract Background: Despite the studies of animals that demonstrate better wound healing after abdominal incisions with the use of a scalpel rather than electocautery, clinical experience does not confirm these findings. The purpose of this study was to compare the early postoperative and late-term wound complication rates between the scalpel and electrocautery in patients with gastrointestinal malignancies undergoing midline abdominal incisions. Methods: Patients undergoing midline abdominal incisions for gastrointestinal malignancies were randomly divided into two groups according to the method used to perform the incisions: scalpel or electrocautery. Complications were investigated, diagnosed and compared in the early postoperative and late-term follow-up periods. The independent samples, chi-square, and Student’s t tests were used for statistical analysis. Results: Two hundred and eighteen patients were included to this study, of whom 97 (44.5%) were in the scalpel group and 121 (55.5%) in the electrocautery group. Both groups were similar with respect to their demographic, operative and postoperative characteristics. The analysis revealed no significant statistical differences in consideration of the incidences of either wound infection in the early postoperative period or incisional hernia in the late-term follow-up period between these two study groups (p > 0.05). Conclusions: Scalpel and electrocautery are similar in terms of early postoperative and late-term wound complications when used to perform midline abdominal incisions. Therefore, the choice of method remains a matter of the surgeon’s preference.

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.