Dursun Bugra

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.

False aneurysm of the hepatic artery after laparoscopic cholecystectomy.

Abstract Purpose: A rare complication of laparoscopic cholecystectomy is defined: iatrogenic injuries to hepatic artery system which may evolve to pseudoaneurysms in the late postoperative period. This rare phenomenon may be overlooked and pose a challenge to surgeons. Material and methods: We will describe three cases with iatrogenic pseudoaneurysms after laparoscopic cholecystectomy. The onset of symptoms and the course of the disease was not uniform. Diagnosis was made after a considerable delay. In the first case, a small, uncomplicated extrahepatic pseudoaneurysm was successfully treated with coil embolization. The second patient who had an intrahepatic pseudoaneurysm with multiple injuries to the common bile duct and portal vein, did not survive despite surgical and endovascular interventions. In the latter, surgical treatment for a large pseudoa-neurysm that had ruptured into the liver parenchyma was successfully conducted. Review of the literature reveals fifty-four more cholecystectomy-related pseudoaneurysms. The site of injury was the right hepatic artery in 61% of the cases and the presenting symptom was upper gastrointestinal bleeding (haemobilia) in two-third of the patients. Embolization was performed in 82% of the cases, and surgery was undertaken in the remaining 18%. Conclusion: Pseudoaneurysm is an uncommon complication of laparoscopic cholecystectomy. Prompt attention is necessary since the lesion has a high risk of rupture. Embolization is the first line of treatment and surgery is reserved for more complex injuries and cases with life-threatening rupture of the aneurysm.

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.

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.

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.

H3K9me3/H4K20me3 Ratio in Circulating Nucleosomes as Potential Biomarker for Colorectal Cancer

Detection of cancer-related histone modifications of nucleosomes in the circulating blood may be useful in early cancer diagnosis. We have analyzed the trimethylation of histone H3 lysine 9 (H3K9me3) and histone H4 lysine 9 (H4K20me3), two modifications involved in heterochromatin formation, at pericentric heterochromatin of circulating nucleosomes in the blood plasma of healthy individuals, patients with either colorectal cancer or multiple myeloma. H3K9me3 was found to be decreased in colorectal cancer and increased in multiple myeloma while H4K20me3 levels were similar in all study groups. Therefore, we used the H3K9me3/H4K20me3 ratio for normalizing H3K9me3 concentrations; it significantly distinguished patients with colorectal cancer (median 0.8) from the healthy group (median 3) and multiple myeloma (median 4.7) (both p < 0.001). We conclude that if validated in a larger series of cases the ratio H3K9me3/H4K20me3 might be a potential diagnostic biomarker for colorectal cancer.

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.