Mehmet Levhi Akin

COLOR: A Randomized Clinical Trial Comparing Laparoscopic and Open Resection for Colon Cancer

Background: Laparoscopic surgery has proven to be safe and effective. However, the value of laparoscopic resection for malignancy in terms of cancer outcome can only be assessed by large prospective randomized clinical trials with sufficient follow-up. Methods: COLOR (COlon carcinoma Laparoscopic or Open Resection) is a European multicenter randomized trial which has started in September 1997. In 24 hospitals in Sweden, The Netherlands, Germany, France, Italy and Spain, 1,200 patients will be included. The primary end point of the study is cancer-free survival after 3 years. Results: Within <2 years, more than 540 patients have been randomized for right hemicolectomy (45%), left hemicolectomy (10%) and sigmoidectomy (45%). 33 patients (6%) were excluded after randomization. The accrual rate is approximately 25 patients/month. Current survival rates for the whole study group are: stage I: 95%, stage II: 98%, stage III: 93%, stage IV: 64%. For all patients with stage I disease, the mortality was not cancer related. Conclusions: Although laparoscopic surgery appears of value in colorectal malignancy, results of randomized trials have to be awaited to determine the definitive place of laparoscopy in colorectal cancer. Considering the current accrual rate, the COLOR study will be completed in 2002.

Pretreatment Neutrophil/Lymphocyte Ratio as a Prognostic Aid in Colorectal Cancer

BACKGROUND Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. MATERIAL-METHODS Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. RESULTS Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082- 3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. CONCLUSIONS High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

Angiogenesis predicts poor prognosis in gastric carcinoma.

Background/Aims: New prognostic factors in gastric carcinoma to determine the prognosis of the disease or to identify patients who will benefit from adjuvant therapy are being researched. The aim of this study is to investigate the correlation between microvessel count (MVC) and various clinicopathologic features in gastric carcinoma in order to evaluate the role of angiogenesis on the prognosis of gastric cancer. Methods: Fifty-seven patients who underwent surgical intervention for gastric carcinoma between 1993 and 1997 were reviewed retrospectively. The relationship between MVC and various clinicopathological features was assessed. The effect of angiogenesis on overall survival and the role of MVC and other prognostic factors on distant metastases were assessed by multivariate analysis. Microvessels were outlined by anti-factor VIII, which is a specific monoclonal antibody to factor VIII in vessel endothelial cells, using the streptavidin-biotin method and counted under light microscopy ×200 magnification. Results: There was no correlation between MVC and age or sex of the patient, duration of symptoms or tumor size. Proximally located, undifferentiated, diffuse type, serosal invasion positive, lymph node invasion positive, advanced stage, or distantly metastasized tumors had higher MVCs. Higher MVCs affected the overall survival adversely. Lymph node metastasis, serosal invasion and MVC were found as independent prognostic factors affecting distant metastases. MVC was the sole factor affecting recurrent liver metastasis. Conclusion: It is concluded that MVC in gastric carcinoma may be a valuable prognostic factor to predict patients at high-risk for possible recurrences and to decide on postoperative adjuvant therapy.

D-Dimer in the Early Diagnosis of Acute Mesenteric Ischemia Secondary to Arterial Occlusion in Rats

Background: Early diagnosis of mesenteric ischemia can be life saving. The aim of this study is to investigate the time-dependent diagnostic value of plasma D-dimer and other ancillary laboratory evaluations such as creatine phosphokinase, lactic dehydrogenase, aspartate aminotransferase, alanine aminotransferase, amylase, and leukocyte count in an experimental superior mesenteric arterial occlusion (SMA-O) model in rats. Methods: Forty male Wistar-Albino rats were separated into 4 groups: 2-, 4-, 6-, and 12-hour SMA-O groups. After laparotomy, the SMA was identified and ligated for 2, 4, 6 and 12 h in the 4 respective study groups. Blood samples were taken for laboratory tests 2 h after laparotomy in the control group and at the end of the ischemic period in the study groups. Results: The longer the duration of mesenteric ischemia, the higher were the serum D-dimer levels in the study groups, and statistical significance was obtained at 2 h (p = 0.021). Sensitivity, positive predictive value, negative predictive value, and accuracy of the relation were 88.8, 88.8, 100 and 90%, respectively. Leukocyte count was significantly higher than controls after 12 h. No other laboratory parameter correlated positively with the duration of mesenteric ischemia. Conclusion: Serum D-dimer measurements may be a valuable diagnostic parameter in the early diagnosis of mesenteric ischemia.

Missed injuries in military patients with major trauma : Original study

OBJECTIVE The incidence and subsequent outcomes of missed injuries and the primary factors contributing to each missed injury were analyzed. METHODS Records of 709 trauma patients were reviewed between December 2003 and December 2004. Demographic data were compared and analyzed for two patient groups: those with multiple injuries diagnosed in 24 hours and those with multiple injuries diagnosed in >24 hours. RESULTS Fifty-two missed injuries were determined in 34 (4.8%) patients. There were significant differences between the patients with and without delayed diagnoses, including the mean injury severity scores (23 vs. 16.9), morbidity, and mortality (p < 0.05 for all). Among 69 contributing factors identified, 28 (40.6%) were unavoidable and 41 (59.4%) were potentially avoidable. CONCLUSIONS Missed injuries could usually be encountered in the most seriously injured patients, particularly in those with altered levels of consciousness. Missed injuries were mostly avoidable and most were the result of inadequate clinical examination.

The survival effect of E-cadherin and catenins in colorectal carcinomas

Aim  The E‐cadherin/catenin complex plays an important role in epithelial tissue architecture. Decreased expression of cell adhesion molecules (E‐cadherin, α‐, β‐ and γ‐catenin) have been reported to correlate with invasive behaviour. The aim of this study was to investigate the relation between the expression of adhesion molecules and clinicopathological characteristics and survival in colorectal carcinoma.

Necrotizing fasciitis: A life-threatening clinical disorder in uncontrolled type 2 diabetic patients.

We presented 23 patients with necrotizing fasciitis (NF), 15 of whom had uncontrolled diabetes mellitus (DM), for risk factors, clinical signs, laboratory findings and prognosis during the period 1998 and 2006 in Istanbul. A hospital incidence of NF was 14.2/100,000 admissions. Other risk factors were obesity in 9 and recent surgical trauma in 10 patients. The mean age of the patients with DM was higher than that of the patients with non-DM (58.6+/-12.8 vs 43.0+/-17.2 years, p=0.028). The most frequently isolated microorganisms from tissue cultures were Escherichia coli, Klebsiella pneumoniae and Group A streptococci. Of the 23 patients, 9 (39%), of whom 8 had DM, died between 2 and 29 days after admission. The mortality rate and length of hospitalization were longer in diabetic patients than in others (p=0.02 and p=0.286, respectively). The mean blood glucose levels and HbA1C were higher in non-survival group than in survival group (195.6+/-41.5 vs 133.7+/-22.1 and 10.6 vs 7.4) (p=0.04, r=0.39 and p=0.03, r=0.50, respectively). In the univariate analysis, the hospitalization time (r=0.72), white blood cell count (r=0.52) and surgical debridement count (r=0.47) were found to be prognostic risk factors. Our results showed that NF is a very serious life-threatening disorder in especially diabetic patients with bad metabolic control.

Hyperbaric Oxygen Ameliorates Bacterial Translocation in Rats with Mechanical Intestinal Obstruction

AbstractPURPOSE: The aim of this study was to demonstrate bacterial translocation after experimentally induced intestinal obstruction as well as investigate the preventive effects of hyperbaric oxygen on obstruction-induced bacterial translocation in rats. METHODS: Forty Wistar-albino male and female rats were used. Although no procedure was done in the control group (n = 8), hyperbaric oxygen treatment under 2.5 atm absolute for 90 minutes daily was applied for two days in the hyperbaric oxygen group (n = 8). In the sham group (n = 8), after laparotomy the small bowel was only handled gently, and tissue sampling was done 48 hours later. In the obstruction group (n = 8) the ileum was ligated by 5-0 polypropylene just 5 cm proximal to the ileocecal valve. In the obstruction and hyperbaric oxygen group (n = 8), after obstruction hyperbaric oxygen treatment was applied. Forty-eight hours after the procedures, tissue samples from small bowel, mesenteric lymph nodes, spleen, and liver were taken and 1 ml of blood from the portal vein was withdrawn. All samples were cultured for microbiologic examination. RESULTS: Hyperbaric oxygen treatment significantly reduced the endogenous bacterial overgrowth in the small intestine of normal rats. Endogenous bacteria in the small intestine were significantly increased in the obstruction group, and the presence of bacterial overgrowth was proven by bacterial presence on mesenteric lymph nodes, spleen, liver, and blood. Hyperbaric oxygen treatment significantly reduced the endogenous bacterial overgrowth in the small intestine and prevented the bacterial translocation almost completely in obstruction-induced rats. CONCLUSIONS: Intestinal obstruction causes bacterial overgrowth and translocation. Hyperbaric oxygen treatment prevents the bacterial translocation effectively.

Hyperbaric oxygen prevents bacterial translocation in rats with obstructive jaundice.

This study was designed to demonstrate bacterial translocation following bile duct ligation and investigate preventive effects of hyperbaric oxygen on obstructive jaundice-related bacterial translocation in an animal model. Hyperbaric oxygen treatment significantly reduced the endogenous colony counts in distal ileum of normal rats both in the short (two days) and long (seven days) term. Endogenous bacteria in distal ileum significantly increased in bile duct ligated rats in the short and long term, and presence of bacterial translocation was proven by bacterial growth in mesenteric lymph nodes, liver, spleen, and blood. Short- and long-term hyperbaric oxygen treatments significantly reduced the intestinal colony counts and prevented the bacterial translocation almost completely in rats with bile duct ligation. It is concluded that obstructive jaundice causes bacterial overgrowth and translocation, and hyperbaric oxygen treatment can prevent both bacterial overgrowth and translocation effectively.

Prognostic value of oncoprotein expressions in thyroid papillary carcinoma

The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC.