Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients.

PURPOSE: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients. METHODS: Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves. RESULTS: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease. CONCLUSION: No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.

XELOX followed by XELIRI or the reverse sequence in advanced colorectal cancer.

BACKGROUND: Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (mCRC). In this non-randomized pilot study, we investigated the efficacy and safety of sequentially administered XELOX and XELIRI regimens or the reverse sequence in patients with advanced colorectal cancer. PATIENTS AND METHODS: Entry criteria were histologically confirmed mCRC, ECOG performance status (PS) < or =2 and adequate bone marrow, renal and hepatic function. All patients consecutively received XELOX followed by XELIRI at disease progression or vice versa. RESULTS: In multivariate analysis, independent prognostic factors with worse overall survival were: lower PS (p = 0.0001), multiple metastatic sites (p = 0.016) and high tumor grade. Higher serum levels of alkaline phosphatase and worse ECOG PS were associated with a shorter progression-free survival. Grade 3/4 mucositis, nausea/vomiting, grade 3/4 alopecia and grade 3 diarrhea were more frequent with XELIRI, whereas major toxicity events with XELOX were grade 3 neutropenia, thrombocytopenia and grade 2/3 neurotoxicity. CONCLUSION: Capecitabine appears to be an acceptable alternative to continuous-infusion fluorouracil (FU)/leucovorin (LV) in combination therapy and offers an effective, but more convenient alternative to continuous infusion FU/LV in the first-line treatment of patients with mCRC.

Adjuvant chemoradiation for patients with adenocarcinoma of the pancreas: an expirence of single institute.

Only a small percentage of patients with pancreatic cancer have limited disease suitable for curative resection. Even with surgery, patients often have poor long-term survival due to relapse of the disease. There are controversies about the adjuvant treatment of these patients. We reported the survival of resected pancreatic cancer from a single institute. About 128 consecutive patients who had complete resection of the pancreatic ductal adenocarcinoma were evaluated, retrospectively. Chemoradiotherapy (45 Gy plus 5-fluorouracil) was given to 63 patients. Fifty-five patients declined to take chemoradiotherapy or with poor performance status were observed without additional treatment. Eight patients took only chemotherapy and two patients took only radiotherapy. The median survival of chemoradiotherapy group was significantly higher than the observation group (13 months vs. 4 months, respectively; P < 0.001). In multivariate analyses the most important factors improving survival were the application of chemoradiation (P < 0.001), low-level serum LDH (P = 0.026), good performance status (P = 0.033) and low serum CA19-9 (P = 0.037). Although adjuvant chemoradiotherapy has a significant survival benefit when compared with the observation group, the survival data are still poor for pancreatic cancer. Therefore, we need more effective additional or adjuvant treatment modalities.

Diagnostic value of interleukin-6 and C-reactive protein in acute appendicitis.

The aim of this study is prospectively to evaluate the serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels in detection of acute appendicitis in patients with right iliac fossa pain. Data were collected in prospective manner on 102 consecutive patients with right iliac fossa pain. Laparotomy was performed for suspected acute appendicitis for 55 of the 102 patients, of whom 49 patients had appendicitis, 6 patients non-appendicitis (NA), and the other 47 patients had nonspecific abdominal pain (NSAP) and they did not undergo operation. Among those with appendicitis 31 had acute appendix (AA), 8 had gangrenous appendix (GA), and 10 had perforated appendix (PA). The WBC and CRP the mean (SEM) values were significantly different in AA, GA, and PA groups compared with NSAP and NA groups (P < 0.05). Although the mean IL-6 levels were significantly different only in PA group than the others groups (P < 0.05). The sensitivity and specificity of serum CRP measurements were calculated as 96% and 87%, respectively whereas these were 33% and 83% for IL-6 levels for the diagnosis of the acute appendicitis. As a result, measurement of the CRP levels and WBC have an additional diagnostic value on the diagnosis of the acute appendicitis but determination of IL-6 levels which added to the test combination of WBC and CRP, the sensitivity for the diagnosis of the acute appendicitis was not changed whereas the specificity was decreased to 66%.

Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients).

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.