The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial.

There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2-4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25-0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53-1.34 and HR: 0.76; 95% CI: 0.50-1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.

Reduction of ischaemia-reperfusion injury in a rat lung transplantation model by low-concentration GV1001.

OBJECTIVES: Lung ischaemia-reperfusion (IR) injury is one of the major complications following lung transplantation. The novel peptide GV1001, which is derived from human telomerase reverse transcriptase, has been reported to possess both antitumour and anti-inflammatory effects. In this study, we focused on the anti-inflammatory effects of GV1001 to investigate the IR injury prevention effect of GV1001 in a rat lung transplantation model. METHODS: An orthotopic left lung transplantation rat model was established using the modified cuff technique. We applied 50 ml of normal saline (control), Perfadex (low-potassium standard dextran containing perfusion solution), Perfadex with 5 mg GV1001 (5-mg GV, low concentration) and Perfadex with 50 mg GV1001 (50-mg GV, high concentration) as both flushing and preservation solutions. The left lung was stored in the same solution as the flushing solution at 4°C for 3 h. After transplantation, the recipient rats were monitored for 3 h. Arterial blood gas analysis (ABGA), bronchoalveolar lavage (BAL) analysis, wet/dry ratio, histological analysis, apoptotic cell analysis and cytokine [tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)] analysis were performed to determine the reduction or prevention effect of GV1001 regarding lung IR injury. RESULTS: Compared with the control group, the neutrophil count in BAL, reperfusion oedema and cytokine (TNF-α, IL-6) levels of the transplanted lung were significantly decreased in the 5-mg GV group. Compared with the Perfadex group (16.85 ± 2.43), the neutrophil count in BAL was also significantly decreased in the 5-mg GV group (5.39 ± 0.81) (P< 0.001). In addition, the cytokine (TNF-α, IL-6) levels of the transplanted lung were also significantly decreased in the 5-mg GV group (41.99 ± 12.79, 1069.74 ± 98.48 pg/ml) compared with the Perfadex group (90.73 ± 23.87, 2051.92 ± 243.57 pg/ml) (P < 0.05 and P < 0.001, respectively). However, the 50-mg GV group showed less effect than the 5-mg GV group. CONCLUSIONS: Adding a low concentration of GV1001 to the lung preservation solution (Perfadex) provided potential protective effects against IR injury after lung transplantation in rats. Therefore, GV1001 should be considered as a promising anti-inflammatory agent for IR injury.

Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. METHODS: This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS: Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index >/=18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of >4 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. CONCLUSIONS: Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB.

Adjuvant chemotherapy with 5-fluorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma.

BACKGROUND: In this study we explored the effectiveness of adjuvant chemotherapy in node-positive, resected thoracic esophageal squamous cell carcinoma patients. METHODS: A prospective study of postoperative chemotherapy in N1 esophageal cancer patients who received curative resection was conducted and compared with the historical control group in regard to recurrence rate, patterns of failure, disease-free survival rate, and overall survival rate. The postoperative chemotherapy consisted of cisplatin (60 mg/m2 intravenously) and 5-fluorouracil (1,000 mg/m2 per day) in a continuous infusion for 4 days. Three cycles were administered at 3-week intervals. RESULTS: Forty patients were accrued from January 1998 to January 2003 at Samsung Medical Center for adjuvant chemotherapy. The historical control group consisted of 52 patients who received curative resection but not adjuvant chemotherapy during the same period of time. The 3-year disease-free survival rate was 47.6% in the adjuvant group and 35.6% in the control group (p = 0.049). The estimated 5-year overall survival rates were 50.7% in the adjuvant group and 43.7% in the control group (p = 0.228). The significant predictive factors for tumor recurrence were the number of positive lymph nodes (p = 0.008) and the adjuvant chemotherapy (p = 0.030). CONCLUSIONS: This study suggests that the postoperative chemotherapy may prolong disease-free survival in lymph node-positive, curatively resected esophageal cancer patients. The postoperative treatment modality for esophageal cancer patients should be determined according to the lymph node status and a randomized phase III clinical trial is warranted using adjuvant chemotherapy if the esophageal cancer is lymph node-positive.