Updating controversies on the multidisciplinary management of gastric cancer.

The rates of relapse and death remain high in gastric cancer patients, especially in advanced stages. Local relapses in the tumour bed and regional lymph nodes, peritoneal spread as abdominal carcinomatosis, and distant metastasis are common mechanisms of failure after a R0 resection. To overcome this, a multidisciplinary approach has been prompted. In recent years, multidisciplinary treatment has been strengthened by some randomised controlled trials and it is now considered the standard by most groups, although the improvement in long-term survival rates achieved is still limited. This new therapeutic approach in gastric cancer is rapidly evolving and has led to a series of controversies on the best strategy to follow. Some of these controversies are discussed in this paper.

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model.

BACKGROUND: There is strong evidence demonstrating that activation of epidermal growth factor receptors (EGFRs) leads to tumor growth, progression, invasion and metastasis. Erlotinib and gefitinib, two EGFR-targeted agents, have been shown to be relevant drugs for lung cancer treatment. Recent studies demonstrate that lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2 receptors, is clinically effective against HER-2-overexpressing metastatic breast cancer. In this report, we investigated the activity of lapatinib against non-small cell lung cancer (NSCLC). METHODS: We selected the lung cancer cell line A549, which harbors genomic amplification of EGFR and HER-2. Proliferation, cell cycle analysis, clonogenic assays, and signaling cascade analyses (by western blot) were performed in vitro. In vivo experiments with A549 cells xenotransplanted into nude mice treated with lapatinib (with or without radiotherapy) were also carried out. RESULTS: Lapatinib dramatically reduced cell proliferation (P < 0.0001), DNA synthesis (P < 0.006), and colony formation capacity (P < 0.0001) in A549 cells in vitro. Furthermore, lapatinib induced G1 cell cycle arrest (P < 0.0001) and apoptotic cell death (P < 0.0006) and reduced cyclin A and B1 levels, which are regulators of S and G2/M cell cycle stages, respectively. Stimulation of apoptosis in lapatinib-treated A549 cells was correlated with increased cleaved PARP, active caspase-3, and proapoptotic Bak-1 levels, and reduction in the antiapoptotic IAP-2 and Bcl-xL protein levels. We also demonstrate that lapatinib altered EGFR/HER-2 signaling pathways reducing p-EGFR, p-HER-2, p-ERK1/2, p-AKT, c-Myc and PCNA levels. In vivo experiments revealed that A549 tumor-bearing mice treated with lapatinib had significantly less active tumors (as assessed by PET analysis) (P < 0.04) and smaller in size than controls. In addition, tumors from lapatinib-treated mice showed a dramatic reduction in angiogenesis (P < 0.0001). CONCLUSION: Overall, these data suggest that lapatinib may be a clinically useful agent for the treatment of lung cancer.

Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer.

PURPOSE: To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy. PATIENTS AND METHODS: Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m(2) twice daily Monday through Friday and oxaliplatin 60 mg/m(2) intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively. RESULTS: No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2. CONCLUSION: The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study.

Meduloepitelioma maligno del adulto no teratoide con invasión a las fosas nasales / Adult's malignant non teratoid medulloepithelioma with nasal invasion

Se presenta un caso de meduloepitelioma maligno del adulto de la variedad no teratoide. La neoplasia se originó en el globo ocular, invadió a la órbita y secundariamente a las fosas nasales. Se discute la biología e histogénesis de esta rara neoplasia y la clasificación general de los tumores neuroectodérmicos de las fosas nasales. Se hace énfasis en la importancia del diagnóstico diferencial en especial por la confusión diagnóstica histopatológica inicial