Surgical Strategy for Primary Colorectal Carcinoma and Synchronous Pulmonary Metastasis Resection.

BACKGROUND: The surgical strategy for single-stage resection of primary colorectal cancer (CRC) and synchronous pulmonary metastases remains a matter of debate. METHODS: Perioperative data of patients who underwent single-stage resection of primary CRC and synchronous pulmonary metastases were compared to those of patients who underwent 2-stage resections. The demographic data, number of metastases, type of pulmonary and colorectal resections, operation time, blood loss, postoperative complications, morbidities, mortality, medical costs, and length of hospital stay were analyzed. RESULTS: Twenty-two patients underwent single-stage resection of primary CRC and pulmonary metastases, while 27 patients underwent 2-stage resection. Tumor size and the number of pulmonary metastases were not significantly different between the 2 groups. The extent of pulmonary metastasectomy and abdominal procedures were similar in both groups, as was the thoracic surgical approach (video-assisted thoracic surgery vs. thoracotomy). However, open laparotomy was performed more frequently in the 2-stage group than in the single-stage group (p=0.045), which also had a longer total anesthetic time (p=0.013). The operation time, medical costs, estimated blood loss, complication rates, and severity were similar in both groups, but the length of hospital stay was shorter in the single-stage group (p<0.001). CONCLUSION: Single-stage colorectal and pulmonary resection shortened the overall hospital stay, with no significant changes in operation time, medical costs, hospital mortality, and morbidity. Therefore, single-stage resection could be a good surgical strategy in selected patients.

Molecular profiles of EGFR, K-ras, c-met, and FGFR in pulmonary pleomorphic carcinoma, a rare lung malignancy.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare type of lung cancer characterized by the poor response to conventional chemotherapy and subsequent disappointing outcomes. Therefore, it is paramount to delineate the molecular characteristics of this disease entity. METHODS: In this study, we retrospectively examined the surgical specimens of 61 patients who underwent lung surgery. Mutational or gene amplification statuses of epidermal growth factor receptor (EGFR), k-ras, c-kit, c-met, and fibroblast growth factor receptor (FGFR) were examined using genomic DNA sequencing, real-time PCR and/or fluorescence in situ hybridization (FISH). RESULTS: The median age was 61 years, and 50 patients were men and 11 were women. In the histologic review of epithelial component, adenocarcinoma were in 44 cases (72%), squamous cell carcinoma in 15 (25%) and large cell carcinoma in 2 patients (3%). Overall, 30 cases (49%) had any molecular alterations. Nine patients (15%) possessed EGFR deletion in exon 19 (n = 8) or L858R mutations in exon 21 (n = 1), while 3 other cases having atypical EGFR mutations. Six patients (9.8%) had k-ras mutations in exon 12, and 3 had c-kit mutations. High gene copy number of c-met was found in 11 patients (18.0%) and that of FGFR was in 6 patients (9.8%). No significant relationships were identified among the occurrence and type of mutations and patient survival or any other clinicopathological variables. CONCLUSIONS: Given the diverse repertoire of mutational profiles observed in PPC samples, clinical trials based on accurate cancer-genotyping should be considered as a legitimate treatment scheme for this rare disease entity in the future.

Possibility of skin epithelial cell transdifferentiation in tracheal reconstruction.

In tissue engineering, injured tissue is normally reconstructed with cells obtained from that tissue itself. However, it is difficult to obtain cells for reconstruction of the trachea because of its shape and limited accessibility. Therefore, other cell sources having similar form and function or stem cells are used for tracheal reconstruction. In a previous study, we used autologous skin epithelial cells and successfully reconstructed canine tracheas. We found that the tracheal epithelial layer was completely covered with ciliated cells, which is a remarkable finding because skin and tracheal epithelial cells originate from different germinal layers and have very different forms. In this study, to elucidate the origin of the ciliated cells, we identified the stem cell contents of skin epithelial cells on primary culture, marked the skin epithelial cells with PKH26 dye, and transplanted them onto canine tracheas. After 5 months, we identified PKH26 fluorescence on the tracheal epithelial layers, especially over the tracheal cartilages. Consequently, we demonstrated that transplanted autologous skin epithelial stem cells can remain viable on the trachea for a few months and can transdifferentiate into tracheal epithelial cells and chondrocytes.

Aurora A regulates prometaphase progression by inhibiting the ability of RASSF1A to suppress APC-Cdc20 activity.

The Aurora (Ipl) kinase family plays important roles in the regulation of mitosis and tumorigenesis. The tumor suppressor RASSF1A controls mitotic progression by regulating anaphase-promoting complex (APC)-Cdc20 activity and microtubule stability, but the mechanism by which this action is regulated has not been previously established. Here, we show that Aurora A and B associate with and phosphorylate RASSF1A on serine 203 in vivo at different times and in different subcellular compartments during mitosis. Notably, both depletion of Aurora A by RNA interference and expression of a nonphosphorylatable RASSF1A (S203A) mutant gene led to a marked delay in prometaphase progression. This is likely because of the failure of RASSF1A to dissociate from Cdc20, constitutive inhibition of APC-Cdc20, and accumulation of mitotic cyclins. In contrast, the delay in prometaphase progression caused by Aurora A depletion was largely normalized by phosphomimetic RASSF1A (S203D). Finally, RASSF1A phosphorylation on serine 203 was up-regulated in Aurora A-overexpressing human tumors. These findings indicate that Aurora A plays a critical role in RASSF1A-APC-Cdc20 regulatory mechanisms that control normal prometaphase progression and that are involved in tumorigenesis. [Cancer Res 2009;69(6):2314-23.

Prognosis of non-small cell lung cancer with synchronous brain metastases treated with gamma knife radiosurgery.

The clinical outcome and prognostic factors of patients with synchronous brain metastases from non-small cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKS) were analyzed. A total of 35 patients with NSCLC underwent GKS as an initial treatment for metastatic brain lesions of synchronous onset. The period of survival and various prognostic factors such as age, gender, performance status, multiplicity of the brain lesions, intracranial tumor volume, and extent of the primary tumor were analyzed. The overall median survival time for this series was 12 months (range 0.75 to 43 months) from the diagnosis. Of the 21 patients who were no longer alive at the conclusion of this study, only 7 (33.3%) died of neurological causes. Multivariate analysis of these data revealed that N stage, whole-brain radiotherapy (WBRT), and chemotherapy were significant predictors for survival (p<0.05). Survival of patients with NSCLC and synchronous brain metastases is mainly dependent upon the progression of the systemic disease, provided that the cerebral lesions are treated adequately with local treatment modalities including radiosurgery. Application of radiosurgery as an initial treatment option and aggressive local and systemic modalities to control extracranial disease may improve survival.