ATF2 contributes to cisplatin resistance in non-small cell lung cancer and celastrol induces cisplatin resensitization through inhibition of JNK/ATF2 pathway.

ATF2 is a transcription factor involved in stress and DNA damage. A correlation between ATF2 JNK-mediated activation and resistance to damaging agents has already been reported. The purpose of the present study was to investigate whether ATF2 may have a role in acquired resistance to cisplatin in non-small cell lung cancer (NSCLC). mRNA and protein analysis on matched cancer and corresponding normal tissues from surgically resected NSCLC have been performed. Furthermore, in NSCLC cell lines, ATF2 expression levels were evaluated and correlated to platinum (CDDP) resistance. Celastrol-mediated ATF2/cJUN activity was measured. High expression levels of both ATF2 transcript and proteins were observed in lung cancer specimens (p << 0.01, Log2 (FC) = +4.7). CDDP-resistant NSCLC cell lines expressed high levels of ATF2 protein. By contrast, Celastrol-mediated ATF2/cJUN functional inhibition restored the response to CDDP. Moreover, ATF2 protein activation correlates with worse outcome in advanced CDDP-treated patients. For the first time, it has been shown NSCLC ATF2 upregulation at both mRNA/protein levels in NSCLC. In addition, we reported that in NSCLC cell lines a correlation between ATF2 protein expression and CDDP resistance occurs. Altogether, our results indicate a potential increase in CDDP sensitivity, on Celastrol-mediated ATF2/cJUN inhibition. These data suggest a possible involvement of ATF2 in NSCLC CDDP-resistance.

Repeated resection of colorectal cancer pulmonary oligometastases: pooled analysis and prognostic assessment.

BACKGROUND: Repeated resection of colorectal cancer pulmonary metastasis is associated with long-term survival. Nevertheless, very limited data addressing the best candidates for repeated pulmonary resection is available. PATIENTS AND METHODS: We searched the PubMed database for retrospective studies evaluating lung metastasectomy for metastatic colorectal cancer (CRC). We included studies with available data about repeated pulmonary metastasectomy. Potential prognostic factors were analyzed for possible impact on survival following the second metastasectomy through univariate and multivariate analysis. RESULTS: Between 1983 and 2008, 944 lung metastasectomies were carried out on 759 patients. Of those, 148 patients had a second metastasectomy. The 5-year survival rate was 52 % for patients who had 1 metastasectomy and 57.9 % from the second metastasectomy for patients who had repeated resection. More than 2 metastatic pulmonary nodules and maximum diameter of largest pulmonary nodule ≥3 cm were the only independent factors associated with inferior survival following repeated pulmonary resection. CONCLUSIONS: In selected patients with metastatic CRC, repeated pulmonary metastasectomy offers an excellent chance for long-term survival and is associated with a quite low operative mortality. Patients with more than 2 metastatic nodules and a maximum diameter of the largest metastatic lung nodule of ≥3 cm have a significantly inferior survival.

Role of surgical resection in colorectal lung metastases: analysis of 137 patients.

PURPOSE: The aim of this study is to investigate clinicopathologic characteristics and to identify prognostic factors in patients undergoing pulmonary metastasectomy for colorectal carcinoma. METHODS: This study is a single-institution retrospective study of 137 consecutive patients who underwent 158 pulmonary resections for metastatic colorectal carcinoma between January 1989 and June 2008. RESULTS: Median disease-free interval between colorectal resection and pulmonary metastasectomy was 35.6 months (range, 0.6 to 154.3 months). No perioperative deaths occurred. Follow-up was 100% complete and mean follow-up was 41.6 ± 27.6 months. Median survival was 36.2 months (range, 4.6 to 126 months). Overall 5- and 10-year survival rates were 55.4% and 30.8%, respectively, after pulmonary metastasectomy. At univariate analysis of patient survival, number of lung metastases (p = 0.002), disease-free interval of more than 24 month (p = 0.013), and absence of residual tumor (p = 0.024) were significant prognostic factors. At multivariate analysis, presence of solitary lung metastasis and disease-free interval of more than 24 months remained significant prognostic factors. There was no significant difference in the 5-year survival for 121 patients undergoing single thoracotomy compared with 16 patients undergoing repeated resection(s) for recurrent colorectal lung metastasis (55.1% vs 59.5%; p = 0.79). Nor was the presence of hepatic metastasis associated with lower outcome (p = 0.77). CONCLUSIONS: Disease-free interval and number of metastases are the most significant prognostic factors for survival after pulmonary metastasectomy for colorectal carcinoma. Recurrent pulmonary disease can benefit from repeated resection. Prior hepatectomy for liver involvement does not influence survival.

The Role of Core Biopsy versus Vacuum-Assisted Breast Biopsy In Primary Breast Angiosarcoma.

We report the case of a 45-year-old woman with a slow-growing palpable nodule on the left breast, confirmed as a well-defined opacity on mammography, corresponding to a 5 cm hyperechoic lesion on ultrasound, and considered, on the basis of clinical examination and radiological findings, to be consistent with a lipoma. One year later, the patient represented with an enlarged left breast mass and underwent further imaging investigation with subsequent diagnosis of primary breast angiosarcoma obtained via a Vacuum-Assisted Breast Biopsy. The patient developed metastatic disease and succumbed to the disease one year after definitive diagnosis. Primary breast angiosarcoma is a rare malignant vascular neoplasia, characterized by aggressive patterns, poor prognosis, and absence of pathognomonic radiological features. Currently, there are no evidence-based guidelines regarding treatment, even though wide surgical resection followed by chemo- and radiotherapy appears to improve survival.

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer.

BACKGROUND: Higher blood levels of C-reactive protein (CRP) have been associated with shorter survival in patients with cardiovascular, chronic obstructive pulmonary disease and cancer. We investigated the impact of baseline and postoperative CRP levels on survival of patients with operable lung cancer (LC). PATIENTS AND METHODS: CRP values at baseline (CRP0) and 3 days after surgery (CRP3) were measured in a consecutive series of 1750 LC patients who underwent complete resection between 2003 and 2015. Patients were classified as having 0 (N = 593), 1 (N = 658) or 2 (N = 553) risk factors: CRP0 and/or CRP3 values above the respective median value. The effect of higher CRP was evaluated by Kaplan-Meier mortality curves and adjusted hazard ratio (HR) with 95% confidence interval (CI), by fitting Cox proportional hazards models. RESULTS: Cumulative proportions of 5-year survival were 67% for 0 risk factors, 58% for 1 risk factor and 41% for 2 risk factors (P < 0.0001). The overall 5-year mortality risk was significantly higher in patients with 1 risk factor (adjusted hazard ratio [aHR] 1.43 [95% CI 1.14-1.79]), or 2 risk factors (aHR 2.49 [95% CI 1.99-3.11]). A significant impact on survival was observed in each tumour-node-metastasis stage group, and in the subset of non-smokers. Postoperative 30-day mortality was significantly higher in patients with 2 risk factors only (aHR 2.2% versus 0.6%, p < 0.0475). CONCLUSIONS: Baseline and postoperative CRP levels predict immediate and long-term mortality in all stages of operable lung cancer. Patients with higher CRP levels could be candidate to randomised adjuvant trials with anti-inflammatory agents.

Baseline C-reactive protein level predicts survival of early-stage lung cancer: evidence from a systematic review and meta-analysis.

PURPOSE: The prognostic impact of baseline C-reactive protein (CRP) in non-small-cell lung cancer (NSCLC) is debated. To evaluate this issue, we performed a systematic review and meta-analysis to explore the role of CRP value in predicting early-stage NSCLC survival. METHODS: Ten articles on early-stage NSCLC were eligible and included in our study. We performed a random-effects meta-analysis and assessed heterogeneity and publication bias. We pooled hazard ratio (HR) estimates and their 95% confidence intervals (CIs) on mortality for the comparison between the study-specific highest category of CRP level versus the lowest one. RESULTS: In overall analysis, elevated pretreatment CRP values were significantly associated with poor overall survival (HR 1.60, 95% CI 1.30-1.97, p<0.001, I2 = 71.9%). Similar results were observed across considered strata. However, higher mortality risk was reported in studies in which CRP was combined with other factors (HR 1.96, 95% CI 1.58-2.45) and in those using a cutoff value of 3 mg/L (HR 1.89, 95% CI 1.52-2.35). CONCLUSIONS: Based on our analysis, baseline high CRP level is significantly associated with poor prognosis in early-stage NSCLC. Further prospective controlled studies are needed to confirm these data.

Small and large bowel hernia migrated into the chest 6 years after sternal resection.

Sternal resection represents a rare, peculiar subgroup of chest wall operations. Abdominal or lung hernia could be a serious complication after extended chest wall or sternal resection for cancer. We present a case of a late abdominal hernia in the chest underneath the skin, 7 years after a total sternal resection for a sarcoma.

A suitable system of reconstruction with titanium rib prosthesis after chest wall resection for Ewing sarcoma.

The recent improvements in chemotherapy and surgical resection in Ewing sarcoma (ES) increased the overall survival as well as the importance of chest wall reconstruction. These improvements are in order to avoid asymmetrical growth, functional and cosmetic compromise after surgery. Chest wall reconstruction still remains a big issue in young patients with ES. We present a case of ES of the left chest wall, arising from a rib, in a 14-year-old patient. He was admitted after neoadjuvant chemotherapy and radiotherapy. The patient underwent a chest wall resection of three ribs and a wedge lung resection of the upper lobe followed by chest wall reconstruction with Stratos™ rib titanium prostheses. This new device is suitable for reconstruction after major chest wall resection with good cosmetic and functional results. During the follow-up, there was no evidence of local and distant recurrence, the pain was under control and there were no functional alterations in the chest wall.

Suitable device for thoracoscopic talc poudrage in malignant pleural effusion.

Chemical pleurodesis is widely used in symptomatic patients with malignant pleural effusion to relieve symptoms, prevent fluid recurrence, and improve quality of life. Talc has been repeatedly found to be the most effective sclerosant agent, and thoracoscopic talc poudrage has been found to be the most effective pleurodesis technique. A homogeneous talc distribution on the visceral and parietal pleura helps to achieve complete pleural symphysis. We have recently adopted a new suitable sterile device that delivers talc under low and constant pressure, facilitating uniform coating of the whole pleural surface and avoiding inappropriate deposition of talc clumps.

Air leaks following pulmonary resection for malignancy: risk factors, qualitative and quantitative analysis.

Air leaks are a common complication of pulmonary resection. The aims of this study were to analyze risk factors for postoperative air leak and to evaluate the role of air leak measurement in identifying patients at increased risk for cardiorespiratory morbidity and prolonged air leak. From March to December 2009, 142 consecutive patients underwent pulmonary resection for malignancy and were prospectively followed up. Preoperative and intraoperative risk factors for air leak were evaluated. Air leaks were qualitatively and quantitatively labeled twice daily. There were 52 (36.6%) patients who had an air leak on day 1, and 32 (22.5%) who had an air leak on day 2. Air leak was ≥180 ml/min in 12 (37.5%) of these patients. Independent predictors of air leak on day 2 included type of pulmonary resection, presence of adhesions, and incomplete fissures. Cardiorespiratory morbidity was significantly higher (34.4%) in patients who experienced air leak on day 2 than in those who did not (10.9%) (P=0.002). Nine (75%) out of 12 patients with air leak ≥180 ml/min on day 2 had prolonged air leak (greater than five days) (P=0.0001).