Jacopo Vannucci

Isolated cardiophrenic angle node metastasis from ovarian primary. report of two cases

Ovarian cancer is the most lethal gynaecologic malignancy. It usually spreads out of the abdomen involving thoraco-abdominal organs and serosal surface. This disease is poorly curable and surgery, at early stage, is supposed to achieve the best survival outcome. In systemic dissemination, chemiotherapy is indicated, sometimes with neoadjuvant aim. The most common clinical expressions of advanced ovarian carcinoma are multiple adenopathy, neoplastic pleuritis, peritoneal seeding and distant metastasis, mainly hepatic and pulmonary. Isolated adenopathy of the mediastinum is rare and isolated bilateral have never been described before. We report two cases of isolated bilateral cardiophrenic angle lymphnode metastasis from ovarian carcinoma, without peritoneal and pleural involvement. Both patients were successfully resected through minimally invasive thoracic surgery. About the role of surgery, few data are available but survival seems to be longer after resection thus, more investigation is required to make the indication to surgery more appropriate in advanced cases.

Impact of epidermal growth factor receptor and KRAS mutations on clinical outcome in resected non-small cell lung cancer patients.

Objectives:Surgery yields best results for non–small cell lung cancer (NSCLC) patients. Epidermal growth factor receptor (EGFR) and its downstream factor Kirsten rat sarcoma viral oncogene homolog (KRAS) are variably mutated in NSCLC. Such mutations predict clinical response to tyrosine kinase inhibitors. This study evaluated incidence and correlation of EGFR and KRAS mutations with clinicopathologic parameters and outcome in resected stage I to III NSCLC. Methods:We analyzed the clinical characteristics and outcome data for 230 patients who underwent resection at our institution for stage I to III NSCLC. The tumors were assessed for both EGFR (exons 18 to 21) and KRAS (exons 2 and 3) mutations by nested polymerase chain reaction and sequenced in both sense and antisense direction. Kaplan-Meier estimates of overall survival and disease-free survival were calculated for clinical and biological variables using Cox model. Results:EGFR and KRAS mutations were detected in 22 (9.6%) and 39 (16.9%) patients, respectively. In the whole population, both EGFR and KRAS mutations were significantly correlated with adenocarcinoma (ADC). Overall, EGFR mutations were more frequent in women (P<0.0001) and in nonsmokers (P<0.0001). In the ADC/BAC group, KRAS mutations were more frequent in man (P<0.02) and EGFR mutations (exon 19 deletion and L858R) demonstrated a tendency towards worse disease-free survival (P=0.056). No difference in outcome was seen between patients harboring KRAS mutations compared with KRAS wild type. Conclusions:EGFR and KRAS mutations are frequent in ADCs and are not prognostic factors for survival. EGFR mutations could be used to identify patients suitable for adjuvant treatment with targeted therapy resulting in potentially improved outcomes.

Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis.

Risk assessment and treatment choice remains a challenge in early non-smallcell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR). A gene network computational analysis was performed to select predictive genes. An independent set of 79 ADs stage I samples was used to validate selected genes by Q-PCR. From microarray analysis we selected 50 genes, using the fold change ratio of ER versus NR. They were validated both in pool and individually in patient samples (ER and NR) by Q-PCR. Fourteen increased and 25 decreased genes showed a concordance between two methods. They were used to perform a computational gene network analysis that identified 4 increased (HOXA10, CLCA2, AKR1B10, FABP3) and 6 decreased (SCGB1A1, PGC, TFF1, PSCA, SPRR1B and PRSS1) genes. Moreover, in an independent dataset of ADs samples, we showed that both high FABP3 expression and low SCGB1A1 expression was associated with a worse disease-free survival (DFS). Our results indicate that it is possible to define, through gene expression and computational analysis, a characteristic gene profiling of patients with an increased risk of relapse that may become a tool for patient selection for adjuvant therapy.

Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors

Little is known about the complex signaling architecture of KRAS and the interconnected RAS-driven protein-protein interactions, especially as it occurs in human clinical specimens. This study explored the activated and interconnected signaling network of KRAS mutant lung adenocarcinomas (AD) to identify novel therapeutic targets. Thirty-four KRAS mutant (MT) and twenty-four KRAS wild-type (WT) frozen biospecimens were obtained from surgically treated lung ADs. Samples were subjected to laser capture microdissection and reverse phase protein microarray analysis to explore the expression/activation levels of 150 signaling proteins along with co-activation concordance mapping. An independent set of 90 non-small cell lung cancers (NSCLC) was used to validate selected findings by immunohistochemistry (IHC). Compared to KRAS WT tumors, the signaling architecture of KRAS MT ADs revealed significant interactions between KRAS downstream substrates, the AKT/mTOR pathway, and a number of Receptor Tyrosine Kinases (RTK). Approximately one-third of the KRAS MT tumors had ERK activation greater than the WT counterpart (p<0.01). Notably 18% of the KRAS MT tumors had elevated activation of the Estrogen Receptor alpha (ER-α) (p=0.02). This finding was verified in an independent population by IHC (p=0.03). KRAS MT lung ADs appear to have a more intricate RAS linked signaling network than WT tumors with linkage to many RTKs and to the AKT-mTOR pathway. Combination therapy targeting different nodes of this network may be necessary to treat this group of patients. In addition, for patients with KRAS MT tumors and activation of the ER-α, anti-estrogen therapy may have important clinical implications.

Experience with the autologous pulmonary vein for pulmonary arterioplasty

OBJECTIVE Lobectomy with pulmonary artery resection and reconstruction is seldom performed in order to avoid pneumonectomy in selected cases. The aim of this study is to determine how safe and effective the graft reconstruction of the pulmonary artery is, using autologous tissue taken from the pulmonary vein. METHODS Eight patients with diagnosed non-small-cell lung cancer were treated by lobectomy with pulmonary artery reconstruction with curative intent. All patients could have tolerated pneumonectomy. Patch or conduit angioplasty was performed by using a tailored graft, harvested from the autologous pulmonary vein of the resected lobe. Patients were followed up and the clinical records were analyzed retrospectively. Long-term patency of the reconstructed pulmonary artery was investigated by computed tomographic pulmonary angiogram. RESULTS No procedure-related complications and no perioperative mortality were observed. No blood transfusion was required. Follow-up varied from 10 to 64 months. No local recurrences were found next to the angioplasty. Ideal long-term patency of the pulmonary artery was demonstrated in all cases. Two patients are alive with evidence of extrathoracic metastatic disease and four patients are apparently healthy. Two patients died of progressive disease. CONCLUSIONS The use of pulmonary vein tissue as a graft to repair the pulmonary artery is feasible, reproducible, and seems to be oncologically correct. Pulmonary vein tissue can be easily harvested during surgery and offers a high-quality vascular tissue for pulmonary angioplasty.

Pulmonary sequestration supplied by giant aneurysmal aortic branch.

We report a case of an intralobar sequestration supplied by a 13-cm aneurysmal vessel originating from the abdominal aorta. The malformation was discovered during a roentgenogram investigation of an abdominal infrarenal aneurysm. During the endovascular repair of the abdominal aneurysm, the giant feeding vessel of the pulmonary sequestration was embolized. Two days later the patient underwent an uneventful resection of the malformation en bloc with the right lower lobe through a standard right thoracotomy.

Thyroid cancer invading the airway: diagnosis and management.

INTRODUCTION Aim of this study is to analyze outcome and the decision making process to approach airway invasion by thyroid tumors. METHODS Retrospective study of 30 years experience in thyroid surgery for cancer invading airway. Clinical records, surgical and pathology reports have been analyzed to assess which principles and procedural details are significant to facilitate efficient diagnosis, staging and treatment. Medical therapy was not evaluated. RESULTS Out of a consecutive series of 2165 thyroid cancer patients, T4a cancers are 303 (14%). Airway invasion was found in 141 (6.5%) cases. Well-differentiated pattern was determined in 110 (78%) while other histology was reported in 31 (22%). Airway-related symptoms have been recorded in 111 (78%) patients. Flexible bronchoscopy was performed in all patients. Rapidly evolving disease or non-resectable airway was found in 105 (74.5%) cases. Permanent tracheotomy was performed in 43 (30.5%) cases, airway lumen restoration with or without stenting in 39 (27.7%), laryngectomy in 8 (5.7%), segmental airway resection and reconstruction in 28 (19.9%). Perioperative mortality was recorded after palliative treatment only. In resected patients, completely radical surgery was not always achievable. All patients with positive margin after resection underwent adjuvant treatment and showed comparable survival to radical surgery patients after 5 years. Tumor relapse occurred in 8 (28.6%) cases (distant or locoregional). Patients with unresectable disease require treatment for symptoms relief but survival is poor. CONCLUSION Although some patients are currently referred with a severely advanced disease, the indication for tracheotomy, salvage procedures or supportive care has decreased over time. Resection is feasible for differentiated tumors with an overall good outcome.

MYC and human telomerase gene (TERC) copy number gain in early-stage non-small cell lung cancer.

Objectives:We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non–small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. Materials and Methods:Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. Results:When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P=0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P=0.032 [UCCC criteria] or P=0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P=0.02) and the ROC classification (P=0.008). Conclusions:Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology.

Mediastinitis and sternal prosthesis infection successfully treated by minimally invasive omental flap transposition.

Purulent mediastinitis is a possible serious complication after mediastinal surgery. We report the case of a localized sternal plasmocytoma treated by sternectomy and prosthetic repair, who needed a second surgery for a fistulizing mediastinitis. Five months earlier, in another Hospital, the patient underwent sternal resection and reconstruction with a “sandwich” prosthesis (Methyl-methacrylate and Marlex mesh). Suppurative mediastinitis occurred and septic shock resolution was observed after the spontaneous opening of a mediastinal cutaneous fistula. After referring to our Unit the patient underwent extensive local and systemic preparation and nutritional support; the infected prosthesis was then removed and the gap filled by a laparoscopically-prepared omental flap. Adequate preoperative management, removal of any infected material and minimally invasive omental flap transposition allowed the successful treatment of this life-threatening condition.

External longitudinal titanium support for the repair of complex pectus excavatum in adults

Several techniques exist for the repair of complex pectus excavatum. The placement of retrosternal metal bars improves the results by reducing the recurrence rate, but entails several possible risks, complications and disadvantages. A new method, specifically conceived for the repair of severe, asymmetric forms in adult patients, is reported. The corrected bone is fixed in the proper position by two, patient-customized, titanium struts, externally screwed to the manubrium and sternal body. Any retrosternal bar is thus avoided, reducing possible complications, without hampering the chest wall dynamic. In this particularly difficult issue, this technique provides long-term good functional, mechanical and cosmetic results and does not entail a second surgery for struts removal.