Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine.

PURPOSE: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. MATERIALS AND METHODS: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. RESULTS: Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a "private" oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. CONCLUSION: In the era of precision medicine, this report emphasizes the importance of an "omic" approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.

The prognostic significance of proliferative indices in surgically resected IIIA-N2 non-small cell lung cancer after induction chemotherapy.

BACKGROUND: The aim of this study was to assess the prognostic significance of Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after induction chemotherapy in surgically resected IIIA-N2 patients. METHODS: Between January 2002 and November 2008, we reviewed 50 consecutive patients (39 males) with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who underwent radical resection following induction chemotherapy. Five-year survival in the series was evaluated in relation to lymph node downstaging, histology, extent of resection, number of chemotherapy cycles, pT status, sex and age. It was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib 1 expression), dividing the patients into two groups according to whether they were above or below the 50th percentile for each parameter. The associations between mortality and the abovementioned prognostic factors were explored using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. RESULTS: The monovariate analysis confirmed the positive prognostic role of lymph node downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1 expression under the 50th percentile were also associated with better 5-yr survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither apoptosis nor the other prognostic factors showed any statistical impact on long-term survival. The multivariate analysis showed Mi to be an independent prognostic factor (P=0.005). CONCLUSIONS: Although lymph node downstaging has been considered the principal prognostic factor after induction chemotherapy and surgical resection, Mi and Mib1 expression in residual tumor can predict long-term survival more accurately.

Time-Trend Analysis of Pulmonary and Diaphragmatic Functionality in Patients with Diaphragmatic Palsy or with Chronic Diaphragmatic Hernia after Surgical Treatment.

Background The aim of this study was to assess long-term pulmonary and diaphragmatic function in two cohorts of patients: the first one affected by diaphragmatic palsy (DP) who underwent plication reinforced by rib-fixed mesh and the second one affected by chronic diaphragmatic hernia (TDH) who underwent surgical reduction and direct suture. Materials and Methods From 1996 to 2011, 10 patients with unilateral DP and 6 patients with TDH underwent elective surgery. Preoperative and long-term (12 months) follow-up assessments were completed in all patients, including pulmonary function tests (PFTs) with diffusion of the lung for carbon monoxide (DLCO), measure of maximum inspiratory pressure (MIP) assessed both in standing and in supine positions, blood gas analysis, chest computed tomographic (CT) scan, and dyspnea score. The Pearson chi-square test, Fisher exact test, and Student t-test were applied when indicated. Results At long-term (12 months) postoperative follow-up, patients operated for DP showed a significant improvement in terms of forced expiratory volume in 1 second (FEV1%) (+ 18.2%, p < 0.001), forced vital capacity (FVC%) (+ 12.8%, p < 0.001), DLCO% (+ 8.3%, p = 0.04), and Po 2 (+ 9.86 mm Hg, p < 0.001) when compared with baseline values. Conversely, when considering the TDH group, only the levels of Po 2 were found to be significantly higher in the postoperative assessment (+ 8.3 mm Hg, p = 0.04). Although MIP increased in both the groups after surgery, a persistent and significant decrease of MIP was detected in TDH group when comparing the levels assessed in supine position with those measured in the standing position (p < 0.001). Medical Research Council dyspnea scale improved in the DP group by a factor of 0.80 (p < 0.001) and in the TDH group by a factor of 0.33 (p = 0.175). Conclusion In patients who underwent surgery for DP, good long-term results may be predicted in terms of pulmonary flows, volumes, and DLCO. Conversely, in patients who underwent elective surgery for chronic TDH, a persistent overall restrictive pattern, lower MIP values in supine position, and paradoxical motion could be expected.

Prognostic factors and clinical outcome in patients with surgically resected peripheral N0 adenocarcinoma <3 cm.

BACKGROUND: Many reports emphasize the role of sub-lobar resections in the treatment of small peripheral lung cancer. The aim of this study was to investigate a range of prognostic factors, including the extension of resection, which may affect the prognosis in a homogeneous group of patients. METHODS: We retrospectively reviewed the clinical records of 279 patients affected by N0 small peripheral adenocarcinoma (ADK) <3 cm that underwent surgery between 2000 and 2010. Eleven patients were excluded due to non-tumour-related death. RESULTS: There were 176 (66%) males and 92 (34%) females with a median age of 74 years (range 47-93). In the series, 229 (85%) patients received a lobar resection and only 39 (15%) a sub-lobar resection. One hundred ninety-five patients (72%) resulted stage IA while 73 (28%) stage IB. No differences in 5-year survival were observed according to: age (P=0.32), sex (P=0.42), T1a vs. T1b (P=0.31), stage IA vs. IB (P=0.51) and type of resection (P=0.29). Patients affected by ADK with a predominant lepidic growth showed a better 5-year survival (91.3% vs. 81.5%; P=0.044). The multivariate analysis confirmed the growth pattern as an independent risk factor (P=0.048). In patients with visceral pleura infiltration, the sub-lobar resection was associated with a significantly lower 5-year survival compared to lobectomy (63% vs. 90%; P=0.033). The visceral pleural infiltration was independent from ADK growth pattern, predominant lepidic vs. non-lepidic (P=0.51), but it was significantly more frequent in the ADK>2 cm (P=0.012). CONCLUSIONS: Small peripheral (<3 cm) N0 lung ADK can be easily resected by wedge or anatomical segmentectomy. The lepidic growth pattern is the main prognostic factor independently from the extension of resection however, in case of visceral pleural involvement, lobectomy reduces significantly the risk of recurrence.

Sternal reconstruction by extracellular matrix: a rare case of phaces syndrome.

Congenital defects of the sternum are rare and due to a failure of midline development and fusion of the sternal bones. Surgical correction of a sternal cleft should be preferred during infancy for functional reasons. Chest wall reconstruction represented a complex problem in the last decades. We report our successful outcome of sternal reconstruction in a rare case of PHACES syndrome, in which the patient was submitted to reconstruction of the sternum and complete closure of the thoracic defect by the employ of an extracellular matrix XCM Biologic tissue matrix. We promote the use of extracellular matrix in surgical reconstruction of chest defects for its maneuverability, plasticity, tolerability and the possibility of growing with the children's chest getting a good compliance and optimal cosmetic results.

Primary chest wall chondrosarcomas: results of surgical resection and analysis of prognostic factors.

OBJECTIVES: Wide surgical excision with tumour-free margins is the mainstay of therapy for primary chest wall chondrosarcoma (PCWC). Few studies on treatment outcome and prognostic factors of PCWC requiring chest wall resection are available. We analysed our experience on surgical treatment of PCWC with emphasis on survival and recurrence prognostic factors. METHODS: From 1986 to 2012, 89 patients (65.2% males, median age 55 years) with PCWC were operated on. The median tumour maximum diameter was 7 cm (range 2-30 cm). RESULTS: We performed 23 sternectomies and 66 lateral chest wall resections (median ribs resected: 2; range 1-7). Resections were extended to lung (n = 19), diaphragm (n = 13), vertebral body (n = 6) or clavicle (n = 1). Negative margins were obtained in 85.4% of cases. Chest wall reconstruction was obtained mainly by prosthetic non-rigid or rigid materials and muscle flap coverage. In the last years, 3 patients received a sternal replacement with cadaveric allograft, and 2 had a chest wall reconstruction with titanium bars and 17 with a rib-like prosthesis. Perioperative mortality and morbidity rates were 0 and 12.4%, and 5- and 10-year overall and disease-free (on R0 resections) survival rates were 67.1 and 57.8%, and 70 and 52%, respectively. A favourable outcome (univariate analysis) was seen for G1 tumours (P < 0.0001), negative surgical margins (P < 0.0001), age ≤55 years (P = 0.005), no adjuvant treatment (P < 0.001) and diameter ≤6 cm (P = 0.005). Independent predictors of better survival (multivariate analysis) were negative surgical margins (P = 0.0001), G1 tumours (P = 0.02), age ≤55 years (P = 0.006) and diameter ≤6 cm (P = 0.006). A predictive risk factor for recurrence was histological grade. CONCLUSIONS: Surgical resection of PCWC leads to good oncological outcome. Wide surgical margins and G1 tumours predicted a better prognosis and a lower recurrence rate. The evolution of surgical technique and the introduction in clinical practice of new prosthetic materials allowed larger resections, and safe and anatomical reconstruction.

Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids.

OBJECTIVES: To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. METHODS: We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. RESULTS: Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis. CONCLUSIONS: ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

Impact of interstitial lung disease on short-term and long-term survival of patients undergoing surgery for non-small-cell lung cancer: analysis of risk factors.

OBJECTIVES: The study aimed to determine the impact of interstitial lung disease (ILD) on postoperative morbidity, mortality and long-term survival of patients with non-small-cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS: We performed a retrospective chart review of 775 consecutive patients who had undergone lung resection for NSCLC between 2000 and 2009. ILD, defined by medical history, physical examination and abnormalities compatible with bilateral lung fibrosis on high-resolution computed tomography, was diagnosed in 37 (4.8%) patients (ILD group). The remaining 738 patients were classified as non-ILD (control group). We also attempted to identify the predictive factors for early and late survival in patients with ILD following pulmonary resection. RESULTS: There was no significant difference between the two groups in terms of age (69 vs 66 years), sex (79 vs 72% male), smoking history (93 vs 90% smokers), forced expiratory volume in 1 s % of predicted (89 vs 84%), predicted values of forced vital capacity (FVC)% (92 vs 94%), types of surgical resection and histology. Patients with ILD had a higher incidence of postoperative acute respiratory distress syndrome (ARDS; 13 vs 1.8%, P < 0.01) and higher postoperative mortality (8 vs 1.4%, P < 0.01). The overall 5-year survival rate was 52% in the ILD and 65% in the non-ILD patients, respectively (P = 0.019). In the ILD group, at the median follow-up of 26 months (range 4-119), 19 (51%) patients were still alive and 18 (49%) had died in the ILD group. The major cause of late death was respiratory failure due to the progression of fibrosis (n = 7, 39%). In the ILD group, lower preoperative FVC% (mean 77 vs 93%, P < 0.01) and lower diffusing capacity of the lung for carbon monoxide (DLCO%; 47 vs 62%; P < 0.01) were significantly associated with postoperative ARDS. CONCLUSIONS: In conclusion, major lung resection in patients with NSCLC and ILD is associated with an increased postoperative morbidity and mortality. Patients with a low preoperative FVC% should be carefully assessed prior to undergoing surgery, particularly in the presence of a lower DLCO%. Long-term survival is significantly lower when compared with patients without ILD, but still achievable in a substantial subgroup. Thus, surgery can be offered to properly selected patients with lung cancer and ILD, keeping in mind the risk of respiratory failure during the evaluation of such patients.

Incremental value of pocket-sized imaging device for bedside diagnosis of unilateral pleural effusions and ultrasound-guided thoracentesis.

OBJECTIVES: The present study aimed to assess the additional value of a pocket-sized imaging device (PSID) as an adjunct to plain chest X-rays in the diagnosis of pleural effusion (PE), mainly for those requiring pleural thoracentesis. METHODS: We performed a thoracic ultrasound examination using a PSID in 73 patients with an abnormal chest X-ray diagnostic for unilateral PE. Abundant PE was defined as an interpleural distance between the diaphragm and visceral pleura (VP) of ≥ 30 mm at the apex of the 50 mm bisector line of the costodiaphragmatic recess at end expiration. RESULTS: According to PSID ultrasound evaluation, abundant PE was present in 46 patients (63%), while 27 (37%) patients showed the presence of mild PE or absence of PE. Thoracentesis was performed successfully and without procedure-induced complications in all 46 patients with abundant PE. Using the above-mentioned method, we obtained a high diagnostic accuracy (area under the curve = 0.99) and excellent sensitivity and specificity of 91.7 and 99.9%, respectively, to predict a PE >1000 ml, when VP was >6.3 cm. CONCLUSIONS: PSID is a useful tool that may integrate and complete the physical examination, also providing additional information to chest X-ray in the clinical management of patients with suspected PE. PSID evaluation can also increase the effectiveness and safety of thoracentesis.

Patients with thymomas have an increased risk of developing additional malignancies: lack of immunological surveillance?

AIMS: To assess the risk, for patients with thymoma, of developing an additional malignancy (AM). METHODS AND RESULTS: We studied 68 patients with thymomas. Based on the World Health Organization classification, the tumours were categorised as A, AB or B (B1, B2, B3) thymomas. Control populations comprised 114 patients with colorectal cancer, 108 patients with lymphoma and 123 patients with thyroid carcinoma. Patients with thymomas showed a higher risk of developing an AM (22 of 68 patients versus 11 of 114, eight of 108, and eight of 123 patients, respectively; P = 0.0002). The association between thymomas and AMs was related to the thymoma histotype, with B1, B2, B3 and AB tumours showing a higher risk of developing an AM than A thymomas (P = 0.0474). CONCLUSIONS: Patients affected by thymomas showed a significantly higher risk of developing additional malignancies than those in the control groups, and cases that exhibited a predominantly cortical component were more likely to develop other neoplasms. This may be related to the functions of cortical thymic epithelial cells in providing for T lymphocyte maturation through interaction with major histocompatibility complexes.

Phase II trial of bevacizumab and dose/dense chemotherapy with cisplatin and metronomic daily oral etoposide in advanced non-small-cell-lung cancer patients.

Bevacizumab, is a humanized monoclonal antibody to vasculo-endothelial-growth-factor, with anticancer activity in non-small-cell-lung cancer (NSCLC) patients. Our previous results from a dose/finding phase I trial in NSCLC patients, demonstrated the anti-angiogenic effects and toxicity of a newest bevacizumab-based combination with fractioned cisplatin and daily oral etoposide. We designed a phase II trial to evaluate in advanced NSCLC patients the antitumor activity and the safety of this novel regimen. In particular, 45 patients (36 males and 9 females), with a mean age of 54 years, an ECOG ≤ 2, stage IIIB/IV and NSCLC (28 adenocarcinomas, 11 squamous-cell carcinomas, 2 large-cell carcinomas, 4 undifferentiated carcinomas), were enrolled. They received cisplatin (30 mg/sqm, days 1-3), oral etoposide (50 mg, days 1-15) and bevacizumab (5 mg/kg, day 3) every three weeks (mPEBev regimen). Patients who achieved an objective response or stable disease received maintenance treatment with bevacizumab in combination with erlotinib until progression. Grade I-II hematological, mucosal toxicity and alopecia were the most common adverse events. The occurrence of infections (17%), thromboembolic events (4.4%) and severe mood depression (6.7%) was also recorded. A partial response was achieved in 31 (68.8%) patients, disease remained stable in 8 (17.8%), and disease progressed in 6 (13.3%) with a progression-free-survival of 9.53 months (95%CI, 7.7-11.46). Our bio-chemotherapy regimen resulted very active in advanced NSCLC, however, the toxicity associated with the treatment requires strict selection of the patients to enroll in future studies.

Effects of intravenous zoledronic acid and oral ibandronate on early changes in markers of bone turnover in patients with bone metastases from non-small cell lung cancer.

BACKGROUND: The aim of this study was to assess the early effects of zoledronic acid (ZOL) and oral ibandronate (IBA) on the bone resorption marker s-CTX (serum C-telopeptide of collagen type I) and the bone formation marker B-ALP (bone-alkaline phosphatase) in patients with bone metastases from non-small cell lung cancer (NSCLC). METHODS: Fifty-five patients with at least one site of bone metastasis secondary to NSCLC were randomly assigned to receive intravenous ZOL 4 mg every 4 weeks, or oral IBA 50 mg/day. RESULTS: At 1 month of treatment, s-CTX was reduced by 54.8% (95% CI 40.4-59.8%) in the ZOL group (26 evaluable patients) compared with 38.2% (95% CI 29.8-48.7%) in the oral IBA group (27 evaluable patients) (p = 0.03). At 3 months, s-CTX was reduced by 72.6% (95% CI 58.6-71.3%) in the ZOL group, compared with 66.4% (95% CI 54.3-79.5%) in the oral IBA group (p = 0.22). Both bisphosphonates similarly decreased the bone marker B-ALP at 1 month (ZOL 24.7%, 95% CI 3.6-39.5%, and IBA 24.2%, 95% CI 2.8-43.4%) and 3 months (ZOL 28.6%, 95% CI +2.8-43.3%, and IBA 24.2%, 95% CI 3.2-47.4%). Both bisphosphonates were well tolerated. CONCLUSION: Considering the changes in bone markers, ZOL and oral IBA show comparable efficacy in patients with NSCLC and bone metastases.

Impact of lobectomy for non-small-cell lung cancer on respiratory function in octogenarian patients with mild to moderate chronic obstructive pulmonary disease.

OBJECTIVE: To assess the long-term impact of standard lobectomy on respiratory function in octogenarian patients with mild/moderate chronic obstructive pulmonary disease (COPD). METHODS: We reviewed all octogenarians (n=38), who underwent lobectomy for stage I-II non-small-cell lung cancer (NSCLC) from 2000 to 2006. Inclusion criteria were: Tiffenau index<0.7, no adjuvant therapies, smoking cessation after surgery, spirometric data available after 12±3 months from surgery in the absence of relapsing disease. RESULTS: After excluding 14 patients (three died perioperatively), 24 fulfilled the inclusion criteria. The median preoperative forced expiratory volume in 1s (FEV1) was 80% (range 56.7-100%). The mean change in FEV1 after lobectomy resulted in a loss of 11% (range -32% to +7%, p=0.004). Considering two groups on the basis of median FEV1 (group 1: FEV1≤80%, group 2: FEV1>80%), mean FEV1 loss after surgery was 7.9% in group 1 and 14.9% in group 2, respectively (p=0.17). No statistical differences were found between the two groups in changes after surgery of forced vital capacity (FVC), arterial oxygen and carbon-dioxide tension. Diffusion capacity of the lung for carbon monoxide (DLCO)% loss was significantly higher in group 2 compared with group 1 (-22.5% vs +1.5%, p=0.001). Six patients showed an improvement of postoperative FEV1: all had a preoperative FEV1 less than 60%, an upper or homogeneous pattern of emphysema, and received an upper lobectomy. In group 2, the FEV1 loss was not affected by the type of lobectomy whereas in group 1, the resection of lower lobe was associated to a major FEV1 loss (-14.5% vs +5.3%, p=0.05). CONCLUSIONS: Octogenarians with lower preoperative FEV1% have a better late preservation of pulmonary function after lobectomy. Upper lobectomy seems to produce a lung-volume reduction effect, leading to an improvement in the expiratory volume in patients with higher airflow obstruction.

MSCT multi-criteria: a novel approach in assessment of mediastinal lymph node metastases in non-small cell lung cancer.

PURPOSE: To evaluate the accuracy of multi-slice computed tomography (MSCT) in diagnosing mediastinal lymph node metastases in patients with non-small cell lung cancer (NSCLC) using a multi-criteria approach. METHODS: We retrospectively reviewed contrast-enhanced MSCT of the chest in 86 consecutive patients with histopathologically proven NSCLC. All patients underwent surgical lymph node resection within 30 days from the CT examination. In all cases pathological and CT results were reviewed and correlated. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of MSCT using a multi-criteria approach in the detection of the N2 stage were 100%, 98.5%, 100%, 94.4% and 98.8% respectively, whereas using the size criterion alone 64%, 61%, 87%, 40%, and 62% respectively. CONCLUSIONS: To improve MSCT accuracy for diagnosing N staging other criteria can be associated with lymph node size. The use of different dimensional cut-offs for each mediastinal lymph node station, the matching of positive nodal stations with tumour location, the structural characteristics and the type of enhancement allow for a high accuracy of MSCT in the staging of mediastinal nodes in NSCLC.

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.

BACKGROUND: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer (NSCLC) the anti-angiogenic effects of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF). We also evaluated the antitumor activity of this combination. RESULTS: The combined treatment induced a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab an objective response and a disease stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15%, respectively, were recorded with a time to progression of 7.6 mo. Grade I-II hematological toxicity was the most common adverse event. Four early deaths within 3 mo, three cases of pneumonia, and six cases of mood depression at higher bevacizumab dosage were observed. The most active biological and maximum tolerated dose were 5 and 7.5 mg/kg, respectively. PATIENTS AND METHODS: Forty-eight patients (42 males and six females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOG

Video-assisted mediastinoscopic resection of two bronchogenic cysts: a novel approach.

The treatment of bronchogenic cysts (BCs) is still controversial. Many authors advocate the complete surgical excision of cysts [by video-assisted thoracoscopic surgery (VATS) or thoracotomy] to prevent their high rate of recurrence. Nevertheless, some recent works have attracted attention to a less invasive endoscopic management of benign mediastinal cysts. Here, we report a novel, safe, effective and minimally invasive mediastinoscopic technique used in the complete resection of two mediastinal BCs. We believe that this approach can be applied, with some restrictions: lesions located in the superior mediastinum, absence of severe adhesions, absence of infection, no previous mediastinal surgery. More experience of mediastinoscopic treatment of BCs is needed in order to better define its indications, contraindications, risks and complications.

Surgical treatment of synchronous multiple lung cancer located in a different lobe or lung: high survival in node-negative subgroup.

BACKGROUND: The International Association for Study of Lung Cancer Staging Committee proposes for the next revision of TNM (tumour, nodes, metastases) classification that additional nodules in a different lobe of the ipsilateral lung moves from an M1 designation to T4, while additional nodule(s) in the contralateral lung should be classified as M1a, because of poorer survival. We analysed the survival after surgery of patients presenting with synchronous lung cancers located in a different lobe or lung. METHODS: A database of 1551 patients operated on for non-small-cell lung cancer (NSCLC) between 1990 and 2007 was evaluated for unilateral (other lobe) (n=15) and bilateral (n=28) synchronous multiple lung cancers. The relationships among the location of tumours, histology, date of surgery (before and after 2000), lymph node metastasis, type of surgery, adjuvant therapy and survival were analysed. RESULTS: The 5-year survival for all synchronous multiple lung cancers (n=43) was 34%, with a median survival of 32 months. Postoperative mortality was 7%. On univariate analysis, only lymph node metastasis and surgery before the year 2000 affected the overall survival adversely, and both prognostic factors maintained a statistical significance on multivariate analysis. The 5-year survivals were 57% and 0% for patients without (n=25) and with (n=18) lymph node metastasis, respectively (p=0.004), and were 43% and 18% for patients operated upon after (n=27) and before (n=16) the year 2000, respectively (p=0.01), perhaps reflecting a better selection process related to the extensive use of positron emission tomography (PET) scanning. The 5-year survival was not different between bilateral (43%) and unilateral (27%) synchronous lung cancers (p=n.s.). CONCLUSIONS: Our data support complete surgical resection of synchronous multiple lung cancers in patients with node-negative NSCLC. Even patients with bilateral lung cancer should not be treated as metastatic disease. Provided there is no evidence of node and distant metastasis, after an extensive preoperative work-up, including PET scanning and mediastinoscopy, bilateral surgical resection should be performed in fit patients.

Surgery for bronchogenic cysts: always easy?

A few cases of major complications after surgery for bronchogenic cyst have been reported. The purpose of this study was to analyze the complicated and unusual cases among 30 consecutive patients with bronchogenic cysts treated surgically at our institution between 1975 and 2007. There were 3 cases of mediastinal bronchogenic cyst characterized by significant surgical complications or very unusual pathological findings. The operations were performed through a thoracotomy in 25 patients, and by video-assisted thoracoscopic surgery in 5. Two patients suffered iatrogenic injury of the contralateral main bronchus during excision of a mediastinal cyst; in one of them, late development of foreign body granuloma was related to migration towards the bronchial wall of cyanoacrylate used to reinforce suturing of the bronchial tear. Histological examination of one resected specimen showed a large-cell anaplastic carcinoma arising from the wall of a mediastinal bronchogenic cyst. Bronchogenic cysts should be excised before they become symptomatic or infected, which leads to more difficult surgery and complications. The small risk of developing malignancy within a bronchogenic cyst also justifies early intervention.