P.L. Filosso

Supraventricular arrhythmias after resection surgery of the lung

OBJECTIVE Two hundred consecutive patients undergoing resection surgery of the lung during 1999 were retrospectively reviewed to define prevalence, type, clinical course and risk factors for postoperative supraventricular arrhythmias (SVA) with particular reference to atrial fibrillation or flutter (AF). METHODS Records of 200 lung patients were collected and analysed with particular attention to preoperative physiologic values and associated pathologies, lung functional status, electrocardiogram registration, extent of surgical resection of the lung and were also analysed to confirm or exclude correlation between them and postoperative AF; three patients were excluded as they were affected preoperatively by SVA. RESULTS Forty-five episodes of SVA, 41 of AF were identified in 197 patients (22%) and were more prevalent in several groups of patients such as those with increased age, pneumonectomy and superior lobectomy. Rhythm disturbances were most likely to develop on the second day after surgery. Ninety-eight percent of AF disappeared within a day of discharge and sinus rhythm was restored with digitalis or other antiarrhythmic drugs in all patients except one who was discharged with persistent atrial fibrillation. Arrhythmias were not direct causes of any in-hospital deaths. There is a tendency in the difference of the AF rate between pneumonectomy and upper lobectomy patients versus inferior lobectomy ones, probably related to the different anatomic structure of the proximal trunks of the upper and inferior veins of the lung, respectively. CONCLUSIONS Statistical analysis revealed that increased age, extent and type of pulmonary resection, such as pneumonectomy and superior lobectomy were significant risk factors. Despite these factors, arrhythmias after lung surgery could be managed easily and were not closely related to higher mortality. Direct cause of AF after lung resection surgery remains unclear; anatomical substrate such as surgical damage to the cardiac plexus or to the proximal trunks of the pulmonary veins covered by myocardial sleeves with electrical properties are to be considered.

Malignant solitary fibrous tumors of the pleura: retrospective review of a multicenter series.

Introduction: Available data on the malignant solitary fibrous tumor of the pleura (mSFTP), a very rare neoplasm with unpredictable prognosis, are scarce. The aim of this study is to collectively analyze the aggregated data from the largest series in the English literature to date, a multicenter, 10-year study of 50-cases. Methods: We retrospectively reviewed the clinical records of patients who underwent surgical resection for mSFTP in the period between January 2000 to July 2010. Long-term survival (LTS) and 5-year disease-free survival were analyzed in detail. Results: There were 24 men and 26 women (median age, 66 years; age range, 44–83 years). Thirty-two patients (64%) were symptomatic. A malignant pleural effusion was diagnosed in 12 cases. Surgical resection included isolated mass excision in 13 patients and extended resection in 35. In the remaining two cases only biopsies were undertaken. The resection was complete in 46 cases (92%). Adjuvant treatment was administered to 15 patients. Median follow-up was 116 months (range, 18–311 months). Overall LTS and disease-free survival were 81.1% and 72.1%, respectively. Fifteen patients (30%) experienced a relapse of the disease. Complete resection yielded much better LTS than partial resection (87.1% versus 0%; p < 0.001). At the Cox regression analysis, incomplete resection (hazards ratio [HR]: 39.02; 95% confidence interval [CI]:4.04–380.36; p = 0.002) and malignant pleural effusion (HR: 3.44; 95%CI: 0.98–12.05; p = 0.053) were demonstrated to be risk factors for earlier death. At multivariate analysis, chest-wall invasion and malignant pleural effusion increased the risk of recurrence (HR: 4.34; 95%CI: 1.5%–12.6%; p = 0.007 and HR: 3.48; 95%CI: 1.1%–11.0%; p = 0.038, respectively). Conclusions: Surgical resection remains the treatment of choice for mSFTP. Relapse is common (approximately 30%). Incomplete resection and malignant pleural effusion at diagnosis impact LTS negatively.

Bronchoplastic and angioplastic techniques in the treatment of bronchogenic carcinoma

From 1979 to 1991, 51 bronchoplasties, 18 angioplasties, and 4 combined broncho-angioplasties were performed for bronchogenic carcinoma. Sixteen patients underwent operation because of compromised pulmonary function; bronchoplasty, angioplasty, or the combined procedure was performed in the remaining 57 patients because of a suitable anatomic location of the neoplasm. Twenty-four patients had stage I disease, 32 stage II, and 17 stage IIIa. Three patients died postoperatively (3.65%). Major postoperative complications occurred in 20 patients (27.3%) (10 early, and 10 late). A completion pneumonectomy was required in 4 patients (5.4%), 2 for anastomotic stricture, 1 because of vascular thrombosis after angioplasty, and 1 for local recurrence after angioplasty. Three-year and 5-year survival rates for the entire group were 55.4% and 40.8%, respectively. One-year and 3-year survival rates after angioplasty were 78.6% and 31.4%. Of the 4 patients who underwent a combined bronchoangioplastic procedure, 1 died after 23 months and 3 are alive and well after 11, 15, and 20 months. Survival was more favorable in the combined N0-N1 group (62% and 43.1%) than in the N2 group (23.4%), but the difference was not significant (p < 0.2). Three-year survival after angioplasty was found to be lower than, although not significantly different from, the overall 3-year survival rate (31.4% versus 55.4%; p = not significant). No statistically significant differences were found among survival rates of patients with compromised and noncompromised pulmonary reserve. We conclude that bronchoplastic and angioplastic procedures are valid techniques as curative operations in carefully selected patients with bronchogenic carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Imatinib inhibits in vitro proliferation of cells derived from a pleural solitary fibrous tumor expressing platelet-derived growth factor receptor-beta.

We examined the in vitro effects of imatinib (Novartis Pharma AG, Basel, Switzerland) as a possible inhibitor of PDGFR pathway on cells derived from a recurrence of a pleural malignant solitary fibrous tumor (SFT). Primary cell culture was characterised by immunofluorescence. SFT-derived cells were treated with imatinib at different time points. Western blotting for PDGFR-beta, phospho-PDGFR-beta or smooth muscle actin (SMA) was performed before and after 96 h of treatment with imatinib. SFT-derived cells treated with imatinib for 96 h showed a dose dependent decrease of Ki67 expression. Results were confirmed by growth curve. Western blotting showed that PDGFR-beta was highly expressed and phosphorylated in SFT-derived cells and imatinib treatment reduced PDGFR-beta phosphorylation and SMA expression. With the limit of experimental findings, our results support a possible future application of imatinib as a candidate molecule in the target therapy of malignant SFTs over-expressing wild-type PDGFR.

Is 18F-FDG PET useful in predicting the WHO grade of malignancy in thymic epithelial tumors? A meta-analysis

AIM To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs). METHODS A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUVmax) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUVmax between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI). RESULTS Eleven studies were selected for the meta-analysis. The pooled WMD of SUVmax between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4-2.0). The pooled WMD of SUVmax between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4-6.1). Finally, the pooled WMD of SUVmax between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7-4.3). CONCLUSIONS (18)F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUVmax between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas).

Long-Term Results after Treatment for Recurrent Thymoma: A Multicenter Analysis

Objectives: The treatment for recurrent thymoma remains a very controversial issue. This study aims to investigate the long-term outcomes in patients with relapse according to treatment strategies and clinicopathological features. Methods: We retrospectively analyzed the database of three tertiary centers of thoracic surgery with the aim of reviewing the clinical records of 81 patients who experienced a recurrent thymoma after radical thymectomy, in the period between January 2001 and June 2013. The staging of both primitive and recurrent thymomas were based on the surgical and pathological criteria described by Masaoka. Experienced pathologists reassessed independently the histology of the initial thymoma and its relapse, according to the WHO classification. To the purposes of this study R+ resection or thymic carcinoma were considered as exclusion criteria. The overall outcome for long-term (5 years and 10 years) survival and disease-free survival after initial thymectomy and after treatment of recurrent thymoma were analyzed using standard statistics. Results: The population was gender balanced (41 M, 40 F), mean age: 46.4 ± 12.3 years. Fifty-four patients (66.7%) were affected by myasthenia gravis, while the other 14 by other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,), and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up duration after recurrence onset was 66.3 ± 56.4 months. Adjuvant therapy had no effect on prolonging the disease-free survival: no differences were found when investigating the administration of adjuvant chemotherapy (no CHT = 91.5 ± 76.4 months versus yes CHT=64.0 ± 41.3) and radiotherapy (no RT=86.2 ± 72.8 months versus yes RT= 93.0 ± 62.3; p = 0.8). Relapses were mostly local (mediastinum: 15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15 cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined as the “migration” of WHO class at initial thymectomy to more aggressive WHO class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%), but this phenomenon apparently did not influence patient’s prognosis. Overall, the 5- and 10-year survival rates after the initial thymectomy were 94.8% and 71.7%, respectively, while the 5- and 10-year survival rates after the treatment of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4% at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The analysis on the trends of disease-free survival indicated that the site of recurrence (hematogenous diffusion) seems to be associated to a higher risk of re-relapse (p = 0.01). Conclusions: Even following a thymectomy performed with radical intent, thymoma may recur several years later, usually as a locoregional relapse. A rewarding long-term survival may be expected after treatment, especially when a re-resection (radical) is performed (82.4% at 5 years). An histopathological “WHO upgrade” (from “low-risk” WHO classes at thymectomy to “high-risk classes” at relapse) may be observed in a remarkable percentage of patients (nearly 40% in this series), but this phenomenon seems to be not correlated with any worsening of the prognosis.

Completion pneumonectomy: a multicentre international study on 165 patients

OBJECTIVES We evaluated factors that influenced morbidity and mortality in patients undergoing completion pneumonectomy (CP). METHODS A retrospective review of a consecutive series of patients who underwent CP at six international centres. RESULTS In total, 165 CP were performed between March 1990 and December 2009: 152 for malignant disease and 13 for benign disease. Forty-two patients (25.4%) underwent neoadjuvant therapy. Right CP was performed in 99 patients (60%) and left in 66 (40%). Thoracotomy was employed in 161 patients and median sternotomy in 4. Stapled closure of the bronchus was performed in 121 patients and hand closure in 44. The overall operative mortality was 10.3% (17 of 165). Operative mortality was 10.5% (16 of 152) in malignant diseases and 7.7% (1 of 13) in benign diseases. Complications occurred in 55.1% (91 of 165) of patients. Mean hospital stay was 16.02 ± 16.8 days (range: 3-151 days). Thirteen patients (7.9%) developed bronchopleural fistulas. No statistically significant relationship was found in mortality or morbidity according to side, gender, induction therapy and surgical approach. Stapled compared with hand closure for the bronchus did not affect the bronchopleural fistula rate (P = 0.4). The overall 5-year survival was 37.6%: 70.1% in benign disease (13 patients), 48.9% in squamous cell carcinoma of the lung (63 patients), 23.9% in primary lung adenocarcinoma (62 patients), 50% in grade 1 and grade 2 neuroendocrine carcinoma of the lung (4 patients), 54.7% in metastatic disease (14 patients) and 0% in primary lung sarcomas. A statistically significant better survival was observed in patients with squamous cell carcinoma versus adenocarcinoma (P = 0.04). CONCLUSIONS CP shows an acceptable operative mortality with a high morbidity rate. The overall 5-year survival is acceptable in properly selected patients (i.e. squamous cell carcinoma, metastatic disease). Side, gender, induction therapy and surgical approach did not influence mortality and morbidity.

Inflammatory cytokines and VEGF measured in exhaled breath condensate are correlated with tumor mass in non-small cell lung cancer

Inflammation mediated by the immune system is known to be important in carcinogenesis and, specifically, T helper 17 cells have been reported to play a role in tumor progression by promoting neo-angiogenesis. The aim of this study was to investigate whether inflammatory cytokines and vascular endothelial growth factor (VEGF) levels in exhaled breath condensate (EBC) and in serum were related to tumor size in patients with non-small cell lung cancer (NSCLC). Il-6, IL-17, TNF-α and VEGF levels were measured in EBC and serum of 15 patients with stage I-IIA NSCLC and in 30 healthy controls by immunoassay. The tumor size was measured by a CT scan. The concentrations of IL-6, IL-17 and VEGF were significantly higher in EBC of patients with lung cancer, compared with controls, while only serum IL-6 concentration was higher in patients compared to controls. A significant correlation (r = 0.78, p = 0.001) was observed between EBC levels of IL-6 and IL-17; IL-17 was also correlated to EBC levels of the VEGF (r = 0.83, p < 0.001) and TNF-α (r = 0.62, p = 0.014). The tumor diameter was significantly correlated with EBC concentrations of VEGF (r = 0.58, p = 0.039), IL-6 (r = 0.67, p = 0.013) and IL-17 (r = 0.66, p = 0.017). Our results show a significant relationship between inflammatory and angiogenic markers, measured in EBC by a non-invasive method, and tumor mass.

Postoperative exacerbation of chronic obstructive pulmonary disease. Does it exist

BACKGROUND One of the characteristics of chronic obstructive pulmonary disease (COPD) is the tendency to develop acute exacerbation, defined by the presence of different clinical findings as worsening dyspnea, increase in sputum purulence and volume. This study was designed to verify if definition of acute COPD exacerbation is applicable to patients who underwent pulmonary surgery, and if it has any impact on postoperative morbidity and mortality. METHODS This study was designed to prospectively enrol 1000 patients undergoing pulmonary resection for lung cancer from five different centres. Postoperative exacerbation of COPD was defined by the concomitant presence of three of the following five signs: deteriorating dyspnea, purulent sputum, bronchial secretion volume >10 ml/24 h, fever without apparent cause, and wheezing. The presence of concomitant pulmonary complications excluded the diagnosis of exacerbation, as they may present one or more of these signs. RESULTS In the absence of respiratory complications, postoperative stay in exacerbated patients was significantly longer as compared to patients without exacerbation (6.3+/-1.3 vs 8.3+/-1.1, p=0.001). A postoperative exacerbation of COPD was recorded in 276 patients and 152 of them (55%) subsequently developed respiratory complications. Multivariate analysis established that risk factors for postoperative exacerbation are sex (female OR 0.54, CI 0.2-0.8), COPD class (OR 1.5, CI 1.1-8.1), and the postoperative prolonged use of antibiotics (OR 0.6, CI 0.2-0.9). CONCLUSIONS Postoperative exacerbation of COPD is an existing, frequent clinical entity after lung resection and, when present, it increases the risk of pulmonary complications. The existing guidelines for the treatment of acute exacerbation should be adapted for the management of patients after lung resection in order to test the hypothesis that they could reduce respiratory morbidity.

Tapias Score for Predicting Recurrences in Resected Solitary Fibrous Tumor of the Pleura: Controversial Points and Future Perspectives Emerging From an External Validation

To the Editor: Solitary fi brous tumor of the pleura (SFTP) is uncommon and has uncertain and unpredictable prognosis. Rarely attempted, the standardization of prognostic criteria has, so far, failed. 1 , 2 Th e eff ort from Tapias et al 3 recently reported in CHEST (January 2015) is, therefore, very welcome. By fi rst proposing 4 and subsequently validating 3 a scoring system able to predict the recurrence aft er (radical) surgical resection for SFTP, they have provided a benchmark for discussion on the issue. Inspired by this, we have analyzed data from our multicentric malig nant SFTP database, 5 testing the accuracy of the “Tapias score.” Among 50 male patients with SFTP, 43 were eligible. 3 Th e Tapias score (0–6) was as follows: n 5 3, 2 points; n 5 7, 3 points; n 5 13, 4 points; n 5 18, 5 points; and n 5 2, 6 points . Tapias score 5 0 was not recorded. With a cutoff 3, 3 , 4 40 patients (93%) were labeled as high risk for recurrence, and three (7%) were labeled as low risk. Th e Cox regression analysis was reanalyzed, exploring the value of Tapias score in predicting recurrence or death ( Table 1 ).