Marco Anile

Long-Term Outcome after Multimodality Treatment for Stage III Thymic Tumors

BACKGROUND Surgery remains the cornerstone of therapy for thymic tumors, but the optimal treatment for advanced, infiltrative lesions is still controversial. The introduction of multimodality protocols has substantially modified survival and recurrence rate. We reviewed our 13-year prospective experience with multimodality treatment of stage III thymoma and thymic carcinoma. METHODS Since 1989 we have prospectively used a multimodality approach in 45 stage III thymic tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%) had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well-differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma (group 3). Tumors that were not considered radically resectable at preoperative workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by surgical resection; all patients were referred for adjuvant chemoradiotherapy. RESULTS No operative mortality was recorded; 1 treatment-related death during adjuvant chemotherapy was observed in group 1. Complete resection was feasible in 91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%, respectively; 8-year survival for group 3 was 56%. During follow-up, tumor recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and 3 (27%) from group 3. CONCLUSIONS Multimodality treatment with induction chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging results for stage III thymic tumors; the outcome is more favorable for cortical thymoma and well-differentiated thymic carcinoma.

Thymoma and thymic carcinoma

Thymoma and thymic carcinoma are an extremely heterogeneous group of neoplastic lesions with an exceedingly wide spectrum of morphologic appearances. They show different presentations with a variable and unpredictable evolution ranging from an indolent non-invasive attitude to a highly infiltrative and metastasising one. Prognosis can be predicted on the basis of a number of variables, mainly staging, the WHO histological pattern and diameter of the tumour. Complete surgical resection is certainly the gold standard to achieve cure. However, especially in patients with lesions at advanced stage, complete resection may be difficult and recurrence often occurs; at these stages, disease-free long-term survival may be difficult to be accomplished. Chemo- and radiotherapy protocols have been designed to complete surgical treatment and improve results in inoperable patients as well, based on the reported sensitivity of thymic tumours to these treatment modalities. The integration of clinical staging and histology, with the new histogenetic morphological classification, has contributed to design multimodality treatment protocols that help to improve prognosis. Induction therapy can now be applied before surgery in patients with tumours considered inoperable, improving resectability and outcome without adding morbidity and mortality to the surgical procedure. This newly developed approach helps to reduce the recurrence rate and to ameliorate disease-free survival. New therapies are now being evaluated as for many other tumours; however, they still need confirmation in prospective randomised studies. In the future, integrated treatment modality should be incorporated in a standardised approach that goes from a careful assessment of histology, staging and lymph node status, and a constructive and non-empirical co-operation between medical and radiation oncologists, pathologists and thoracic surgeons.

Dysfunctional CFTR Alters the Bactericidal Activity of Human Macrophages against Pseudomonas aeruginosa

Chronic inflammation of the lung, as a consequence of persistent bacterial infections by several opportunistic pathogens represents the main cause of mortality and morbidity in cystic fibrosis (CF) patients. Mechanisms leading to increased susceptibility to bacterial infections in CF are not completely known, although the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in microbicidal functions of macrophages is emerging. Tissue macrophages differentiate in situ from infiltrating monocytes, additionally, mature macrophages from different tissues, although having a number of common activities, exhibit variation in some molecular and cellular functions. In order to highlight possible intrinsic macrophage defects due to CFTR dysfunction, we have focused our attention on in vitro differentiated macrophages from human peripheral blood monocytes. Here we report on the contribution of CFTR in the bactericidal activity against Pseudomonas aeruginosa of monocyte derived human macrophages. At first, by real time PCR, immunofluorescence and patch clamp recordings we demonstrated that CFTR is expressed and is mainly localized to surface plasma membranes of human monocyte derived macrophages (MDM) where it acts as a cAMP-dependent chloride channel. Next, we evaluated the bactericidal activity of P. aeruginosa infected macrophages from healthy donors and CF patients by antibiotic protection assays. Our results demonstrate that control and CF macrophages do not differ in the phagocytic activity when infected with P. aeruginosa. Rather, although a reduction of intracellular live bacteria was detected in both non-CF and CF cells, the percentage of surviving bacteria was significantly higher in CF cells. These findings further support the role of CFTR in the fundamental functions of innate immune cells including eradication of bacterial infections by macrophages.

Long-term follow-up after bronchoscopic lung volume reduction in patients with emphysema

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves. 40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV1) was 0.88 L·s−1 (23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures. 33 patients had a follow-up of >12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV1, RV, 6MWT and MRC score showed a statistically significant improvement (p≤0.0001, p=0.004, p=0.03, p=0.003 and p<0.0001, respectively). Patients with visible fissures had a functional advantage. BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.

Reconstruction of the pulmonary artery for lung cancer: Long-term results

OBJECTIVE Reconstruction of the pulmonary artery in association with lung resection is technically feasible with low morbidity and mortality. To assess long-term outcome, we report our 20-year experience. METHODS Between 1989 and 2008, we performed pulmonary artery reconstruction in 105 patients with non-small cell lung cancer (tangential resections not included). Twenty-seven patients received induction therapy. We performed 47 pulmonary artery sleeve resections, 55 reconstructions by pericardial patch (with 3 left pneumonectomies under cardiopulmonary bypass), and 3 by pericardial conduit. In 65 patients, a bronchial sleeve resection was associated; in 6 cases superior vena caval reconstruction was also required. Fifteen patients had stage IB disease, 37 stage II, 31 IIIA, and 22 IIIB. Sixty-one patients had epidermoid carcinoma, and 38 adenocarcinoma. Mean follow-up was 46 +/- 40 months. RESULTS The procedure-related complications were 1 pulmonary artery thrombosis requiring completion pneumonectomy and 1 massive hemoptysis leading to death (operative mortality, 0.95%); 28 patients had other complications, with the most frequent prolonged air leakage. Overall 5-year survival was 44%. Five- and 10-year survivals for stages I and II versus stage III were, respectively, 60% versus 28% and 25% versus 12%. Five-year survivals were 52.6% for N0 and N1 nodal involvement versus 20% for N2; 10-year survivals were 28% versus 3%. Multivariate analysis yielded induction therapy, N2 status, adenocarcinoma, and isolated pulmonary artery reconstruction as negative prognostic factors. CONCLUSIONS Pulmonary artery reconstruction is safe, with excellent long-term survival. Our results support this technique as an effective option for patients with lung cancer.

Thoracoscopic resection of mediastinal bronchogenic cysts in adults

OBJECTIVE Bronchogenic cysts are uncommon congenital anomalies of foregut origin usually located within the mediastinum and the lung and rarely diagnosed in adults. Surgical excision is recommended to establish diagnosis based on histologic examination, alleviate symptoms if present, and prevent future complications. Thoracoscopic approach is becoming the primary therapeutic option. METHODS Between January 1995 and July 2008, 30 patients with mediastinal bronchogenic cyst (MBC) underwent thoracoscopic operation (19 male, 11 female with a mean age of 39 years, range 19-59 years). Symptoms were present in 11 patients (37). RESULTS The cysts averaged 5.2 cm in their greatest diameter (range 3-10.5 cm). In two cases thoracoscopy was converted to thoracotomy because of major pleural adhesions. There were no operative deaths and no intra-operative complications. Postoperative course was uneventful in all cases and the 28 patients who underwent thoracoscopy were discharged after a mean of 3.7 days (range 2-5 days). CONCLUSIONS Considering the low conversion and complication rate, thoracoscopic excision of bronchogenic mediastinal cyst should be considered the primary therapeutic option.

Sleeve Lobectomy Compared with Pneumonectomy after Induction Therapy for Non–Small-Cell Lung Cancer

Background: We compared morbidity, mortality, and oncological results of bronchial and/or vascular sleeve lobectomy (SL) with those of pneumonectomy (PN) after induction therapy for lung cancer. Methods: Between 1998 and 2011, 82 patients receiving induction therapy (chemo or chemo-radiotherapy) for non–small-cell-lung-cancer underwent sleeve lobectomy (n = 39) or pneumonectomy (n= 43). Only patients undergoing preoperative chemotherapy (39 in the SL group and 39 in the PN group) were included in the study. SL was bronchial in 21, vascular in 12, and broncho-vascular in six cases, respectively. Clinical stage before induction therapy was IIb in seven patients (1 in PN group; 6 in SL group), IIIa in 66 (36 in PN group; 30 in SL group), and IIIb in five patients (2 in PN group; 3 in SL group), respectively. N3 patients were not included in this series. Results: The rate of downstaged patients (pathological complete response and stage I–II) was 79.5% in the SL group and 53.8% in the PN group (p = 0.01).Postpneumonectomy mortality rate was 2.6 %. There was no postoperative mortality after SL. Complications occurred in 12 patients (30.8%) after PN and in 11 patients (28.2%) after SL (p = 0.6). Three-year and 5-year survival rates were 68 ± 3% and 64 ± 8% in the SL group; and 59.5 ± 5% and 34.5 ± 8% in the PN group (p = 0.02). The difference in terms of recurrence rate (locoregional and distant) between the two groups was not significant (p = 0.2). Conclusions: SL represents a valid therapeutic option even after induction chemotherapy, providing better long-term survival than PN, with no increase of postoperative complications or recurrence rate. Pathological downstaging is a favorable prognostic factor.

Extracorporeal Removal CO2 Using a Venovenous, Low-Flow System (Decapsmart) in a Lung Transplanted Patient: A Case Report

BACKGROUND Primary graft dysfunction (PGD) is a syndrome that may occur after lung transplantation. In some cases of severe PGD, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and surfactant and intravenous prostacyclins are inadequate to achieve adequate gas exchange. The only lifesaving option is to use an extracorporeal membrane oxygenator. The Decapsmart is a new venovenous, low-flow extracorporeal device to removal carbon dioxide (CO(2)). It does not need a specialized staff. Herein we have presented a case report of a patient who underwent single lung transplantation and experienced respiratory failure. METHODS On November 2007, a 52-year-old woman underwent a single right lung transplantation, and developed severe PGD in the postoperative period. After institution of conventional treatments, including ventilatory and hemodynamic support, iNO, and prostaglandine E1, we started treatment with Decapsmart to remove CO(2). Hemodynamic and respiratory parameters were assessed at baseline and after 3, 12, 24, and 48 hours. RESULTS No adverse events occurred. From baseline to 48 hours, pH values increased and partial pressure of CO(2) reduced. At the same time ventilatory support was reduced, thereby mitigating barotrauma and risk of overdistension. CONCLUSION The use of Decapsmart may be an important aid for patients with severe respiratory acidosis in association with conventional therapy during the perioperative period after lung transplantation.

Thoracoscopic sympathectomy for symptomatic arterial obstruction of the upper extremities

BACKGROUND Severely symptomatic arterial insufficiency of the hand and upper extremities requires adequate treatment. Medical therapy and local care are usually unsuccessful, and thoracic sympathectomy can represent an effective procedure to control pain, to help ulcer healing, and to prevent or delay amputation. METHODS We performed 20 thoracoscopic sympathectomies in 15 patients (13 men and 2 women) with upper extremity ischemia. Mean age was 47 years (range 21 to 72 years). All patients were thought to have organic blockage of digital arteries. The condition was unilateral in 10 patients and bilateral in 5. Primary diagnosis was digital arteriosclerosis in 8 patients, Buergers disease in 4 patients and the remaining 3 were drug abusers with severe ischemia due to accidental intraarterial injection of drugs. Eleven patients (73%) presented with terminal digital necrosis, gangrene, or ulceration of the fingers associated with severe pain. Four patients complained of coldness, pain, and some degree of soft tissue infection without permanent loss of tissue. RESULTS We performed 10 unilateral and five bilateral staged (mean interval was 3 months) thoracoscopic sympathectomies. We had two minor complications and no mortality. Mean duration of postoperative chest drainage was 2.5 +/- 0.4 days and mean postoperative hospital stay was 5.3 +/- 0.5 days. Follow-up ranged from 3 to 71 months, with a mean of 33 months. All patients demonstrated clinical benefit after operation. CONCLUSIONS Thoracoscopic sympathectomy in patients with severe ischemia of upper limb extremities permits optimal symptomatic control and maximum tissue salvage. Because the procedure is minimally invasive, safe, and associated with a low rate of complications, it should be considered earlier the natural course of this disease.

Thymoma and the increased risk of developing extrathymic malignancies: A multicentre study

OBJECTIVES Although thymoma is considered a relatively indolent neoplasia, patients affected by this disease are at high risk of developing second tumours (STs). The aim of this study is to assess the risk of developing STs after surgical thymoma resection. METHODS A multicentre retrospective study of patients operated on for thymoma within five Italian Thoracic Surgery Institutions, between 2000 and 2011, was conducted. The overall STs number and incidence were calculated. The number of metachronous STs was compared with the expected cancer number (ECN) in an Italian population, and the standardized incidence ratio (SIR) and 95% confidence intervals were calculated. Potential variables of STs predictors were also evaluated. RESULTS There were 302 patients; myasthenia gravis (MG) was observed in 166 (55%) and other autoimmune syndromes in 49 of them. In 118 patients (39.1%), the Masaoka thymoma stage was greater than II and in 194, the WHO histological type ranged from B1 to C. Fifty STs were observed (28 metachronous, 4 synchronous and 18 detected before thymoma). The observed metachronous STs number was significantly higher than ECN. An increased risk of STs development was observed in advanced stage thymomas and in those with histological high grade. On the contrary, MG seems to be a protective factor in STs development. CONCLUSIONS Our study confirms the high risk of developing STs in patients with thymoma. Aggressive forms of thymoma are those in which this risk appears to be more evident. The central role of an intrinsic immune system alteration might be the key to interpret this phenomenon.