Pio Maniscalco

A3 Receptors Are Overexpressed in Pleura from Patients with Mesothelioma and Reduce Cell Growth via Akt/Nuclear Factor-κB Pathway

RATIONALE A strong link has been established between exposure to asbestos and increased risk for pleural malignant mesothelioma (MM). Adenosine plays a key role in inflammatory processes and cancer, where it is involved in the regulation of cell death and proliferation. OBJECTIVES The primary aim of this study was to investigate the presence of adenosine receptors (ARs) in human MM pleura (MMP) and healthy mesothelial pleura (HMP). To shed some light on the interaction between adenosine and MM, the presence and functionality of ARs were explored in human healthy mesothelial cells (HMC) and in malignant mesothelioma cells (MMC). METHODS ARs were analyzed by using reverse transcriptase-polymerase chain reaction, Western blotting, and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor for MM. The role of A₃ ARs on these cellular models, evaluating cAMP production, Akt phosphorylation, and nuclear factor (NF)-κB activation, was investigated. The dual effect of A₃AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis, and cytotoxicity assays. MEASUREMENTS AND MAIN RESULTS A₃AR was up-regulated by 2.5-fold (P < 0.01) in MMP when compared with HMP. Stimulation of A₃ARs decreased proliferation and exerted a cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and tumor necrosis factor-α, but not on HMC with an involvement of the deregulation of Akt/NF-κB cell survival pathway. CONCLUSIONS These new findings suggest that A₃AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full-blown MM.

P2X7 targeting inhibits growth of human mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti-blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2×7 (P2RX7 or P2×7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation. In this report we show that the P2×7R is expressed by three MPM cell lines established from MPM patients but not by mesothelial cells from healthy subjects (healthy mesothelial cells, HMCs). MPM cell proliferation was inhibited by in vitro incubation in the presence of selective P2×7R antagonists, as well as by stimulation with the P2×7R agonist BzATP. Systemic administration of the selective P2×7R blocker AZ10606120 inhibited in vivo growth of MPM tumors whether implanted subcutaneously (s.c.) or intraperitoneally (i.p.). Our findings suggest that the P2×7R might be a novel target for the therapy of mesothelioma.

Long-Term Outcome for Early Stage Thymoma: Comparison between Thoracoscopic and Open Approaches

BACKGROUND Complete surgical excision is the most important long-term prognostic factor of thymomas. Although video-assisted thoracoscopic surgery (VATS) has been reported as an effective treatment to excise mediastinal thymic lesions, it has not replaced median sternotomy as the standard approach because of the lack of long-term follow-up studies. The objective of this study was to analyze and to compare the outcome of VATS extended thymectomy with the traditional open approach. METHODS This is a single centers retrospective study of 27 patients submitted to surgery for early stage thymomas between 1995 and 2007. Histologic subtype and clinicopathologic staging were classified, respectively, according to World Health Organization and Masaoka criteria. Patients with preoperative computed tomography scan evidence of clinical Masaoka stage 1 thymomas were selected for VATS thymectomy with unilateral technique. RESULTS All patients successfully underwent surgery: 3 with VATS and 4 with an open approach. There were no differences in time of surgery and postoperative complication between the two groups. Patients who had VATS had shorter postoperative hospital stay than patients who had open technique. After a median follow-up of 123 months, there were no postoperative recurrences. CONCLUSION VATS is a safe operation and has comparable effectiveness to the open technique in terms of oncological radicality for small, early stage thymoma.

Cost-effectiveness analysis of sealant impact in management of moderate intraoperative alveolar air leaks during video-assisted thoracoscopic surgery lobectomy: a multicentre randomised controlled trial

Background Intraoperative alveolar air leak (IOAAL) is one of most common complications after video-assisted thoracoscopic surgery (VATS) lobectomy. The study aimed to evaluate if, in moderate IOAAL, intraoperative polymeric biodegradable sealant (ProgelTM) reduced postoperative air leak (PAL) and consequently was cost-effective. Methods Patients with moderate IOAAL were randomised in a multicentre trial to intraoperative use of a sealant (Sealant group) or standard management of air leaks (Control group). Primary endpoint was the postoperative duration of air leakage. Secondary outcomes included: time to drainage removal, length of hospital stay, postoperative complications within 2 months, and cost analysis. Results Between January 2015 and January 2017, 255 VATS lobectomies were performed in four centres. Fifty-five met inclusion criteria and were randomly assigned to Sealant group [28] and Control group [27]. The mean air leakage duration was statistically different between groups (Sealant group =1.60 days, Control group =5.04 days; P<0.001). The average length of drainage was significantly (P=0.008) shorter in Sealant group (4.1 days) than in Controls (6.74 days). The mean time of hospital stay was statistically shorter in sealant group (Sealant =5.75 days, Control =7.85 days; P=0.026). Sealant group observed a statistically significant reduction of costs. Conclusions In moderate IOAAL after VATS lobectomy, polymeric biodegradable sealants are safe and efficient. Compared with standard treatments, sealant significantly reduces PAL, time to drain removal and length of hospital stay resulting in significant costs benefits.

Multidisciplinary management improves survival at 1 year after surgical treatment for non-small-cell lung cancer: a propensity score-matched study†

OBJECTIVES The management of patients affected by lung cancer requires the expertise of specialists from different disciplines. Although the advantages of multidisciplinary team discussions seem obvious, there are limited studies evaluating the influence of this approach on postoperative outcomes in non-small-cell lung cancer (NSCLC). The aim of this study is to examine the impact of a multidisciplinary approach on survival of patients undergoing surgery for NSCLC. METHODS A retrospective analysis was performed on consecutive patients who underwent surgery for NSCLC between January 2008 and December 2015. Data were compared between patients treated before the implementation of a multidisciplinary tumour board (MTB), between 2008 and 2012, and those who received treatment after the implementation of the MTB, between 2012 and 2015. Patients were matched one to one according to the discussion of the MTB and on the basis of a propensity score built using several patient characteristics. A propensity score-matched analysis was performed to compare patient outcomes. RESULTS A total of 246 patients were treated prior to the initiation of the MTB and 231 patients after the initiation of the MTB. Based on the propensity score, 2 well-matched groups of 170 patients were identified. Patients who were discussed at the MTB were noted to have better outcomes when compared with those who were not discussed at the MTB on different terms including complete staging evaluation, early tumour, node and metastasis (TNM) stages and 1-year survival rate. CONCLUSIONS Implementation of a multidisciplinary thoracic malignancy conference increased the 1-year survival rate of patients who underwent a surgical resection for NSCLC.

Capsaicin patch for persistent postoperative pain after thoracoscopic surgery, report of two cases

Effective postoperative pain control after thoracic surgery is a significant clinical issue because it reduces pulmonary complications and accelerates the pace of recovery. Persistent postoperative pain syndrome is a recognized and frequent complication after thoracoscopic surgery. The capsaicin 8% patch contains a high concentration of synthetic capsaicin approved for treatment of peripheral neuropathic pain in adults. Little clinical data exist on the use of capsaicin patch in thoracic persistent postoperative pain syndrome. This report included two patients who were evaluated after receiving capsaicin for thoracic surgery. Satisfactory pain relief was achieved in both cases without side effects.

Diffuse pulmonary meningothelial like nodules simulating metastatic thymoma

Diffuse pulmonary meningotheliomatosis (DPM) is a parenchymal lung disease characterized by disseminated bilateral minute pulmonary meningothelial-like nodules (MPMNs). These meningothelial-like nodules are classically encountered as benign solitary or multiple pulmonary nodules containing small epithelioid cell collections nestled within normal pulmonary parenchyma.

A rare case of intralobar pulmonary sequestration: combined endovascular and video-assisted thoracoscopic approach

Pulmonary sequestration is a congenital malformation characterized by cystic, non-functioning embryonic lung tissue supplied by an abnormal systemic artery. Its a rare disease widely variable in clinical presentation and severity, depending mostly on the degree of lung involvement and location in the thoracic cavity. Most patients have recurrent infections and inflammatory conditions in the affected lobe. Surgical resection continues to be the gold standard of therapy and in this context anatomical resection is the procedure of choice and yields excellent long-term results. There are few studies reporting the use of combined endovascular and thoracoscopic approaches for pulmonary sequestration. We describe a case of intralobar pulmonary sequestration located in the lower lobe of the right lung, which was treated with video-assisted thoracoscopic surgery (VATS) after endovascular embolization of systemic artery arising from celiac trunk.

Primary septic arthritis of the manubriosternal joint in an immunocompetent young patient: A case report

The aim of this article was to illustrate a case of primary septic arthritis of the manubriosternal joint, due to Staphylococcus aureus infection, in an immunocompetent 28-year-old male patient. The manubriosternal joint can be rarely involved in inflammatory processes, but pyarthrosis is even more unusual in an otherwise healthy adult. Although rare, pyarthrosis could be associated with significant morbidity and mortality, first of all because of spreading to mediastinal structures. Diagnosis is generally made thanks to imaging findings after clinical suspicion in a patient with anterior chest pain and swelling, fever, and raised inflammatory markers, especially when any risk factors are known. Management is generally aggressive because intravenous antibiotics and surgical debridement are necessary.

A Rare Case of Solitary Rib MetastasisThirty-Two Years after Resection ofParotid Gland Adenocarcinoma

Context: Parotid adenocarcinoma is a rare salivary gland neoplasm, showing distant metastases in 12%-26% of cases, according to histologic grade. The most frequent locations are the cervical lymph nodes, liver, lungs and bones and metastatic disease is usually associated with poor prognosis. Single late-onset rib metastasis from adenocarcinoma of parotid gland has never been reported in the literature. Case report: We describe the case of a sixty-three-years-old male presenting with an osteolytic rib lesion 32 yrs after surgery for parotid gland adenocarcinoma. The patient was successfully treated with en bloc resection of the 11th rib for parotid gland adenocarcinoma metastasis. The patient has no evidence of local recurrence or metastatic disease 40 months after resection. Conclusion: This case may be useful for making clinical decisions because underlines the challenges of giving patients the optimal treatment considering the limited ability to predict prognosis and highlights the need for careful follow-up even in absence of recurrence for 10 yrs after curative resection.