Ilir Hysi

Overexpression and promoter mutation of the TERT gene in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a very aggressive tumor with no known curative treatment. Better knowledge of the molecular mechanisms of mesothelial carcinogenesis is required to develop new therapeutic strategies. MPM, like all cancer cells, needs to maintain telomere length to prevent senescence. Previous studies suggested that the telomere lengthening mechanism in MPM is based mainly on telomerase activity. For this reason, we focused on the key catalytic enzyme, TERT (telomerase reverse transcriptase), by analyzing its gene expression in MPM and by studying the mechanism underlying its upregulation. We used our large collection of MPM composed of 61 MPM in culture and 71 frozen MPM tumor samples. Evaluation of TERT mRNA expression by quantitative RT–PCR showed overexpression in MPM in culture compared with normal mesothelial cells, and in MPM tumor samples compared with normal pleura. We identified a ‘hot spot’ of mutations in the TERT gene core promoter in both MPM in culture and in MPM tumor samples with an overall frequency of 15%. Furthermore, data clearly identified mutation in the TERT promoter as a mechanism of TERT mRNA upregulation in MPM. In contrast, gene copy number amplification was not associated with TERT overexpression. Then, we analyzed the clinicopathological, etiological and genetic characteristics of MPM with mutations in the TERT promoter. TERT promoter mutations were more frequent in MPM with sarcomatoid histologic subtype (P<0.01), and they were frequently associated with CDKN2A gene inactivation (P=0.03). In conclusion, a subgroup of MPM presents TERT promoter mutations, which lead to TERT mRNA upregulation. This is the first recurrent gain-of-function oncogenic mutations identified in MPM.

Simplified open repair for anterior chest wall deformities. Analysis of results in 205 patients

INTRODUCTIONnPectus deformities are the most frequently seen congenital thoracic wall anomalies. The cause of these conditions is thought to be abnormal elongation of the rib cartilages. We here report our clinical experience and the results of a sternochondroplasty procedure based on the subperichondrial resection of the elongated cartilages.nnnHYPOTHESISnThis technique is a valuable surgical strategy to treat the wide variety of pectus deformities.nnnPATIENTS AND METHODSnDuring the period from October 2001 through September 2009, 205 adult patients (171 men and 34 women) underwent pectus excavatum (181), carinatum (19) or arcuatum (5) repair. The patients pre and postoperative data were collected using a computerized database, and the results were assessed with a minimum 2-year follow-up.nnnRESULTSnThe postoperative morbidity rate was minimal and the mortality was nil. The surgeon graded cosmetic results as excellent (72.5%), good (25%) or fair (2.5%), while patients reported better results. Patients with pectus excavatum were found to have much more patent foramen ovale (PFO) than the normal adult population, which occluded after the procedure in 61% of patients, and significant improvement was found in exercise cardiopulmonary function and exercise tolerance at the 1-year follow-up.nnnDISCUSSIONnOur sternochondroplasty technique based on the subperichondrial resection of the elongated cartilages allows satisfactory repair of both pectus excavatum and sternal prominence. It is a safe procedure that might improve the effectiveness of surgical therapy in patients with pectus deformities.

Primary pulmonary myoepithelial carcinoma

Primary salivary gland-type tumors of the lung are rare neoplasms. The pulmonary myoepithelial carcinoma belongs to this group. Since it was first described in 1998, we have identified only seven actual cases reported in the literature so far. We describe the case of a non-smoker 60-year-old Caucasian female, who was referred to our institution for the treatment of three peripheral nodules. Her medical history revealed that a wedge resection, for pulmonary myoepithelial carcinoma, was performed in another center 15 months previously. After resection of the current nodules, the histological findings showed three myoepithelial carcinomas of the lung. There was no vascular or lymphatic invasion. The hilar and mediastinal lymph nodes were negatives. The patient is doing well without any sign of recurrence. Herein we shall discuss the case of a primary pulmonary myoepithelial carcinoma in a female and propose a brief review of the literature.

Open Window Thoracostomy and Thoracoplasty to Manage 90 Postpneumonectomy Empyemas

BACKGROUNDnPostpneumonectomy empyema (PPE) is a serious complication. The treatment options are similar to the management of any abscess, with drainage, ideally open, often of critical importance. After infection control, many techniques for space obliteration have been described. This study summarizes a 10-year experience in the management of PPE in our center.nnnMETHODSnFrom 2000 to 2010, 90 patients (83 men) with PPE were treated. Median follow-up was 5.3 years. Once the diagnosis of empyema was confirmed, chest drainage was performed through open window thoracostomy (OWT), with ensuing extramusculoperiosteal thoracoplasties if healthy tissue was present.nnnRESULTSnPneumonectomy was performed in 72 patients with lung cancer. Mortality after PPE was 2.2%. OWT achieved infection control in 89 patients. Seven OWT spontaneously healed, and 24 were never closed. The remaining 59 patients with OWT underwent thoracoplasty. Mortality after thoracoplasty was 5%. Empyema recurred in 3 patients. Overall success rate of PPE control after pleural obliteration was 91.5%.nnnCONCLUSIONSnThoracoplasty is a reliable filling procedure. It has a significantly higher success rate and a lower mortality rate than the other techniques. We believe that this procedure has a part to play in the future management of PPE.

Cardiac surgery and repair of pectus deformities: When and how?

OBJECTIVESnThere is currently a lack of recommendations about patients with pectus deformities requiring cardiac surgery. This study reports the results of our surgical strategy on this issue.nnnMETHODSnEleven patients, from three centers treated over a 9-year period were included in this study. Pectus deformities were operated with a modified Ravitch procedure. In the case of pectus excavatum repair and concomitant cardiac surgery, subperichondrial resection of abnormal rib cartilages was always performed before the sternotomy and an easily removable retrosternal metallic strut was inserted at the end of the procedure ensuring anterior chest wall stability. During follow-up patients had to estimate their current appearance with a numeric scale ranging from 0 to 100.nnnRESULTSnMean age was 27 ± 9.4 years. Pectus excavatum was present in 8 patients and pectus arcuatum in 3. There were 6 Marfan syndrome patients. Nine patients had concomitant surgery and, 2 underwent pectus repair after a history of cardiac surgery. There was no operative mortality. In the case of concomitant surgery, heart exposure through median sternotomy was facilitated by abnormal rib cartilage resection. Median follow-up was 54 months (range 16.7-119.7). Mean cosmetic result evaluated by the patients was 97.3 (±2.5).nnnCONCLUSIONSnIn adults, concomitant scheduled surgery is reliable and offers excellent long-term cosmetic results. Moreover, it allows a better thoracic exposition with no added perioperative risk. The modified Ravitch technique seems more adequate in these patients as it can be used in all types of pectus deformities.

Lymph node involvement and metastatic lymph node ratio influence the survival of malignant pleural mesothelioma: a French multicenter retrospective study.

Malignant pleural mesothelioma (MPM) is a rare tumor with disastrous evolution. The prognostic value of nodal involvement is still debated. We analyzed the impact of nodal involvement on overall survival (OS) in patients treated by multimodal therapy including extra pleural pneumonectomy (EPP). We evaluated the role, as a prognostic factor, of the metastatic lymph node ratio (LNR), corresponding to the number of involved nodes out of the total number of removed nodes. In this retrospective multicentric study, we reviewed the data of 99 MPM patients. Information regarding lymph node involvement was assessed from the final pathology reports. N1-N3 patients were pooled as N+ group. The OS, calculated by the Kaplan-Meier method, was compared using the log-rank test. A multivariate Cox proportional hazards model was used to identify independent prognostic factors. For the whole cohort, median OS was 18.3 months and 5-year survival was 17.5%. N+ status reduced significantly the median survival (22.4 months for N0 patients vs 12.7 months for N+ patients, P=0.002). A lower metastatic LNR (≤13%) was associated with a significantly improved median survival (19.9 vs. 11.7 months, P=0.01). OS was not related to the number of involved or total removed lymph nodes. In multivariate analysis, only adjuvant radiotherapy (P=0.001) was identified as an independent positive prognostic factor. Metastatic LNR is a more reliable prognostic factor than the number of involved lymph nodes or the total number of removed nodes. However, it could not be identified as an independent prognostic factor.

Stentless Porcine Bioprosthesis in Pulmonary Position After Ross Procedure: Midterm Results

BACKGROUNDnStentless porcine roots (SPV) have been proposed for right ventricular outflow tract reconstruction in the Ross procedure due to the relative availability of pulmonary homografts in large diameters. We report here our experience with SPV used in the Ross procedure.nnnMETHODSnBetween March 1992 and February 2011, 360 patients had a Ross procedure; 61 patients received a SPV in pulmonary position and they represent the study population. Mean age was 38 ± 7.6 years. Indication for surgery was an infective endocarditis in 15 cases, there were 3 redo operations. Median SPV diameter was 29 mm (range, 25 to 29 mm). Pulmonary stenosis was defined as a peak transvalvular gradient of more than 50 mm Hg.nnnRESULTSnPerioperative mortality was 4.9% (3 patients) and late mortality was 3.3% (2 patients). Median follow-up was 4 years (range, 7 days to 14.9 years). There was no reoperation on the right ventricle outflow tract, and freedom from pulmonary stenosis was 100% at 5 years. Mean transpulmonary gradients were 7.1 ± 3.1 mm Hg and 13.5 ± 6.8 mm Hg postoperatively and at 5 years, respectively. Mean transpulmonary gradient increased faster over time when the SPV diameter was less than 29 mm (pxa0= 0.03).nnnCONCLUSIONSnThe SPV could represent an alternative to cryopreserved pulmonary homografts during the Ross procedure in adult patients. Hemodynamic results were improved by using large diameter SPV, but longer follow-up is mandatory to confirm those results.

Conservative management of postintubation tracheal membrane ruptures

Dear Editor, Tracheal ruptures occur rarely as the consequence of blunt trauma or iatrogenically, mainly from endotracheal intubation. In these patients, the tracheal membrane is typically injured and there is a possibility of spontaneous healing. A 62-year-old woman underwent endotracheal intubation for elective surgery (thyroidectomy). Subcutaneous emphysema developed and she was referred to our institution on suspicion of postintubation tracheal injury. On evaluation, she was found to have a subcutaneous emphysema and dyspnea. Fiber-optic bronchoscopy revealed a severe tracheal membrane rupture (TMR) extending up to the cricoid cartilage down to 3 cm above the carina and overall measuring 9 cm in length (Animation 1). Computed tomography (CT) showed moderate pneumomediastinum and retropneumoperitoneum associated with fullthickness TMR, with no evidence of esophageal injury (Fig. 1). The patient was conservatively treated with antibiotics and observed for 7 days, while symptoms decreased. Fiber-optic bronchoscopy before discharge showed a favorable healing process. On day 17, follow-up bronchoscopy showed minimal granulation tissue at the level of laceration and revealed the lesion to be completely healed on day 63 (Animation 2). The patient later underwent a thyroidectomy with preoperative intubation under fiber-optic guidance. The postoperative course was uneventful and she was discharged on day 2. Follow-up bronchoscopy at 1 year demonstrated ad integrum recovery of the tracheal lumen. Recent literature focuses attention on the effectiveness of nonoperative treatment of isolated TMR [1–4]. In 1997, Ross and colleagues [1] proposed restrictive selection criteria to be used as guidelines for conservative treatment, which might be updated according to our previous experience of 30 consecutive patients [3] and the present case. In fact, in patients in whom air leak leads to clinical instability, provided pneumothorax and/or extensive subcutaneous emphysema are properly drained, the consequences of TMR on the respiratory mechanics are usually minimal. Furthermore, a full-thickness TMR associated with herniation of the esophagus into the tracheal lumen leading to mild respiratory distress may be treated by low

Aortic root surgery improves long-term survival after acute type A aortic dissection

OBJECTIVEnOur objective was to analyze the long term survival of patient operated on for acute type A aortic dissection.nnnMETHODSnBetween 1990 and 2010, 226 patients underwent emergency surgical operation for acute type A aortic dissection. We have followed the long-term outcomes.nnnRESULTSn144 patients were operated on with a supracommissural replacement of the ascending aorta (SCR) and 82 with an aortic root surgery (ARS, including 77 Bentall procedures and 5 Tirone David operations). Aortic cross-clamp was longer in ARS group (150.8 vs. 103.6 min, p<0.0001). Overall in-hospital mortality was lower in ARS group (20% vs. 34%, p 0.03). Median follow-up was 11.6 years. 10-year survival was higher in ARS group (85.7% vs. 65.9%, p 0.03) and 10-year freedom from aortic root reoperation was significantly lower in ARS group (93.4% vs. 82.9%, p 0.02). In a multivariate analysis aortic root surgery was an independent protective factor for proximal reoperations OR 0.393, CI 95% [0.206-0.748], p=0.005.nnnCONCLUSIONSnOur study suggests that complete aortic root replacement in type A aortic dissection does not burden short-term outcomes, improves long-term survivals and decreases the rate of late reoperation. Whether this approach has to be preferred in younger patient has to be demonstrated in further studies.

Extracorporeal membrane oxygenation with direct axillary artery perfusion.

Extracorporeal membrane oxygenation can be done through several cannulation sites. Axillary artery cannulation is commonly performed through a Dacron graft sutured in an end‐to‐side fashion to the axillary artery. Direct cannulation of the axillary artery appears a reliable technique with low rate of complications. We report our experience in 16 patients using the direct cannulation technique. doi: 10.1111/jocs.12229 (J Card Surg 2014;29:268–269)