Surgical approaches to apical thoracic malignancies

ObjectiveSeveral surgical approaches have been described to access apical thoracic malignancies extending into the thoracic inlet. However, most publications have focused on a specific approach and considered the thoracic inlet as 1 entity. In the present analysis, we divided the thoracic inlet into 5 different zones requiring specific surgical considerations to identify the best approach for each zone.MethodsA review of 22 consecutive patients undergoing surgery for apical thoracic malignancies extending into the thoracic inlet from January 2005 to November 2011 was performed.ResultsDifferent surgical approaches were used for each zone. The first (anterolateral) zone required a subclavicular approach to open the costoclavicular space and expose the subclavian vein with or without elevating or removing the clavicle (n = 4). The second (anterocentral) zone required a transverse supraclavicular approach with or without extension to a partial (trapdoor) or full sternotomy (n = 10). The third (posterosuperior) zone located between the top of the subclavian artery and the T1 vertebra along the posterior superior border of the first rib was the most difficult area to access (n = 5). The transclavicular approach was ideally suited to expose this zone in our experience. The fourth (posteroinferior) zone and fifth (inferolateral) zone located posteriorly and laterally along the inferior border of the first rib were accessed using a posterolateral and posterotransaxillary approach, respectively (n = 3).ConclusionsThe thoracic inlet could be divided into 5 zones requiring specific surgical considerations and different approaches. Division of the thoracic inlet into these zones could provide more clarity and guidance for thoracic surgeons to select the correct surgical approach

Time trend in the surgical management of patients with lung carcinoma

Objective: The goal of the study was to analyze the histological and clinical trends in lung carcinoma and their influence upon the preoperative evaluation, surgical procedures and survival. Methods: We retrospectively reviewed the charts of 1079 consecutive patients who underwent surgery for primary lung carcinoma between 1977 and 1996 in our institution. Patients were divided into five equal 4-year periods according to the year of surgery (1977-1980; 1981-1984; 1985-1988; 1989-1992; 1993-1996). Results: Between 1977-1980 and 1993-1996, the incidence of squamous cell carcinoma significantly declined, whereas the incidence of adenocarcinoma and bronchioloalveolar carcinoma increased. During the same period, the proportion of squamous cell carcinoma visualized at bronchoscopy and the rate of preoperative histological diagnosis significantly decreased. An increasing proportion of lobectomy and less extended resection was associated with an increasing number of patients with stage I carcinoma. Meanwhile, the operative mortality significantly declined from 9 to 4% and the 5-year survival improved from 25 up to 40%. Conclusion: Over the last two decades, the shift in histological distribution was associated with an increasing proportion of patients with stage I disease, a lower operative mortality and a better 5-year surviva

Spontaneous hemorrhage of thymus and thymoma in adults

Spontaneous hemorrhage from the thymus is extremely rare. In adults, it may occur in patients without underlying coagulopathy and mimic aortic dissection. To the best of our knowledge, only three previous adult cases have been reported in the English literature. This report presents two additional adult patients who were admitted in our institution with different clinical presentations of spontaneous thymic hemorrhag

Pulmonary blastoma: report of five cases and identification of clinical features suggestive of the disease

Objective: Identification of clinical features suggestive of pulmonary blastoma (PB) through a retrospective comparison with cases of non-small cell lung cancer (NSCLC) operated during the same period. Methods: Between 1977 and 1999, five patients were operated for PB at Geneva University Hospital (four women and one man, aged 32-46 years - mean 36.8) versus 1913 consecutive patients (1558 men and 355 women, mean age 61.2) for primary NSCLC. In the PB subgroup (0.3%), the pulmonary tumor was single, located in an upper lobe in all but one instance, and measured between 5 and 13 cm (mean 9.6), whereas in the total NSCLC group, 27% of patients had tumors <3 cm (T1), evenly distributed in both lungs. All but one PB patients were symptomatic, compared to 45% in the NSCLC group. Results: The five patients with PB underwent curative pulmonary excisions (lobectomy in three and pneumonectomy in two) with mediastinal lymph node sampling. Pathological examination revealed extensive tumor necrosis in four, and N2 lymph node metastases in four (in the total NSCLC group, N2 disease was diagnosed in 21%). Postoperatively, three PB patients received radio- and/or chemotherapy. Four patients died between six and 30 months after the operation (mean 15), whereas 5-year survival in the NSCLC group was 32%, with a median survival of 3.7 years; the fifth patient is alive 28 months later, without any sign of recurrence. Conclusions: Compared to operated NSCLC, PB are rare, large, and symptomatic tumors; they affect younger patients and carry a worse prognosi

Stem cell factor-based identification and functional properties of in vitro-selected subpopulations of malignant mesothelioma cells

Malignant mesothelioma (MM) is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs) are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. Overexpression of NF2 (neurofibromatosis 2, merlin), a tumor suppressor often mutated or lost in MM, did not affect proliferation and viability of CSC-enriched MM populations but robustly decreased the viability of reporter-negative cells. In contrast, downregulation of calretinin strongly decreased proliferation and viability of both populations. In summary, we have enriched and characterized a small MM cell subpopulation that bears the expected CSC characteristics

Long-term results after carinal resection for carcinoma: Does the benefit warrant the risk?

ObjectiveWe sought to determine whether the benefit warrants the risk in patients undergoing carinal resection for carcinoma.MethodsThis was a retrospective single-center study.ResultsBetween June 1981 and August 2004, 119 patients underwent carinal resection for carcinoma in our institution. Carinal pneumonectomy was performed in 103 cases (96 right and 7 left pneumonectomies), carinal resection plus right upper lobectomy in 3, carinal resection after left pneumonectomy in 2, and carinal resection without pulmonary resection in 11. Superior vena caval resection was combined with carinal pneumonectomy in 25 patients with bronchogenic carcinoma (13 patients had complete superior vena caval resection with graft interposition). Nine (7.6%) patients died in the hospital or within 30 days of the operation. Follow-up was complete for 117 (98%) patients up to August 2004 or to the date of death. The 5- and 10-year survivals were 44% and 25%, respectively, for patients with bronchogenic carcinoma (n = 100). However, survival was significantly better in patients with N0 or N1 disease (n = 73) than in those with N2 or N3 disease (n = 27; 53% vs 15% at 5 years, respectively). The 5- and 10-year survivals in the remaining 19 patients reached 66% and 48%, respectively, and were best in patients with neuroendocrine carcinoma (100% survival at 10 years) and adenoid cystic carcinoma (69% survival at 10 years).ConclusionsSurgical intervention for carcinoma involving the carina is feasible, with acceptable mortality and good long-term survival in selected patients. The presence of positive N2 disease should, however, be considered a potential contraindication to carinal resection in patients with bronchogenic carcinoma because of the poor long-term survival

Stem Cell Factor-Based Identification and Functional Properties of In Vitro-Selected Subpopulations of Malignant Mesothelioma Cells

Malignant mesothelioma (MM) is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs) are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. Overexpression of NF2 (neurofibromatosis 2, merlin), a tumor suppressor often mutated or lost in MM, did not affect proliferation and viability of CSC-enriched MM populations but robustly decreased the viability of reporter-negative cells. In contrast, downregulation of calretinin strongly decreased proliferation and viability of both populations. In summary, we have enriched and characterized a small MM cell subpopulation that bears the expected CSC characteristics

Risk factors for reperfusion injury after lung transplantation

Objective: To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. Design and setting: Retrospective study in the surgical intensive care unit (ICU) of auniversity hospital. Methods: We collected data on 60 lung transplantation donor/recipient pairs from June1993 to May2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. Results: The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48 h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p = 0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48 h after surgery (p = 0.014). The extubation was delayed (p = 0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p < 0.01). Conclusions: Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigate

190: In how many patients with Wolff-Parkinson-White syndrome-related adverse presentation isoproterenol infusion was required to reproduce the arrhythmia?

Electrophysiological study is the main method for the detection of patients with a Wolff-Parkinson-White syndrome (WPW) at risk of adverse presentation (resuscitated ventricular fibrillation (VF), documented life-threatening arrhythmia): the protocol is debated. The purpose of the study was to look in how many patients with WPW-related adverse presentation, atrial fibrillation (AF) or atrial tachycardia with the shortest RR cycle length (CL) with 1/1 conduction over accessory pathway (AP)<250msec was induced in control state (CS) and when isoproterenol was required.Methods63 patients, mean age 38±18, were referred for WPW-related adverse presentation (VF 6, other 56). EPS included in CS atrial pacing and measurement of the shortest CL with 1/1 conduction over AP and programmed stimulation with 1 and 2 extrastimuli. AP effective refractory period (ERP) was determined. In absence of induction of a tachycardia with a CL <250msec, isoproterenol (0.02 to 1μg. min-1) was infused to increase sinus rate to 130bpm; the protocol was repeated.ResultsMean shortest CL conducted over AP was 223±30msec in CS, 192±25msec after isoproterenol. APERP was 225±29msec in CS, 191±19msec after isoproterenol. Atrioventricular orthodromic tachycardia (AVRT) was induced in 34 patients (54%), antidromic tachycardia (ATD) in 13 (21%), AF in 43 (68%). Criteria for a malignant form (induction of AF or ATD with a shortest CL <250mesc) were noted in 42 patients (67%) in CS and were obtained after isoproterenol in remaining 21 patients (33%). Among these patients, 12 had inducible tachycardia in CS (AVRT (n=6), ATD (n=3), AF (n=3) but the shortest CL was >240msec. A tachycardia was only induced after isoproterenol in 9 patients (14%).ConclusionsInfusion of isoproterenol should be systematic when WPW is evaluated. EPS performed only in CS missed at least 14% of patients at risk of life-threatening arrhythmias who had no inducible supraventricular tachyarrhythmia and 33% of patients with a WPW without the classical criteria for a malignant form. Isoproterenol increased the sensitivity of EPS for the detection of malignant form from 67 to 100%

Prognostic Value of EMT Gene Signature in Malignant Mesothelioma

Malignant mesothelioma (MESO) consists of epithelioid, biphasic, and sarcomatoid subtypes with different epithelial–mesenchymal transition (EMT) phenotypes. We previously identified a panel of four MESO EMT genes correlating with an immunosuppressive tumor microenvironment and poor survival. In this study, we investigated the correlation between these MESO EMT genes, the immune profile, and the genomic and epigenomic alterations to identify potential therapeutic targets to prevent or reverse the EMT process. Using multiomic analysis, we observed that the MESO EMT genes were positively correlated with hypermethylation of epigenetic genes and loss of CDKN2A/B expression. MESO EMT genes such as COL5A2, ITGAV, SERPINH1, CALD1, SPARC, and ACTA2 were associated with upregulation of TGF-β signaling, hedgehog signaling, and IL-2-STAT5 signaling and downregulation of the IFN-α and IFN-γ response. Immune checkpoints such as CTLA4, CD274 (PD-L1), PDCD1LG2 (PD-L2), PDCD1 (PD-1), and TIGIT were upregulated, while LAG3, LGALS9, and VTCN1 were downregulated with the expression of MESO EMT genes. CD160, KIR2DL1, and KIR2DL3 were also broadly downregulated with the expression of MESO EMT genes. In conclusion, we observed that the expression of a panel of MESO EMT genes was associated with hypermethylation of epigenetic genes and loss of expression of CDKN2A and CDKN2B. Expression of MESO EMT genes was associated with downregulation of the type I and type II IFN response, loss of cytotoxicity and NK cell activity, and upregulation of specific immune checkpoints, as well as upregulation of the TGF-β1/TGFBR1 pathway