Alper Toker

Standard terms, definitions, and policies for minimally invasive resection of thymoma.

Having a common language including well-defined terms and adherence to certain policies and procedures in the management of patients with thymic malignancies is necessary to facilitate progress. This is especially true for minimally invasive resections. Different technical approaches have been used,1,2 and a careful examination of results is needed to understand the impact of the minimally invasive approach itself, as opposed to other factors. For example, during an open approach, most surgeons perform a complete en bloc resection of the tumor and a complete thymectomy with removal of the upper cervical poles and the surrounding mediastinal fat3; whether this is done during minimally invasive resections is hard to decipher at present. This article identifies key aspects that should be reported, common definitions that should be adopted and proposes certain standard policies that should be adhered to when performing a minimally invasive resection of a thymic malignancy. These definitions and policies do not apply to biopsies. These policies are not meant to stifle innovation; on the contrary, they should facilitate progress by providing a framework, so that experiences and outcomes can be compared and analyzed more clearly. These standards have been adopted by members of the International Thymic Malignancy Interest Group (ITMIG), which is a worldwide collaborative organization of individuals interested in mediastinal tumors. METHODS An initial work group of surgeons experienced in minimally invasive thymic resections was assembled to review definitions, terms, and procedures in the existing literature for minimally invasive thymoma resections (Alper Toker, Joshua Sonett, Marcin Zielinski, Federico Rea, Victor Tomulescu, and Frank C. Detterbeck). This work group formulated preliminary recommendations, which were refined by an extended work group (Harmik Soukiasian, Jens Ruckert, Mahmoud Ismail, Jeffrey Port, and Paul Van Schil). These were then debated among a large diverse group of specialists at an ITMIG workshop, which was supported by the International Association for the Study of Lung Cancer. After further comments by the entire ITMIG membership, the definitions and policies presented in this article were approved and adopted as a standard to follow in reporting data and discussing outcomes by the members of ITMIG.

Thymic Carcinoma: A Cohort Study of Patients from the European Society of Thoracic Surgeons Database

Introduction: Thymic carcinoma is a rare and aggressive thymic neoplasm. The European Society of Thoracic Surgeons developed a retrospective database collecting patients undergoing resection for thymic tumors from 1990 to 2010. Methods: Of 2265 patients with thymic tumors, there were 229 thymic carcinomas. Clinicopathological characteristics were analyzed including age, associated paraneoplastic diseases, stage (Masaoka-Koga), World Health Organization histologic subtypes, type of resection (total/subtotal/biopsy/no resection), tumor size, pre/postoperative treatments, and recurrence. Outcome measures included overall survival (OS), freedom from recurrence, and cumulative incidence of recurrence. Results: A complete resection was achieved in 140 patients (69%). Recurrence occurred in 54 patients (28%). Five- and 10-year OS rates were 0.61 and 0.37. Five- and 10-year freedom from recurrence rates were 0.60 and 0.43. Cumulative incidence of recurrence was 0.21 (3 yr), 0.27 (5 yr), and 0.32 (10 yr). Survival was better after surgical resection versus biopsy/no resection (p < 0.001), after complete resection versus subtotal resection (p < 0.001), and when using Masaoka-Koga system (stages I–II versus III versus IV) (p < 0.001). The use of multidisciplinary treatments resulted in a survival advantage which was significant in the surgery + radiotherapy group (p = 0.02). Incomplete resection (p < 0.0001) and advanced stage (Masaoka-Koga III–IV) (p = 0.02) had a negative impact on OS at multivariable analysis. Administration of adjuvant radiotherapy was beneficial in increasing OS (p = 0.02). Conclusions: The results of our study indicate that patients with thymic carcinoma should undertake surgical resection whenever possible; a complete resection and early Masaoka-Koga stage are independent predictors of improved survival; our results also suggest that postoperative radiotherapy is beneficial in improving survival.

The additional value of FDG PET imaging for distinguishing N0 or N1 from N2 stage in preoperative staging of non-small cell lung cancer in region where the prevalence of inflammatory lung disease is high.

Purpose: The aim of this study was to evaluate the efficacy of PET imaging and compare it with the performance of CT in mediastinal and hilar lymph node staging in potentially operable non-small cell lung cancer (NSCLC). Methods: Fifty-nine patients with potentially resectable NSCLC who underwent preoperative PET and CT imaging were enrolled into this prospective study. All patients underwent surgical evaluation by means of mediastinoscopy with mediastinal lymph node sampling (14 patients) or thoracotomy (45 patients). Results: The prevalence of lymph node metastases was 53%. Overall, the sensitivity, specificity, accuracy, PPV, and NPV of PET were 79%, 76%, 78%, 86%, and 76% for N0 and N1 lymph nodes and 76%, 79%, 80%, 67%, and 83% for N2 lymph nodes, while those values for CT were 66%, 43%, 58%, 68%, and 43% for N0 and N1 stations and 43%, 66%, 54%, 41%, and 66% for N2 lymph nodes, respectively. PET correctly differentiated cases with mediastinal lymph node involvement (N2) from those without such involvement (N0 or N1) in 76% of cases. Statistical analysis of the diagnostic accuracy of nodal involvement showed that PET improves diagnostic accuracy significantly in the detection of both N0 or N1 and N2 status in the individual patient based on analysis, compared with CT (P < 0.01 and P < 0.01, respectively). When preoperative nodal staging was compared with postoperative histopathological staging, 38 (65%) patients were correctly staged, 9 (15%) were overstaged, and 12 (20%) were understaged by PET, while 29 patients (49%) were correctly staged, 13 (22%) were overstaged, and 17 (29%) were understaged by CT. Conclusion: It has been clearly shown that PET is more accurate than CT for the differentiation of N0 or N1 from N2 disease in patients with NSCLC. However, PET imaging alone does not appear to be sufficient to replace mediastinoscopy for mediastinal staging in patients with lung cancer, especially in geographic regions with high granulomatous or inflammatory mediastinal disease prevalence.

A complication of pectus excavatum operation: endomyocardial steel strut.

An 18-year-old patient who had correction of pectus excavatum deformity in our department 4 years earlier was admitted because of stabbing chest pain. He had not attended to postoperative controls and had not come for extraction of the steel strut, although he had been contacted. He was diagnosed to have a broken steel strut, and the strut was noted to be embedded in the myocardium. This unreported complication of pectus excavatum operation forced us to review sternal support techniques.

Effects of thoracic epidural anaesthesia on pulmonary venous admixture and oxygenation during one-lung ventilation

Background:  In this clinical randomized study, the effects of four anaesthesia techniques during one‐lung ventilation [total intravenous anesthesia (TIVA) with or without thoracic epidural anaesthesia (TEA) (G‐TIVA‐TEA and G‐TIVA), isoflurane anaesthesia with or without TEA (G‐ISO‐TEA and G‐ISO)] on pulmonary venous admixture (Qs/Qt) and oxygenation (OLV) were investigated.

Rocuronium and sugammadex in patients with myasthenia gravis undergoing thymectomy

The use of neuromuscular blocking agents is still controversial in myasthenic patients but rocuronium could be useful after the introduction of sugammadex as a selective antagonist. The aim of the study was to evaluate the use of rocuronium‐sugammadex in myasthenic patients undergoing thoracoscopic thymectomy.

WWOX gene may contribute to progression of non-small-cell lung cancer (NSCLC)

Lung cancer is the most common cause of cancer-related death worldwide and, like many other cancers, is affected by different genetic, epigenetic, and environmental factors. The WW domain-containing oxidoreductase (WWOX) gene is a tumor-suppressor gene located on chromosome 16q23.3–24.1, and it has been shown that it loses its function due to alterations in genetic and epigenetic mechanisms. The aim of this study is to investigate the relationship between lung cancer and WWOX gene. Tumor tissue samples, corresponding normal tissues, and blood samples obtained from 50 lung cancer patients were involved in the study. We analyzed methylation profile by methylation-specific PCR and mutations and polymorphisms by DNA sequencing. Methylation analysis showed that promoter hypermethylation was present in 38 of 50 (76%) patients. In addition, promoter region of WWOX gene of younger patients was more frequently methylated than older patients. Using DNA sequencing, we found four genetic alterations in WWOX gene. Two of them were germline mutations (Exon 4 and 7), and two of them were polymorphic (Exon 6 and 8). We found a new mutation in exon 7 (Arg-254→Cys) which has not been described previously. The changes in the short-chain dehydrogenase domain of the protein caused by the genetic alterations may affect the function of the gene. We conclude that hypermethylation of WWOX gene promoter region and mutations in the gene might be related to lung carcinogenesis.

Oxygen uptake kinetics during cardiopulmonary exercise testing and postoperative complications in patients with lung cancer.

It is accepted that cardiopulmonary exercise testing is one of the most valuable parameters, especially peak oxygen uptake (VO(2)), for the evaluation of risk assessment in lung cancer surgery. It therefore represents an attractive way of identifying a patient at high risk for postoperative complications. However, many patients do not achieve the maximal or predictive level during an incremental exercise testing. The purpose of the current investigation was to study the value of the oxygen uptake efficiency slope (OUES), which shows exercise capacity during submaximal testing, in predicting postoperative mortality in patients with bronchogenic carcinoma scheduled for lung resection. Forty-nine patients with bronchogenic carcinoma participated in studies with exercise tests as a preoperative evaluation. The peak VO(2) was calculated for each subject by averaging values obtained during the final 10s of exercise. The following equation was used to determine OUES: VO(2)/log(10)VE. Peak VO(2) without postoperative complication was 22.8+/-3.3 ml/(kg min), however, peak VO(2) in patients with present complications was 19.1+/-4.2 ml/(kg min) (p=0.001). In addition, although the mean OUES in patients with present complications was 11.1+/-1.2, the mean OUES in the absent group was 13.3+/-2.1 (p<0.001). Although peak VO(2) is useful in evaluating selected patients with bronchogenic carcinoma, OUES is also a beneficial parameter and should be calculated and recorded with peak VO(2), a better predictor of poor surgical outcome than absolute values, and should be integrated into preoperative decision making.

Clinical significance of P16INK4A and retinoblastoma proteins in non-small-cell lung carcinoma

This study was performed to determine the frequency of expression loss of p16 and pRb; their relations with each other, tumour histology, tumour stage, nodal status, and survival in formalin fixed, paraffin embedded tumour tissues of patients with non-small-cell lung carcinoma (NSCLC). P16 and/or pRb expression loss is observed in 72 (75.8%) out of 95 patients, and 70 (73.7%) of them showed inverse correlation (P<0.05). Thirty-six (37.9%) of the p16 positive cases usually showed weak or moderate immunohistochemical staining. Loss of p16 expression was found to be significantly greater in squamous cell carcinoma than in adenocarcinoma cases, whilst no relation was observed with other clinical parameters. Immunohistochemical reactivity for pRb was generally moderate or strong. PRb expression loss was observed in 15.8% of the cases, and no relation was found between pRb loss and age, sex, tumour histology, tumour stage, or nodal status. PRb negative squamous cell carcinoma cases had significantly shorter survival independent of nodal status. These results suggest that disruption of p16/pRb pathway is frequently involved in NSCLC, and pRb expression loss in cases with squamous cell carcinoma may predict clinical outcome.

Invasive mediastinal staging is irrelevant for PET/CT positive N2 lung cancer if the primary tumour and ipsilateral lymph nodes are resectable.

e.lim@rbht.nhs.uk Academic Division of Thoracic Surgery, The Royal Brompton Hospital, London, SW3 6NP, UK (EL); Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle University, Newcastle upon Tyne, UK (PJM); Division of Thoracic Surgical Oncology, Istituto Nazionale Tumori, Fondazione Pascale, IRCCS, Naples, Italy (GR); St James’s University Hospital, Leeds, UK (AB); Service de Chirurgie Thoracique, Hopitaux Universitaires de Strasbourg, Strasbourg, France (GM); Istanbul University, Istanbul Medical School Department of Thoracic Surgery, Istanbul, Turkey (AT); University Medical Center Freiburg, Department of Thoracic Surgery, Freiburg, Germany (BP); School of Medicine and University Hospital, Salamanca University, Salamanca, Spain (GV); Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland (WW)