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We present a simplified model of lung xenotransplantation from hamster to rat with a total non-suture technique using 14G cuffs for the main pulmonary artery, the trachea and the left atrium. This technique provides a technically easier and more reliable model to study xenotransplantation of the lung.

We report on a case of successful bilateral sequential lung transplantation using a donor with the right upper lobe bronchus arising from the trachea. After en-bloc donor lung retrieval, the right bronchial stump was fashioned to create one lumen including the bronchus intermedius and the aberrant right upper lobe bronchus. A carinoplasty was performed in the recipient with resection of a portion of the lateral wall of trachea. The anastomosis was completed using a telescoping technique without any complication. This case demonstrates the possibility of successfully using donor lungs with such anatomic abnormality for transplantation.

Background: Thymectomy has become an accepted option in the treatment of myasthenia gravis (MG). However, the optimal selection of patients for surgery remains controversial. Objective: The objective of the study is to define factors influencing improvement and remission rates after thymectomy for MG. Methods: We retrospectively reviewed our experience in the surgical management of patients with MG over the last 20 years, and analyzed if patient’s age, sex, preoperative Osserman Stage, thymic histology, duration of symptoms, or radiological findings influenced outcome. Results: There were 25 women and 10 men. Most of them presented with Osserman stage IIA (n = 12) and stage IIB (n = 17). Hyperplasia of the thymus was observed in 15 patients (43%), thymoma in 12 (34%), and atrophic or normal thymus in 8 (23%). Computed tomography (CT) had a positive predictive value of 91% in detecting thymoma and of 80% in detecting thymic hyperplasia. Over a mean follow-up of 96 months, MG improved markedly in 26 patients. Postoperative improvement was significantly greater in patients with advanced MG (stage IIB, III and IV), whereas a higher rate of remission occurred in patients with mild MG (stage I and IIA), and in those with thymic hyperplasia. No relation was observed between outcome and age, sex, duration of symptoms and abnormal CT findings. Conclusions: The beneficial effects of thymectomy are characterized by postoperative clinical improvement in most patients with moderate to severe preoperative myasthenic involvement and by a higher remission rate in patients with thymic hyperplasia and/or mild myasthenic symptoms.

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 prognosis. q 2002 Elsevier Science B.V. All rights reserved.

Objective: Although mechanical ventilation can potentially worsen preexisting lung injury, its importance in the setting of lung transplantation has not been explored. This study was undertaken to examine the effect of 2 ventilatory strategies on the development of ischemia-reperfusion injury after lung transplantation. Methods: In a rat lung transplant model animals were randomized into 2 groups defined by the ventilatory strategy during the early reperfusion period. In conventional mechanical ventilation the transplanted lung was ventilated with a tidal volume equal to 50% of the inspiratory capacity of the left lung and a low positive end-expiratory pressure. In minimal mechanical stress ventilation the transplanted lung was ventilated with a tidal volume equal to 20% of the inspiratory capacity of the left lung, and positive end-expiratory pressure was adjusted according to the shape of the pressure-time curve to minimize pulmonary stress. Results: After 3 hours of reperfusion, oxygenation from the transplanted lung was significantly higher with minimal mechanical stress ventilation than with conventional ventilation. In addition, elastance, cytokine levels, and morphologic signs of injury were significantly lower in the group with minimal mechanical stress ventilation. Conclusions: This study demonstrates that the mode of mechanical ventilation used in the early phase of reperfusion of the transplanted lung can influence ischemia-reperfusion injury, and a protective ventilatory strategy on the basis of minimizing pulmonary mechanical stress can lead to improved lung function after lung transplantation. J Thorac Cardiovasc Surg 2002;124:1137-44

10597 Background: Isolated lung perfusion (ILP) can enhance the treatment of lung metastases, allowing the localized delivery of drugs to the lungs, without systemic exposure. Previously, short-ter...

During lung transplantation, the venous anastomosis is performed between the atrial cuffs of the donor and the receiver. In certain rare circumstances, however, the surgeon may find two veins and no possibility to reposition the clamp more proximally. A simple technique can be used in this case: both veins are reunited and the venous anastomosis carried out as usual between two large lumens.

To present the long-term outcome after surgery for breast carcinoma in men.Retrospective study.University Hospital, Switzerland.37 consecutive men who were operated on for breast carcinoma between 1968 and 1998.The mean age was 67 years (range 41-89). The delay between the first clinical presentation and operation ranged from 1 month to 3 years (median 3.5 months). Operations included modified radical mastectomy (n = 19), radical mastectomy (n = 12), simple mastectomy (n = 3), Halsted procedure (n = 1), and conservative resection (n = 1). One patient had only a biopsy and was excluded from survival analysis. There were 30 infiltrating ductal carcinomas, 4 in situ ductal carcinomas, 2 papillary carcinomas, and 1 adenoid cystic carcinoma. Most tumors (n = 25, 68%) were in the subareolar region. The overall survival at 10 years was 44%, but it was significantly influenced by the stage of disease, ranging from 57% in stage I (n = 12), to 26% in stage II (n = 15), and 0 in stage III (n = 8).Although the long term survival in stage I and II is similar in men and women, the rarity of breast carcinoma in men and its location in the subareolar region may delay diagnosis and treatment.

Appendectomy is the most common nonobstetric operation during pregnancy, but laparoscopy has not been considered to be the preferred procedure until recently. The objective of this study was to report the authors' experience with laparoscopic appendectomy during pregnancy and to review the available literature. Six patients underwent laparoscopic appendectomy during pregnancy, and 24 additional cases from the literature were reviewed. Two patients underwent surgery during the first trimester of pregnancy, three patients underwent surgery during the second trimester, and one patient underwent surgery during the third trimester. The Hasson open technique was used in five cases, and the Veress needle was used in one case. Port site locations were adapted to the size of the gravid uterus. Three patients had histologically confirmed appendicitis and underwent delivery of a neonate after 36 weeks (n = 1) and 37 weeks (n = 2) of gestation. Two patients had uterine infections and underwent abortions 2 days after surgery and 6 weeks after surgery, respectively. One patient had an isolated torsion of the right fallopian tube that was diagnosed using laparoscopy. These results show that laparoscopic appendectomy can be safely performed during pregnancy. One limitation may be the size of the gravid uterus, which interferes with adequate visualization and instrumentation in the third trimester of pregnancy.

To describe the evolution of the perioperative management of myasthenia gravis (MG) patients undergoing thymectomy and to question the need for systematic postoperative ventilation. We collected data retrospectively from 36 consecutive MG patients who underwent thymectomy over a 21-yr period, via transthoracic, -cervical or -sternal incisions (n = 5,n=7,n=24, respectively). From 1980 to 1993, a balanced anesthetic technique (n=24) included various inhalational agents with opiates and myorelaxants (in eight cases); 22 patients were admitted to the intensive care unit (ICU). Since 1994,iv propofol was combined with epidural bupivacaine and sufentanil (n= 12); all patients were admitted to the postanesthesia care unit. Short-term postoperative ventilation (median time four hours, range from three to 48 hr) was required in eight patients who had longer hospital stay (median stay= 12 days, range (8–28)vs five days (4–15) for patients with early extubation, P < 0.05) but similar clinical improvement six months after thymectomy. Postoperative ventilatory support was required more frequently when a balanced anesthetic technique was used (odds ratio=4.2 (1.1–9.7),P=0.03) and particularly when myorelaxants were given (odds ratio= 13.9 (2.1–89.8),P=0.009). Leventhal’s scoring system had low sensitivity (22.2%) and positive predictive values (25%). Our data show that the severity of MG failed to predict the need for postoperative ventilation. A combined anesthetic technique was a safe and cost-effective alternative to balanced anesthesia as it provided optimal operating conditions and resulted in fewer admissions in ICU and shorter hospital stays.

40 Background: Cigarette smoking, alcohol consumption and co-morbidities are important determinants of health in lung cancer patients. The gold standard for obtaining accurate data is PRQ. The purpose of this study is to ascertain the accuracy of abstracting health-related behaviour data from retrospective chart review compared to data directly obtained from PRQ in a lung cancer patient population. Methods: 731 lung cancer patients completed a PRQ related to lifetime tobacco use, alcohol consumption and co-morbidity. Relevant smoking, alcohol and co-morbidity data was collected independently from EPR. Results: Ever/never status for smoking showed almost perfect agreement (k=0.95) between PRQ and EPR and surpassed all other health behavioural measures and co-morbidity agreement values. Both the sensitivity and specificity were high (0.94 and 0.99 respectively). The calculation of pack-years from EPR and PRQ showed substantial agreement (k=0.77); However, categorizing the smoking status into current/ former / never, resulted in moderate agreement (k=0.46). Alcohol ever/ never status agreement was moderate (0.43) with high sensitivity (0.90) but low specificity (0.50). Agreement for co-morbidities varied by condition showing moderate to substantial agreement for hypertension (K=0.57), heart attack (K=0.80) and diabetes (K=0.76) while fair to slight agreement (K

We describe a patient who accidentally received an infusion of cyclosporin at a rate of 30 mg/hr during 13 hr instead of the prescribed dose of 3 mg/hr and who concomitantly developed massive intracerebral edema with brainstem compression and death. A cyclosporin level as high as 1700 ng/ml could have been reached before the drug was withdrawn. To the best of our knowledge, this is the first case of fatal cyclosporin overdose reported in an adult patient.

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 hemorrhage.

Bronchopleural fistula after pneumonectomy is a dreaded complication, because of its high morbidity and mortality. We describe a successful technique using closed-chest irrigation of the pleural cavity continued with transposition of a latissimus dorsi island flap.

Separation of the lungs with a double-lumen endobronchial tube facilitates the surgical approach and protects the bronchial system from contamination by pus or blood from the operated lung. We report a case of a 49-year-old man who suffered a gram-negative pneumonia requiring mechanical ventilatory support and prolonged hospitalization after pulmonary resection. Contamination of the ventilated-dependent lung was documented intraoperatively. Current information on postoperative infectious complications and preventive measures are discussed.

Background . Solitary fibrous tumors of the pleura are rare and present unpredictable clinical behavior. Methods . Between 1981 and 1998, 11 solitary fibrous tumors of the pleura were resected in 10 patients at the University Hospital of Geneva. Their clinical behavior and outcome were reviewed. Results . Seven tumors arose from the visceral pleura, and three arose from the parietal pleura. Tumors arising from the parietal pleura were revealed to be more difficult to resect than those from the visceral pleura because of their size and adhesion to the chest wall requiring extrapleural resection. Eight tumors showed benign features, whereas two showed distinct features of malignity. One additional patient presented marked pleomorphism that could represent an intermediate form before frank malignity. Four tumors had been followed expectandly for 2 to 10 years before surgery. Although three enlarged rapidly, no signs of malignity were observed on histological examination. All patients are alive, from 2 months to 14 years after surgery (mean 55 months). In one case, however, a malignant tumor recurred 6 years after resection of a benign variant. Conclusions . Although histologically benign, solitary fibrous tumors of the pleura may enlarge rapidly and occasionally transform into malignant variants after several years. Therefore, complete surgical resection and long-term follow-up is recommended for all patients.

There is some evidence that complete resection of both primary and metastatic sites of non-small cell lung carcinoma has more influence on survival than the locoregional stage of the lung cancer. We describe prolonged survival (> 5 years) after complete surgical resection of a bronchogenic carcinoma (T3N0M1) and solitary adrenal metastasis.

Bilateral lung volume reduction produces significant clinical and physiologic improvement in selected patients with end-stage emphysema. Current surgical approaches consist of median sternotomy and video-assisted thoracoscopy. This report describes an alternate technique of single-stage, bilateral lung volume reduction using muscle-sparing anterior thoracotomy in 18 patients with severe lung emphysema.

7516 Background: Erlotinib has demonstrated major activity in EGFR mutation positive NSCLC, but may also benefit those with wild-type tumours. We conducted a single-arm trial of pre-operative erlotinib in early stage NSCLC to assess radiologic and functional response as well as correlation with known and investigational biomarkers. Methods: Patients with clinical stage IA-IIB NSCLC received erlotinib 150 mg daily for 4 weeks followed by surgical resection. Tumor response was assessed using pre- and post-treatment CT and PET imaging. Pharmacodynamic changes were assessed through comparison of pre- and post-treatment tumour samples (including Sequenom MassARRAY analysis) and measurement of circulating markers/ligands for EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR SNP, EGFR ECD). Secondary endpoints included pathological response, toxicity and progression-free survival. Results: Twenty-five patients were enrolled; 22 received erlotinib treatment with a median follow up of 4.4 years (range 2.2 to 6.4 years). Histology was predominantly adenocarcinoma (14) with smaller numbers of squamous carcinoma (7) and large cell carcinoma (1). PET response (25% SUV reduction) was observed in 2 patients (9%), both with confirmed squamous carcinoma histology. All patients met criteria for stable disease by RECIST and several experienced minor radiographic regression with histologic findings of fibrosis/necrosis, including 2 with squamous histology. The presence of an EGFR exon 19 deletion was detected in one adenocarcinoma case; the patient experienced a minor radiographic response to treatment. Genotyping, functional protein assays and ligand analysis are ongoing. Conclusions: Erlotinib appears to demonstrate some activity in patients with squamous histology. While EGFR mutations have been infrequently demonstrated in squamous NSCLC, the potential exists for other biomarkers predictive of benefit. Clinical trial information: NCT00462995.

e18503 Background: Treatment of locally advanced NSCLC is debated. While survival for inoperable disease ranges between 3-17%, carefully selected patients can be cured when treated surgically in a multimodality concept. Here, we conducted a systematic literature review and pooled data analysis of patients after en bloc resection for pulmonary sulcus NSCLC invading the spine. Outcome and prognostic factors were described. Methods: The MEDLINE database was searched using the PubMed engine to retrieve all relevant articles related to en bloc resection for pulmonary sulcus NSCLC invading the spine. All articles’ corresponding authors were contacted to share their most updated anonymized patient’s data. Data were pooled and analyzed, focusing on outcome and prognostic factors. Results: Search strategy yielded a total of 134 articles. Out of these, only 6 were relevant and non-duplicative. Four out of 6 authors were able to share updated data for a total of 135 patients. All tumors were resected en bloc with the lung, chest wall and spine. Induction treatment was administered in 87 (64%) patients and consisted of chemotherapy (n=32), radiation (n=1) or concurrent chemoradiation (n=54). Spine resections included total (n=23), hemi- (n=94) and partial (n=18) vertebrectomies. Complete resection was achieved in 120 (89%) patients. Five patients died in the postoperative period (4%). Adjuvant treatment was administered in 70 (52%) patients and included chemotherapy (n=16), radiotherapy (n=22) or chemoradiation (n=32). Median follow-up was 26 months. Overall 3-, 5- and 10-year survivals were 57%, 43% and 27%, respectively. Results of the univariate analysis (Cox, Breslow tests) identified incomplete surgical resection (R0 vs R1/2, p

7526 Background: We developed a protocol with accelerated hypofractionated hemithoracic IMRT followed by EPP for MPM. Advantages include optimal delivery of radiation to the whole tumor bed in a short period limiting the risk of viable tumor cell spread during surgery. Methods: Patients with resectable clinical T1-3N0M0 histology proven MPM were eligible for the study. 25 Gy in 5 daily fractions over 1 week was delivered to the entire ipsilateral hemithorax by IMRT with concomitant boost of 5 Gy to volumes at high risk based on CT and PET scan findings. EPP was performed one week after the end of radiation. Adjuvant chemotherapy was offered to patients with ypN2 on final pathology. The primary end-point was treatment related mortality. Secondary endpoint included overall survival and disease-free survival (DFS). Initial sites of recurrence were also recorded. Results: Twenty five patients were accrued between 11/2008 and 10/2012. Patients had a median age of 64 years (range, 45-75), 76% were males, 64% had epithelioid histology. All patients completed IMRT and EPP. IMRT was well tolerated with no grade 3-5 toxicity. EPP was performed 6±2 days after completion of IMRT. Surgical complications occurred in 18 patients. One patient died from empyema at 88 days. All but one patient (stage IB) had stage III (n=11) or IV (n=13) disease on final pathology. Five out of 13 patients with ypN2 disease underwent adjuvant chemotherapy. After a median follow-up of 19 months (range, 3-51), the estimated 3-year survival reached 62%. Survival was significantly better in epithelioid compared to biphasic pathologic subtypes (83% survival at 3 years vs 19%, respectively; p=0.004). 14 patients remain disease free after a median follow-up of 17 months (range, 3-37). 2-year DFS was 85% in stage III and 37% in stage IV disease (p=0.03). Recurrences occurred in the ipsilateral chest only (n=2), ipsilateral chest and distant sites (n=2), and distant sites only (n=6). Conclusions: Accelerated hypofractionated hemithoracic IMRT followed by EPP is feasible. This treatment could improve survival in selected patients with epithelial subtype. Clinical trial information: NCT00797719.

11109 Background: Cytoreductive surgery for malignant pleural mesothelioma (MPM) should be reserved for patients with favorable tumor biology. Osteopontin (OPN) and the ratio of absolute neutrophil to absolute lymphocyte counts (NLR) have been reported as possible prognostic biomarkers. These were studied with other clinical/ laboratory variables in a mixed surgical/non-surgical MPM population to define independent predictors of survival (OS) and progression (TTP). Methods: Forty-four MPM patients (12 F, 32M; 26 cytoreduction, 18 no cytoreduction; 31 epithelial, 13 non-epithelial; 15 Stage I/II, 29 Stage III/IV) were examined with regard to pretreatment plasma OPN (ELISA, R&D, Minneapolis, MN), NLR age, gender, therapy, histology, stage, platelet count and WBC count. Cut points for age, OPN, NLR, platelets, and WBC were determined by X-tile Software (Yale, New Haven, CT) and univariate/multivariate Cox analyses performed. Results: Median OS were 11 m, 21m, and 8m for all 44 MPMs, cytoreduced and non-cytoreduced MPMs, respectively. Of platelet count, WBC, NLR, and OPN, only OPN was statistically significant between Stage I/II and Stage III/IV (80.3 ng/ml vs 148 ng/ml, p

A 24-year-old woman presented with 8-week history of recurrent left pleuritic chest pain, shortness of breath, and hemoptysis. Past medical history was significant for d-transposition of the great arteries, repaired with an arterial switch operation at birth, followed by homograft patch repair of the stenotic pulmonary trunk during childhood. CT pulmonary angiogram showed a large calcified mass in the pulmonary trunk ( Panel A , …

Objective The study objective was to compare endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with mediastinoscopy for mediastinal lymph node staging of potentially resectable non–small cell lung cancer. Methods Patients with confirmed or suspected non–small cell lung cancer who required mediastinoscopy to determine suitability for lung cancer resection were entered into the trial. All patients underwent EBUS-TBNA followed by mediastinoscopy under general anesthesia. If both were negative for N2 or N3 disease, the patient underwent pulmonary resection and mediastinal lymphadenectomy. Results Between July 2006 and August 2010, 190 patients were registered in the study, 159 enrolled, and 153 were eligible for analysis. EBUS-TBNA and mediastinoscopy sampled an average of 3 and 4 lymph node stations per patient, respectively. The mean short axis of the lymph node biopsied by EBUS-TBNA was 6.9 ± 2.9 mm. The prevalence of N2/N3 disease was 35% (53/153). There was excellent agreement between EBUS-TBNA and mediastinoscopy for mediastinal staging in 136 patients (91%; Kappa, 0.8; 95% confidence interval, 0.7–0.9). Specificity and positive predictive value for both techniques were 100%. The sensitivity, negative predictive value, and diagnostic accuracy for mediastinal lymph node staging for EBUS-TBNA and mediastinoscopy were 81%, 91%, 93%, and 79%, 90%, 93%, respectively. No significant differences were found between EBUS-TBNA and mediastinoscopy in determining the true pathologic N stage (McNemar's test, P = .78). There were no complications from EBUS-TBNA. Minor complications from mediastinoscopy were observed in 4 patients (2.6%). Conclusions EBUS-TBNA and mediastinoscopy achieve similar results for the mediastinal staging of lung cancer. As performed in this study, EBUS-TBNA can replace mediastinoscopy in patients with potentially resectable non–small cell lung cancer.

Introduction: NKT cells can provide adjuvant activity against cancer by producing large amounts of IFN-gamma which activate other immune cells, and orchestrate protective anti-tumor immunity. Recently, induction of the NKT cell-dependent anti-tumor immune response using its ligand alpha-galactosylceramide has been attempted in several tumor types. However, the role of NKT cells in the tumor microenvironment has not yet been fully addressed. Our aim is to elucidate the role of NKT cells in the thoracic cavity by using a murine malignant mesothelioma model. Methods: Half a million of AB12 murine malignant mesothelioma cells were injected into the right pleural cavity of female Balb/c mice for tumor development. The control mice were injected with the same amount of PBS. In this model, thoracic cavity was filled with tumors and pleural effusion by day 14. On days 0 (before tumor cell injection), 3, 6, 10 and 14 after tumor cell injection, mice were sacrificed and the pleural effusion and tumors were collected. Lymphocytes were isolated by performing a Ficoll gradient centrifugation. Cell phenotype was identified by cell surface marker staining and cytokine expression was analyzed by intracellular cytokine staining using flow cytometry. Cytokine concentrations in the pleural effusion were measured by ELISA. Resluts: The absolute number of CD3 positive cells in the pleural cavity did not increase between day 0 (4.7±0.9 x105), day 3 (5.5±0.7 x105) and day 6 (7.1x±1.6 x105) but did start to increase from day 10 (1.2±0.2 x106) after tumor cell injection. In the control mice, the absolute number of CD3 positive cells was not different throughout the experiment. Although the absolute number of CD8 positive cells and CD4 positive cells were not different between day 0 (CD8: 1.5±0.2 x105, CD4: 2.8±0.2 x105, respectively), day 3 (CD8: 1.8±0.2 x105, CD4: 2.6±0.2 x105, respectively) and day 6 (CD8: 1.9±0.4 x105, CD4: 4.3±0.2 x105, respectively) after tumor cell injection, the absolute number of NKT cells (CD3 and DX5 double positive cells) increased dramatically at relatively earlier phase from 1.6±0.1 x104 on day 0, to 6.4±0.3 x104 on day 3 and 12.1±1.0 x104 on day 14. Intracellular IFN-gamma staining of NKT and CD8 T cells showed that the ratio of IFN-gamma positive NKT to whole NKT cells started increasing from day 3 (day0: 7.0±1.3%, day3: 31±3%, respectively) and peaked on day 6 (59±11%) whereas the ratio of IFN-gamma positive to whole CD8 T cells started increasing from day 6 (day0: 12.1±3.5%, day6: 36±6.5%) and peaked on day 10 (39±3.4%). Conclusion: These results indicate that the NKT cells are recruited to the pleural cavity at a relatively early phase of tumor formation and could potentially affect the subsequent CD8 T cell response by the production of IFN-gamma. Further experiments are on going to see the role of NKT cells and to test the impact of chemotherapy on these cells in this model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 777. doi:10.1158/1538-7445.AM2011-777

A 39-year-old man with no notable medical history was being examined because of a transient ischemic attack. On a chest radiograph, a mediastinal mass was detected when the patient was in the supine position (Panel A, arrow) but disappeared when he was standing (Panel B). This finding indicates an aneurysm of the superior mediastinal venous system. Computed tomography with the administration of intravenous contrast material confirmed a large aneurysm of the azygos vein (Panels C and D). Because of the risk of complications, such as venous thrombosis, the aneurysm was surgically removed and the azygos vein ligated. The patient had . . .

ObjectiveWe evaluated the outcome, long-term results, and factors affecting outcome of induction chemoradiotherapy followed by surgical resection for T4 non–small cell lung cancer invading the spine.MethodsRetrospective analysis of 23 consecutive patients undergoing radical vertebral resection for non–small cell lung cancer invading the spine between 1996 and 2007 was performed. In most cases, induction chemoradiotherapy consisted of cisplatin and etoposide followed by 45 Gy of radiation. Surgical resection with vertebrectomy was performed en bloc in either a 1-stage or 2-stage operation. Survival was estimated by Kaplan–Meier techniques. The log–rank comparison was used to compare groups.ResultsThere were 13 men and 10 women with a median age of 61 years (range 32–75). Twenty-two patients had induction chemoradiotherapy and 1 had induction chemotherapy alone. Vertebral resections included 6 total vertebrectomies, 15 hemivertebrectomies, and 2 partial vertebrectomies. Complete resection was achieved in 19 (83%) patients. Two (8.7%) patients died postoperatively. Pathologic complete response was observed in 10 (43%) patients. The 3-year survival was 58% (median follow-up, 34 months). Patients who achieved pathologic complete response or near complete response (viable tumor cells < 1%) demonstrated significantly better survival than those who did not (3-year survival, 92% vs 20%; P = .006).ConclusionHighly selected patients with lung cancer invading the spine can potentially be cured with induction chemoradiation therapy followed by radical en bloc resection of the tumor. A multidisciplinary operative strategy allows a significant chance of achieving complete resection in patients requiring multilevel hemivertebrectomy or total vertebrectomy and an appreciable cure rate.

Chronic thromboembolic pulmonary hypertension (CTEPH) is the end result of persistent obstruction of the pulmonary arteries by acute or recurrent pulmonary emboli. In the era of successful surgical therapy, CTEPH, although historically considered a rare entity, is being diagnosed more frequently. In

Summary Background Lung transplantation is a life-saving option for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) and interstitial lung disease (SSc-ILD) patients. However, some programs may be concerned about the possibility of excess post-transplantation mortality related to the extra-pulmonary manifestations of SSc. The objective of this study was to evaluate survival of SSc patients post-lung transplantation. We secondarily evaluated SSc lung transplant recipient characteristics (age, sex, and type of SSc lung disease), and discussed post-lung transplantation survival of SSc patients and non-SSc patients (idiopathic PAH, and ILD). Methods A systematic review of MEDLINE, EMBASE, Cochrane Central Registry of Controlled Trials and CINAHL (all inception to 2012) was performed to identify studies evaluating post-lung transplant survival in SSc compared to PAH and ILD patients. Two reviewers independently abstracted study and survival data. Results Two hundred twenty-six citations were screened to identify 7 observational studies reporting SSc patients who underwent single lung, double lung, or heart-lung transplantation. Mean age at transplantation ranged 46–53 years. SSc post-transplantation survival ranged 69%–91% at 30-days, 69%–85% at 6-months, 59%–93% at 1-year, 49%–80% at 2-years, and 46%–79% at 3-years. Causes of death included graft failure, infection, cardiac events, hemorrhagic stroke, respiratory failure, malignancy, pulmonary hypertension, complications of bronchiolitis obliterans syndrome, anesthetic complication, and scleroderma renal crisis. There were no reports of recurrence of SSc in the lung allograft. Conclusion The short-term and intermediate-term survival post-lung transplantation are similar to IPAH and ILD patients requiring lung transplantation.

Objective We examined the outcome of lung transplantation with the use of donors aged 60 years or more. Methods From May 1994 to May 2005, 467 lung transplants were performed at our institution. A total of 60 recipients received lungs from donors aged 60 years or more (range 60–77 years, median 65 years), whereas 407 recipients received lungs from younger donors (range 9–59, median 39 years). Results A total of 48 patients (10%) died within 30 days of surgery: 10 (17%) in the older donor group versus 38 (9%) in the younger donor group ( P = .08). The operative mortality varied with the underlying lung disease and was higher in recipients presenting with pulmonary hypertension and pulmonary fibrosis than with emphysema or cystic fibrosis. A total of 210 patients died after a median follow-up of 25 months (range 0–136 months). The overall 5- and 10-year survivals were 57% and 38%, respectively. However, the 10-year survival tended to be worse in the older donor group (16% vs 39% in the younger donor group, P = .07). Bronchiolitis obliterans syndrome was the predominant cause of death in recipients of older donors who survived for more than 90 days after surgery (11/17, 65% vs 45/132, 34% in recipients of younger donors surviving for >90 days after surgery, P = .01). Conclusions Given the lack of organ donors, lungs from donors aged 60 years or more should be considered for transplantation. However, the use of donors aged 60 years or more is associated with a lower 10-year survival, and bronchiolitis obliterans syndrome plays a significant role as the cause of late death.

Background Management of solitary adrenal metastasis from non-small cell lung cancer is still debated. Although classically considered incurable, various reports with small numbers of patients have shown that surgical treatment might improve long-term survival. The aim of this study was to review our experience and to identify factors that could affect survival. Methods From January 1989 through April 2003, 23 patients underwent complete resection of an isolated adrenal metastasis after surgical treatment of non-small cell lung cancer. There were 19 men and 4 women, with a mean age of 54 ± 10 years. The diagnosis of adrenal metastasis was synchronous with the diagnosis of non-small cell lung cancer in 6 patients and metachronous in 17 patients. The median disease-free interval for patients with metachronous metastasis was 12.5 months (range, 4.5–60.1 months). Results The overall 5-year survival was 23.3%. Univariate and multivariate analysis demonstrated that a disease-free interval of greater than 6 months was an independent and significant predictor of increased survival in patients after adrenalectomy. All patients with a disease-free interval of less than 6 months died within 2 years of the operation. The 5-year survival was 38% after resection of an isolated adrenal metastasis that occurred more than 6 months after lung resection. Adjuvant therapy and pathologic staging of non-small cell lung cancer did not affect survival. Conclusions Surgical resection of metachronous isolated adrenal metastasis with a disease-free interval of greater than 6 months can provide long-term survival in patients previously undergoing complete resection of the primary non-small cell lung cancer.

Objectives The objective of this study was to examine the long-term patient outcomes of lung transplantation in a single center. Methods Between 1983 and 2003, 521 lung transplants were performed in 501 patients. Major indications were cystic fibrosis (n = 124), chronic obstructive pulmonary disease (n = 88), alpha-1 antitrypsin deficiency (n = 63), pulmonary fibrosis (n = 97), primary pulmonary hypertension (n = 35), Eisenmenger syndrome (n = 21), and miscellaneous end-stage lung diseases (n = 93). Results The 5-, 10-, and 15-year survivals for all recipients were 55.1% (95% confidence interval: ±5%), 35.3% (±6%), and 26.5% (±11%), respectively. The most common causes of death were sepsis and bronchiolitis obliterans syndrome. Despite an increased postoperative mortality rate, patients with primary pulmonary hypertension achieved the best long-term survival (10-year survival: 59%). Recipients with cystic fibrosis without Burkholderia cepacia infection achieved significantly better long-term survival (10-year survival: 52%) than those with Burkholderia cepacia infection (10-year survival: 15%). The 10-year survival was also significantly better in recipients with chronic obstructive pulmonary disease (43%) than in recipients with alpha-1 antitrypsin deficiency (23%). Although the incidence of bronchiolitis obliterans syndrome was similar between recipients with chronic obstructive pulmonary disease (39%) and alpha-1 antitrypsin deficiency (46%), recipients with alpha-1 antitrypsin deficiency died of sepsis more frequently than recipients with chronic obstructive pulmonary disease (27% vs 6%, respectively; P = .0003). Conclusions Although bronchiolitis obliterans syndrome and sepsis still limit the durability of the benefit, lung transplantation returns many patients with end-stage lung disease to active and productive lives. Differences in the complications and long-term survival show the important contribution of the recipient diagnosis to the success of lung transplantation.

Introduction: To determine long-term outcome and risk factors for recurrence after thymectomy. Methods: Patients who underwent thymectomy ( n = 262) for a thymic tumor (1986–2010) were identified from a prospective database. Patients were classified according to World Helath Organization (WHO) histologic classification, Masaoka staging system, and completeness of resection. Risk factors for recurrence: WHO histology, tumor size, Masaoka stage and completeness of resection were analyzed. Results: Of 262 patients, 51% were female, median age was 55 years, and 39% had myasthenia gravis. Median follow-up was 7.5 years, median tumor size was 5.4 cm, and Masaoka stage distribution was: I (25%), II (47%), III (17%), IV (4%), and (7%) not classified. Of 200 patients classified under the WHO system, there were (7%) type A, (22%) type AB, and (71%) type B; 83% had complete resection. One-hundred and sixty-nine patients received adjuvant radiotherapy, eight adjuvant chemoradiotherapy and 14 neoadjuvant chemoradiotherapy. Overall survival was 95% at 5 years, 91% at 10 years and 91% at 15 years. Recurrence occurred in 12 patients and disease-related death in four patients. Five patients underwent re-resection for recurrence with survival of 2–15 years. Only Masaoka stage and tumor size were associated with statistically significant risk of recurrence on multivariate analysis. Conclusion: Resectable thymoma is associated with excellent prognosis. Aggressive resection of recurrent disease yielded excellent long-term results. Higher Masaoka stage is associated with a greater chance of incomplete resection. Higher Masaoka stage and increasing tumor size are independent factors associated with recurrence.

Objective Optimal management of stage IIIA-N2 non–small cell lung cancer remains controversial. The surgical arm of the North American Intergroup 0139 trial was adopted as the standard treatment for patients with resectable N2 disease at the University Health Network. Results after 7 years of experience are reported. Methods This is a retrospective study of consecutive patients with biopsy-proved T1-3 N2 M0 lung cancer who underwent induction chemoradiation before surgical intervention from January 1997 through August 2004. Induction chemotherapy consisted of cisplatin, 50 mg/m 2 , on days 1 and 8; etoposide, 50 mg/m 2 , on days 1 to 5, weeks 1 and 5; and concurrent daily external beam radiotherapy to 45 Gy. Lung resection was performed within 6 weeks of completion of chemoradiation, followed by 2 further cycles of consolidation chemotherapy. Results Between January 1997 and August 2004, 40 patients were treated according to this protocol (25% T1, 62.5% T2, 7.5% T3, and 5% T4). Overall and disease-free median survivals were 40 and 37.1 months, respectively, whereas overall and disease-free 3-year survivals were 51.7% and 52.3%, respectively. R0 resection was achieved in 92.5%. The overall operative mortality rate was 7.5% (0% for lobectomy and 27% for pneumonectomy). Notably, all mortalities occurred within the first 2 years of our experience with this regimen. Conclusion Chemoradiation before pulmonary resection in carefully selected patients with surgically resectable stage IIIA (N2) non–small cell lung cancer can lead to improved overall and disease-free survival.

Background:Treatment of elderly patients with stage III NSCLC is controversial. Limited data exist, as the elderly are underrepresented in clinical trials.Methods:After ethics approval, we performed a retrospective review of 1372 stage III NSCLC patients treated at our institution during the period 1997–2007. Patients with malignant effusions and microscopic N2 discovered only postoperatively were excluded, leaving 740 who were classified by treatment plan: palliative (palliative chemotherapy or radiation [≤40 Gy]); nonsurgical multimodality (>40 Gy radiation ± chemotherapy); or surgical multimodality (chemotherapy, radiation, and surgery). Demographics, treatment, toxicity, and survival were analyzed by age, 0 to 65 years, n = 384; 66 to 75 years, n = 256; 76+ years, n = 100, and compared using log-rank, univariate, and multivariate statistical tests.Results:Patients older than 65 years were more likely to have poor performance status (p < 0.0001), multiple comorbidities (p < 0.0001), and to receive palliative therapy only (p < 0.0001). Older and younger patients treated with curative intent with nonsurgical bimodality therapy or trimodality therapy including surgery had similar rates of grade 3/4 toxicity (0–65 years, 39%; 66–75 years, 43%; 76+ years, 5%; p = 0.18) and toxic death (0–65 years, 4%; 66–75 years, 4%; 76+ years, 0%; p = 0.76). Survival was worse with increasing age (p < 0.0001), likely due to greater use of palliative treatment in the elderly. When survival was analyzed for patients treated with curative intent, there was no difference between age groups for nonsurgical (p = 0.32) or surgical (p = 0.53) therapy.Conclusion:In select fit elderly patients, combined modality therapy is tolerable and is associated with survival similar to that of younger patients.

Myasthenia gravis (MG) is an autoimmune disorder diagnosed clinically for the first time at the end of the 17th century. Intense research into the pathogenesis of the disease has led to the discovery of an antibody directed against the muscle nicotinic acetylcholine receptor (AchR) in 1973 and, more recently, to the finding of a new antibody directed against the muscle-specific receptor tyrosine kinase (MuSK) in a subgroup of patients that remain seronegative for AchR antibodies. 1 Blalock’s initial experience in the early 1940s and subsequently published series of surgically treated patients led to the widespread acceptance of thymectomy in the treatment of MG despite the absence of a prospective randomized trial comparing surgery with medical treatment alone. 2 Controversiesremain,however,withregardtothetimingandextent of surgery to be performed. Some authors recommend thymectomyearlyinthecourseofthedisease,whereasothers reserve surgery for when medical therapy fails or if a thymoma is suspected. Different surgical approaches have been recommended including transcervical, transsternal, and more recently a transthoracic thoracoscopic thymectomy. All procedures allow extracapsular resection of the thymus and vary somewhat in the extent of mediastinal fat removal, which may contain foci of thymic tissue. The most extensive resection combines the transcervical and transsternal thymectomy procedures and includes removal of all mediastinal fatty tissue, both sheets of mediastinal pleura along with a sharp dissection of the pericardium. The transcervical approach was first described in the late 19th century for thymic enlargement in children and consisted of an enucleation of the thymus from within its capsule. Although initially reported in an adult patient with MG by Sauerbruch in 1912, the transcervical approach was modified to completely remove the thymus with its capsule and reintroduced in the 1960s for patients with MG. Through this approach, Kark and his colleagues reported fewer postoperative complications when compared with the transsternal approach. 3 Consequently, their patients were operated on earlier in the course of the disease and were shown to have more rapid rate of improvement. To improve exposure and to facilitate removal of the thymic gland and extracapsular thymic tissue through the neck, Cooper and colleagues described the use of a special rightangle manubrial retractor to elevate the sternum (Cooper retractor, Pilling Company, Fort Washington, PA). Using the same retractor, we observed that the routine use of a videothoracoscope introduced through the cervicotomy further improves visualization of the mediastinum and permits teaching of the technique under direct supervision. 4 Currently, the combination of early surgical referral, optimization of medical status when necessary by plasmapheresis, video-assisted transcervical thymectomy, and careful perioperative management have led to optimized care for patients with MG.