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We describe a case in which fludeoxyglucose F 18 positron emission tomography (PET) led directly to the diagnosis of giant cell arteritis in an elderly woman with a fever of unknown origin. The patient presented with a 3-month history of fatigue, fever, headache, visual disturbance, jaw claudication, and anemia. A computed tomographic scan showed an anterior mediastinal mass that was suspected of being malignant. A fludeoxyglucose F 18 PET scan performed for preoperative evaluation identified striking uptake of fludeoxyglucose F 18 in the walls of the entire aorta, left main coronary artery, and subclavian, carotid, and common iliac arteries bilaterally, suggestive of an arteritis, a diagnosis subsequently confirmed by the findings of an arterial biopsy. Her erythrocyte sedimentation rate was 129 mm/h. There was normalizaton of the PET scan 2 weeks following treatment with prednisolone. This case suggests that fludeoxyglucose F 18 PET contributes to the noninvasive diagnosis of giant cell arteritis, as well as to the evaluation of the extent of disease, response to therapy, and disease recurrence.

• Background. —Metastasectomy for colorectal carcinoma to the lung is controversial. We analyzed results of this approach to justify its credibility. Methods. —We studied 144 patients by retrospective review after complete resection of lung metastases from colorectal cancer from 1965 through 1988. Patient selection and prognostic factors influencing survival were analyzed. Survival was analyzed by the Kaplan-Meier method, and comparisons were made by log-rank analysis. Results. —A total of 170 thoracotomies were performed in 144 patients. The overall 5- and 10-year survival was 40% and 30%, respectively. Those patients undergoing complete resection of their metastases survived significantly longer than those undergoing incomplete resections. Conclusion. —It appears that resection of pulmonary metastases from colorectal carcinoma translates into long-term survival benefit. (Arch Surg. 1992;127:1403-1406)

• Traumatic rupture of the thoracic aorta is increasing in incidence and remains a highly lethal injury. The morbidity associated with this injury also remains high. We retrospectively reviewed the records of all patients admitted to our emergency department with ruptured thoracic aortas during a 15-year period to determine the reason for this persistently high morbidity and mortality and to identify any factors that might improve the outcome. We found that patients who are in unstable condition on arrival in the emergency department or who become unstable before reaching the operating room are not likely to survive. Patients who are injured in automobile accidents have a greater chance of survival than do those injured in motorcycle accidents or car-pedestrian accidents. Patients who are in hemodynamically stable condition after aortic injury survive only if diagnosis and treatment are prompt. Major complications of repair following thoracic aortic injury relate primarily to the length of cross-clamp time, and every effort should be devoted to keeping the cross-clamp time less than 30 minutes. ( Arch Surg. 1990;125:1351-1356)

Forty-six cases of malignant pleural mesothelioma were analyzed for histologic subtype, DNA content, and cell cycle characteristics. Sixty-five percent of cases were diploid in DNA content, with intermediate to low proliferative rates. Thirty-one nonmesothelial malignant neoplasms of the lung, of histologic types most easily confused with malignant mesothelioma, were also examined. In contrast to the mesotheliomas, 85% of these nonmesothelial malignant neoplasms of the lung were aneuploid; the aneuploid neoplasms exhibited higher mean proliferative rates (S = 10.6%) than diploid nonmesothelial neoplasms of the lung (S less than 6%). Unlike most malignant neoplasms, mesotheliomas most often display diploid DNA contents and low proliferative rates despite their clinically aggressive behavior.

Between October 1983 and April 1987, 20 patients with malignant mesothelioma underwent computed tomography scans of the chest and upper abdomen to evaluate the extent of disease before treatment. Twelve of these 20 patients deemed to have some potential for long-term survival had scans performed every 3 months after operation to help detect recurrent disease. Anatomic correlation of computed tomography scan findings was available in all 20 patients. The limitations of computed tomography in initial evaluation were its difficulties in assessing (1) chest wall involvement (nine patients), (2) mediastinal lymph nodes (four patients), (3) transdiaphragmatic extension of tumor (four patients), and (4) peritoneal studding and solid organ metastases less than 2 mm in size (one patient). Computed tomography was helpful in detecting recurrent disease in the 12 patients having long-term follow-up. In six of eight cases with histologically proved recurrence, computed tomography detected tumors from 1 to 8 months before the onset of signs or symptoms. Although computed tomography is known to provide far more information about the extent of disease than plain radiographs, it remains an imperfect tool for the staging of disease in patients with malignant mesothelioma. Despite its limitations, computed tomography is probably the most accurate way to provide follow-up for patients during treatment

Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

The authors report the case of a 39-year-old woman with a massive malignant pulmonary hemangiopericytoma. The clinical presentation and histologic findings were typical of this rare entity, but workup and treatment were challenging because of the size and location of the tumor. Magnetic resonance imaging (MRI) proved to be critical in the preoperative evaluation because of its unique ability to delineate the precise anatomical extent of this highly vascular neoplasm. Previous treatment of this patient with exploratory thoracotomy and chemotherapy had been unsuccessful. The authors used an innovative approach to treatment which included complete surgical resection via combined median sternotomy and thoracotomy, along with intraoperative and postoperative radiotherapy. The patient is disease-free 28 months after surgery.

In order to compare the performance of four pleural drainage units (PDU [Emerson Post-Operative Pump, Pleur-Evac, Sentinel Seal, Thora-Klex]), we created an animal model of bronchopleural fistula that simulated the type of air leak seen clinically (mean maximal flow = 5 L/min). The PDU were tested at 0 cm (water seal), -20 cm and -40 cmH2O suction. Compared to water seal, -20 cmH2O suction significantly increased the ability of all four PDU to evacuate air via the chest tube and abolished small differences in chest tube air leak seen among the PDU at water seal. An increase in suction to -40 cmH2O did not significantly alter flow via the chest tube. Previously demonstrated differences among the PDU in handling large air flows were not seen in this lower flow model of bronchopleural fistula. However, because of their higher resistance, use of the Sentinel Seal and of the Thora-Klex was technically impractical even at air leaks of 4 to 5 L/min.

We studied the behavior of the cell cycle of cultured, early-passage human diploid pulmonary fibroblastlike cells (HDPFC) when grown in the presence of several growth factors. The rates of growth and growth fractions were studied in cultures from different origins. As much as 85 +/- 5% (SE) of HDPFC cultured from specimens with early fibrosis were cycling when the cells were grown in basal media supplemented with 10% serum or growth factors. In contrast, 55% +/- 8% (SE) of HDPFC from normal lung and only 31% +/- 5% (SE) of HDPFC cultured from specimens with dense fibrosis were cycling in those culture conditions. Results obtained by removal of any of the five growth factors from the defined medium indicated that the altered growth patterns were not related to any single growth factor tested. These studies are consistent with the hypothesis that HDPFC cultured from specimens with early fibrosis have a greater proliferative potential than HDPFC from late fibrosis.

Introduction Extrapleural pneumonectomy (EPP) and adjuvant high-dose radiation therapy (RT) are associated with a median survival of 3 years in early-stage malignant pleural mesothelioma (MPM) but of less than 1 year in locally advanced disease. Although local control after EPP and RT is excellent, most patients die of distant metastases. We designed this clinical trial to test the feasibility of induction chemotherapy followed by EPP and RT in locally advanced MPM with the ultimate aim of improving survival. Methods Patients with MPM and stage III or IV disease were eligible. Induction therapy was four cycles of gemcitabine and cisplatin. Patients without disease progression by computed tomography underwent EPP followed by adjuvant hemithoracic RT (54 cGy). Results From January 2002 to January 2004, 21 patients (17 men, four women; median age 60 years) were entered into the study. Histology was epithelioid in 14 patients and mixed or sarcomatoid five patients. Pretreatment disease stage was III in 13 patients and IV in six patients. Nineteen patients received induction chemotherapy. Response to induction therapy was complete in zero patients, partial in five patients, stable disease in six patients, and progression of disease in eight patients. Eight of nine patients undergoing surgical exploration had EPP. The median survival of all patients was 19 months. Patients who had an EPP had a median survival of 33.5 months. Patients with unresectable tumors had a median survival of 9 months ( p = 0.01). Conclusion Induction chemotherapy with gemcitabine and cisplatin followed by EPP and adjuvant RT for locally advanced MPM is feasible and leads to a better median overall survival than that previously reported with EPP and RT alone.

Introduction In a previous study of prognostic factors in patients with loco-regionally advanced adenocarcinoma of the esophagus treated with chemo-radiotherapy (CRT) followed by resection, we found that residual nodal disease was most prognostic of outcome. In this study, we evaluated prognostic factors among patients with squamous cell carcinoma (SCC) of the esophagus who have undergone a similar treatment regimen. Methods A retrospective review of patients with SCC of the esophagus who received CRT before esophagectomy. Data collected included demographics, CRT details, pathologic findings, and survival. Statistical methods included recursive partitioning and Kaplan-Meier analyses. Results From 1996 to 2006, 91 patients were appropriate for this analysis. Complete pathologic response in the primary tumor (pt-pCR) occurred in 49 patients (53.8%), including 10 of 91 (10.9%) who had a pt-pCR but residual nodal disease. Recursive partitioning analysis identified three prognostic groups: (1) group 1 (n = 52), patients with minimal residual local disease (pt-pCR and T1-N any); (2) group 2 (n = 28), patients with residual T2 disease (N0 and N1) and patients with T3-4N0 disease; and (3) group 3 (n = 11), patients with residual T3-4N1 disease. Three-year survival was 68.4% in group 1, 45.6% in group 2, and 0 % in group 3 (p Conclusions Unlike adenocarcinoma, in which residual nodal disease after CRT is the most significant predictor of survival, in SCC of the esophagus, pt-pCR or minimal residual local disease after CRT predicts the best survival. These findings aid the design of future clinical trials.

Introduction: Despite increasing use of tunneled pleural catheters (TPCs), their efficacy as a definitive procedure for achieving palliation or spontaneous pleurodesis (SP) in the management of malignant pleural effusion (MPE) remains unclear. In the largest TPC series to date, we evaluate the efficacy for palliation and review the rate and predictors of SP. Methods: Retrospective review of 418 TPCs (355 patients) over 2 years (September 2007–September 2009) was performed. Palliation was deemed successful when the patient did not require any other subsequent effusion-directed drainage procedure. SP was defined as satisfying the following criteria: (a) TPC removal without need for further effusion-directed intervention during the patient's lifespan and (b) no evidence of effusion reaccumulation by clinical and radiographic evidence at 1-month postremoval follow-up. Results: After TPC placement, no subsequent effusion-directed procedure was required for 380 of 418 (91%). SP was achieved after only 26% of TPCs (110 of 418), in which the median time to catheter removal was 44 days. Neither demographics nor primary tumor type predicted SP. In patients selected for TPC placement in the operating room, SP occurred in 36% (39 of 107), with 45% in loculated MPE (13 of 29, p = 0.014). Complications occurred after 20 TPCs (4.8%), with none occurring after bedside placement. Conclusion: TPC placement is safe and provides durable palliation, most often obviating the need for subsequent procedures in MPE patients. TPC, however, remains suboptimal at achieving pleurodesis.

Objective Reports have questioned the oncologic efficacy of video-assisted thoracoscopic surgery when compared with thoracotomy despite similar survival results. In response, we investigated the pattern of recurrent disease and the incidence of second primary tumors after lobectomy by means of video-assisted thoracoscopic surgery and thoracotomy. Methods All patients who underwent lobectomy for clinical stage IA lung cancer determined by means of computed tomographic and positron emission tomographic analysis were identified from a prospective database at a single institution. All patients were selected for video-assisted thoracoscopic surgery or thoracotomy by an individual surgeon. Patients' characteristics, perioperative results, recurrences, and second primary tumors were recorded. Variables were compared by using Student's t test, the Pearson χ2 test, and Fisher's exact test. A logistic regression model was constructed to identify variables influencing the development of recurrent disease or metachronous tumors. Results From 2002 to 2009, 520 patients underwent lobectomy by means of video-assisted thoracoscopic surgery, and 652 underwent lobectomy by means of thoracotomy. Final pathological stage was similar in the video-assisted thoracoscopic surgery and thoracotomy groups. Logistic regression demonstrated a lower risk (odds ratio, 0.65; P = .01) of recurrent disease in patients undergoing video-assisted thoracoscopic surgery after adjusting for age, stage, sex, histology, tumor location, and synchronous primary tumors. Conclusions Recurrence rates for video-assisted thoracoscopic surgery appear to be at least equivalent to those for thoracotomy. This study supports lobectomy by means of video-assisted thoracoscopic surgery as an oncologically sound technique.

Introduction Distinguishing synchronous primary lung cancers (SPLCs) from advanced disease is important because prognosis and treatments are very different and a surgical approach to SPLC may result in survival similar to solitary cancers. Determining this distinction with certainty, however, is challenging. We reviewed our experience with surgical resection of presumed SPLC to analyze outcomes and identify factors associated with prolonged survival. Patients and Methods A retrospective review identified patients treated for presumptive SPLC. Cases were defined using modified criteria set forth by Martini and Melamed and histologic subtyping. Survival was estimated using the Kaplan-Meier method, and factors associated with survival were evaluated using a log-rank test or Cox proportional hazards model for categorical and continuous variables, respectively. Results From January 1995 to July 2006, 175 patients met study criteria and underwent complete resection. Tumors were more often in different lobes of an ipsilateral chest (55 of 175, 31%) or contralateral lesions (45 of 175, 26%). More than half (104 of 175, 59%) of the patients underwent a single operation. Median follow-up was 50.3 months (4.8-164.7); median overall survival (OS) for the group was 67.4 months (46.4-80.0) with a 3-year OS of 64%. On multivariable analysis controlling for stage, only female gender was a significant predictor of better OS ( p = 0.001). Conclusions An aggressive surgical approach to patients with apparent SPLC can result in survival that is comparable with patients with single lung cancers of similar stage. The Martini and Melamed criteria and histologic subtyping can identify appropriate patients for resection. Female gender was associated with superior OS.

IntroductionFor lung squamous cell carcinomas, there are no pathological findings that have been universally accepted as prognostic factors, with the exception of pathological stage. Tumor budding and nuclear grade have been recognized as a poor prognostic factor in other carcinomas. In this study, we investigated whether pathological findings could determine prognosis in lung squamous cell carcinomas.MethodsAll available tumor slides from patients with surgically resected, solitary lung squamous cell carcinomas (1999–2009) were reviewed (n = 485; stage I/II/III, 281/136/68). Tumors were evaluated for differentiation, subtypes (keratinizing, nonkeratinizing, basaloid pattern, papillary growth, and clear cell feature), tumor nest size (tumor budding and single cell invasion), and nuclear grade (nuclear diameter and mitosis). Overall survival (OS) was estimated using the Kaplan-Meier method (stratified by pathological stage), and group differences were investigated using the stratified log-rank test and the Cox proportional hazards model.ResultsOS was significantly decreased in patients with versus without single cell invasion (p = 0.002 for the entire tumor and p = 0.001 for tumor edge), with large versus small nuclei (p = 0.011), and with high versus low grade tumor budding (p < 0.001 for maximum and p = 0.007 for total). In multivariate analyses, single cell invasion (hazard ratio [HR], 1.47–1.49), nuclear diameter (HR, 1.09–1.33), and tumor budding (HR, 1.04) were independent prognostic factors of OS. However, histologic subtyping including keratinizing, nonkeratinizing, basaloid, and clear cell subtypes did not show prognostic significance.ConclusionsPathological factors can help stratify prognosis in patients with lung squamous cell carcinomas.

ObjectivesRecent studies suggest that standard uptake value on fluorodeoxyglucose positron emission tomography scan can predict mediastinal lymph node status in malignant pleural mesothelioma. Because mediastinal nodal metastasis is known to be associated with poor prognosis, we hypothesized that standard uptake value on fluorodeoxyglucose positron emission tomography might independently predict survival.MethodsPatients with pathologically proven mesothelioma underwent fluorodeoxyglucose positron emission tomography scanning. Patients fasted and received a minimum of 10 mCi of F18-fluorodeoxyglucose. Whole-body emission studies were acquired, followed by whole-body transmission scans with iterative reconstruction. On the basis of the maximal chi-square method, a standard uptake value of 10 was chosen to classify patients as low versus high standard uptake value. Survival probabilities for both standard uptake value groups were estimated by the Kaplan-Meier method. A Cox proportional hazards model assessed the joint influence of standard uptake value, histology, and stage on survival.ResultsFrom 1998 to 2005, 137 patients with malignant pleural mesothelioma underwent positron emission tomography scans. The median follow-up for all surviving patients was 24 months. Median survivals were 9 and 21 months for the high and low standard uptake value groups, respectively (P = .02). In a multivariable analysis, high standard uptake value tumors were associated with a 1.9 times greater risk of death than low standard uptake value tumors (P < .01). Mixed histology carried a 2.9 times greater risk of death than epithelioid histology (P < .01), and stages III and IV had a 1.8 times greater risk of death than stages I and II (P = .05).ConclusionsStandard uptake value greater than 10, mixed histology, and stages III and IV are poor risk factors in malignant pleural mesothelioma. These findings suggest that fluorodeoxyglucose positron emission tomography can be used to stratify patients for treatment and clinical trials.

IntroductionPrevious prognostic scoring systems for malignant pleural mesothelioma (MPM) included patients managed surgically and predated the use of pemetrexed. We analyzed prognostic factors in a contemporary cohort of patients with unresectable MPM who received pemetrexed-based chemotherapy.MethodsThis single-institution analysis included patients with MPM who were managed nonsurgically from 2000 to 2013. Variables correlated with overall survival (OS) included sex, performance status (PS), asbestos exposure, tumor laterality, histology, clinical stage, initial positron emission tomography maximum standardized uptake value, hemoglobin level, platelet count, lymphocyte count, white cell and neutrophil counts, treatment type, and clinical benefit from treatment. OS was analyzed by the Kaplan-Meier method, and significance (p < 0.05) of prognostic factors was analyzed by the log-rank test and Cox regression.ResultsA total of 191 patients met the study criteria: median age 71 years (range 46–90), 147 men (77%), 128 epithelioid tumors (67%), and 157 cases of stage III or IV MPM (82%). Median OS for all patients was 13.4 months. According to a univariate analysis, histology (p < 0.001), platelet count (≤450,000 versus >450,000, p < 0.001), initial PS (0–1 versus ≥2), maximum standardized uptake value (≤8.1 versus >8.1, p = 0.037), and lymphocyte counts (p = 0.019) were associated with OS. According to a multivariable analysis, only histology, platelet count, and PS were independent prognostic factors. Epithelioid histology, PS, and elevated lymphocyte count at diagnosis were significantly associated with clinical benefit from first-line chemotherapy.ConclusionsOur results confirm the significance of elements of the Cancer and Leukemia Group B and European Organisation for Research and Treatment of Cancer prognostic scoring systems, identify factors associated with clinical benefit from chemotherapy, and emphasize the impact of histology and clinical benefit of chemotherapy on outcomes.

ObjectiveIn the cancer population, pericardial effusions are a common and potentially life-threatening occurrence. Although decompression benefits most patients, paradoxical hemodynamic instability (PHI) develops in some, with hypotension and shock in the immediate postoperative period. This study examines paradoxical hemodynamic instability after pericardial window and identifies prognostic factors in patients with cancer who are treated for pericardial effusion.MethodsRetrospective review of 179 consecutive pericardial windows performed for pericardial effusion in a tertiary cancer center over a 5-year period (January 2004 through March 2009). Demographic, surgical, pathologic, and echocardiographic data were analyzed for the end points of paradoxical hemodynamic instability (pressor-dependent hypotension requiring intensive care unit admission) and overall survival.ResultsThe most common malignancies were lung (44%), breast (20%), hematologic (10%), and gastrointestinal (7%). Overall survival for the group was poor (median, 5 months); patients with hematologic malignant disease fared significantly better than the others (median survival 36 months; P = .008). Paradoxical hemodynamic instability occurred in 19 (11%) patients. These patients were more likely to have evidence of tamponade on echocardiogram (89% vs 56%; P = .005), positive cytology/pathology (68% vs 41%; P = .03), and higher volume drained (674 mL vs 495 mL; P = .003). Overall survival was significantly shorter in those in whom paradoxical hemodynamic instability developed (median survival 35 vs 189 days; hazard ratio = 3; P

Objective: The effectiveness of chest wall resection for locally recurrent breast cancer as cancer treatment remains poorly defined, possibly because of the general impression that locally recurrent disease is a harbinger of rapidly progressive metastatic disease and that extensive surgical treatment in these patients is inappropriate. Reports to date have focused on technical feasibility, not long-term outcome. Methods: We reviewed our experience with 38 women who underwent chest wall resection for locally recurrent breast cancer between October 1987 and May 1997. Overall survival was calculated by the Kaplan-Meier method and the significance of prognostic variables evaluated by log-rank and Cox regression analyses. Results: The operative mortality rate was 0%. Overall survival at 1, 3, and 5 years after chest wall resection was 74%, 41%, and 18%, respectively, and the proportion of patients free of local recurrence at 1, 3, and 5 years was 59%, 42%, and 13%, respectively. Regional nodal disease and size of largest tumor nodule (>4 cm) were significant predictors of local re-recurrence (P < .01, P = .04); lymph node metastasis was the only predictor of long-term survival (P < .01). Patients with and without synchronous sites of metastatic disease had near-identical 3-year survivals. Conclusions: Chest wall resection for locally recurrent breast cancer has a low mortality. However, a significant number of patients have the development of local re-recurrence or metastases, and 5-year survival is limited. It is unlikely that complete resection of all locally recurrent disease improves survival. Future studies should focus on the quality of palliation achieved. (J Thorac Cardiovasc Surg 2000;119:420-8)

Objective The objective was to define the incidence of atrial fibrillation after video-assisted thoracic surgery lobectomy and determine whether video-assisted thoracic surgery reduces atrial fibrillation rate compared with thoracotomy. Methods With the use of a single-institution database of patients who underwent lobectomy for clinical stage I non–small cell lung cancer, 389 patients were identified who were in sinus rhythm preoperatively and received no prophylactic antiarrhythmics. Patients undergoing video-assisted thoracic surgery were age and gender matched with those undergoing thoracotomy. Results After matching, 122 patients undergoing video-assisted thoracic surgery and 122 patients undergoing thoracotomy were eligible for analysis. Patients undergoing video-assisted thoracic surgery had a higher preoperative diffusion capacity (92% ± 28% vs 80% ± 18% predicted, P = .001) and a lower rate of induction chemotherapy (5/122, 4% vs 11/122, 11%, P = .05) than patients undergoing thoracotomy. Atrial fibrillation occurred in 12% of patients (15/122) undergoing video-assisted thoracic surgery and 16% of patients (20/122) undergoing thoracotomy ( P = .36). Overall, complications were lower in the video-assisted thoracic surgery group (17.2% vs 27.9%, P = .046). Patients with atrial fibrillation were older in both video-assisted thoracic surgery (73 ± 7 years vs 66 ± 9 years, P = .002) and thoracotomy groups (72 ± 7 years vs 66 ± 10 years, P = .005). Length of stay for patients with atrial fibrillation was greater in both video-assisted thoracic surgery (6.0 ± 1.5 days vs 4.7 ± 2.5 days, P = .01) and thoracotomy groups (9.2 ± 4.3 days vs 6.8 ± 3.6 days, P = .03). Conclusions Regardless of surgical approach, atrial fibrillation after lobectomy occurred with equal frequency. This supports the theory that autonomic denervation and stress-mediated neurohumoral mechanisms are responsible for the pathogenesis of postoperative atrial fibrillation. Prophylaxis regimens against atrial fibrillation should be the same for either operative approach.

Background: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival. Methods: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning. Results: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors ( P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30. Conclusion: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.

Introduction While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non–small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. Methods Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes ( CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3 , and ADAMTS8 ) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. Results A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1 , and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS ( p = 0.03). The total number of genes with methylated promoters did not correlate with RFS ( p = 0.89) or OS ( p = 0.55). Conclusion Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation ( CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1 , and ADAMTS8 ) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs.

Purpose The purposes of this study were (1) to calculate the tumor volume in patients with malignant pleural mesothelioma using computed tomography (CT) scan images and a computer-aided measurement technique and (2) to investigate whether the baseline volume, or volume change after chemotherapy, predicts patient survival. Methods We compiled the clinical characteristics and outcome from 30 patients enrolled in two clinical trials at our cancer center in which the patients were treated with induction chemotherapy followed by surgery and radiation. CT scans of 30 patients were obtained at baseline and after two cycles of chemotherapy. Tumor volumes were calculated using a semiautomated computer algorithm. Overall survival was measured using a landmark time at 3 months post-treatment start date such that all patients had already received two cycles of chemotherapy and a follow-up scan. Association of volume changes with overall survival were determined by a Cox Proportional Hazards Model or log-rank test. The relationship between both pre and postoperative clinical stage and baseline tumor volume was analyzed using the rank sum test. Results The median baseline tumor volume was 473 cm 3 (range, 61 cm 3 –2108 cm 3 ). Patients with high preoperative stages (III and IV) had larger baseline tumor volume than those with low preoperative stages (I and II) ( p = 0.05). Patients with baseline volumes smaller than 619 cm 3 tended to survive longer than those with baseline volumes larger than or equal to 619 cm 3 ( p = 0.07). Percentage change of tumor volume from baseline to first follow-up CT after two cycles of chemotherapy was significantly associated with overall survival (hazard ratio: 1.94 [95% confidence interval, 1.05–3.60], p = 0.04). Whereas the relative change in modified RECIST measurements was not significantly associated with overall survival (hazard ratio: 1.06 [95% confidence interval, 0.96–1.16], p = 0.25). By classifying changes of tumor volumes between two scans into two groups, i.e., "increase" and "decrease," a significant difference in survival was found between those who increased and decreased after two cycles of chemotherapy ( p = 0.03). Conclusions Changes in tumor volume after two cycles of chemotherapy predicted overall survival in patients with malignant pleural mesothelioma. Tumor volume at baseline was shown to be associated with preoperative clinical stage and survival. Computer-aided volumetric measurements may enable more reliable therapeutic response assessment and could provide additional prognostic information.

Primary endodermal sinus tumor (EST) of the mediastinum has been regarded as a rare and rapidly fatal germ cell neoplasm. We describe two cases of extensive EST treated with a new high-dose sequential combination chemotherapy regimen (CISCA-VB) followed by radical surgical excision. They are alive at 11 and 20 months, respectively, postoperatively. These cases stand in marked contrast to previously reported series. A new approach to the management of this tumor is proposed.

The records of 20 patients with Crohn's disease who underwent incidental appendectomy and later required bowel resection were reviewed and the following conclusions ascertained. If the patient had had abdominal pain for less than 1 week, appendectomy is followed by minimal problems. If the patient has had abdominal pain for longer than 1 week, incidental appendectomy is followed by an 83 percent incidence of fistula or sinus tract, arising not from the appendiceal stump but from the terminal ileum. The natural history of patients with resection after appendectomy includes more medication and a higher symptom recurrence rate and perhaps operative recurrence rate than their counterparts who have not undergone incidental appendectomy.

Over a 3 year period, 52 patients underwent thoracoscopy for the diagnosis and management of a variety of pleural diseases. In 46 of the 52 patients, thoracoscopy was performed under regional anesthesia. The procedure was associated with no operative deaths and essentially no morbidity. In all 52 patients, thoracoscopy averted the need for formal thoracotomy. Thoracoscopy proved valuable as (1) the ultimate diagnostic tool for determining the presence or absence of pleural malignancy in patients with recurrent pleural effusions; (2) a method for obtaining tissue in cases where cytologic study was inadequate for diagnosis; (3) a highly successful approach to chemical pleurodesis in patients with malignant pleural effusions, multiloculated effusions, or failed tetracycline pleurodesis; (4) a means for determining whether a loculated fluid collection was intrapleural or parenchymal in location when radiologic study had failed to clarify this; (5) a way to completely drain the pleural space in patients with multiloculated empyemas not amenable to tube thoracostomy; and (6) an alternative to open lung biopsy in the immunosuppressed patient with diffuse pulmonary infiltrates. Thoracoscopy is a safe, effective, and relatively simple procedure which can be easily performed under regional anesthesia, even in ill or elderly patients. It is an often overlooked alternative to thoracotomy and should be used more widely.

Background Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial. Methods Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days. Results Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration. Conclusion The rate of data completion met our predefined criterion for determining a randomized trial to be feasible (at least 75% of patients tolerated the intervention and provided evaluable data). This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial.

99 Background: Targeting PD-L1/PD-1 to activate anti-tumor immunity is associated with improved response and survival compared to chemo in NSCLC pts. We present a preliminary analysis of the clinical efficacy, safety and peripheral blood (PB) immunophenotyping from an ongoing multicenter atezolizumab (atezo) neoadjuvant immunotherapy study in resectable NSCLC. Methods: Pts received 2 cycles of atezo, 1200mg, days 1, 22 before resection. Tumor biopsies and PB were obtained pre-atezo & pre-surgery. The biomarker evaluable population (BEP) included pts with paired PB analyzed within 72 hrs by 10-color flow cytometry (IMMUNOME) and major pathological response (MPR) assessment (defined as ≤ 10% residual tumor). The primary endpoint was MPR. Secondary endpoints included safety, MPR by PD-L1, OS, and DFS. Immunophenotypic analyses were correlated with treatment, MPR and PD-L1 expression. Results: 116 patients have been enrolled as of October 31, 2018 and here we report on 54 of 180 planned pts with follow-up through surgery. 15 pts had Gr 3-4 AEs (3 treatment related), one Gr 5 AE (sudden death) was unrelated. By RECIST there were 3 PR, 49 SD, and 2 PD. 50/54 pts underwent the planned surgery, 47 pts had MPR assessment: 4 pts discontinued study preop (2 radiographic PD, 2 other reasons); 3 were unresectable. Excluding 5 pts with EGFR or ALK mutations, MPR rate was 10/45 (22%, 95% CI 11-37%). Baseline PD-L1 status was evaluable in 44/54 pts; BEP included 31 pts, 23 had tissue PD-L1 status: 16 PD-L1+. We observed significant increases in natural killer (NK) cells, CD8+ T-cells, Th1-response related dendritic cells (DC), and decreases in B-cells after atezo. Non-MPR pts showed significant increases in late activated NK cells, monocytic myeloid cells and Th2 and Th17-response–related DCs. PD-L1+ pts showed significant decreases of senescent T cells, monocytic myeloid cells, and increases of Th1-response–related DCs. We analyzed 22/54 tumor pairs, PD-L1+ cells increased in most pts after atezo treatment. Conclusions: Neoadjuvant atezo was well tolerated and the MPR rate is encouraging. Preliminary immunophenotyping data showed significant changes in PB with immunotherapy. Clinical trial information: NCT02927301.

7180 Background: The role of pleurectomy/decortication (PD) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM) is controversial. We conducted a retrospective re...

In human lung adenocarcinomas harboring EGFR mutations, a second-site point mutation that substitutes methionine for threonine at position 790 (T790M) is associated with approximately half of cases of acquired resistance to the EGFR kinase inhibitors, gefitinib and erlotinib. To identify other potential mechanisms that contribute to disease progression, we used array-based comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR mutant tumors from untreated patients with those from patients with acquired resistance. Among three loci demonstrating recurrent copy number alterations (CNAs) specific to the acquired resistance set, one contained the MET proto-oncogene. Collectively, analysis of tumor samples from multiple independent patient cohorts revealed that MET was amplified in tumors from 9 of 43 (21%) patients with acquired resistance but in only two tumors from 62 untreated patients (3%) ( P = 0.007, Fisher's Exact test). Among 10 resistant tumors from the nine patients with MET amplification, 4 also harbored the EGFR T790M mutation. We also found that an existing EGFR mutant lung adenocarcinoma cell line, NCI-H820, harbors MET amplification in addition to a drug-sensitive EGFR mutation and the T790M change. Growth inhibition studies demonstrate that these cells are resistant to both erlotinib and an irreversible EGFR inhibitor (CL-387,785) but sensitive to a multikinase inhibitor (XL880) with potent activity against MET. Taken together, these data suggest that MET amplification occurs independently of EGFR T790M mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib.

4023 Background: Response on PET scan during preoperative chemotherapy (chemo) for esophageal cancer (EC) has prognostic significance [JCO 19:3058;2001]. Induction chemo with weekly irinotecan(I)/cisplatin(C) relieves dysphagia, and weekly I/C administered with radiotherapy (RT) is well tolerated [ProcASCO 23:Abs 4017;2005]. We completed a Phase II trial of induction I/C followed by I/C/RT followed by surgery. Repeat PET scan was performed after induction chemo and prior to RT. Methods: Patients (pts) with resectable EC/GE junction carcinoma were staged with EUS, PET, and CT scan. Induction chemo consisted of I-65 mg/m2 and C-30 mg/m2 weeks 1,2,4,5, and weeks 7,8,10,11 with RT (180 cGy daily fractions to 5040 cGy). PET scan was repeated at week 6. Esophagectomy was planned 4–8 weeks after RT. Results: 60 pts were enrolled: 6 inevaluable, 54 evaluable, 3 await surgery; 49 male (91%), 5 female (9%), 41 adenocarcinoma (76%), 13 squamous (24%), median age 59, median PS 0, EUS T3N1 35 (65%), N1 40 (74%). Of 41 pts with dysphagia, 31 (76%) had resolution/improvement with induction chemo and 3/54 (6%) required a feeding tube. Of 51 pts, 3 clinical complete responders (CR) deferred surgery (1 refusal, 2 medically inoperable). Of 48 pts, 4 progressed during induction (8%), 9 progressed during RT (19%), and 35 underwent R0 resection (73%). 9/48 (19%) achieved pathologic CR. The median overall survival was 35.4 mos (median follow up 15 mos). In exploratory analysis in 54 pts, response after induction on the week 6 PET scan measured as a decline in SUV, correlated with time to tumor progression (TTP). The mean change in SUV was 43%. A set point of 22% or greater decline in SUV (PET responder) yielded the greatest distinction in TTP (PET responders TTP 18.5 mos, vs nonresponders 5.5 mos, p = 0.03). 4 pts with progression during induction crossed over to RT with paclitaxel: 3 (2 squamous, 1 adenocarcinoma) achieved durable disease control (one pathologic CR, one pathologic PR, one clinical CR). Conclusions: Response on PET scan during induction chemo for EC may identify early treatment failures, and may direct pts to successful salvage with alternative chemo during RT. Supported by a grant from Pfizer. [Table: see text]

7021 Background: Induction therapy provides a unique opportunity for the objective assessment of therapies in patients with NSCLC to facilitate care and advance research. We designed this 40 patient prospective trial to measure gefitinib’s ability to induce regressions preoperatively in individuals with NSCLC and to simultaneously correlate response with mutations in EGFR exons 19 and 21. Patients with ‘in-vivo‘ gefitinib sensitivity and/or mutations receive gefitinib postoperatively as well. To facilitate our goals, we enriched the population studied to select individuals with tumors more likely to harbor mutations in EGFR. Methods: At diagnosis, patients with stage I or II NSCLC had baseline chest CT imaging and a core-needle biopsy to detect EGFR mutations. All participants smoked cigarettes ≤ 10 pack years and/or had tumors with bronchioloalveolar features. All received gefitinib 250 mg daily. After 21 days, CT imaging was repeated and resection followed. Surgical specimens were agained assayed for EGFR mutations. Patients with mutation and/or a ≥ 25% regression (WHO) were given gefitinib 250 mg for 2 years. Results: 20 patients enrolled to date. EGFR mutations were detected in both pre and post gefitinib specimens in 4/19 tested (21%). Five of 19 (26%) had a ≥ 25% bidimensional tumor reduction after 3 weeks. Regressions ≥ 25% were seen in 2/4 (50%) with exon 19 and 21 EGFR mutations and 3/15 (20%) with WT EGFR. The other 2 patients with mutations had 11% and 23% tumor regressions. The 6 patients who had either a ≥ 25% lesion reduction and/or mutation received gefitinib postoperatively. No perioperative complications related to gefitinib occurred. All patients are relapse free. Conclusions: In this ongoing trial, 1) Our ‘enrichment strategy‘ resulted in the detection of twice the expected number of EGFR mutations in USA patients with NSCLC. 2) Gefitinib sensitivity can be assessed by CT in 3 weeks. 3) Results of mutation detection were identical in pre- and post-treatment specimens. 4) The rate of response is numerically higher in patients with EGFR mutations in exons 19 and 21. 5) We are using the surgical specimens to elucidate determinants of gefitinib sensitivity in the absence of EGFR mutation. Support: CA05826, CA113653. [Table: see text]

7193 Background: Approximately 25% of patients (pts) with malignant pleural mesothelioma (MPM) prove unresectable at surgery and the median survival of stage III MPM is

Although the presence of nodal disease is prognostic in thymic malignancy, the significance of the extent of nodal disease has yet to be defined. Lymph node dissection has not been routinely performed, and there is currently no node map defined for thymic malignancy. To establish a universal language for reporting as well as characterize the staging of this disease more accurately, an empiric node map is proposed here. This was developed using prior classification systems, series reporting specifics of nodal involvement, anatomical studies of lymphatic drainage, and preexisting node maps of the chest as defined by the International Association for the Study of Lung Cancer and the neck as defined by the American Academy of OtolaryngologyHead and Neck Surgery and the American Society for Head and Neck Surgery. The development of this node map was a joint effort by the International Thymic Malignancy Interest Group and the Thymic Domain of the IASLC Staging and Prognostic Factors Committee. It was reviewed and subsequently approved by the members of ITMIG. This map will be used as an adjunct to define node staging as part of a universal stage classification for thymic malignancy. As more data are gathered using definitions set forth by this node map, a revision may be undertaken in the future.