Philip A. Linden

Five-year survival does not equal cure in non–small cell lung cancer: A Surveillance, Epidemiology, and End Results–based analysis of variables affecting 10- to 18-year survival

OBJECTIVE Five-year survival after the diagnosis of non-small cell lung cancer is the most common benchmark used to evaluate long-term survival. Data on survival beyond 5 years are sparse. We sought to elucidate variables affecting 10- to 18-year survival. METHODS A total of 31,206 patients alive at least 5 years after diagnosis of non-small cell lung cancer who were registered in the Surveillance, Epidemiology, and End Results database from 1988 to 2001 were examined. Primary end points were disease-specific survival and overall survival. Survival analysis was performed with Kaplan-Meier estimates, multivariable Cox proportional hazards regression, and competing risk models. RESULTS Overall survival at 10, 15, and 18 years was 55.4%, 33.1%, and 24.3%, respectively. Disease-specific survival at 10, 15, and 18 years was 76.6%, 65.4%, and 59.4%, respectively. In multivariable regression analysis, squamous cell cancers had a disease-specific survival advantage (hazard ratio, 0.88; P < .0001) but an overall survival disadvantage (hazard ratio, 1.082; P = .0002) compared with adenocarcinoma. Pneumonectomy (hazard ratio, 0.44) and lobectomy (hazard ratio, 0.474) had improved disease-specific survival compared with no surgery (P < .0001). Left-sided tumors (hazard ratio, 0.723; P = .036) and node-negative cancers (hazard ratio, 0.562; P < .001) also had a better disease-specific survival and, to a lesser extent, overall survival advantage. CONCLUSIONS Five-year survivors of non-small cell lung cancer have a persistent risk of death from lung cancer up to 18 years from diagnosis. More than one half of all deaths in 5-year survivors are related to lung cancer. In multivariable regression analysis, age, node-negative disease, and lobar or greater resection were strong predictors of long-term survival (ie, 10-18 years).

Quantifying the Safety Benefits of Wedge Resection: A Society of Thoracic Surgery Database Propensity-Matched Analysis

BACKGROUND Wedge resection is often used instead of anatomic resection in an attempt to mitigate perioperative risk. In propensity-matched populations, we sought to compare the perioperative outcomes of patients undergoing wedge resection with those undergoing anatomic resection. METHODS The Society of Thoracic Surgery database was reviewed for stage I and II non-small cell lung cancer patients undergoing wedge resection and anatomic resection to analyze postoperative morbidity and mortality. Propensity scores were estimated using a logistic model adjusted for a variety of risk factors. Patients were then matched by propensity score using a greedy 5- to 1-digit matching algorithm, and compared using McNemars test. RESULTS Between 2009 and 2011, 3,733 wedge resection and 3,733 anatomic resection patients were matched. The operative mortality was 1.21% for wedge resection versus 1.93% for anatomic resection (p=0.0118). Major morbidity occurred in 4.53% of wedge resection patients versus 8.97% of anatomic resection patients (p<0.0001). A reduction was noted in the incidence of pulmonary complications, but not cardiovascular or neurologic complications. There was a consistent reduction in major morbidity regardless of age, lung function, or type of incision. Mortality was reduced in patients with preoperative forced expiratory volume in 1 second less than 85% predicted. CONCLUSIONS Wedge resection has a 37% lower mortality and 50% lower major morbidity rate than anatomic resection in these propensity-matched populations. The mortality benefit is most apparent in patients with forced expiratory volume in 1 second less than 85% predicted. These perioperative benefits must be carefully weighed against the increase in locoregional recurrence and possible decrease in long-term survival associated with the use of wedge resection for primary lung cancers.

VATS pericardiotomy for patients with known malignancy and pericardial effusion: Survival and prognosis of positive cytology and metastatic involvement of the pericardium: A case control study

BACKGROUND Pericardiotomy for cancer patients with effusion can alleviate symptoms, but with unclear effect on long term survival. Our experience with VATS technique has produced some long-term survivors. METHODS A retrospective review of 62 VATS pericardiotomy for pericardial effusion in patients with known malignancy. Kaplan-Meier survival curves and Log-Rank tests were used for analysis. RESULTS The mean age was 54.8+/-14.3 years (ranging from 19 to 79). The mean hospital stay was 8.7+/-5.5 days. The median survival was 6.75 months (range 1 month-10 years). Overall one-year survival was 44.2%, 3-year survival 17.6%, and 5-year survival 10% after drainage of pericardial effusion. The mean survival in cytology negative patients (n=21) was 13.4+/-0.98 months, compared to 4.89+/-0.9 months in cytology positive patients (n=27) (p=0.0175). The 5-year survival in cytology negative patients was 19.6%, while none of the patients with positive cytology were alive after 36 months. The mean survival in patients with no evidence of metastatic disease on the pericardium (n=28) was 12.8+/-0.9 months, compared to patients with metastatic disease of the pericardium (n=22) 4.66+/-0.8 months (p=0.026). CONCLUSIONS VATS Pericardiotomy can provide effective long-term drainage in patients with symptomatic pericardial effusion. Positive cytology and metastatic involvement of the pericardium are predictive of worse survival. Survival greater than 5 years can be expected in 19% and 17% of patients with negative fluid cytology and negative metastatic disease of the pericardium, respectively.

Section V: Techniques of esophageal resection

Esophagectomy the treatment of choice for esophageal cancer, is a procedure which, nationwide, carries a mortality rate of 10% and a morbidity rate of 50%. The five-year survival rate for esophagectomy for cancer remains at 20%. With great care in surgical planning, technique, and patient care, the mortality rate has been lowered to 3% at several large academic centers. The methods of esophagectomy including Ivor-Lewis, transhiatal, left thoracoabdominal, and cervical exenteration are discussed. The technique of tri-incisional esophagectomy is detailed in this chapter. This technique combines the best aspects of the Ivor-Lewis and transhiatal approaches, those being a cervical anastomosis (avoiding an intrathoracic leak, minimizing reflux, and allowing for a complete esophagectomy) and transthoracic dissection of the esophagus (allowing for a safe dissection and complete lymphadenectomy).

Extending Indications for Radiofrequency Ablation of Lung Tumors Through an Intraoperative Approach

BACKGROUND Radiofrequency ablation (RFA) is a means of local destruction of lung tumors. The role of this technique in regards to improved survival or quality of life has yet to be well defined. RFA can be performed through an intraoperative or percutaneous route. Percutaneous RFA can be performed without single-lung ventilation under local anesthesia with sedation and is often the preferred route of ablation. We detail instances of RFA in patients who were either not candidates for percutaneous RFA or in whom the tumor was found to be unresectable at operation. METHODS Ten patients with either primary or secondary lung tumors who underwent operation with consideration of intraoperative RFA were reviewed. Patients were followed up with chest computed tomography scans at least every 6 months. Preoperative characteristics, intraoperative techniques, complications, and tumor response were noted. RESULTS The median patient age was 60 years (range, 40 to 85 years). Six patients had lung cancer, 4 had cancer metastatic to the lung, and 5 patients had hilar lesions. Combined lung resection and RFA was done in 4 patients; 6 underwent RFA only. The average size of the ablated lesion was 3.0 cm (range, 1.0 to 5.8 cm). No serious intraoperative or perioperative complications were noted. No immediate or delayed hemorrhage or hemoptysis has been noted. Of patients at least 6 months out from ablation, 4 had no growth of the ablated tumor at an average of 13.5 months (range, 8 to 23 months) after ablation, and 5 have had growth of the tumor first noted at an average of 12.8 months (range, 9 to 14) after ablation. CONCLUSIONS Intraoperative RFA is useful (1) when the lesion is near vital structures such as the great vessels, hilum, or heart, (2) if resectability can only be determined at the time of operation, and (3) when used in patients with secondary tumors of the lung combined with limited resection to preserve lung parenchyma.

Video-assisted anterior approach to Pancoast tumors

References 1. Comoglio C, Boffini M, El Qarra S, Sansone F, D’amico M, Marra S, et al. Aortic valve replacement and mitral valve repair as treatment of complications after percutaneous core valve implantation. J Thorac Cardiovasc Surg. 2009;138:1025-7. 2. Wong DR, Boone RH, Thompson CR, Allard MF, Altwegg L, Carere RG, et al. Mitral valve injury late after transcatheter aortic valve implantation. J Thorac Cardiovasc Surg. 2009;137:1547-9.

Serial Drain Amylase Can Accurately Detect Anastomotic Leak After Esophagectomy and May Facilitate Early Discharge

BACKGROUND Anastomotic leaks after esophagectomy are a significant cause of postoperative morbidity and death. Barium esophagram and esophagogastroduodenoscopy are commonly used to survey for leaks; however, each has inherent risks and limitations. We sought to evaluate the effectiveness of daily drain amylase levels in detecting anastomotic leaks after esophagectomy. METHODS We retrospectively reviewed 146 consecutive patients who underwent esophagectomy with cervical and intrathoracic anastomosis using gastric conduit. We collected daily drain amylase levels and obtained postoperative barium esophagrams routinely. Receiver operating characteristic analysis was performed to evaluate the ability of drain amylase to detect anastomotic leaks and to determine the sensitivity and specificity at various cutoff values. RESULTS There were no in-hospital or outpatient deaths within 30 days of operation in this consecutive series of patients. A leak occurred in 22 of 146 esophagectomy patients (15%) that required postoperative intervention. An additional 13 patients (9%) had a leak requiring only alteration of diet or antibiotics. The sensitivity and specificity for barium esophagram was 36.9% and 95%, respectively. For drain amylase obtained on postoperative day 4, a cutoff of 38 IU/L yielded a sensitivity of 100% and a specificity of 52.0%, and a cutoff of 250 IU/L yielded a sensitivity of 66.7% and a specificity of 95.9% in detecting leaks eventually requiring intervention. CONCLUSIONS Drain amylase levels recorded on day 4 after esophagectomy are more accurate for the detection of esophageal anastomotic leak than barium esophagram. Drain amylase levels represent a noninvasive test that may facilitate safe, early discharge after esophagectomy.

Seven-year disease-free survival after radical pneumonectomy for a pulmonary artery sarcoma

FIGURE 1. Postneoadjuvant chemotherapy computed tomography scan showing a persistent right hilar mass approximately 3 cm in diameter, which had shrunk from a preoperative measurement of 11 cm in diameter. A 50-year-old woman without significant medical history presentedwith fatigue, fever, and shortness of breath. She underwent a pulmonary embolus protocol chest computed tomography in January of 2004 that showed filling defects of the proximal right pulmonary artery and an 11-cm right hilar mass.Anendobronchial ultrasound–guidedbiopsy revealed a diagnosis ofmixed spindle cell and epithelioid cell neoplasm. She was treated with a standard ifosfamide doxorubicin neoadjuvant regimen, receiving ifosfamide 2500 mg/m on days 1 to 3 for each of 6 cycles, togetherwith 25mg/m doxorubicin on days 1 to 3 for each of 4 cycles, and then 20mg/m doxorubicin on days 1 to 3 for cycles 5 and 6, with a marked response. She underwent exploratory thoracotomy at an outside hospital where invasion of the atrium was noted, and the patient was closed without resection. On arrival at our institution in September 2004 she had a chest computed tomography (Figure 1) and a positron emission tomography scan that only showed activity in the right hilum. Pulmonary function tests showed a forced expiratory volume in the first second of expiration of 2.24 (89% predicted). A cardiac magnetic resonance image showed thickening of the left atrial wall, but did not suggest involvement of the interatrial septum. In October 2004 she underwent a sternotomy. The right pulmonary artery was divided with a stapler just lateral to the superior vena cava (SVC). On bypass, the heart was arrested, the left atrium was opened, and a cuff of left atrium was resected en bloc with primary closure of the left atrium. The bronchus was stapled and divided at its takeoff from the carina. Intraoperative frozen section returned positive on the pulmonary artery, and negative on the bronchus and atrium. The right pulmonary artery was dissected behind the SVC and aorta to its origin off the main pulmonary artery. A portion of

Covered stents for the treatment of life-threatening cervical esophageal anastomotic leaks

Esophagectomy with a cervical anastomosis is associated with a leak rate of approximately 10% to 20%. These leaks are usually managed by drainage and are allowed to heal over several days to weeks. Rarely, a cervical anastomotic leak may drain into the chest and cause a life-threatening infection. In such instances, repair of the leak is often not possible, and takedown of the gastric conduit is necessary. After several weeks tomonths of recovery, reoperation is required to restore gastrointestinal continuity. Restoration of gastrointestinal continuity generally requires a major reoperation rerouting the gastric conduit through the left side of the chest or use of a colon interposition. We describe the use of a temporary fully covered silastic expandable metallic esophageal stent to treat cervical leaks that otherwise would have required takedown of the conduit.

An integrated segmentation and shape-based classification scheme for distinguishing adenocarcinomas from granulomas on lung CT

Purpose Distinguishing between benign granulmoas and adenocarcinomas is confounded by their similar visual appearance on routine CT scans. Unfortunately, owing to the inability to discriminate these lesions radigraphically, many patients with benign granulomas are subjected to unnecessary surgical wedge resections and biopsies for pathologic confirmation of cancer presence or absence. This suggests the need for improved computerized characterization of these nodules in order to distinguish between these two classes of lesions on CT scans. While there has been substantial interest in the use of textural analysis for radiomic characterization of lung nodules, relatively less work has been done in shape based characterization of lung nodules, particularly with respect to granulmoas and adenocarcinomas. The primary goal of this study is to evaluate the role of 3D shape features for discrimination of benign granulomas from malignant adenocarcinomas on lung CT images. Towards this end we present an integrated framework for segmentation, feature characterization and classification of these nodules on CT. Methods The nodule segmentation method starts with separation of lung regions from the surrounding lung anatomy. Next, the lung CT scans are projected into and represented in a three dimensional spectral embedding (SE) space, allowing for better determination of the boundaries of the nodule. This then enables the application of a gradient vector flow active contour (SEGvAC) model for nodule boundary extraction. A set of 24 shape features from both 2D slices and 3D surface of the segmented nodules are extracted, including features pertaining to the angularity, spiculation, elongation and nodule compactness. A feature selection scheme, PCA‐VIP, is employed to identify the most discriminating set of features to distinguish granulmoas from adenocarcinomas within a learning set of 82 patients. The features thus identified were then combined with a support vector machine classifier and independently validated on a distinct test set comprising 67 patients. The performance of the classifier for both of the training and validation cohorts was evaluated by the area under receiver characteristic curve (ROC). Results We used 82 and 67 studies from two different institutions respectively for training and independent validation of the model and the shape features. The Dice coefficient between automatically segmented nodules by SEGvAC and the manual delineations by expert radiologists (readers) was 0.84± 0.04 whereas inter‐reader segmentation agreement was 0.79± 0.12. We also identified a set of consistent features (Roughness, Convexity and Spherecity) that were found to be strongly correlated across both manual and automated nodule segmentations (R > 0.80, p < 0.0001) and capture the marginal smoothness and 3D compactness of the nodules. On the independent validation set of 67 studies our classifier yielded a ROC AUC of 0.72 and 0.64 for manually‐ and automatically segmented nodules respectively. On a subset of 20 studies, the AUCs for the two expert radiologists and 1 pulmonologist were found to be 0.82, 0.68 and 0.58 respectively. Conclusions The major finding of this study was that certain shape features appear to differentially express between granulomas and adenocarcinomas and thus computer extracted shape cues could be used to distinguish these radiographically similar pathologies.