Mark Hennon

Temporal trends in outcomes following sublobar and lobar resections for small (≤ 2 cm) non-small cell lung cancers--a Surveillance Epidemiology End Results database analysis.

BACKGROUND Since the randomized, controlled study that favored lobectomy for resection of stage I non-small cell lung cancers (NSCLCs) by the Lung Cancer Study Group, there have been improvements in staging. The liberal use of computed tomography also may have altered the types of early lung cancer diagnosed. Studies published since then have drawn contradictory conclusions on the benefit of lobectomy over sublobar resections for early-stage NSCLC. We examined the Surveillance Epidemiology End Results database to test our hypothesis that the relationship between extent of resection and outcome has changed since the Lung Cancer Study Group study was published. METHODS We examined stage I NSCLCs ≤ 2 cm in size over three periods: 1988-1998 (Early), 1999-2004 (Intermediate), and 2005-2008 (Late). For each period, we assessed overall and disease-specific survivals and their associations with the extents of resection, by univariate and multivariate analyses. Sublobar resections in the Early group could not be categorized into segmentectomies and wedge resections because these were not coded separately. RESULTS The proportion of NSCLCs ≤ 2 cm increased from 0.98% in 1988 to 2.2% in 2008. Multivariate analyses showed that sublobar resection was inferior to lobectomy in the Early period (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.21-1.65). This effect decreased in the Intermediate period, in which segmentectomies but not wedge resections were equivalent to lobectomies (wedge versus lobectomy HR, 1.19; 95% CI, 1.01-1.41; segmentectomy versus lobectomy HR, 1.04; 95% CI, 0.8-1.36). The difference disappeared in the Late period, when both wedge resections and segmentectomies were equivalent to lobectomy (wedge versus lobectomy HR, 1.09; 95% CI, 0.79-1.5; segmentectomy versus lobectomy HR, 0.83; 95% CI, 0.47-1.45). Trends for both overall survival and disease-specific survival were identical. CONCLUSIONS The survival benefit of lobectomy over sublobar resection decreased over the past 2 decades with no discernible difference in the most contemporary cases. These results support reevaluation of lobectomy as the standard of care for small (≤ 2-cm) NSCLCs.

Video-assisted thoracoscopic surgery (VATS) for locally advanced lung cancer.

Initial fears regarding the oncologic equivalence of the thoracoscopic and open techniques for resecting NSCLC have not been realized. Reported data to date indicate that even in advanced NSCLC requiring pneumonectomy, the overall and disease free survival are equivalent for patients undergoing VATS versus thoracotomy. Furthermore, these results have occurred during a time where the complex procedures are still in a relatively early stage of refinement and we sense that results will improve as we make adjustments to speed the operations and further reduce conversions and complications. VATS lobectomy for early stage disease produces oncologically similar results with open techniques, and long term studies will determine if the same hold true for more advanced case. Early indications are favorable. This finding is in accordance with others who have hypothesized that the reduced inflammatory response associated with thoracoscopy may be associated with equivalent or even improved long-term survival (22,23). VATS lobectomy, pneumonectomy, and chest wall resection for advanced lung cancer can be performed safely with an acceptable mortality rate. VATS offers the benefit of increased tolerance for adjuvant therapy so if high VATS reliability is achieved, it may be reasonable someday to consider resection first for some patients who currently undergo induction chemoradiotherapy for their disease. The low morbidity of VATS reported for early stage lung carcinoma, though not definitively proven for advanced stage NSCLC, will be expected as experience builds. Further analyses of outcomes for thoracoscopic resection of advanced stage disease are ongoing. This is particularly important given the large number of frail patients with advanced stage disease who require multimodality therapy, which can be difficult to tolerate. Conversions, though increased in frequency, are not associated with a significant change in short-term or long-term outcomes. Continued improvements in instrument technology and surgical technique will only continue to expand the possibilities for minimally invasive pulmonary resections, as well as those for primary chest wall tumors.

Thoracoscopic pneumonectomy: an 11-year experience.

BACKGROUND It is unclear whether thoracoscopic (video-assisted thoracoscopic surgery [VATS]) pneumonectomy improves outcomes compared with open approaches. METHODS One hundred seven consecutive pneumonectomies performed at an experienced center from January 2002 to December 2012 were studied retrospectively. Forty cases were open, and 50 successful VATS and 17 conversions were combined (intent-to-treat [ITT] analysis). RESULTS The VATS cohort had more preoperative comorbidities (three vs two, P = .003), women (57% vs 30%, P = .009), and older ages (65 years vs 63 years, P = .07). Although advanced clinical stage was less for VATS (26% vs 50% stage III, P = .035), final pathologic staging was similar (25% vs 38%, P = .77). Pursuing a VATS approach yielded similar complications (two vs two, median, P = .73) with no catastrophic intraoperative events like bleeding. Successful VATS pneumonectomy rates rose from 50%-82% by the second half of the series (P < .001). Completion pneumonectomy cases (13.4% VATS, 7.5% open) had similar outcomes. Having similar initial discomforts as patients undergoing open surgery, more patients undergoing VATS were pain-free at 1 year (53% vs 19%, P = .03). Conversions resulted in longer ICU stays (4 days vs 2 days, P = .01). Advanced clinical stage (III-IV) ITT VATS had longer median overall survival (OS) (42 months vs 13 months, log-rank P = .042). Successful VATS cases with early pathologic stage (0-II) had a median OS of 80 vs 16 months for converted and 28 months for open (log rank = 0.083). CONCLUSIONS Attempting thoracoscopic pneumonectomy at an experienced center appears safe but does not yield the early pain/complication reductions observed for VATS lobectomy. There may be long-term pain/survival advantages for certain stages that warrant further study and refinement of this approach.

Thoracoscopic maneuvers for chest wall resection and reconstruction

OBJECTIVE The aim of this report is to describe technical maneuvers used to complete minimally invasive resections of the chest wall successfully. METHODS Case videos of advanced thoracoscopic chest wall resections performed at a comprehensive cancer center were reviewed, as were published reports. These were analyzed for similarities and also categorized to summarize alternative approaches. RESULTS Limited chest wall resections en bloc with lobectomy can be accomplished with port placement similar to that used for typical thoracoscopic anatomic resections, particularly when the utility incision is close to the region of excision. Generally, chest wall resection precedes lobectomy. Ribs can be transected with Gigli saws, endoscopic shears, or high-speed drills. Division of bone and overlying soft tissue can be planned precisely using thoracoscopic guidance. Isolated primary chest wall masses may require different port position and selective reconstruction using synthetic materials. Patch anchoring can be accomplished by devices that facilitate laparoscopic port site fascial closure. CONCLUSIONS Thoracoscopic chest wall resections have been accomplished safely using tools and maneuvers summarized here. Further outcomes research is necessary to identify the benefits of thoracoscopic chest wall resection over an open approach.

Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: Correlation with vascular endothelial growth factor expression

OBJECTIVES Lymph node staging provides critical information in patients with non-small cell lung cancer (NSCLC). Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with vascular endothelial growth factors (VEGFs) A, C, and D as well as VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes. METHODS Forty patients with NSCLC underwent preoperative positron emission tomography-computed tomography and mediastinoscopy. Real-time polymerase chain reaction (RT-PCR) assays for messenger RNA expression of epithelial markers (ie, cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; and palate, lung, and nasal epithelium carcinoma-associated protein) were performed in selected fluorodeoxyglucose-avid lymph nodes. VEGF-A, VEGF-C, VEGF-D, and VEGF receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the lymph nodes. RESULTS RT-PCR for cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; or palate, lung, and nasal epithelium carcinoma-associated protein indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A, VEGF-C, VEGF-D, or VEGF receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months. CONCLUSIONS RT-PCR analysis of fluorodeoxyglucose-avid lymph nodes results in up-staging a patients cancer. Micrometastases correlate with the expression of VEGF in lymph nodes in patients with NSCLC. This may reflect the role of lymphangiogenesis in promoting metastases.

Advances in lung cancer surgery

The last few years have witnessed an explosion of the use of minimally invasive techniques for the detection, diagnosis, and treatment of all stages of lung Cancer. The use of these techniques has improved the risk-benefit ratio of surgery and has made it more acceptable to patients considering lung surgery. They have also facilitated the delivery of multi-modality therapy to patients with advanced lung cancer. This review article summarizes current surgical techniques that represent the “cutting edge” of thoracic surgery for lung cancer.

Implementation of an Acuity Adaptable Patient Care Unit is associated with improved outcomes after major pulmonary resections.

BACKGROUND Many centers have adapted an Acuity Adaptable Cardiothoracic Unit (AACU) to fast track cardiac surgery patients, yet few data exist on the impact of such a unit on general thoracic surgery outcomes. We examined the effects of implementing an Acuity Adaptable Cardiothoracic Unit on patients undergoing major pulmonary resections. METHODS We reviewed data from an IRB-approved, prospective thoracic surgery database for patients during the 3-y periods pre- and post-adoption of an Acuity Adaptable Cardiothoracic Unit. As surrogate endpoints to quality and cost, we examined length of stay, place of discharge, readmission rate, and 30-d mortality during these two time periods. RESULTS A total of 488 patients underwent major pulmonary resections (416 lobectomies, 72 pneumonectomies) in this 6-y time period. Patients cared for in the AACU model had a shorter length of stay (LOS) compared with patients in a traditional ICU/general care model. The mean and median LOS for patients in the AACU model was 4.2 ± 0.3 d and 3 d, and for the traditional ICU/general care model these were 7.8 ± 1.2 d and 5 d, respectively (P < 0.001). Relative risk of readmission was 0.86 (95% CI = 0.45, 1.66, P = 0.392) and 30-d mortality was 0.49 (95% CI = 0.14, 1.68, P = 0.205) for patients in the AACU model compared with patients in the traditional ICU/general care unit. CONCLUSIONS Implementation of an Acuity Adaptable Cardiothoracic Unit is associated with reduced length of hospital stay in patients undergoing major lung resections, without increased risk of readmission or 30-d mortality. Future studies will evaluate post-operative events unique to an AACU model.

Thoracoscopic resection and re-resection of an anterior chest wall chondrosarcoma.

The limits of thoracoscopic resections are expanding, with improved instruments for manipulating and dividing tissues such as the bone. We encountered a patient with a primary chest wall tumor that had exposure characteristics similar to our limited, but promising, experience with en bloc rib resections for primary lung cancer. A 71-year-old female patient presented with a symptomatic right meningocele, at which time a 7.7-cm left anterior mediastinal mass bulging through the second interspace was detected. With the patient in the lateral decubitus position, a modified three-incision approach similar to that for a video-assisted thorascopic surgery (VATS) lobectomy was performed but angled slightly different to expose the anterior chest wall. Using this approach, the mass was excised intact en bloc, with ribs 2 and 3 (9.5-cm total specimen with 6-cm longest rib). No chest wall reconstruction was necessary. The patient did well and had her chest tube removed on postoperative day (POD) 1, was discharged with minimal pain on POD 3, and was pain free on POD 14. Because a microscopic focus of chondrosarcoma was found at the second rib intramedullary margin on the final pathologic review, she returned for VATS re-resection of an additional 5 cm of rib on POD 43 using the same incisions, and her postoperative recovery was replicated. The operative times were 160 and 90 minutes, and blood loss was 400 and 100 mL, respectively. This case demonstrates that if traditional surgical values of exposure and oncologic safety can be replicated using enhanced instrumentation, it is reasonable to attempt more complex operations thoracoscopically. Even though ribs were removed, pain control was similar to other VATS operations.

Impact of the Number of Lymph Nodes Examined on the Survival of Patients with Stage I Non-Small Cell Lung Cancer Undergoing Sublobar Resection

Objectives: Early stage lung cancer is being detected at a higher frequency with the implementation of screening programs. At the same time, medically complex patients with multiple comorbidities are presenting for surgery, with a concomitant rise in rates of sublobar resection. We sought to examine the effect of sampling lymph nodes on the outcomes of patients who undergo sublobar resection for small (<2 cm) stage I non–small cell lung cancer (NSCLC). Methods: All patients in the Surveillance, Epidemiology, and End Results database from 2004 to 2013 with small (<2 cm) stage I NSCLC who underwent sublobar resection (wedge/segmentectomy) and no other cancer history were included. The association of the number of lymph nodes examined (LNE; categories none, 1‐3, 4‐6, 7‐9, >9) with the overall survival as well as disease‐specific survival were examined using univariate as well as multivariate analyses while controlling for covariates such as age, size (<1 cm, >1 cm), grade, histology (adenocarcinoma vs others), and extent of resection (wedge/segmentectomy). Results: Data from 3916 eligible patients were analyzed. Seven hundred fifteen patients (18.3%) had segmentectomy. No lymph nodes were examined in 49% and 23% of wedge resection and segmentectomy patients, respectively. Among all eligible patients, 1132 (29%), 474 (12%), 228 (6%), and 328 (8%) patients had 1 to 3, 4 to 6, 7 to 9 and >9 LNE, respectively. Univariate analyses showed significant associations between overall and disease‐specific survivals with age, grade, histology, sex, extent of surgery, and LNE. The association between the number of LNE and survival remained significant even after adjusting for significant covariates including extent of sublobar resection (hazard ratio for groups with LNE 1‐3, 4‐6, 7‐9, and >9 compared with 0 LNE were 0.79, 0.77, 0.68, and 0.45 for overall survival; P < .001) and 0.85, 0.77, 0.71, and 0.44 for disease‐specific survival (P < .05), respectively. In multivariate modeling, LNE was retained as a significant variable and extent of resection was not. In patients in whom at least 1 lymph node was examined, extent of resection was not predictive of outcome. Conclusions: Many patients having sublobar resection for early stage NSCLC in the United States do not have a single lymph node removed for pathologic examination. The number of LNE is associated with improved survival, presumably due to avoidance of mis‐staging. This association seems greater than the association with extent of resection (segmentectomy vs wedge resection). Appropriate lymph node examination remains an important part of resection for lung cancer even if the resection is sublobar.

Clinical characteristics of adenosquamous esophageal carcinoma

BACKGROUND Current published information of adenosquamous carcinoma (ASC) of the esophagus in the United States is limited to isolated case reports. We sought to study the clinical characteristics of this tumor using the Surveillance, Epidemiology and End Results (SEER) database. METHODS Relevant data of all patients with esophageal cancer in the SEER database diagnosed from 1998-2010 was obtained. Demographic, grade, stage, treatment and survival characteristics of patients with ASC were summarized and compared to those patients with adenocarcinoma (ACA) and squamous cell carcinoma (SqCC). Univariate analyses across comparison groups were performed using Wilcoxon rank sum test for continuous covariates and the Pearson Chi-square test for categorical covariates. To evaluate the association of selected covariates to survival by histology, unadjusted and adjusted proportional hazards models were generated for the entire study population. To further control for the difference in covariates among the histology groups, propensity weighted Cox regression modeling was performed using the inverse propensity to treat weighting (IPTW) approach. RESULTS Of 29,890 patients with the histological subgroups, only 284 patients had ASC (1%). Patients with ACA had a higher grade (72.9% with grade III/IV) and presented with advanced stage (48.2% distant disease) than their comparison group. Patients with ASC had worse overall survival compared to ACA but not SqCC in both univariate and multivariate analyses (OR =0.76; P<0.05 and OR =0.86; P<0.05 respectively). These results were further confirmed by the propensity weighted Cox regression analysis. Analysis of the ASC population alone demonstrated that decreasing stage, radiation therapy (OR =0.59; P<0.001) and surgery (OR =0.86; P<0.001) were associated with better overall survival, but grade was not. CONCLUSIONS ASC of the esophagus is a rare histological variant comprising 1% of esophageal ACA in the Unites States. This histological subtype presents in later stages, at a higher grade and portends a poorer survival than the more common ACA. Radiation therapy and surgical resection of appropriate stage patients provide the best chance of survival.