Sidhu P. Gangadharan

Electromagnetic Navigation Bronchoscopy-Guided Fiducial Placement for Robotic Stereotactic Radiosurgery of Lung Tumors: A Feasibility Study

BACKGROUND Stereotactic radiosurgery (Cyberknife; Accuray Incorporated; Sunnyvale, CA) is a treatment option for patients who are medically unfit to undergo lung tumor resection. For precise tumor ablation, the Cyberknife requires fiducial marker placement in or near the target tumor. Fiducial placement under transthoracic CT guidance is associated with a high risk of iatrogenic pneumothorax. Electromagnetic navigation bronchoscopy (ENB) may offer a less morbid alternative to accurately deploy fiducials to bronchoscopically invisible peripheral lung lesions. OBJECTIVE Open-label, feasibility study to assess fiducial placement in peripheral lung tumors by ENB. METHOD Consecutive patients with peripheral lung tumors and who were evaluated to be nonsurgical candidates underwent fiducial placement under ENB. This procedure was considered successful if fiducials were placed in or near the tumors and remained in place without migration for radiosurgery to proceed. The need for alternative or additional intrathoracic fiducial placement was documented as procedure failure. RESULTS A total of 39 fiducials markers were successfully deployed in eight of nine patients (89%). Of these eight successful cases, seven had fiducials placed directly within the tumor (88%). At Cyberknife planning, 7 to 10 days after fiducial placement, 35 of 39 fiducial markers (90%) were still in place and were adequate to allow radiosurgery to proceed. No immediate bronchoscopic complications were observed. One patient had a COPD exacerbation. Another patient returned within 1 day with transient, self-limiting fever. CONCLUSIONS ENB can be used to deploy fiducial markers for Cyberknife radiosurgery of lung tumors safely and accurately without the complications associated with transthoracic placement.

Open, Video-Assisted Thoracic Surgery, and Robotic Lobectomy: Review of a National Database

BACKGROUND To date, reports on outcomes after robotic-assisted pulmonary resection have been confined to small, single-institution case series. Furthermore, no comparison has been made between robotic, open, and video-assisted thoracic surgery (VATS) procedures. We sought to compare the outcomes between these approaches using the State Inpatient Databases (SID). METHODS Using the 2008 to 2010 SID, we identified patients who underwent an open, VATS, or robotic lobectomy from 8 states. Patients who underwent segmentectomy were also included. A comparison of outcomes was performed using a propensity-matched analysis. RESULTS We identified a total of 33,095 patients (open: 20,238; VATS: 12,427; robotic: 430). Case volumes for robotic resections increased over the study period from 0.2% in 2008 to 3.4% in 2010. Robotic resections were performed in all 8 states, and 38% were conducted in a community hospital. In propensity-matched analysis, robotic resections were associated with significant reductions in mortality (0.2% vs 2.0%, p = 0.016), length of stay (5.9 vs 8.2 days, p < 0.0001), and overall complication rates (43.8% vs 54.1%, p = 0.003) when compared with open thoracotomy. Robotic resection was also associated with reductions in mortality (0.2% vs 1.1%, p = 0.12), length of stay (5.9 days vs 6.3 days, p = 0.45), and overall complication rates (43.8% vs 45.3%, p = 0.68) when compared with VATS; however, none of these differences were statistically significant. CONCLUSIONS Case volume for robotic pulmonary resections has increased significantly during the study period, and thoracic surgeons have been able to adopt the robotic approach safely. Robotic resection appears to be an appropriate alternative to VATS and is associated with improved outcomes compared with open thoracotomy.

ORIGINAL RESEARCHINTERVENTIONAL PULMONOLOGYElectromagnetic Navigation Bronchoscopy-Guided Fiducial Placement for Robotic Stereotactic Radiosurgery of Lung Tumors: A Feasibility Study

BACKGROUND Stereotactic radiosurgery (Cyberknife; Accuray Incorporated; Sunnyvale, CA) is a treatment option for patients who are medically unfit to undergo lung tumor resection. For precise tumor ablation, the Cyberknife requires fiducial marker placement in or near the target tumor. Fiducial placement under transthoracic CT guidance is associated with a high risk of iatrogenic pneumothorax. Electromagnetic navigation bronchoscopy (ENB) may offer a less morbid alternative to accurately deploy fiducials to bronchoscopically invisible peripheral lung lesions. OBJECTIVE Open-label, feasibility study to assess fiducial placement in peripheral lung tumors by ENB. METHOD Consecutive patients with peripheral lung tumors and who were evaluated to be nonsurgical candidates underwent fiducial placement under ENB. This procedure was considered successful if fiducials were placed in or near the tumors and remained in place without migration for radiosurgery to proceed. The need for alternative or additional intrathoracic fiducial placement was documented as procedure failure. RESULTS A total of 39 fiducials markers were successfully deployed in eight of nine patients (89%). Of these eight successful cases, seven had fiducials placed directly within the tumor (88%). At Cyberknife planning, 7 to 10 days after fiducial placement, 35 of 39 fiducial markers (90%) were still in place and were adequate to allow radiosurgery to proceed. No immediate bronchoscopic complications were observed. One patient had a COPD exacerbation. Another patient returned within 1 day with transient, self-limiting fever. CONCLUSIONS ENB can be used to deploy fiducial markers for Cyberknife radiosurgery of lung tumors safely and accurately without the complications associated with transthoracic placement.

Tracheobronchoplasty for Severe Tracheobronchomalacia: A Prospective Outcome Analysis

RATIONALE Central airway stabilization with silicone stents can improve respiratory symptoms in patients with severe symptomatic tracheobronchomalacia (TBM) but is associated with a relatively high rate of complications. Surgery with posterior tracheobronchial splinting using a polypropylene mesh has also been used for this condition but to date has not been evaluated prospectively and objectively for patient outcomes. OBJECTIVES To evaluate the effect of surgical tracheobronchoplasty on symptoms, functional status, quality of life, lung function, and exercise capacity in patients with severe and symptomatic TBM. METHODS A prospective observational study in which baseline measurements were compared to those obtained 3 months after surgical tracheobronchoplasty. MEASUREMENTS AND MAIN RESULTS Of 104 referred patients to our complex airway center for severe TBM, 77 had baseline measurements. Of this group, 57 patients had severe malacia and underwent stent placement for central airway stabilization. Of those, 37 patients reported improvement in respiratory symptoms and 35 were considered for surgical tracheobronchoplasty. Two patients were excluded from surgery for medical reasons. Median age was 61 years (range, 39 to 83 years), 20 patients were men, 11 patients (31%) had COPD, 9 patients (26%) had asthma, and 4 patients (11%) had Mounier-Kuhn syndrome. Thirty-three patients (94%) presented with severe dyspnea, 26 patients (74%) with uncontrollable cough, and 18 patients (51%) reported recurrent pulmonary infections. Two patients (3%) presented with respiratory failure requiring mechanical ventilation. After surgery, quality of life scores improved in 25 of 31 patients (p < 0.0001), dyspnea scores improved in 19 of 26 patients (p = 0.007), functional status scores improved in 20 of 31 patients (p = 0.003), and mean exercise capacity improved in 10 patients (p = 0.012). CONCLUSIONS In experienced hands, surgical central airway stabilization with posterior tracheobronchial splinting using a polypropylene mesh improves respiratory symptoms, health-related quality of life, and functional status in highly selected patients with severe symptomatic TBM.

Impact of the Surgical Technique on Pulmonary Morbidity After Esophagectomy

BACKGROUND Pulmonary complications occur frequently after esophagectomy. Although multifactorial, these complications could be influenced by surgical technique. We sought to compare the respiratory complications of patients undergoing esophagectomy through different approaches, and identify technical risk factors. METHODS We conducted a retrospective analysis of consecutive esophagectomies performed at 2 institutions from January 2002 to January 2009. Primary outcome measures included postoperative ventilatory requirements, pneumonia, effusion requiring intervention, length of stay, and mortality. RESULTS A total of 220 esophagectomies were performed through 6 different approaches: 79 minimally invasive (MIE) with neck anastomosis, 20 MIE with chest anastomosis, 37 transhiatal, 33 McKeown, 36 Ivor Lewis, and 15 left thoracoabdominal. Patients who underwent MIE were more likely to be extubated in the operating room (p<0.01) and had fewer pleural effusions (p<0.01). A thoracotomy was associated with a higher incidence of tracheostomy (p=0.02) and pleural effusions (p=0.02). Neck anastomoses were negatively associated with early extubation (p=0.04) and predicted recurrent laryngeal nerve injury (p=0.04), but were not associated with pneumonia or other pulmonary complications. Multivariate analysis showed that pneumonia was independently associated with advancing age (p=0.02), lack of a pyloric drainage procedure (p=0.03), and less significantly with MIE (p=0.06, fewer events). Surgical approach was not a significant predictor of length of stay or mortality. CONCLUSIONS Patients undergoing MIE are less likely to remain intubated. Omission of a pyloric drainage procedure or performance of thoracic or neck incisions appear to be important determinants of respiratory complications. Technical aspects of the procedure in addition to the surgical approach influence important respiratory outcomes.

Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer

INTRODUCTION Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. METHODS Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. RESULTS From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). CONCLUSIONS Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.

Standard Uptake Value Predicts Survival in Non–Small Cell Lung Cancer

BACKGROUND Integrated [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan is a widely used modality in the evaluation of lung cancer. Our goal was to determine the ability of the standard uptake value (SUV) of the primary tumor (SUV-T) and regional lymph nodes (SUV-N) to predict survival. METHODS From January 2005 through June 2007, 584 consecutive patients undergoing integrated PET-CT scan for suspected lung cancer were studied. Results of integrated PET-CT scans, including the maximum SUV-T and SUV-N, were recorded. A patient was defined as having a positive PET scan if the maximum SUV (T or N) was greater than 2.5. Overall survival was documented from clinical records and the Social Security Death Index. Cox regression analysis was used to evaluate the correlation between SUV and survival. RESULTS Among patients with a positive PET scan (n = 329), both SUV-T and SUV-N were predictors of survival. As maximum SUV of the primary mass increased, survival decreased (hazard ratio, 1.05; p < 0.001). As maximum SUV of locoregional lymph nodes increased, survival also decreased (hazard ratio, 1.06; p < 0.001). Furthermore, among patients with no mediastinal disease identified by PET-CT scan, increased SUV-T continued to predict poor survival (hazard ratio, 1.06; p = 0.001). CONCLUSIONS Local and regional maximum SUVs defined by integrated PET-CT scanning have a strong correlation with survival in patients with non-small cell lung cancer. An elevated SUV is known preoperatively and may assist clinicians in stratifying patients at increased overall risk preoperatively.

Smoking status and self-reported race affect the frequency of clinically relevant oncogenic alterations in non-small-cell lung cancers at a United States-based academic medical practice

INTRODUCTION The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient-tumor sample pairs. METHODS Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient-tumor samples. RESULTS Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. CONCLUSIONS The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC.

Central Airway Stabilization for Tracheobronchomalacia Improves Quality of Life in Patients With COPD

BACKGROUND Tracheobronchomalacia (TBM) is characterized by excessive collapsibility of the central airways, typically during expiration. TBM may be present in as many as 50% of patients evaluated for COPD. The impact of central airway stabilization on symptom pattern and quality of life is poorly understood in this patient population. METHODS Patients with documented COPD were identified from a cohort of 238 patients assessed for TBM at our complex airway referral center. Pulmonary function testing, exercise tolerance, and health-related quality-of-life (HRQOL) measures were assessed at baseline and 2 to 4 weeks following tracheal stent placement/operative tracheobronchoplasty (TBP). Severity of COPD was classified according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) staging system. RESULTS One hundred three patients (48 women) with COPD and moderately severe to severe TBM were identified. Statistically and clinically significant improvements were seen in HRQOL measures, including the transitional dyspnea index (stent, P = .001; TBP, P = .008), the St. George Respiratory Questionnaire (stent, P = .002; TBP, P < .0001), and the Karnofsky performance score (stent, P = .163; TBP, P < .0001). The improvement appeared greatest following TBP and was seen in all GOLD stages. Clinical improvement was also seen in measured FEV(1) and exercise capacity as assessed by 6-min walk test. CONCLUSIONS Central airway stabilization may provide symptomatic benefit for patients with severe COPD and concomitant severe airway malacia. Operative airway stabilization appears to impart the greatest advantage. Long-term follow-up study is needed to fully ascertain the ultimate efficacy of both stenting and surgical airway stabilization in this patient group.

Design and characterization of an optimized simultaneous color and near-infrared fluorescence rigid endoscopic imaging system

Abstract. We report the design, characterization, and validation of an optimized simultaneous color and near-infrared (NIR) fluorescence rigid endoscopic imaging system for minimally invasive surgery. This system is optimized for illumination and collection of NIR wavelengths allowing the simultaneous acquisition of both color and NIR fluorescence at frame rates higher than 6.8 fps with high sensitivity. The system employs a custom 10-mm diameter rigid endoscope optimized for NIR transmission. A dual-channel light source compatible with the constraints of an endoscope was built and includes a plasma source for white light illumination and NIR laser diodes for fluorescence excitation. A prism-based 2-CCD camera was customized for simultaneous color and NIR detection with a highly efficient filtration scheme for fluorescence imaging of both 700- and 800-nm emission dyes. The performance characterization studies indicate that the endoscope can efficiently detect fluorescence signal from both indocyanine green and methylene blue in dimethyl sulfoxide at the concentrations of 100 to 185 nM depending on the background optical properties. Finally, we performed the validation of this imaging system in vivo during a minimally invasive procedure for thoracic sentinel lymph node mapping in a porcine model.