Description of an activity-based enzyme biosensor for lung cancer detection.

BACKGROUND: Lung cancer is associated with the greatest cancer mortality as it typically presents with incurable distributed disease. Biomarkers relevant to risk assessment for the detection of lung cancer continue to be a challenge because they are often not detectable during the asymptomatic curable stage of the disease. A solution to population-scale testing for lung cancer will require a combination of performance, scalability, cost-effectiveness, and simplicity. METHODS: One solution is to measure the activity of serum available enzymes that contribute to the transformation process rather than counting biomarkers. Protease enzymes modify the environment during tumor growth and present an attractive target for detection. An activity based sensor platform sensitive to active protease enzymes is presented. A panel of 18 sensors was used to measure 750 sera samples from participants at increased risk for lung cancer with or without the disease. RESULTS: A machine learning approach is applied to generate algorithms that detect 90% of cancer patients overall with a specificity of 82% including 90% sensitivity in Stage I when disease intervention is most effective and detection more challenging. CONCLUSION: This approach is promising as a scalable, clinically useful platform to help detect patients who have lung cancer using a simple blood sample. The performance and cost profile is being pursued in studies as a platform for population wide screening.

Lung cancer is responsible for more deaths worldwide than all other cancers. It is often detected with the appearance of symptoms when treatment is limited and outcomes for the patient are much worse. While imaging chest scans can detect disease, they are poorly used even in the United States where it is an approved screening method. When cancer is present, protease enzymes are responsible for making space and modifying the lung tissue for the growing tumor. This report describes a panel of 18 sensors that release a fluorescent signal when these enzymes are present in a blood sample. The signal acts like a fingerprint of activity that can be used to identify people with lung cancer. This sensor platform can detect patients with curable lung cancer and could provide a platform for screening very large populations of at-risk individuals.

A phase II study of perioperative pembrolizumab plus mFOLFOX in patients with potentially resectable esophagus, gastroesophageal junction (GEJ), and stomach adenocarcinoma.

BACKGROUND: Perioperative chemotherapy/chemoradiation is standard in esophageal/gastric/gastroesophageal junction (GEJ) adenocarcinoma, immune checkpoint inhibitors (ICI) effect in setting of metastatic and postoperatively. This study is to assess ICI + chemotherapy perioperatively. METHODS: Patients with locally advanced (T1N1-3M0 or T2-3NanyM0) potentially resectable esophageal/gastric/GEJ adenocarcinoma by PET/EUS/CT and staging-laparoscopy, were treated preoperative 4 cycles mFOLFOX6 (Oxaliplatin 85 mg/m2 /Leucovorin 400 mg/m2 /5-FU bolus 400 mg/m2 then infusion 2400 mg/m2 for 46 h q2weeks) and 3 cycles pembrolizumab (200 mg q3week). Those without distal disease post-neoadjuvant and eligible for resection underwent surgery. Postoperative treatment was initiated at 4-8 weeks with 4 cycles mFOLFOX and 12 cycles pembrolizumab. The primary objective is pathological response (ypRR with tumor regression score, TRS ≤2). The expression of ICI-related markers PD-L1 (CPS), CD8, and CD20 were analyzed before and after preoperative therapy. RESULTS: Thirty-seven patients completed the preoperative treatment. Twenty-nine patients had curative R0 resection. 6/29 (21%; 95% CI: 0.08-0.40) achieved ypCR with TRS 0 in resected patients. 26/29 (90%; 95% CI: 0.73-0.98) had ypRR with TRS ≤2. Twenty-six patients finished adjuvant therapy with a median 36.3-month follow-up. Three patients had recurrence/metastatic disease (at 9-, 10-, 22 months enrollment) with one dead at 23 months, and two are still alive at 28 and 36.5 months. The remaining (23/26) are free of disease with 3 years DFS of 88.5% and 3 years OS of 92.3%. There were no unexpected toxicities. Preoperative ICI + chemotherapy enhanced immune responses significantly with increasing expression of PD-L1 (CPS ≥10, p = 0.0078) and CD8 (>5%, p = 0.0059). CONCLUSIONS: The perioperative pembrolizumab and mFOLFOX combination in resectable esophageal/gastric/GEJ adenocarcinoma is very effective with 90% ypRR, 21% ypCR, and impressive long-time survival benefits.

Rural-Urban Differences in Esophagectomy for Cancer.

INTRODUCTION: Patients who are disadvantaged socioeconomically or live in rural areas may not pursue surgery at high-volume centers where outcomes are better for some complex procedures. The objective of this study was to compare rural and urban patient differences directly by location of residence and outcomes after undergoing esophagectomy for cancer. METHODS: An analysis of the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) database was performed, capturing adult patients with esophageal cancer who underwent esophagectomy. Patients were stratified into rural or urban groups by the National Center for Health Statistics Urban-Rural Classification Scheme. Demographics, hospital variables, and outcomes were compared. RESULTS: A total of 2,877 patients undergoing esophagectomy for esophageal cancer were captured by the database, with 228 (7.92%) rural and 2,575 (89.50%) urban patients. The rural and urban groups had no differences in age, race, and insurance status, and shared many common comorbidities. Major outcomes of mortality (3.95% versus 4.27%, p = 0.815) and length of stay (15.75 ± 13.22 vs. 15.55 ± 14.91 days, p = 0.828) were similar for both rural and urban patients. There was a trend for rural patients to more likely be discharged home (35.96% vs. 29.79%, OR 0.667 [95% CI 0.479 - 0.929]; p = 0.0167). CONCLUSIONS: This retrospective administrative database study indicated that rural and urban patients received equivalent postoperative care after undergoing esophagectomy. The findings were reassuring as there did not appear to be a disparity in major outcomes depending on the location of residence, but further studies are necessary to assure equitable treatment for rural patients.

Pathologically Complete Response after Triple Therapy in Locally Advanced Esophageal Cancer in a Hereditary Hemorrhagic Telangiectasia Patient.

Hereditary hemorrhagic telangiectasia (HHT) is a disorder characterized by vascular manifestations including mucocutaneous and visceral telangiectasias and arteriovenous malformations. Herein we present the case of a relatively young patient with HHT with an incidentally discovered locally advanced esophageal cancer on endoscopic screening and pathologically complete response after neoadjuvant chemoradiation. This case highlights an unusual tumor response to chemoradiation in locally advanced esophageal cancer, and the surveillance care of HHT patients.

Incidental dedifferentiated mediastinal liposarcoma on F-18-fluciclovine PET/CT.

Fat-containing mediastinal masses, particularly mediastinal liposarcomas, are rare neoplasms that can grow to large sizes before becoming symptomatic and may be incidentally found on radiology examinations. In this case report, a 67-year-old male with a history of prostate cancer status post prostatectomy presented for an F-18-fluciclovine PET/CT for a rising, clinically detectable PSA and indeterminate pelvic lymph nodes seen on multiparametric MRI of the prostate. No local tumor recurrence or metastatic disease from prostate cancer was identified, but the PET/CT demonstrated a mixed soft tissue and fat density prevascular (anterior) mediastinal mass with low-level radiotracer uptake. Following surgical consultation and resection, the final pathology revealed a dedifferentiated mediastinal liposarcoma. The case presented describes the appearance of an uncommon fat-containing mediastinal mass and describes several other fat-containing mediastinal masses that are important for radiologists to recognize in order to formulate accurate differential diagnoses and ensure appropriate further management for patients. Additionally, this case demonstrates that the radiotracer F-18-fluciclovine is not specific for prostate cancer, and its uptake can be seen with other entities such as in this case of sarcomatous malignancy.

Predictors of hospital discharge to an extended care facility after major general thoracic surgery.

Failure to anticipate the need to discharge patients to rehabilitation centers and skilled nursing facilities results in expensive delays in the discharge of patients after surgery. Early identification of patients at high risk for discharge to these extended care facilities could mitigate these delays and expenditures. The purpose of this study was to identify preoperative patient factors associated with discharge to extended care facilities after major general thoracic surgery. Discharge records were identified for all patients undergoing major general thoracic surgery admitted to a university hospital between January 2006 and May 2009 who had a stay of longer than one day. The following risk factors were selected a priori based on clinical judgment: age, preoperative albumin, preoperative Zubrod score, history of peripheral vascular disease, and use of home oxygen. Multiple logistic regression analysis was used to estimate the statistical significance and magnitude of risk associated with each predictor of patient discharge to extended care facilities. Of the 1646 patients identified, 68 (4.1%) were discharged to extended care facilities. Hospital length of stay was on average six days longer for patients discharged to these facilities than for patients discharged home (P < 0.0001). Multivariate analysis demonstrated that advanced age, lower preoperative albumin, and increased preoperative Zubrod score were statistically significant predictors of discharge to extended care facilities. Age, preoperative nutritional status, and functional status are strong predictors of patient discharge to extended care facilities. Early identification of these patients may improve patient discharge planning and reduce hospital length of stay after major thoracic surgery.

Holmium:YAG laser bronchoscopy ablation of benign and malignant airway obstructions: an 8-year experience.

Patients suffering from severe tracheobronchial obstruction are vulnerable to dyspnea, respiratory failure, obstructive pneumonia, and death. Treatment with a holmium:YAG laser, an alternative to the neodymium:YAG laser, may provide symptomatic relief. This is the largest case series to date describing the application of the holmium:YAG laser via bronchoscopy for benign and malignant obstructive disease. The data were retrospectively collected from 99 patients, with either benign or malignant tracheobronchial obstruction, who underwent 261 interventional bronchoscopy procedures in the operating room with laser ablation between January 2004 and November 2011. Categorical variables were analyzed with the chi-square and Fisher's exact tests as appropriate in contingency tables, whereas Student's t-test was performed for comparison of continuous variables. Patient follow-up was concluded on September 15, 2013. The holmium:YAG laser was used in 261 procedures performed on 99 patients with either benign or malignant disease. Symptomatic improvement was demonstrated in 90 % of all benign etiology cases and 77 % of all malignant etiology cases. Within the benign and malignant subgroups, improvement was dependent on anatomical location rather than etiology of the lesion. Complications occurred in 2.3 % of the procedures, with mortality in less than 1 % of procedures. Results confirm the usefulness and safety of the holmium:YAG laser in the treatment of patients with severe benign and malignant obstructive tracheobronchial obstructions. The holmium:YAG laser is an appealing alternative to the neodymium:YAG laser.

BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone acetyltransferase p300.

The mechanisms through which the metastasis suppressor gene BRMS1 functions are poorly understood. Herein, we report the identification of a previously undescribed E3 ligase function of BRMS1 on the histone acetyltransferase p300. BRMS1 induces polyubiquitination of p300, resulting in its proteasome-mediated degradation. We identify BRMS1 as the first eukaryote structural mimic of the bacterial IpaH E3 ligase family and establish that the evolutionarily conserved CXD motif located in BRMS1 is responsible for its E3 ligase function. Mutation of this E3 ligase motif not only abolishes BRMS1-induced p300 polyubiquitination and degradation, but importantly, dramatically reduces the metastasis suppressor function of BRMS1 in both in vitro and in vivo models of lung cancer metastasis.

Tumor recurrence after complete resection for non-small cell lung cancer.

BACKGROUND: Long-term survival after R0 resection for non-small cell lung cancer (NSCLC) is less than 50%. The majority of mortality after resection is related to tumor recurrence. The purpose of this study was to identify independent perioperative and pathologic variables that are associated with NSCLC recurrence after complete surgical resection. METHODS: A retrospective examination was performed of a prospectively maintained database of patients who underwent resection for NSCLC from July 1999 to August 2008 at a single institution. Clinicopathologic variables were evaluated for their influence on time to recurrence. Cox's proportional regression hazard model examined the association of recurrence in NSCLC. RESULTS: A total of 1,143 patients met inclusion criteria and had complete follow-up information. Of these patients, 378 (33.1%) had recurrence of the primary cancer. Median follow-up was 24 months (range, 3-134 months). Preoperative tumor maximum standardized uptake value (SUVmax) greater than 5 was associated with increased risk of recurrence (hazard ratio [HR], 1.81; p=0.01). Preoperative radiation was independently associated with recurrence (HR, 1.98; p=0.05) as well as the presence of pathologic stage II and stage III disease (stage II: HR, 2.53; p=0.05; stage III: HR, 6.49; p=0.006). Subgroup analysis found that sublobar resection was also associated with locoregional recurrence after resection (HR, 4.17; p=0.02) and lymphovascular invasion of distant recurrence (HR, 4.21; p=0.002). CONCLUSIONS: In the largest series reported to date on postresectional recurrence of NSCLC, SUVmax greater than 5, increasing pathologic stage, and the administration of preoperative radiation were independently associated with NSCLC recurrence after resection. Sublobar resection was independently associated with locoregional recurrence, and lymphovascular invasion was associated with distant recurrence.

S-nitrosoglutathione reductase in human lung cancer.

S-Nitrosoglutathione (GSNO) reductase regulates cell signaling pathways relevant to asthma and protects cells from nitrosative stress. Recent evidence suggests that this enzyme may prevent human hepatocellular carcinoma arising in the setting of chronic hepatitis. We hypothesized that GSNO reductase may also protect the lung against potentially carcinogenic reactions associated with nitrosative stress. We report that wild-type Ras is S-nitrosylated and activated by nitrosative stress and that it is denitrosylated by GSNO reductase. In human lung cancer, the activity and expression of GSNO reductase are decreased. Further, the distribution of the enzyme (including its colocalization with wild-type Ras) is abnormal. We conclude that decreased activity of GSNO reductase could leave the human lung vulnerable to the oncogenic effects of nitrosative stress, as is the case in the liver. This potential should be considered when developing therapies that inhibit pulmonary GSNO reductase to treat asthma and other conditions.

Concomitant left ventricular assist device placement and cryoablation for treatment of ventricular tachyarrhythmias associated with heart failure.

Refractory ventricular tachyarrythmias (VTs) are potentially life-threatening rhythms in patients with cardiomyopathies, particularly when they result in hemodynamic instability. Here we report two cases of patients with intractable ventricular tachyarrythmias that were unresponsive to anti-arrhythmic medications and repeated catheter ablation, and for whom concomitant cryoablation and left ventricular assist device implantation was successfully performed. Both patients tolerated the procedure well with no complications and were free from ventricular tachyarrythmias postoperatively. Concomitant surgical ventricular ablation at the time of left ventricular assist device surgery may be a reasonable approach for this subset of patients as it provides excellent visualization and the ability to ablate both epicardial and endocardial sites.

Seasonal variation influences outcomes following lung cancer resections.

OBJECTIVE: The effect of seasonal variation on postoperative outcomes following lung cancer resections is unknown. We hypothesized that postoperative outcomes following surgical resection for lung cancer within the United States would not be impacted by operative season. METHODS: From 2002 to 2007, 182507 isolated lung cancer resections (lobectomy (n = 147 937), sublobar resection (n = 21650), and pneumonectomy (n = 13916)) were evaluated using the Nationwide Inpatient Sample (NIS) database. Patients were stratified according to operative season: spring (n = 47382), summer (n = 46131), fall (n = 45370) and winter (n = 43624). Multivariate regression models were applied to assess the effect of operative season on adjusted postoperative outcomes. RESULTS: Patient co-morbidities and risk factors were similar despite the operative season. Lobectomy was the most common operation performed: spring (80.0%), summer (81.3%), fall (81.8%), and winter (81.1%). Lung cancer resections were more commonly performed at large, high-volume (>75th percentile operative volume) centers (P < 0.001). Unadjusted mortality was lowest during the spring (2.6%, P < 0.001) season compared with summer (3.1%), fall (3.0%) and winter (3.2%), while complications were most common in the fall (31.7%, P < 0.001). Hospital length of stay was longest for operations performed in the winter season (8.92 ± 0.11 days, P < 0.001). Importantly, multivariable logistic regression revealed that operative season was an independent predictor of in-hospital mortality (P < 0.001) and of postoperative complications (P < 0.001). Risk-adjusted odds of in-hospital mortality were increased for lung cancer resections occurring during all other seasons compared with those occurring in the spring. CONCLUSIONS: Outcomes following surgical resection for lung cancer are independently influenced by time of year. Risk-adjusted in-hospital mortality and hospital length of stay were lowest during the spring season.

Multigene expression-based predictors for sensitivity to Vorinostat and Velcade in non-small cell lung cancer.

The ability to predict the efficacy of molecularly targeted therapies for non-small cell lung cancer (NSCLC) for an individual patient remains problematic. The purpose of this study was to identify, using a refined "coexpression extrapolation (COXEN)" algorithm with a continuous spectrum of drug activity, tumor biomarkers that predict drug sensitivity and therapeutic efficacy in NSCLC to Vorinostat, a histone deacetylase inhibitor, and Velcade, a proteasome inhibitor. Using our refined COXEN algorithm, biomarker prediction models were discovered and trained for Vorinostat and Velcade based on the in vitro drug activity profiles of nine NSCLC cell lines (NCI-9). Independently, a panel of 40 NSCLC cell lines (UVA-40) were treated with Vorinostat or Velcade to obtain 50% growth inhibition values. Genome-wide expression profiles for both the NCI-9 and UVA-40 cell lines were determined using the Affymetrix HG-U133A platform. Modeling generated multigene expression signatures for Vorinostat (45-gene; P = 0.002) and Velcade (15-gene; P = 0.0002), with one overlapping gene (CFLAR). Examination of Vorinostat gene ontogeny revealed a predilection for cellular replication and death, whereas that of Velcade suggested involvement in cellular development and carcinogenesis. Multivariate regression modeling of the refined COXEN scores significantly predicted the activity of combination therapy in NSCLC cells (P = 0.007). Through the refinement of the COXEN algorithm, we provide an in silico method to generate biomarkers that predict tumor sensitivity to molecularly targeted therapies. Use of this refined COXEN method has significant implications for the a priori examination of targeted therapies to more effectively streamline subsequent clinical trial design and cost.

Donor age is associated with chronic allograft vasculopathy after adult heart transplantation: implications for donor allocation.

BACKGROUND: Chronic allograft vasculopathy (CAV) is a major cause of long-term complications and mortality after heart transplantation. Although recipient factors have been implicated, little is known of the role of donor factors in CAV development. We sought to identify donor factors associated with development of CAV after heart transplantation. METHODS: We reviewed the United Network for Organ Sharing heart transplant database from August 1987 to May 2008. Univariate and multivariate analyses were performed to assess the association between donor variables and the onset of CAV for adult recipients. Donor age was matched to recipient age and analyzed with respect to development of CAV. RESULTS: Of the 39,704 recipients, a total of 11,714 (29.5%) experienced CAV. Multivariate analysis demonstrated seven donor factors as independent predictors of CAV: age, ethnicity, sex, weight, history of diabetes, hypertension, and tobacco use. When matching young donors (0 to 19.9 years) and old donors (> or =50 years) to each recipient age group, older donors (> or =50 years) conferred a higher risk of developing CAV. Further modeling demonstrated that for each recipient group, older donor age (> or =50 years) conferred a higher risk of CAV development compared with younger donor age (0 to 19.9 years; p < 0.0001). CONCLUSIONS: Donor factors including sex, hypertension, diabetes, and tobacco use are independently associated with recipient CAV. Older donor age confers a greater risk of CAV development regardless of the age of the recipient. A heightened awareness for the development of CAV is warranted when using older donors in adult cardiac transplantation, in particular with recipients 40 years of age or older.

BRMS1 transcriptional repression correlates with CpG island methylation and advanced pathological stage in non-small cell lung cancer.

Breast cancer metastasis suppressor gene-1 (BRMS1) mRNA and protein expression are significantly decreased in non-small cell lung cancer (NSCLC) and this is a poor prognostic indicator. Given that the BRMS1 promoter region contains a promoter-associated CpG island (CGI) that encompasses the transcriptional start site, we hypothesized that decreased BRMS1 mRNA and protein levels in NSCLC was secondary to increased BRMS1 promoter methylation. Methylation-specific PCR (MSP) of the two known CGIs (-3477 to - 2214 and - 531 to + 608) in the BRMS1 genome was performed in NSCLC cells. This demonstrated a robust increase in methylation of the promoter-associated CGI (-531 to + 608) but not of the upstream CGI (-3477 to - 2214). To experimentally verify that methylation contributes to BRMS1 transcriptional repression, we cloned the BRMS1 promoter region, including the promoter-associated CGI, into a luciferase reporter gene and found that BRMS1 promoter activity was dramatically inhibited under methylated conditions. We then assessed the BRMS1 methylation profile with MSP and bisulphite-sequencing PCR in human NSCLC adenocarcinoma (n = 20) and squamous cell carcinoma (n = 20) relative to adjacent non-cancerous bronchial epithelium. There was a significant increase in BRMS1 promoter methylation in all NSCLC specimens relative to non-cancerous tissues, with the most dramatic difference in squamous cell cancer histology. Subsequent immunostaining demonstrated that nuclear BRMS1 expression is reduced in lung cancer specimens compared to normal bronchial epithelium. The association between BRMS1 promoter methylation and specific clinical and histopathological variables was examined using a general linear model. Pathological tumour stage was associated with increased BRMS1 methylation in squamous cell cancers. These observations demonstrate that methylation of the promoter-associated CGI in BRMS1 results in its transcriptional repression, and highlight the potential clinical relevance of this methylation event with respect to NSCLC tumour histology and pathological stage.

The legends behind cardiothoracic surgical instruments.

Every day in operating rooms around the world cardiothoracic surgeons use instruments that were originally designed and popularized by some of the legends of our specialty. As is often the case, these surgery legends usually designed the instruments secondary to perceived clinical needs or occasionally to suit their own anatomic characteristics. Surprisingly little has been written on the development of cardiothoracic surgical instrumentation and the surgeons who drove their design and development of these instruments. In this report, we highlight common surgical instruments used in cardiac and thoracic operations, and we provide a brief historical glimpse of the surgeons whose names are attached to these instruments.

Combined proteasome and histone deacetylase inhibition attenuates epithelial-mesenchymal transition through E-cadherin in esophageal cancer cells.

OBJECTIVE: Metastasis is thought to be governed partially by induction of epithelial-mesenchymal transition. Combination of proteasome and histone deacetylase inhibitors has shown significant promise, but no studies have investigated this in esophageal cancer. This study investigated effects of vorinostat (histone deacetylase inhibitor) and bortezomib (proteasome inhibitor) on esophageal cancer epithelial-mesenchymal transition. METHODS: Three-dimensional tumor spheroids mimicking tumor architecture were created with esophageal squamous and adenocarcinoma cancer cells. Cells were treated with tumor necrosis factor alpha (to simulate proinflammatory tumor milieu) and transforming growth factor beta (cytokine critical for induction of epithelial-mesenchymal transition). Tumor models were then treated with vorinostat, bortezomib, or both. Cytotoxic assays assessed cell death. Messenger RNA and protein expressions of metastasis suppressor genes were assessed. After treatment, Boyden chamber invasion assays were performed. RESULTS: Combined therapy resulted in 3.7-fold decrease in adenocarcinoma cell invasion (P = .002) and 2.8-fold decrease in squamous cell invasion (P = .003). Three-dimensional invasion assays demonstrated significant decrease in epithelial-mesenchymal transition after combined therapy. Quantitative reverse transcriptase polymerase chain reaction and Western blot analyses revealed robust rescue of E-cadherin transcription and protein expression after combined therapy. Importantly, inhibition of the E-cadherin gene resulted in abolition of the salutary benefits of combined therapy, highlighting the importance of this metastasis suppressor gene in the epithelial-mesenchymal transition process. CONCLUSIONS: Combined vorinostat and bortezomib therapy significantly decreased esophageal cancer epithelial-mesenchymal transition. This combined therapeutic effect on esophageal cancer epithelial-mesenchymal transition was associated with upregulation of E-cadherin protein expression.

Radiotracer-guided thoracoscopic resection is a cost-effective technique for the evaluation of subcentimeter pulmonary nodules.

BACKGROUND: Excisional biopsy of small subcentimeter pulmonary nodules can be difficult using standard thoracoscopic techniques and may require thoracotomy. Radiotracer-guided thoracoscopic resection (RGTR) was developed to facilitate resection of intraparenchymal subcentimeter pulmonary nodules. Decision analysis, used to model cost and effectiveness, is useful to compare treatment options. We hypothesize that RGTR strategy is more cost-effective compared with thoracotomy for subcentimeter pulmonary nodules. METHODS: The cost-effectiveness of RGTR versus thoracotomy for evaluating highly suspicious subcentimeter pulmonary nodules was examined with a decision analysis model (Fig 1). A 40-patient institutional cohort who underwent RGTR was used to estimate probabilities and costs of the two treatment options within the model. Effectiveness was estimated using 5-year, stage-specific cancer survival and population survival curves. The Society of Thoracic Surgeons General Thoracic Database was queried obtaining mortality estimates for thoracotomy and thoracoscopic wedge resections. These were used to adjust the 5-year survival estimates of patients with benign disease. Sensitivity analyses determined model robustness and the thresholds at which the most cost-effective strategy changed. RESULTS: Radiotracer-guided thoracoscopic resection was 95% successful with no mortality. The average cost-to-effectiveness ratio of RGTR strategy was $27,887 versus $32,271 for thoracotomy. Sensitivity analyses demonstrated that the thoracotomy strategy was more cost-effective if the estimated cost of RGTR increased by 33% or the estimated cost-effectiveness of thoracotomy decreased by 14% or more. Radiotracer-guided thoracoscopic resection was more cost-effective as long as the probability of success was greater than 44%. CONCLUSIONS: Decision analysis is a useful tool to evaluate treatment options for thoracic surgeons, and RGTR is a more cost-effective strategy than thoracotomy for subcentimeter pulmonary nodules.

Certification pass rate of 100% for fundamentals of laparoscopic surgery skills after proficiency-based training.

BACKGROUND: The fundamentals of laparoscopic surgery (FLS) program has been extensively validated for use as a high-stakes examination for certification purposes, but optimal methods for its use in skills training have not been described. This study aimed to investigate the feasibility of implementing a proficiency-based FLS skills training curriculum and to evaluate its effectiveness in preparing trainees for certification. METHODS: For this study, 21 novice medical students at two institutions viewed video tutorials, then performed one repetition of the five FLS tasks as a pretest. The pretests were scored using standard testing metrics. The trainees next practiced the tasks over a 2-month period until they achieved proficiency for all the tasks. A modified on-the-fly scoring system based on expert-derived performance was used. The trainees were posttested using the high-stakes examination format. RESULTS: No trainee passed the certification examination at pretesting. The trainees achieved proficiency for 96% of the five tasks during training, which required 9.7 +/- 2.4 h (range, 6-14 h) and 119 +/- 31 repetitions (range, 66-161 repetitions). The trainees rated the proficiency levels as "moderately difficult" (3.0 +/- 0.7 on a 5-point scale) and "highly appropriate" (4.7 +/- 0.1 on a 5-point scale). At posttesting, 100% of the trainees passed the certification examination and demonstrated significant improvement compared with pretesting for normalized score (468 +/- 24 vs 126 +/- 75; p < 0.001), self-rated laparoscopic comfort (89.4% vs 4.8%; p < 0.001), and skill level (3.6 +/- 0.9 vs 1.2 +/- 0.5; p < 0.001, 5-point scale). CONCLUSIONS: This proficiency-based curriculum is feasible for training novices and uniformly allows sufficient skill acquisition for FLS certification. Endorsed by the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), this curriculum is available for use as an optimal method for FLS skills training. More widespread adoption of this curriculum is encouraged.