Image-Guided VATS in the Hybrid Operation Room Facilitates Early Diagnosis and Concurrent Treatment of Subcentimeter Nonpalpable Lung Nodules.

OBJECTIVE: As lung cancer screening increases, the detection of small, nonpalpable lung lesions is on the rise. The hybrid operation room (OR), which combines percutaneous or endobronchial fiducial placement with on-table computed tomography (CT) and fluoroscopic guidance, improves localization and facilitates the diagnosis and treatment of smaller, nonpalpable lung nodules with greater accuracy. METHODS: In 35 consecutive months, 55 veterans underwent 60 image-guided video-assisted thoracic surgery procedures for lesion resection. Of the cases, 36% were found during lung cancer screening. All patients received their care in the hybrid OR, where cone-beam CT scan technology was used to place an average of 1.6 fiducials percutaneously (n = 55) or via augmented navigational bronchoscopy (n = 5). RESULTS: A total of 66 lesions were resected. The median lesion size was 8 mm with an interquartile range of 6 to 14. The patients underwent nonanatomical resection with lymph node dissection using radiologic guidance. When indicated, an anatomical resection was subsequently performed. Of 47 total non-small cell lung cancer lesions, 83% were diagnosed at stage IA1 or IA2. The median surgical margin was 15 mm; the margin was usually 1.5 times as wide as the lesion. CONCLUSIONS: The hybrid OR technology gives a 3-dimensional assessment of the small lung lesions, allowing for a tissue-saving resection while achieving good surgical margins. During lung cancer screening, smaller, nonpalpable lung nodules are frequently found. This technology allows resection of subcentimeter lesions, which would otherwise be unresectable at this early stage, possibly improving survival.

Potential Financial Impact of Incidental Cardiac Pathology Detected During Lung Cancer Screening.

BACKGROUND: Lung cancer screening (LCS) is broadly accepted. Screening also identifies incidental cardiac findings (S findings) that need follow-up. We report the magnitude of the potential downstream revenue generated by appropriate S finding management after 4 years of our free LCS program. MATERIALS AND METHODS: A retrospective database and chart review of a single-center free LCS program in the underserved southeast were performed. All patients who were enrolled in the screening required a primary care physician (PCP) as part of the decision-making model. Referrals to cardiac specialists for S findings found on LCS were recorded. Cost analysis was performed to track potential downstream revenue generated for the institution based upon Medicare allowable or Diagnosis-related group calculations. RESULTS: One thousand one hundred thirty-two scans were reviewed with 262 (23%) yielding positive S findings for 1 or more organ systems. 181/262 (69%) patients had cardiac findings, only 64/181 (35%) of these patients were referred to cardiology specialists by the PCP. The total Medicare billable amount for all cardiac referrals/interventions was $284 379, representing 35% of the potential billable amount of $804 260. Percutaneous coronary intervention (PCI) was the highest billable amount at $18 568. Eight percent of the patients undergoing appropriate cardiac evaluation required a PCI. If not for the screening and cardiac specialist referral, this patient group may not have received appropriate cardiovascular diagnosis and treatment. DISCUSSION: Lung cancer screening also identifies patients with significant cardiac disease, many of whom may not be appropriately referred. Identification and treatment of incidentally noted cardiovascular findings may both improve patient care and justify supporting free LCS programs.

Hybrid Operating Room: One-Stop-Shop for Diagnosis, Staging, and Treatment.

The Hybrid Operating Room allows the thoracic surgeon to image, biopsy, diagnose, and operate in the same setting. With this streamlined model, time from referral to diagnosis to treatment is reduced. Increased efficiency allows for diagnosis and definitive surgical therapy sooner, thereby improving patient outcomes. A team-based approach is required for this one-stop-shop model of thoracic surgical practice to succeed. We present a series of prospective registry chart reviews demonstrating the utility of same-day diagnosis for thoracic oncology patient outcomes. Of the 21 patients presented, we were able to successfully obtain a diagnosis in 20 patients, resulting in a >95% single-session diagnostic rate.

Clear Cell Myoepithelial Carcinoma Arising from the Hard Palate with Metastasis to the Lungs.

Myoepithelial carcinoma is an uncommon tumor of the salivary glands, most commonly the parotid gland. Clear cell myoepithelial carcinoma is a rare variant with an aggressive behavior. Here, we describe a case of clear cell myoepithelial carcinoma arising from the hard palate in an elderly male who underwent resection of the tumor and postop radiation. Posttreatment imaging demonstrated bilateral pulmonary nodules and a C2 body lesion concerning for metastasis. Biopsy of the lung lesions revealed a monomorphous population of optically clear cells with hyperchromatic and pleomorphic nuclei which were morphologically similar to the prior resection specimen. There are few reported cases of clear cell myoepithelial carcinoma arising from the hard palate, and there are even fewer reports on metastases to the lungs. Due to the low number of reported cases, prognosis and treatment of this neoplasm is not well defined.

Financial Analysis of Free Lung Cancer Screening Program Shows Profitability Using Broader NCCN Guidelines.

BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) chest scans in high-risk populations has been established as an effective measure of preventive medicine by the National Lung Screening Trial. However, the sustainability of funding a program is still controversial. We present a 2.5-year profitability analysis of our screening program by using the broader National Comprehensive Cancer Network criteria. METHODS: Retrospective chart review was performed on the initial 2.5-year data set of a free LDCT chest scan program that targeted the underserved Southeastern United States. Patients were selected by the National Comprehensive Cancer Network high-risk criteria, screening twice as many patients compared with Centers for Medicare and Medicaid Services criteria. LDCT scans were performed during the off-service hours of our positron emission tomography CT scanner. Analysis of fiscal years 2015 to 2017 was done to evaluate indirect cost, direct cost, and adjusted net margin per case after factoring downstream revenue from positive scans and other findings. RESULTS: A total of 705 scans were performed with 418 patients referred for subsequent procedures or specialist evaluations. The mean overhead cost over total cost was 42.3%. The adjusted net margin per case was -$212 in the first year but turned positive to $177 in the third fiscal year. The total break-even point of adjusted net margin was between 6% and 7% of indirect cost as a function of charges. Of the 60 new patients introduced to the hospital system, a gross margin per case of $211 was found. CONCLUSIONS: Free lung cancer screening can demonstrate profitability from downstream revenue with a lag time of 2 years.

Using the Hybrid Operating Room in Thoracic Surgery: A Paradigm Shift.

We describe the integration of the hybrid operation room cone-beam computed tomography (CT) scan technology into the practice of general thoracic surgery. The combination of the following three techniques: (1) cone-beam CT scan augmented navigational bronchoscopy, (2) cone-beam CT-guided percutaneous biopsy and/or fiducial placement, and (3) fiducial or image-guided video-assisted thoracic surgery resection, into a single-stage, single-provider procedure allows for diagnosis and treatment in one setting. Rapid on-site evaluation of cytological or pathology specimens is key to this "all-in-one" approach. The time from diagnosis to curative treatment can significantly be reduced using the hybrid operation room technology, leading to decreased upstaging, increased survival and facilitating the otherwise difficult intraoperative detection and resection of small and deeper lesions. Not only does this benefit the overall thoracic healthcare of the community but also provides a cost-effective paradigm for the institution.

Transesophageal Echocardiography-Guided Epicardial Left Ventricular Lead Placement by Video-Assisted Thoracoscopic Surgery in Nonresponders to Biventricular Pacing and Previous Chest Surgery.

OBJECTIVE: The aim of the study was to study the feasibility, safety, and efficacy of transesophageal echocardiography-guided intraoperative left ventricular lead placement via a video-assisted thoracoscopic surgery approach in patients with failed conventional biventricular pacing. METHODS: Twelve patients who could not have the left ventricular lead placed conventionally underwent epicardial left ventricular lead placement by video-assisted thoracoscopic surgery. Eight patients had previous chest surgery (66%). Operative positioning was a modified far lateral supine exposure with 30-degree bed tilt, allowing for groin and sternal access. To determine the optimal left ventricular location for lead placement, the left ventricular surface was divided arbitrarily into nine segments. These segments were transpericardially paced using a hand-held malleable pacing probe identifying the optimal site verified by transesophageal echocardiography. The pacing leads were screwed into position via a limited pericardiotomy. RESULTS: The video-assisted thoracoscopic surgery approach was successful in all patients. Biventricular pacing was achieved in all patients and all reported symptomatic benefit with reduction in New York Heart Association class from III to I-II (P = 0.016). Baseline ejection fraction was 23 ± 3%; within 1-year follow-up, the ejection fraction increased to 32 ± 10% (P = 0.05). The mean follow-up was 566 days. The median length of hospital stay was 7 days with chest tube removal between postoperative days 2 and 5. CONCLUSIONS: In patients who are nonresponders to conventional biventricular pacing, intraoperative left ventricular lead placement using anatomical and functional characteristics via a video-assisted thoracoscopic surgery approach is effective in improving heart failure symptoms. This optimized left ventricular lead placement is feasible and safe. Previous chest surgery is no longer an exclusion criterion for a video-assisted thoracoscopic surgery approach.

Label-free ferrohydrodynamic cell separation of circulating tumor cells.

Circulating tumor cells (CTCs) have significant implications in both basic cancer research and clinical applications. To address the limited availability of viable CTCs for fundamental and clinical investigations, effective separation of extremely rare CTCs from blood is critical. Ferrohydrodynamic cell separation (FCS), a label-free method that conducted cell sorting based on cell size difference in biocompatible ferrofluids, has thus far not been able to enrich low-concentration CTCs from cancer patients' blood because of technical challenges associated with processing clinical samples. In this study, we demonstrated the development of a laminar-flow microfluidic FCS device that was capable of enriching rare CTCs from patients' blood in a biocompatible manner with a high throughput (6 mL h-1) and a high rate of recovery (92.9%). Systematic optimization of the FCS devices through a validated analytical model was performed to determine optimal magnetic field and its gradient, ferrofluid properties, and cell throughput that could process clinically relevant amount of blood. We first validated the capability of the FCS devices by successfully separating low-concentration (∼100 cells per mL) cancer cells using six cultured cell lines from undiluted white blood cells (WBCs), with an average 92.9% cancer cell recovery rate and an average 11.7% purity of separated cancer cells, at a throughput of 6 mL per hour. Specifically, at ∼100 cancer cells per mL spike ratio, the recovery rates of cancer cells were 92.3 ± 3.6% (H1299 lung cancer), 88.3 ± 5.5% (A549 lung cancer), 93.7 ± 5.5% (H3122 lung cancer), 95.3 ± 6.0% (PC-3 prostate cancer), 94.7 ± 4.0% (MCF-7 breast cancer), and 93.0 ± 5.3% (HCC1806 breast cancer), and the corresponding purities of separated cancer cells were 11.1 ± 1.2% (H1299 lung cancer), 10.1 ± 1.7% (A549 lung cancer), 12.1 ± 2.1% (H3122 lung cancer), 12.8 ± 1.6% (PC-3 prostate cancer), 11.9 ± 1.8% (MCF-7 breast cancer), and 12.2 ± 1.6% (HCC1806 breast cancer). Biocompatibility study on H1299 cell line and HCC1806 cell line showed that separated cancer cells had excellent short-term viability, normal proliferation and unaffected key biomarker expressions. We then demonstrated the enrichment of CTCs in blood samples obtained from two patients with newly diagnosed advanced non-small cell lung cancer (NSCLC). While still at its early stage of development, FCS could become a complementary tool for CTC separation for its high recovery rate and excellent biocompatibility, as well as its potential for further optimization and integration with other separation methods.

Free Lung Cancer Screening Trends Toward a Twofold Increase in Lung Cancer Prevalence in the Underserved Southeastern United States.

OBJECTIVES: The National Lung Screening Trial (NLST) reported that the prevalence of lung cancer in individuals at high risk for the disease is 1%, and that screening these individuals using low-dose helical computed tomography of the chest saves lives. To increase screening accessibility in the underserved southeastern United States, we developed a free lung screening program, modeled after the Lahey Hospital & Medical Center Free Lung Screening Program, for individuals meeting National Comprehensive Cancer Network high-risk criteria. METHODS: This was a chart review of 264 participants screened in the first year of our program. Participants were divided into categories based on the Lung Imaging Reporting and Diagnostic System. Categories three and four were considered positive findings, with demographic and disease criteria collected on these patients. RESULTS: Of 264 participants screened, 28 (10.6%) were Lung Imaging Reporting and Diagnostic System category four, 23 (8.7%) were category three, 78 (29.5%) were category two, and 135 (51.1%) were category one. Eight of the 264 participants (3.0%) had lung cancer, with 75% detected in early stages. CONCLUSIONS: We found a lung cancer prevalence in our high-risk screened population of 3.0% (8 of 264). After adjusting for patients who were symptomatic on clinical evaluation, we report a prevalence of cancer at 2.2% compared with 1.1% in the first year of the National Lung Screening Trial and a prevalence of 1.9% versus 0.6% compared with the National Comprehensive Cancer Network criteria in the first 10 months at Lahey Hospital & Medical Center. This study justifies low-dose helical computed tomography screening in high-risk regions because lung cancer treatment before symptoms appear is more effective, and the prevalence of disease in the detectable preclinical phase is high.

YM155 inhibits topoisomerase function.

YM155 (sepantronium bromide) has been evaluated in clinical trials as a survivin suppressant, but despite positive signals from early work, later studies were negative. Clarification of the mechanism of action of YM155 is important for its further development. YM155 affects cells in a cell cycle-specific manner. When cells are in G1, YM155 prevented their progression through the S phase, leaving the cells at G1/S when exposed to YM155. Passage through mitosis from G2 is also defective following YM155 exposure. In this study, YM155 did not behave like a typical DNA intercalator in viscosity, circular dichroism, and absorption spectroscopy studies. In addition, molecular modeling experiments ruled out YM155 DNA interaction to produce DNA intercalation. We show that YM155 inhibited topoisomerase 2α decatenation and topoisomerase 1-mediated cleavage of DNA, suggesting that YM155 inhibits the enzyme function. Consistent with these findings, DNA double-strand break repair was also inhibited by YM155.

Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age.

A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life-threatening. She had disease progression 9 months into treatment.

Uneven Distribution of Cancer Histology in the National Lung Screening Trial.

The National Lung Screening Trial reported a 20% lower mortality due to lung cancer in the patients screened with low-dose computed tomography (LDCT) compared with plain chest radiography (XRAY). A hypothesis was raised that LDCT should detect more cases of all tissue types or else the distribution of tissue types should be equal between groups. Data were extracted regarding the tissue types of lung cancer and presenting stages from the 2011 NSLT report. A total of 1,993 cases of tissue diagnosed lung cancer were reported, 1,054 for the LDCT group and 939 for the XRAY group. Two tissue types were more prevalent in the XRAY group: small cell carcinomas (16.9% versus 13%; P < 0.05) and other non-small cell (ONSC) carcinomas (16.8% versus 12.4%; P < 0.05). The ONSC category excluded the usual non-small cell tissue types: adenocarcinomas, squamous, and large cell carcinomas and did include other known biologically unfavorable tissue types. The XRAY group also had a disproportionately large number of stage IV small cell and ONSC tumors (P < 0.05 for ONSC). Bronchoalveolar cell carcinomas were more prevalent in the LDCT group (10.4% versus 3.7%, P < 0.05), likely reflecting greater sensitivity for detection. In summary, this review found uneven distribution of cases and higher preponderance of stage IV tumors for 2 adverse tissue types in the XRAY group. The results are consistent with greater severity of disease in the XRAY group with potential for length time bias and reduced mortality benefit from LDCT screening.