Use of Sodium Bicarbonate Purge Solution in Impella Devices for Heparin-Induced Thrombocytopenia.

Heparin purge solution is recommended to be used in Impella devices to prevent biomaterial buildup and subsequent device dysfunction. The use of sodium bicarbonate purge solution in an Impella device is described in two patients with heparin-induced thrombocytopenia (HIT). The first case details a patient with severe mitral regurgitation and cardiogenic shock who had an Impella CP placed who developed HIT. Heparin purge solution was replaced by sodium bicarbonate purge solution in addition to systemic direct thrombin inhibitor (DTI) initiation. There was no significant change in Impella purge pressure or flow over the 13 days of Impella use. The second case describes a patient who developed an acute myocardial infarction and subsequent cardiogenic shock for which an Impella CP was placed who also developed HIT. Heparin purge solution was replaced by sodium bicarbonate purge solution. There was no significant change in purge pressure, flow, or motor current spikes over 11 days of use. In conclusion, we describe the successful use of a novel sodium bicarbonate purge solution utilized in patients with HIT for Impella management alone and in combination with systemic direct thrombin inhibitor therapy. This resulted in no protein deposition in the device gaps or device dysfunction.

Adjuvant Radiation Therapy for Thoracic Soft Tissue Sarcomas: A Population-Based Analysis.

BACKGROUND: The role of adjuvant radiation therapy (RT) in the management of thoracic soft tissue sarcomas (STSs) remains unclear. We aimed to study the characteristics of patients with thoracic STS who received RT after surgical resection and investigate the impact of RT on survival outcomes. METHODS: We queried National Cancer Database to identify patients with surgically resected thoracic STS from 2004 to 2012. Factors associated with receiving adjuvant RT were identified. Analyses were performed to identify prognostic factors and compare overall survival (OS) in both unmatched and propensity score-matched cohorts. RESULTS: Overall, 1215 patients were identified, of whom 557 (45.8%) received adjuvant RT. Tumor grade (odds ratio [OR], 2.87; 95% confidence interval [CI], 2.18-3.77), tumor size (OR, 1.82; 95% CI, 1.36-2.42), and tumor margins (OR, 1.97; 95% CI, 1.43-2.72) were found to be significant predictors of receiving RT. Mean OS of patients receiving RT in the unmatched cohort was 91 months vs 88 months for patients who did not (P = .556). When adjusted for all variables, adjuvant RT was found to be associated with improved survival (hazard ratio, 0.79; 95% CI, 0.61-0.96). Survival analysis of the matched cohort also demonstrated improved survival with adjuvant RT (120 months vs 100 months; P = .02). Subgroup analysis in both the unmatched and matched cohorts showed patients with high-grade tumors more likely to benefit from adjuvant RT. CONCLUSIONS: This population-based analysis is the largest dataset of primary thoracic STSs to date and suggests significant survival benefit associated with adjuvant RT. The improvement in OS was more notable in patients with high-grade tumors. Randomized prospective studies are warranted to further understand the benefit of RT in this group.

Radiation therapy improves survival for unresectable postpneumonectomy lung tumors.

BACKGROUND: Additional resection for cancer in the single lung is often considered a prohibitive risk. The role of radiation therapy (RT) in this patient population is less clear with very limited available data. In this study, we sought to examine patients with postpneumonectomy lung cancer not amenable to surgery, identify factors associated with receiving RT, and determine the impact of RT on survival outcomes. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1988-2013) was queried for patients with inoperable contralateral lung cancer after pneumonectomy. Univariate and multivariate analyses were performed to identify factors associated with the receipt of RT. Survival outcomes were examined using the Kaplan-Meier method. RESULTS: In total, 191 patients with inoperable postpneumonectomy lung cancer were included. RT was delivered to 122 (63.9%) patients; 69 (36.1%) patients did not receive RT. On multivariate analysis, disease stage was identified as the only predictor associated with receipt of RT (P < 0.001). The median overall survival (OS) and disease-specific survival (DSS) for patients receiving RT were higher than those for patients who did not receive RT (25 versus 8 mo and 29 versus 10 mo, respectively; P < 0.001). Similarly, patients who received RT had a higher 3-y OS (34% versus 14%, P < 0.001) than those who did not receive RT. On subset analysis, survival benefit with RT was observed in patients with all tumor size groups, and there was a trend toward superior survival in patients with stage I/II disease, who received RT compared with those who did not. On multivariate Cox regression analysis, RT use was independently associated with decreased hazards of death after adjusting for other factors (HR, 0.539; P < 0.001). CONCLUSIONS: Based on our analysis of the Surveillance, Epidemiology, and End Results (SEER) database, RT is associated with improved outcomes in inoperable patients with a contralateral lung cancer after pneumonectomy compared with observation alone.

Racial Disparity in Utilization of High-Volume Hospitals for Surgical Treatment of Esophageal Cancer.

BACKGROUND: Utilization of high-volume hospitals (HVH) for esophagectomy has been associated with improved perioperative outcomes and reduced mortality. We aimed to test the hypothesis that black-white racial disparities exist in HVH utilization and identify predictors of in-hospital surgical outcomes of esophageal cancer while adjusting for HVH utilization patterns. METHODS: We queried the New York Statewide Planning and Research Cooperative System database (1995 to 2012) for esophageal cancer patients who underwent surgical resection exclusively. Only records for patients with self-reported white or black race and a valid New York State ZIP code were included (n = 2,895). Analysis was performed to identify factors associated with HVH hospital (≥20 esophagectomies/year) utilization and determine predictors of complications and in-hospital mortality. RESULTS: Black patients (361 [12.5%]) were significantly different (p < 0.001) than their white counterparts in the proportion of women, Medicaid, income distribution, and privately insured individuals. Although 55% patients overall utilized an HVH, blacks were significantly less likely to utilize an HVH than whites (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.14 to 0.24), even though 74.5% resided within 8.9 miles of one. Operations performed at HVHs were associated with lower in-hospital mortality (OR, 0.48; 95% CI, 0.35 to 0.65); however, mortality remained higher for blacks (OR, 2.04; 95% CI, 1.65 to 3.30; propensity matched OR, 2.45; 95% CI, 1.5 to 4.03). CONCLUSIONS: Black patients were less likely to undergo esophagectomy at an HVH and experienced higher mortality. Efforts should be made to understand factors influencing patients' decision process and improve referral practices to ensure optimal care is provided across all segments of the population, irrespective of race, insurance, or income status.

Pulmonary Resection for Second Lung Cancer After Pneumonectomy: A Population-Based Study.

BACKGROUND: Pulmonary resection for a second lung cancer after pneumonectomy is generally considered to be at prohibitive risk. Using a population-based database, we examined treatment patterns and survival in patients who underwent pulmonary resection after pneumonectomy for lung cancer. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) to identify patients who underwent pneumonectomy and subsequently experienced contralateral non-small cell lung cancer (NSCLC). Multivariate logistic regression was performed to identify the factors associated with the receipt of surgical resection. Survival was estimated with the Kaplan-Meier method. RESULTS: Of 13,370 patients who underwent pneumonectomy, 402 (3.0%) experienced subsequent contralateral NSCLC, and 170 (42%) met the selection criteria. Surgical resection was performed in 63 (37.1%) cases (sublobar n = 56, lobectomy, n = 7). Patients with stage I/II disease and tumor size 2 cm or smaller were more likely to undergo surgical procedures. The 1-month and 3-month mortality after resection was 11.1% (sublobar resection 10.7%, lobectomy 14.3%) and 12.7% (sublobar 12.5%, lobectomy 14.3%), respectively. The overall 1-year and 3-year survival after surgical resection was 79% and 54%, respectively. The patients who underwent sublobar resection had higher median overall survival than did those who underwent lobectomy (42 vs 18 months). Similarly, median survival after resection for metachronous tumors was higher than after resection for metastatic cancers (40 vs 28 months). CONCLUSIONS: On the basis of our analysis of the SEER database, sublobar resection can be performed in selected patients with small tumors (≤2 cm) and early-stage disease (stage I/II). Although perioperative mortality is significant, the favorable 1-year and 3-year survival may justify the role of an additional procedure on the single lung.

Three-Dimensional-Printed Bioengineered Tracheal Grafts: Preclinical Results and Potential for Human Use.

BACKGROUND: We aimed to develop a process using three-dimensional (3D) printing to create bioengineered tracheal grafts (BETGs) for reconstruction of anterior tracheal defects in a large-animal model (porcine) that would have translational relevance for potential human use. METHODS: Preoperative computed tomographic scans were used to create virtual 3D models of the animal airways. Anatomically scaled tracheal grafts were subsequently developed using 3D-printed polycaprolactone and extracellular matrix. A 4-cm anterior tracheal defect (about 50% of the length of the subject trachea) was surgically created in 4-week-old female Yorkshire pigs and reconstructed using the customized grafts. Gross and microscopic analyses of the grafts were performed. RESULTS: The BETGs were implanted in 7 animals. There was adequate graft-native trachea size match at the operation. The trachea was successfully reconstructed in all cases. Gross examination at autopsy showed a structurally intact, well-incorporated graft. Histologic evaluation showed respiratory mucosal coverage and vascularity of the graft. Five of 7 animals outlived the 3-month study period. The animals had approximately 100% growth during the study period. CONCLUSIONS: We report of a 3D-printed BETG to repair long-segment anterior tracheal defects in a large-animal model. Although the study duration is short, this work presents an efficient strategy for tracheal graft bioengineering with potential translational relevance for human use.

Circumferential Three-Dimensional-Printed Tracheal Grafts: Research Model Feasibility and Early Results.

BACKGROUND: Methods for tracheal graft research have presented persistent challenges to investigators, and three-dimensional (3D)-printed biosynthetic grafts offer one potential development platform. We aimed to develop an efficient research platform for customizable circumferential 3D-printed tracheal grafts and evaluate feasibility and early structural integrity with a large-animal model. METHODS: Virtual 3D models of porcine subject tracheas were generated using preoperative computed tomography scans. Two designs were used to test graft customizability and the limits of the construction process. Designs I and II used 270-degree and 360-degree external polycaprolactone scaffolds, respectively, both encompassing a circumferential extracellular matrix collagen layer. The polycaprolactone scaffolds were made in a fused-deposition modeling 3D printer and customized to the recipient's anatomy. Design I was implanted in 3 pigs and design II in 2 pigs, replacing 4-ring tracheal segments. Data collected included details of graft construction, clinical outcomes, bronchoscopy, and gross and histologic examination. RESULTS: The 3D-printed biosynthetic grafts were produced with high fidelity to the native organ. The fabrication process took 36 hours. Grafts were implanted without immediate complication. Bronchoscopy immediately postoperatively and at 1 week demonstrated patent grafts and appropriate healing. All animals lived beyond a predetermined 1-week survival period. Bronchoscopy at 2 weeks showed significant paraanastomotic granulation tissue, which, along with partial paraanastomotic epithelialization, was confirmed on pathology. Overall survival was 17 to 34 days. CONCLUSIONS: We propose a rapid, reproducible, resource efficient method to develop various anatomically precise grafts. Further graft refinement and strategies for granulation tissue management are needed to improve outcomes.

Primary Non-Hodgkin's Lymphoma of the Gallbladder: A Population-based Analysis.

BACKGROUND/AIM: Primary Non-Hodgkin's lymphoma of the gallbladder (PNHL-GB) is extremely rare and data on clinical characteristics, optimal management and outcomes of these patients are limited to anecdotal reporting. We, therefore, sought to examine these patients using a population-based database. MATERIALS AND METHODS: Surveillance, epidemiology, and end results (SEER) database was queried between 1973 and 2013. RESULTS: One hundred and six cases with PNHL-GB were identified (mean age=70.5 ±15 years, whites 92%, male: female 1.03:1). The majority of patients had loco-regional disease (61%) and DLBCL histology (33%). Ninenty cases (85%) had undergone surgical resection, 6 (5.6%) received radiotherapy. Median overall survival (OS) of the entire cohort was 41 months with a 5-year survival rate of 40%. Patients receiving adjuvant RT had superior OS compared to surgery alone (140 ±27 vs. 86 ±16 months, respectively) and patients with DLBCL demonstrated lower survival compared to other histologies (13 vs. 53 months, respectively, p=0.034). CONCLUSION: Our study presents the largest dataset of PNHL-GB describing clinical features and outcomes of these patients in addition to summarizing the literature.

Stents for airway strictures: selection and results.

Airway stents can provide effective and timely relief in patients with central airway obstruction. Silicone based stents are the most commonly used airway stents worldwide with a long track record of safety. Metallic stents continue to evolve from the earliest uncovered versions to a variety of newly designed covered stents. Despite the availability of a variety of stent materials and designs, minimal advances have been made towards innovation in stent technology and an ideal stent has unfortunately not yet been developed. Nevertheless, the first generation of biodegradable airway stents are available, work on drug-eluted stents is in the pipeline and three-dimensional printing of a customized airway stent may be the future. In this review, we discuss selection and results for most commonly utilized airway stents.

Reconstruction of Anterior Tracheal Defects Using a Bioengineered Graft in a Porcine Model.

BACKGROUND: Reconstruction of long-segment tracheal defects can be challenging and a suitable tracheal substitute remains lacking. We sought to create a bioengineered tracheal graft to repair such lesions using acellullar bovine dermis extracellular matrix (ECM) and male human mesenchymal stem cells (hMSCs) and implant it in a porcine model. METHODS: hMSCs were seeded on the ECM and incubated for 1 week with chondrogenic factors. An anterior 4 cm × 3 cm defect was surgically created in the trachea of 4-week-old female Yorkshire pigs. The defect was reconstructed using the bioengineered graft (n = 7) or control (n = 3, ECM only). The study duration was 3 months. RESULTS: Survival ranged from 7 days (n = 3) to 3 months (n = 7). Early death was due to graft malacia (n = 1, control), graft infection (n = 1, bioengineered), and pneumonia (n = 1, bioengineered). There was substantial animal growth at 3 months (>200% weight). Surveillance bronchoscopy showed patent airway, mild stenosis, and integration of the graft with the native trachea. On histology, luminal epithelialization and neovascularization with scant submucosa were observed in both the bioengineered graft and control groups. Chondrogenesis was seen only in the bioengineered graft. The neocartilage was less mature and organized compared to native cartilage. SRY immunostain was positive in the neocartilage but not control or native trachea. CONCLUSIONS: We demonstrate the feasibility of the bioengineered graft for reconstruction of long anterior tracheal defects with favorable short-term outcomes. Furthermore, we show its ability to facilitate chondrogenesis, neovascularization, and epithelialization. Importantly, it supported rapid animal growth offering potential solutions for both pediatric and adult applications.

Robotically Assisted Thoracic Surgery: Proposed Guidelines for Privileging and Credentialing.

OBJECTIVE: Increased use of robotically assisted thoracic surgery (RATS) necessitates effective credentialing guidelines to ensure safe outcomes. We provide a stepwise algorithm for granting privileges and credentials in RATS. This algorithm reflects graduated responsibility and complexity of the surgical procedures performed. Furthermore, it takes into account volume, outcomes, surgeon's competency, and appropriateness of robot usage. METHODS: We performed a literature review for available strategies to grant privileges and credentials for implementing robotic surgery. The following terms were queried: robot, robotic, surgery, and credentialing. We provide this algorithm on the basis of review of the literature, our institutional experience, and the experience of other medical centers around the United States. RESULTS: Currently, two pathways for robotic training exist: residency and nonresidency-trained. In the United Sates, Joint Commission: Accreditation, Health Care, Certification requires hospitals to credential and privilege physicians on their medical staff. In the proposed algorithm, a credentialing designee oversees and reviews all requests. Residency-trained surgeons must fulfill 20 cases with program directors' attestation to obtain full privileges. Nonresidency-trained surgeons are required to fulfill simulation, didactics including online modules, wet laboratories (cadaver or animal), and observation of at least two cases before provisional privileges can be granted. A minimum number of cases (10 per year) are required to maintain privileges. All procedures are monitored via departmental QA/QI committee review. Investigational uses of the robot require institutional review board approval, and complex operations may require additional proctoring and QA/QI review. CONCLUSIONS: Safety concerns with the introduction of novel and complex technologies such as RATS must be paramount. Our algorithm takes into consideration appropriate use and serves as a basic guideline for institutions that wish to implement a RATS program.

Surgery for lung cancer invading the mediastinum.

Lung cancer infiltrating the mediastinum is a subset of locally advanced lung tumors for which surgery is not routinely offered. Radical operations that involve removal of adjacent mediastinal structures to obtain free margins may provide a realistic cure. Such extended resections are typically reserved to highly motivated patients seeking more aggressive management, and are only offered following complete evaluation on a case-by-case basis. Positive prognosis depends on complete R0 resection and lack of mediastinal nodal metastases. Careful and exhaustive preoperative planning as well as surgical expertise cannot be overemphasized for successful surgical outcomes. Here we provide a brief summary of the literature as well as our own experience managing these rare and sometimes challenging surgeries.

Treatment of Benign Tracheal Stenosis Using Endoluminal Spray Cryotherapy.

Importance: Tracheal stenosis is a debilitating disorder with heterogeneity in terms of disease characteristics and management. Repeated recurrences substantially alter patients' quality of life. There is limited evidence for the use of spray cryotherapy (SCT) in the management of benign airway disease. Objective: To report our early results for the use of SCT in patients with benign tracheal stenosis. Design, Setting, and Participants: Data were extracted from the medical records of a consecutive series of patients with benign airway stenosis secondary to granulomatosis with polyangiitis (GPA) (n = 13), prior tracheotomy or tracheal intubation (n = 8), and idiopathic strictures (n = 5) treated from September 1, 2013, to September 30, 2015, at a tertiary care hospital. Main Outcomes and Measures: Airway narrowing was quantified on a standard quartile grading scale. Response to treatment was assessed by improvement in airway caliber and the time interval for reintervention. Exposures: Delivery of 4 5-second SCT cycles and 2 balloon dilatations. Results: Twenty-six patients (median [range] age, 53 [16-83] years; 20 [77%] female) underwent 48 SCT sessions. Spray cryotherapy was successfully used without any substantial intraoperative or postoperative complications in all patients. In a median (range) follow-up of 11 (1-26) months, all patients had improvement in symptoms. Before the institution of SCT, 23 patients (88%) had grade III or IV stenosis. At the last evaluation after induction of SCT, 4 (15%) had grade III or IV stenosis, with a mean (SD) change of 1.39 (0.51) (P < .001). Patients with GPA required significantly fewer SCT procedures (mean [SD], 1.38 [0.96] vs 2.31 [1.18]; P = .03) during the study period. Conclusions and Relevance: Spray cryotherapy was a safe adjunct modality to accomplish airway patency in patients with benign tracheal stenosis. Although efficacy evidence is limited for SCT, it may be useful for patients who have experienced treatment failure with conventional modalities. Further analysis of this cohort will determine the physiologic durability of the reported short-term changes. Additional trials are warranted for further evaluation of this modality.

Management of CT screen-detected lung nodule: the thoracic surgeon perspective.

Implementation of lung cancer CT screening programs will increase the incidence of pulmonary nodules and require multidisciplinary efforts for devising appropriate treatment plans. The role of the thoracic surgeon is paramount in leading the discussion and shaping the treatment strategies. Management of CT screen-detected lung nodules differ from conventional lung cancer nodules given their smaller size, varied histologies and potentially indolent growth. Here we present a brief overview of the thoracic surgeon's perspective on the clinical evaluation, diagnostic tests and surgical approach to these nodules in the setting of a comprehensive lung cancer screening program.

Lung cancer screening: did we really need a randomized controlled trial?

Lung cancer is the leading cause of cancer mortality in the USA. Within the past decade, two large trials (the National Lung Screening Trial Research and the International Early Lung Cancer Action Program) confirmed a significant role for low-dose CT (LDCT) screening in identifying early stages of cancer leading to reduced mortality in high-risk patients. Given the evidence, the US Preventive Services Task Force issued a recommendation in favour of LDCT screening for high-risk individuals. Despite the strong support for LDCT among physicians who treat lung cancer and cumulative data demonstrating a survival benefit for screening and early detection, it took more than a decade for lung cancer screening to be embraced at the policy level. With many lives lost in the interim, did we really need a randomized controlled trial to make this decision?

Diffuse pulmonary neuroendocrine cell hyperplasia involving the chest wall.

Diffuse pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterized by a diffuse hypertrophy of neuroendocrine cells along the distal bronchioles. This condition is characterized by obstructive lung physiology and the development of small carcinoid tumors. We present a case of DIPNECH in a patient undergoing surgery for a primary lung adenocarcinoma. Interestingly, the chest wall also demonstrated involvement of DIPNECH indicated by the presence of small carcinoid tumors. The absence of any lung carcinoid tumor greater than 5 mm and the absence of lymph node metastases render the chest wall involvement unlikely to represent metastatic disease.

Phosphorylation of the alternative mRNA splicing factor 45 (SPF45) by Clk1 regulates its splice site utilization, cell migration and invasion.

Alternative mRNA splicing is a mechanism to regulate protein isoform expression and is regulated by alternative splicing factors. The alternative splicing factor 45 (SPF45) is overexpressed in cancer, although few biological effects of SPF45 are known, and few splicing targets have been identified. We previously showed that Extracellular Regulated Kinase 2 (ERK2) phosphorylation of SPF45 regulates cell proliferation and adhesion to fibronectin. In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues. Clk1 expression enhanced, whereas Clk1 inhibition reduced, SPF45-induced exon 6 exclusion from Fas mRNA. Mutational analysis of the Clk1 phosphorylation sites on SPF45 showed both positive and negative regulation of splicing, with a net effect of inhibiting SPF45-induced exon 6 exclusion, correlating with reduced Fas mRNA binding. However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome-dependent pathway. Overexpression of SPF45 or a phospho-mimetic mutant, but not a phospho-inhibitory mutant, stimulated ovarian cancer cell migration and invasion, correlating with increased fibronectin expression, ERK activation and enhanced splicing and phosphorylation of full-length cortactin. Our results demonstrate for the first time that SPF45 overexpression enhances cell migration and invasion, dependent on biochemical regulation by Clk1.

Mitogen-activated protein kinase phosphorylation of splicing factor 45 (SPF45) regulates SPF45 alternative splicing site utilization, proliferation, and cell adhesion.

The regulation of alternative mRNA splicing factors by extracellular cues and signal transduction cascades is poorly understood. Using an engineered extracellular signal-regulated kinase 2 (ERK2) that can utilize ATP analogs, we have identified the alternative mRNA splicing factor 45 (SPF45), which is overexpressed in cancer, as a novel coimmunoprecipitating ERK2 substrate. ERK2 phosphorylated SPF45 on Thr71 and Ser222 in vitro and in cells in response to H-RasV12, B-RAF-V600E, and activated MEK1. Jun N-terminal kinase 1 (JNK1) and p38α also phosphorylated SPF45 in vitro and associated with SPF45 in cells. SPF45 was differentially phosphorylated in cells by all three mitogen-activated protein (MAP) kinases in response to phorbol myristate acid (PMA), H(2)O(2), UV, and anisomycin stimulation. ERK and p38 activation decreased SPF45-dependent exon 6 exclusion from fas mRNA in a minigene assay in cells. Stable overexpression of SPF45 in SKOV-3 cells dramatically inhibited cell proliferation in a phosphorylation-dependent manner through inhibition of ErbB2 expression. SPF45 overexpression also induced EDA inclusion into fibronectin transcripts and fibronectin expression in a phosphorylation-dependent and -independent manner, respectively, specifically affecting cellular adhesion to a fibronectin matrix. These data identify SPF45 as the first splicing factor regulated by multiple MAP kinase pathways and show effects of both SPF45 overexpression and phosphorylation.