Ex vivo pleural effusion cultures to study chimeric antigen receptor T cell cytotoxicity in an immunocompetent environment.

Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate drug potency and limitations of efficacy. Herein, we describe an ex vivo pleural effusion culture (ePEC) assay, using malignant pleural-effusion-derived soluble and cellular factors that differentially affected the cytotoxicity of chimeric antigen receptor (CAR) T cells. Following identification of CAR T cell-suppressive factors, blocking of individual factors reveals their contribution to compromising T cell efficacy. ePEC is a human component assay that can be utilized for developing next-generation cell and antibody therapies that counteract immunosuppression.

A case report on a large, peduncular intra-abdominal hepatocellular carcinoma extending into the retroperitoneum.

Here, we discuss a relatively uncommon presentation of a hepatocellular carcinoma and discuss its preoperative planning and surgical intervention required to reach complete resection.

Lean Lobectomy: Streamlining Video-Assisted Lobectomy to Increase the Value of Lung Cancer Care.

PURPOSE: A review of the outcomes of patients who received our video-assisted thoracic surgery (VATS) lung lobectomy in 2015 revealed long lengths of stay, inefficient care transitions, and overuse of resources. Focused process redesign offers a proven method for instituting improvement and changes in health care. We sought to use systems process improvement to streamline VATS lobectomies at our institution, and we targeted cost drivers to optimize quality of care and minimize overuse of resources. METHODS: We performed a retrospective review of perioperative practices between January 2015 and March 2016 for patients undergoing VATS lobectomy that helped establish a value stream map, used a granular cost database, and performed real-time analysis. We used an outcomes database, which allowed us to identify cost drivers, practice variability, and rent seeking. We implemented process redesign with constant review and formal value stream reanalysis at 6-month intervals over a 2-year period. RESULTS: We ultimately experienced an overall 187% reduction of time in the operating room (297 v 159 minutes). Our process redesign also resulted in significantly fewer chest x-rays per patient (mean, 6.7 v 2), laboratory draws (100% v 5.7%), and consultations (100% v 5.7%), which resulted in a 234% reduction in mean length of stay (4.4 v 1.88 days) and an overall cost reduction of 40%. These changes did not have a detrimental effect on patient outcomes: pulmonary complications (16.9% v 8.6%), cardiac complications (13.2% v 8.6%), and readmission rates (13.6% v 2.9%) all decreased. CONCLUSION: By using value stream analysis and process redesign methodologies, closely paired with highly granular cost and outcomes data, we were able to achieve significant improvements in patient outcomes and use of resources.

Tumor Spread Through Air Spaces Is a Predictor of Occult Lymph Node Metastasis in Clinical Stage IA Lung Adenocarcinoma.

INTRODUCTION: In patients with stage IA lung adenocarcinoma (ADC), sublobar resection and tumor spread through air spaces (STAS) are associated with high rates of locoregional recurrence, half of which occur within the regional lymph nodes (LNs). Our objectives were to investigate the association between occult LN metastasis (ONM) and STAS and to assess their prognostic value in patients with clinical stage IA lung ADC. METHODS: The association between STAS and ONM was analyzed in patients who underwent lobectomy and LN dissection for clinical stage IA lung ADC (n = 809). Multivariable logistic regression analysis was carried out to identify predictors of ONM. Site-specific recurrence by surgical procedure was investigated in patients with pathologic node-negative disease (n = 1055) using a competing risk approach. RESULTS: ONM was identified in 129 patients (16%)-one-third of ONMs were located only in intrapulmonary nodes. STAS was more common in patients with ONM than in those without ONM (67% versus 39%; p < 0.001) and in patients with multiple ONMs than in those with a single ONM (86%-89% versus 60%-67%). STAS was a significant predictor of ONM (p = 0.004) on multivariable analysis, independent of tumor size, maximum standardized uptake value, and lymphovascular invasion. In patients with STAS-positive ADC (high ONM risk), the risk of recurrence in the treated lobe and regional LNs increased as the extent of resection decreased (recurrence risk: lobectomy < segmentectomy < wedge resection). In patients with STAS-negative ADC, the risk of locoregional recurrence did not differ by procedure type. CONCLUSIONS: Presence of STAS predicts ONM in patients with clinical stage IA lung ADC and can help stratify risk of recurrence by extent and type of resection.

Decreasing use of epidural analgesia with increasing minimally invasive lobectomy: Impact on postoperative morbidity.

OBJECTIVE: The goal of this study is to investigate the use of EA and its impact on the postoperative short-term outcomes of patients with non-small cell lung cancer (NSCLC) who received a lobectomy by either minimally invasive surgery (MIS) or thoracotomy. MATERIALS AND METHODS: We investigated 793 patients who underwent lobectomy for pathological stage I-III NSCLC without induction therapy during two time periods, an early-time period (2009-2010: MIS, n = 204 [53%]; and thoracotomy, n = 182 [47%]) and a late-period (2014-2015: MIS, n = 308 [76%]; and thoracotomy, n = 99 [24%]). Patient characteristics, including pulmonary function tests, comorbidities, and use of EA, as well as short-term outcomes, including length of stay, morbidity, and mortality were assessed and compared between early-and late-time periods. We also compared patients who received EA (n = 150) with patients who did not receive EA (n = 158) following MIS lobectomy in the late-time period. RESULTS: The use of MIS lobectomy increased during the late-time period compared to the early-time period (p < 0.001). In patients who underwent MIS lobectomy, the use of EA significantly decreased in the late-time period compared to the early-time period (2009-2010 vs. 2014-2015, 95% vs. 51%; p < 0.001). There was no difference in postoperative morbidity and mortality between the two time periods in both MIS and thoracotomy. In the late-time period MIS group, the length of stay in the no EA group (n = 150) was shorter than that in the EA group (n = 158) (3 vs. 4 days, p = 0.038). There was no difference in morbidity and mortality between the EA and no EA groups. CONCLUSION: In our study cohort, the observed decrease in the use of EA with the increasing rate of MIS lobectomy did not negatively affect postoperative short-term outcomes.

Immunotherapy for malignant pleural mesothelioma: current status and future directions.

Malignant pleural mesothelioma (MPM) has been marked historically by poor prognosis. Current standard of care for this deadly disease results in sub-optimal improvements in overall survival (OS), which has prompted researchers to explore innovative treatment alternatives. Immunotherapy is an emerging therapeutic modality that harnesses the power of the human immune system. In this review, we summarize the different methods of immunotherapy for malignant pleural mesothelioma. Using ClinicalTrials.gov we searched the terms "immunotherapy" and "immune therapy" combined with "pleural mesothelioma". Our search yielded 75 trials, among which 37 trials met our specific criteria. Our search identified immune checkpoint blockade, immunotoxin therapy, anticancer vaccines, oncolytic viral therapy, and adoptive cell therapy as the most common and pertinent methods of immunotherapy currently being assessed in clinical trials. We have reviewed the most up-to-date clinical trials involving immunotherapeutic approaches for the treatment of malignant pleural mesothelioma. In addition to highlighting some of the successes of immunotherapy, we also have identified limitations that must be overcome to improve the efficacy of these therapies.

CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.

Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell antitumor effector function and have gained momentum to investigate in solid tumors based on recent successes of clinical trials treating patients with B-cell hematologic malignancies. This review summarizes target antigens for CAR T-cell therapy that are being investigated in preclinical studies and clinical trials for both NSCLC and MPM patients. We discuss the rationale for combination immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the challenges and strategies for overcoming the obstacles facing translation of CAR T-cell therapy to solid tumors.

Massive malignant solitary fibrous tumor arising from the bladder serosa: a case report.

INTRODUCTION: Solitary fibrous tumors are rare neoplasms of mesenchymal origin. They are often of low malignant potential and rarely metastasize. While they frequently arise from the pleura, they can occur at any soft tissue site in the body. We present a case of a large (28 × 21 cm) malignant solitary fibrous tumor arising from the bladder serosa. In addition, the clinicopathologic features, differential diagnosis, cytogenetics and management of this rare disease are discussed, along with a review of the existing literature on this topic. CASE PRESENTATION: An otherwise healthy 41-year-old Caucasian man presented with weight loss and progressive abdominal bloating. A subsequent computed tomography scan of his chest, abdomen and pelvis revealed a 26.8 × 21 cm intra-abdominal mass occupying most of his abdominal cavity. The inferior vena cava was compressed, and the mass extended inferiorly to his upper pelvis abutting the superior dome of his bladder. He underwent operative resection and the resected mass measured 28 × 21 × 18 cm and weighed 4.8 kg. The cut surface revealed a gray-white mass with an ill-defined whorled-like pattern, with randomly assorted tan fleshy nodules. A histologic evaluation revealed variable, alternating hypercellular and hypocellular areas, with areas of necrosis. The tumor cells varied from spindle to epithelioid within a hyalinized stroma. In the hypercellular areas, the tumor cells showed moderate atypia with high mitotic activity. The histological features combined with immunophenotyping were suggestive of a malignant solitary fibrous tumor that grossly appeared to be growing from the bladder serosa, specifically the intraperitoneal superior dome of the bladder. Our patient is currently eight months post-surgery without evidence of recurrence. CONCLUSIONS: Extrapleural occurrences of solitary fibrosis tumors are being increasingly observed. Malignant solitary fibrosis tumors of the urinary bladder, however, are very rare. As there are no pathognomonic features of malignancy, surgical resection is often both diagnostic and therapeutic, as was the case in our report.