Gopal Singh

Decellularization of Human and Porcine Lung Tissues for Pulmonary Tissue Engineering

BACKGROUNDnThe only definitive treatment for end-stage organ failure is orthotopic transplantation. Lung extracellular matrix (LECM) holds great potential as a scaffold for lung tissue engineering because it retains the complex architecture, biomechanics, and topologic specificity of the lung. Decellularization of human lungs rejected from transplantation could provide ideal biologic scaffolds for lung tissue engineering, but the availability of such lungs remains limited. The present study was designed to determine whether porcine lung could serve as a suitable substitute for human lung to study tissue engineering therapies.nnnMETHODSnHuman and porcine lungs were procured, sliced into sheets, and decellularized by three different methods. Compositional, ultrastructural, and biomechanical changes to the LECM were characterized. The suitability of LECM for cellular repopulation was evaluated by assessing the viability, growth, and metabolic activity of human lung fibroblasts, human small airway epithelial cells, and human adipose-derived mesenchymal stem cells over a period of 7 days.nnnRESULTSnDecellularization with 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best maintenance of both human and porcine LECM, with similar retention of LECM proteins except for elastin. Human and porcine LECM supported the cultivation of pulmonary cells in a similar way, except that the human LECM was stiffer and resulted in higher metabolic activity of the cells than porcine LECM.nnnCONCLUSIONSnPorcine lungs can be decellularized with CHAPS to produce LECM scaffolds with properties resembling those of human lungs, for pulmonary tissue engineering. We propose that porcine LECM can be an excellent screening platform for the envisioned human tissue engineering applications of decellularized lungs.

Pulmonary Kirsten Rat Sarcoma Virus Mutation Positive Mucinous Adenocarcinoma Arising in a Congenital Pulmonary Airway Malformation, Mixed Type 1 and 2

Congenital pulmonary airway malformation (CPAM) is a developmental abnormality of the lung, which results from an abnormality of branching during fetal development of the lung. We report the case of an 18 year-old woman who developed Kirsten rat sarcoma virus (KRAS) mutation positive mucinous adenocarcinoma of the lung (AC) in association with mixed CPAM type 1 and 2. This case is unique as KRAS mutation positive AC is present in a setting of both CPAM 1 and 2 in the same lesion.

Minimally invasive Ivor Lewis oesophagogastrectomy in a patient with situs inversus totalis

Situs inversus totalis (SIT) is a rare congenital condition in which the internal organs of the thoracic and abdominal cavities experience a right-to-left reflection across the sagittal plane. We describe a case of locally advanced adenocarcinoma of the oesophagus treated with minimally invasive oesophagectomy using a laparoscopic and left video-assisted thoracoscopic surgery approach in a patient with situs inversus totalis.

Physician assistant model for lung procurements: a paradigm worth considering.

BACKGROUNDnThoracic procurements have traditionally been performed by surgical fellows or attending cardiothoracic surgeons. Donor lung procurement protocols are well established and fairly standardized; however, specific procurement training and judgment are essential to optimizing donor utilization. Although the predicted future deficits of cardiothoracic surgeons are based on a variety of analytic models and scenarios, it appears evident that there will not be a sufficient number of trained cardiothoracic surgeons over the next 2 decades. Over the past 5 years in our institution, lung procurements have been performed by a specifically trained physician assistant; as the lead donor surgeon. This model may serve as a cost effective, reproducible, and safe alternative to using surgical fellows and attending surgeons, assuring continuity, ongoing technical expertise, and teaching while addressing future workforce issues as related to transplant.nnnMETHODSnThis is a single institution review of 287 consecutive lung procurements performed by either a physician assistant or fellow over 5 years. This study was approved by the Institutional Review Board of Columbia University, which waived the need for informed consent (IRB#AAAL7107).nnnRESULTSnFrom 2008 to 2012, fellows served as senior surgeon in 90 cases (31.4%) versus 197 cases (68.6%) by the physician assistant, including 12 Donations after Cardiac Death and 6 reoperative donors. Injury rate was significantly lower for the physician assistant compared with the resident cohort (1 of 197 [0.5%] vs 22 of 90 [24%], respectively). Rates for pulmonary graft dysfunction grade 2 and 3 were found to be significantly lower in cases where the physician assistant served as senior surgeon (combined rates of 32.2% [29 of 90] vs 9.6% [19 of 197] in the physician assistant group) (p < 0.01).nnnCONCLUSIONSnUse of experienced physician assistants in donor lung procurements is a safe and viable alternative offering continuity of technical expertise and evaluation of lung allografts.

Use of Oncogenic Driver Mutations in Staging of Multiple Primary Lung Carcinomas: A Single-Center Experience

Objective: The staging of multiple pulmonary adenocarcinomas requires the distinction of intrapulmonary metastasis (IPM) from multiple primary lung cancers (MPLCs). This can be challenging in some patients, and the addition of data from oncogenic driver mutations in these tumors may be helpful in this determination. Methods: As a proof of principle, molecular driver results from primary tumors and their metastases in 45 patients were compared (cohort 1). Then, 69 patients with a total of 154 synchronous or metachronous lung carcinomas were identified, and the pathologic findings were compared with oncogenic driver mutation. Each patient was assigned a highest potential T or M category on the basis of clinical, histopathologic, and molecular findings (cohort 2). Results: The concordance rate of EGFR, KRAS, BRAF, and ALK receptor tyrosine kinase gene (ALK) mutations was 96% in cohort 1. In cohort 2, 36% of multiple same‐lobe nodules were MPLCs, 40% were IPM, and 24% were noninformative by molecular findings. Of nodules with multiple lobe involvement, 81.5% were MPLCs and 7.4% were IPM, with 11% noninformative. Of metachronous tumors, 52.9% were MPLCs. Overall survival was 100% at 2 years, 95% at 3 years, and 80% at 4 years in patients with available follow‐up. Conclusions: Oncogenic driver mutations are concordant between primary tumors and metastasis. The largest proportion of MPLCs was seen in tumors of multiple lobes, but with a substantial proportion of MPLCs among single‐lobe nodules and with metachronous tumors. Overall survival was higher than expected for the respective highest T or M category, which is in support of the high frequency of MPLC.

Heart Procurement from a Donor on Venovenous ECMO Support.

We report the case of a 37-year-old woman with acute respiratory distress syndrome and became a candidate for organ donation after anoxic brain injury and was on a venovenous extracorporeal membrane oxygenation (VV-ECMO) support. On preoperative evaluation and gross examination, the donor’s heart was acceptable for heart transplantation to a 62-year-old female patient with a history of nonischemic cardiomyopathy with a HeartMate II mechanical assist device. Orthotopic heart transplantation was successfully performed in the recipient. We report a case that suggests that the procurement of a heart from a donor on ECMO support can potentially expand the donor heart pool in carefully selected patients.

A novel ECMO circuit using a SYNERGY circulite pump in a swine model.

Extracorporeal membrane oxygenation (ECMO) is used in the management of refractory cardiopulmonary failure. With improvements in technology, patients can be transferred between hospitals, ambulated, and supported for extended periods of time while on ECMO. The SYNERGY CircuLite micropump is a blood pump that has been used as a ventricular assist device for partial support. In this study, we assessed the blood biocompatibility of the SYNERGY blood pump in conjunction with a Quadrox D oxygenator for use in a novel ECMO circuit in a swine model. This clinical design was used to demonstrate early feasibility of this pump system. Four pigs were placed on venovenous ECMO circuit, which consisted of a SYNERGY pump, Quadrox D oxygenator, and Cobe E Pack 3/8 inch tubing. All animals survived the 6 hour ECMO run without catastrophic biocompatibility issues. There was no statistically discernible change from baseline in hematologic parameters, including hemoglobin, plasma-free hemoglobin, total bilirubin, lactate dehydrogenase, D-dimer, fibrinogen, platelets, and P-selectin. We believe that this study serves as a proof of concept and basis for further studies using the SYNERGY pump as a component of ECMO systems.