The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.

Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol. Using these methods we achieved ∼75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens.

Pulmonary fibrosis is a scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe a peptide-based PET probe (68Ga-CBP8) that targets collagen type I. We evaluated 68Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. 68Ga-CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. The lung PET signal and lung 68Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r2=0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the 68Ga-CBP8 probe could be used to monitor response to treatment in a second mouse model of pulmonary fibrosis associated with vascular leak. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings. These studies indicate that 68Ga-CBP8 is a promising candidate for non-invasive imaging of human pulmonary fibrosis.

PURPOSE OF REVIEW Patients suffering from end-stage organ failure requiring organ transplantation face donor organ shortage and adverse effect of chronic immunosuppression. Recent progress in the field of organ bioengineering based on decellularized organ scaffolds and patient derived cells holds great promise to address these issues. RECENT FINDINGS Perfusion-decellularization is the most consistent method to obtain decellularized whole-organ scaffolds to serve as a platform for organ bioengineering. Important advances have occurred in organ bioengineering using decellularized scaffolds in small animal models. However, the function exhibited by bioengineered organs has been rudimentary. Pluripotent stem cells seem hold promise as the ideal regenerative cells to be used with this approach but the techniques to effectively and reliably manipulate their fate are still to be discovered. Finally, this technology needs to be scaled up to human size to be of clinical relevance. SUMMARY The search for alternatives to allogeneic organ transplantation continues. Important milestones have been achieved in organ bioengineering with the use of decellularized scaffolds. However, many challenges remain on the way to producing an autologous, fully functional organ that can be transplanted similar to a donor organ.

No abstract

MIE proves its safety after neoadjuvant therapy because it leads to faster progression during the early postoperative period while reducing pulmonary complications. Open and MIE approaches appear equivalent with regards to perioperative oncologic outcomes after neoadjuvant therapy. Long-term outcomes need further validation.

Background As worldwide life expectancy rises, the number of candidates for surgical treatment of esophageal cancer over 70 years will increase. This study aims to examine outcomes after esophagectomy in elderly patients. Methods Retrospective review of 474 patients undergoing esophagectomy for cancer during 2002–2011. 334 (70.5%) patients were <70 years old (group A), 124 (26.2%) 70–79 years (group B) and 16 (3.4%) ≥80 years (group C). We analyzed the effect of age on outcome variables including overall and disease specific survival. Results Major morbidity was observed to occur in 115 (35.6%) patients of group A, 58 (47.9%) of group B and 10 (62.5%) of group C (p=0.010). Mortality, both 30- and 90-day was observed in 2(0.6%) and 7(2.2%) of group A, 4(3.2%) and 7 (6.1%) of group B, and 1(6.3%) and 2(14.3%) of group C, respectively (p=0.032 and p=0.013). Anastomotic leak was observed in 16(4.8%) patients of group A, 6(4.8%) of group B and 0(0%) of group C (p=0.685). Anastomotic stricture (defined by the need for ≥2 dilations) was observed in 76(22.8%) of group A, 13(10.5%) of group B and 1(6.3%) of group C (p=0.005). Five-year overall and disease specific survival was 64.8% and 72.4% for group A, 41.7% and 53.4% for group B, 49.2% and 49.2% for group C patients (p=0.0006), respectively. Conclusions Esophagectomy should be carefully considered in patients 70–79 years old and can be justified with low mortality. Outcomes in octogenarians are worse suggesting esophagectomy be considered on a case by case basis. Stricture rate is inversely associated to age.

The proposed scoring system is simple, easily obtained from existing pathological description and reliably predicts recurrence in this patient population harbouring SFTP. The SFTP score may stratify patient risk and guide postoperative surveillance. We recommend validation in additional clinical series.