Outcomes in Renal Cell Carcinoma With IVC Thrombectomy: A Multiteam Analysis Between an NCI-Designated Cancer Center and a Quaternary Care Teaching Hospital.

INTRODUCTION: Interteam performance and Clavien-Dindo (C-D) complications in renal cell carcinoma with inferior vena cava thrombectomy (RCC-IVCT) have not been reported. We aimed to describe complications by the degree of complexity and surgical teams in a collaborative effort between a National Cancer Institute-designated Comprehensive Cancer Center and a Quaternary Care Teaching Hospital. METHODS: Between January 2011 and May 2019, 73 consecutive RCC-IVCT were included. C-D grades III or higher were captured. Teams involved were urologic-oncology, vascular, hepatobiliary/transplant, and cardiothoracic. The Mayo Clinic tumor thrombus classification was used. RESULTS: Overall complication rate was 42% (n = 31). Nineteen percent had grade III, 18% had grade IV, and 6% had grade V complications. Patients with level IV thrombus had the highest in-hospital mortality rate (75%). Thrombus level did not show a correlation to complication rates (14% level I, 45% level II, 32% level III, 42% level IV). A positive correlation found between the number of teams involved and complication rates (35% with 2-team, 59% with 3-team, P = .059). Thromboembolic events (6% vs 24%, P = .02) and disposition other than home (22% vs 48%, P = .01) were statistically lower for the 2-team groups. Two-team in-hospital mortality was 1/51 (2%) versus 3-team (3/22,14%, (P = .07). No statistical differences were found in infections, thromboembolic events, and grades of complications between surgical teams. CONCLUSIONS: Despite similar interteam performance, the consistency of surgeons in high complexity cases could improve outcomes further. Complexity was higher for hepatobiliary/transplant and cardiothoracic teams. A combination of intraoperative events and patient selection (comorbidities and age) contributed to death. Overall, in-hospital mortality was lower than in most reported series.

BMP signaling regulates murine enteric nervous system precursor migration, neurite fasciculation, and patterning via altered Ncam1 polysialic acid addition.

The enteric nervous system (ENS) forms from migrating neural crest-derived precursors that differentiate into neurons and glia, aggregate into ganglion cell clusters, and extend neuronal processes to form a complex interacting network that controls many aspects of intestinal function. Bone morphogenetic proteins (BMPs) have diverse roles in development and influence the differentiation, proliferation, and survival of ENS precursors. We hypothesized that BMP signaling might also be important for the ENS precursor migration, ganglion cell aggregation, and neurite fasciculation necessary to form the enteric nervous system. We now demonstrate that BMP signaling restricts murine ENS precursors to the outer bowel wall during migration. In addition, blocking BMP signaling causes faster colonization of the murine colon, reduces ganglion cell aggregation, and reduces neurite fasciculation. BMP signaling also influences patterns of neurite extension within the developing bowel wall. These effects on ENS precursor migration and neurite fasciculation appear to be mediated at least in part by increased polysialic acid addition to neural cell adhesion molecule (Ncam1) in response to BMP. Removing PSA enzymatically reverses the BMP effects on ENS precursor migration and neurite fasciculation. These studies demonstrate several novel roles for BMP signaling and highlight new functions for sialyltransferases in the developing ENS.

Differential gene expression and functional analysis implicate novel mechanisms in enteric nervous system precursor migration and neuritogenesis.

Enteric nervous system (ENS) development requires complex interactions between migrating neural-crest-derived cells and the intestinal microenvironment. Although some molecules influencing ENS development are known, many aspects remain poorly understood. To identify additional molecules critical for ENS development, we used DNA microarray, quantitative real-time PCR and in situ hybridization to compare gene expression in E14 and P0 aganglionic or wild type mouse intestine. Eighty-three genes were identified with at least two-fold higher expression in wild type than aganglionic bowel. ENS expression was verified for 39 of 42 selected genes by in situ hybridization. Additionally, nine identified genes had higher levels in aganglionic bowel than in WT animals suggesting that intestinal innervation may influence gene expression in adjacent cells. Strikingly, many synaptic function genes were expressed at E14, a time when the ENS is not needed for survival. To test for developmental roles for these genes, we used pharmacologic inhibitors of Snap25 or vesicle-associated membrane protein (VAMP)/synaptobrevin and found reduced neural-crest-derived cell migration and decreased neurite extension from ENS precursors. These results provide an extensive set of ENS biomarkers, demonstrate a role for SNARE proteins in ENS development and highlight additional candidate genes that could modify Hirschsprung's disease penetrance.