To evaluate the use of donor-derived cell-free DNA (dd-cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family-related living donors.
PURPOSE: We recently performed living donor small bowel transplant (LDSBT) in three patients with hypoganglionosis. We report here the peri- and post-operative management and discuss several issues about LDSBT. PATIENTS: The patients were 14 (Case1), 11(Case2) and 15(Case 3) years old boy. All of them were with total parenteral nutrition associated with hypoganglionosis. Transplantation Procedure: One third of the donor bowel was harvested. The graft vessels were connected to the recipient's infra renal aorta and inferior vena cava (Case 1), or SMA and SMV (Case 2,3) Postoperative course:The immunosuppressive regimen consisted of daclizumab, tacrolimus, and steroids. The first patient developed liver dysfunction on POD 7, subsided spontaneously on POD 12, requiring no additional therapy. Two months after transplantation, he was weaned off TPN, tolerating oral intake with a fully functioning graft. The second patient was weaned off TPN on 3 months after transplantation with a functioning graft. He developed mild acute cellular rejection on day 111, which was successfully treated with bolus injections of steroid. The third patient encountered mild rejection at 1 year after transplantation. Subsequently intestinal perforation of graft occurred maybe due to adverse effect of steroid therapy. This was fortunately successfully managed. However, graft function deteriorated due to chronic rejection. We had to remove the graft. Re-transplantation is currently under consideration. CONCLUSION: LDSBTs were performed to the three patients with hypoganglionosis successfully. Long-term well functioning grafts were obtained in two of three cases. It is advisable that LDSBT would be performed before getting more serious liver dysfunction or blood access route problem. It would lead to physical and psychological improvement of quality of life.
Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.
Objectives The aim of this study was to determine whether computer-assisted digital analysis and acoustic radiation force impulse (ARFI) imaging were useful for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative pancreatic fistula (POPF). Methods Seventy-eight patients scheduled to undergo pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic neck was measured preoperatively using ARFI imaging. Pancreatic tissue components on a whole slide image were quantified using an automatic image processing software. The relationship between SWV, fibrotic tissue content, and POPF incidence and clinical severity was analyzed. Results The median collagen fiber, fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively. Unlike fatty tissue, collagen fiber content and acinar cells were correlated with SWV ( ρ = 0.440, P < 0.001 and ρ = −0.428, P < 0.001, respectively). Although collagen fiber content and SWV were associated with the overall incidence of POPF ( P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no statistical correlation with clinically relevant POPF ( P = 0.268 and 0.052, respectively). Conclusions We objectively quantified the pancreatic tissue components using an automatic image processing software. Shear wave velocity was significantly related to collagen fiber content and suggests that ARFI imaging can be useful for evaluating pancreatic fibrosis.
Abstract Background: The abundance of cytotoxic T cell infiltrates has important implications for patient outcome and therapeutic design in pancreatic ductal adenocarcinoma (PDAC), although intratumoral heterogeneity remains a major challenge for the better understanding of complicated immune microenvironment of PDAC. We aimed to characterize spatial CD8+ cell distribution within PDAC tissues, which might refine the prognostic role of tumor-infiltrating CD8+ lymphocytes. Methods: We measured CD8+ cell density in tumor center, tumor margin, or whole tumor area, as well as CD8+ cell proximity to carcinoma cells, using fluorescent multiplex immunohistochemistry-based tissue computation on whole tissue sections of 214 surgically resected PDACs. Multivariable Cox proportional hazards regression analysis was performed to assess the association of CD8+ cell density with pancreatic cancer-specific survival, adjusting for major clinicopathologic and immune-related features, including the programmed cell death 1 ligand 1 (CD274, PD-L1) expression and the extent of tertiary lymphoid structures. Results: We found a substantial heterogeneity in CD8+ cell density with, on average, a 2-fold-lower density in tumor center than in tumor margin. In multivariable model, the trend of prolonged survival with higher CD8+ cell density was stronger for tumor center, compared to tumor margin or whole tumor area (P for trend = 0.002, 0.07, or 0.009, respectively). Tumor CD274 expression and extensive tertiary lymphoid structures were appeared to be associated with higher CD8+ cell density in tumor margin, but not with CD8+ cell density in tumor center. The mean distance from tumor cells to the adjacent CD8+ cells correlated inversely with CD8+ cell density in tumor center (Spearman correlation efficient, -0.89), although the density of CD8+ cells proximate to cancer cells did not show any prognostic correlation. Conclusion: Our data have shown a prognostic significance of CD8+ cell density in tumor center of PDAC, where CD8+ cell infiltration has been severely limited, suggesting a major role of pro-tumorigenic effect of immunosuppressive microenvironment in pancreatic cancer. Citation Format: Yohei Masugi, Tokiya Abe, Minoru Kitago, Masahiro Shinoda, Michiie Sakamoto. Characterization of spatial distribution of tumor-infiltrating CD8+ T cells refines their prognostic impact in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1101.
