JAK2 Loss Arising From Tumor-SpreadThrough-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma:A Machine Learning Approach

Background@#Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. @*Methods@#This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. @*Results@#The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. @*Conclusion@#In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

A novel pancreaticogastrostomy method using only two transpancreatic sutures: early postoperative surgical results compared with conventional pancreaticojejunostomy

PURPOSE: To evaluate the surgical outcomes of pancreaticogastrostomy (PG) using two transpancreatic sutures with a buttress method through an anterior gastrostomy (PGt), and compare these results with our previous experience with pancreaticojejunostomy (PJ) including the dunking and duct to mucosa methods after pancreaticoduodenectomy (PD). METHODS: In this study, 171 patients who had undergone PD between January 2005 and April 2013 were classified into three groups according to the method of the pancreaticoenteric anastomosis: dunking PJ (PJu group; n = 67, 39.1%), duct to mucosa PJ (PJm group; n = 41, 23.9%), and PGt (PGt group; n = 63, 36.8%). We retrospectively analyzed patient characteristics, perioperative outcomes, and surgical results. RESULTS: Both groups had comparable demographics and pathology, and there were no significant differences in operative time, estimated blood loss, or postoperative hospital stay. Within the two groups, morbidities occurred in 49 cases (10.7%), and were not significantly different between the two groups, excepting postoperative pancreatic fistula (POPF). The PGt group had a lower rate of POPF (18/63, 28.6%) than the PJu and PJm groups (21/67, 31.3% and 19/41, 46.3%; P = 0.048), especially in terms of grades B and C POPF (4/63 [6.3%] in the PGt group vs. 7/67 [10.4%] in the PJu group and 9/41 [22.0%] in the PJm group, P = 0.049). CONCLUSION: The PGt method showed feasible outcomes for POPF and had advantages over dunking PJ and duct to mucosa PJ with respect to immediate postoperative results. PGt may be a promising technique for pancreaticoenteric anastomosis after PD.

A Case of Severe Rhabdomyolysis with Acute Renal Failure after Doxylamine Overdose / 대한신장학회잡지

Doxylamine succinate is an over-the-counter drug widely used for treating insomnia. We experienced a case of severe rhabdomyolysis complicating acute renal failure after doxylamine overdose in a 24-year- old male. The maximum values of creatine kinase and creatinine level during hospitalization were 264,141 IU/L and 8.4 mg/dL, respectively. Oliguria and severe dyspnea occurred on the sixth hospital day and were treated with hemodialysis. Then, he recovered without any sequelae. To the best of our knowledge, the maximum creatine kinase level of 264,141 IU/L in the present case is the highest value among the case reports on doxylamine-induced rhabdomyolysis and this is the first case report in Korea of doxylamine-induced severe rhabdomyolysis accompanying oliguric acute renal failure and requiring treatment with hemodialysis.