Protective effects of simultaneous splenectomy on small‐for‐size liver graft injury in rat liver transplantation

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small‐for‐size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)‐1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET‐1 mRNA and hepatic protein levels of ET‐1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET‐1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET‐1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET‐1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET‐1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.     

Authors’ Reply: Relevance of Level IIb Neck Dissection in Patients with Head and Neck Squamous Cell Carcinomas

World Journal of Surgery -     

ASO Visual Abstract: Fecal Microbes Associated with the Outcomes After Esophagectomy in Patients with Esophageal Cancer

Annals of Surgical Oncology -     

Significance of D-dimer-based screening for detecting pre-operative venous thromboembolism in patients with esophageal cancer after neoadjuvant chemotherapy

International Journal of Clinical Oncology - A limited number of studies have evaluated the risk of developing venous thromboembolism (VTE) during neoadjuvant chemotherapy (NAC) for esophageal...     

17Beta-hydroxysteroid dehydrogenases in human endometrium and its disorders

In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinoma. 17Beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes involved in the formation of active sex steroids, including testosterone, estrone (E1) and estradiol (E2). Estrogens are interchanged by two enzymes, 17-HSD types 1 and 2, type 1 converts E1 to E2, and type 2 does reverse actions. 17-HSD type 5 catalyzes the reduction of androstenedione to testosterone. 17-HSD type 2 expression was decreased through normal endometrium, hyperplasia and carcinoma accordingly. There was a significant inverse correlation between intratumoral E2 concentration and the level of 17-HSD type 2 mRNA in endometrial carcinoma. 17-HSD type 5 expression was significantly increased through normal endometrium, hyperplasia and carcinoma accordingly. These results indicated that 17-HSD types 2 and 5 play an important role in the regulation of in situ estrogen production in endometrial carcinoma.     

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.     

Pharmacokinetics of Gefitinib in a Patient with Non-Small Cell Lung Cancer Undergoing Continuous Ambulatory Peritoneal Dialysis

A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure and who had undergone right upper lobectomy for lung adenocarcinoma (pT2aN0M0) 2 years ago was admitted for recurrence of lung cancer presenting as multiple brain metastases. An epidermal growth factor receptor mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746-A750) in exon 19. After whole-brain radiotherapy, we started daily administration of 250 mg gefitinib under the continuation of CAPD and performed a pharmacokinetic analysis. We speculated that the plasma concentration of gefitinib reached the steady state at least by day 16 after the start of gefitinib (626.6 ng/ml at trough level). On day 46, the plasma concentration was 538.4 ng/ml at trough level and the concentration in the peritoneal dialysis fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the pharmacokinetics of gefitinib. During gefitinib therapy, there were no significant adverse events except for grade 2 diarrhea. Gefitinib could be safely administered to a patient undergoing CAPD.Key Words: Gefitinib, Continuous ambulatory peritoneal dialysis, Chronic renal failure, Epidermal growth factor receptor, Non-small cell lung cancer