Naoto Nishigori

von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy

Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6) and without (n = 17) bevacizumab were analyzed. CALI (n = 6) and splenomegaly (n = 9) were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag) and serum aspartate aminotransferase (AST) levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9), but not in patients without splenomegaly (n = 14). Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation.

Erythropoietin attenuates intestinal inflammation and promotes tissue regeneration.

Abstract Background. The prevalence of inflammatory bowel disease (IBD) is increasing. Since patients usually need long-term treatment and suffer from reduced quality of life, there is a need to develop new therapeutic strategy. The aim of this study was to investigate the therapeutic potential of erythropoietin (EPO) for the treatment of IBD. Methods. Murine colitis was induced by 3.0% Dextran Sulfate Sodium (DSS). Recombinant human EPO (rhEPO) was given to evaluate the anti-inflammatory and regenerative effects on intestinal inflammation. The effect of rhEPO on human colon epithelial cells was also evaluated. Immunohistochemical analysis of EPO receptor was performed in human IBD tissues. Results. While about 62% of control mice with severe colitis induced by 5-day DSS died, 85% of mice treated with rhEPO survived. Histological analysis confirmed that EPO treatment reduced the colonic inflammation. Furthermore, EPO treatment significantly downregulated the local expressions of IFN-γ, TNF-α and E-selectin in the colon, suggesting that the effect was associated with inhibiting local immune activation. In a 4-day DSS-induced colitis model, rhEPO significantly improved the recovery of body weight loss compared to controls. Furthermore, proliferating cell nuclear antigen expression was significantly upregulated in the colon tissue from mice treated with rhEPO compared to controls. In addition, rhEPO increased the growth of cultured human colon epithelial cells in a dose-dependent manner. Furthermore, EPO-receptor expression was confirmed in human IBD colon tissues. Conclusion. Three major functions of EPO, hematopoiesis, anti-inflammation and regeneration, may produce significant effects on intestinal inflammation, therefore suggesting that rhEPO might be useful for IBD.

Local recurrence after rectal endoscopic submucosal dissection: a case of tumor cell implantation

We report a case of local recurrence of cancer after rectal endoscopic submucosal dissection (ESD). A 52-year-old male underwent a curative resection with ESD for rectal intramucosal cancer. Seventy-four months after ESD, surveillance colonoscopy showed an elevated lesion on the ESD scar, suspicious of a recurrence. The patient subsequently underwent a low anterior resection (intersphincteric) with lymph node dissection. Pathology revealed a well-differentiated adenocarcinoma, similar to the ESD specimen. We suspected that the local recurrence was caused by implantation of tumor cells during the ESD, due to surgical manipulation performed with the tumor in an exposed setting for a long period of time.

Laparoscopic surgery after endoscopic resection for rectal cancer and neuroendocrine tumors

BackgroundEndoscopic resection (ER) of tumors causes inflammation, edema, fibrosis, and adhesions in the surrounding tissue. However, little is known about the effect of ER on subsequent laparoscopic surgery for rectal tumors. The objective of this retrospective study was to analyze the effect of ER on subsequent laparoscopic surgery for rectal tumors.MethodsTwenty-eight patients underwent laparoscopic surgery for rectal adenocarcinoma with submucosal invasion or a rectal neuroendocrine tumor at our hospital between January 2005 and December 2012. A group of 14 patients who underwent laparoscopic surgery with previous ER was compared to a group of 14 patients who underwent laparoscopic surgery without previous ER.ResultsThough most fibrosis involved the submucosa after polypectomy and endoscopic mucosal resection, fibrosis after endoscopic submucosal dissection involved the muscularis propria in two patients, and the subserosa in one patient. There were no statistically significant differences in clinical outcomes between the groups.ConclusionLaparoscopic surgery after ER for rectal tumors is safe and feasible. Laparoscopic surgery is the reasonable first-choice for radical treatment of rectal tumors after ER.