オキサリプラチン誘発性類洞閉塞症候群の臨床モデル

京都大学新制・課程博士博士(医学)甲第24497号医博第4939号新制||医||1064(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 中島 貴子, 教授 永井 純正, 教授 寺田 智祐学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

A tropical analogue of Fay's trisecant identity and the ultra-discrete periodic Toda lattice

We introduce a tropical analogue of Fay's trisecant identity for a special family of hyperelliptic tropical curves. We apply it to obtain the general solution of the ultra-discrete Toda lattice with periodic boundary conditions in terms of the tropical Riemann's theta function.Comment: 25 pages, 3 figure

Integrable structure of box-ball systems: crystal, Bethe ansatz, ultradiscretization and tropical geometry

The box-ball system is an integrable cellular automaton on one dimensional lattice. It arises from either quantum or classical integrable systems by the procedures called crystallization and ultradiscretization, respectively. The double origin of the integrability has endowed the box-ball system with a variety of aspects related to Yang-Baxter integrable models in statistical mechanics, crystal base theory in quantum groups, combinatorial Bethe ansatz, geometric crystals, classical theory of solitons, tau functions, inverse scattering method, action-angle variables and invariant tori in completely integrable systems, spectral curves, tropical geometry and so forth. In this review article, we demonstrate these integrable structures of the box-ball system and its generalizations based on the developments in the last two decades.Comment: 73 page

Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K‐RAS status for unresectable colorectal liver metastasis (BECK study): Long‐term results of survival

[Background/Purpose]To investigate the long‐term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. [Methods]Recurrence and survival data with long‐term follow‐up were analyzed in the cohort of a multi‐institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). [Results]A total of 22/12 patients with K‐RAS wild‐type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left‐sided primary tumors than in right‐sided tumors (75.0% vs 30.0%, P = .022). The median follow‐up was 72.6 months. The 5‐year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5‐year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow‐up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5‐year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1‐4). [Conclusions]Conversion hepatectomy achieved a similar long‐term survival to the results of previous studies in initially resectable patients, although many of them experienced several post‐hepatectomy recurrences. Left‐sided primary was found to be the predictor for conversion hepatectomy

A Propensity Score-Based Analysis of Laparoscopic Liver Resection for Liver Malignancies in Elderly Patients

Purpose: Laparoscopic liver resection is safe, feasible and associated with less blood loss, shorter hospital stays and fewer postoperative complications in the working age patients with malignant liver tumors. However, it is still unclear if the elderly patients with malignant liver tumors would also benefit from that approach as the younger patients. So, the aim of the study was to compare the clinical outcomes of laparoscopic versus open liver resection for malignant liver tumors in elderly patients. Materials and Methods: Between March 2009 and July 2016, all elderly patients (≥70 years old) who underwent laparoscopic (n = 40) and open (n = 202) liver resection for malignant liver tumors were included. A one to one propensity score matching analysis was performed, based on 6 covariates, to decrease the selection bias. Results: There was no significant difference between the laparoscopic and open liver resection groups regarding the patient characteristics and tumor features. The operative time was comparable between both groups (Laparoscopic group 259 min vs Open group 308 min, p = .86), while patients who underwent laparoscopic liver resection had lower intraoperative blood loss (30 ml vs 517 ml, p < .0001), shorter hospital stays (10 days vs 23 days, p < .0001), and less overall morbidity (15% vs 38%, p = .04). The one-, three-, and five-year survival for patients with hepatocellular carcinoma was comparable between both groups (Laparoscopic group 96%, 74%, 47%, vs Open group 94%, 71%, 48%, p = .82), whereas The one-, three-, and five-year recurrence-free survival for patients with hepatocellular carcinoma was significantly higher in the laparoscopic group (88%, 60%, 60% vs 54%, 25%, 19%, p = .019). Conclusions: Laparoscopic approach for minor liver resection in elderly patients is safe and feasible with less blood loss, a shorter hospital stay, less postoperative complications and a better oncological outcome

Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression via CCR5

Mesenchymal stem cells (MSCs) are recruited from BM to the stroma of developing tumors, where they serve as critical components of the tumor microenvironment by secreting growth factors, cytokines, and chemokines. The role of MSCs in colorectal cancer (CRC) progression was controversial. In this study, we found that C-C chemokine receptor type 5 (CCR5) ligands (i.e., C-C motif chemokine ligand 3 (CCL3), CCL4, and CCL5) were highly produced from MSCs using a chemokine array screening with conditioned media from the cultured human MSCs. A relatively strong CCR5 expression could be detected within the cytoplasm of several CRC cell lines. Regarding the effect of MSC, we found that the xenografts in which CCR5-overexpressing HCT116 cells were inoculated into immunocompromised mice were highly promoted in vivo by a mixture with MSCs. Notably, the CCR5 inhibitor, maraviroc, significantly abolished the MSC-induced tumor growth in vivo. In human clinical specimens (n = 89), 20 cases (29%) were high for CCR5, whereas 69 cases (71%) were low. Statistical analyses indicated that CCR5 expression in primary CRC was associated with CRC patients’ prognosis. Especially, stage III/IV patients with CCR5-high CRCs exhibited a significantly poorer prognosis than those with CCR5-low CRCs. Furthermore, we investigated the effects of preoperative serum CCR5 ligands on patients’ prognosis (n = 114), and found that CRC patients with high serum levels of CCL3 and CCL4 exhibited a poorer prognosis compared to those with low levels of CCL3 and CCL4, while there was no association between CCL5 and prognosis. These results suggest that the inhibition of MSC–CRC interaction by a CCR5 inhibitor could provide the possibility of a novel therapeutic strategy for CRC, and that serum levels of CCL3 and CCL4 could be predictive biomarkers for the prognosis of CRC patients