ヒト肝細胞癌においてherpesvirus entry mediatorの発現がもたらす影響

BACKGROUND: Herpes virus entry mediator (HVEM), also known as tumour necrosis factor receptor (TNFR) superfamily 14, regulates a variety of physiological and pathological responses in both innate and acquired immunity. Although HVEM is also suggested to be a critical regulator in tumours, actual roles in human cancer are largely unknown. This study aimed to clarify clinical importance of HVEM in human hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We studied HVEM expression in 150 HCC patients to explore its clinical relevance, and we examined tumour infiltrating T cells and local immune status of them. RESULTS: HVEM was expressed in HCC cells, while no or only limited expression was observed in normal tissues in the liver. Tumour HVEM expression was significantly correlated with age, serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level, vascular invasion and tumour node metastasis (TNM) stage. Furthermore, tumour HVEM expression significantly correlated with postoperative recurrence and survival. Importantly, multivariate analysis indicated that the HVEM status had an independent prognostic value. Furthermore, HVEM status was inversely correlated with tumour-infiltrating CD4(+), CD8(+) and CD45RO(+) lymphocytes. In addition, it was also associated with reduced expression of perforin, granzyme B and interferon-γ (IFN-γ). Taken together, tumour-expressing HVEM plays a functionally important role in HCC. CONCLUSION: Tumour-expressing HVEM plays a critical role in human HCC, possibly through regulating immune evasion. Therefore, targeting HVEM may be a novel promising therapeutic strategy for HCC.博士（医学）・乙第1359号・平成27年5月28日Copyright © 2014 Elsevier Ltd

無症候性腎機能障害が結腸癌術後の臨床経過に及ぼす影響

Purpose: To evaluate the effect of mild renal dysfunction on the clinical course after colectomy in patients with colon cancer. Methods: The subjects of this retrospective study were 263 patients who underwent surgical resection for colon cancer at our hospital between 2011 and 2015. Renal function was assessed based on preoperative estimated glomerular filtration rate (eGFR) values. Patients were divided into groups based on their eGFR value of 55 ml/min/1.73 m2. The Mann-Whitney U test, chi-square or Fisher exact test, and log-rank test were used in the data analysis. Results: There were 59 patients (22.4%) in the low eGFR group and 204 patients in the normal eGFR group. There were differences between the groups in age, comorbidities, and the levels of hemoglobin, albumin, and serum creatinine. The overall postoperative complication rate, frequency of severe complications, and length of stay were significantly higher in the low eGFR group than in the normal eGFR group. Multivariate analysis revealed that low eGFR was the only independent risk factor for severe complications (Clavien-Dindo classification III/IV). There were no differences in survival between the groups. Conclusion: Preoperative asymptomatic renal dysfunction may be correlated with the development of postoperative complications and a possible significant risk factor for severe complications after colon cancer surgery.博士（医学）・甲第804号・令和3年12月21日© 2021. Springer Nature Singapore Pte Ltd.The version of record of this article, first published in Surgery Today, is available online at Publisher’s website: http://dx.doi.org/10.1007/s00595-021-02363-w.発行元が定める登録猶予期間終了の後、本文を登録予定（2021.01

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

下部直腸癌における側方リンパ節転移に関して、造影MRI で描出される中直腸動脈の転移予測因子に関する検討

Purpose: Lateral lymph node (LLN) metastasis is one of the leading causes of local recurrence in patients with lower rectal cancer. Unfortunately, no diagnostic biomarkers are currently available that can predict LLN metastasis preoperatively. Accordingly, we investigated the relationship between the middle rectal artery (MRA) identified by contrast-enhanced magnetic resonance imaging (ceMRI) and LLN metastases. Methods: Data from 102 patients with lower rectal cancer who underwent surgery, and were evaluated by preoperative ceMRI, between 2008 and 2016 were reviewed retrospectively. Two expert radiologists evaluated the MRA findings. The diagnostic performance of MRA for LLN metastasis was evaluated by a multivariate analysis with conventional clinicopathological factors. Results: The MRA was detected in 67 patients (65.7%), including 32 (31.4%) with bilateral MRA and 35 (34.3%) with unilateral MRA. The tumor size, presence of the MRA, and clinical LLN status were significantly correlated with LLN metastasis. A multivariate analysis demonstrated that the presence of MRA (P = 0.045) and clinical LLN status (P = 0.001) were independent predictive factors for LLN metastasis. Furthermore, the sensitivity and negative predictive value of MRA for LLN metastasis were 95% and 97.1%, respectively. Conclusion: We successfully demonstrated that MRAs could be clearly detected by ceMRI, and the presence of MRA robustly predicted LLN metastasis in patients with lower rectal cancer, highlighting its clinical significance in the selection of more appropriate treatment strategies. Trial registration: Trial registration number: retrospectively registered 2126 Trial registration date of registration: August 23, 2019.博士（医学）・乙第1512号・令和3年12月21日© 2021. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/

ヒト大腸癌におけるHVEM発現は腫瘍の進行と予後に影響する

Background: Herpesvirus entry mediator (HVEM) has been recently suggested to play certain roles in cancer biology. We examined HVEM expression in human colorectal cancer (CRC) to reveal its clinical importance. Materials and Methods: Immunohistochemical staining was carried-out in normal epithelium, benign and malignant lesions. Results: While intense HVEM expression was not observed in normal epithelium and hyperplastic polyps, 24% of adenoma and more than half of CRCs had high HVEM expression. In 234 CRCs, HVEM expression was significantly associated with tumor status and pathological stage. Patients with high HVEM expression had a significantly poorer prognosis than those with low expression. Importantly, HVEM status had an independent prognostic value in CRC. Furthermore, HVEM status was inversely corrected with the presence of tumor-infiltrating T-cells. Conclusion: HVEM may play a critical role in tumor progression and immune evasion, and may also be a novel prognostic marker and potential therapeutic target in human CRC.博士（医学）・乙第1363号・平成27年7月31日発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://ar.iiarjournals.org/content/35/3/1361.abstract"　（※全文閲覧は学内限定

根治切除後の結腸癌StageⅡ、StageⅢ、及び大腸癌肝転移における原発部位が与える影響

Purpose: Primary tumor location of colon cancer has been reported to affect the prognosis after curative resection. However, some reports suggested the impact was varied by tumor stage. This study analyzed the prognostic impact of the sidedness of colon cancer in stages II, III, and liver metastasis after curative resection using propensity-matched analysis. Methods: Right-sided colon cancer was defined as a tumor located from cecum to splenic flexure, while any more distal colon cancer was defined as left-sided colon cancer. Patients who underwent curative resection at Nara Medical University hospital between 2000 and 2016 were analyzed. Results: There were 110 patients with stage II, 100 patients with stage III, and 106 patients with liver metastasis. After propensity matching, 28 pairs with stage II and 32 pairs with stage III were identified. In the patients with stage II, overall survival (OS) and recurrence-free survival (RFS) were not significantly different for right- and left-sided colon cancers. In the patients with stage III, OS and RFS were significantly worse in right-sided colon cancer. In those with liver metastasis, OS of right-sided colon cancer was significantly worse than left-sided disease, while RFS was similar. Regarding metachronous liver metastasis, the difference was observed only in the patients whose primary colon cancer was stage III. In each stage, significantly higher rate of peritoneal recurrence was found in those with right-sided colon cancer. Conclusion: Sidedness of colon cancer had a significant and varied prognostic impact in patients with stage II, III, and liver metastasis after curative resection.博士（医学）・乙第1495号・令和3年3月15日Copyright © 2021 The Korean Society of Coloproctology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

Reexamination of Refrigeration Power of the LHD Cryogenic System After Fire and Restart of Operation

The Large Helical Device (LHD), built in the 1990s, is a heliotron-type fusion plasma experimental device with the world\u27s first fully superconducting magnetic confinement system. The LHD cryogenic system operated stably for 18 years from 1998 to 2015 with high availability exceeding 99%. Unfortunately, in August 2015, a fire occurred in the cold box of the He refrigerator during maintenance, and nonmetallic components such as multilayer insulation films, temperature sensors, and measuring instruments were burnt down. Repair work started in November 2015 and completed at the end of July 2016. In August 2016, a test operation of the He refrigerator was conducted, and the refrigeration power was compared with that measured in the initial performance test conducted in 1995. The measured equivalent refrigeration power at 4.4 K was 9.19 kW, representing a decrease ~2% from the value of 9.38 kW measured in 1995. We attributed this slight decrease in refrigeration power to performance deterioration owing to aging over 18 years and not to the fire. The LHD restarted operation in January 2017, and its 19th operational cycle for a deuterium plasma experiment was conducted successfully up to August 2017. This paper reports the operational history and restart of the LHD superconducting magnet and cryogenic system

Hepatic artery injury during left hepatic trisectionectomy for colorectal liver metastasis treated by portal vein arterialization

Portal vein arterialization (PVA) has been applied as a salvage procedure in hepatopancreatobiliary surgeries, including transplantation and liver resection, with revascularization for malignancies. Here we describe the use PVA as a salvage procedure following accidental injury of the hepatic artery to the remnant liver occurred during left hepatic trisectionectomy for colorectal liver metastases (CRLM). A 60-year-old man with cancer of the sigmoid colon and initially unresectable CRLM received 11 cycles of hepatic arterial infusion chemotherapy with 5-fluorouracil (1500 mg/week), after which CRLM was downstaged to resectable. One month after laparoscopic sigmoidectomy, a left trisectionectomy and wedge resection of segment 6 were performed. The posterior branch of the right hepatic artery, the only feeding artery to the remnant liver, was injured and totally dissected. Because microsurgical reconstruction of the artery was impossible, PVA was used; PVA is the sole known procedure available when hepatic artery reconstruction is impossible. The patient then suffered portal hypertension, and closure of arterio-portal anastomosis using an interventional technique with angiography was eventually performed on postoperative day 73. Therefore, it is considered that because PVA is associated with severe postoperative portal hypertension, closure of the arterio-portal shunt should be performed as soon as possible on diagnosing portal hypertension

Huge hepatocellular carcinoma with multiple intrahepatic metastases: An aggressive multimodal treatment

Introduction: Huge hepatocellular carcinoma (HCC) possesses a potential risk for spontaneous rupture, which leads to a life-threatening complication with a high mortality rate. In addition, a large HCC is frequently accompanied by intrahepatic metastases. Presentation of case: We describe, the case of a 74-year-old woman with a huge extrahepatically expanding HCC with multiple intrahepatic metastases who was treated by liver resection with repeated transcatheter arterial chemoembolization (TACE). To prevent tumor rupture or bleeding, we performed right hepatectomy. After the operation, TACE was applied for multiple intrahepatic metastases in the remnant liver. Furthermore, the elevated protein induced vitamin K absence (PIVKA II) level had decreased to limits within the normal range. Three months after the first TACE, computed tomography revealed several recurrences in the liver. TACE was applied for the second and third time and the tumors were well controlled. Discussion: Although, liver resection is occasionally performed for patients with huge HCC to avoid spontaneous tumor rupture, only surgical approach might not be sufficient for such advanced HCC. To achieve long-term survival, it is necessary to control the residual intrahepatic tumors. We could control multiple intrahepatic metastases with repeated TACEs after hepatectomy. Conclusion: Multimodal treatment involving hepatectomy and TACE might be a good treatment strategy for patients with huge HCC with multiple intrahepatic metastases if the tumors are localized in the liver without distant or peritoneal metastasis

結腸直腸内視鏡的粘膜下層剥離術後腸管内洗浄液中遊離腫瘍細胞に対する in vitro 解析

Purpose: Colorectal endoscopic submucosal dissection (ESD) produces exfoliated tumor cells that occasionally cause local recurrence. However, the biological characteristics of these tumor cells have not been clarified. The aim of this study was to clarify the genetic background and viability of exfoliated tumor cells in colorectal ESDs, as well as possible method for their elimination. Methods: Post-ESD intraluminal lavage samples from 19 patients who underwent colorectal ESDs were collected. In four patients with adenocarcinoma, gene mutations in the primary tumors and exfoliated cells in lavage samples were analyzed using a next-generation sequencer (NGS). In 15 patients with adenoma or adenocarcinoma, the viability of exfoliated cells and the cell-killing effect of povidone-iodine on exfoliated cells were evaluated. Results: The analysis using a NGS demonstrated that tumors targeted for ESD had already acquired mutations in many genes involved in cell proliferation, angiogenesis, and invasions. Furthermore, gene mutations between the exfoliated tumor cells and tumors resected by ESDs showed a 92 to 100% concordance. The median viable cell counts and the median viability of exfoliated cells in intraluminal lavage samples after ESDs were 4.9 × 105 cells/mL and 24%, respectively. The viability of the exfoliated cells did not decrease even 12 h after ESD. However, contact with 2.0% povidone-iodine solution reduced both viable cell counts and viability, significantly. Conclusion: A large number of tumor cells exfoliated during colorectal ESDs had acquired survival-favorable gene mutations and could survive for some time. Therefore, a lavage using a solution of 2.0% povidone-iodine may be effective against such cells. Trial registration: The prospective study registered 1317, and the retrospective study registered 2729. The prospective study approved on June 20, 2016, and the retrospective study approved on October 6, 2020.博士（医学）・乙第1520号・令和4年3月15日© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00384-021-04037-y.発行元が定める登録猶予期間終了の後、本文を登録予定（2023.01