複数異種移植マウスモデルにおけるPentagamavunone-1の膵臓癌に対する単剤および併用療法としての前臨床評価

We previously reported that pentagamavunone-1 (PGV-1) effectively inhibited cell proliferation in many types of human tumors, including pancreatic cancer, by inducing M phase (prometaphase) arrest, senescence, and apoptosis with few side effects. However, a detailed evaluation of the effects of PGV-1 on pancreatic cancer cells in an in vivo setting has not yet been conducted. The present study investigated the potential efficacy of PGV-1 as both monotherapy and combination therapy for pancreatic cancer using multiple xenograft mouse assays. A cell-line derived xenograft model (CDX-M) with pancreatic cancer cell line and a patient-derived xenograft mouse model (PDX-M) using resected pancreatic cancer samples without neoadjuvant chemotherapy were established in both heterotopic and orthotopic manners. PGV-1 effectively suppressed tumor formation at the heterotopic and orthotopic sites in CDX-M than in untreated mice. Combination therapy with PGV-1 and gemcitabine more effectively suppressed tumor formation than monotherapy with PGV-1 or gemcitabine when administered after tumor formation. Monotherapy with PGV-1 or gemcitabine less effectively suppressed tumor formation in PDX-M than in CDX-M, whereas combination therapy with PGV-1 and gemcitabine more effectively suppressed tumor formation. PGV-1 as monotherapy and combination therapy with gemcitabine effectively inhibited tumor formation and has potential as an anticancer candidate for pancreatic cancer.権利情報：© The Author(s) 2022. 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/

大腸癌肝転移におけるCD200発現の臨床的意義

Background: Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). Methods: We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. Results: The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p < 0.001), primary CRC N2-3 (p = 0.049), and high-CD200 expression (p = 0.004). Furthermore, CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes in CRLM were significantly higher in the low-CD200 group than in the high-CD200 group (p = 0.005, p = 0.001, and p < 0.001, respectively). In addition, patients who had received preoperative chemotherapy had higher CD200 expression than those who had not received preoperative chemotherapy, and OS was significantly worse in patients in the high-CD200 group who had received preoperative chemotherapy. Conclusions: CD200 expression was an independent prognostic factor in CRLM. CD200 may play a critical role in tumor immunity in CRLM, and can therefore be used as a potential therapeutic target in CRLM.博士（医学）・乙第1497号・令和3年3月15日© 2021. Society of Surgical Oncology.© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Annals of Surgical Oncology. The final authenticated version is available online at: https://doi.org/10.1245/s10434-020-09471-w

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

Preventative effects of ramelteon against postoperative delirium after elective liver resection.

BackgroundPostoperative delirium was reported to be associated with increased postoperative mortality after liver resection. Therefore, it is crucial to prevent postoperative delirium in such cases. Ramelteon, an agonist of melatonin receptor has been suggested to be useful for preventing delirium. The aim of this study was to examine whether ramelteon is effective at preventing delirium after elective liver resection.MethodsThe cases of patients who underwent liver resection at Nara Medical University (Nara, Japan) between January 2014 and August 2018 were analyzed. During the period from January 2017 to August 2018, ramelteon was prospectively administered to patients who underwent liver resection [8 mg/day on the day before surgery and on postoperative days 1 to 3] (ramelteon group), whereas ramelteon was not administered during the period from January 2014 to December 2016 (control group). The perioperative outcomes of the two groups were compared.ResultsThere were 120 patients in the ramelteon group and 186 patients in the control group. No significant intergroup differences in background factors, including age, gender, and preoperative serological laboratory data, were detected. The incidence of postoperative delirium was significantly lower in the ramelteon group (5.8% vs. 15.1%, P = 0.035). Multivariate analysis revealed that being aged ≥75 (P = 0.002), being male (P = 0.020), cardiovascular disease (P = 0.023), blood loss ≥1000ml (P = 0.001) and the absence of ramelteon treatment (P = 0.046) were independent risk factors for postoperative delirium.ConclusionThe administration of ramelteon might reduce the risk of postoperative delirium after elective liver resection

Preclinical evaluation of pentagamavunone-1 as monotherapy and combination therapy for pancreatic cancer in multiple xenograft models

Abstract We previously reported that pentagamavunone-1 (PGV-1) effectively inhibited cell proliferation in many types of human tumors, including pancreatic cancer, by inducing M phase (prometaphase) arrest, senescence, and apoptosis with few side effects. However, a detailed evaluation of the effects of PGV-1 on pancreatic cancer cells in an in vivo setting has not yet been conducted. The present study investigated the potential efficacy of PGV-1 as both monotherapy and combination therapy for pancreatic cancer using multiple xenograft mouse assays. A cell-line derived xenograft model (CDX-M) with pancreatic cancer cell line and a patient-derived xenograft mouse model (PDX-M) using resected pancreatic cancer samples without neoadjuvant chemotherapy were established in both heterotopic and orthotopic manners. PGV-1 effectively suppressed tumor formation at the heterotopic and orthotopic sites in CDX-M than in untreated mice. Combination therapy with PGV-1 and gemcitabine more effectively suppressed tumor formation than monotherapy with PGV-1 or gemcitabine when administered after tumor formation. Monotherapy with PGV-1 or gemcitabine less effectively suppressed tumor formation in PDX-M than in CDX-M, whereas combination therapy with PGV-1 and gemcitabine more effectively suppressed tumor formation. PGV-1 as monotherapy and combination therapy with gemcitabine effectively inhibited tumor formation and has potential as an anticancer candidate for pancreatic cancer

Current status of laparoscopic repeat liver resection for recurrent hepatocellular carcinoma

Repeat liver resection (RLR) is an effective treatment approach for recurrent hepatocellular carcinoma (HCC) and can provide acceptable long-term outcomes in select patients. Recent randomized controlled trials comparing RLR with radiofrequency ablation revealed that the latter approach was associated with a higher rate of early recurrence compared with RLR. With recent advances in laparoscopic liver resection (LLR), RLR has been increasingly performed using laparoscopy. Several propensity score-matched studies reported that laparoscopic RLR achieved lower blood loss and shorter hospital stays compared to open RLR. However, laparoscopic RLR requires more advanced techniques because of adhesions formed after the previous liver resection, changes in anatomical landmarks, and deformity of the remnant liver. The recently described difficulty classification of laparoscopic RLR is based on five factors including type of previous liver resection (open or laparoscopic), number of previous liver resections, surgical procedure used in previous liver resections, tumor location in previous liver resections, and difficulty score of LLR for recurrent HCC. We reviewed the available literature to summarize available evidence suggesting that laparoscopic RLR might be considered a more minimally invasive surgical treatment approach for recurrent HCC as long as the indication for laparoscopic RLR is carefully determined

Heterogeneous Redistribution of Facial Subcategory Information Within and Outside the Face-Selective Domain in Primate Inferior Temporal Cortex

The inferior temporal cortex (ITC) contains neurons selective to multiple levels of visual categories. However, the mechanismsby which these neurons collectively construct hierarchical category percepts remain unclear. By comparing decoding accuracywith simultaneously acquired electrocorticogram (ECoG), local field potentials (LFPs), and multi-unit activity in the macaqueITC, we show that low-frequency LFPs/ECoG in the early evoked visual response phase contain sufficient coarse category (e.g.,face) information, which is homogeneous and enhanced by spatial summation of up to several millimeters. Late-induced highfrequencyLFPs additionally carry spike-coupled finer category (e.g., species, view, and identity of the face) information, which isheterogeneous and reduced by spatial summation. Face-encoding neural activity forms a cluster in similar cortical locationsregardless of whether it is defined by early evoked low-frequency signals or late-induced high-gamma signals. By contrast,facial subcategory-encoding activity is distributed, not confined to the face cluster, and dynamically increases its heterogeneityfrom the early evoked to late-induced phases. These findings support a view that, in contrast to the homogeneous and staticcoarse category-encoding neural cluster, finer category-encoding clusters are heterogeneously distributed even outside theirparent category cluster and dynamically increase heterogeneity along with the local cortical processing in the ITC

Acceleration of knee magnetic resonance imaging using a combination of compressed sensing and commercially available deep learning reconstruction: a preliminary study

Abstract Purpose To evaluate whether deep learning reconstruction (DLR) accelerates the acquisition of 1.5-T magnetic resonance imaging (MRI) knee data without image deterioration. Materials and methods Twenty-one healthy volunteers underwent MRI of the right knee on a 1.5-T MRI scanner. Proton-density-weighted images with one or four numbers of signal averages (NSAs) were obtained via compressed sensing, and DLR was applied to the images with 1 NSA to obtain 1NSA-DLR images. The 1NSA-DLR and 4NSA images were compared objectively (by deriving the signal-to-noise ratios of the lateral and the medial menisci and the contrast-to-noise ratios of the lateral and the medial menisci and articular cartilages) and subjectively (in terms of the visibility of the anterior cruciate ligament, the medial collateral ligament, the medial and lateral menisci, and bone) and in terms of image noise, artifacts, and overall diagnostic acceptability. The paired t-test and Wilcoxon signed-rank test were used for statistical analyses. Results The 1NSA-DLR images were obtained within 100 s. The signal-to-noise ratios (lateral: 3.27 ± 0.30 vs. 1.90 ± 0.13, medial: 2.71 ± 0.24 vs. 1.80 ± 0.15, both p < 0.001) and contrast-to-noise ratios (lateral: 2.61 ± 0.51 vs. 2.18 ± 0.58, medial 2.19 ± 0.32 vs. 1.97 ± 0.36, both p < 0.001) were significantly higher for 1NSA-DLR than 4NSA images. Subjectively, all anatomical structures (except bone) were significantly clearer on the 1NSA-DLR than on the 4NSA images. Also, in the former images, the noise was lower, and the overall diagnostic acceptability was higher. Conclusion Compared with the 4NSA images, the 1NSA-DLR images exhibited less noise, higher overall image quality, and allowed more precise visualization of the menisci and ligaments