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Published Papers 【 display / non-display 】

• Field experiment of a telesurgery system using a surgical robot with haptic feedback.

  Ota M, Oki E, Nakanoko T, Tanaka Y, Toyota S, Hu Q, Nakaji Y, Nakanishi R, Ando K, Kimura Y, Hisamatsu Y, Mimori K, Takahashi Y, Morohashi H, Kanno T, Tadano K, Kawashima K, Takano H, Ebihara Y, Shiota M, Inokuchi J, Eto M, Yoshizumi T, Hakamada K, Hirano S, Mori M

  Surgery today ( Surgery Today )  54 ( 4 ) 375 - 381   2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Purpose: To verify the usefulness of haptic feedback in telesurgery and improve the safety of telerobotic surgery. Methods: The surgeon's console was installed at two sites (Fukuoka and Beppu; 140 km apart), and the patient cart was installed in Fukuoka. During the experiment, the surgeon was blinded to the haptic feedback levels and asked to grasp the intestinal tract in an animal model. The surgeon then performed the tasks at each location. Results: No marked differences in task accuracy or average grasping force were observed between the surgeon locations. However, the average task completion time was significantly longer, and the system usability scale (SUS) was significantly lower rating for remote operations than for local ones. No marked differences in task accuracy or task completion time were observed between the haptic feedback levels. However, with haptic feedback, the organ was grasped with a significantly weaker force than that without it. Furthermore, with haptic feedback, experienced surgeons in robotic surgery tended to perform an equivalent task with weaker grasping forces than inexperienced surgeons. Conclusion: The haptic feedback function is a tool that allows the surgeon to perform surgery with an appropriate grasping force, both on site and remotely. Improved safety is necessary in telesurgery; haptic feedback will thus be an essential technology in robotic telesurgery going forward.

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• The Role of Adipocytokines and their Receptors in Prostate Cancer: Adiponectin May Protect Against Progression.

  Kashiwagi E, Kawahara T, Kinoshita F, Shiota M, Inokuchi J, Miyamoto H, Eto M

  Anticancer research ( Anticancer Research )  44 ( 4 ) 1369 - 1376   2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Background/Aim: Obesity is correlated with an increased risk of developing malignancies, including prostate cancer. Adipocytokines, such as leptin and adiponectin, are a family of hormones derived from adipose tissue that are involved not only in metabolism, but also in the development and progression of various malignancies. However, little is known about their role in prostate cancer. This study aimed to determine how leptin, adiponectin, and their receptors impact the spread of prostate cancer. Materials and Methods: We first performed immunohistochemical analysis of prostate cancer tissue microarrays to detect leptin, leptin receptor (Ob-R), adiponectin, and adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). Wound healing assays and western blot analysis were then performed in human prostate cancer cell lines. Results: Immunohistochemistry showed that prostate tissue was not significantly positive for adiponectin. However, its expression tended to decrease according to the International Society of Urological Pathology (ISUP) grade of prostate cancer (p=0.056). In prostate cancer cell lines, administration of the synthetic adiponectin AdipoRon suppressed cell migration as well as the expression of phospho-NF-κB and cyclooxygenase-2, whereas leptin stimulated these effects. Conclusion: Adiponectin expression tended to be suppressed according to ISUP grade in prostate cancer tissues. In vitro, tumor cell migration was induced by leptin but suppressed by adiponectin. Targeting adipocytokines could be a novel treatment strategy for prostate cancer.

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• Validation of schedules for optimal prostate-specific antigen monitoring after radical prostatectomy.

  Blas L, Shiota M, Tanegashima T, Tsukahara S, Ueda S, Mutaguchi J, Goto S, Kobayashi S, Matsumoto T, Inokuchi J, Eto M

  International journal of urology : official journal of the Japanese Urological Association ( International Journal of Urology )  31 ( 4 ) 404 - 408   2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Background: Early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is crucial for early treatment and improving survival outcomes. The optimal prostate-specific antigen (PSA) monitoring remains unclear, and several models have been proposed. We aimed to externally validate four models for optimal PSA monitoring after RP and propose modifications to improve them. Methods: We reviewed the clinicopathological data of 896 patients who underwent robot-assisted RP between 2009 and 2022. We examined all PSA values and estimated the PSA value for four monitoring schedules at each time point in the virtual follow-up. We defined the ideal PSA for BCR detection between 0.2 and 0.4 ng/mL. Results: During the median follow-up of 21.4 months, 128 (14.3%) patients presented BCR. The original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model detected BCR in 14 (10.9%), three (2.3%), 12 (9.4%), and 11 (8.6%) patients with PSA >0.4 ng/mL. Most patients experienced BCR detected with PSA >0.4 ng/mL during the first year postoperative. The modification of interval within 6 months postoperative avoided BCR detection with PSA >0.4 ng/mL within the first year postoperative in 8/9 (88.9%), 1/2 (50.0%), 5/6 (83.3%), and 4/4 (100%) for the original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model, respectively. Conclusion: We validated four models for PSA monitoring after RP to detect BCR and suggested modifications to avoid detections out of the desired range of PSA. These modifications could help to establish an optimal PSA monitoring schedule after RP.

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• Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis.

  Nishimura N, Miyake M, Iida K, Miyamoto T, Tomida R, Numakura K, Inokuchi J, Yoneyama T, Okajima E, Yajima S, Masuda H, Terada N, Taoka R, Kobayashi T, Kojima T, Matsui Y, Nishiyama N, Kitamura H, Nishiyama H, Fujimoto K

  World journal of urology ( World Journal of Urology )  42 ( 1 ) 185   2024.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Purpose: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette–Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as “BCG-exposed high-risk NMIBC” to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. Methods: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as “BCG-treated NMIBC.” In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. Results: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. Conclusions: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.

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• Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

  Matsuda A, Taoka R, Miki J, Saito R, Fukuokaya W, Hatakeyama S, Kawahara T, Fujii Y, Kato M, Sazuka T, Sano T, Urabe F, Kashima S, Naito H, Murakami Y, Miyake M, Daizumoto K, Matsushita Y, Hayashi T, Inokuchi J, Sugino Y, Shiga K, Yamaguchi N, Iio H, Yasue K, Abe T, Nakanishi S, Matsumura M, Fujii M, Nishihara K, Matsumoto H, Tatarano S, Wada K, Sekito S, Maruyama R, Nishiyama N, Nishiyama H, Kitamura H, Matsui Y, Japanese Urological Oncology Group

  BJU international ( BJU International )    2024.02 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. Patients and methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. Results: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil–lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil–lymphocyte ratio and pathological stage were independent prognostic factors for OS.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• Clinical statistics at the urological department of kyushu university hospital for the period 2008-2010

  Satoshi Otsubo, Akira Yokomizo, Katsunori Tatsugami, Kentaro Kuroiwa, Takakazu Yunoki, Junichi Inokuchi, Keijiro Kiyoshima, Song Yh, Takahito Negishi, Shingo Tanaka, Kunikazu Miyoshi, Eiji Kashiwagi, Hidenori Iwai, Takeshi Kobayashi, Seiji Naito

  Nishinihon Journal of Urology   74 ( 12 ) 724 - 728   2012.12  [Refereed]

   

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Development and investigation of clinical utility of simple sensor device for novel urinary cancer biomarkers detection

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2023.04  -  2026.03 

  Direct: 3,600,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 1,080,000 (YEN)

• Smart nanomedicine-mediated functional switching of macrophage and treatment of chronic kidney disease (CKD)

  Grant-in-Aid for Scientific Research(B)

  Project Year: 2022.04  -  2025.03 

  Direct: 10,200,000 (YEN)  Overheads: 13,260,000 (YEN)  Total: 3,060,000 (YEN)

• Development of a novel diagnostic method for urothelial carcinoma targeting urinary activated protein kinase C-alpha

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2019.04  -  2022.03 

  Investigator(s): Inokuchi Junichi 

  Direct: 3,400,000 (YEN)  Overheads: 4,420,000 (YEN)  Total: 1,020,000 (YEN)

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  Urinary activated protein kinase Cα (PKCα) showed high sensitivity and specificity for detecting urothelial carcinoma (UC), even in low grade UC which had been shown low sensitivity to date. This result indicates the usefulness of activated PKCα as a novel urinary biomarker for urothelial carcinoma. Furthermore, we developed an electronic biosensor device using an anti-phosphopeptide antibody as a cheaper and simpler examination.

• Development of novel diagnostic procedure for detection of upper urinary tract urothelial cancer

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2016.04  -  2019.03 

  Investigator(s): Inokuchi Junichi, Grollman Arthur P. 

  Direct: 3,600,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 1,080,000 (YEN)

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  We hypothesized that a fraction of upper urinary tract urothelial carcinoma (UTUC) cases in Japan might result from past intake of aristolochic acid (AA), a powerful nephrotoxin and human carcinogen, which cause UTUC. In contrast to the high incidence of AA-associated UTUC in Taiwan cohort, our study indicated that confirmed AA-exposure in Japanese UTUC patients were rare. We examined the efficacy of activated protein kinase X in urine sample to detect urothelial cancer. We found the high sensitivity and specificity of this assay, and suggested the activated protein kinase X as promising biomarker for detecting urothelial cancer.

• Analysis of prostate carcinogenesis using in vitro three-dimensional culture assay

  Grant-in-Aid for Young Scientists(B)

  Project Year: 2009  -  2011 

  Investigator(s): INOKUCHI Junichi 

  Direct: 3,100,000 (YEN)  Overheads: 4,030,000 (YEN)  Total: 930,000 (YEN)

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  The mechanism of prostate carcinogenesis is not elucidated yet. In this study, we established a new experimental procedure for analyzing prostate carcinogenesis using in vitro three dimensional culture(3D) assays. Using this method, we showed a direct role for decreased annexin A1 expression in prostate carcinogenesis via the up-regulation of IL-6. Furthermore, we indicated an important role for androgen receptor(AR) in forming normal acinar structure in 3D culture. We reported several mechanisms of prostate carcinogenesis by regulating AR expression and its activity.

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