Publications by authors named "Toshio Takagi"

211 Publications

Analyses of operative time according to procedure phases during robot-assisted laparoscopic partial nephrectomy using the iPhone application "My Intuitives".

Authors:
Toshio Takagi Kazuhiko Yoshida Hironori Fukuda Yuki Kobari Junpei Iizuka

Int J Urol 2022 Aug 9. Epub 2022 Aug 9.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Purpose: We investigated operative time according to procedure phases in robot-assisted laparoscopic partial nephrectomy (RAPN) and identify variables associated with longer operative time in each procedure phase.

Methods: This retrospective, single-center study included 108 patients who underwent RAPN conducted by an experienced surgeon. Operative time was divided into dissection, resection, tumor bed suture, and renorrhaphy and hemostasis phases, which were derived from the iPhone application "My Intuitives." Multivariate analyses were performed to identify possible predictors such as sex, body mass index, tumor complexity, and surgical approach for longer operative time in each phase.

Results: The median console time was 65 min, and median operative times in dissection, resection, tumor bed suture, and renorrhaphy and hemostasis phases were 41, 8, 9, and 8 min, respectively. In the multivariate analysis, longer console time was observed in high complexity tumors (vs. low, OR: 8.01, 95% CI: 1.94-33.0) and transperitoneal approach (vs. retroperitoneal approach, OR: 3.62, 95% CI: 1.94-33.0). High complexity tumors were significantly associated with longer operative time in all procedure phases, and the male sex was associated with a longer operative time in the dissection phase than the female sex (OR: 3.61, 95% CI: 1.18-11.0).

Conclusion: The identified significant predictive factors associated with longer operative time were the male sex and high complexity in the dissection phase, high complexity in the resection phase, in the tumor bed suture phase as well as in the renorrhaphy and hemostasis phase. These findings may help to predict the difficulty of performing RAPN in terms of operative time.
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http://dx.doi.org/10.1111/iju.15001DOI Listing
August 2022

Robot-assisted laparoscopic versus open partial nephrectomy for renal cell carcinoma in patients with severe chronic kidney disease.

Authors:
Kazuhiko Yoshida Yuki Kobari Junpei Iizuka Tsunenori Kondo Hideki Ishida Kazunari Tanabe Toshio Takagi

Int J Urol 2022 Aug 8. Epub 2022 Aug 8.

Department of Urology, Tokyo Women's Medical University Hospital, Tokyo, Japan.

Objectives: To compare surgical and functional outcomes between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy in patients with renal cell carcinoma with stage 4 chronic kidney disease.

Methods: This was a retrospective analysis of 60 patients with stage 4 chronic kidney disease (estimated glomerular filtration rate 15-30 ml/min/1.73 m ) who underwent partial nephrectomy for T1 renal cell carcinoma between April 2004 and April 2020. We compared perioperative outcomes according to the surgical approach. Multivariable analysis was performed to identify predictive factors for end-stage renal disease.

Results: Robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy were performed in 31 and 29 patients, respectively. The median age was 68 years and 17% of all patients were women. Patient and tumor characteristics did not differ between groups. The operative time (155.2 vs. 221.0 min, p < 0.0001) and the postoperative length of hospital stay (5.2 vs. 10.6 days, p = 0.0083) were significantly shorter, and the estimated blood loss was lower (53.4 vs. 363.2 ml, p = 0.0003) in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group. Preoperative estimated glomerular filtration rate was the only significant predictor of end-stage renal disease after partial nephrectomy on multivariable analysis.

Conclusions: Both procedures preserved renal function in this patient cohort, delaying the requirement for postoperative dialysis. Furthermore, robot-assisted laparoscopic partial nephrectomy was associated with shorter operative time and postoperative length of hospital stay, as well as lesser estimated blood loss than open partial nephrectomy.
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http://dx.doi.org/10.1111/iju.14995DOI Listing
August 2022

Surgical and functional outcomes of robot-assisted laparoscopic partial nephrectomy for renal cell carcinoma in adolescents and young adults: a propensity score matching study.

Authors:
Kazuhiko Yoshida Tsunenori Kondo Junpei Iizuka Hironori Fukuda Hiroki Ishihara Hirohito Kobayashi Masayoshi Okumi Hideki Ishida Kazunari Tanabe Toshio Takagi

Int J Clin Oncol 2022 Jul 25. Epub 2022 Jul 25.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Background: Cancer development in adolescents and young adults (AYAs) has elicited recent interest. We investigated the surgical and functional outcomes of robot-assisted laparoscopic partial nephrectomy (RAPN) for renal cell carcinoma (RCC) in AYAs.

Methods: We retrospectively reviewed the medical records of 1023 patients with clinical stage I RCC who underwent RAPN before January 2021. Patients were divided into two groups: AYAs (aged 18-39 years) and non-AYAs (aged 40-89 years). The trifecta criteria, defined as a negative surgical margin, no perioperative complications (Clavien-Dindo grade > 2), and preserved postoperative renal function (1-year postoperative estimated glomerular filtration rate > 90% of baseline), were used to compare outcomes. We performed 1:1 propensity-score matching on the patient cohort.

Results: There were initially 125 and 898 patients in the AYAs and non-AYAs groups, respectively, and 108 patients were included in each group after propensity score matching. There were no significant differences in surgical factors (operation time, clamping ischemia time, estimated blood loss, length of hospital stay, surgical complication rate) or renal function in the early postoperative period. The mean postoperative renal function was better (p = 0.0200) and the decrease in estimated glomerular filtration rate was lower (p = 0.0026) in AYAs than in non-AYAs 12 months postoperatively. The trifecta achievement rates in the AYAs and non-AYAs groups were significantly different (67.6% and 53.7%, respectively, p = 0.0220).

Conclusion: Although there was no difference in surgical burden between the groups, the estimated glomerular filtration rate was better preserved in AYAs than in non-AYAs at 6 and 12 months post-RAPN.
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http://dx.doi.org/10.1007/s10147-022-02222-9DOI Listing
July 2022

Efficacy and Safety of Immunotherapy-Based Combinations as First-Line Therapy for Metastatic Renal Cell Carcinoma in Patients Who Do Not Meet Trial Eligibility Criteria.

Authors:
Yuki Nemoto Hiroki Ishihara Kazutaka Nakamura Hidekazu Tachibana Hironori Fukuda Kazuhiko Yoshida Hirohito Kobayashi Junpei Iizuka Hiroaki Shimmura Yasunobu Hashimoto Kazunari Tanabe Tsunenori Kondo Toshio Takagi

Target Oncol 2022 Jul 5;17(4):475-482. Epub 2022 Jul 5.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.

Background: Data regarding the efficacy and safety profiles of immune checkpoint inhibitors (ICIs) for metastatic renal cell carcinoma (mRCC) trial-ineligible patients in the real world remain unclear.

Objectives: The aim of this study was to clarify the impact of trial eligibility on ICI-based combination therapy for mRCC.

Patients And Methods: We collected clinical data of mRCC patients receiving ICIs since 2016, and 222 patients were registered. Among these patients, we evaluated 93 patients treated with ICI-based combination therapy, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, or avelumab plus axitinib, as first-line therapy. Patients were classified into the trial-ineligible group when they had at least one of the following factors at the time of treatment initiation: Karnofsky performance status (KPS) < 70%, hemoglobin level < 9.0 g/dL, estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m, platelet count < 100,000/µL, neutrophil count < 1500/µL, non-clear cell histology, or brain metastasis. The remaining patients were classified into the trial-eligible group.

Results: Forty-eight patients (52%) were classified into the trial-ineligible group. The frequency of patients with trial-ineligible factors was highest for low eGFR (n = 20, 45%), followed by non-clear cell histology (n = 17, 36%) and low KPS score (n = 12, 25%). There was no significant difference in progression-free survival (median: 24.0 vs. 11.0 months, p = 0.416), overall survival (1-year rate: 87.0% vs. 85.3%, p = 0.634), or objective response rate (52% vs. 42%, p = 0.308) between the trial-eligible and -ineligible patients. The incidence rate of adverse events was higher in the trial-eligible patients than in the trial-ineligible patients (91% vs. 75%, p = 0.0397); however, the rate of grade 3 or higher adverse events was comparable between the two groups (42% vs. 40%, p = 0.796).

Conclusions: There are many trial-ineligible patients in the real world. Nevertheless, the efficacy and safety of ICI-based combination therapy in trial-ineligible patients were non-inferior compared with those of trial-eligible patients.
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http://dx.doi.org/10.1007/s11523-022-00896-9DOI Listing
July 2022

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

Authors:
Maki Yoshino Hiroki Ishihara Yuki Nemoto Kazutaka Nakamura Koichi Nishimura Hidekazu Tachibana Hironori Fukuda Daisuke Toki Kazuhiko Yoshida Hirohito Kobayashi Junpei Iizuka Hiroaki Shimmura Yasunobu Hashimoto Kazunari Tanabe Tsunenori Kondo Toshio Takagi

Jpn J Clin Oncol 2022 Jul 2. Epub 2022 Jul 2.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Objectives: To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

Patients And Methods: Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared.

Results: During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613).

Conclusions: The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.
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http://dx.doi.org/10.1093/jjco/hyac099DOI Listing
July 2022

Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model.

Authors:
Hidetoshi Ishigooka Haruki Katsumata Kan Saiga Daisuke Tokita Sotaro Motoi Chiyuki Matsui Yuta Suzuki Ayaka Tomimatsu Tomoya Nakatani Yoshikazu Kuboi Takafumi Yamakawa Takashi Ikeda Rumi Ishii Toshio Imai Toshio Takagi Kazunari Tanabe

Transplantation 2022 Jun 24. Epub 2022 Jun 24.

Department of Urology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.

Background: Prophylaxis of antibody-mediated rejection (AMR) caused by donor-specific antibodies remains challenging. Given the critical roles of complement activity in antibody-mediated graft injury, we developed a lipid nanoparticle (LNP) formulation of small-interfering RNA against complement C5 (C5 siRNA-LNP) and investigated whether C5 siRNA-LNP could downregulate the complement activity and act as an effective treatment for AMR.

Methods: Lewis recipient rats were sensitized by skin grafting from Brown Norway donor rats. Kidney transplantation was performed at 4 wk post-skin grafting.C5 siRNA- or control siRNA-LNP was administered intravenously, and the weekly injections were continued until the study's conclusion. Cyclosporin (CsA) and/or deoxyspergualin (DSG) were used as adjunctive immunosuppressants. Complement activity was evaluated using hemolysis assays. The deposition of C5b9 in the grafts was evaluated using immunohistochemical analysis on day 7 posttransplantation.

Results: C5 siRNA-LNP completely suppressed C5 expression and complement activity (hemolytic activity ≤ 20%) 7 d postadministration. C5 siRNA-LNP in combination with CsA and DSG (median survival time: 56.0 d) prolonged graft survival compared with control siRNA-LNP in combination with CsA and DSG (median survival time: 21.0 d; P = 0.0012; log-rank test). Immunohistochemical analysis of the grafts revealed that downregulation of C5 expression was associated with a reduction in C5b9-positive area (P = 0.0141, Steel-Dwass test).

Conclusions: C5 siRNA-LNP combined with immunosuppressants CsA and DSG downregulated C5 activity and significantly prolonged graft survival compared with control siRNA-LNP with CsA and DSG. Downregulation of C5 expression using C5 siRNA-LNP may be an effective therapeutic approach for AMR.
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http://dx.doi.org/10.1097/TP.0000000000004207DOI Listing
June 2022

Assessment of Feasibility of Robot-assisted Radical Cystectomy in Patients With Advanced Bladder Cancer Treated With Maintenance Hemodialysis Therapy.

Authors:
Koichi Nishimura Hiroki Ishihara Tsunenori Kondo Makoto Toguchi Hironori Fukuda Hidekazu Tachibana Daisuke Toki Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

In Vivo 2022 Jul-Aug;36(4):1801-1806

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background/aim: To clarify the perioperative and oncological outcomes of robot-assisted radical cystectomy (RARC) in advanced bladder cancer (BC) patients treated with maintenance hemodialysis (HD) therapy.

Patients And Methods: We retrospectively evaluated patients receiving HD therapy who had undergone RARC or open radical cystectomy (ORC) for BC between April 1988 and December 2021 at two affiliated institutions. We compared the surgical outcomes and survival after radical cystectomy between patients treated with RARC and those treated with ORC.

Results: Thirty-six patients were evaluated, and eight (22%) and 28 (78%) received RARC and ORC, respectively. RARC was more frequently conducted than ORC in elderly patients (median: 75.5 vs. 68.2 years, p<0.05). Regarding postoperative surgical outcomes, the estimated blood loss volume (median: 75 ml vs. 627 ml, p<0.05) was significantly lower in the RARC group than that in the ORC group. A lower blood transfusion rate (25% vs. 67%, p=0.170) was observed. Moreover, there were no differences in operative time (median: 255 vs. 294 min, p=0.232) or complication rate (Clavien-Dindo grade, any grade: 50% vs. 46%, p=0.858; grade 3 or more: 13% vs. 14%, p=0.897). The 11-year overall survival rate did not differ between the two groups (88% vs. 74%, p=0.365).

Conclusion: The perioperative outcomes of RARC in patients undergoing HD therapy were comparable to those of ORC. RARC is a potentially feasible surgical option even in patients with high comorbidities.
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http://dx.doi.org/10.21873/invivo.12895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301427PMC
June 2022

Efficacy of Cabozantinib for Papillary Compared With Clear-cell Renal Cell Carcinoma Following Immune Checkpoint Inhibitor Treatment.

Authors:
Hidekazu Tachibana Toru Inakawa Yuki Nemoto Hiroki Ishihara Hironori Fukuda Kazuhiko Yoshida Junpei Iizuka Yasunobu Hashimoto Kazunari Tanabe Tsunenori Kondo Toshio Takagi

Anticancer Res 2022 Jun;42(6):3151-3158

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background: The efficacy of combined immunotherapy for papillary renal cell carcinoma (pRCC) based on prolonged progression-free survival (PFS) and overall survival in several clinical trials remains unknown. We aimed to compare the efficacy of cabozantinib in patients with pRCC and those with clear-cell renal cell carcinoma (ccRCC).

Patients And Methods: This retrospective study included 27 patients with metastatic RCC who received cabozantinib as second-line or later therapy between June 2020 and October 2021. Objective response, PFS, and toxicity were compared between the ccRCC and pRCC groups.

Results: Out of 27 patients, seven and 20 were diagnosed with pRCC and ccRCC, respectively. Out of the seven patients with pRCC, cabozantinib was used as second-line treatment in four patients and as third-line treatment in three patients, and all seven patients had had prior immunotherapy. One and two patients achieved complete and partial responses, respectively; four patients had stable disease, and none had progressive disease. The rates of objective response (43% vs. 30%, p=0.65) and disease control (100% vs. 85%, p=0.54) were similarly high in patients with pRCC and ccRCC. Changes in the target lesions were -19% and -10% (p=0.11), respectively. With a median follow-up of 7.1 months, the median PFS tended to be longer in patients with pRCC than in those with ccRCC (not reached vs. 10.7 months, p=0.12). Discontinuation due to toxicity was observed in four (57%) patients with pRCC and 10 (50%) patients with ccRCC.

Conclusion: Cabozantinib is effective for pRCC, similar to ccRCC. This information may help physicians to select treatment options for pRCC.
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http://dx.doi.org/10.21873/anticanres.15804DOI Listing
June 2022

Perioperative outcomes following robot-assisted partial nephrectomy for renal cell carcinoma according to surgeon generation.

Authors:
Makoto Toguchi Tsunenori Kondo Kazuhiko Yoshida Kazunari Tanabe Toshio Takagi

BMC Surg 2022 May 26;22(1):205. Epub 2022 May 26.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Objective: The experience of performing robot-assisted partial nephrectomy (RAPN) is associated with better surgical outcomes. However, surgeon's generation may impact surgical outcomes. We evaluated the perioperative outcomes of RAPN between first- and second-generation surgeons according to the surgeon's experience.

Methods: This study included 529 patients who underwent RAPN for renal cell carcinoma from January 2013 to November 2018. Four specific surgeons performed the surgery. According to the surgeon's generation, the patients were divided into two groups: first-generation and second-generation. To reflect the learning curve of RAPN, the surgical outcomes of each case (1-50, 51-100, 101-150) were evaluated between these groups.

Results: Between 1 to 50 cases and 101-150 cases, no significant differences in patient characteristics were observed between the two generations. Between 51-100 cases, age at surgery was significantly younger in the first-generation than in the second-generation group (58 years vs. 64 years, p = 0.04). The second-generation group had a shorter operation time in cases 1-50 (169 min vs. 188 min, p = 0.0001), 51-100 (145 min vs. 169 min, p = 0.008), and 101-150 (142 min vs. 165 min, p = 0.009), than the first-generation group. Although shorter WIT and higher trifecta achievement were observed in the second-generation group than in the first-generation group between 1-50 cases, the difference was not noted between 51-100 cases and 101-150 cases.

Conclusion: Patients operated by second-generation surgeons had better surgical outcomes than first-generation surgeons, especially during the early experience period, which might result from their assistance experience, sophisticated surgical procedures refined by the first-generation, and the first-generation surgeon's introduction.
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http://dx.doi.org/10.1186/s12893-022-01654-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137184PMC
May 2022

Antibody Response to SARS-CoV-2 mRNA Vaccine Among Kidney Transplant Recipients: A Retrospective Cohort Study at a Single Transplant Institute in Japan.

Authors:
Hideki Ishida Miyuki Furusawa Kouhei Unagami Kazuya Omoto Jumpei Iizuka Toshio Takagi

Exp Clin Transplant 2022 05 23;20(5):463-471. Epub 2022 May 23.

From the Department of Urology, , Women's Medical University Hospital, Tokyo, Japan.

Objectives: Although the effectiveness of vaccines in protecting the host from infection has been proven, few surveys have been conducted on changes in antibody levels after vaccination of kidney transplant recipients in Japan.

Materials And Methods: We analyzed serological responses in kidney transplant recipients after BNT162B2 COVID-19 mRNA vaccine with the use of a reagent capable of simultaneously specifying the antibody response to 5 proteins: a full-spike protein (extracellular domain), 3 individual domains of the spike protein (S1, S2, and receptor-binding domain), and nucleocapsid. The analysis involved 111 patients who had follow-up over 1 month after having received the second of 2 coronavirus vaccines after kidney transplant.

Results: Antibodies were detected in 46 of 111 patients (41%). The antibody-positive rate in the kidney transplant group tended to be lower than that in the healthy control group, which showed an antibody- positive rate of 100%. When the antibody-positive rate was analyzed by the type of immunosuppressor used, the rate was 36% (37/100) for patients who used tacrolimus at the time of vaccination and 90% (9/10) for patients who used cyclosporine. Patients administered CD20 antibody (rituximab) before and/or after transplant showed a lower production of antibodies, which was supported by a smaller number of CD19- and CD20-positive cells in the peripheral blood as well as a shorter period between rituximab administration and vaccination. The percentage of responding viral fragments varied greatly among individual patients and showed no uniformity in the kidney transplant group, whereas the mean fluorescence intensity of individual fragments showed a certain tendency in the control group.

Conclusions: The appropriate timing of vaccination should be considered in transplant recipients who use tacrolimus-mycophenolate mofetil combination and rituximab as these drugs are deeply related to a lower antibody response to SARS-CoV-2 BNT162b2 vaccination.
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http://dx.doi.org/10.6002/ect.2022.0020DOI Listing
May 2022

Editorial Comment from Dr Ishihara et al. to Nomogram for predicting survival of renal cell carcinoma with tumor thrombus based on perioperative clinicopathological factors from a Chinese high-volume center.

Authors:
Hiroki Ishihara Tsunenori Kondo Toshio Takagi

Int J Urol 2022 May 21. Epub 2022 May 21.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

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http://dx.doi.org/10.1111/iju.14943DOI Listing
May 2022

Treatment with bortezomib for recurrent proliferative glomerulonephritis with monoclonal IgG deposits in kidney allograft. Case report and review of the literature.

Authors:
Rikako Oki Kohei Unagami Sekiko Taneda Toshio Takagi Hideki Ishida

J Nephrol 2022 05 6;35(4):1289-1293. Epub 2022 May 6.

Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Proliferative glomerulonephritis with monoclonal immunoglobulin IgG deposits (PGNMID) is an already described form of renal involvement by monoclonal gammopathy. PGNMID is known to recur in kidney allografts. Bortezomib has shown clinical success in the treatment of multiple myeloma. However, its effect for recurrent PGNMID in kidney allografts has rarely been reported. We present the case of a 61-year-old woman who developed recurrent PGNMID 3 weeks after kidney transplantation. This patient was initially treated with steroid pulses (500 mg/day for 2 days) and two cycles of rituximab therapy (200 mg/body). However, disease progression was observed with mesangial matrix expansion and subendothelial deposits by light microscopy and stronger staining for IgG3 and kappa in the mesangial area by Immunofluorescence (IF) microscopy. Thus, we started treatment with bortezomib therapy (1.3 mg/m2, once weekly, on days 1, 8, 15, and 22 in a 5-week cycle, for a total of six cycles). Bortezomib therapy reduced massive proteinuria, although monoclonal immune deposits on IF and the serum creatinine level did not change during the treatment period. Seven months after completion of the first bortezomib course, we decided to prescribe a second course of bortezomib with the same regimen. Each course resulted in a > 50% reduction of proteinuria. Bortezomib may delay the progress of PGNMID in kidney allograft patients.
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http://dx.doi.org/10.1007/s40620-022-01332-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107408PMC
May 2022

Changes in Real-World Outcomes in Patients with Metastatic Renal Cell Carcinoma from the Molecular-Targeted Therapy Era to the Immune Checkpoint Inhibitor Era.

Authors:
Hiroki Ishihara Yuki Nemoto Kazutaka Nakamura Hidekazu Tachibana Hironori Fukuda Kazuhiko Yoshida Hirohito Kobayashi Junpei Iizuka Hiroaki Shimmura Yasunobu Hashimoto Kazunari Tanabe Tsunenori Kondo Toshio Takagi

Target Oncol 2022 05 23;17(3):307-319. Epub 2022 Apr 23.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Knowledge of changes in the outcome in patients with metastatic renal cell carcinoma from the molecular-targeted therapy era to the immune checkpoint inhibitor (ICI) era remains limited in the real-world setting.

Objectives: We aimed to clarify outcome changes from the previous molecular-targeted therapy era to the current ICI era in patients with metastatic renal cell carcinoma using multi-institution real-world data.

Methods: We retrospectively evaluated 415 patients with metastatic renal cell carcinoma who received first-line systemic therapy at five Japanese institutions between January 2008 and August 2021. We divided the patients into two groups based on the treatment era: molecular-targeted therapy era (January 2008-August 2018) and ICI era (September 2018-August 2021). According to the era, progression-free survival, overall survival, and objective response rate from first-line systemic therapy were compared.

Results: Overall, 304 (73.3%) and 111 (26.7%) patients were categorized into the molecular-targeted therapy and ICI eras, respectively. The proportion of patients without prior nephrectomy (p = 0.0030) or those with low Karnofsky Performance Status scores [≤ 70] (p = 0.0258) were significantly higher in the ICI era group. The patients in the ICI era group had significantly longer overall survival (median: not reached vs 23.2 months, p = 0.0001) and a higher objective response rate (47.8% vs 24.7%, p < 0.0001) than those in the molecular-targeted therapy era group, and progression-free survival tended to be longer in the ICI era group (median: 13.3 vs 8.75 months, p = 0.0579). Multivariate analysis further showed that the treatment era (ICI vs molecular-targeted therapy) was an independent factor for overall survival and objective response (both, p < 0.0001).

Conclusions: The present multi-institution real-world data showed the improved outcome of previously untreated patients with metastatic renal cell carcinoma in the ICI era group compared with that in the molecular-targeted therapy era group. These findings strongly encourage the use of ICI-based treatment for patients with metastatic renal cell carcinoma in the real-world setting. Further studies with extended follow-up periods are needed to confirm our findings.
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http://dx.doi.org/10.1007/s11523-022-00879-wDOI Listing
May 2022

Outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma: a real-world multi-institution data with a minimum of 2 years of follow-up.

Authors:
Hiroki Ishihara Yuki Nemoto Hidekazu Tachibana Hironori Fukuda Kazuhiko Yoshida Hirohito Kobayashi Junpei Iizuka Yasunobu Hashimoto Toshio Takagi Hideki Ishida Tsunenori Kondo Kazunari Tanabe

Jpn J Clin Oncol 2022 Jul;52(7):777-782

Department of Urology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.

Objectives: To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data.

Methods: A total of 121 patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions. To evaluate the outcome after 2 years or more, we selected patients in whom nivolumab therapy was started in December 2019 or earlier because data collection was performed until the end of December 2021.

Results: Seventy-four patients were evaluated. During the median follow-up period of 25.8 months, 62 (84%) and 40 (54%) patients had disease progression and died, respectively. Nivolumab was administered as second-line therapy in 43 patients (58%). The median progression-free survival and overall survival were 5.52 and 31.1 months, respectively, and objective response rate was 36%. There was no difference in progression-free survival or overall survival based on the treatment line of nivolumab (P = 0.915, P = 0.559). The magnitude of tumor response and development of immune-related adverse events were significantly associated with progression-free survival (P < 0.0001, P < 0.0001, respectively) and overall survival (P < 0.0001, P = 0.0002, respectively). Treatment-related adverse events developed in 38 patients (51%), including 33 (45%) who had immune-related adverse events. Steroid administration was needed in nine patients (12%).

Conclusions: The present real-world multi-institution study with long-term follow-up data demonstrates that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response and has a manageable safety profile.
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http://dx.doi.org/10.1093/jjco/hyac044DOI Listing
July 2022

"Thrombus-first" or "thrombus-last" approach for surgical management of renal cell carcinoma with inferior vena cava thrombus.

Authors:
Yudai Ishiyama Tsunenori Kondo Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

Int J Urol 2022 06 13;29(6):559-565. Epub 2022 Mar 13.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Objectives: To compare the perioperative outcomes between thrombectomy first then nephrectomy ("thrombus-first") and vice-versa ("thrombus-last") approaches for patients with renal cell carcinoma and inferior vena cava thrombus.

Methods: We retrospectively evaluated 130 patients who underwent nephrectomy and thrombectomy at two institutions between 1992 and 2020. The cohort was classified into the thrombus-first and thrombus-last groups according to the techniques used. Outcomes including the operative time, blood loss, and complications, especially the occurrence of intraoperative tumor embolism of pulmonary artery and postoperative pulmonary embolism, were compared.

Results: The thrombus-first and thrombus-last groups comprised 48 and 82 patients, respectively. Characteristics such as age, performance status, Charlson Comorbidity Index, renal function, and level of tumour thrombus were comparable between the two groups. Approximately 41% of the patients had distant metastasis. There were four cases (3.1%) of intraoperative tumor embolism, all from the thrombus-last group. Three patients overall (2.3%) experienced pulmonary embolism postoperatively with two in the thrombus-last group (2.4%) and one in the thrombus-first group (2.1%) (P > 0.999). The surgical time (291.0 min vs 369.0 min, P < 0.001) and the blood loss (1323.0 vs 2100.0 mL, P < 0.001) were significantly smaller for the thrombus-first group than for the thrombus-last group. Occurrence of complications was 25.0% and 43.9% in thrombus-first and thrombus-last groups, respectively (P = 0.029), and 8.3% and 23.2% for events graded ≥3 (P = 0.035).

Conclusion: In surgery for renal cell carcinoma with inferior vena cava thrombus, performing thrombectomy before nephrectomy may serve to lessen complications, blood loss, and surgical time compared to nephrectomy before thrombectomy.
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http://dx.doi.org/10.1111/iju.14846DOI Listing
June 2022

A case of novel coronavirus disease after combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma.

Authors:
Yu Kijima Tomokazu Shimizu Shinya Kato Eri Sekido Kana Kano Makoto Toguchi Toshihide Horiuchi Hiroshi Toma Shoichi Iida Toshio Takagi

IJU Case Rep 2022 Mar 30;5(2):126-128. Epub 2021 Dec 30.

Department of Urology Tokyo Women's Medical University Tokyo Japan.

Introduction: We present a case of novel coronavirus disease-2019 that underwent combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma.

Case Presentation: A 50-year-old man complained of anorexia and weight loss. Contrast-enhanced computed tomography revealed a solid mass of 57 mm in diameter with cysts in the right kidney, along with liver, lung, and multiple bone metastases. Computed tomography-guided biopsy of the right kidney was performed, and a diagnosis of clear cell renal cell carcinoma was made. Three weeks after nivolumab and ipilimumab administration, the patient contracted coronavirus disease-2019. Anticoagulation therapy (dalteparin) was administered for 4 days once infection was confirmed, after which dexamethasone was administered for 10 days. The patient survived without experiencing worsened respiratory symptoms.

Conclusion: We administered nivolumab and ipilimumab combination therapy as treatment for metastatic renal cell carcinoma. No side effects or immune-related adverse events were observed for a short time.
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http://dx.doi.org/10.1002/iju5.12412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888016PMC
March 2022

Immune Checkpoint Inhibitor Combination Therapy for Renal Cell Carcinomas With Concomitant Inferior Vena Cava Thrombi.

Authors:
Kazuhiko Yoshida Keisuke Hata Junpei Iizuka Tsunenori Kondo Hiroki Ishihara Hideki Ishida Yoji Nagashima Kazunari Tanabe Toshio Takagi

In Vivo 2022 Mar-Apr;36(2):1030-1034

Department of Urology, Tokyo Women's Medical University Hospital, Tokyo, Japan.

Background/aim: The efficacy of immune checkpoint inhibitor (ICI) combinations in treating inferior vena cava (IVC) tumour thrombi has not yet been reported. We aimed to evaluate the clinical efficacy of ICIs for patients with renal cell carcinoma (RCC) and a concomitant IVC tumour thrombus.

Patients And Methods: Three men and two women with RCC and an IVC tumour thrombus were administered ICIs in 2020-2021. Three and two patients received nivolumab plus ipilimumab and pembrolizumab plus axitinib therapy, respectively.

Results: All ICI-treated patients showed tumour shrinkage. The IVC thrombus level was downstaged in two patients. The mean reduction in maximum primary tumour diameter and IVC thrombus height was 34 and 33 mm, respectively.

Conclusion: Presurgical ICI therapy in three patients who underwent radical nephrectomy with thrombectomy resulted in a modified surgical strategy and approach and reduced surgical risk. Thus, ICIs may treat select cases of RCC with an IVC tumour thrombus effectively.
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http://dx.doi.org/10.21873/invivo.12798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931899PMC
March 2022

Effectiveness of Retzius-Sparing Robot-Assisted Radical Prostatectomy in a Renal Transplant Recipient: a Case Report.

Authors:
Yuki Kobari Junpei Iizuka Keisuke Hata Shinya Kato Ryo Minoda Kazuhiko Yoshida Hideki Ishida Yoji Nagashima Kazunari Tanabe Toshio Takagi

Transplant Proc 2022 Mar 11;54(2):525-527. Epub 2022 Feb 11.

Department of Urology, Tokyo Women's Medical University, Tokyo.

Background: Prostate cancer (PCa) has increased as a long-term outcome of advanced immunosuppression in renal transplant recipients (RTRs). Retzius-sparing robot-assisted radical prostatectomy (Rs-RARP) is reportedly less time-consuming and has a higher continence recovery rate than the standard RARP without increasing the risk of complications. However, only a few cases of Rs-RARP in RTRs have been reported.

Case Presentation: A 65-year-old man, who received a renal transplant 2 years prior, was diagnosed with low-risk PCa, per the D'Amico risk classification system, and underwent Rs-RARP with the da Vinci Xi robotic system. All port sites were placed contralateral to the allograft and compared with the standard RARP. The operative time was 187 min, and the estimated blood loss was 100 mL. The urethral catheter was removed on postoperative day 7 after confirming the absence of leakage using voiding cystourethrography. The patient was discharged on postoperative day 8. Pathologic findings showed localized PCa with a Gleason score of 3 + 3 and negative surgical margins. One year after the surgery, the patient had adequate urinary continence. His prostate-specific antigen level was <0.01 ng/mL, and his renal function was similar to that before surgery.

Conclusions: We reported a case of PCa in an RTR, successfully treated via Rs-RARP, resulting in adequate continence without complications.
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http://dx.doi.org/10.1016/j.transproceed.2021.08.063DOI Listing
March 2022

C-reactive protein kinetics to predict recurrence of high-risk renal cell carcinoma after radical surgery.

Authors:
Yudai Ishiyama Tsunenori Kondo Hiroki Ishihara Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

Int J Clin Oncol 2022 May 12;27(5):969-976. Epub 2022 Feb 12.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.

Background: With new options in adjuvant settings, clinical biomarkers to predict recurrence after radical surgery for high-risk renal cell carcinoma (hrRCC) are in need but are scarcely investigated. We aimed to verify the predictive value of perioperative C-reactive protein (CRP) kinetics on hrRCC recurrence.

Methods: We retrospectively evaluated 154 patients who underwent radical surgery for hrRCC (≥ pT3 and/or N1-2 and M0) at two institutions. Patients were classified into Normal (< 0.5) and High (≥ 0.5) according to their preoperative serum CRP (mg/dL). The High group were further classified into Normalized (< 0.5 at post) or Non-normalized (≥ 0.5 at post), and recurrence-free survival (RFS) was compared between groups. Factors for RFS were further analysed, and Harrell's concordance index (C-index) for the accuracy of predicting RFS was compared with and without the addition of CRP-related variables to pre-existing models.

Results: The RFS was significantly shorter in the High (n = 72, 46.8%) compared to the Normal (n = 82, 53.2%) group (9.7 vs. 66.7 months, p < 0.001). Within the High group, Non-normalized (n = 27, 17.5%) patients showed a significantly shorter RFS compared to the Normalized (n = 45, 29.2%) group (6.2 vs. 20.3, p = 0.009). In the multivariable stepwise analysis, CRP kinetics (hazard ratio 2.15, p = 0.029) effectively predicted RFS while baseline CRP fell short of significance. Higher C-index improvement was observed with CRP non-normalization than the baseline value when added to factors in the Karakiewicz and University of California Los Angeles Integrated Staging System models.

Conclusions: CRP kinetics effectively predicted RCC recurrence after surgery and may aid in decision-making for adjuvant systemic therapy.
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http://dx.doi.org/10.1007/s10147-022-02136-6DOI Listing
May 2022

Comparison of surgical outcomes after robot-assisted laparoscopic partial nephrectomy between patients continuing and discontinuing aspirin therapy: a Japanese single-centre study.

Authors:
Arisa Wada Kenji Omae Kazuhiko Yoshida Tsunenori Kondo Kazunari Tanabe Toshio Takagi

Jpn J Clin Oncol 2022 May;52(5):499-505

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Purpose: To investigate the feasibility of continuing aspirin therapy in patients with renal tumours undergoing robot-assisted laparoscopic partial nephrectomy.

Methods: This retrospective, single-centre study included 106 patients receiving aspirin therapy who underwent robot-assisted laparoscopic partial nephrectomy. The patients were divided into two groups, including those continuing and discontinuing aspirin therapy, and their surgical outcomes were compared. To minimise potential bias, variables including patient and tumour characteristics were adjusted using 1:1 propensity score matching.

Results: Aspirin therapy was used for ischaemic heart disease in 38 patients (36%), cerebrovascular disease in 21 (20%) and others in 47 (44%). Of the 106 patients, 49 were classified to the continuing group and 57 to the discontinuing group. After matching, 24 patients were included in each group. The surgical outcomes, such as changes in the estimated glomerular filtration rate, estimated blood loss, and surgical margin positivity rate, were not significantly different between the groups. In addition, no significant difference was observed in haemoglobin level changes during surgery (continuing: -2.3 g/dl; discontinuing: -1.7 g/dl, P = 0.0676) and haemorrhagic complications (continuing: 8%; discontinuing: 4%, P = 0.500). Multivariate analysis of predictors for haemoglobin level decrease >2 g/dl or haemorrhagic complications showed that, whereas tumour complexity was an independent predictor, continuation or discontinuation of aspirin therapy was not.

Conclusion: The surgical outcomes of robot-assisted laparoscopic partial nephrectomy between patients continuing and discontinuing aspirin therapy were not significantly different, thus suggesting the feasibility of continuing aspirin therapy in selected Japanese patients.
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http://dx.doi.org/10.1093/jjco/hyac001DOI Listing
May 2022

Case Report of COVID-19 Infection After Kidney Transplant Treated With Casirivimab-Imdevimab and Mycophenolate Mofetil Changed to Everolimus.

Authors:
Yu Kijima Tomokazu Shimizu Shinya Kato Kana Kano Toshihide Horiuchi Taiji Nozaki Kazuya Omoto Masashi Inui Hiroshi Toma Shoichi Iida Toshio Takagi

Transplant Proc 2021 Dec 31. Epub 2021 Dec 31.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Casirivimab-imdevimab is a cocktail of 2 monoclonal antibodies designed to prevent infection by SARS-CoV-2, the virus that causes COVID-19. Casirivimab-imdevimab has been approved in Japan for treating mild to moderate COVID-19; however, to our knowledge, there are no reports of its use after kidney transplant from a live donor. Everolimus, an antineoplastic chemotherapy drug, is expected to be effective in inhibiting the spread of SARS-CoV-2 and preventing its replication, which may facilitate treatment. Here, we report a case of COVID-19 infection after kidney transplant that was initially treated with casirivimab-imdevimab and mycophenolate mofetil but was later changed to everolimus.

Case Report: A 47-year-old man underwent living donor kidney transplant from his mother in 2017. Immunosuppression therapy was underway through the administration of tacrolimus, mycophenolate mofetil, and methylprednisolone. In early September 2021, he was diagnosed as having COVID-19 and was hospitalized on day 3. On hospitalization, mycophenolate mofetil was discontinued and casirivimab-imdevimab and heparin were started. The patient started an everolimus regimen on day 5. The clinical course was successful without rejection. There was no exacerbation of COVID-19; the patient's serum creatinine levels and renal function had otherwise remained stable.

Conclusions: We could safely treat a patient with casirivimab-imdevimab after kidney transplant. It is suggested that casirivimab-imdevimab can prevent COVID-19 from becoming severe and can be administered without worsening renal function. In addition, everolimus may have inhibited the spread of the virus and prevented it from replicating.
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http://dx.doi.org/10.1016/j.transproceed.2021.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718884PMC
December 2021

Efficacy and feasibility of robot-assisted partial nephrectomy for octogenarians: comparison with younger counterparts.

Authors:
Yudai Ishiyama Tsunenori Kondo Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

J Robot Surg 2022 Jan 21. Epub 2022 Jan 21.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan.

To compare short-term functional and surgical outcomes of robot-assisted partial nephrectomy (RAPN) in patients ≥ 80 years old and their younger counterparts, we retrospectively analyzed 1234 patients who underwent robot-assisted partial nephrectomy. The cohort was classified into three groups (young [< 65, N = 802], old [65-79, N = 376], and very old [≥ 80, N = 56]) based on the age at the time of surgery. The perioperative outcomes, including acute/mid-term renal function, perioperative safety profiles, and trifecta attainment, were compared among the three groups. Preoperative estimated glomerular filtration rate (eGFR) was significantly lower in the very old group (49.0 mL/min/1.73 m), compared to young (71.6) or old (60.9) (all, p < 0.001). The decline in %eGFR at acute kidney injury (young: - 6.1 mL/min/1.73 m, old: - 6.2, very old: - 5.3; all, p > 0.05) and occurrence of AKI (all, p > 0.05) was comparable among groups. Similarly, change in %eGFR at 6 months was comparable across the three groups (young: - 5.0, old: - 6.3, very old: - 5.0; all, p > 0.05). Operative time and estimated blood loss were smaller in the very old group compared to the young or old groups. Furthermore, there were no differences in trifecta attainment rates among the groups. In the multivariable analyses using the reported possible confounders, age group was not shown to be a significant factor for predicting the renal function outcomes (acute or chronic) or trifecta attainment. Hence, RAPN for patients ≥ 80 years old showed comparable renal function and safety profiles compared to younger counterparts.
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http://dx.doi.org/10.1007/s11701-021-01350-0DOI Listing
January 2022

Surgical outcomes for older patients with renal cell carcinoma and inferior vena cava thrombus.

Authors:
Yudai Ishiyama Tsunenori Kondo Hidekazu Tachibana Hiroki Ishihara Kazuhiko Yoshida Toshio Takagi Junpei Iizuka Kazunari Tanabe

Urol Oncol 2022 03 10;40(3):110.e11-110.e18. Epub 2022 Jan 10.

Department of Urology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.

Objectives: To compare the surgical and oncological outcomes of older patients undergoing surgery for renal cell carcinoma (RCC) with a tumor in the inferior vena cava (IVC) and those of younger patients.

Materials And Methods: We retrospectively evaluated 123 patients who underwent surgery for RCC-IVC at two institutions between 2008 and 2019. We classified them into the ≥70 years and the <70 years group, based on their age during surgery. The patients' perioperative outcomes as well as survival (overall survival [OS] and cancer-specific survival [CSS]) were evaluated and compared before and after 1:1 propensity score matching. Sensitivity analyses were performed at age thresholds of 75 and 80 years.

Results: The ≥70 and the <70 groups comprised 43 and 80 patients, respectively. Most patients in the ≥70 group demonstrated an American Society of Anesthesiologists score of 2 or 3. They were more likely to have a statistically insignificant high (≥3) Charlson Comorbidity index score (16.3 vs. 6.3%) and a lower hemoglobin level (10.4 vs. 11.7 g/dL) than the <70 group. Eighteen (41.9%) and 32 (40.0%) patients had at least one distant metastasis at the time of surgery in the ≥70 and <70 group, respectively. The complication rates (any grade and grade ≥3), the length of hospitalization, readmission rates, and mortality were comparable between the groups, both before and after matching (all, non-specific). There was no statistically significant difference in the OS (median 66.6 vs. not reached [N.R.], P = 0.695) or CSS (N.R. vs. N.R., P = 0.605) between the groups before matching. The OS and CSS results were similar and comparable following matching (both, non-specific). Further, OS and CSS were comparable between the ≥75 and <75 groups, and between the ≥80 and <80 age groups, respectively.

Conclusion: The surgical outcomes of older patients with RCC-IVC were not inferior to those of younger patients. With careful patient selection, surgery can still be a treatment option.
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http://dx.doi.org/10.1016/j.urolonc.2021.12.013DOI Listing
March 2022

Association Between Anesthetic Technique and Survival After Radical Nephroureterectomy: A Propensity Score-matching Study.

Authors:
Yudai Ishiyama Tsunenori Kondo Hidekazu Tachibana Hiroki Ishihara Haruka Ito Nishioki Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

In Vivo 2022 Jan-Feb;36(1):458-464

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background/aim: Whether anesthesia can affect oncological outcomes in urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy (RNU) is not clear.

Patients And Methods: One-hundred an ninety-seven patients who underwent RNU were retrospectively recruited and divided into total intravenous (TIVA, n=90) and volatile inhalation anesthesia (VIA, n=107) groups. A 1:1 propensity score-matching method was employed to minimize selection bias (n=70 each). Cancer-specific (CSS), overall (OS) and metastasis-free (MFS) survival were compared between groups before and after matching.

Results: For all survival endpoints, no significant differences were observed between the two study groups, both before (hazard ratio for TIVA: CSS: 0.70, OS: 0.75, MFS: 0.78) and after (hazard ratios for TIV: CSS: 1.21, OS: 0.82, MFS: 0.84) matching.

Conclusion: With no survival difference observed according to anesthetic technique for RNU, the choice should be based on factors such as accessibility, prevention of side-effects, or costs.
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http://dx.doi.org/10.21873/invivo.12725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765133PMC
January 2022

New Longitudinal Component of the RENAL Nephrometry Score for Predicting the Operative Complexity in Transperitoneal Robot-Assisted Partial Nephrectomy.

Authors:
Hidekazu Tachibana Tsunenori Kondo Yudai Ishiyama Maki Yoshino Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

J Endourol 2022 06;36(6):762-769

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

In transperitoneal robot-assisted partial nephrectomy (RAPN), an L score of 3 points according to the RENAL nephrometry scoring system does not necessarily denote operative complexity. This study aimed to assess the efficacy of the newly defined longitudinal component to analyze the operative complexity of RAPN. We retrospectively analyzed transperitoneal RAPNs performed by a single experienced surgeon for renal tumors between 2017 and 2020. L component was defined as L'1 for midlocated tumors, L'2 for >50% below the polar line, and L'3 for >50% above the polar line. Multivariate regression analysis was performed to test associations between prolonged console time and preoperative factors. The perioperative outcomes were compared among the three cohorts of L' components using propensity score matching: L'1 L'3 and L'1 L'2. A total of 220 cases (L'1: 107, L'2: 65, L'3: 48) were analyzed. The median console time was prolonged (>130 minutes) in 55 patients (median 108, interquartile range: 90-130 minutes). Longitudinal location (L'3 odds ratio [OR]: 2.93,  = 0.01; L'2 OR: 2.32,  = 0.04), high Mayo adhesive probability score ( = 0.001), multiple renal arteries ( = 0.03), and large size ( = 0.04) were significantly associated with prolonged console time. After matching, 26 cases of L'1 and L'3 and 43 cases of L'1 and L'2 were selected. Console time (108 minutes 132 minutes,  = 0.017) and warm ischemia time (17 minutes 22 minutes,  = 0.03) were significantly longer in L'3 than in L'1. The difference in console time between L'1 and L'2 was not statistically significant (100 minutes 111 minutes,  = 0.08). In the new longitudinal assessment, upper location predicted prolonged console time compared with a middle or lower location. The L' component may help preoperatively assess operative complexity.
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http://dx.doi.org/10.1089/end.2021.0716DOI Listing
June 2022

Two Laparotomy Surgeries to Achieve Hemostasis After Kidney Transplantation in a Patient With Frailty: A Case Report.

Authors:
Yu Kijima Tomokazu Shimizu Shinya Kato Eri Sekido Kana Kano Makoto Toguchi Toshihide Horiuchi Taiji Nozaki Kazuya Omoto Masashi Inui Hiroshi Toma Shoichi Iida Toshio Takagi

Transplant Proc 2022 Jan-Feb;54(1):120-122. Epub 2021 Dec 24.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background: The assessment of frailty before and after kidney transplantation is becoming more important in the aging population. It is recommended to recognize the post-transplant risks and establish a treatment strategy. We report the case of a patient who underwent 2 laparotomy hemostasis procedures due to frailty after kidney transplantation.

Case Report: A 72-year-old woman presented with end-stage renal failure due to an unknown primary disease. She was also found to be frail when assessed using the physical frailty phenotype. She underwent ABO-incompatible kidney transplantation from her husband at the end of March 2020. On the first postoperative day, re-operation for hematoma evacuation was performed. The bleeding point could not be identified at that time. Progression of anemia was observed on the sixth postoperative day, and computed tomography showed no obvious bleeding. Subsequently, the renal allograft started functioning immediately, without rejection. However, emergency laparotomy for hematoma removal was performed on the 22nd postoperative day. Bleeding had occurred from the anastomotic region of the renal allograft artery and the external iliac artery. Her serum creatinine levels and renal function remained stable one month after surgery.

Conclusions: We encountered a case of living-donor kidney transplantation in a frail older woman who underwent 2 laparotomies due to hemorrhage. Perioperative risk management is necessary for patients with a high risk of postoperative bleeding. To ensure a good outcome, preoperative and postoperative rehabilitation is important for patients with frailty.
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http://dx.doi.org/10.1016/j.transproceed.2021.11.021DOI Listing
February 2022

Association between Ureteral Clamping Time and Acute Kidney Injury during Robot-Assisted Radical Cystectomy.

Authors:
Yudai Ishiyama Tsunenori Kondo Hiroki Ishihara Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Toshio Takagi

Curr Oncol 2021 11 29;28(6):4986-4997. Epub 2021 Nov 29.

Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 1620054, Japan.

Robot-assisted radical cystectomy (RARC) is replacing open radical cystectomy (ORC) and requires clamping of the ureters, resulting in a predisposition to postrenal acute kidney injury (AKI). We investigated the association between ureteral clamping or its duration and acute/chronic postoperative kidney function. Patients who underwent radical cystectomy (robotic or open) at two tertiary institutions during 2002-2021 were retrospectively enrolled. In those who underwent RARC, the maximum postoperative percentage serum creatinine level (%sCre) change was plotted against ureteral clamping duration. They were divided into two groups using the median clamping time (210 min), and the maximum %sCre change and percentage estimated glomerular filtration rate (%eGFR) change at 3-6 months (chronic) were compared between the ORC (no clamp), RARC < 210, and RARC ≥ 210 groups. In 44 RARC patients, a weak correlation was observed between the duration of ureteral clamping and %Cre change (R = 0.22, = 0.001). Baseline serum creatinine levels were comparable between the groups. However, %sCre change was significantly larger in the RARC ≥ 210 group (N = 17, +32.1%) than those in the RARC < 210 (N = 27, +6.1%) and ORC (N = 76, +9.5%) groups (both, < 0.001). Chronic %eGFR change was comparable between the groups. Longer clamping of the ureter during RARC may precipitate AKI; therefore, the clamping duration should be minimized.
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http://dx.doi.org/10.3390/curroncol28060418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700330PMC
November 2021

Validation of a Predictive Model for New Baseline Renal Function After Radical Nephrectomy or Robot-Assisted Partial Nephrectomy in Japanese Patients.

Authors:
Hidekazu Tachibana Kenji Omae Hiroki Ishihara Hironori Fukuda Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe Tsunenori Kondo Toshio Takagi

J Endourol 2022 06 20;36(6):745-751. Epub 2022 May 20.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

The study's aim was to externally validate a new predictive model for the new baseline glomerular filtration rate (NB-GFR) postnephrectomy among Japanese patients. Patients with renal tumors who underwent radical nephrectomy (RN) or robot-assisted laparoscopic partial nephrectomy (PN) at a single Japanese institution during the period 2000-2020 were retrospectively analyzed. The NB-GFR is defined as the final estimated glomerular filtration rate within postoperative 3-12 months. The correlation/bias/accuracy/precision of the equation was examined by comparing the calculated NB-GFR with the observed rate. The study included 485 cases of RN and 1030 cases of robot-assisted laparoscopic PN. The correlation/bias/accuracy/precision of the new equation predicting the NB-GFR was 0.86/-0.92/95.9/-5.65-3.62 in robot-assisted laparoscopic PN and 0.79/-1.02/87.8/-6.26-3.91 in RN, respectively. The fractional polynomial regression line approximated zero and its pointwise 95% confidence interval (CI) was considerably tight for the majority of both cohorts. The 95% CI to discriminate NB-GFRs ≥45 mL/min/1.73 m from receiver operating curves was 0.96 (0.95-0.97) and 0.89 (0.87-0.92) in robot-assisted laparoscopic PN and RN, respectively. Various preoperative factors, including age, tumor size, complexity, body mass index, hypertension, and diabetes, did not affect the predictive ability (correlation >0.7) of the subgroup analysis. The novel simple equation can accurately predict NB-GFRs after radical and robot-assisted laparoscopic partial nephrectomies in Japanese patients. This model will help physicians choose surgical treatments for renal tumors in daily clinical practice.
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http://dx.doi.org/10.1089/end.2021.0655DOI Listing
June 2022

Predictive Impact of Early Changes in Serum C-Reactive Protein Levels in Nivolumab Plus Ipilimumab Therapy for Metastatic Renal Cell Carcinoma.

Authors:
Hidekazu Tachibana Yuki Nemoto Hiroki Ishihara Hironori Fukuda Kazuhiko Yoshida Junpei Iizuka Yasunobu Hashimoto Tsunenori Kondo Kazunari Tanabe Toshio Takagi

Clin Genitourin Cancer 2022 02 13;20(1):e81-e88. Epub 2021 Oct 13.

Department of Urology, Tokyo Women's Medical University Tokyo, Tokyo, Japan.

Background: Serum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy.

Methods: Forty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥ 1.0 mg/dL and < 1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first 3 months of NIVO-IPI, patients were placed in the normal group (CRP remains < 1.0 mg/dL), normalized group (CRP decreased < 1.0 mg/dL), and non-normalized group (CRP remained or increased to ≥ 1.0 mg/dL). The predictive association between CRP change and PFS was evaluated.

Results: PFS was significantly lower in the high initial CRP group (n = 24, 50%) compared to the normal CRP group (n = 24, 50%) (median: 4.3 vs. 28.1 months, P = .03). As for the early CRP change, the normal (2.7 vs. 28.1, P = .0002) and normalized (2.7 vs. 11.0, P = .0094) groups showed significantly higher PFS, compared to the non-normalized group. Meanwhile, there was no significant difference between normal, and normalized groups (P = .51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P = .015) and normalized (81.8 vs. 18.7%, P = .0008) groups, compared to the non-normalized group. Multivariate Cox regression analysis showed that normal [Hazard ratio (HR) = 0.15, 95% Confidence interval (CI) = 0.02-0.70, P = .026] and normalized (HR 0.21, 95% CI = 0.05-0.73, P = .015) CRP showed significant association with PFS.

Conclusion: In the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies.
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http://dx.doi.org/10.1016/j.clgc.2021.10.005DOI Listing
February 2022

Allogeneic Kidney Transplantation After COVID-19: A Case Report.

Authors:
Yu Kijima Tomokazu Shimizu Eri Sekido Shinya Kato Kana Kano Makoto Toguchi Toshihide Horiuchi Taiji Nozaki Kazuya Omoto Masashi Inui Hiroshi Toma Shoichi Iida Toshio Takagi

Transplant Proc 2021 Oct 15. Epub 2021 Oct 15.

Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Patients undergoing organ transplantation are immunosuppressed and already at risk of various diseases. We report about a patient who underwent ABO-incompatible kidney transplantation after coronavirus disease 2019 (COVID-19) without a recurrence of infection.

Case Report: A 68-year-old woman presented with end-stage renal failure owing to primary autosomal dominant polycystic kidney disease; accordingly, hemodialysis was initiated in September 2020. Her medical history included bilateral osteoarthritis, lumbar spinal stenosis, hypertension, and hyperuricemia. In mid-January 2021, she contracted severe acute respiratory syndrome coronavirus 2 infection from her husband. Both of them were hospitalized and received conservative treatment. Because their symptoms were mild, they were discharged after 10 days. The patient subsequently underwent ABO-incompatible kidney transplantation from her husband who recovered from COVID-19 in March 2021. Before kidney transplantation, her COVID-19 polymerase chain reaction test was negative, confirming the absence of pre-existing COVID-19 immediately before the procedure. Computed tomography revealed no pneumonia. Initial immunosuppression was induced by administering tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, rituximab, and 30 g of intravenous immunoglobulin. Double-filtration plasmapheresis and plasma exchange were performed once before ABO-incompatible kidney transplantation. The renal allograft functioned immediately, and the postoperative course was normal without rejection. COVID-19 did not recur. In addition, her serum creatinine levels and renal function had otherwise remained stable.

Conclusion: Living kidney transplantation was safely performed in a patient with COVID-19 without postoperative complications or rejection. During the COVID-19 pandemic, the possibility of severe acute respiratory syndrome coronavirus 2 infection during transplantation surgery must be considered.
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http://dx.doi.org/10.1016/j.transproceed.2021.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516720PMC
October 2021
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