Publications by authors named "Toshio Takagi"

163 Publications

Predictive Impact of Prognostic Nutritional Index on Pembrolizumab for Metastatic Urothelial Carcinoma Resistant to Platinum-based Chemotherapy.

Anticancer Res 2021 Mar;41(3):1607-1614

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

Background/aim: We investigated the prognostic nutritional index (PNI), comprised of lymphocytes and albumin, as a potential prognosticator of metastatic urothelial carcinoma (mUC) patients receiving pembrolizumab.

Patients And Methods: Sixty-five patients were retrospectively enrolled and classified as low (<40) and high (≥40) based on pretreatment PNI. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated.

Results: In the low PNI group, significantly shorter PFS and OS were observed. PNI was shown to be an independent predictor of PFS and OS in the multivariate analysis. C-index for both PFS and OS improved with the addition of PNI to the model described in the KEYNOTE-045 study. Significantly more patients experienced initial disease progression in the low PNI group.

Conclusion: PNI is a useful predictor of prognosis and disease progression in mUC patients receiving pembrolizumab.
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http://dx.doi.org/10.21873/anticanres.14922DOI Listing
March 2021

Outcome of advanced renal cell carcinoma arising in end-stage renal disease: comparison with sporadic renal cell carcinoma.

Clin Exp Nephrol 2021 Feb 27. Epub 2021 Feb 27.

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

Background: The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited.

Methods: Patients diagnosed with advanced RCC on maintenance dialysis therapy (ESRD-RCC) and treated with tyrosine kinase inhibitors (TKIs) were retrospectively evaluated. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after initiation of first-line TKI therapy in ESRD-RCC patients were compared to those in RCC arising in the general population (sporadic RCC).

Results: A total of 36 and 240 patients were diagnosed with advanced ESRD-RCC and sporadic RCC, respectively. PFS and OS were significantly shorter in patients with ESRD-RCC than in those with sporadic RCC (p = 0.0004 and p = 0.0045). After adjusting for histopathological type, MSKCC risk and liver metastasis status, ESRD status (ESRD-RCC vs. sporadic RCC) was not an independent risk factor for PFS or OS (both, p > 0.05). The ORR tended to be lower in patients with ESRD-RCC than in those with sporadic RCC (11% vs. 28%, p = 0.0833). In 34 patients with ESRD-RCC treated with sorafenib, longer duration of dialysis was an independent prognostic factor for shorter OS (hazard ratio 3.21, p = 0.0370).

Conclusions: Outcome of advanced ESRD-RCC was poorer than that of sporadic RCC, but this finding was affected by other prognostic factors. Nevertheless, the study suggested that advanced ESRD-RCC was not an indolent disease. Additionally, patients with a longer duration of dialysis therapy might require careful monitoring.
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http://dx.doi.org/10.1007/s10157-021-02038-3DOI Listing
February 2021

The Controlling Nutritional Status CONUT Score in Patients With Advanced Bladder Cancer After Radical Cystectomy.

In Vivo 2021 Mar-Apr;35(2):999-1006

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

Background/aim: The impact of the controlling nutritional status (CONUT) score on oncological outcomes after radical cystectomy (RC) for advanced bladder cancer (BC) is unknown.

Patients And Methods: We retrospectively evaluated 115 patients who underwent RC for advanced BC at our department between November 2003 and February 2019. The CONUT score was calculated from serum albumin levels, total lymphocyte counts, and total cholesterol levels. Relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RC were analyzed.

Results: For the CONUT score, the area under curve was 0.651 and the optimal cut-off value determined using the Youden index was 3. The high CONUT group had significantly shorter RFS, CSS, and OS than the low CONUT group. Multivariate analyses showed that the CONUT score was an independent prognostic factor of RFS, CSS, and OS.

Conclusion: The CONUT score could be an effective predictor for survival and tolerability following RC for advanced BC.
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http://dx.doi.org/10.21873/invivo.12343DOI Listing
December 2020

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.

N Engl J Med 2021 04 13;384(14):1289-1300. Epub 2021 Feb 13.

From Memorial Sloan Kettering Cancer Center, New York (R.M.); P. Hertsen Moscow Oncology Research Institute, Moscow (B.A.), the State Institution of Health Care Regional Clinical Oncology Dispensary, Omsk (E.K.), the State Budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary, Novosibirsk (V.K.), and Prevoljskiy Region Medical Center, Novgorod (A.A.) - all in Russia; Yonsei Cancer Center, Yonsei University Health System (S.Y.R.), Seoul St. Mary's Hospital, Catholic University of Korea (S.-H.H.), and Seoul National University Hospital (M.K.), Seoul, South Korea; San Matteo University Hospital Foundation, Pavia (C.P.), Istituto Nazionale dei Tumori IRCCS, Milan (G.P.), and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola (U.D.G.) - all in Italy; Kyushu University, Fukuoka (M.E.), and Tokyo Women's Medical University, Tokyo (T.T.) - both in Japan; the Royal Free NHS Trust, London (T.P.), and Eisai, Hatfield (A.D.S.) - both in the United Kingdom; University Hospital Essen, Essen (V.G.), and the University of Tübingen, Tübingen (J.B.) - both in Germany; Texas Oncology, Dallas (T.E.H.); Maimonides Institute for Biomedical Research of Cordoba Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba (M.J.M.-V.), Hospital Universitario Ramón y Cajal, Madrid (T.A.G.), and Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.) - all in Spain; McMaster University, Hamilton (A.K.), and Western University, London (E.W.) - both in Ontario, Canada; the University of Miami Sylvester Comprehensive Cancer Center, Miami (J.R.M.), and Florida Cancer Specialists, Gainesville (V.P.); ICON Research, South Brisbane, and University of Queensland, St. Lucia, QLD (J.C.G.), Macquarie University, Sydney (H.G.), and Western Health, Melbourne, VIC (S.W.) - all in Australia; Rambam Health Care Campus, Haifa, Israel (A.P.); Palacky University and University Hospital Olomouc, Olomouc, Czech Republic (B.M.); Centre René Gauducheau, Saint Herblain, France (F.R.); the Department of Urology, Medical University of Vienna, Vienna (M.S.); Eisai, Woodcliff Lake (C.E.D., L.D., K.M., D.X.), and Merck, Kenilworth (R.F.P.) - both in New Jersey; and Dana-Farber Cancer Institute, Boston (T.K.C.).

Background: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.

Methods: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.

Results: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.

Conclusions: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
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http://dx.doi.org/10.1056/NEJMoa2035716DOI Listing
April 2021

Effect of improved systemic therapy on patient survival in metastatic non-clear-cell renal cell carcinoma.

Int J Urol 2021 Feb 22. Epub 2021 Feb 22.

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

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http://dx.doi.org/10.1111/iju.14523DOI Listing
February 2021

Early dark cortical band sign on CT for differentiating clear cell renal cell carcinoma from fat poor angiomyolipoma and detecting peritumoral pseudocapsule.

Eur Radiol 2021 Feb 9. Epub 2021 Feb 9.

Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Objectives: To retrospectively evaluate whether the early dark cortical band (EDCB) on CT can be a predictor to differentiate clear cell renal cell carcinoma (ccRCC) from fat poor angiomyolipoma (Fp-AML) and to detect peritumoral pseudocapsules in ccRCC.

Methods: The EDCBs, which are comprised of unenhanced thin lines at the tumor-renal cortex border in the corticomedullary phase, on the CT images of 342 patients who underwent partial nephrectomy were evaluated. Independent predictors among the clinical and CT findings for differentiating ccRCC from Fp-AML were identified using multivariate analyses. The diagnostic performance of the EDCB for diagnosing peritumoral pseudocapsule in ccRCC and differentiating ccRCC from Fp-AML was calculated.

Results: The EDCB was observed in 157 of 254 (61.8%) ccRCCs, 4 of 31 (12.9%) chromophobe RCCs, 1 of 21 (4.8%) papillary RCCs, 3 of 11 (27.3%) clear cell papillary RCCs, 3 of 8 (37.5%) oncocytomas, and 0 of 17 (0%) Fp-AMLs. There was substantial interobserver agreement for the EDCB (k = 0.719). The EDCB was a significant predictor for differentiating ccRCC from Fp-AML (p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of the EDCB for differentiating ccRCC from Fp-AML were 61.8%, 100%, 100%, and 14.9%, respectively, and those for detecting pseudocapsule in 236 ccRCCs were 62.3%, 68.8%, 96.5%, and 11.7%, respectively.

Conclusion: Although diagnostic accuracy of the EDCB for detecting peritumoral pseudocapsule in RCC is inadequate, it can be a predictor for differentiating ccRCC from Fp-AML with high specificity and PPV.

Key Points: • The early dark cortical band (EDCB) sign is observed in nearly two-thirds of clear cell renal cell carcinoma (ccRCC) that are treated by partial nephrectomy and have substantial interobserver agreement. • The EDCB is a significant predictor for differentiating ccRCCs from fat poor angiomyolipomas, with a high specificity and positive predictive value. • Diagnostic accuracy of the EDCB for detecting peritumoral pseudocapsule in ccRCC is inadequate, though better than those in the nephrographic and excretory-phase images.
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http://dx.doi.org/10.1007/s00330-021-07717-zDOI Listing
February 2021

Impact of sarcopenia on post-operative outcomes following nephrectomy and tumor thrombectomy for renal cell carcinoma with inferior vena cava thrombus.

Jpn J Clin Oncol 2021 Feb 9. Epub 2021 Feb 9.

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

Objective: Sarcopenia is associated with oncological outcomes in various types of cancer. However, the impact of sarcopenia in renal cell carcinoma with inferior vena cava thrombus remains unclear. We herein evaluated the prognostic significance of sarcopenia for renal cell carcinoma with inferior vena cava thrombus following nephrectomy and thrombectomy.

Methods: Patients who underwent nephrectomy and thrombectomy for renal cell carcinoma with inferior vena cava thrombus at our department between 2004 and 2019 were retrospectively evaluated. Their sarcopenic status, determined by sex, body mass index and skeletal muscle index, was calculated using pre-surgical radiographic imaging. We compared the post-operative cancer-specific survival and overall survival, surgical data and duration of post-operative hospitalization of sarcopenic and non-sarcopenic patients.

Results: Out of 83 patients, 54 (65%) were sarcopenic. Sarcopenic patients had significantly shorter cancer-specific survival (median: 33.3 months vs. not reached, P = 0.0323) and overall survival (32.0 months vs. not reached, P = 0.0173) than non-sarcopenic patients. Furthermore, multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.76, P = 0.0212) and overall survival (hazard ratio: 2.93, P = 0.014). The incidence rate of surgical complications (any grade: 35.2% vs. 27.6%, P = 0.482; grades ≥ 3: 7.4% vs. 10.3%, P = 0.648) or duration of post-operative hospitalization (median: 11 vs. 10 days, P = 0.148) was not significantly different between sarcopenic and non-sarcopenic patients.

Conclusions: In conclusion, this study showed that sarcopenia was an independent prognostic factor for renal cell carcinoma with inferior vena cava thrombus after nephrectomy and tumor thrombectomy. Thus, sarcopenia evaluation can be utilized as an effective prognosticator of post-operative survival.
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http://dx.doi.org/10.1093/jjco/hyaa275DOI Listing
February 2021

Detection of a peritumoral pseudocapsule in patients with renal cell carcinoma undergoing robot-assisted partial nephrectomy using enhanced MDCT.

Sci Rep 2021 Jan 26;11(1):2245. Epub 2021 Jan 26.

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

To investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.
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http://dx.doi.org/10.1038/s41598-021-81922-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838255PMC
January 2021

Therapeutic benefit of lymphadenectomy for older patients with urothelial carcinoma of the upper urinary tract: a propensity score matching study.

Jpn J Clin Oncol 2021 Jan 13. Epub 2021 Jan 13.

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

Objectives: Regional lymphadenectomy for urothelial carcinoma of the upper urinary tract is sometimes avoided in older patients to reduce surgical burden. We aimed to evaluate the therapeutic impact of lymphadenectomy in older patients undergoing curative therapy for upper urinary tract urothelial carcinoma.

Methods: The patients with urothelial carcinoma of the upper urinary tract older than 75 years at the time of surgery and without lymph node or distant metastasis who underwent curative therapy at two tertiary hospitals between 1994 and 2019 were retrospectively analyzed. Complete-lymphadenectomy was performed as per our protocol. Cancer-specific survival, overall survival and metastasis-free survival after surgery were evaluated between complete-lymphadenectomy and no/incomplete-lymphadenectomy groups before and after 1:1 propensity score matching.

Results: The original cohort included 150 patients (median age, 80.71 years), and complete-lymphadenectomy was performed in 42 (28.00%) patients. Patients in complete-lymphadenectomy group were younger and less likely to be aged >80 years (both, P < 0.0001). After matching, 30 patients were allocated to each group and the ages were comparable (78.58 vs. 77.48 years, P = 0.1738). High-grade perioperative complication rates did not differ between groups both before and after matching. Cancer-specific survival, overall survival and metastasis-free survival were significantly longer in the complete-lymphadenectomy group both before and after matching (all, P < 0.05).

Conclusions: This study suggests that complete-lymphadenectomy may provide therapeutic benefits for older patients. The decision to perform complete-lymphadenectomy must be based on the patient's physical condition, rather than his/her chronological age.
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http://dx.doi.org/10.1093/jjco/hyaa256DOI Listing
January 2021

Editorial Comment to Successful recovery from coronavirus disease 2019 in a living kidney transplant recipient using low-dose methylprednisolone.

Authors:
Toshio Takagi

IJU Case Rep 2021 Jan 25;4(1):25. Epub 2020 Oct 25.

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

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http://dx.doi.org/10.1002/iju5.12238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784767PMC
January 2021

Assessing improvements in metastatic renal cell carcinoma systemic treatments from the pre-cytokine to the immune checkpoint inhibitor eras: a retrospective analysis of real-world data.

Jpn J Clin Oncol 2020 Dec 15. Epub 2020 Dec 15.

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

Objective: Studies assessing outcome improvements over a long period according to systemic therapy strategies for metastatic renal cell carcinoma using real-world data, including the results of the recent era of immune checkpoint inhibitors, are limited. Herein, we retrospectively evaluated patients who were diagnosed with metastatic renal cell carcinoma over a 40-year span.

Methods: Patients were classified into four groups based on when their metastases were diagnosed as follows: (i) the pre-cytokine era (1980-1986), (ii) the cytokine era (1987-2007), (iii) the molecular-targeted therapy (mTT) era (2008 to August 2016) and (iv) the immune checkpoint inhibitor era (September 2016 to 2018). The immune checkpoint inhibitor era consisted of second- or later-line nivolumab. Overall survival from the diagnoses of metastases was evaluated.

Results: In total, 576 patients were evaluated, including 22 (3.82%), 231 (40.1%), 253 (43.9%) and 70 (12.2%) patients from the pre-cytokine, cytokine, molecular-targeted therapy and immune checkpoint inhibitor eras, respectively. The overall survival significantly improved with each successive era (median: 13.1 vs. 24.5 vs. 44.4 months vs. not reached in pre-cytokine vs. cytokine vs. molecular-targeted therapy vs. immune checkpoint inhibitor eras, P < 0.0001). The implementation of molecular-targeted therapy improved overall survival compared with that of cytokine (cytokine vs. molecular-targeted therapy eras, P < 0.0001). Multivariate analysis demonstrated that the era was an independent factor for overall survival (P < 0.0001), together with histopathological type; metastasis status (i.e. synchronous or metachronous); systemic therapy status (i.e. absence or presence) and bone, liver or lymph node metastasis status (all, P < 0.05).

Conclusion: This retrospective study of real-world data indicated that metastatic renal cell carcinoma outcomes improved with successive systemic therapy paradigms.
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http://dx.doi.org/10.1093/jjco/hyaa232DOI Listing
December 2020

Modest efficacy of nivolumab plus ipilimumab in patients with papillary renal cell carcinoma.

Jpn J Clin Oncol 2021 Apr;51(4):646-653

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

Purpose: Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma.

Materials And Methods: This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma).

Results: Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity.

Conclusion: Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.
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http://dx.doi.org/10.1093/jjco/hyaa229DOI Listing
April 2021

Efficacy of nivolumab versus molecular-targeted therapy as second-line therapy for metastatic renal cell carcinoma: Real-world data from two Japanese institutions.

Int J Urol 2021 Jan 6;28(1):99-106. Epub 2020 Nov 6.

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

Objectives: To compare the efficacy of nivolumab with that of molecular-targeted therapy as a second-line therapy for metastatic renal cell carcinoma using real-world data.

Methods: We retrospectively evaluated patients who received nivolumab or molecular-targeted therapy after the failure of first-line molecular-targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression-free survival and overall survival after the initiation of second-line therapy were calculated using the Kaplan-Meier method and compared using the log-rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1.

Results: Among 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular-targeted therapy as second-line therapy, respectively. During follow up (median 11.1 months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression-free survival was comparable between the two treatments (median 5.06 vs 5.95 months, P = 0.881), whereas overall survival was significantly longer with nivolumab than with molecular-targeted therapy (not reached vs 13.0 months, P = 0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P = 0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular-targeted therapy (n = 14/41 [34%] vs n = 20/110 [18%], P = 0.0485).

Conclusions: Real-world data analysis suggests superior efficacy of nivolumab over molecular-targeted therapy as second-line therapy for metastatic renal cell carcinoma.
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http://dx.doi.org/10.1111/iju.14412DOI Listing
January 2021

Comparison of postoperative recovery after robot-assisted partial nephrectomy of T1 renal tumors through retroperitoneal or transperitoneal approach: A Japanese single institutional analysis.

Int J Urol 2021 Feb 3;28(2):183-188. Epub 2020 Nov 3.

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

Objective: To evaluate the quality of recovery in patients who underwent robot-assisted partial nephrectomy and to compare the outcomes of the transperitoneal or retroperitoneal approach.

Methods: This study included 121 patients who underwent robot-assisted partial nephrectomy under general anesthesia from April 2019 to September 2019 at Tokyo Women's Medical University, Tokyo, Japan. Quality of recovery was defined according to the QoR-40 Japanese version. The participants responded to the QoR-40 Japanese version on three designated days. The patients were assigned to two groups according to the surgical approach: transperitoneal or retroperitoneal. A multivariate logistic regression analysis was carried out to identify independent factors associated with better quality of recovery.

Results: Out of the 121 patients, 56 (46%) and 65 (54%) patients were included in the transperitoneal and retroperitoneal group, respectively. Although the QoR-40 Japanese version scores were not different between the two groups at admission, a better quality of recovery was observed in the retroperitoneal group than in the transperitoneal group at discharge based on the total score: physical comfort, emotional state, physical independence and pain. A multivariate analysis showed that the retroperitoneal approach and male sex were associated with a better QoR-40 Japanese version score at discharge.

Conclusions: A retroperitoneal approach offers better quality of recovery than a transperitoneal approach, and therefore it might represent the optimal approach in selected patients undergoing robot-assisted partial nephrectomy.
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http://dx.doi.org/10.1111/iju.14424DOI Listing
February 2021

Predictive role of γ-glutamyltransferase in patients receiving nivolumab therapy for metastatic renal cell carcinoma.

Int J Clin Oncol 2021 Mar 1;26(3):552-561. Epub 2020 Nov 1.

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

Introduction: γ-Glutamyltransferase is reportedly associated with survival in local and metastatic renal cell carcinoma patients; however, its predictive role among patients treated with immune-checkpoint inhibitors are unknown. This study aimed to investigate the role of γ-glutamyltransferase as a predictive marker among metastatic renal cell carcinoma patients undergoing nivolumab therapy.

Methods: We retrospectively evaluated 69 nivolumab-treated metastatic renal cell carcinoma patients upon failure of one or more systematic therapies. Serum γ-glutamyltransferase levels were determined at baseline and 2 months after nivolumab treatment initiation. Patients were classified as high (≥ 49 U/L) and low (< 49 mg/dL) from baseline GGT levels and the outcomes were compared between the two groups. Furthermore, increased (after/baseline ≥ 2) and non-increased (after/baseline < 2) groups were compared. Progression-free survival and overall survival were evaluated after nivolumab initiation.

Results: Overall survival was significantly shorter in the high baseline γ-glutamyltransferase group (20.3%) than in the low group (79.7%) (median 2.33 vs not reached [months], p = 0.0051). Progression-free survival and the overall survival were significantly shorter in the increased than in the non-increased group (24.6% and 75.4%, respectively) (median PFS: 4.43 vs 7.23 [months], p = 0.0373/OS: 24.00 vs not reached, p = 0.0467). On multivariate analyses, high baseline γ-glutamyltransferase was an independent factor for overall survival (p = 0.0345) and increased γ-glutamyltransferase was an independent factor for progression-free survival (p = 0.0276) and overall survival (p = 0.0160).

Conclusions: High baseline γ-glutamyltransferase and its early increase are associated with a poor prognosis in metastatic renal cell carcinoma patients receiving nivolumab. Serum γ-glutamyltransferase levels may help predict treatment outcomes.
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http://dx.doi.org/10.1007/s10147-020-01819-2DOI Listing
March 2021

Outcomes of minimally invasive partial nephrectomy among very elderly patients: report from the RESURGE collaborative international database.

Cent European J Urol 2020 8;73(3):273-279. Epub 2020 Sep 8.

Unit of Urology, Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy.

The aim of the study was to perform a comprehensive investigation of clinical outcomes of robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) in elderly patients presenting with a renal mass. The REnal SURGery in Elderly (RESURGE) collaborative database was queried to identify patients aged 75 or older diagnosed with cT1-2 renal mass and treated with RAPN or LPN. Study outcomes were: overall complications (OC); warm ischemia time (WIT) and 6-month estimated glomerular filtration rate (eGFR); positive surgical margins (PSM), disease recurrence (REC), cancer-specific mortality (CSM) and other-cause mortality (OCM). Descriptive statistics, Kaplan-Meier, smoothed Poisson plots and logistic and linear regression models (MVA) were used. Overall, 216 patients were included in this analysis. OC rate was 34%, most of them being of low Clavien grade. Median WIT was 17 minutes and median 6-month eGFR was 54 ml/min/1.73 m. PSM rate was 5%. After a median follow-up of 20 months, the 5-year rates of REC, CSM and OCM were 4, 4 and 5%, respectively. At MVA predicting perioperative morbidity, RAPN relative to LPN (odds ratio [OR] 0.33; p <0.0001) was associated with lower OC rate. At MVA predicting functional outcomes, RAPN relative to LPN was associated with shorter WIT (estimate [EST] -4.09; p <0.0001), and with higher 6-month eGFR (EST 6.03; p = 0.01). In appropriately selected patients with small renal masses, minimally-invasive PN is associated with acceptable perioperative outcomes. The use of a robotic approach over a standard laparoscopic approach can be advantageous with respect to clinically relevant outcomes, and it should be preferred when available.
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http://dx.doi.org/10.5173/ceju.2020.0179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587491PMC
September 2020

Difficulty in differential diagnosis for renal cancer with microscopic papillary architecture: overlapped pathological features among papillary renal cell carcinoma (RCC), mutinous tubular and spindle cell carcinoma, and unclassified RCC. Lessons from a Japanese multicenter study.

Jpn J Clin Oncol 2020 Oct;50(11):1313-1320

Department of Urology, National Defense Medical College, Saitama, Japan.

Objectives: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC.

Methods: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features.

Results: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years.

Conclusion: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.
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http://dx.doi.org/10.1093/jjco/hyaa114DOI Listing
October 2020

Active surveillance for small renal masses in elderly patients does not increase overall mortality rates compared to primary intervention: a propensity score weighted analysis.

Minerva Urol Nefrol 2020 Sep 29. Epub 2020 Sep 29.

Department of Urology, Instituto Valenciano de Oncología (IVO), Valencia, Spain -

Background: To test the effect of active surveillance (AS) versus primary intervention (PI) on overall mortality (OM) in elderly patients diagnosed with SRM.

Methods: Elderly patients (75 years or older) diagnosed with SRMs (< 4cm) and treated with either PI [i.e. partial nephrectomy or kidney ablation] or AS between 2009 and 2018 were abstracted from the REnal SURGery in the Elderly (RESURGE) and Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) datasets, respectively. OM rates were estimated among groups with Kaplan Meier method and Cox proportional hazards regression models after applying inverse probability of treatment weighting (IPTW). Multivariable logistic regression model was used to estimate IPTW. Covariates of interest were those unbalanced and/or significantly correlated with the treatment choice or with OM.

Results: A total of 483 patients were included; 121 (25.1%) underwent AS. 60 patients (12.4%) died. Overall, 6.7% of all deaths were related to cancer. IPTW-Kaplan Meier curves showed a 5-year overall survival rates of 70.0 ± 3.5% and 73.2 ± 4.8% in AS and PI groups, respectively (IPTW-Log-rank p-value=0.308). IPTW-Cox regression model did not show meaningfully increased OM rates in AS group (HR=1.31, 95% CI: 0.69-2.49).

Conclusions: AS represents an appealing treatment option for very elderly patients presenting with SRM, as it avoids the risks of a PI while not compromising the survival outcomes of these patients.
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http://dx.doi.org/10.23736/S0393-2249.20.03785-6DOI Listing
September 2020

Prognostic impact of systemic therapy change in metastatic renal cell carcinoma treated with cytoreductive nephrectomy.

Jpn J Clin Oncol 2021 Feb;51(2):296-304

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

Objective: Limited data are available regarding the effect of systemic therapy change in the post-cytokine era on survival of metastatic renal cell carcinoma (mRCC) patients undergoing cytoreductive nephrectomy (CN).

Methods: Overall, 161 patients with synchronously mRCC were retrospectively evaluated. The patients were classified into three groups based on the time of diagnosis: (i) early molecular-targeted therapy (mTT) (2008-2011), (ii) late mTT (2012-8/2016) and (iii) immune checkpoint inhibitor (ICI) eras (9/2016-2018). Overall survival (OS) after the diagnosis was compared among the eras.

Results: Of the 161 patients, 52 (32%), 75 (46%), and 34 patients (21%) were classified into the early mTT, late mTT and ICI eras, respectively. OS was significantly longer in the ICI and late mTT eras than that in the early mTT era (P = 0.0065 and P = 0.0010, respectively) but did not significantly differ between the ICI and late mTT eras (P = 0.389). In 112 patients undergoing CN and systemic therapy, OS was significantly longer in the ICI and late mTT eras than that in the early mTT era (P = 0.0432 and P = 0.0498, respectively) but did not significantly differ between the ICI and late mTT eras (P = 0.320). Multivariate analysis of OS in the 161 synchronous mRCC patients revealed that the era was an independent factor (P < 0.0001), together with the histopathological type (P = 0.0130), CN status (P = 0.0010), International Metastatic Renal Cell Carcinoma Database Consortium risk (P = 0.0002) and liver metastasis status (P = 0.0124).

Conclusion: This retrospective analysis showed that systemic therapy change in the post-cytokine era improved OS of mRCC patients undergoing CN.
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http://dx.doi.org/10.1093/jjco/hyaa171DOI Listing
February 2021

Mid-term outcome of transarterial embolization of renal artery pseudoaneurysm and arteriovenous fistula after partial nephrectomy screened by early postoperative contrast-enhanced CT.

CVIR Endovasc 2020 Sep 16;3(1):68. Epub 2020 Sep 16.

Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Purpose: To retrospectively evaluate the mid-term outcome of transarterial embolization (TAE) of renal artery pseudoaneurysm (RAP) including arteriovenous fistula (AVF) after partial nephrectomy screened by early postoperative contrast-enhanced CT (CE-CT).

Materials And Methods: Eighty-two patients (7.0%) who underwent TAE after partial nephrectomy were reviewed, from 1166 partial nephrectomies performed over 6 years. In 18 patients (22.0%), TAE was performed emergently on the median postoperative day (POD) seven. In the remaining patients, elective TAE was performed on the median POD six for RAP detected by early postoperative CE-CT or that emerged on follow-up CE-CT.

Results: In one patient (1.2%), TAE was performed twice because one of two RAPs could not be embolized during the first TAE, being successfully embolized at the second TAE after readmission with hematuria. Otherwise, no bleeding recurrence or RAPs were observed during the median 1354 follow-up days. Thus, the primary and secondary success rates of TAE were 98.8% (81 of 82 patients) and 100% (82 of 82 patients), respectively. On angiography, the average number of lesions was 1.7 ± 0.9 and the average RAP size was 12.8 ± 6.0 mm. The shapes of the lesions varied: oval-round 60, oval-round + AVF 36, irregular + AVF 14, AVF 12, irregular 10, disruption 4, and extravasation 3. No major complications were observed. The median inpatient days after TAE were two. No estimated glomerular filtration rate deterioration was observed (64.6 ± 18.6 vs. 64.2 ± 18.4 mL/min/1.73 m, p = 0.902).

Conclusion: TAE is largely effective and safe for treating bleedings or RAPs, including AVFs, after partial nephrectomy, as screened by early postoperative CE-CT.
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http://dx.doi.org/10.1186/s42155-020-00160-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494709PMC
September 2020

Prognostic impact of metastasectomy in renal cell carcinoma in the postcytokine therapy era.

Urol Oncol 2021 01 28;39(1):77.e17-77.e25. Epub 2020 Aug 28.

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

Objectives: To explore the real-world data regarding survival following metastasectomy (MS) for renal cell carcinoma (RCC) in the postcytokine therapy era.

Patients And Methods: Patients diagnosed with metastatic renal cell carcinoma (mRCC) between January 2008 and December 2018 at our institutions were retrospectively evaluated. The patients were classified into three groups according to their MS status: (1) complete MS (cMS), (2) incomplete MS (icMS), and (3) without MS (nonMS). Factors for overall survival (OS) after diagnosis were analyzed.

Results: Overall, 314 patients were evaluated. During the follow-up period (median: 25.3 months), a total of 98 patients (31.2%) underwent at least one MS. The cMS group (n = 45, 14.3%) had a significantly longer OS (median: not reached [N.R.]) than the icMS (n = 53, 16.9%) (81.5 months, P= 0.0042) and nonMS groups (28.1 months, P< 0.0001). The icMS group had a significantly longer OS than the nonMS group did (P= 0.0010). Multivariate analysis showed that the MS status was an independent factor for OS (cMS vs. nonMS: P= 0.0004; icMS vs. nonMS: P= 0.0176), together with histopathological type, International Metastatic Renal Cell Carcinoma Database Consortium risk, liver metastasis status, and prior nephrectomy status (all, P< 0.05). In addition, the OS was comparable throughout the eras of systemic therapy (early molecular-targeted therapy, late molecular-targeted therapy, and immune checkpoint inhibitor eras) in the MS group (median: 121.9 vs. N.R. vs. N.R. months, P= 0.948).

Conclusions: MS, especially cMS improved survival in selected patients with mRCC in the postcytokine therapy era. In addition, MS still plays a significant role in the current systemic therapy.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.011DOI Listing
January 2021

Genetic and epigenetic profiling indicates the proximal tubule origin of renal cancers in end-stage renal disease.

Cancer Sci 2020 Nov 18;111(11):4276-4287. Epub 2020 Sep 18.

Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.

End-stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of 2 major histopathological types: clear-cell RCCs (ESRD-ccRCCs) and acquired cystic disease (ACD)-associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. Here, we investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD-ccRCCs and 7 ACD-associated RCCs to identify their molecular alterations and cellular origins. Targeted sequencing of 409 cancer-related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD-ccRCCs harbored frequent VHL mutations, while ACD-associated RCCs did not. CNA analysis showed that ESRD-ccRCCs had a frequent loss of chromosome 3p while ACD-associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD-ccRCCs had methylation profiles similar to those of sporadic ccRCCs, while ACD-associated RCCs had profiles similar to those of papillary RCCs. Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD-ccRCCs and ACD-associated RCCs had high expression of proximal tubule cell marker genes, while chromophobe RCCs had high expression of distal tubule cell/collecting duct cell marker genes. In conclusion, ESRD-ccRCCs and ACD-associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these 2 histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron.
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http://dx.doi.org/10.1111/cas.14633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648048PMC
November 2020

Possible abscopal effect in urothelial carcinoma of the upper urinary tract after treatment with immune checkpoint inhibitors.

IJU Case Rep 2020 Jan 3;3(1):25-27. Epub 2019 Dec 3.

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

Introduction: Regression of non-irradiated metastatic lesions after radiation therapy is known as the abscopal effect. We report a case of urothelial carcinoma in which the abscopal effect was possibly observed after immune checkpoint inhibitor administration.

Case Presentation: A 68-year-old woman diagnosed with left renal pelvic cancer underwent total nephroureterectomy and regional lymph node dissection. Eight months later, imaging studies detected local recurrence and paraaortic lymph node metastasis. The tumor progressed despite cisplatin + gemcitabine, pembrolizumab, and gemcitabine + docetaxel therapy. Radiation therapy was administered to a painful back lesion, which resulted in dramatic symptom relief. Computed tomography 2 months after radiation therapy indicated reduced size of the irradiated lesion and some non-irradiated lymph nodes.

Conclusion: Combined radiation therapy and immune checkpoint inhibitors can provide additional benefits for certain cancers, possibly due to negative immunomodulatory response blockade. Thus, this combined therapy may be a new metastatic urothelial carcinoma treatment strategy.
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http://dx.doi.org/10.1002/iju5.12133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292173PMC
January 2020

Lower Incidence of Postoperative Acute Kidney Injury in Robot-Assisted Partial Nephrectomy Than in Open Partial Nephrectomy: A Propensity Score-Matched Study.

J Endourol 2020 07 28;34(7):754-762. Epub 2020 May 28.

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

Acute kidney injury (AKI) after partial nephrectomy is attributed to parenchymal reduction and ischemia, but the extent of its effect remains unclear. This study aimed to compare the incidence of postoperative AKI among surgical modalities, robot-assisted partial nephrectomy (RAPN), laparoscopic partial nephrectomy (LPN), and open partial nephrectomy (OPN), and to evaluate the validity of RAPN by comparing it with LPN and OPN in terms of postoperative AKI, perioperative complications, and long-term renal function. Patients who underwent RAPN, LPN, and OPN for renal tumors at our institutions between 2004 and 2018 were retrospectively analyzed. RAPN and LPN were performed under warm ischemia and OPN under cold ischemia. En bloc hilar clamping was employed for LPN and OPN and arterial clamping for RAPN. AKI was defined as % decrease in estimated glomerular filtration rate (eGFR) >25% from preoperative eGFR to postoperative nadir eGFR. Multivariate regression analysis was used to test associations of AKI with perioperative factors. Then, we compared the incidence of AKI with two propensity score-matched cohorts: RAPN OPN and RAPN LPN. This study included 1762 cases (RAPN: 959, LPN: 215, and OPN: 588). After matching, 147 cases each from RAPN and LPN groups and 368 cases each from RAPN and OPN groups were selected. RAPN had shorter warm ischemia time than LPN, lower incidence of AKI, and lower % decrease in eGFR after 6 months. RAPN had a shorter ischemia time and a lower incidence of AKI than OPN, although the % decrease in eGFR after 6 months did not differ significantly. AKI incidence was lower in RAPN than in LPN or OPN, which may be due to the shorter ischemia time or clamping of only arteries in RAPN. Although long-term renal outcomes did not differ between RAPN and OPN, RAPN can help prevent AKI. This supports the validity of RAPN for patients with chronic kidney disease.
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http://dx.doi.org/10.1089/end.2019.0622DOI Listing
July 2020

Comparisons of surgical outcomes between transperitoneal and retroperitoneal approaches in robot-assisted laparoscopic partial nephrectomy for lateral renal tumors: a propensity score-matched comparative analysis.

J Robot Surg 2021 Feb 1;15(1):99-104. Epub 2020 May 1.

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

Objective: To compare the surgical outcomes between the transperitoneal (TP) and retroperitoneal (RP) approaches in robot-assisted laparoscopic partial nephrectomy (RAPN) for lateral tumors.

Methods: This study included patients who underwent RAPN for lateral renal tumors between 2013 and 2019. Lateral tumors were defined as X of A factors in the RENAL nephrometry score. In total, 290 and 48 patients with TP and RP, respectively, were included in the analysis. To minimize the effects of selection bias, the following variables were adjusted using 1:1 propensity score matching: age, sex, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate, tumor size, and RENAL nephrometry score.

Results: After matching, 48 patients were allocated to each group. The mean age was 55 years, and the mean preoperative estimated glomerular filtration rate (eGFR) was 68-69 mL/min/1.73 m. The mean tumor size was 30-31 mm. The RP group had a shorter operative time (124 vs. 151 min, p = 0.0002), shorter console time (74 vs. 110 min, p < 0.0001), shorter warm ischemic time (14 vs. 17 min, p = 0.0343), lower estimated blood loss (EBL) (33 vs. 52 ml, p = 0.0002), and shorter postoperative length of hospital stay (PLOS) (3.3 vs. 4.0 days, p < 0.0001) than the TP group. The change in eGFR, incidence rate of perioperative complication, and positive surgical margin rate did not significantly differ between the two groups.

Conclusion: RP had better surgical outcomes, including shorter operative time, lower EBL, and shorter PLOS for lateral renal tumors, which may suggest that RP is the optimal approach for selected lateral renal tumors.
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http://dx.doi.org/10.1007/s11701-020-01086-3DOI Listing
February 2021

Efficacy of Axitinib After Nivolumab Failure in Metastatic Renal Cell Carcinoma.

In Vivo 2020 May-Jun;34(3):1541-1546

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

Background/aim: Whether molecular-targeted therapy, particularly axitinib, is effective after failure of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) remains unclear. Here, we evaluated the therapeutic effect of axitinib as a third-line therapy following second-line nivolumab monotherapy for mRCC.

Patients And Methods: Data from patients treated with axitinib as a third-line therapy after failure of first-line tyrosine kinase inhibitor (TKI) and second-line nivolumab monotherapy were reviewed. The progression-free survival (PFS), overall survival (OS), and objective response rate during axitinib therapy were retrospectively evaluated. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Results: Seventeen patients were treated with third-line axitinib after failure of prior TKI and nivolumab. During a median follow-up of 8.15 months, eight (47.1%) and three (17.6%) patients showed disease progression and died, respectively. The median PFS was 12.8 months [95% confidence interval=(CI)4.08-21.7], the 1-year PFS rate was 51.3%, and the 1-year OS rate was 71.6%. The median magnitude of maximum changes of targeted lesions from baseline was -11.9% (95%CI=-36.1-0.44%). The objective response rate and disease control rates were 29.4% (n=5) and 94.1% (n=16), respectively. Univariate analysis for PFS showed a shorter PFS in patients with non-clear cell histopathological types or those with liver metastases (p-Value<0.0001 for both).

Conclusion: Axitinib as a third-line therapy showed reasonable therapeutic efficacy after the failure of first-line TKI and second-line nivolumab monotherapy for mRCC. Further studies are needed to confirm our findings.
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http://dx.doi.org/10.21873/invivo.11943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279840PMC
February 2021

Editorial Comment to Validation of a kidney model made of N-composite gel as a training tool for laparoscopic partial nephrectomy.

Authors:
Toshio Takagi

Int J Urol 2020 06 19;27(6):568. Epub 2020 Apr 19.

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

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http://dx.doi.org/10.1111/iju.14255DOI Listing
June 2020

Prognostic impact of sarcopenia in patients with metastatic hormone-sensitive prostate cancer.

Jpn J Clin Oncol 2020 Aug;50(8):933-939

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

Background: Cancer cachexia is associated with a poor prognosis. This study aimed to investigate the association between sarcopenia and survival in patients with metastatic hormone-sensitive prostate cancer.

Methods: We retrospectively evaluated 197 patients diagnosed with metastatic hormone-sensitive prostate cancer in our department and its affiliated institution between January 2008 and December 2015. Sarcopenia was diagnosed according to the sex-specific consensus definition. Castration-resistance prostate cancer-free survival, cancer-specific survival and overall survival from the metastatic hormone-sensitive prostate cancer diagnoses were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk factors affecting the survival outcomes were analyzed using the Cox proportional regression analysis.

Results: In total, 163 patients (82.7%) had sarcopenia. Cancer-specific survival and overall survival were significantly shorter in sarcopenic patients than in non-sarcopenic patients (median cancer-specific survival: 77.0 months vs. not reached, P = 0.0099; overall survival: 72.0 months vs. not reached, P = 0.0465), whereas castration-resistance prostate cancer-free survival did not significantly differ between the groups (P = 0.6063). Multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.18, P = 0.0451), together with the Gleason score (hazard ratio: 1.87, P = 0.0272) and LATITUDE risk classification (hazard ratio: 2.73, P = 0.0008). Moreover, the prognostic association of sarcopenia was remarkable in patients aged <73.0 years (cancer-specific survival: 82.0 months vs. not reached, P = 0.0027; overall survival: 72.0 months vs. not reached, P = 0.0078 in sarcopenic vs. non-sarcopenic patients), whereas the association was not significant in patients aged ≥73.0 years (cancer-specific survival: 76.0 and 75.0 months, respectively, P = 0.7879; overall survival: 67.0 and 52.0 months, respectively, P = 0.7263).

Conclusion: Sarcopenia was an independent risk factor of cancer-specific survival in patients with metastatic hormone-sensitive prostate cancer, especially in younger patients.
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http://dx.doi.org/10.1093/jjco/hyaa045DOI Listing
August 2020

Impact of donor-related arteriosclerosis in pretransplant biopsy on long-term outcome of living-kidney transplantation: A propensity score-matched cohort study.

Int J Urol 2020 May 11;27(5):423-430. Epub 2020 Mar 11.

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

Objectives: To compare the long-term outcome and complications of living-kidney grafts with arteriosclerosis to those without abnormal findings diagnosed using pretransplant graft biopsy, and to assess the impact of the arteriosclerosis in living-donor kidneys.

Methods: The influence of arteriosclerosis in pretransplant biopsy on long-term outcomes and complications was evaluated in both unmatched (n = 1351, without arteriosclerosis n = 788 vs with arteriosclerosis n = 563) and propensity score-matched cohorts (n = 984, without arteriosclerosis n = 492 vs with arteriosclerosis n = 492) of adults who underwent living-kidney transplant.

Results: In both the unmatched and matched cohort, there was no significant difference in patient and death-censored graft survival at 10 years between the without arteriosclerosis and with arteriosclerosis groups. The with arteriosclerosis group had a higher incidence rate of overall rejection than did the without arteriosclerosis group in both the unmatched (P = 0.026) and matched (P = 0.060) cohorts. The with arteriosclerosis group had significantly higher chronic antibody-mediated rejection than did the without arteriosclerosis group (P = 0.006) in the unmatched cohort. The with arteriosclerosis group had a significantly lower estimated glomerular filtration rate in recipients, but there was no significant difference after matching. The incidence rates of calcineurin inhibitor nephrotoxicity and post-transplant anemia were significantly higher in the with arteriosclerosis group than in the without arteriosclerosis group in both the unmatched and matched cohorts. Long-term postoperative kidney function of living donors was lower in the with arteriosclerosis group.

Conclusions: Kidney graft with arteriosclerosis might affect the incidence of rejection, complications and postoperative kidney function of donors. Long-term careful observation is required for both the recipients who received grafts with arteriosclerosis and the donors who had kidneys with arteriosclerosis.
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http://dx.doi.org/10.1111/iju.14212DOI Listing
May 2020