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Hosogoe, Shogo ; Hatakeyama, Shingo ; Kusaka, Ayumu ; Hamano, Itsuto ; Tanaka, Yoshimi ; Hagiwara, kazuhisa ; Hirai, Hideaki ; Morohashi, Satoko ; Kijima, Hiroshi ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Ohyama, Chikara
概要:
Background and Objective: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and
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pathological response in patients with advanced RCC who underwent presurgical therapy. Results: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were -19%, -24%, and -49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. Materials and Methods: Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. Conclusions: CMER may predict tumor response after presurgical moleculartargeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.
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Hamano, Itsuto ; Hatakeyama, Shingo ; Iwamura, Hiromichi ; Fujita, Naoki ; Fukushi, Ken ; Narita, Takuma ; Hagiwara, kazuhisa ; Kusaka, Ayumu ; Hosogoe, Shogo ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Ito, Hiroyuki ; Yoshikawa, Kazuaki ; Kawaguchi, Toshiaki ; Ohyama, Chikara
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Objective: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. Methods: A total of 581 patients who underwent radical
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cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram. Results: Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). Conclusions: Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.
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Kusaka, Ayumu ; Hatakeyama, Shingo ; Hosogoe, Shogo ; Hamano, Itsuto ; Iwamura, Hiromichi ; Fujita, Naoki ; Fukushi, Ken ; Narita, Takuma ; Hagiwara, kazuhisa ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Ito, Hiroyuki ; Yoshikawa, Kazuaki ; Kawaguchi, Toshiaki ; Ohyama, Chikara
概要:
Background: The recurrence risk stratification and the cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost
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effectiveness after radical cystectomy. Results: Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival between normal-and high-risk patients, but the medical expense was high, especially in normal-risk (<= pT2pN0) patients. Cox regression analysis identified six factors associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. Materials and Methods: We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal-and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. Conclusions: Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.
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Kodama, Hirotake ; Hatakeyama, Shingo ; Fujita, Naoki ; Iwamura, Hiromichi ; Anan, Go ; Fukushi, Ken ; Narita, Takuma ; Tanaka, Toshikazu ; Kubota, Yuka ; Horiguchi, Hirotaka ; Momota, Masaki ; Kido, Koichi ; Matsumoto, Teppei ; Soma, Osamu ; Hamano, Itsuto ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Ito, Hiroyuki ; Yoshikawa, Kazuaki ; Sasaki, Atsushi ; Kawaguchi, Toshiaki ; Sato, Makoto ; Ohyama, Chikara
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Objective: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. Methods: A total of 426 patients who
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underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed. Results: Of the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS (c-index = 0.85 and 0.83, respectively). Conclusions: Upper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.
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Anan, Go ; Hatakeyama, Shingo ; Fujita, Naoki ; Iwamura, Hiromichi ; Tanaka, Toshikazu ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Ito, Hiroyuki ; Yoshikawa, Kazuaki ; Kawaguchi, Toshiaki ; Sato, Makoto ; Ohyama, Chikara
概要:
Objective: Despite benefits of neoadjuvant chemotherapy (NAC), the adoption of guideline recommendations for NAC use in patients with muscle-invasive bladder cancer (MIBC) has been slow. We aimed to evaluate temporal trends in NAC use and
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oncological outcomes in a representative cohort of patients with MIBC. Methods: We included 532 patients from 4 hospitals who underwent radical cystectomy (RC) for >= cT2 MIBC in 1996-2017. We retrospectively evaluated temporal changes in NAC use and progression-free and overall survival. Candidates for NAC were administered with either cisplatin- or carboplatin-based regimens. The impact of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. Results: Of 532 patients, 336 underwent NAC followed by RC (NAC group) and 196 underwent RC alone (Ctrl group). NAC use significantly increased from 10% (1996-2004) to 83% (2005-2016). The number of patients administered with cisplatin- and carboplatin-based regimens was 43 and 280, respectively. Oncological outcomes in the NAC group were significantly improved compared to those in the Ctrl group. Multivariable analysis with IPTW models revealed that NAC significantly improved oncological outcomes in patients with MIBC. A nomogram for 5-year overall survival predicted 16% improvement in patients undergoing NAC. Conclusions: NAC use for MIBC increased after 2005. Platinum-based NAC for MIBC potentially improves oncological outcomes.
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Kubota, Yuka ; Hatakeyama, Shingo ; Tanaka, Toshikazu ; Fujita, Naoki ; Iwamura, Hiromichi ; Mikami, Jotaro ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Ito, Hiroyuki ; Yoshikawa, Kazuaki ; Sasaki, Atsushi ; Kawaguchi, Toshiaki ; Ohyama, Chikara
概要:
Objective: The clinical impact of neoadjuvant chemotherapy (NAC) on oncological outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC) remains unclear. We investigated the oncological outcomes of
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platinum-based NAC for locally advanced UTUC. Results: Of 234 patients, 101 received NAC (NAC group) and 133 did not (Control [Ctrl] group). The regimens in the NAC group included gemcitabine and carboplatin (75%), and gemcitabine and cisplatin (21%). Pathological downstagings of the primary tumor and lymphovascular invasion were significantly improved in the NAC than in the Ctrl groups. NAC for locally advanced UTUC significantly prolonged recurrence-free and cancer-specific survival. Multivariate Cox regression analysis using an inverse probability of treatment weighted (IPTW) method showed that NAC was selected as an independent predictor for prolonged recurrence-free and cancer-specific survival. However, the influence of NAC on overall survival was not statistically significant. Materials and Methods: A total of 426 patients who underwent radical nephroureterectomy at five medical centers between January 1995 and April 2017 were examined retrospectively. Of the 426 patients, 234 were treated for a highrisk disease (stages cT3-4 or locally advanced [cN+] disease) with or without NAC. NAC regimens were selected based on eligibility of cisplatin. We retrospectively evaluated post-therapy pathological downstaging, lymphovascular invasion, and prognosis stratified by NAC use. Multivariate Cox regression analysis was performed for independent factors for prognosis. Conclusions: Platinum-based NAC for locally advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed to clarify the clinical benefit of NAC for locally advanced UTUC.
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Tanaka, Yoshimi ; Hatakeyama, Shingo ; Tanaka, Toshikazu ; Yamamoto, Hayato ; Narita, Takuma ; Hamano, Itsuto ; Matsumoto, Teppei ; Soma, Osamu ; Okamoto, Teppei ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Takahashi, Ippei ; Nakaji, Shigeyuki ; Terayama, Yuriko ; Funyu, Tomihisa ; Ohyama, Chikara
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Objectives To determine the influence of serum uric acid (UA) levels on renal impairment in patients with UA stone. Materials and methods We retrospectively analyzed 463 patients with calcium oxalate and/or calcium phosphate stones
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(CaOx/CaP), and 139 patients with UA stones. The subjects were divided into the serum UA-high (UA > 7.0 mg/dL) or the UA-low group (UA < 7.0 mg/dL). The control group comprised 3082 community-dwelling individuals that were pair-matched according to age, sex, body mass index, comorbidities, hemoglobin, serum albumin, and serum UA using propensity score matching. We compared renal function between controls and patients with UA stone (analysis 1), and between patients with CaOx/CaP and with UA stone (analysis 2). Logistic regression analysis was used to evaluate the impact of the hyperuricemia on the development of stage 3 and 3B chronic kidney disease (CKD) (analysis 3). Results The renal function was significantly associated with serum UA levels in the controls and patients with CaOx/CaP and UA stones. In pair-matched subgroups, patients with UA stone had significantly lower renal function than the control subjects (analysis 1) and patients with CaOx/CaP stones (analysis 2) regardless of hyperuricemia. Multivariate logistic regression analysis revealed that patients with UA stone, CaOx/CaP, hyperuricemia, presence of cardiovascular disease, higher body mass index, older age and lower hemoglobin had significantly higher risk of stage 3 and 3B CKD (analysis 3). Conclusion Patients with UA stones had significantly worse renal function than controls and CaOx/CaP patients regardless of hyperuricemia. Urolithiasis (CaOx/CaP and UA stone) and hyperuricemia had an association with impaired renal function. Our findings encourage clinicians to initiate intensive treatment and education approaches in patients with urolithiasis and/or hyperuricemia in order to prevent the progression of renal impairment.
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Fukushi, Ken ; Hatakeyama, Shingo ; Yamamoto, Hayato ; Tobisawa, Yuki ; Yoneyama, Tohru ; Soma, Osamu ; Matsumoto, Teppei ; Hamano, Itsuto ; Narita, Takuma ; Imai, Atsushi ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Terayama, Yuriko ; Funyu, Tomihisa ; Ohyama, Chikara
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Background: Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery.
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We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Methods: Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of >= 60 mL/min/1.73 m(2) or < 60 mL/min/1.73 m(2), respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre-and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. Results: The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m(2), and 8.3%, respectively. Higher ACI (>= 8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Conclusions: Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy.
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Tanaka, Toshikazu ; Hatakeyama, Shingo ; Yamamoto, Hayato ; Narita, Takuma ; Hamano, Itsuto ; Matsumoto, Teppei ; Soma, Osamu ; Tobisawa, Yuki ; Yoneyama, Tohru ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Koie, Takuya ; Takahashi, Ippei ; Nakaji, Shigeyuki ; Terayama, Yuriko ; Funyu, Tomihisa ; Ohyama, Chikara
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Background: The aim of the present study is to investigate the clinical relevance of aortic calcification in urolithiasis patients. Methods: Between January 2010 and September 2014, 1221 patients with urolithiasis were treated in
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Oyokyo Kidney Research Institute and Hirosaki University Hospital. Among these, 287 patients( Stone group) on whom adequate data were available were included in this retrospective study. We also selected 148 subjects with early stage( pT1N0M0) renal cell carcinoma from 607 renal cell carcinoma patients who underwent radical nephrectomy at Hirosaki University Hospital( Non-stone group) as control subjects. Validity of the Non-stone group was evaluated by comparison with pair-matched 296 volunteers from 1166 subjects who participated in the Iwaki Health Promotion Project in 2014. Thereafter, age, body mass index, aortic calcification index( ACI), renal function, serum uric acid concentrations, and comorbidities( diabetes, hypertension, or cardiovascular disease) were compared between the Non-stone and Stone groups. Independent factors for higher ACI and impaired renal function were assessed using multivariate logistic regression analysis. Results: We confirmed relevance of Non-stone group patients as a control subject by comparing the pairmatched community-dwelling volunteers. Backgrounds of patients between the Non-stone and Stone groups were not significantly different except for the presence of hypertension in the Stone group. ACI was not significantly high in the Stone group compared with the Non-stone group. However, age-adjusted ACI was greater in the Stone group than the Non-stone group. Among urolithiasis patients, ACI was significantly higher in uric acid containing stone patients. The number of patients with stage 3B chronic kidney disease( CKD) was significantly higher in the Stone group than in the Non-stone group( 12% vs. 4%, P = 0.008). Multivariate logistic regression analysis showed higher aortic calcification index(>13%), and being a stone former were independent factors for stage 3B CKD at the time of diagnosis. Conclusion: Aortic calcification and being a stone former had harmful influence on renal function
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Narita, Takuma ; Hatakeyama, Shingo ; Koie, Takuya ; Hosogoe, Shogo ; Matsumoto, Teppei ; Soma, Osamu ; Yamamoto, Hayato ; Yoneyama, Tohru ; Tobisawa, Yuki ; Yoneyama, Takahiro ; Hashimoto, Yasuhiro ; Ohyama, Chikara
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Background: Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis
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and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Methods: Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. Results: There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. Conclusions: The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.
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