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Yoneyama, Tohru ; Hatakeyama, Shingo ; Yamamoto, Hayato ; Imanishi, Kengo ; Okamoto, Teppei ; Tokui, Noriko ; Sugiyama, Naoki ; Suzuki, Yuichiro ; Kudo, Shigemasa ; Hashimoto, Yasuhiro ; Koie, Takuya ; Kamimura, Noritaka ; Fukuda, Michiko N. ; Ohyama, Chikara
概要:
Background. Antibody-mediated rejection （AMR） after ABO-incompatible kidney transplantation （ABO-I KTx） is a major barri
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er to the success of transplantation. The advent of immunosuppressive therapy has markedly improved graft survival in ABO-I KTx. However, compare with a normal KTx, clinical conditions during ABO-IKTx are difficult to control due to over-immunosuppression. To reduce the immunosuppression we try to develop the blood group antigen-neutralizing therapy.Methods. We screened an ABO blood group antigen targeting peptide （BATP） by peptide library displayed T7 phage screening. After screening, a hemagglutination（ HA） inhibition assay and ELISA assay was used to analyze the blood group antigen blocking effect of the BATP. We also tested the inhibitory effect of anti-blood group Ab binding in normal human kidney tissues blocked with BATP.Results. We identified six peptide sequences. BATP efficiently suppresses hemagglutination of red blood cells caused by anti-ABO blood group antibodies and binding of these antibodies to ABO histo-blood group antigens on kidney tissue.Conclusions. These data indicating that blood group A/B-antigen on RBCs and on kidney tissues may neutralize by BATP. This approach may enable the development of novel blood group antigen neutralizing therapy to overcome the challenges of ABO-I KTx.
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| 2.
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Yoneyama, Tohru ; Ishibashi, Yusuke ; Okamoto, Teppei ; Suzuki, Yuichiro ; Tobisawa, Yuki ; Hatakeyama, Shingo ; Kudo, Shigemasa ; Koie, Takuya ; Kamimura, Noritaka ; Ohyama, Chikara
概要:
Background. We re-started living kidney transplant in June 2006 after 20 years of interval at Hirosaki University Hospit
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al. We sequentially changed procedure of living donor nephrectomy. First, donor nephrectomy was carried out by open surgery with a small incision （10 cm）. We then introduced laparoscopic retroperitoneal approach followed by laparoscopic intraperitoneal approach. Here, operative and clinical outcome of the three alternatives of donor nephrectomy was evaluated.Methods. Twenty-seven cases who underwent living donor nephrectomy between June 2006 and July 2011 at Hirosaki University Hospital were enrolled. There were 12 males and 15 females with a mean age of 54.3 years. We performed 7 open donor nephrectomy with a small incision, 5 laparoscopic retroperitoneal donor nephrectomy, and 15 laparoscopic intraperitoneal donor nephrectomy.Results. Operation time was 155 min., 250 min., and 214 min., respectively. Estimated blood loss was 310 g, 100g, and 95g, respectively. Warm ischemic time was 2.0 min., 3.0 min., and 3.0 min., respectively. Patients who underwent laparoscopic donor nephrectomy cloud start to walk significantly earlier than those who underwent open donor nephrectomy. There were no surgical complications, nor conversion to open donor nephrectomy from laparoscopic donor nephrectomy. There were no significant difference with post-operative serum creatinine concentration in the donors among the three operation procedures.Conclusions. Safety procedure is the most important for living donor nephrectomy. Laparoscopic donor nephrectomy is safe and associated with early recovery of the donors. Longer and careful observation is necessary for renal function of the donors.
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Narita, Takuma ; Hatakeyama, Shingo ; Yoneyama, Tohru ; Narita, Shintaro ; Yamashita, Shinichi ; Mitsuzuka, Koji ; Sakurai, Toshihiko ; Kawamura, Sadafumi ; Tochigi, Tatsuo ; Takahashi, Ippei ; Nakaji, Shigeyuki ; Tobisawa, Yuki ; Yamamoto, Hayato ; Koie, Yoichi ; Tsuchiya, Norihiko ; Habuchi, Tomonori ; Arai, Yoichi ; Ohyama, Chikara
概要:
Serum biomarker monitoring is essential for management of germ-cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N-glycan-based biomarkers can be applied for detection
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and prognosis in patients with GCT. We performed a comprehensive N-glycan structural analysis of sera from 54 untreated GCT patients and 103 age-adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N-glycans were selected from those with the highest association; cutoff concentration values were established, and an N-glycan score was created based on the number of positive N-glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N-glycans significantly associated with GCT patients. The accuracy of the N-glycan score for GCT was significant with an area-under-the-curve (AUC) value of 0.87. Diagnostically, the N-glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N-glycan score comprised four candidate N-glycans. The predictive value of the prognostic N-glycan score was significant, with an AUC value of 0.89. A high value prognostic N-glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N-glycan analysis and compared to whole sera. Candidate N-glycans in Ig-fractions were significantly decreased; therefore, the carrier protein for candidate N-glycans is likely not an immunoglobulin. In summary, our newly developed N-glycan score seems to be a practical diagnostic and prognostic method for GCT.
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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
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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
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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
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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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