Norikata Takada

Peri-operative morbidity and mortality related to radical cystectomy: a multi-institutional retrospective study in Japan.

Study Type – Therapy (outcomes) Level of Evidence 2b Whats known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high‐volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90‐day mortality rate = 2%), which were compatible with reports from Western high‐volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy.

Comparison of 90-day complications between ileal conduit and neobladder reconstruction after radical cystectomy: A retrospective multi-institutional study in Japan

To determine the differences in the type, incidence, and severity of 90‐day morbidity after radical cystectomy between two different methods of urinary diversion, ileal conduit and neobladder.

Pathological characteristics and clinical course of bladder tumour developing after nephroureterectomy

Study Type – Therapy (case series)
Level of Evidence 4

A Multi-Center International Study Assessing the Impact of Differences in Baseline Characteristics and Perioperative Care Following Radical Cystectomy.

Background: To identify potential avenues for quality improvement, we compared the variations in clinical practice and their association with perioperative morbidity and mortality following radical cystectomy (RC) for bladder cancer in the United States (US) and Japan. Methods: We reviewed our retrospectively collected database of 2240 patients who underwent RC for bladder cancer at the University of Michigan (n = 1427) and in 21 Japanese institutions (n = 813) between 1997 and 2014. We performed a systematic comparison of clinical and perioperative factors and assessed predictors of perioperative morbidity and mortality. Death within 90 days of surgery was the primary outcome. Results: There were apparent differences between the two study populations. Notably, US patients had a significantly greater BMI and higher ASA score. In Japanese institutions, median postoperative hospital stay was significantly higher (40 days vs. 7 days, p <  0.001) and 90-day readmission rates were significantly lower (0.6% vs. 26.8% , p <  0.001). There was a total of 1372/2240 (61.2%) patients with complications within 90 days and 66/2240 (2.9%) patient deaths. Significant predictors of 90-day mortality were older age (OR 1.04, CI 1.01–1.07), higher body mass index (OR 1.07, CI 1.02–1.12), node-positive disease (OR 3.14, CI 1.78–5.47), increased blood loss (OR 1.02, CI 1.01–1.03), and major (Clavien-grade 3 or greater) complication (OR 3.29, CI 1.88–5.71). Conclusion: Despite major differences in baseline characteristics and care of cystectomy patients between the two study populations, peri-operative mortality rates proved to be comparable. This data supports an exploration of non-traditional factors that may influence mortality after cystectomy.

Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis

OBJECTIVE To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. METHODS A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed by open surgery (n = 23) or laparoscopically (n = 37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan-Meier method. RESULTS The median number of lymph nodes removed was 29 (range: 10-103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routine pathological examination. After excluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n = 2, adenocarcinoma: n = 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up. CONCLUSIONS We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis (pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease.

Successful rescue of late-onset acute T-cell mediated rejection with anti-CD25 antibody: a case report

Abstract:  A 56‐yr‐old Japanese male with a history of diabetic nephropathy underwent a HLA 5/6 mismatch and ABO‐compatible living‐related kidney transplantation (donor: his 49‐yr‐old wife). A pre‐transplant standard NIH complement‐dependent cytotoxicity cross‐match (Xm) test, a flow‐cytometric T‐cell Xm, and a FlowPRA™ test were totally negative. Inductionimmunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab (BAS). The patient’s post‐operative course was almost uneventful, and the graft was functioning well (sCr 1.1 mg/dL). He developed general fatigue, and his sCr was elevated to 2.2 mg/dL 792 d after transplant. A graft biopsy showed acute T‐cell mediated rejection Banff grade IB (i3, t3, g0, v0, ptc0, C4d staining negative). The conventional anti‐rejection therapy could not improve his graft function; therefore, we added BAS to eliminate activated graft‐infiltrating T‐cells. He responded to the rescue therapy, and the improvement in graft function was confirmed by a subsequent graft biopsy. He enjoyed his health without any opportunistic infections.

Severe acute‐hybrid rejection occurring nine months after kidney transplantation: a report of rescue by orchestration of antirejection therapies

Abstract:  Although a majority of acute rejection (AR) in non‐sensitized recipients is T‐cell‐mediated by primed T cells, recent studies have shown that antibody‐mediated acute rejection occurs in 20–30% of AR, and that it is often refractory to conventional antirejection therapy; possibly leading to graft loss. We report a case of severe acute‐hybrid rejection consisting of both features in a non‐sensitized kidney recipient, which was rescued by the orchestration of antirejection therapies. A 33‐yr‐old Japanese male, with advanced‐stage chronic kidney disease with an unknown etiology, underwent a HLA 3/6 mismatch and ABO‐compatible living‐related kidney transplantation preemptively. He had an excellent clinical course, except for initial cytomegalovirus infection, with good graft function [serum creatinine (sCr) 1.1 mg/dL]. Nine months later, his creatinine abruptly increased to 2.1 mg/dL, when graft biopsy revealed acute T cell‐mediated rejection (ATMR) grade IA, and simultaneous acute antibody‐mediated rejection (AAMR) grade I. Antirejeciton therapy, comprising methyl‐prednisolone pulse and 15‐deoxyspergualin, and second line rituximab and plasmapheresis, was ineffective. Moreover, histologically and clinically, the rejection status deteriorated (ATMR grade III and AAMR grade III, max sCr 4.0 mg/dL). Next, we administered muromonab CD3 and basiliximab, which could eradicate the complicated severe AR without opportunistic infection, even under the strong immunosuppression. The present case implies that high‐grade combined rejection can respond to anti‐CD 20 and anti‐CD25 mAbs, without serious complication; however, post‐operative, thorough appropriate monitoring of immunosuppression is important because its effects are limited.

Comparative study of lymph node dissection, and oncological outcomes of laparoscopic and open radical nephroureterectomy for patients with urothelial carcinoma of the upper urinary tract undergoing regional lymph node dissection

We revealed the feasibility of lymph node dissection (LND) with a laparoscopic approach and the equivalent oncological outcome of laparoscopic nephroureterectomy compared with open nephroureterectomy when regional LND is performed.

Validation of the nomogram for predicting 90‐day mortality after radical cystectomy in a Japanese cohort

DOI: 10.1111/iju.13584 RC often causes morbidities and is associated with high perioperative mortality rates (ranging from 2 to 8%). Therefore, identifying the factors related to mortality after RC is critical for aiding treatment decisions and patient counseling before surgery. In 2014, Aziz et al. developed a nomogram using a European multicenter prospective cohort including 597 patients, and reported that age, the ASA score, the annual number of RC carried out at each institution, lymphatic metastatic disease and distant metastatic disease were significant independent predictors of 90-day mortality after RC with a predictive accuracy of 78.8%. Although several nomograms for predicting postoperative mortality after RC have been reported, Aziz’s nomogram shows the highest accuracy (it recently showed 71% accuracy in an external validation study involving an Italian multicenter cohort). The primary end-point was the external validation of Aziz’s nomogram using a Japanese multicenter cohort. After obtaining approval from each institutional review board, we retrospectively evaluated the data of 834 patients who underwent RC without simultaneous nephroureterectomy at 21 Japanese institutions (Hokkaido University Hospital and 20 affiliated institutions) between 1997 and 2010. Of these, complete data for calculating nomograms were available for 744 patients. The postoperative care provided at these institutions was described previously. Patient information, including regarding age, sex, body mass index, the ASA score, the administration of neoadjuvant chemotherapy and pathological stage were obtained from the patients’ charts. Pathological staging was carried out according to the AJCC staging system (7th edition). Categorical variables were compared with Pearson’s v-test and Fisher’s exact test. Aziz’s nomogram was investigated to evaluate its discriminative ability and predictive accuracy for 90-day mortality after RC. The discriminative ability of this nomogram was assessed by ROC analysis. All statistical analyses were carried out using the JMP software (SAS Institute, Cary, NC, USA). The patient and tumor characteristics of the retrospective Japanese validation cohort and the model-development prospective cohort of Aziz et al. are shown in Table S1. The median age of our validation cohort was 70 years, and 577 (77.6%) patients were men. In terms of surgical volume, the median number of annual cystectomies carried out per institution was 49 in the model-development cohort and four in the validation cohort. The model-development cohort tended to show higher body mass index and ASA scores, and increased frequencies of distant metastasis (5.9% vs 1.0%, P < 0.01) and high-grade disease (grade 3) according to transurethral removal of bladder tumor examinations (85.8% vs 63.6%, P < 0.01), whereas the validation cohort tended to show a higher frequency of locally advanced disease (≥cT3) (42.1 vs 30.3, P < 0.01). Overall, the model-development and validation cohorts had comparable sex and neoadjuvant chemotherapy distributions. The 90-day mortality rate of the Japanese validation cohort was significantly lower than that of the model-development cohort (1.2% vs 9.0%, P < 0.01). An evaluation of the predictive performance of Aziz’s nomogram showed an AUC of 0.79 for the Japanese validation cohort, which was identical to that for the model-development cohort (0.79; Fig. 1). In a subanalysis of each type of diversion, the highest AUC value (0.90) was obtained for the patients who underwent incontinent conduit diversion (Table S2). In previous studies, the 90-day mortality rate after RC was inversely associated with the surgical volume, but this did not hold true for the Japanese validation cohort. In Japan, although very few hospitals carry out high numbers of RC procedures, 90-day mortality after RC was reported to be relatively low. Thus, the hospital volume of our multicenter series contributed few points to the final score in Aziz’s nomogram because of the small number of cases treated at each institution. Even though it is true, this nomogram showed excellent performance, which indicates its potential generalizability to different racial groups. The present study had several limitations that should be considered. The small number of deaths after RC resulted in there being relatively few events available for analysis. The long recruitment period and the retrospective nature of this study (e.g. no information was

MP71-17 COMPARATIVE STUDY OF ONCOLOGICAL OUTCOMES OF LAPAROSCOPIC AND OPEN RADICAL NEPHROURETERECTOMY FOR PATIENTS WITH UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT UNDERGOING REGIONAL LYMPH NODE DISSECTION

INTRODUCTION AND OBJECTIVES: Chronological age is an important factor in in determining the treatment option and clinical response of patients with upper-tract urothelial carcinoma (UTUC). Much evidence suggests that chronological age alone is an inadequate indicator to predict the clinical response to radical nephroureterecyomy (RNU). On the other hand, prognostic impact of biological age has not been reported previously. Defining the biological age consists of the determination of a number of biological age markers including telomeres, chromatin, and some blood sampling data which is commonly measured in clinical practice. Therefore, the aim of our study was the validation of the prognostic significance of biological age related factors in a large cohort of UTUC patients. METHODS: We retrospectively reviewed the data from 1349 patients with localized UTUC (Ta-4N0M0) treated by RNU. WBC, NLR, Hb, PLT, CRP, Alb, ALP, LDH, Cr, corrected Ca were tested by the Spearman correlation to indicate the direction of association to chronological age. The test yielded significant, negative associations of Hb (P<0.001) and WBC (P1⁄40.010) with chronological age. Hb (g/dl) and WBC (counts/ml) were analyzed to compare the 10-year cancer-specific survival (CSS) by Cox regression analysis as categorical variables (>14, 13-13.9, 12-12.9, 11-11.9, and <11), and (9200-8500, 84996000, 5999-4500, 4499-3200, <3200, and >9200), respectively. To establish the scoring system, we assigned points for these categories, and then correlated the total points to predicted probability of the surviving outcome as follows; point 00000 for Hb >14 (reference) and 13-13.9 (OR: 1.533), point 00100 for 12-12.9 (OR: 2.391), point 00200 for 11-11.9 (OR: 3.015), and point 00300 for <11 (OR: 3.584). For WBC, point 00100 was assigned for >9200 (OR: 2.541) and 00000 was assigned for the rest; 9200-8500 (reference), 8499-6000 (OR: 0.873), 5999-4500 (OR: 0.772), 4499-3200 (OR: 0.486), and <3200 (OR: 1.277). RESULTS: 10-year CSS in higher risk group with score 4 or larger in age<60 was worse than score-0, or 1 in age >80 (mean estimated survival 69.7 months, CI: 33.3-106 v.s. 103.5. CI: 91-115.9). Concordance index between biological age scoring and chronological age was 0.704 for CSS and 0.798 for recurrence-free survival. CONCLUSIONS: The biological age scoring developed for patients with UTUC undergoing RNU. It was applicable to those with localized disease, and performed well in diverse age populations