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To compare the therapeutic effect of Bacille Calmette-Guérin (BCG) intravesical instillation in older and younger patients with high-risk non-muscle-invasive bladder cancer. The comparison was performed with propensity score matching (PSM) without terminating the death of the older patients using relatively large-scale retrospective data from multiple institutes in Japan.Overall, 3283 patients diagnosed with non-muscle-invasive bladder cancer treated with intravesical BCG instillation during 2000-2018 in 31 institutes were examined; 1437 and 602 patients with high-grade T1 and Tis tumors were divided into those aged ≥75 and75 years. Multivariate analysis using the Fine-Gray competing risks regression model before PSM and survival analysis using the cumulative incidence method after PSM were performed.In the pre-PSM series of high-grade T1 tumors, age ≥75 years was an independent prognostic factor for both recurrence and progression in multivariate analysis (P = .015 and P = .013). In the pre-PSM series with Tis tumor, no variables to predict recurrence and progression was found. In the post-PSM series of 870 high-grade T1 tumors, cumulative probability of recurrence after BCG intravesical instillation were significantly higher in patients aged ≥75 years than in those aged75 years (P = .008). The frequency of discontinuation of BCG instillation in patients aged ≥75 years with high-grade T1 and Tis was not significantly different from those in patients aged75 years (P = .564 and P = .869).The cumulative probability of recurrence after intravesical BCG instillation was significantly higher in older than in younger patients with high-grade T1 bladder cancer.

Background/Aim: The duration of pembrolizumab use in actual daily practice might be shorter than that in clinical trials because termination of pembrolizumab therapy is at the discretion of the physician. We retrospectively reviewed the response to pembrolizumab in Japanese patients with metastatic urothelial carcinoma (mUC) in relation to the time to response (TTR). Patients and Methods: The records of 165 patients treated with pembrolizumab for mUC were retrospectively analyzed. Response was evaluated at 2, 4, 6 and 8 months. TTR along with time to best response were analyzed. Phase II-III clinical trials were also reviewed to compare the TTR and time to best overall response. Results: The median patient age was 70 years. The objective response rate in the total cohort was 27.1% (42 out of 155 patients). Median TTR was 2.4 months and the time to best response was 3.1 months. Radiological evaluation at each time point significantly predicted overall survival (OS). Considering the evaluation of response at 2, 4, 6 and 8 months, the response at later time points tended to predict OS better. Multivariate analysis showed that the evaluation of response at 8 months (hazard ratio=1.91, 95% confidence interval=1.16-3.16 months; p

Background The objective of the present study was to evaluate the prognostic impact of the upper urinary tract cancer status on recurrence-free survival and progression-free survival, and to develop risk stratification systems that include the upper urinary tract cancer status for patients with non-muscle invasive bladder cancer. Patients and Methods The present study included 40 (upper urinary tract cancer-non-muscle invasive bladder cancer group) and 285 (non-muscle invasive bladder cancer alone group) patients with and without a history of prior or concomitant upper urinary tract cancer, respectively. Nine clinicopathological findings between the two groups were compared, and risk stratification systems for the recurrence and progression of non-muscle invasive bladder cancer were developed. Results Recurrence-free survival and progression-free survival in the upper urinary tract cancer-non-muscle invasive bladder cancer group were significantly inferior to those in the NMIBC alone group (P Conclusion The present results suggest the significant impact of a history of prior or concomitant UUTC on recurrence-free survival and progression-free survival in non-muscle invasive bladder cancer patients, and risk stratification systems that include the upper urinary tract cancer status for the recurrence and progression of non-muscle invasive bladder cancer are promising tools for predicting the outcomes of these patients.

Transurethral resection of bladder tumor with photodynamic diagnosis has been reported to result in lower residual tumor and intravesical recurrence rates in non-muscle invasive bladder cancer. We aimed to evaluate the usefulness of photodynamic diagnosis-transurethral resection of bladder tumor combined with oral 5-aminolevulinic acid hydrochloride for high-risk non-muscle invasive bladder cancer.High-risk non-muscle invasive bladder cancer patients with an initial photodynamic diagnosis-transurethral resection of bladder tumor (photodynamic diagnosis group) were prospectively registered between 2018 to 2020. High-risk non-muscle invasive bladder cancer cases with a history of initial white-light transurethral resection of bladder tumor (white-light group) were retrospectively registered. Propensity score-matching analysis was used to compare residual tumor rates, and factors that could predict residual tumors at the first transurethral resection of bladder tumor were evaluated.Analyses were conducted with 177 and 306 cases in the photodynamic diagnosis and white-light groups, respectively. The residual tumor rates in the photodynamic diagnosis and white-light groups were 25.7% and 47.3%, respectively. Factor analysis for predicting residual tumors in the photodynamic diagnosis group showed that the residual tumor rate was significantly higher in cases with a current/past smoking history, multiple tumors, and pT1/pTis. When each factor was set as a risk level of 1, cases with a total risk score ≤1 showed a significantly lower residual tumor rate than cases with a total risk score ≥2 (8.3% vs 33.3%, odds ratio 5.46 [1.81-22.28]).In high-risk non-muscle invasive bladder cancer cases, the odds of a residual tumor after initial photodynamic diagnosis-transurethral resection of bladder tumor were 0.39-fold that of the odds of those after initial white-light transurethral resection of bladder tumor. A risk stratification model could be used to omit the second transurethral resection of bladder tumor in 27% of the cases.

To evaluate the impact of the interaortocaval clamping technique for the right renal artery on perioperative outcomes of patients who underwent robot-assisted partial nephrectomy (RAPN).This study included 111 consecutive patients with right renal masses undergoing RAPN via the transperitoneal approach. In this series, standard and interaortocaval clamping techniques were defined as those for the right renal artery at the renal hilus and interaortocaval space, respectively. Based on the 3D images reconstructed from CT, interaortocaval clamping was preoperatively selected for patients in whom standard clamping of the main renal artery at the right hilum was judged to be technically difficult due to complicated vascular distribution, such as multiple branches of right renal arteries and veins and/or intertwining of these vessels.Of 111 patients, 95 and 16 were classified into the standard and interaortocaval clamping groups, respectively, and interaortocaval clamping was uneventfully performed as planned in all 16. After adjusting patient variables by 1:3 propensity score-matching, 33 and 11 patients were included in the respective groups, and there were no significant differences in major clinical characteristics between them, while the incidences of multiple branches of right renal vessels as well as their intertwining beside the right renal hilus were significantly higher in the interaortocaval clamping group. However, no significant difference was noted in any of the perioperative outcomes, including operative time or intraoperative blood loss, between the two groups.The interaortocaval clamping technique during RAPN is a feasible procedure with acceptable perioperative outcomes compared with standard hilar clamping, making it possible to more accurately resect renal tumors under clear visualization without unnecessary arterial bleeding from the tumor bed in patients with complex vascular distribution at the right renal hilus; however, special attention should be paid to the considerable individual variability of the interaortocaval anatomy.

The present study comprehensively investigated the significance of several factors reflecting the therapeutic effects of anticancer treatment on overall survival (OS) in advanced urothelial cancer (UC) patients receiving sequential systemic therapy.This study included 101 consecutive advanced UC patients who received first-line platinum-based combination chemotherapy followed by second-line pembrolizumab. The impacts of the following factors on OS in these patients were analyzed: responses to chemotherapy, responses to pembrolizumab, progression-free survival (PFS) with chemotherapy, PFS with pembrolizumab, and second PFS (PFS2).The median age of patients was 71 years, and 35 and 66 had UC in the upper urinary tract and bladder, respectively. objective response rate to first-line chemotherapy and second-line pembrolizumab were 37.6% and 19.8%, respectively. Median PFS with chemotherapy, pembrolizumab, and PFS2 were 5, 4, and 9 months, respectively. Uni- and multivariate analyses of the five factors examined identified PFS with pembrolizumab and PFS2 as independent surrogates for OS, with PFS2 (hazard ratio [HR] = 0.23) being more closely associated with OS than PFS with pembrolizumab (HR = 0.31). Furthermore, uni- and multivariate analyses of various prognostic parameters showed the independent impacts of baseline performance status (PS) and neutrophil-to-lymphocyte ratio (NLR) on PFS2.The present results suggest the potential of PFS2 as an optimal surrogate for OS in advanced UC patients receiving standard sequential systemic therapy and indicate that intensive treatment needs to be considered for those with poor PS and/or high NLR prior to the introduction of first-line chemotherapy.

Introduction: Magnetic resonance imaging (MRI) has helped clarify the relationship between pelvic anatomical structures and functional outcomes after robot-assisted radical prostatectomy (RARP). Th...

Introduction To evaluate the initial experience of robot-assisted radical nephrectomy (RARN) in a single institution in Japan. Methods This study included a total of 12 patients with renal tumors who were not preoperatively regarded as optimal candidates for robot-assisted partial nephrectomy (RAPN) and subsequently treated with RARN between April 2019 and June 2021 at our institution. Comprehensive perioperative outcomes in these patients were retrospectively analyzed. Results Of the 12 included patients, 10 and two were male and female, respectively, and the median age was 66 years. The median tumor diameter was 44 mm, and four, four and four patients were classified into cT1a, cT1b and cT3a, respectively. There was no patient requiring open conversion, and the median operative and console times were 167 and 79 minutes, respectively. The median estimated blood loss was 42 cc, and no patient required blood transfusion. During the perioperative period, no major complication corresponding to Clavien-Dindo grade ≥3 occurred. Nine, two and one patient were pathologically diagnosed with clear cell carcinoma (CCC), non-CCC and benign cyst, respectively, and there was no patient who developed recurrent diseases. Conclusions Considering complicated tumor characteristics not amenable to RAPN in this series, such as an intravenous tumor thrombus or previous history of open partial nephrectomy, perioperative outcomes of initial experience with RARN in Japan could be considered favorable. Collectively, these findings suggest that RARN may be a promising alternative to laparoscopic radical nephrectomy for patients with complicated renal tumors, contraindicated for RAPN.

Background/Aim: Sexual function in patients with benign prostatic hyperplasia (BPH) could be affected by surgical intervention, such as holmium laser enucleation of the prostate (HoLEP). The objective of the present study was to investigate whether changes in erectile function (EF) after HoLEP affect postoperative outcomes in patients with BPH. Patients and Methods: We retrospectively reviewed 54 consecutive Japanese patients with BPH undergoing HoLEP at our institution between August 2017 and December 2020, and analyzed data obtained before and 6 months after HoLEP, including the Erection Hardness Score (EHS), International Prostate Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QOL), Overactive Bladder Symptom Score (OABSS), and the Medical Outcomes Study 8-Item Short-Form Health Survey consisting of a mental health component summary (MCS) and physical health component summary (PCS). Results: Although no significant differences were observed between preoperative and postoperative EHS, postoperative EHS deteriorated in 19 out of 54 patients. Total IPSS, IPSS-QOL, and OABSS significantly improved after HoLEP, irrespective of the deterioration of EHS; however, despite the lack of significant changes in MCS and PCS in 19 patients with deteriorated EHS, significant improvements in MCS, but not PCS, were postoperatively observed in the remaining 35. A multivariable analysis of several factors identified a preoperative estimated prostate volume >100 cm(3) as an independent risk factor associated with the postoperative deterioration of EHS. Conclusion: HoLEP had limited impact on postoperative EF in BPH patients; however, favorable QOL may be expected in patients without the postoperative deterioration of EF. Accordingly, it may be important to consider the prostate volume and its effect on postoperative EF when selecting indications for HoLEP.

Systemic therapy using immune checkpoint inhibitors (ICIs) has recently become prevalent in the treatment of patients with various types of advanced cancers; however, difficulties are still associated with predicting the outcomes of patients receiving ICIs due to heterogenous responses to these agents.To develop a prognostic model for advanced cancer patients treated with ICIs.This study retrospectively analyzed the impact of clinical parameters on overall survival (OS) in 329 patients with several advanced solid malignant tumors who received systemic therapy using ICIs.The primary tumors of 329 patients were as follows: lung (n = 89), kidney (n = 70), urinary tract (n = 52), skin (n = 50), stomach (n = 30), esophagus (n = 21), and head and neck (n = 17). Median OS after the introduction of ICIs was 17.3 months. Among the factors that correlated with OS in a univariate analysis, body mass index, C-reactive protein, hemoglobin, lymphocytes, and platelets were identified as independent predictors of OS in a multivariate analysis. Following the classification of patients into 3 groups based on positive numbers of these independent risk factors, median OS was not reached in the favorable risk group with 0 or 1 risk factor (n = 76), 19.5 months in the intermediate-risk group with 2 or 3 risk factors (n = 182), and 7.2 months in the poor risk group (n = 71) with 4 or 5 risk factors.Although this is a simple and objective model, it may be used as a reliable tool to predict the outcomes of advanced cancer patients receiving ICIs across multiple tumor types.

Cabazitaxel has played an important role in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC); however, several types of sequential therapy against mCRPC have been performed in routine clinical practice. The objective of this study was to investigate the impact of third-line treatment on prognostic outcomes of mCRPC patients. This study retrospectively analyzed the clinical outcomes of 166 patients who received 3 agents following the diagnosis of mCRPC, consisting of 81 sequentially treated with either abiraterone or enzalutamide and then docetaxel, followed by third-line cabazitaxel (group A) and 85 treated with 3 agents, including abiraterone, enzalutamide, and docetaxel (group B). There were no significant differences in major characteristics at the introduction of the third-line agent between these 2 groups. The proportion of patients with prostate-specific antigen (PSA) reduction > 50% by cabazitaxel in group A was significantly greater than that by either third-line agent in group B. Both PSA progression-free survival (PFS) and overall survival (OS) following third-line therapy in group A were significantly longer than those in group B. Furthermore, OS after the diagnosis of mCRPC in group A was significantly longer than that in group B. Multivariate analysis identified independent predictors of favorable prognostic outcomes after third-line therapy as follows: high-performance status (PS), low PSA level and third-line cabazitaxel for PSA PFS, and high PS, low lactate dehydrogenase level and third-line cabazitaxel for OS. The introduction of cabazitaxel as a third-line agent could markedly improve the prognostic outcomes of mCRPC patients.

Background/Aim: Transurethral resection of bladder tumors (TURBT) guided by photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) has been shown to be superior to conventional white light (WL) cystoscopy with regard to diagnostic accuracy, for non-muscle invasive bladder cancer (NMIBC); however, PDD is usually performed prior to WL TURBT. The objective of this study was to investigate the diagnostic significance of 5-ALA-mediated PDD following TUR of NMIBC. Patients and Methods: In 83 NMIBC patients, all visible tumors were completely resected under the conventional WL guidance followed by additional resection if fluorescent lesions were observed under the blue light (BL) guidance, and random biopsy was further conducted. Results: With the BL source, 39 (47.0%) patients were judged to have fluorescent lesions. Twenty (51.3%) of the 39 patients with positive findings by PDD were diagnosed with residual cancer by additional resection, while random biopsy detected cancers in 2 (4.5%) of the 44 patients with negative findings by PDD. Accordingly, the sensitivity, specificity, positive predictive value and negative predictive value in diagnosing residual cancer by our PDD system were 90.9, 68.9, 51.3 and 95.5%, respectively. Univariate analysis showed that the presence of residual cancers shown by WL TURBT was significantly associated with the preoperative findings of urinary cytology, tumor multiplicity, pathological T stage and tumor grade, of which only the preoperative finding on urinary cytology was shown to have an independent impact on the diagnosis of residual cancer. Conclusion: 5-ALA-mediated PDD following standard WL TURBT could improve the diagnostic accuracy in NMIBC patients, particularly those who are positive for preoperative urinary cytology.

Background Recently, several types of systemic therapy using tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) have been performed for advanced renal cell carcinoma (aRCC) patients; however, the optimal strategy of sequential treatment with these agents has not been well established. The objective of this study was to determine the optimal timing for the introduction of TKI and ICI using a mouse RCC, RenCa model. Materials and Methods The effects of combined treatment of TKI and/or ICI with axitinib, anti-mouse programmed death (PD)-1, or PD-ligand 1 (PD-L1) antibody on tumor growth and survival after subcutaneous and intravenous injection of RenCa cells, respectively, were compared according to three different treatment schedules: simultaneous administration, initial axitinib administration, and initial ICI administration. Infiltrating patterns of lymphocytes into tumors after combined treatments were evaluated by immunohistochemical staining. Results In both the patients with anti-PD-1 and anti-PD-L1 antibodies, significantly marked inhibitory effects on subcutaneous growth of tumors were observed in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to those in the control without treatment. Survival intervals of mice after intravenous injection of RenCa cells were significantly longer in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to the control. Furthermore, both CD8 + to CD3 + and CD8 + to CD11b + T-lymphocyte ratios in subcutaneous RenCa tumors were significantly higher in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to the control. Conclusions Favorable control against aRCC progression may be achieved by administering TKI and ICI simultaneously or ICI followed by TKI.

Background A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this “DNA adductome approach” in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. Aim Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. Materials and methods From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. Results Seven DNA adducts, including modified bases, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. Conclusions We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

Background: Surgical treatment of synchronous multifocal renal tumors arising in a solitary kidney remains an extremely unique and stressful challenge, since it is not easy to completely remove multiple tumors and effectively preserve the renal function without perioperative complications. In this report, we describe our experience of three patients with multifocal renal tumors detected in a solitary kidney who were treated by robot-assisted partial nephrectomy (RAPN). Case Presentation: Two men and one woman were found to have two small renal tumors in a solitary kidney, and subsequently underwent RAPN at our institution. The location of the renal tumors and surgical approach in each patient were as follows: one tumor on the abdominal side and another on the dorsal side with a transperitoneal approach, both on the abdominal side with a transperitoneal approach, and both on the dorsal side with a retroperitoneal approach. In this series, after clamping the main renal artery and resection of one tumor, an inner running suture was placed, followed by early declamping of the renal artery and then renorrhaphy, and the same procedure was repeated to manage the remaining tumor. In all patients, the trifecta outcomes were achieved, and there were no changes in the chronic kidney disease stage 1 month after RAPN, resulting in no requirement of postoperative dialysis. Conclusion: Although it is necessary to carefully select optimal candidates, RAPN with an early declamping technique could be a safe and feasible approach for the treatment of patients with synchronous multifocal renal tumors arising in a solitary kidney, facilitating the complete resection of tumor foci, minimization of warm ischemic injury, and effective preservation of the renal function.

To assess the postoperative status of clinically localized prostate cancer patients who underwent robot-assisted radical prostatectomy (RARP) with a focus on de novo overactive bladder (OAB).The present study included 156 patients who did not have preoperative OAB and underwent RARP between December 2015 and April 2020 at our institution. Patients were divided into the de novo OAB group and non-OAB group based on the findings of overactive bladder symptoms score (OABSS) 6 months after RARP, and comparative assessments were performed between the two groups.Six months after RARP, de novo OAB was detected in 38 (24.4%) out of 156 patients. Body mass index (BMI) and the proportion of patients with hypertension were significantly higher in the de novo OAB group than in the non-OAB group. No significant differences were observed in the other characteristics examined. Furthermore, the preoperative findings of uroflowmetry and a urodynamic study did not significantly differ between the two groups. Despite the lack of significant differences in preoperative OABSS, total international prostate symptom score, the voiding symptom score, storage symptom score, and quality of life score between the two groups, all of these findings 6 months after RARP were significantly worse in the de novo OAB group than in the non-OAB group. Among the several factors examined, only BMI was independently associated with the development of de novo OAB 6 months after RARP.Patients with a high BMI may develop de novo OAB after RARP, resulting in the significant deterioration of lower urinary tract symptoms.

To assess real-world oncological outcomes between the radical cystectomy (RC) group and non-RC group for early relapse and refractory disease.We retrospectively analyzed 953 patients with recurrent non-muscle-invasive bladder cancer (NMIBC) who received bacillus Calmette-Guérin (BCG) at 31 affiliated hospitals from 2000 to 2019. Patients with missing data on the timing of failure were excluded and 871 patients remained eligible, of whom 447, 357, and 67 were classified as early relapse/refractory disease, intermediate/late relapse disease, and intolerant disease, respectively. For early relapse/refractory disease, patients were divided into two salvage treatment groups: RC and non-RC. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios with matched score analyses to compare oncological outcomes between the two groups.Significantly worse progression-free survival and cancer-specific survival (CSS) were confirmed in the early relapse/refractory disease group compared to the intermediate/late relapse group. Of the 88 salvage patients in the RC group with early relapse/refractory disease, ≤pT1 was observed in 47, pT2 in 11, and ≥pT3 in 28 (two patients with unknown pT category). In early relapse/refractory disease, the RC group showed significantly high-risk tumor compared to the non-RC group. However, no significant difference was observed in CSS after matched score analyses (p = 0.45) between the RC and non-RC groups.This study found that the RC group showed no significant superiority compared to the non-RC group in CSS for early relapse/refractory disease in terms of first salvage therapy.

Introduction The aim of this study was to investigate the effects of renal tumor complexity on perioperative outcomes in patients receiving robot-assisted partial nephrectomy (RAPN). Methods This study included 153 consecutive patients with cT1 renal masses undergoing RAPN and analyzed their perioperative outcomes, particularly tumor complexity. In this series, cT1b, completely endophytic, hilar, and cystic tumors were considered complex tumors. Patients with tumors that met at least one of the complex criterion were placed in the complex tumor group; patients with tumors that did not meet any of the complex criteria were placed in the non-complex tumor group. Results Of the 153 patients, 54 (35.3%) had complex tumors; specifically, 18 (11.8%) had cT1b tumors, 15 (9.8%) had completely endophytic tumors, 28 (18.3%) had hilar tumors, and 8 (5.2%) had cystic tumors. The non-complex group included 99 patients (64.7%). The complex tumor group had significantly longer warm ischemia and console times than the non-complex tumor group, but there was no significant difference between them in the achievement of the trifecta. Both warm ischemia and console times were significantly correlated with the number of complex factors. Multivariate analyses of complex factors demonstrated that completely endophytic and cT1b tumors were independently associated with warm ischemia time and console time, respectively. Conclusions For patients with complex tumors, RAPN may be a feasible procedure with acceptable perioperative outcomes. However, special attention should be paid to long warm ischemia and console times, particularly in those with completely endophytic and/or cT1b tumors.

Background/aim Despite recent introduction of several novel agents, limited data exist regarding parameters that help predict the progression of non-metastatic castration-resistant prostate cancer (nmCRPC). The objective of this study was to identify prognostic predictors in nmCRPC patients. Patients and methods This study included 127 consecutive Japanese nmCRPC patients treated in routine clinical practice. Prognostic outcomes in these patients were analyzed to evaluate the impact of several parameters on prostate-specific antigen progression-free survival (PSA PFS) and metastasis-free survival (MFS). Results When the 127 patients were diagnosed with nmCRPC, the PSA and PSA doubling time (PSADT) were 13.5 ng/ml and 17.9 months, respectively. Of these, 77 (60.6%) and 50 (39.4%) were treated with first-generation anti-androgen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA), respectively, as first-line therapy for nmCRPC. The median PSA PFS and MFS after the diagnosis of nmCRPC in these patients were 29.5 months and not reached, respectively. Multivariate analyses identified the following independent prognostic factors: PSA at nmCRPC, PSADT and first-line therapy for nmCRPC for PSA PFS, and PSA at nmCRPC and PSADT for MFS. Conclusion nmCRPC patients with higher PSA and/or shorter PSADT should be treated with ARATA rather than FGA.

Background/aim The prognosis of patients with invasive bladder cancer remains poor. The objective of this study was to evaluate the efficacy of NVP-BEZ235 (NVP), a dual PI3K/mTOR inhibitor, combined with the inactivation of p62/SQSTM1 (p62) in a human bladder cancer KoTCC-1 model. Materials and methods An expression plasmid with short hairpin RNA targeted against p62 was transfected into KoTCC-1 cells (KoTCC-1/sh-p62). The antitumor effects of NVP on KoTCC-1/sh-p62 were investigated in comparison with those on KoTCC-1 transfected with a control plasmid alone (KoTCC-1/C). Results KoTCC-1/sh-p62 showed significantly higher sensitivity to NVP than KoTCC-1/C. Treatment of both cell lines with NVP markedly inactivated the PI3K/Akt/mTOR signaling pathway. However, NVP treatment stimulated the autophagic pathway in KoTCC-1/C, but not in KoTCC-1/sh-p62. Furthermore, compared with KoTCC-1/C, NVP treatment induced apoptosis of KoTCC-1/sh-p62 cells, which was accompanied by significant downregulation of c-IAP-1 and XIAP as well as upregulation of Bax. Moreover, the in vivo growth of KoTCC-1/sh-p62 tumors was significantly suppressed by treatment with NVP compared to KoTCC-1/C tumors. Conclusion Inhibition of p62 expression combined with NVP may represent an effective therapeutic approach for patients with invasive bladder cancer.

Background We aimed to evaluate the effect of transvaginal mesh surgery on overactive bladder symptoms in women with pelvic organ prolapse and to identify predictive factors for persistence of a preoperative overactive bladder after surgery. Materials and methods We retrospectively evaluated 102 patients who underwent transvaginal mesh surgery. All patients had stage 2 or greater pelvic organ prolapse accompanied by cystocele. The Overactive Bladder Symptom Score, International Prostate Symptom Score, uroflowmetry, and postvoid residual urine volume were evaluated preoperatively and 6 months postoperatively. To identify predictive factors for the persistence of a preoperative overactive bladder after surgery, preoperative parameters were statistically compared between patients with and without the persistence of preoperative overactive bladder symptoms. Receiver operator characteristic curves were generated, and the area under the curve was calculated. Results Preoperatively, 54 women (53%) had an overactive bladder. After surgery, the symptoms disappeared in 34 (63%) and persisted in 20 (37%) women. There were no significant differences in preoperative parameters including age, body mass index, parity, or severity of pelvic organ prolapse between patients with and without persistent preoperative overactive bladder. Preoperative Overactive Bladder Symptom Score and International Prostate Symptom Score were significantly higher in patients with persistent preoperative overactive bladder symptoms. The International Prostate Symptom Score storage subscore had the highest area under the curve, with a cutoff value of 9.5. Conclusion Transvaginal mesh surgery eliminates overactive bladder symptoms in about two-thirds of pelvic organ prolapse patients. The preoperative International Prostate Symptom Score storage subscore was the most useful predictive factor for the persistence of preoperative overactive bladder symptoms after surgery.

Purpose To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC). Methods The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test. Results A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P

Background DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer. Method To elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed. Results C5-Methyl-2′-deoxycytidine, C5-hydroxymethyl-2′-deoxycytidine (5hmdC), C5-formyl-2′-deoxycytidine, 2′-deoxyinosine, C8-oxo-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p = 0.048 and p = 0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n = 10) than in the urothelium of patients without urothelial carcinoma (n = 15) (p = 0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman’s rank correlation test revealed a negative correlation between age and 5hmdC levels (r = − 0.46, p = 0.018 and r = − 0.45, p = 0.042, respectively). Conclusions The present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer.

To investigate the impact of erectile function on health-related quality of life in Japanese prostate cancer patients following robot-assisted radical prostatectomy.Time-dependent changes in erectile function and health-related quality of life were assessed using the erection hardness score and Medical Outcomes Study 8-Item Short Form Health Survey, respectively, in 229 consecutive Japanese patients undergoing robot-assisted radical prostatectomy. In this series, patients with erection hardness score ≥2 were considered to those having a certain erectile function.Among the 229 patients examined, erection hardness score ≥2 was observed in 134 (58.5%) and 34 (14.9%) before and 12 months after robot-assisted radical prostatectomy, respectively. Prior to robot-assisted radical prostatectomy, all eight scale scores of 8-Item Short Form Health Survey were significantly superior in patients with erection hardness score ≥2 than in those with erection hardness score = 0 or 1. However, significant differences were observed in two scale scores between patients with erection hardness score ≥2 and those with erection hardness score = 0 or 1 at 12 months after robot-assisted radical prostatectomy. Furthermore, among patients with erection hardness score ≥2 before robot-assisted radical prostatectomy, no significant differences were noted in any of the eight scale scores between patients with erection hardness score ≥2 and erection hardness score = 0 or 1 at 12 months after robot-assisted radical prostatectomy.These findings suggest the limited impact of erectile function on postoperative health-related quality of life in Japanese patients undergoing robot-assisted radical prostatectomy.

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.

Objectives: Systematic regional lymph node dissection (LND) combined with radical nephroureterectomy (RNU) has been reported to improve the outcomes of upper tract urothelial carcinoma (UTUC) patients. The objective of the present study was to assess the prognostic outcomes of UTUC patients undergoing systematic regional LND combined with RNU. Patients and methods: We conducted a retrospective evaluation of prognostic outcomes of 68 consecutive UTUC patients treated with RUN and systematic regional LND. Results: The median durations of recurrence-free survival (RFS) and overall survival (OS) were 45 and 166 months, respectively. Univariate analyses of several parameters showed that despite the lack of a significant predictor for RFS, the presence of lymph node metastasis correlated with poor OS. Conclusion: These results suggest that comparatively favorable outcomes are achievable in UTUC patients by RNU and systematic regional LND; however, special attention is needed for patients with nodal involvement even after systematic regional LND due to the adverse impact of this factor on OS.

Simple Summary The geospatial distribution of DNA adducts, the presumable origins of mutations causing human cancers in the stomach was described. In human stomach resections for gastric cancer, seven different DNA adducts, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in various parts and zones of the human stomach, namely, the upper, middle and lower zones, anterior and posterior walls, and lesser and greater curvatures. This DNA adductomics approach will reveal the exposure and risk of individual gastric mucosa in humans. Basic information on multiple DNA adduct profiles in terms of the correlation with the preferred locations of gastric cancer in the stomach will provide the reality of “field cancerization” in human gastric carcinogenesis. Abstract Background: Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. Methods: Seven DNA adducts, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. Conclusions: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.

Introduction Renal artery fibromuscular dysplasia is generally considered a contraindication of kidney transplantation, since fibromuscular dysplasia occasionally induces hypertension or renal insufficiency in the recipient and/or donor. To date, limited information remains available with respect to whether kidneys with renal arterial fibromuscular dysplasia can be successfully transplanted. Case presentation A 53‐year‐old potential donor was diagnosed with fibromuscular dysplasia of the right renal artery. Laparoscopic right nephrectomy was performed, and the affected portion was resected and reconstructed using the harvested internal iliac artery. Transplantation was successful and the serum creatinine level was

Background The objective of this study was to evaluate our experience with robot-assisted partial nephrectomy (RAPN) in comparison with conventional open partial nephrectomy (OPN). Patients and methods This study included 37 and 50 patients undergoing OPN and RAPN for small renal masses, respectively. A single surgeon performed RAPN for all 50 cases using the da Vinci Xi. Trifecta was defined as satisfying all of the following 3 criteria: ischemic time of ≤ 25 minutes, negative surgical margin and no major postoperative complications. Results After adjusting patient variables by 1:1 propensity-score matching, 37 patients were included in each group, and no significant differences in major clinicopathological characteristics were noted between these 2 groups. RAPN was significantly superior to OPN with respect to operative time, estimated blood loss and postoperative length of hospital stay. The rate of trifecta achievement was significantly higher in the RAPN group than in the OPN group (91.9 vs. 62.2%). Furthermore, the operative procedure and R.E.N.A.L. nephrometry score were found to be independently associated with trifecta outcome by multivariate analysis of the entire cohort. Conclusions Although this is our early experience with 50 initial cases, RAPN using the da Vinci Xi resulted in more favorable perioperative outcomes than OPN.

Background/aim In renal cell carcinoma (RCC), sorafenib was the first targeted agent demonstrating a definitive benefit in a large phase III clinical trial. The objective of this study was to assess the clinical outcomes of 42 consecutive RCC patients with metastases solely to the lung who received sorafenib as a second-line systemic agent. Patients and methods Of the 42 patients, 14 (33.3%) and 28 (66.7%) received cytokine therapy and sunitinib, respectively, prior to treatment with sorafenib. In this series, all patients initially received 400 mg of sorafenib twice daily on a continuous dosing schedule. The efficacy and safety of second-line sorafenib in these 42 patients were retrospectively evaluated. Results As the best response to sorafenib, 2 (4.8%), 14 (33.3%), 22 (52.4%) and 4 (9.5%) patients were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) after the introduction of sorafenib was 10.6 and 30.2 months, respectively. Multivariate analyses of several parameters identified the following independent prognostic predictors: C-reactive protein (CRP) level for PFS, and International Renal Cell Carcinoma Database Consortium classification and CRP level for OS. The common adverse events associated with sorafenib were hand-foot syndrome, hypertension and diarrhea, which developed in 22 (52.4%), 17 (40.5%) and 13 (31.0%), respectively; however, any AEs corresponding to ≥grade 3 occurred in only 16 (38.1%). Conclusion Favorable disease control with acceptable tolerability might be expected by introducing sorafenib as second-line therapy for RCC patients with metastases solely to the lung; therefore, sorafenib could be the optimal option for this category of patients.

Due to recent advancement of DNA sequencing technologies, cancer genome analysis has shown that somatic mutations have different trends in various tissues and individuals. Some of trends has been associated with exposure of chemically reactive compounds derived from exogenous or endogenous sources and genetic deficiencies in DNA repair and DNA replication as mutational signatures. Accumulation of these information will ultimately expect to identify carcinogenic etiologies in an individual case. However, what types of DNA damage caused the mutational signatures and how extent they contribute to human carcinogenesis has not yet fully explained.To directly evaluate the chemical types of DNA damage in human colorectal tissues, we performed comprehensive identification of DNA adducts by a liquid chromatography coupled with mass spectrometry. In this DNA adductome methodology, genome DNA was enzymatically hydrolyzed into mononucleoside and separated using a reversed-phase chromatography. Chemical structure of DNA adducts including products of epigenetic modification in genome DNA was identified using column retention time and m/z of chemical standard library of DNA adducts. Peak areas of DNA adducts were normalized by that of naturally-occurring isotopologues of canonical DNA nucleoside and compared with clinicopathological information. We identified several DNA adducts in human colorectal tissue. These included DNA adducts of alkylation, oxidation, and lipid peroxidation. C5-methyl-2’-deoxycytidine was most abundant atypical DNA in human colorectal tissue and prevalent in all cases. C5-hydroxymethyl-2’-deoxycytdine was decreased in colorectal cancer cases compared with non-colorectal cancer cases. Other DNA adducts like 1,N6-etheno-2’-deoxyadenosine were present with group- or individual-specificity. Compared with our previous results of DNA adductome analysis in human stomach mucosae and kidney tissues, DNA adducts observed in human colorectal tissue showed some tissue specificity. We will discuss whether profiles of DNA adducts are based on similar contexts of chemical exposure among individuals. DNA adducts observed in our study potentially indicated chemical causes of DNA mutation in human colorectal tissue. We propose that the integration of DNA adductomics using mass spectrometric profiling with other genetic analysis such as mutational signature analysis leverage the exploration of chemical and genetic etiology in an individual carcinogenic context and evaluate gene-environment interaction in human carcinogenesis. Citation Format: Yuji Iwashita, Shunsuke Ohtsuka, Ippei Ohnishi, Yuto Matsushita, Takashi Yamashita, Keisuke Inaba, Atsuko Fukazawa, Hideto Ochiai, Keigo Matsumoto, Nobuhito Kurono, Yoshitaka Matsushima, Hiroki Mori, Shioto Suzuki, Shohachi Suzuki, Fumihiko Tanioka, Haruhiko Sugimura. DNA adductome analysis in human colorectal tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2257.

Objective The aim of this study was to determine whether a history of treatment for non-muscle invasive bladder cancer (NMIBC), including intravesical bacillus Calmette-Guerin (BCG) therapy, affects the treatment outcomes of pembrolizumab in patients with metastatic, chemo-resistant urothelial carcinoma (UC). Materials and methods The clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. Best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed with regard to the history of NMIBC treatment and BCG usage using propensity score matching (PSM). Results A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 10.0 months), the OS from the initiation of pembrolizumab for patients with a NMIBC history (13.3 months, HR [95% CI] 0.79 [0.62–1.02], P = 0.073), those with a NMIBC history and BCG (12.1 months, HR 0.87 [0.64–1.17], P = 0.356), or those with a NMIBC history but not BCG (14.5 months, HR 0.68 [0.45–1.12], P = 0.061) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 24.5% vs. 31.0%, P = 0.222) and disease control rate (DCR, 56.1% vs. 52.1%, P = 0.501) of the 155 patients with an NMIBC history did not differ from those of 155 matched patients without an NMIBC history. Among those with an NMIBC history, the prior use of BCG did not affect OS (with vs. without BCG, 12.1 vs. 14.5 months, HR 1.29 [0.80–2.09], P = 0.295), ORR (24.5% vs. 34.0%, P = 0.298) or DCR (57.1% vs. 56.0%, P = 0.908). The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P = 0.042), whereas DCR between the 2 groups did not differ significantly (55.8% vs. 54.4%, P = 0.855). Conclusions Our risk-adjusted analyses revealed that a history of prior NMIBC treatment, including intravesical BCG therapy, did not affect the treatment outcomes of pembrolizumab in metastatic UC patients.

Introduction: There have been insufficient data regarding the impact of partial nephrectomy (PN) with minimal invasive approaches, including robot-assisted PN (RAPN), on postoperative quality of li...

Objectives To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo-resistant urothelial carcinoma (UC). Patients and methods The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). Results Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68-1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15-0.90; P = 0.023) compared to patients with PUC. Conclusions The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo-resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.

Background/aim There are limited data on comprehensive assessments of several treatments as second-line therapy against advanced urothelial cancer (UC). The objective of this study was to compare clinical outcomes between advanced UC patients receiving either pembrolizumab (Pem) or combined chemotherapy with gemcitabine and paclitaxel (GP) as second-line therapy. Patients and methods This study retrospectively analyzed the clinical outcomes of 89 patients with platinum-refractory advanced UC, consisting of 46 and 43 who received Pem and GP therapy, respectively, as second-line treatment. Results There were no significant differences in major clinicopathological parameters between Pem and GP groups. No significant difference in the objective response rate was noted between the two groups. Progression-free survival (PFS) in the Pem group was significantly longer than that in the GP group; however, there was no significant difference in overall survival (OS) between them. Multivariate analyses identified performance status ≤2 and liver metastasis as independent factors associated with poor outcomes in both PFS and OS. The incidence of adverse events in the GP group was significantly higher than that in the Pem group. Conclusion Pem could be regarded as standard agent for platinum-refractory advanced UC patients.

Additional file 3: Table S2. Comparison of variables according to patterns of intravesical BCG treatment: before propensity score matching.

Additional file 1. Supplementary Figure S1: Chromatograms of standard compounds of DNA adducts. Representative chromatograms of blank (left panel) and standard compounds (right panel) in each mass transition and column retention times are shown (a: C5-methyl-dC, b: dI, c: C5-hydroxymethyl-dC, d: N6-methyl-dA, e: etheno-dA, f: N6-hydroxymethyl-dA, g: C8-oxo-dG). Supplementary Figure S2: Histogram of the quantity of each DNA adduct. The distributions according to the various amounts (molar ratios; horizontal axis) of DNA adducts (a: C5-methyl-dC, b: dI, c: C5-hydroxymethyl-dC, d: N6-methyl-dA, e: etheno-dA, f: N6-hydroxymethyl-dA, g: C8-oxo-dG) in nontumor sites of gastric cancer cases are shown. We assigned a zero value in some of the cases with considerably low or undetectable levels of adducts and depicted the histograms of molar ratios among 306 samples.

Additional file 5: Fig. S2. Landmark analysis of recurrence among patients treated with non-maintenance induction BCG (iBCG) or iBCG plus maintenance BCG (mBCG) at 24 months. Landmark RFS at 6, 12, and 18 months among patients treated with non-maintenance iBCG or iBCG plus mBCG are plotted and compared between matched groups A and B (left panel) and between matched groups B and C (right panel). The P values, hazard ratios (HRs), and 95% confidence intervals (CIs) are shown in the figures.