Prognostic outcomes in Japanese patients with metastatic castration-sensitive prostate cancer: Comparative assessments between conventional androgen deprivation therapy (ADT) and ADT with novel androgen receptor signal inhibitor.

OBJECTIVE: The objective of this study was to compare the prognostic outcomes between metastatic castration-sensitive prostate cancer (mCSPC) patients receiving conventional androgen deprivation therapy (ADT) and those receiving ADT plus a novel androgen-receptor signaling inhibitor (ARSI) in routine clinical practice in Japan. METHODS: This was conducted as a retrospective multicenter study including 581 mCSPC patients, consisting of 305 receiving ADT alone or in combination with bicalutamide (group 1) and 276 receiving ADT plus one of the following ARSIs: abiraterone acetate, apalutamide, or enzalutamide (group 2). Prognostic outcomes between these 2 groups were comprehensively compared. RESULTS: In the entire cohort, prostate-specific antigen-progression-free survival (PSA-PFS) in group 2 was significantly longer than that in group 1, while no significant difference was noted in overall survival (OS) between the two groups. In patients corresponding to the LATITUDE high-risk group, however, both PSA-PFS and OS in group 2 were significantly longer than those in group 1. Of several factors examined, the following were identified as independent predictors of poor PSA-PFS in the entire cohort as well as the LATITUDE high-risk group: high C-reactive protein, high lactate dehydrogenase, high alkaline phosphatase, high Gleason score, and group 1. Furthermore, it was possible to precisely classify both the entire cohort and LATITUDE high-risk group into 3 risk groups regarding PSA-PFS according to the positive numbers of independent factors: positive for ≤1 factor, favorable; 2 factors, intermediate; and ≥3 factors, poor. CONCLUSION: Combined use of ARSIs with ADT could improve the prognostic outcomes of mCSPC patients, particularly those in the LATITUDE high-risk group, in real-world clinical practice in Japan.

Robot-assisted radical nephrectomy using novel surgical robot platform, hinotori: Report of initial series of 13 cases.

OBJECTIVES: The aims of the present study were to describe the perioperative findings of the first series of patients undergoing robot-assisted radical nephrectomy (RARN) with a newly launched platform, the hinotori surgical robot system, and compare the findings with a similar set receiving RARN with the existing system, da Vinci. METHODS: This study included 34 patients, consisting of 13 and 21 undergoing RARN using the hinotori and da Vinci robotic systems, respectively. As a rule, RARN was performed via an intraperitoneal approach employing 3 robotic arms, irrespective of the robotic systems. RESULTS: In the hinotori group, the median age, body mass index and tumor diameter were 65 years, 23.3 kg/m2 and 50 mm, respectively. All surgical procedures with hinotori could be completed by a purely robotic approach. In the hinotori group, the median operative time, time using the robotic system, estimated blood loss and length of hospital stay were 157, 83 min, 11 mL and 6 days, respectively, and major perioperative complications did not occur. In this group, 3, 1 and 9 patients were pathologically diagnosed with pT1a, pT1b and pT3a tumors, respectively. No significant differences in baseline characteristics were noted between the hinotori and da Vinci groups, and there were also no significant differences in perioperative findings between them. CONCLUSIONS: Despite a case series with a small sample size, this is the first report evaluating RARN using the hinotori surgical robot system, which could be safely conducted and achieved perioperative outcomes similar to that using the da Vinci system.

Predictive factors of de novo overactive bladder in clinically localized prostate cancer patients after robot-assisted radical prostatectomy.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Patients with a high BMI may develop de novo OAB after RARP, resulting in the significant deterioration of lower urinary tract symptoms.

Significance of second progression-free survival in patients with advanced urothelial cancer who received platinum-based combination chemotherapy followed by pembrolizumab.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Significant impact of a history of prior or concomitant upper urinary tract cancer on the recurrence and progression of non-muscle invasive bladder cancer.

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 < 0.001 and P = 0.006, respectively). Multivariate analyses identified the following independent prognosticators: multiplicity and upper urinary tract cancer status for recurrence-free survival, and pT category and upper urinary tract cancer status for progression-free survival. Significant differences were noted by the risk stratification systems based on the positive number of independent predictors of recurrence-free survival and progression-free survival (P < 0.001 and P = 0.007, respectively). The concordance indices of recurrence-free survival were 0.627, 0.588 and 0.499 in this study stratification, EORTC risk table and CUETO model, respectively. Those of progression-free survival were 0.752, 0.740 and 0.714, respectively. 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.

Limited impact of erectile function on health-related quality of life in Japanese men undergoing robot-assisted radical prostatectomy.

OBJECTIVE: To investigate the impact of erectile function on health-related quality of life in Japanese prostate cancer patients following robot-assisted radical prostatectomy. METHODS: 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. RESULTS: 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. CONCLUSION: These findings suggest the limited impact of erectile function on postoperative health-related quality of life in Japanese patients undergoing robot-assisted radical prostatectomy.

Prognostic significance of third-line treatment for patients with metastatic castration-resistant prostate cancer: comparative assessments between cabazitaxel and other agents.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: The introduction of cabazitaxel as a third-line agent could markedly improve the prognostic outcomes of mCRPC patients.

Second transurethral resection for high-risk non-muscle invasive bladder cancer patients: a propensity score matched analysis.

OBJECTIVES: Second transurethral resection is recommended for patients diagnosed with high-risk non-muscle invasive bladder cancer; however, there have been several studies showing conflicting findings regarding the advantage of second transurethral resection. The objective of this study was to investigate the prognostic significance of second transurethral resection using propensity score matched analysis. PATIENTS AND METHODS: This study retrospectively included 164 consecutive patients who underwent initial transurethral resection and were diagnosed with high-risk non-muscle invasive bladder cancer. Of these, 56 subsequently received second transurethral resection, and the remaining 108 underwent initial transurethral resection alone. RESULTS: After adjusting patient variables by propensity score matching, 44 patients were included in each group. There was no significant difference in recurrence-free, progression-free or overall survival between these two groups. CONCLUSIONS: These findings suggested no significant impact of second transurethral resection on the prognosis of high-risk non-muscle invasive bladder cancer patients; therefore, it may be necessary to perform a reassessment focusing on the indication for second transurethral resection by conducting a large-scale prospective study.

Significant impact of three-dimensional volumetry of perinephric fat on the console time during robot-assisted partial nephrectomy.

BACKGROUND: To assess the impact of volumetry of perinephric fat (PNF) on the perioperative outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: Between 2016 and 2019, a single surgeon performed RAPN for 128 patients with clinical T1a-b renal tumors at our institution, and the 70 most recent patients were included in this study to minimize the effects of surgical experience. PNF was defined as a fatty area around the kidney within the anatomical structures, including the lateroconal fascia, fusion fascia, psoas muscle, lumbar quadrate muscle and diaphragm, and its volume was calculated based on reconstructed three-dimensional computed tomography images using the SYNAPSE VINCENT system. RESULTS: In this series, the trifecta and MIC (margin, ischemia and complications) score system outcomes were achieved in 69 (98.6%) and 64 patients (91.4%), respectively. The median PNF volume in the 70 patients was 166.05 cm3, which was significantly correlated with both the body mass index (BMI) and Mayo adhesive probability (MAP) score (correlation coefficient = 0.68 and 0.74, respectively). There was no significant difference in the R.E.N.A.L. nephrometry score, PNF volume or console time during RAPN among 5 groups consisting of 14 consecutive patients. Of several factors examined, the console time was significantly affected by the sex, MAP score and PNF volume, and only the PNF volume was independently associated with the console time. CONCLUSION: Even if performed by an experienced robotic surgeon beyond the initial learning curve, the PNF volume may influence the console time during RAPN.

Comparative assessment of prognostic outcomes between first-generation antiandrogens and novel androgen-receptor-axis-targeted agents in patients with non-metastatic castration-resistant prostate cancer.

BACKGROUND: To compare the prognostic outcomes between first-generation antiandrogen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA) as first-line therapy in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). METHODS: This study retrospectively included a total of 103 consecutive nmCRPC patients consisting of 47 (45.6%) and 56 (54.4%) who received FGA (bicalutamide or flutamide) and ARATA (abiraterone acetate or enzalutamide), respectively, as the first-line agent after the failure of primary androgen deprivation therapy (ADT). RESULTS: There were no significant differences in the major clinicopathological parameters and previous therapeutic histories between the FGA and ARATA groups. During the observation period, 31 (66.0%) and 29 (51.8%) discontinued first-line therapy in the FGA and ARATA groups, respectively, and of these, 27 (87.1%) and 23 (79.3%) in the FGA and ARATA groups, respectively, were subsequently treated with approved agents as second-line therapy. The prostate-specific antigen (PSA) response rate in the FGA group was significantly lower than that in the ARATA group. Although no significant difference in overall survival was noted between the FGA and ARATA groups, there were significant differences in the PSA progression-free survival on first-line therapy and metastasis-free survival between the two groups, favoring the ARATA group compared with FGA group. CONCLUSIONS: Collectively, these findings suggest that among nmCRPC patients who progressed following treatment with the primary ADT, the introduction of ARATA may result in the delay of disease progression compared with FGA.

Overexpression of Rev1 promotes the development of carcinogen-induced intestinal adenomas via accumulation of point mutation and suppression of apoptosis proportionally to the Rev1 expression level.

Cancer development often involves mutagenic replication of damaged DNA by the error-prone translesion synthesis (TLS) pathway. Aberrant activation of this pathway plays a role in tumorigenesis by promoting genetic mutations. Rev1 controls the function of the TLS pathway, and Rev1 expression levels are associated with DNA damage induced cytotoxicity and mutagenicity. However, it remains unclear whether deregulated Rev1 expression triggers or promotes tumorigenesis in vivo. In this study, we generated a novel Rev1-overexpressing transgenic (Tg) mouse and characterized its susceptibility to tumorigenesis. Using a small intestinal tumor model induced by N-methyl-N-nitrosourea (MNU), we found that transgenic expression of Rev1 accelerated intestinal adenoma development in proportion to the Rev1 expression level; however, overexpression of Rev1 alone did not cause spontaneous development of intestinal adenomas. In Rev1 Tg mice, MNU-induced mutagenesis was elevated, whereas apoptosis was suppressed. The effects of hREV1 expression levels on the cytotoxicity and mutagenicity of MNU were confirmed in the human cancer cell line HT1080. These data indicate that dysregulation of cellular Rev1 levels leads to the accumulation of mutations and suppression of cell death, which accelerates the tumorigenic activities of DNA-damaging agents.

Impact of metabolic syndrome on early recovery of continence after robot-assisted radical prostatectomy.

OBJECTIVES: To evaluate the impact of metabolic syndrome on the early recovery of urinary continence after robot-assisted radical prostatectomy. METHODS: The present study included a total of 302 consecutive Japanese patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy. In this study, postoperative urinary continence was defined as no leak or the use of a security pad. The continence status was assessed by interviews before and 1 and 3 months after robot-assisted radical prostatectomy. Metabolic syndrome was defined as follows: body mass index ≥25 kg/m2 and two or more of the following: hypertension, diabetes mellitus and dyslipidemia. The effect of the presence of metabolic syndrome on the continence status of these patients was retrospectively examined. RESULTS: A total of 116 (38.4%) and 203 (67.2%) of the 302 patients were continent at 1 and 3 months after robot-assisted radical prostatectomy, respectively. A total of 31 (10.3%) patients were judged to have metabolic syndrome. Despite the operative time being longer in patients with metabolic syndrome, no significant differences were observed in the remaining preoperative, intraoperative or postoperative variables between patients with or without metabolic syndrome. On multivariate logistic regression analysis, metabolic syndrome and the duration of hospitalization were significantly correlated with the 1-month continence status. Similarly, metabolic syndrome and estimated blood loss during surgery were independent predictors of continence rates at 3 months after robot-assisted radical prostatectomy. CONCLUSIONS: These findings suggest that the presence of metabolic syndrome could have a significant impact on the early recovery of urinary continence after robot-assisted radical prostatectomy.

Effects of extremely low-frequency electromagnetic fields (ELF-EMF) exposure on B6C3F1 mice.

OBJECTIVE: Long-term exposure study was conducted to investigate the effects of extremely low-frequency electromagnetic field on the tumor promotion process and fertility. METHODS: Ten pregnant C57BL/6NCrj mice were exposed to 50 Hz field 500 mG for 1 week (12 h per day), and 24 male and 42 female B6C3F1mice born from them were further exposed up to 15.5 months. As a control group, 10 pregnant mice were bred without exposure, and 30 produced male and 32 female mice were observed without exposure for the same period. RESULTS: Mean body weights of exposed groups of male and female mice were decreased significantly than those of the control groups. In exposed mice, there was no increased incidence of liver and lung tumor. In female mice, the incidence of chronic myeloid leukemia [3/42 (7%)] in the exposed group was significantly greater than in the control group. The size of seminiferous tubules in the EMF exposed groups were significantly less than the control group. CONCLUSIONS: These data support the hypothesis that long-term exposure of 50 Hz magnetic fields is a significant risk factor for neoplastic development and fertility in mice.

Assessment of Therapeutic Effects of Combined Treatment With Cisplatin and Anti-mouse Programmed Death (PD)-1 Antibody in a Mouse Urothelial Cancer Model.

BACKGROUND/AIM: The therapeutic impact of combination treatment with an immune checkpoint inhibitor (ICI) and chemotherapeutic agent on patients with urothelial cancer (UC) remains controversial. Therefore, the present study investigated differences in the therapeutic effects of combination therapy with cisplatin plus anti-mouse programmed death (PD)-1 antibody according to the dose of cisplatin using the mouse bladder tumor model MBT2. MATERIALS AND METHODS: The effects of treatment with two different doses cisplatin and/or anti-mouse PD-1 antibody on tumor growth after the subcutaneous injection of MBT2 cells were compared. Infiltrating patterns of lymphocytes into tumors after treatment were assessed using immunohistochemical staining. RESULTS: MBT2 tumor volumes were significantly larger in mice receiving high-dose cisplatin alone than in those receiving low-dose cisplatin alone. Combination treatment with cisplatin plus anti-mouse PD-1 antibody exerted significantly stronger growth inhibitory effects on MBT2 tumors than treatment with either agent alone, irrespective of cisplatin doses; however, no significant differences were observed in MBT2 tumor volumes between mice receiving anti-mouse PD-1 antibody plus high-dose cisplatin and those receiving anti-mouse PD-1 antibody plus low-dose cisplatin. Furthermore, CD8+ to CD3+ and CD8+ to CD11b+ T-lymphocyte ratios in MBT2 tumors were both significantly higher in the low-dose cisplatin alone group than in the high-dose cisplatin alone group, whereas no significant differences were noted in either ratio between the two different combination treatment regimens. CONCLUSION: When combined with ICI, a lower dose of cisplatin may achieve favorable antitumor effects in UC patients by preventing lymphocyte exhaustion.

Robot-assisted radical nephrectomy and inferior vena cava tumor thrombectomy using the novel surgical robot platform, hinotori: Initial experience with two cases.

Introduction: A newly developed surgical robot system, hinotori, with various unique advantages has been in clinical use in Japan; however, there have not been any studies of robot-assisted radical nephrectomy and inferior vena cava tumor thrombectomy using hinotori. Case presentation: We describe two male patients aged 67 and 76 years old with right renal cell carcinoma and a level II and I inferior vena cava tumor thrombus, respectively, undergoing robot-assisted radical nephrectomy and inferior vena cava tumor thrombectomy using hinotori. Both operations were successfully completed with a purely robotic procedure without any major perioperative complications, resulting in the following findings: time using robotic system, 158 and 156 min; total operative time, 228 and 214 min; estimated blood loss, 535 and 200 mL, respectively. Conclusion: Based on our first experience, robot-assisted radical nephrectomy and inferior vena cava tumor thrombectomy using hinotori may be an effective treatment for renal cell carcinoma with inferior vena cava tumor thrombus ≤level II.

Preoperative factors predicting poor therapeutic efficacy of holmium laser enucleation of the prostate in patients with benign prostatic hyperplasia.

OBJECTIVES: We assessed preoperative factors predicting the poor therapeutic efficacy of holmium laser enucleation of the prostate (HoLEP) in benign prostatic hyperplasia (BPH) patients. METHODS: The present study included 159 patients who underwent HoLEP between August 2015 and June 2021 at our institution. Overall therapeutic efficacy was divided into good and poor therapeutic efficacies according to changes in the international prostate symptom score (IPSS), IPSS quality of life (IPSS-QOL), and the maximum urinary flow rate. Patients were divided into good and poor therapeutic efficacy groups based on findings obtained 3 months after HoLEP, and comparative assessments were performed between the two groups. RESULTS: The therapeutic efficacy of HoLEP was poor in 53 (33.3%) out of 159 patients. Intravesical prostatic protrusion (IPP), IPSS, IPSS-QOL, post-void residual volume (PVR), and the presence of overactive bladder (OAB) were significantly higher in the poor therapeutic efficacy group than in the good therapeutic efficacy group. A multivariable analysis of several factors identified the preoperative presence of OAB and short IPP as independent risk factors for the poor therapeutic efficacy of HoLEP. When treatment efficacy was divided according to risk factors, poor therapeutic efficacy was observed in only 14% of patients with prolonged IPP and the absence of OAB. CONCLUSIONS: The therapeutic efficacy of HoLEP may be poor in patients with OAB and short IPP, resulting in the significant deterioration of lower urinary tract symptoms. Accordingly, it is important to consider the presence or absence of OAB and IPP measurements when selecting indications for HoLEP.

Real-world experience of Doxorubicin Monotherapy for Advanced or Metastatic Retroperitoneal Sarcoma: A Single Institutional Study of 16 Cases.

BACKGROUND/AIM: Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma (RPS); however, few studies have reported the outcomes of doxorubicin monotherapy for these patients. We herein investigated the oncological efficacy and safety of doxorubicin monotherapy for patients with advanced or metastatic RPS in real-world clinical practice. PATIENTS AND METHODS: Sixteen patients diagnosed with advanced or metastatic retroperitoneal sarcoma, receiving doxorubicin monotherapy as first-line treatment between February 2017 and March 2023 at our Institution were analyzed. Response rate, progression-free survival (PFS) periods, overall survival (OS) period, and adverse event (AE) profiles were retrospectively investigated. RESULTS: The median age of patients was 69.5 years. Best responses to doxorubicin were as follows: complete response, 0 patients (0.0%); partial response, 3 (18.8%); stable disease, 9 (56.3%); and progressive disease, 4 (25.0%). The objective response rate and disease control rate were 18.8 and 75.0%, respectively. During the observation period (median, 22 months, range=2-53 months), median PFS and OS periods were 8.0 and 24.0 months, respectively. The following AEs Grade ≥3 occurred: neutropenia in 14 patients (87.5%), febrile neutropenia in 5 (31.3%), leukopenia in 2 (12.5%), thrombocytopenia in 1 (6.3%), and heart failure in 1 (6.3%). Grade ≥3 nausea and vomiting did not occur and there was no treatment-related death. CONCLUSION: The oncological outcomes of doxorubicin monotherapy for RPS in real-world clinical practice were not inferior to those of the EORTC trial. The incidence of hematological AEs was higher; however, severe gastrointestinal AEs were prevented by prophylactic antiemetics and there were no treatment-related deaths. Collectively, doxorubicin monotherapy with appropriate prophylactic agents is a valid option for patients with advanced or metastatic RPS.

Relationship Between Adverse Events and Progression-free Survival in Patients Receiving Cabozantinib for Previously Treated Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: Although the adverse events (AEs) of drugs, such as sunitinib and axitinib, have been shown to predict treatment responses, evidence to support cabozantinib-induced AEs as predictors of responses to treatment for metastatic renal cell carcinoma (mRCC) is limited. Therefore, we herein investigated the relationship between AE profiles and progression-free survival (PFS) in patients receiving cabozantinib for previously treated mRCC. PATIENTS AND METHODS: The present study retrospectively analyzed 40 patients receiving cabozantinib for previously treated mRCC between July 2020 and August 2022. PFS was estimated using the Kaplan-Meier method and the impact of several parameters, including cabozantinib-induced AEs, on PFS was investigated by a Cox proportional regression analysis. RESULTS: The median observation period was 15 (2-29) months, during which time 31 patients (77.5%) progressed, with median PFS of 11 months. Thirty-nine patients (97.5%) developed at least one AE. Liver toxicity occurred in 16 patients (40.0%) and hand-foot syndrome, hypertension, and diarrhea in 14 each (17.5%). Only hypertension correlated with longer PFS. A multivariate analysis identified hypertension as an independent prognostic factor for PFS (p=0.049). CONCLUSION: These results suggest the potential of treatment-induced hypertension as a significant predictor of prolonged PFS in patients receiving cabozantinib for mRCC.

Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice.

Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15 d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent.

Effects of a water-soluble extract of Ganoderma lucidum mycelia on aberrant crypt foci induced by azoxymethane and small-intestinal injury by 5-FU in F344 rats.

The present study investigated whether a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (Japanese: Reishi or Mannentake) (designated as MAK) exerted a protective effect against induction of aberrant crypt foci (ACF) by azoxymethane (AOM) and small-intestinal damage induced by the anticancer drug 5-FU. Six-week-old male F344 rats were fed a basic diet (MF), either alone or containing 2.5 % MAK, beginning 1 week before treatment with AOM. The rats were then given subcutaneous injections of AOM (15 mg/kg body weight) once in a week for 3 weeks. Next, beginning 1 day after the final AOM treatment, 25 or 80 mg/kg 5-FU was injected intraperitoneally three times at 5-day intervals. Finally, the rats were killed 3.5 days after the last injection of 5-FU. The large and small intestines were removed, and tissue specimens were examined for both ACF in the large intestine and regeneration of small-intestinal crypts. The number of ACF was significantly decreased by treatment with 25 mg 5-FU and further decreased by 25 mg 5-FU + MAK in comparison with 5-FU alone. Moreover, there was a greater degree of recovery from small-intestinal damage in the 5-FU + MAK groups than in rats that had received 5-FU alone. The present results indicate that MAK ameliorates the colon precancerous lesions induced by AOM and the small-intestinal injury caused by 5-FU, suggesting that MAK could have potential as a preventive agent against colonic precancer, which is a common adverse effect of chemotherapy.