Development and validation of a survival nomogram and calculator for male patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate and/or enzalutamide.

BACKGROUND: Despite the widespread availability of medication choices for metastatic castration-resistant prostate cancer (mCRPC), biomarkers to predict the efficacy of each mCRPC treatment have not yet been established. This study developed a prognostic nomogram and a calculator to predict the prognosis of patients with mCRPC who received abiraterone acetate (ABI) and/or enzalutamide (ENZ). METHODS: In total, 568 patients with mCRPC who underwent ABI and/or ENZ between 2012 and 2017 were enrolled. A prognostic nomogram based on the risk factors was developed using the Cox proportional hazards regression model and clinically important factors. The discriminatory ability of the nomogram was assessed according to the concordance index (C-index). A 5-fold cross-validation was repeated 2000 times to estimate the C-index, and the means of the estimated C-index for the training and validation sets were determined. A calculator based on this nomogram was then developed. RESULTS: The median overall survival (OS) was 24.7 months. Multivariate analysis showed that the time to CRPC, pre-chemotherapy, baseline prostate-specific antigen, baseline alkaline phosphatase, and baseline lactate dehydrogenase levels were independent risk factors for OS (hazard ratio [HR]: 0.521, 1.681, 1.439, 1.827, and 12.123, p = 0.001, 0.001, < 0.001, 0.019, and < 0.001, respectively). The C-index was 0.72 in the training cohort and 0.71 in the validation cohort. CONCLUSIONS: We developed a nomogram and calculator to predict OS in Japanese patients with mCRPC who received ABI and/or ENZ. Reproducible prognostic prediction calculators for mCRPC will facilitate greater accessibility for clinical use.

A high neutrophil-to-lymphocyte ratio is a poor prognostic factor for castration-resistant prostate cancer patients who undergo abiraterone acetate or enzalutamide treatment.

BACKGROUND: Inflammatory cytokine markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-lymphocyte ratio, and platelet-to-lymphocyte ratio, play important roles as prognostic markers in several solid malignancies, including prostate cancer. We previously reported the NLR as a poor prognostic marker in bladder cancer, upper-urothelial carcinoma, adrenocortical carcinoma, penile cancer, and prostate cancer. This study examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received abiraterone acetate or enzalutamide. METHODS: A total of 805 prostate cancer patients developed in CRPC status were enrolled in this study. Of these patients, 449 received abiraterone acetate (ABI; 188 cases) or enzalutamide (ENZ; 261 cases) treatment, and the pre-treatment NLR values of these patients were obtained. We investigated the prognosis in those with higher and lower NLR values. RESULTS: The median NLR was 2.90, and a receiver operating characteristics analysis suggested a candidate cut-off point of 3.02. The median overall survival (OS) was 17.3 months in the higher NLR group (≥3.02) and 27.3 months in the lower NLR group (< 3.02) (p < 0.0001). This trend was also observed in both the ABI and ENZ groups (ABI: 29.3 vs. 15.1 months; ENZ: NR vs. 19.5 months; p < 0.0001 and < 0.0001, respectively). A multivariate analysis revealed that a higher NLR was an independent risk factor. The NLR value was thus shown to be correlated with the prostate cancer progression. CONCLUSIONS: A higher NLR was associated with a poorer OS for CRPC patients who received ABI or ENZ. The NLR was positively correlated with prostate cancer progression.

[ADOPTION OF ENHANCED RECOVERY AFTER SURGERY (ERAS) PROTOCOL FOR THE MANAGEMENT OF PATIENTS UNDERGOING RADICAL CYSTECTOMY IN JAPAN].

(Objectives) The Enhanced Recovery After Surgery (ERAS) protocols are standardized and multimodal perioperative care pathways designed to improve surgical outcomes by minimizing stress response and inflammation following surgery. First adopted in colorectal surgery, ERAS is now being employed in various other types of surgeries, most recently in patients undergoing radical cystectomy (RC). Implementation of ERAS protocols resulted in reductions in perioperative complication rates and length of hospital stay (LOS). However, information on the adoption of ERAS in patients undergoing RC in Japan is limited. The objective of this study was to evaluate the safety and efficacy of ERAS implemented in the Toyohashi Municipal Hospital in 2017 for the management of patients with RC. (Patients and methods) This was a retrospective study of 103 patients who underwent RC and urinary diversion from January 2012 to March 2019. Of the 103 patients, 71 underwent surgery prior to the introduction of the ERAS were allocated to the 'traditional' group, while 32 were exposed to the ERAS protocol were allocated to the 'ERAS' group. In this study, ERAS included no bowel preparation, preoperative carbohydrate loading, preoperative fluid reduction, preoperative fasting, reduced drainage use, no nasogastric intubation, and early postoperative drinking and eating. A comparative analysis was performed to evaluate LOS and postoperative complication rate (Clavien classification ≥2) after RC between the 'traditional' and 'ERAS' groups. (Results) Patient characteristics and intraoperative variables such as median age, sex, body mass index, clinical and pathological cancer stage, amount of bleeding, need for transfusion, and technique of urinary diversion did not differ between groups. However, duration of surgery was significantly shorter in the ERAS group than in the traditional group (402 min vs. 470 min; P = 0.03). Further, rate of complication was significantly lower (43.8% vs. 67.6%; P=0.03) and LOS after RC was significantly shorter (21 days vs. 28 days; P<0.001) in the ERAS group compared to the traditional group. Moreover, ERAS was an independent factor affecting shorter LOS after RC (OR, 5.22; 95% CI, 1.52-17.90; P = 0.009) in multivariate analyses. (Conclusions) It is possible that the ERAS protocol adopted in this study reduced the LOS and postoperative complication rate after RC at this site in Japan.

Corticobasal ganglia projecting neurons are required for juvenile vocal learning but not for adult vocal plasticity in songbirds.

Birdsong, like human speech, consists of a sequence of temporally precise movements acquired through vocal learning. The learning of such sequential vocalizations depends on the neural function of the motor cortex and basal ganglia. However, it is unknown how the connections between cortical and basal ganglia components contribute to vocal motor skill learning, as mammalian motor cortices serve multiple types of motor action and most experimentally tractable animals do not exhibit vocal learning. Here, we leveraged the zebra finch, a songbird, as an animal model to explore the function of the connectivity between cortex-like (HVC) and basal ganglia (area X), connected by HVC(X) projection neurons with temporally precise firing during singing. By specifically ablating HVC(X) neurons, juvenile zebra finches failed to copy tutored syllable acoustics and developed temporally unstable songs with less sequence consistency. In contrast, HVC(X)-ablated adults did not alter their learned song structure, but generated acoustic fluctuations and responded to auditory feedback disruption by the introduction of song deterioration, as did normal adults. These results indicate that the corticobasal ganglia input is important for learning the acoustic and temporal aspects of song structure, but not for generating vocal fluctuations that contribute to the maintenance of an already learned vocal pattern.

Efficacy of zoledronic acid in older prostate cancer patients undergoing androgen deprivation therapy.

OBJECTIVES: The purpose of this study is to evaluate the efficacy of annual zoledronic acid treatment in Japanese patients with nonmetastatic prostate cancer during androgen deprivation therapy (ADT). METHODS: This is a single institution 12-month study. Between 2016 and 2019, patients aged 70 years or older on ADT for nonmetastatic prostate cancer had bone mineral density (BMD) measured and 10-year probability of fracture calculated using fracture risk assessment tool (FRAX). Patients who showed osteopenia or had a 10-year hip fracture risk ≥ 3% or a 10-year probability of major osteoporotic fracture ≥ 20% were offered treatment with zoledronic acid 5 mg intravenously (ZA group). The patients who did not receive treatment were set as the control group. Lumbar and hip BMD were measured 6 and 12 months after treatment in the ZA group and 12 months after baseline in the control group. The yearly BMD change of both groups was compared. RESULTS: The mean ages of the ZA group (n = 26) and control group (n = 12) were 80.5 ± 9.1 and 76.1 ± 6.7 years, respectively. In the ZA group, lumbar and hip BMD changes at 12 months were +2.1% and +0.8%, respectively. In the control group, lumbar and hip BMD changes were -0.9% and -4.9%, respectively. There were statistically significant differences between the 2 groups in BMD percent changes (P < 0.05). CONCLUSIONS: Without intervention, BMD tends to continue to decrease during ADT. Our findings suggest that administration of zoledronic acid enables maintenance of BMD in the older adults.

[A CASE OF RETROPERITONEAL HEMORRHAGE CAUSED BY THE INSERTION OF A URETERAL ACCESS SHEATH. A RARE COMPLICATION ASSOCIATED WITH FLEXIBLE TRANSURETHRAL LITHOTRIPSY (fTUL)].

A 77-year-old man with a right kidney stone was admitted to our hospital. A ureteroscope was introduced into the ureter without dilation under direct vision. We then performed flexible transurethral lithotripsy (f-TUL) using a ureteral access sheath and successfully fragmented the stone and extracted almost all the stone fragments without any complications. Just 3 hours after the operation, he suddenly developed right abdominal pain with a decrease in hemoglobin. A CT scan showed a retroperitoneal hemorrhage around the lower ureter. We herein describe a rare complication associated with flexible transurethral lithotripsy.

CHARACTERISTICS OF STRESS URINARY INCONTINENCE AFTER PELVIC ORGAN PROLAPSE SURGERY.

(Objective) We examined the morphology and function of lower urinary tract in order to know characteristics of stress urinary incontinence after pelvic organ prolapse (POP) surgery. (Methods) One hundred twenty-five female patients (mean age 64.9 years, mean parity 2.2, mean body mass index (BMI) 24.4) were performed anti-incontinence surgery for stress urinary incontinence. Sixty-one of 125 patients underwent POP surgery before anti-incontinence surgery. They were divided into groups as follows: post-POP surgery group and non-POP surgery group. All patients underwent one-hour pad test, chain cystourethrography (chain CG), Urodynamic studies (UDS) as preoperative assessment. Midurethral sling procedure was performed as an anti-incontinence surgery. Preoperative assessment criteria and postoperative treatment results were compared between two groups. (Results) Post-POP surgery group showed a significantly greater amount of urinary leakage per 1-hour pad test than non-POP surgery group (65.2±74.3 g vs 14.3±25.2 g, p<0.05). The diagnosis of type III urinary stress incontinence (Blaivas' classification) was more frequently diagnosed in post-POP surgery group than non-POP surgery group (50.0% vs 25.0%, p<0.05). Maximum urethral closure pressure (MUCP) and functional profile length (FPL) of post-POP surgery group were lower than those of non-POP surgery group (27.4±9.2 vs 35.7±14.7, p<0.05, 27.3±4.7 vs 29.9±5.0, p<0.05). Postoperative treatment results of post-POP surgery group were worse than those of non-POP surgery group (78.7% vs 92.2%, p<0.05). (Conclusions) Post-POP surgery group showed more severe urinary incontinence, lower urinary function and lower cure rate. Therefore we should keep in mind when approaching urinary stress incontinence.

[Study on the treatment of pelvic organ prolapse complicated with uterine myoma].

OBJECTIVE: We studied the association between uterine myoma and recurrent pelvic organ prolapse (POP) after transvaginal mesh (TVM) repair. METHODS: Between June 2010 and January 2012, 103 female patients (mean age 67.8 years, mean parity 2.3, mean body mass index (BMI) 23.7) with POP underwent TVM procedures at our hospital. Sixtynine patients were qualified as stage 3 according to the POP quantification (POP-Q) system and 34 patients were stage 4. Twenty-six patients underwent anterior TVM (A-TVM) and 77 patients underwent anterior and posterior TVM (AP-TVM). All patients underwent a physical examination using the POP-Q system before and 6 month after surgery. Recurrence of prolapse was defined according to the International Continence Society by a measured value ≥ - 1, as most dependent portion of POP stage 2 or greater. One hundred-three patients were divided into group with uterine myoma larger than 5 cm in diameter and group without uterine myoma. Anatomical outcomes before and after TVM repair were compared between two groups. RESULTS: Preoperative Aa value, Ba value and gh value in group with uterine myoma were greater than in group without uterine myoma. Postoperative Aa value and Ba value in group with uterine myoma were greater than in group without uterine myoma, too. Postoperative recurrence of prolapse of stage 2 or greater was not found a statistical difference between two groups. CONCLUSIONS: The risks of anterior vaginal wall descent seem to be high in POP with uterine myoma. Therefore it should be kept in mind on treatment choice.