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author:("Fukui, iwat")
1.  Clinical outcome of patients with pancreatic metastases from renal cell cancer 
BMC Cancer  2015;15:46.
Background
Renal cell cancer (RCC) is one of the most frequent primary sites for metastatic pancreatic tumors although metastatic tumors are rare among pancreatic malignant tumors. The purpose of this study is to disclose the characterization and treatment outcomes of pancreatic metastases from RCC.
Methods
Of 262 patients with metastatic RCC treated at our hospital between 1999 and 2013, the data of 20 (7.6%) who simultaneously developed or subsequently acquired pancreatic metastases were retrospectively reviewed and statistically analyzed.
Results
The median follow-up period from RCC diagnosis and pancreatic metastases was 13.4 years (inter-quartile range: IQR, 7.8–15.5 years) and 3.8 years (IQR, 2.1–5.5 years), respectively. Median duration from diagnosis of RCC to pancreatic metastasis was 7.8 years (IQR, 4.2–12.7 years). During this observation period, the estimated median overall survival (OS) time from the diagnosis of RCC to death or from pancreatic metastasis to death was not reached. The probability of patients surviving after pancreatic metastasis at 1, 3, and 5 years was 100, 87.7, and 78.9%, respectively. The estimated OS period from the diagnosis of metastases to death of the patients with pancreatic metastasis was significantly longer than that of the patients with non-pancreatic metastasis (median OS 2.7 years) (P < 0.0001). Surgical management for pancreatic metastasis was performed in 15 patients (75%). When the median follow-up period for these surgeries was 3.5 years (IQR, 1.9–5.2 years), the estimated median recurrence-free survival was 1.8 years. For the patients with multiple metastatic sites, molecularly targeted therapies were given to six (30%) patients. When the median follow-up period was 4.1 years (IQR, 3.0–4.4 years), no disease progression was observed.
Conclusions
The pancreas is frequently the only metastatic site and metastasis typically occurs a long time after nephrectomy. The OS period of these patients is long and both surgical and medical treatment resulted in good outcomes.
doi:10.1186/s12885-015-1050-2
PMCID: PMC4332740
Renal cell cancer; Outcome; Pancreas metastasis; Prognostic factor; Pseudocapsule
2.  Longitudinal change in health-related quality of life after intensity-modulated radiation monotherapy for clinically localized prostate cancer 
Quality of Life Research  2013;23(5):1641-1650.
Abstract
Purpose
The purpose of the study is to assess longitudinal changes in general and disease-specific health-related quality-of-life (HRQOL) indices after intensity-modulated radiotherapy (IMRT) monotherapy for patients with localized prostate cancer (PCA).
Methods
Between 2006 and 2010, 91 patients with localized PCA underwent IMRT monotherapy and were enrolled into this prospective study. At baseline, and at 3, 6, 12, and 24 months after IMRT, the general and prostate-specific HRQOL were estimated using physical (PCS) and mental component summaries (MCS) calculated using the Medical Outcomes Study 8-Item Short Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC).
Results
For 2 years, there were no significant changes in EPIC scores in all subscales of urinary domain, hormonal function, and bother. Bowel and sexual function scores decreased after IMRT and did not return to those at baseline (p = 0.006 and < 0.001, respectively). PCS began to decrease at 3 months after IMRT and then returned to the baseline score at 24 months. In contrast, the MCS score began to significantly increase after IMRT, and thereafter the score remained constant until 24 months (p < 0.001). On multivariate logistic regression analysis, urinary (p = 0.003) and sexual functions (p = 0.0005) at baseline were identified as significant predictors of EPIC urinary irritative/obstructive score and sexual function at 24 months after IMRT.
Conclusion
Urinary function, including irritative/obstruction symptoms and hormonal function, was not affected by IMRT. However, bowel and sexual function decreased after IMRT. These findings will provide important information for PCA patients considering IMRT.
doi:10.1007/s11136-013-0603-6
PMCID: PMC4031389  PMID: 24338068
Prostate cancer; Quality of life; Radiotherapy; Intensity-modulated
3.  Denosumab: a new option in the treatment of bone metastases from urological cancers 
OncoTargets and therapy  2012;5:221-229.
Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the RANK ligand (RANKL), and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA), a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers.
doi:10.2147/OTT.S30578
PMCID: PMC3457675  PMID: 23055747
bone metastasis; denosumab; prostate cancer; renal cell cancer; urothelial cancer; zoledronic acid
4.  A novel equation and nomogram including body weight for estimating prostate volumes in men with biopsy-proven benign prostatic hyperplasia 
Asian Journal of Andrology  2012;14(5):703-707.
Anthropometric measurements, e.g., body weight (BW), body mass index (BMI), as well as serum prostate-specific antigen (PSA) and percent-free PSA (%fPSA) have been shown to have positive correlations with total prostate volume (TPV). We developed an equation and nomogram for estimating TPV, incorporating these predictors in men with benign prostatic hyperplasia (BPH). A total of 1852 men, including 1113 at Tokyo Medical and Dental University (TMDU) Hospital as a training set and 739 at Cancer Institute Hospital (CIH) as a validation set, with PSA levels of up to 20 ng ml−1, who underwent extended prostate biopsy and were proved to have BPH, were enrolled in this study. We developed an equation for continuously coded TPV and a logistic regression-based nomogram for estimating a TPV greater than 40 ml. Predictive accuracy and performance characteristics were assessed using an area under the receiver operating characteristics curve (AUC) and calibration plots. The final linear regression model indicated age, PSA, %fPSA and BW as independent predictors of continuously coded TPV. For predictions in the training set, the multiple correlation coefficient was increased from 0.38 for PSA alone to 0.60 in the final model. We developed a novel nomogram incorporating age, PSA, %fPSA and BW for estimating TPV greater than 40 ml. External validation confirmed its predictive accuracy, with AUC value of 0.764. Calibration plots showed good agreement between predicted probability and observed proportion. In conclusion, TPV can be easily estimated using these four independent predictors.
doi:10.1038/aja.2012.31
PMCID: PMC3735003  PMID: 22773012
body weight; equation; nomogram; prediction; prostate-specific antigen; prostate volume
5.  GABAergic inhibition sharpens the frequency tuning and enhances phase locking in chicken nucleus magnocellularis neurons 
The Journal of Neuroscience  2010;30(36):12075-12083.
GABAergic modulation of activity in avian cochlear nucleus neurons has been studied extensively in vitro. However, how this modulation actually influences processing in vivo is not known. We investigated responses of chicken nucleus magnocellularis (NM) neurons to sound while pharmacologically manipulating the inhibitory input from the superior olivary nucleus (SON). SON receives excitatory inputs from nucleus angularis (NA) and nucleus laminaris (NL), and provides GABAergic inputs to NM, NA, NL, and putatively to the contralateral SON. Results from single unit extracellular recordings from 2–4 wks posthatch chickens show that firing rates of auditory nerve fibers (ANFs) increased monotonically with sound intensity, while that of NM neurons saturated or even decreased at moderate or loud sound levels. Blocking GABAergic input with local application of TTX into the SON induced an increase in firing rate of ipsilateral NM while that of the contralateral NM decreased at high sound levels. Moreover, local application of bicuculline to NM also increased the firing rate of NM neurons at high sound levels, reduced phase-locking, and broadened the frequency tuning properties of NM neurons. Following application of DNQX, clear evidence of inhibition was observed. Furthermore, the inhibition was tuned to a broader frequency range than the excitatory response areas. We conclude that GABAergic inhibition from SON has at least three physiological influences on the activity of NM neurons: it regulates the firing activity of NM units in a sound-level dependent manner; it improves phase selectivity; and it sharpens frequency tuning of NM neuronal responses.
doi:10.1523/JNEUROSCI.1484-10.2010
PMCID: PMC3376706  PMID: 20826670
Superior olivary nucleus; Cochlear nucleus; Bicuculline; GABA; Auditory; In vivo

Results 1-5 (5)