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Since most patients with metastatic castration-resistant prostate cancer (mCRPC) have bone metastases, it is important to understand the potential impact of therapies on prognostic biomarkers, such as ALP. Clinical studies involving mCRPC life-prolonging agents (i.e., sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, and radium-223) have shown that baseline ALP level is prognostic for overall survival, and may be a better prognostic marker for overall survival than prostate-specific antigen in patients with bone-dominant mCRPC. Mechanism of action differences between therapies may partly explain ALP dynamics during treatment. ALP changes can be interpreted within the context of other parameters while monitoring disease activity to better understand the underlying pathology. This review evaluates the current role of ALP in mCRPC.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.

Background and Aims: Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) is an effective procedure for the treatment of male infertility, obstructive and non‐obstructive azoospermia. We have reviewed our experience to investigate the correlation of TESE‐ICSI with morphological, biophysical and endocrine profiles in 27 men.

Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L

The aim of this study was to identify the clinical predictors related to the risk of high-grade papillary bladder cancer before first-time transurethral resection of a bladder tumor (TUR-Bt), and to develop and validate a nomogram predicting the risk of high-grade papillary bladder cancer. A retrospective clinical study of consecutive patients who underwent first-time TUR-Bt for papillary bladder cancer was performed. Medical records were reviewed uniformly, and the following data were collected: age, sex, episodes of urinary symptoms, tumor size, number of tumors, location of the largest tumor (lateral walls, base, posterior wall, dome, and anterior wall), tumor appearance (papillary or non-papillary, pedunculated or sessile), and urinary cytology. Data from 254 patients (Group A) were used for the development of a nomogram, while data from 170 patients (Group B) were used for its external validation. High-grade papillary bladder cancer was pathologically diagnosed in 51.6 and 74.6% of Group A and Group B patients, respectively. Based on univariable analyses in Group A, macrohematuria, tumor size, multiple tumors, appearance, and positive urinary cytology were selected as variables to incorporate into a nomogram. The AUC value was 0.81 for the internal validation (Group A), and 0.78 for the external validation (Group B). This novel nomogram can predict high-grade papillary bladder cancer accurately. The present nomogram can help clinicians calculate the probability in patients with bladder cancer before TUR-Bt and decide on earlier intervention and priorities for the treatment of patients diagnosed with bladder cancer.

Background: In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics. Objective: To present the report of APCCC 2017. Design, setting, and participants: Ten important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; "oligometastatic" prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process. Results and limitations: Voting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data. Conclusions: The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them. Patient summary: The second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process. At the Advanced Prostate Cancer Consensus Conference, 10 important areas of controversy in advanced prostate cancer management were identified, discussed, and the experts voted on 150 predefined consensus questions. The full report of the results is summarised here.

A 74-year-old female patient, who was diagnosed with neurofibromatosis type 1 (NF1) at the age of 40, was admitted with complaints of flickering vision and gait disturbance for the last 2 years. On admission, neurological examination revealed mild bilateral hearing loss and ataxia in the limb and trunk. Laboratory tests revealed anti-hepatitis C virus (HCV) antibody positivity and elevated HCV RNA by real-time polymerase chain reaction. The cerebrospinal fluid examination revealed a slightly yellowish appearance with elevated total protein levels. Gradient echo T2*-weighted brain magnetic resonance imaging (MRI) demonstrated a rim of hypointense lesions surrounding the surface of the cerebellum, brainstem, frontal and temporal lobes, and thalamus, which was considered as hemosiderin depositions. From these MRI findings, she was diagnosed as having superficial siderosis of the central nervous system. Cerebral angiography revealed an aneurysm-like dilatation at the bifurcation of the right internal carotid-posterior communicating artery. (99m)Tc-ethyl cysteinate dimer single-photon emission computed tomography revealed hypoperfusion in the bilateral frontal and temporal lobes. Pelvic plain X-ray, pelvic computed tomography, and lumbosacral MRI revealed a sacral defect and an anterior sacral polycystic meningocele communicating with the spinal subarachnoid space. The patient's symptoms gradually worsened, and she died of septic shock because of pyelonephritis at the age of 77. An autopsy was performed; on pathological examination, we did not observe any findings associated with rupture of the aneurysm-like dilatation in the bifurcation of the right internal carotid-posterior communicating artery and cerebral amyloid angiopathy. Because duropathies-a new neurological disease concept-have been implicated as a cause of bleeding in the superficial siderosis, the anterior sacral polycystic meningocele, a type of duropathies, was presumed to be the most probable bleeding source of the superficial siderosis in this patient. Bleeding from the meningocele might result from the vulnerability of vessel walls in NF1.

We examined the clinical significance of long-term serum testosterone monitoring to predict the prognosis of patients with prostate cancer treated with combined androgen blockade.We retrospectively analyzed the records of 225 patients who underwent combined androgen blockade as first line therapy for prostate cancer. The prognostic values of testosterone and other clinical factors were evaluated with respect to prostate specific antigen progression-free and overall survival.Median patient age was 73.0 years, median prostate specific antigen was 42.6 ng/ml and median followup was 45.8 months. No variable associated with testosterone was predictive of progression-free survival. With regard to overall survival on univariate analysis nadir testosterone less than 16 ng/dl (p = 0.0190), less than 20 ng/dl (p = 0.0020) and less than 32 ng/dl (p = 0.0146) were significant together with other clinical factors. In contrast, nadir testosterone less than 8 and less than 12 ng/dl were not significant. Multivariate analysis showed that nadir testosterone less than 20 ng/dl was the significant prognostic factor (p = 0.0048). In addition, time to nadir testosterone was about 1 year (11.3 months). Patients were divided into rapid and slow types based on time to testosterone less than 20 ng/dl before and after 6 months, respectively. No significant difference in overall survival was observed between the 2 types. The current results suggest that the critical factor for prognosis was not a rapid decrease but whether nadir testosterone achieved a level of less than 20 ng/dl.Nadir testosterone 20 ng/dl was the most significant cutoff level for overall survival in Japanese patients with prostate cancer treated with combined androgen blockade.

Objectives To validate the ability of contemporary active surveillance protocols to predict pathologically insignificant prostate cancer among Asian men undergoing radical prostatectomy. Methods We retrospectively reviewed data on 132 patients eligible for any active surveillance criteria out of 450 patients that underwent radical prostatectomy at several institutions between 2006 and 2013. We validated the ability of seven contemporary active surveillance protocols to predict pathologically insignificant prostate cancer. Traditional and updated criteria to define pathologically insignificant prostate cancer were used. Predictive factors for pathologically insignificant prostate cancer were determined by logistic regression analysis. Results The predictive rate for updated pathologically insignificant prostate cancer of respective active surveillance criteria was 51% for Johns Hopkins Medical Institution, 41% for Prostate Cancer Research International: Active Surveillance Study, 39% for University of Miami, 32% for University of California, San Francisco, 32% for Memorial Sloan-Kettering Cancer Center, 31% for Kakehi and 27% for University of Toronto. Predictive rates for pathologically insignificant prostate cancer in Asian men were far lower than in USA men. On multivariate analysis, predictive factors of updated pathologically insignificant cancer was prostate volume (odds ratio 1.07, P = 0.004). By adding prostate volume to Prostate Cancer Research International: Active Surveillance Study criteria, the predictive rate for updated insignificant prostate cancer was improved up to 66.7%. Conclusions Active surveillance can be carried out considering the clinical characteristics of prostate cancers depending on ethnicity, as current active surveillance criteria seem to have a lower predictive ability value of insignificant prostate cancer in Asian men compared with men in Western countries.

Many patients with primary aldosteronism (PA) show a significant decline in kidney function after adrenalectomy. Thus, PA patients who undergo surgery are at greater risk of both postoperative renal damage and new-onset metabolic events associated with renal insufficiency. The aim of this study was to explore postoperative changes in serum lipid levels and to identify risk factors associated with postoperative new-onset dyslipidemia in PA patients. The records of 57 Japanese patients who underwent unilateral laparoscopic adrenalectomy for PA were retrospectively surveyed. Clinical and biochemical data were evaluated at baseline and 12 months after surgery. Preoperative and postoperative estimated glomerular filtration (eGFR) and serum lipid profile, including triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol levels, were compared. Furthermore, uni- and multivariate analyses were performed to determine the predictors for postoperative new-onset dyslipidemia. A significant decrease in eGFR and deterioration of serum lipid levels was identified postoperatively in most patients. Of the 39 patients without pre-existing dyslipidemia, 18 developed new-onset dyslipidemia postoperatively. Multivariate analysis identified preoperative lower eGFR and higher body mass index as independent predictors for new-onset dyslipidemia after surgery. On univariate analyses, additional factors associated with new-onset dyslipidemia included older age, male sex, higher LDL-cholesterol, and higher LDL/HDL ratio. PA patients had a higher risk of postoperative new-onset or progressive dyslipidemia. Clinicians should pay attention to not only follow-up of renal impairment but also total management of new-onset metabolic events associated with renal insufficiency in PA patients.

To explore arterial stiffness during the administration of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa), a new indicator, the cardio-ankle vascular index (CAVI), and serum lipid profile changes were monitored. A prospective study assessed the changes in arterial stiffness using the CAVI and clinical laboratory variables among 58 men with prostate cancer treated with ADT for 6 months. Furthermore, patients who had a high risk of developing arterial stiffness after ADT were investigated. The whole cohort had no significant increase in arterial stiffness within 6 months after ADT, but 55.2 % of patients had an increased CAVI. Serum levels of total cholesterol, high-density-lipoprotein cholesterol (HDL-C), and low-density-lipoprotein cholesterol (LDL-C) increased significantly at 1 month after the start of ADT and maintained high values thereafter. At baseline, HDL-C was lower and LDL-C and LDL-C/HDL-C were higher in the group with than without an increased CAVI after 6 months of ADT administration. Although the whole cohort did not show a significant change in arterial stiffness with ADT, some patients showed an increased arterial stiffness monitored with the CAVI. The balance between LDL-C and HDL-C, or LDL-C/HDL-C, might have an impact on the development of arterial stiffness after ADT administration. Thus, clinicians might be able to monitor PCa patients who have a high risk of development of arterial stiffness after ADT administration by referring to LDL-C/HDL-C levels.

We describe an autopsy case of basophilic inclusion body disease (BIBD), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused in sarcoma (FUS) inclusions (FTLD-FUS), clinically presenting corticobasal syndrome (CBS). A 54-year-old man initially developed worsening of stuttering and right hand clumsiness. Neurological examinations revealed rigidity in the right upper and lower extremities, buccofacial apraxia, and right-side dominant limb-kinetic and ideomotor apraxia. Neuroimaging showed asymmetric left-dominant brain atrophy and a cerebral blood flow reduction in the ipsilateral frontal region. At 56 years, his apraxia had advanced, and ideational apraxia was observed. Furthermore, the asymmetry in the limb-kinetic and ideomotor apraxia had disappeared, and both conditions had become bilateral. He had a new onset of aphasia. His symptoms progressed and he died 9 years after the initial symptoms. The brain weighed 955 g. Diffuse brain atrophy was most obvious in the bilateral frontotemporal regions. The atrophy of the left superior frontal and precentral gyri and bilateral basal ganglia was remarkable. Histologically, there was a marked loss of neurons with gliosis in the affected areas, where basophilic neuronal cytoplasmic inclusions were observed. The inclusions were immunoreactive for FUS, p62, and TATA-binding protein-associated factor 15 (TAF15), but not for phosphorylated tau, transactive response DNA-binding protein of 43 kDa (TDP-43), neurofilament protein, or Ewing sarcoma (EWS). From these pathological findings, this case was diagnosed as having BIBD as an FTLD-FUS variant. Spinal cord lower motor neurons were spared in number, similar to primary lateral sclerosis. Mutations in FUS were undetectable. Common background pathologies for CBS include corticobasal degeneration, Alzheimer's disease, PSP, FTLD with phosphorylated TDP-43 inclusions (FTLD-TDP), Pick's disease, Lewy body disease and CJD. However, FTLD-FUS (BIBD) has been rarely reported. Our case suggested further pathological heterogeneity in CBS than had previously been reported. It is necessary to consider FTLD-FUS (BIBD) as a background pathology for CBS in the future.

Background: Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds. Methods: We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations. Results: Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation. Conclusions: A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.

Leiomyoma usually originates from the uterus and alimentary tract, but in extremely rare cases leiomyoma can appear in the external auditory canal. Here we present a 37-year-old man with right auricular fullness. Preoperative findings suggested benign tumor or cholesteatoma in the right external auditory canal. We performed total resection using an endoauricular approach with transcanal endoscopic ear surgery. Histopathological and immunohistochemistry examination confirmed the diagnosis of leiomyoma of external auditory canal. Leiomyoma arising from soft tissue, including that in the external auditory canal, is classified into two types: that from the arrectores pilorum muscles and that from the muscle coats of blood vessels. Only four cases of leiomyoma of external auditor canal have been published in the English literature. The other four cases demonstrated vascular leiomyomas. This is the first report of leiomyoma of the EAC arising from arrectores pilorum muscles.

Androgen deprivation therapy continues to be a mainstream treatment for prostate cancer. Failure after initial hormonal treatment including combined androgen blockade (CAB)/maximum androgen blockade (MAB) does not necessarily imply treatment-refractory disease progression. Antiandrogen withdrawal syndrome (AWS) is a manifestation of a prostate-specific antigen (PSA) decrease with or without subjective or objective symptomatic improvement on discontinuation of the antiandrogen. In general, the incidence of this effect has been reported to be 10–30%, and it lasts for 3–5 months. Some patients with progressive disease who have undergone initial CAB/MAB therapy respond to second- and third-line hormonal therapy after AWS is recognized. Mutations in the androgen receptor (AR) gene are thought to account for this phenomenon by enabling the previous antiandrogens to act as receptor agonists. Alternative antiandrogens probably have different functional interactions with the AR. Alternative antiandrogen therapy has been shown to improve symptoms and decrease pain in patients with prior antiandrogen therapy. A 50% PSA decrease has been reported after second-line treatment with nonsteroidal antiandrogens in 35–50% of cases. Responders to second-line hormonal treatment are expected to survive significantly longer than nonresponders. Responsiveness to second-line regimens is the most important prognostic factor for increased cause-specific and overall survival.

Telomerase reverse transcriptase (TERT) is important for the biology of diffuse gliomas.TERTpromoter mutations are selectively observed among 1p/19q-codeleted oligodendrogliomas and isocitrate dehydrogenase gene-(IDH-)wildtype glioblastoma (GBM). However, TERT transcripts range widely in various cancers including gliomas, and TERT protein expression has been rarely investigated thus far. It would be thus critical to examine the expression level of TERT in tumors in addition to its mutational status, and sensitive and specific methods are urgently needed to examine TERT protein expression for the assessment of TERT biology in gliomas. Using our newly developed TERT-specific monoclonal antibody (TMab-6) applicable to human tissue, we found an unexpected increase in TERT expression inTERT-wildtype as well asTERT-mutated gliomas and in tumor vasculature. This is the first extensive analysis on the expression of TERT immunoreactivity in human glioma tissue, suggesting that TERT protein expression may be regulated by several mechanisms in addition to its promoter mutation.

A 73-year-old man was incidentally diagnosed with a cystic lesion in the pancreatic body. Ultrasonography, abdominal computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasound were performed, and a nodule was detected in the cystic lesion along with an irregularity of the main pancreatic duct. An initial diagnosis of a mixed-type intraductal papillary mucinous neoplasm was made, and a central pancreatectomy was performed. However, the final diagnosis was altered to non-invasive intraductal papillary mucinous carcinoma (IPMC). The histopathological examination revealed a fibrotic lesion that was similar to "tubular complex" findings observed in mouse models of pancreatic cancer. The fibrotic lesion was placed between the main pancreatic duct lesion and branch-duct cystic lesion. The changes reflected in branch-level stenosis may be caused by IPMC growth.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H

A 26-year-old right-handed woman, with a history of left temporal lobe contusion caused by a fall at the age of 9 months, started to have complex partial seizures with oral automatism at the age of 7 years. The seizures occurred once or twice a month despite combination therapy with several antiepileptic agents. Her history and imaging studies suggested the diagnosis of epilepsy arising from traumatic neocortical temporal lesion. Comprehensive assessment including long-term video EEG monitoring, MRI, FDG-PET, MEG, and neuropsychological evaluation was performed at the age of 26 years. The diagnosis was left mesial temporal lobe epilepsy associated with hippocampal atrophy and traumatic temporal cortical lesion. The patient was readmitted for surgical treatment at the age of 27 years. Intracranial EEG monitoring showed that ictal discharges started in the left hippocampus and spread to the traumatic lesion in the left posterior superior temporal gyrus 10 seconds after the onset. This case could not be classified as dual pathology exactly, because the traumatic left temporal cortical lesion did not show independent epileptogenicity. However, the traumatic lesion was highly likely to be the source of the epileptogenicity, and she had right hemispheric dominance for language and functional deterioration in the whole temporal cortex. Therefore, left amygdalo-hippocampectomy and left temporal lobectomy including the traumatic lesion were performed according to the diagnosis of dual pathology. Subsequently, she remained seizure-free for 3 years. Comprehensive assessment of seizure semiology, neurophysiology, neuroradiology, and neuropsychology is important to determine the optimum therapeutic strategies for drug-resistant epilepsy.

The present study aimed to validate and compare the predictive accuracies of the Memorial Sloan Kettering Cancer Center (MSKCC) and Johns Hopkins University (JHU) web-based postoperative nomograms for predicting early biochemical recurrence (BCR) after radical prostatectomy (RP) and to analyze clinicopathological factors to predict early BCR after RP using our dataset. The c-index was 0.72 (95% confidence (CI): 0.61-0.83) for the MSKCC nomogram and 0.71 (95% CI: 0.61-0.81) for the and JHU nomogram, demonstrating fair performance in the Japanese population. Furthermore, we statistically analyzed our 174 patients to elucidate prognostic factors for early BCR within 2 years. Lymphovascular invasion (LVI) including lymphatic vessel invasion (ly) was a significant predictor of early BCR in addition to common variables (pT stage, extraprostatic extension, positive surgical margin and seminal vesicle invasion). LVI, particularly ly, may provide a good predictor of early BCR after RP and improve the accuracy of the nomograms.

Objective The purpose of this study was to clarify clinical features, outcomes, and the role of tumor resection in precocious, synchronous, and metachronous brain metastases. Methods Brain metastases were found before primary cancer detection in the precocious group, within 2 months after primary cancer detection in the synchronous group, and 2 months or later after primary cancer detection in the metachronous group. Results Of 471 patients with brain metastases, 93 (20%) were included in the precocious group, 76 (16%) in the synchronous group, and 302 (64%) in the metachronous group. The precocious group tended to be symptomatic, show a low Karnofsky Performance Status, and have a large single tumor, infrequent extracranial metastases, and frequent tumor resection compared with the other 2 groups. There were no differences in overall survival from the detection of brain metastases among the 3 groups in univariate and multivariate analyses. Of 471 cases, 97 (21%) underwent surgeries. Among this surgical cohort, overall survival from surgery was significantly shorter in the precocious group than in the metachronous group (P = 0.039). After adjustment for age, sex, tumor size, primary cancer, and the Graded Prognostic Assessment score, the hazard ratio for metachronous metastases was 0.52 (confidence interval, 0.29–0.95; P = 0.035). Conclusions The timing of brain metastasis diagnosis is not a modifiable factor but affects patient demographics and treatment strategies. In particular, the precocious group is a unique subset of brain metastases that require special consideration during clinical decision making.

During riserless drilling operations, which are carried out in some scientific drillings and in the initial stages of all drilling operations in oil and gas exploration, a lifting force is generated in addition to a drag forces in ocean current environment owing to the ocean current and the rotation of the drill pipe. This is called the Magnus effect, and it is a critical phenomenon during such operations. First, the lifting and drag forces are calculated using the computational fluid dynamic (CFD), and the lift and drag coefficients are calculated for several rotational velocities of the drill pipe and the velocities of the ocean current. It can be observed through the calculations that the lifting force increases as the rotational velocity of the drill pipe increases, and it reaches a level of approximately several times that of the drag force. The force reaches such a considerably high magnitude that it can induce the motions of the drill pipe, resulting in the generation of a high bending moment. An analytical model of a drill pipe has been established by applying an absolute nodal coordinate formulation (ANCF), which can express a relatively flexible and long pipe, such as a drill pipe. ANCF is a finite element method, and was basically developed to analyze deformable linear objects such as the cable. With ANCF, the absolute slopes of elements are defined based on the absolute nodal coordinate. Finally, the drill pipe motions are simulated using the established model by applying the results of CFD simulations for sample cases and referencing the operation of the Chikyu.

The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high-risk or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow-up time was 88.4 months, and the 5-/10-year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9-10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10-year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10-year follow-up (10-year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P

An important clinical question of great interest to clinicians is how to best sequence androgen receptor targeted agents (ARTAs) and chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), but the answer is still unclear.To evaluate and compare the clinical outcomes of ARTA and docetaxel (DTX) as second-line treatment in the post first-line ARTA, we conducted a retrospective analysis of chemotherapy-naive mCRPC patients who had received sequential treatment with ARTA followed by another ARTA (ARTA-ARTA) or ARTA followed by DTX (ARTA-DTX).A total of 97 patients were treated with the ARTA-ARTA sequence and 42 with the ARTA-DTX sequence. A prostate-specific antigen (PSA) response to the second-line treatment was observed in 18.6% in the ARTA-ARTA and in 33.3% in the ARTA-DTX sequence, but the difference in PSA response was not statistically significant (P = .057). The median progression-free survival (PFS) was significantly different between ARTA and DTX in the second-line treatment (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.24-0.59; P .001). The favorable outcome in the ARTA-DTX sequence compared with the ARTA-ARTA sequence remained (HR, 0.51, 95% CI, 0.33-0.80; P = .004) in the combined PFS (first-line PFS + second-line PFS). However, no statistically significant difference in overall survival (OS) between the 2 groups was observed (HR, 0.60; 95% CI, 0.34-1.09; P = .095). In multivariate analysis, the ARTA-DTX sequence was identified as an independent prognostic factor for combined PFS, but not OS.ARTA-DTX might improve clinical outcomes in terms of second-line PFS and combined PFS, compared with the ARTA-ARTA sequence. However, this significance was not observed for OS.

SummaryAdrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively.

The aim of this study was to determine if molecular alterations are associated with tumor location and radiological characteristics in anaplastic gliomas. We performed a retrospective analysis of 122 anaplastic gliomas for molecular alterations (IDH1/2 mutations, TP53 mutations, and 1p19q co-deletion) to compare MRI features (location and image characteristics). We observed that IDH mutation is strongly associated with frontal location (P = 0.001). However, 13 tumors not located in the cerebral cortex were IDH intact tumors (P

Objective: Abiraterone acetate has been approved in .70 countries for chemotherapy-naive metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naive Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods: Men, � 20 years, with prostate-specific antigen levels of � 5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy end- point was proportion of patients achieving a prostate-specific antigen decline of � 50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. Results: A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was .35% (threshold re- sponse rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: 266.62%. Median prostate-specific antigen response duration and progression- free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event .Grade 1/2. Conclusions: Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naive metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical trial registration no: NCT01756638.

Anaplastic gliomas and glioblastomas are aggressive brain tumors with median survival times ranging from 72.1 to 82.6 months in anaplastic gliomas and 14.6 months in glioblastomas.1,2 One of the main causes of the poor prognosis is chemo- and radioresistance. Thus, elucidation of mechanisms underlying this resistance is urgent to improve the treatment outcomes of malignant gliomas. The system involving Kelch-like ECH (erythroid cell-derived protein with cap'n'collar homology)-associated protein 1 (KEAP1) and nuclear factor erythroid 2–related factor 2 (NRF2) plays pivotal roles in protecting normal and neoplastic cells from oxidative and electrophilic insults by activating cytoprotective genes. These gene products are involved in glutathione synthesis (eg, glutamate cysteine ligase of catalytic [GCLC] and of modifier subunit [GCLM] genes), reactive oxygen species (ROS) elimination, xenobiotic metabolism (eg, NAD(P)H:quinone oxidoreductase gene [NQO1]), and crossmembrane transport, often resulting in multidrug resistance.3 Under normal conditions, KEAP1 ubiquitinates NRF2, and NRF2 is degraded by the proteosome. In the presence of electrophiles or ROS, KEAP1 is inactivated, and NRF2 is stabilized, binds to antioxidant response elements (AREs), and induces the cytoprotective genes. Recently, constitutive activation of NRF2 was found in various cancers. Multiple causes of the constitutive activation of NRF2 have been described, including somatic mutations of KEAP1 or NRF2, reduced expression of KEAP1, and accumulation of p62.4 Increased NRF2 activity confers cell growth advantage and resistance to chemo- and radiotherapy on lung, prostate, gallbladder, and ovarian cancers5–9 and leads to poor prognosis in lung, esophagus, gallbladder, and breast cancers.10–14 Although similar impacts of NRF2 activation on glioblastoma cell lines and a small cohort of glioblastoma patients have been reported,15,16 the prognostic significance of NRF2 activation in malignant gliomas remains to be elucidated. Somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene or IDH2 gene have been identified in adult gliomas.17–19 These mutations occur at a very early stage of gliomatogenesis and confer genetic and prognostic differences on anaplastic gliomas and glioblastomas.17–19 Malignant gliomas with IDH1/2 mutations had better prognoses than those with wild-type IDH1/2.17–19 Although the hypermethylated phenotype is frequently found in World Health Organization grades II and III gliomas with IDH1/2 mutations, underlying mechanisms for better prognosis remain unclear. Recently, IDH1 mutations have been shown to sensitize glioma cells to bis-chloroethylnitrosourea (BCNU)–induced oxidative stress by decreasing the amount of the reduced form of glutathione.20 Because the synthesis and reduction of glutathione is often heavily dependent on NRF2 activity,4 we hypothesized that the NRF2 pathway was suppressed in the presence of mutated IDH1, leading to the better prognosis of malignant gliomas with IDH1/2 mutations. To test this hypothesis, we characterized the prevalence, possible causes, and prognostic value of the NRF2 activation in anaplastic gliomas with mutated or wild-type IDH1/2 and glioblastomas. We also evaluated the association between IDH1/2 mutations and NRF2 activity by analyzing the expression of NRF2 and its target genes in surgical specimens, and confirmed the effect of IDH1 mutation on NRF2 activity, using IDH1 mutant-expressing cells.

Renal cell carcinoma expresses CXCR3 but the function of CXCR3 in renal cell carcinoma has not been clarified. We explored the function of CXCR3 in renal cell carcinoma and investigated CXCR3 regulating factors.We obtained 56 clinical samples of clear cell renal cell carcinoma and corresponding normal renal tissue samples from the surgical specimens of Japanese patients who underwent radical nephrectomy at Chiba University Hospital between 2000 and 2011. As renal cell carcinoma cell lines, we used 786-O, ACHN and Caki-1. The expression profiles of CXCR3 and its splice variants were examined. For functional analyses 786-O and interferon-γ inducible 10 kDa protein or IP-10 (CXCL10) were selected as representatives.CXCR3 and its ligands were abundant in renal cell carcinoma samples compared to corresponding normal kidney samples. The CXCR3-A-to-CXCR3-B ratio was 1.5 times higher in renal cell carcinoma samples than in normal kidney samples. CXCL10 treatment induced 786-O cell migration and invasion, and these effects were inhibited by neutralizing antibody. Phosphorylated RhoA and pro/active matrix metalloproteinase-9 expression was up-regulated by CXCL10 treatment. In clinical samples CXCR3 and CXCR3-A expression was significantly higher in metastatic than in nonmetastatic carcinoma samples. Finally, the expression of CXCR3-A and HIF-1α correlated significantly in clinical samples. In 786-O treatment with CoCl2 up-regulated CXCR3 and HIF-1α expression 4.5 and 2.2-fold, respectively.We determined the association of CXCR3 and renal cell carcinoma metastasis. CXCR3 expression may be regulated by hypoxia.

Primary aldosteronism is the most common curable cause of secondary hypertension. Despite resection, however, many patients with primary aldosteronism continue to require antihypertensive drugs to control their blood pressure. Although many patients with primary aldosteronism want to know the postoperative probability of hypertension cure before surgery, there are no predictive models calculating its probability. We therefore developed a nomogram to predict hypertension cure in patients with primary aldosteronism after laparoscopic adrenalectomy. We retrospectively surveyed 132 Japanese patients with primary aldosteronism who were treated by unilateral laparoscopic adrenalectomy. Hypertension cure was defined as normal blood pressure (

Objective To investigate the hypothesis that 5-alpha-reductase inhibitors exert early ameliorative effects on voiding and storage symptoms in men with lower urinary tract symptom-associated benign prostatic hyperplasia. Methods This was a prospective study involving the participation of eight outpatient clinics in Chiba Prefecture, Japan. The patients received dutasteride (0.5 mg) once daily orally for 24 weeks as an add-on to their ongoing therapy with an alpha-1 blocker. The study patients recorded their urinary symptoms every day for 14 days after starting dutasteride. The International Prostate Symptom Score, prostate volume, uroflowmetry results, and residual urine volume were checked at 3 and 6 months after starting dutasteride. Results A total of eighty-eight patients participated in the present study; 74 were eligible for analysis of the early effects of dutasteride. The median age was 69.6 years (range 54–89), the median prostate volume was 50.3 mL (range 24.7–103.3) and the median International Prostate Symptom Score was 17.6 (range 8–35). The proportion of patients with International Prostate Symptom Score improvements (≥3 points, or ≥25%) or 3 points or more decreased International Prostate Symptom Score were defined effective, 37 (50.0%) and 47 (63.5%) experienced improvement at 1 month after administration, respectively. Conclusion This is the first prospective clinical study to show the early beneficial effects of 5-alpha-reductase inhibitors for lower urinary tract symptom-associated benign prostatic hyperplasia. Patients with severe symptoms were found to be responsive to dutasteride. The influence of the placebo effect was not denied. Further study is necessary.

Background:The purpose of this study was to evaluate the feasibility of a new shortened 3-week treatment schedule of carbon ion radiotherapy (CIRT) for prostate cancer.Methods:Beginning in May 2010, patients with T1b-T3bN0M0, histologically proven prostate adenocarcinoma were enrolled in the phase II trial of CIRT. Patients received 51.6 GyE in 12 fractions over 3 weeks (protocol 1002). The primary end point was defined as the incidence of late adverse events that were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0. Biochemical failure was determined using the Phoenix definition (nadir +2.0 ng ml(-1)).Results:Forty-six patients were enrolled, and all patients were included in the analysis. The number of low-, intermediate-, and high-risk patients was 12 (26%), 9 (20%), and 25 (54%), respectively. The median follow-up period of surviving patients was 32.3 months. Two patients had intercurrent death without recurrence, and the remaining 44 patients were alive at the time of this analysis. In the analysis of late toxicities, grade 1 (G1) rectal haemorrhage was observed in 3 (7%) patients. The incidence of G1 haematuria was observed in 6 (13%) patients, and G1 urinary frequency was observed in 17 (37%) patients. No G2 late toxicities were observed. In the analysis of acute toxicities, 2 (4%) patients showed G2 urinary frequency, and no other G2 acute toxicities were observed.Conclusions:The new shortened CIRT schedule over 3 weeks was considered as feasible. The analysis of long-term outcome is warranted.British Journal of Cancer advance online publication, 10 April 2014; doi:10.1038/bjc.2014.191 www.bjcancer.com.

Background: A novel risk assessment method, Japan Cancer of the Prostate Risk Assessment, has been developed based on database of patients receiving primary androgen deprivation therapy. To investigate the usefulness of Japan Cancer of the Prostate Risk Assessment for non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy. Methods: Patients with non-metastatic, high-risk prostate cancer (T3, initial prostate specific antigen level � 20 ng/ml, and/or Gleason score � 8) were included. The patients were treated with carbon ion radiotherapy (the total dose from 57.6 Gy (relative biological effectiveness)/16 fractions to 66.0 Gy(relative biological effectiveness)/20 fractions), and neoadjuvant as well as adjuvant androgen deprivation therapy for at least 24 months. Results: Four hundred and twenty-six patients were included with the median follow-up of 68.1 months. Of 426, 210 (49.3%), 270 (63.4%) and 251 (58.9%) had Gleason 8‐10, prostate specific antigen � 20 ng/ml and T3, respectively. The 10-year progression-free and cause-specific survival rates in Japan Cancer of the Prostate Risk Assessment 1‐2 group (76.5 and 98.9%) were significantly better than those in Japan Cancer of the Prostate Risk Assessment 3‐6 group (52.6 and 93.1%), (P , 0.001 and P ¼ 0.044, respectively). The median progressionfree survivals in the Japan Cancer of the Prostate Risk Assessment 1‐2 and 3‐6 groups were 158.9 months and 125.9 months (95% confidence interval: 108.6‐143.2 months), respectively. Conclusions: For non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy, Japan Cancer of the Prostate Risk Assessment score was useful for predicting the progression-free and cause-specific survivals.

Objectives: To clarify clinical predictors for a prostate-specific antigen decrease � 50% in response to alternative non-steroidal antiandrogen therapy and to develop a nomogram to predict the prostate-specific antigen decrease � 50% in response to alternative non-steroidal antiandrogen therapy in patients with advanced prostate cancer that relapsed after initial combined androgen blockade. We previously reported that combined androgen blockade with an alternative non-steroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial combined androgen blockade. Methods: We enrolled 161 patients from 14 medical institutions with histologically confirmed prostate cancer who had been treated with combination therapy and in whom cancer progressed after first-line combined androgen blockade therapy. A nomogram for the prostatespecific antigen decrease � 50% from baseline prostate-specific antigen in response to alternative non-steroidal antiandrogen therapy was developed based on the final logistic regression model. Results: Overall prostate-specific antigen decreased � 50% in 75 of 161 patients (46.6%) in response to alternative non-steroidal antiandrogen therapy. Using five independent risk factors (initial serum level of prostate-specific antigen, hemoglobin, C-reactive protein, prostate-specific antigen nadir to second hormone therapy and Gleason sum), a nomogram was developed for the prediction of prostate-specific antigen decrease � 50% in response to alternative nonsteroidal antiandrogen therapy. The receiver operating characteristic curve showed that the accuracy of the predicted probability was 72.5% for the model. Conclusions: This predictive nomogram could predict the prostate-specific antigen decrease � 50% in response to alternative non-steroidal antiandrogen therapy and might be of benefit to determine the sequential treatment strategy in patients with relapse after first combined androgen blockade.

164 Background: TAS-115, a novel multi-kinase (eg, MET, VEGFR) inhibitor has also shown to inhibits Feline McDonough Sarcoma oncogene (FMS) kinase, Anti-tumor activity against bone metastases was observed in the preclinical and phase1 study. In this phase 2 study, the efficacy and safety of TAS-115 were evaluated in castration-resistant prostate cancer (CRPC) patients (pts) with bone metastases. Methods: This was a phase 2, open-label, multi-arm study for CRPC pts with bone metastases to evaluate the clinical anti-tumor activity of TAS-115. Pts who had visceral metastases were ineligible for this study. TAS-115 was given orally, once daily, and schedule of 5 days on/2 days off each week was repeated. This study had 2 cohorts (A and B). In cohort A, TAS-115 ranging from 200 to 400 mg/day with abiraterone acetate was given to pts prior to docetaxel. In cohort B, CRPC pts who had symptomatic bone metastases, post or unfit to docetaxel, were randomized in a 1:1 to 400 or 600 mg/day of TAS-115. The primary endpoint was bone scan index (BSI) response rate at week 12, defined as ≥ 30% decrease of BSI from baseline. BSI is a quantitative assessment of bone scan data calculated by software (BONE NAVI). Results: From Nov 2016 to Jul 2018, a total of 50 pts received TAS-115 (24 pts in cohort A and 26 pts in cohort B). BSI response rate at week 12 and best BSI response was 20.8 % and 37.5% in cohort A, and 15.4 % and 19.2% in cohort B, respectively. Any reduction of BSI was observed in 70.8% of cohort A and 61.5% of cohort B. In cohort B, pain was assessed using the Brief Pain Inventory short form and improvement was observed in 61.5% of pts. Furthermore, the reduction of bone-turnover marker (BAP, P1NP, NTx and TRACP-5b) were observed in both cohorts, but not PSA response. The major (≥ 10%) Grade 3/4 treatment-related adverse drug reactions were hypophosphataemia (21%) in cohort A, and anemia (23%), hypophosphataemia (12%) and neutrophil count decreased (12%) in cohort B. Conclusions: Preliminary anti-tumor activity to bone lesion and improved pain were observed in CRPC pts with bone metastases, and safety of TAS-115 was acceptable. TAS-115 could be a novel therapeutic agent with a favorable safety profile for CRPC with bone metastases. Clinical trial information: JapicCTI-163448.

Keywords Dual pathology ´Temporal lobe epilepsy Ganglioglioma Negative magnetic resonance imagingDear Sir,Hippocampal sclerosis (HS) can appear secondary to neo-cortical epileptogenic lesion in medically refractoryepilepsy, called dual pathology. In the dual pathology, re-moval of both the primary lesion and HS is necessary toachieve better seizure outcome. However, if the primarylesion is not apparent in pre-operative imaging studies,selective surgery to hippocampus may be performed andfollowed by inadequate seizure control. Here, we report acase of dual pathology which was not diagnosed pre-operatively.A 50-year-old man with drug-resistant temporal lobeepilepsy (TLE) was referred to our department forevaluation of surgical treatment. Seizures had started atage 10 years and had become intractable to multiplemedications at age 22 years. He had aura of fear or deja`-vu followed by complex partial seizures 2–3 times amonth despite antiepileptic medications including carba-mazepine and lamotrigine. Previously, he was treatedwith valproic acid, levetiracetam and zonisamide. Com-prehensive presurgical evaluation including video-elec-troencephalography (EEG), ‘‘epilepsy protocol’’ high-fieldmagnetic resonance imaging (MRI), fluoro-deoxy-glucosepositron emission tomography (FDG-PET), neuropsycho-logical testing, was performed. 3.0-T MRI revealed in-creased T2 signal intensity and volume loss of the righthippocampus (Fig. 1). No cystic lesions or other neo-cortical abnormalities were observed by neuroradi-ologists. Gadolinium enhancement was not performed. Nocalcifying lesions were seen in computed tomographyscans. Video-EEG monitoring revealed that complexpartial seizures with automatisms were associated withrhythmic EEG changes in the right anterior temporalregion. FDG-PET showed glucose hypometabolism in theright antero-basal temporal region. Neuropsychologically,mild impairment of verbal memory function was noted.Under a diagnosis of right TLE with hippocampal scle-rosis, trans-sylvian selective amygdalo-hippocampectomywas performed. Histological examination revealed bothType 1b HS (Fig. 2a) and ganglioglioma in the subiculum(Fig. 2b, c) [1]. He has suffered no additional neuro-logical deficits post-operatively. The patient was seizurefree for 2 years with continuing medication. Follow-upMRI at 1 year showed no evidence for recurrence oftumor.Neocortical epileptogenic lesion occasionally coexistswith HS, and is called ‘‘dual pathology.’’ Surgical re-moval of both neocortical lesion and hippocampus isbetter for the achievement of seizure freedom [2]. In thepresent case, the subicular tumor was not identified pre

Demyelinating polyneuropathy associated with amyotrophic lateral sclerosis (ALS) is quite rare. We herein present the case of a woman patient with a 12-year history of chronic inflammatory demyelinating polyneuropathy (CIDP)-like polyneuropathy who later developed bulbar palsy and respiratory failure. The autopsy findings revealed neuronal loss in the anterior horn and primary motor cortex with degeneration of the corticospinal tracts. Diffuse phosphorylated TAR DNA-binding protein of 43 kDa inclusions were observed in the anterior horn and cerebral cortices, including the temporal lobe. The final diagnosis was ALS with CIDP-like polyneuropathy. Compared with other reports of ALS with CIDP-like polyneuropathy, the present patient was younger and followed a relatively long clinical course, with no upper motor neuron signs.

Background: The associations of ERG overexpression with clinical behavior and molecular pathways of prostate cancer are incompletely known. We assessed the association of ERG expression with AR, PTEN, SPINK1, Ki-67, and EZH2 expression levels, deletion, and mutations of chromosomal region 3p14 and TP53, and clinicopathologic variables. Methods: The material consisted of 326 prostatectomies, 166 needle biopsies from men treated primarily with endocrine therapy, 177 transurethral resections of castration-resistant prostate cancers (CRPC), and 114 CRPC metastases obtained from 32 men. Immunohistochemistry, FISH, and sequencing was used for the measurements. Results: ERG expression was found in about 45% of all patient cohorts. In a multivariate analysis, ERG expression showed independent value of favorable prognosis (P = 0.019). ERG positivity was significantly associated with loss of PTEN expression in prostatectomy (P = 0.0348), and locally recurrent CRPCs (P = 0.0042). Loss of PTEN expression was associated (P = 0.0085) with shorter progression-free survival in ERG-positive, but not in negative cases. When metastases in each subject were compared, consistent ERG, PTEN, and AR expression as well as TP53 mutations were found in a majority of subjects. Conclusions: A similar frequency of ERG positivity from early to late stage of the disease suggests lack of selection of ERG expression during disease progression. The prognostic significance of PTEN loss solely in ERG-positive cases indicates interaction of these pathways. The finding of consistent genetic alterations in different metastases suggests that the major genetic alterations take place in the primary tumor. Impact: Interaction of PTEN and ERG pathways warrants further studies. Cancer Epidemiol Biomarkers Prev; 22(12); 2333–44. ©2013 AACR.

Objectives To assess 3-year health-related quality of life of patients treated with carbon ion radiotherapy for prostate cancer. Methods A total of 213 patients received carbon-ion radiotherapy at a total dose of 66 Gy equivalent in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy were administered for high-risk patients for at least 12 months. A health-related quality of life assessment was carried out at four time-points (immediately before the initiation of carbon-ion radiotherapy, immediately after, 12 and 36 months after completion of carbon-ion radiotherapy) using Functional Assessment of Cancer Therapy General and for Prostate Cancer Patients. Results The evaluable response rates among all responses were more than 94%. Overall, a significant decrease in the scores of the health-related quality of life 12 months after carbon-ion radiotherapy returned to their baseline levels at 36 months. Additionally, no significant decrease was observed in the scores at any of the assessment time-points compared with their baseline scores in the group of carbon-ion radiotherapy without androgen deprivation therapy; however, the presence of morbidity and biochemical failure significantly worsened the scores, and the decreases in the scores did not improve even at 36 months after carbon-ion radiotherapy. Conclusions An assessment based on a subjective scoring system shows a significant decrease in health-related quality of life at 12 months after carbon-ion radiation therapy, which tends to return to baseline levels at 36 months. The presence of morbidity and biochemical failure significantly worsen health-related quality of life scores. Further controlled studies focusing on health-related quality of life assessment in patients with prostate cancer are warranted.