Search

Left ventricular (LV) apical hypoplasia is a rare restrictive cardiomyopathy subtype with an unclear pathophysiology. LV apical hypoplasia typically presents with elongated right ventricle (RV) wrapping around a truncated and spherical LV with a deficient apex (the “banana-shape” of the RV). Here we report a case of a young boy with apparent LV apical hypoplasia that developed after birth; no “banana-shaped” RV was observed during the fetal period. Moreover, suprasystemic pulmonary hypertension (PH) developed even after a mitral valve replacement was performed for progressive mitral stenosis and regurgitation at 14 months of age. He underwent surgery for the Potts shunt, a shunt between the pulmonary artery and aorta, at 13 years to secure systemic output. His PH ameliorated and his heart failure remained stable for 3 years after the operation. This case indicates that the “banana-shaped” RV seen in this condition is not always congenital but that it can form and develop after birth. Furthermore, this case supports the usefulness of the Potts shunt as a therapeutic option in patients with severe PH due to LV apical hypoplasia.

Sentinel lymph node biopsy is widely applied for the management of clinically node-negative breast cancer, and a radioisotope with a blue dye are most often used as tracers. Fluorescence of indocyanine green could also potentially be used as tracer. This study aimed to demonstrate the long-term survival results of fluorescence-guided sentinel lymph node biopsy. Patients with clinically node-negative breast cancer who underwent surgery as initial treatment were included in this study. Both fluorescence of indocyanine green and indigo carmine blue dye were used as tracers. Axillary lymph node dissection was omitted unless metastasis was pathologically proven in sentinel nodes. Breast cancer recurrence and death were recorded and prognostic factors were identified using disease-free survival and overall survival data. A total of 565 patients were analyzed. There were 14 (2.5%) patients whose sentinel nodes could not be identified, yielding an identification rate of 97.5%. Axillary dissection was performed in 90 patients. Forty-three recurrences including 6 ipsilateral axilla recurrence and 13 deaths were observed during the median 83 months of follow-up period. Seven-year disease-free and overall survival were 92.4% and 97.3%, respectively. Multivariate analyses demonstrated that pre-menopausal status and invasive lobular carcinoma were significant unfavorable prognostic factors of disease-free survival. Half of ipsilateral axilla recurrences occurred within 5 years after surgery and these recurrences were correlated with inappropriate adjuvant therapy. Fluorescence-guided sentinel lymph node biopsy demonstrated favorable prognostic results and could be alternative to the radioisotope for clinically node-negative breast cancer.

This paper describes a case of renal pelvic cancer with a complete duplication of the renal pelvis and ureter, which is substantially rare. A 76-year-old man was referred to the hospital because of gross hematuria for 2 years. A tumor was detected in the upper right kidney using enhanced computed tomography and magnetic resonance imaging scan, and the downstream ureter was suspected to open into the prostate. Retrograde ureteroscopy via the ectopic ureter orifice showed a hemorrhagic papillary tumor consistent with imaging findings. Laparoscopic radical nephroureterectomy was performed and the prostate was preserved because the tumor was only in the renal pelvis. Histopathological examination showed the tumor as a high-grade urothelial carcinoma. There was no sign of recurrence at one and a half years after operation. Ureteroscopy was effective in detecting an upper urinary tract tumor, even via ectopic ureter orifice, and preserving the prostate was possible.

We established severity banding ranges, bother assessment and key item content in principal patient reported outcomes measures in men seeking therapy for lower urinary tract symptoms.Data for International Prostate Symptom Score (I-PSS) and International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) were derived from a study evaluating 820 men at 26 United Kingdom hospitals. ROC curves were used to establish severity bandings.Classification tree showed that thresholds between mild-moderate and moderate-severe severity bands were 15 and 27 for I-PSS, 16 and 26 for ICIQ-MLUTS/severity, and 22 and 81 for ICIQ-MLUTS/bother, respectively. Highest area under the ROC curve and lowest Akaike's information criteria of univariate logistic regression indicated that ICIQ-MLUTS/bother was more related to global quality of life than were I-PSS and ICIQ-MLUTS/severity. The symptoms affecting I-PSS-quality of life (QoL) were only fully identified by ICIQ-MLUTS, because 2 key symptoms (urinary incontinence and post-micturition dribble) are not measured by I-PSS. ICIQ-MLUTS demonstrated that bother of some lower urinary tract symptoms is disproportionate to severity, and that persisting high bother levels following surgery are more likely due to storage (18% to 25%) and post-voiding (18% to 28%) lower urinary tract symptoms than voiding lower urinary tract symptoms (5% to 13%). Symptom improvement after surgery was uncertain if baseline I-PSS-QoL score was less than 3.The severity threshold scores were measured for the 2 key lower urinary tract symptoms patient reported outcomes measures, and the results indicate suitable categories of symptom severity for use in men referred for urological care. The ICIQ-MLUTS measures all the lower urinary tract symptoms affecting quality of life and includes individual symptom bother scores.

Objective To examine the correlation between smoking habit and lower urinary tract symptoms in women. Methods We first screened 10 000 female patients to examine their smoking habit. A total of 7004 samples were successfully collected for further analysis through a urinary continence survey. The ratio of current smoking to non‐smoking participants was set as 1:3 to allow thorough assessment of the impact of cigarette smoking on lower urinary tract symptoms. Results A total of 4756 complete responses were obtained for the Overactive Bladder Symptom Score and International Consultation on Incontinence Questionnaire‐Short Form questionnaire. The current smokers (2.54 ± 2.91, 2.48 ± 4.01) and ex‐smokers (2.27 ± 2.50, 2.25 ± 3.50) showed significantly higher Overactive Bladder Symptom Score and International Consultation on Incontinence Questionnaire‐Short Form scores than the non‐smokers (1.70 ± 2.05, 1.49 ± 2.73) (P

The 79 years old man was referred to our department due to high value of serum prostate specific antigen (39.54 ng/ml). The magnetic resonance imaging demonstrated diffuse low signal at his prostate. Bone scintigraphy revealed multiple metastatic lesion. Needle biopsy was performed for definite diagnosis. Systemic purpura showed after prostate needle biopsy although he had noticed local purpura at his back before the examination. He was diagnosed as disseminated intravascular coagulation (DIC) syndrome due to advanced prostate cancer. Treatment with anti-DIC therapy, blood transfusion, subcutaneous injection of degarelix acetate settled the DIC. Abiraterone hydrochloride and prednisolone was added as we confirmed Gleason score5+4 in the pathological examination. He has been alive for 15 months after diagnosis without desease progression.

Granulocyte colony-stimulating factor (G-CSF)-producing bladder cancer is a rare variant subtype of bladder cancer with a poor prognosis. Pembrolizumab has improved overall survival in bladder cancer and is widely used as a standard second-line treatment. However, no reports on G-CSF-producing cancer treated by pembrolizumab are available. We report a case of the pathologically evaluated antitumor effect of pembrolizumab, a programmed death-1 immune checkpoint inhibitor antibody, in G-CSF-producing bladder cancer. A 53-year-old male patient underwent 4 courses chemotherapy with a combination of gemcitabine and carboplatin before a radical cystectomy with ileal neobladder. Four months after the surgery, local recurrence was detected in the pelvis and therefore pembrolizumab was used. One week after its administration, the patient showed increased mucus in his urine. A computed tomography scan and cystoscopy revealed a fistula between the ileum and the neobladder. He subsequently underwent partial ileectomy and repair of the neobladder-ileum fistula. Pathology-diagnosed tumor response to pembrolizumab in the metastatic tumor showed predominant infiltration by lymphocytes, unlike that in the primary bladder cancer. The patient has shown complete response and no recurrence at 1 year after the beginning of treatment, and therapy is still continuing. Although many questions still remain regarding the treatment of G-CSF-producing bladder cancer, pathologic evaluation of the present case suggests that treatment with pembrolizumab may be one option for G-CSF-producing bladder cancer that has failed chemotherapy treatment, similar to non-G-CSF-producing bladder cancer.

This study aimed to evaluate predictive factors for graft loss in patients who received kidney transplantation (KT) from living kidney donors (LKDs) at a single institute in Japan.Our study focused on patients with end-stage renal disease who underwent KT from LKDs and were followed up for at least 1 year after surgery. The primary end point was graft survival (GS). GS after KT was analyzed using the Kaplan-Meier method. GS according to subgroup classification was analyzed using the log-rank test. A multivariate analysis was performed using a Cox proportional hazard model.The median follow-up period was 105.5 months after KT. The 5- and 10-year GS rates were 97.8% and 96.0% in KT recipients (KTRs) without posttransplant diabetes mellitus (PTDM) and 89.9% and 63.2% in those with PTDM, respectively. The rate of graft loss was significantly higher in KTRs with PTDM than in those without PTDM (P .001). Of the KTRs whose diabetes mellitus (DM) was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss. In the multivariate analysis, the serum creatinine level at 1 month after KT, PTDM, and human leukocyte antigen mismatches were significantly associated with graft loss after KT.In this study, the rate of graft loss in KTRs with PTDM was significantly higher than that of KTRs without PTDM. However, among KTRs whose DM was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and &gt, 2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and &gt, 215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and &gt, 561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

An 84-year-old woman was referred for lower abdominal pain lasting more than six months. Computed tomography showed a left ovarian varicose vein and a peri-uterine venous plexus. Due to suspected pelvic congestion syndrome, left ovarian venography and left ovarian embolization were performed. Blood flowed back through the dilated left ovarian vein and through the uterine venous plexus to the right ovarian vein. Embolization of the left ovarian vein with a sclerosing agent resulted in the disappearance of the venous congestion. Preoperative Visual Analogue Scale was 7, which decreased to 3 after the operation. As a result, improvements in QOL were recognized. Although pelvic congestion syndrome is a treatable disease, its recognition as a urological disease is low. Here, we have reported a case of pelvic congestion syndrome in which symptoms improved with treatment and have discussed its pathophysiology and treatment.

Introduction The patients with prostate cancer and low-volume osseous metastases who underwent local definitive therapies had lower risks of cancer-specific mortality. The usefulness of local definitive therapy for metastatic prostate cancer remains unclear. Case presentation A 76-year-old man visited a private hospital with a chief complaint of left lower limb pain. His serum prostate-specific antigen level was 365.156 ng/mL. Histological evaluation led to the initial diagnosis of adenocarcinoma of Gleason score 4 + 4 and clinical stage T3a N1 M1b. Although androgen deprivation therapy was performed, he developed metastatic castration-resistant prostate cancer 6 months after the initial treatment. Therefore, he received enzalutamide and attained a serum prostate-specific antigen level of 0.002 ng/mL 7 months after the second treatment. We performed robot-assisted radical prostatectomy 1 year after diagnosis. Histopathological examination revealed that prostate cancer cells disappeared into the prostate. Conclusion Robot-assisted radical prostatectomy in selected patients with metastatic castration-resistant prostate cancer may improve oncological outcomes.

We present the case of a 46-year-old man who underwent successful antegrade ureteroscopy for lithiasis in his allograft ureter. At a scheduled follow-up 15 years after transplantation, computed tomography (CT) detected a 12-mm renal stone in the renal pelvis of the transplanted kidney. During his follow-up, gross hematuria was seen; the stone moved to the ureter, causing hydronephrosis. Ultrasound and non-contrast CT revealed hydronephrosis and a 15-mm stone in the transplanted ureter. Considering the stone size, location, and the difficulty of the access to the anastomosed ureteral orifice, percutaneous ureteroscopic approach was planned. Due to the anatomical difficulty regarding his allograft kidney, we planned to prepare a 3D image and model for selecting the best percutaneous approach. The procedure was performed and a stone-free status was acquired without complication. Under precise simulation, we performed successful antegrade ureteroscopy for lithiasis in the allograft ureter supported by 3D imaging. Use of a 3D printed model may aid in a safe and effective procedure for lithiasis in the allograft kidney and ureter.

An extremely low birth weight infant (810 g) was born with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries accompanied by pulmonary overcirculation, which eventually resulted in intestinal hypoperfusion and focal intestinal perforation from the very early stage of life. Based on the echographic findings, we performed banding operations twice to regulate the pulmonary blood flow on day 2 and day 9. At 6 months of age, a definitive repair simultaneous with unifocalization of major aortopulmonary collateral arteries was performed. At 1 year of age, the right ventricle/left ventricle pressure ratio was 0.44 after balloon angioplasty was performed for the right-sided pulmonary artery stenosis. The patient is in a stable condition and was followed-up for more than 2 years after definitive repair. This is the first known successful repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries in an extremely low birth weight infant.

To evaluate the clinical outcomes of surgical repair of an extracardiac total anomalous pulmonary venous connection (TAPVC) in a functional single-ventricle (f-SV) strategy. This was a retrospective analysis of 48 consecutive cases of extracardiac TAPVC repair, from 1998 to 2015. Demographic and clinical variables were as follows: median age, 24 (range 0–744) days; median weight, 3.1 (range 2.0–9.6) kg; type of TAPVC—supracardiac, 21 patients, infracardiac, 8, and mixed, 19; right atrial isomerism, 45 patients; pulmonary atresia, 24 patients; and obstructed TAPVC, 30 patients. Concomitant procedures included systemic-to-pulmonary shunting in 15 patients, pulmonary artery banding in 12, ventricle-to-pulmonary artery shunting in 2, a Norwood procedure in one, a bidirectional Glenn procedure in 16, and a Fontan procedure in 1. The 1- and 5-year cumulative survival rates were 66.0% and 58.0%, respectively. Of the 28 survivors, 22 (78.6%) underwent Fontan completion and 4 (14.3%) a bidirectional Glenn procedure, and 1 (3.6%) was awaiting a bidirectional Glenn procedure. Recurrent pulmonary venous stenosis (PVS) was observed in 17 patients, with a 1- and 5-year rates of freedom from recurrent PVS 59.8% and 53.5%, respectively. Of the 20 post-operative deaths, only 4 were PVS related. Only pre-operative pulmonary atresia was identified as an independent risk factor of mortality after TAPVC repair. The midterm surgical outcomes of f-SV with extracardiac TAPVC were acceptable. Moreover, among survivors, Fontan completion can be sufficiently expected. Further improvement, with the development of a comprehensive treatment strategy, is required for this patient group.

A 77-year-old woman with lung adenocarcinoma noticed bilateral ptosis 7 weeks after a first pembrolizumab infusion. Her symptoms rapidly progressed to generalized manifestations including limb and neck weakness, dyspnea, and dysphasia within the following two weeks. We diagnosed him with pembrolizumab-related myasthenia gravis and myositis based on clinical symptoms, elevation of muscle enzymes and anti-acetylcholine receptor antibodies, repetitive nerve stimulation and muscle biopsy. We commenced combination immunotherapy, including intravenous and oral steroid therapy, immune absorption therapy and plasma exchange therapy with noninvasive positive-pressure ventilation and tracheotomy positive pressure ventilation. She had gradual symptoms improvement and discharged after 209 days in a hospital. In this case, anti-titin antibodies, one of anti-striational antibodies, was positive and correlated with severity of myasthenia gravis. With the development of immune checkpoint inhibitors for various malignancies, clinicians should closely monitor patients for important immune-related adverse events and coordinate on early treatment.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and &gt, 4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and &gt, 188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR &gt, 188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

Background: Incidental durotomy is a well-known complication of spinal surgery. It can lead to persistent cerebrospinal fluid leakage resulting in significant secondary complications. Here, we present a case in which the cauda equina herniated into a pseudomeningocele that penetrated a facet joint, leading to lower extremity radiculopathy warranting surgical correction. Case Description: One year ago, a 67-year-old male underwent a partial left L4-L5 laminectomy. At surgery, a durotomy was repaired with a nylon suture and reinforced with a fat patch. He subsequently presented with severe left lower extremity radiculopathy and a partial cauda equina syndrome. On MR, the cauda equina had herniated into a pseudomeningocele that penetrated the left facet joint. Once the defect was repaired at surgery, the patient’s symptoms improved. Conclusion: It is critical to correctly repair an intraoperative durotomy to avoid further neurological deficits that may include cauda equina herniation into pseudomeningoceles penetrating facet joints.

Lower urinary tract symptoms (LUTS) are substantially prevalent and increase with age. Research on smoking as a risk factor for LUTS has been inconclusive. The present study examined the association between smoking habits and male LUTS in a population-based study using a web-based questionnaire. We firstly screened a total of 10,000 male participants who were selected according to the age distribution in the Japanese population in government data, in order to check smoking habits. We then performed a web-based survey to further investigate factors associated with LUTS, using the Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and International Prostate Symptom Score (IPSS) questionnaire. Finally, 9042 participants (non-smokers, n = 3545; ex-smokers, n = 3060; and current-smokers, n = 2437) completed the full continence survey. Current-smokers (2.54 ± 2.73, 1.98 ± 3.57, 5.75 ± 7.02) and ex-smokers (2.80 ± 2.52, 1.81 ± 3.10, 6.58 ± 6.96) showed significantly higher OABSS total, ICIQ-SF total, and IPSS total scores than non-smokers (1.98 ± 2.40, 1.35 ± 2.90, 4.23 + -/6.33) (p

Context Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear. Case Description A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg/m2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T>A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH. Conclusion This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.

Studies of prostate-specific antigen (PSA)-based population screening have been conducted in western countries, but there is little data in Asian populations. The objective of this study was to determine the efficacy of PSA screening in Asian men using real-world data over a period of 15 years after introducing population screening in Yokosuka City, Japan.We investigated patients with pathologically diagnosed prostate cancer at four hospitals and two clinics across the Yokosuka area (Miura peninsula) between April 2001 and March 2015. Patients were divided into two groups; the S group consisted of those diagnosed by PSA-based population screening in Yokosuka City and the NS group consisted of those diagnosed by methods other than screening. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated using the Kaplan-Meier method with the log-rank test to compare survival between the two groups. Clinical and pathological factors for cancer-specific mortality were assessed with Cox regression analyses to calculate the hazard ratio (HR) and 95% confidence interval (CI).A total of 3094 patients had been diagnosed with prostate cancer over the 15-year period. The median follow-up period was 77 months. The S group and the NS group consisted of 977 and 2117 patients, respectively. Patients in the S group were younger (age: 71 years vs 73 years, P .001) and had a lower Charlson comorbidity index (CCI) with favorable oncological factors, such as lower initial PSA, Gleason score (GS), and risk category. Kaplan-Meier curves for OS and CSS revealed significant differences between the two groups (OS: P .001, CSS: P .001). Analysis with Cox proportional hazards model indicated the NS group (HR: 1.584, 95% CI, 1.065-2.356, P = .023), a CCI 4 (HR: 1.552, 95% CI, 1.136-2.120, P = .006), a GS ≥ 8 (HR: 4.869, 95% CI, 2.631-9.001, P .001), and nonlocalized cancer (locally advanced; HR: 2.632, 95% CI, 1.676-4.133, P .001, advanced; HR: 9.468, 95% CI, 6.279-14.278, P .001) as independent risk factors for cancer-specific mortality.PSA-based population screening of prostate cancer might be useful in the Japanese population.

A male infant with Kabuki syndrome had trivial congenital mitral regurgitation diagnosed at birth. At the age of 2 years and 9 months, the regurgitation worsened from mild to severe; thus, expedited surgical treatment was pursued. The primary operative finding was severe dysplastic two-leaflet disease. After completing chordal replacement as a conventional repair procedure, more-than-moderate central regurgitation caused by establishing a shallow coaptation between the anterior and posterior leaflets persisted. We report a successful case of mitral valve repair involving the novel option of interannular bridge for valvuloplasty to address congenital mitral regurgitation.

Background Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. Methods A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. Results The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p

We evaluated 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) results as outcome predictors for patients with metastatic renal cell carcinoma (RCC) treated by everolimus (EVL), an inhibitor of mammalian target of rapamycin. We retrospectively reviewed 30 patients who were treated with EVL for metastatic RCC between May 2010 and March 2015, by evaluating their FDG PET/CT result before and 1 month after starting EVL treatment. We examined the relationships between each patient’s maximum standardized uptake value (max SUVmax) assessed by FDG PET/CT on progression-free survival (PFS) and overall survival (OS). Median PFS for all 30 patients was 3.77 months (range 0.72–24.56 months) and median OS after EVL treatment of all 30 patients was 11.67 months (range 1.0–62.98 months). Enrolled patients were divided into two groups by max SUVmax prior to EVL (median = 7.6) and at 1 month after EVL treatment (median = 5.7). PFS were significantly shorter in higher max SUVmax prior to EVL (

Background Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). Objective To report participants’ sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. Design, setting, and participants A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. Intervention Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). Outcome measurements and statistical analysis The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick’s test, and questionnaire items were compared using Pearson’s correlation coefficient. Results and limitations Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. Conclusions Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. Patient summary We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

Skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) are the standard techniques for achieving a cosmetic outcome, but necrosis of a cutaneous flap including the nipple–areolar complex (NAC) is a serious complication. To analyze the risk factors for skin flap necrosis, we retrospectively evaluated a clinical database of breast cancer patients treated with mastectomy followed by immediate breast reconstruction. Four hundred and twelve cases were consecutively recorded between 2006 and 2016. Body weight (BW), body mass index (BMI), distance from NAC to referent tumor, distance from overlying skin to the tumor and weight of breast resection (WBR) as measured in the operating theater were included in the statistical analysis. NSM, SSM and total mastectomy were performed in 123 (30%), 96 (23%) and 193 cases (47%), respectively. A tissue expander was used in 379 cases (92%), a silicone implant in 8 (2%) and autologous breast reconstruction in 25 (6%). Skin flap necrosis was found in 7% of all cases and NAC necrosis in 13% of NSM cases. In a univariate analysis, BW, NSM and WBR were risk factors for skin flap necrosis, and BW, BMI and WBR were risk factors for NAC necrosis. In a multivariate analysis, NSM and WBR remained significant risk factors for skin flap necrosis, and WBR was a significant risk factor for NAC necrosis. WBR is an important risk factor for skin flap necrosis. Especially, NAC necrosis should be considered for patients with large-volume breasts who undergo NSM and immediate breast reconstruction.

Introduction: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. Materials and methods: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)—dapagliflozin ( n = 52) or empagliflozin ( n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. Results: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups ( p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e′ or left atrial volume index, decreased only in Group G at 36 months. Conclusions: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.

Introduction and Objectives. Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a simple marker of the systemic inflammatory response in critical care patients. We previously assessed the utility of NLR as a biomarker to predict tumor recurrence and cancer death in bladder cancer patients who underwent radical cystectomy. In this study, we evaluated the prognostic impact of NLR in bladder cancer patients who received gemcitabine and nedaplatin (GN) chemotherapy.Methods. A total of 23 patients who received GN chemotherapy for advanced bladder cancer were enrolled in this study. The cut-off point of NLR according to the sensitivity and specificity levels was derived from the area under receiver operator characteristics (AUROC) curve plotted for disease progression or overall mortality.Results. The NLR cut-off point was determined as 4.14 for both tumor progression and overall mortality. Median progression-free survival (PFS)/overall survival (OS) in the higher NLR group (NLR ≥ 4.14) and lower NLR group (NLR < 4.14) were 194/468 days versus 73/237 days, respectively. Kaplan-Meier analysis showed that higher NLR significantly correlated with poorer PFS (p=0.011) and OS (p=0.045).Conclusions. NLR may serve as a new biomarker to predict responses to GN-based chemotherapy in advanced bladder cancer patients and/or their prognosis.

Since its discovery, improvements in treating Castleman disease and its variants have centered on interleukin-6 (IL-6). IL-6 was discovered from T-cell factors (BCDF or BSF-2), which induced B-cell maturation. Most symptoms of the plasma cell variant of Castleman disease are linked to the hyperfunction of IL-6, constitutively produced in the affected lymph nodes (1989), suggesting IL-6 is key in the pathogenesis of multicentric Castleman disease (MCD). The results of several studies have shown that most MCD symptoms and abnormal laboratory results are improved by anti-IL-6 MCD treatments, such as tocilizumab, a humanized anti-IL-6 receptor antibody, and siltuximab, an anti-IL-6 antibody.

Background Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. Methods We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. Results There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p

Neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammatory response, has been demonstrated as an independent prognosticator for some solid malignancies, including prostate cancer. In the present study, we evaluated the role of NLR in men who underwent prostate needle biopsy for their initial diagnosis of prostatic carcinoma. Both complete blood counts and free/total (F/T) prostate-specific antigen (PSA) ratio were examined in a total of 3,011 men in our institution. Of these, 1,207 had a PSA level between 4 and 10 ng/mL, and 357 of 810 who subsequently underwent prostate needle biopsy were found to have prostatic adenocarcinoma. NLR value was significantly higher in men with PSA of ≥ 20 ng/mL than in those with PSA of < 20 ng/mL (p < 0.001). NLR was also significantly higher in men with positive biopsy than in those with negative biopsy (p < 0.001). Using NLR cut-off point of 2.40 determined by the AUROC curve, positive/negative predictive values of NLR alone and NLR combined with F/T PSA ratio (cut-off: 0.15) were 56.6%/60.8% and 80.7%/60.1%, respectively. Multivariate analysis revealed that not only F/T PSA ratio (HR = 3.13) but also NLR (HR = 2.21) was an independent risk factor for prostate cancer. NLR is thus likely elevated in patients with prostate cancer. Accordingly, NLR, with or without combination with F/T PSA ratio, may function as a new biomarker to predict prostate cancer in men undergoing prostate needle biopsy.

The objective of the study was to evaluate the clinical factors affecting the operative time of flexible ureteroscopy (fURS). We retrospectively evaluated 233 patients with renal stones who had been treated successfully and had stone-free status 3 months after fURS and holmium laser lithotripsy between December 2009 and December 2013 at a single institute. Operative time was divided into three periods (total, before fragmentation, and after starting fragmentation), and associations between possible factors and these periods were analyzed by a multivariate logistic regression model with backward selection. The mean total operative time was 74.0 ± 32.0 min. There were significant differences in the following clinical factors: sex, body height, stone volume, maximum and mean Hounsfield units (HUs), diameter of the ureteral access sheath, and experience of the surgeon, between patients who underwent procedures with a total operative time of less or more than 90 min. A multivariate assessment revealed four independent factors influencing total operative time (P < 0.05): stone volume (P < 0.001), experience of the surgeon (P < 0.001), maximum HUs (P = 0.014), and lack of preoperative stenting (P = 0.027). Larger stone volume, lower experience level of the surgeon, higher HUs, and the absence of preoperative stenting were identified as parameters prolonging the total operative time of fURS and, in particular, the operative time after starting fragmentation. On the other hand, operative time before starting fragmentation, which represented the time required to identify the stone by ureteroscopy and insert the access sheath, was more difficult to predict preoperatively.

Objective To investigate factors predicting spontaneous clearance of residual renal fragments after flexible ureteroscopy. Methods Among 546 patients who underwent lithotripsy with flexible ureteroscopy, 81 had residual renal fragments, as determined by kidney–ureter–bladder films on postoperative day 1. The final outcome was determined at 3 months after the last flexible ureteroscopy session using non-contrast computed tomography. Patient characteristics and preoperative factors were analyzed using the unpaired t-test and χ2-test. Correlations between the possible predictive factors and the spontaneous clearance of residual renal fragments after flexible ureteroscopy were analyzed using a multivariate logistic regression model with backward selection. Results Non-contrast computed tomography at postoperative month 3 showed that 33 cases (40.7%) had spontaneous clearance of residual renal fragments, whereas 48 (59.3%) showed non-clearance. Significant differences were found between these cases in terms of stone number, stone location, presence of lower pole calculi and preoperative stent placement. Multivariate assessment showed that stone number (P = 0.004), presence of lower pole calculi (P = 0.021) and presence of hydronephrosis (P = 0.024) were independent predictors of the spontaneous clearance of residual renal fragments after flexible ureteroscopy. Conclusions Stone number, presence of lower pole calculi and presence of hydronephrosis are independent predictive factors of the spontaneous clearance of residual renal fragments after flexible ureteroscopy.

Right atrial isomerism and pulmonary atresia combined with major aortopulmonary collateral arteries are very rare. Surgical treatment becomes more challenging when an extracardiac total anomalous pulmonary venous connection (TAPVC) requiring surgical repair neonatally is also present. We describe a successful staged Fontan operation for a neonate with a single ventricle, right atrial isomerism, pulmonary atresia with major aortopulmonary collateral arteries, a small central pulmonary artery and a supracardiac TAPVC. Unifocalization of the pulmonary vasculature was achieved by ligating all dual-supply major aortopulmonary collateral arteries at their origins, concomitant with supracardiac TAPVC repair and modified Blalock-Taussig shunt placement at 15 days. The patient underwent patch augmentation of the small stenosed central pulmonary artery at 8 months and bilateral bidirectional Glenn shunt at 14 months. The Fontan operation was completed at 27 months using an intra-extracardiac conduit with fenestration. One year later, catheter examination revealed good Fontan circulation with acceptable central venous pressure, oxygen saturation and cardiac function. We also describe a new angiographic concept of central pulmonary arteriography to visualize more accurately the complex pulmonary circulation system with both major aortopulmonary collateral arteries and a central pulmonary artery.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is considered the most severe end of the tetralogy of Fallot spectrum, whereas complete atrioventricular septal defect associated with tetralogy of Fallot is a rare congenital defect. However, the combination of pulmonary atresia, major aortopulmonary collateral artery and complete atrioventricular septal defect is extremely rare, and surgical repair has not been reported. We describe a successful, 1-stage correction in a 7-month-old boy with this condition, who had an additional complication of a single aortic outlet from the right ventricle and significant atrioventricular valve regurgitation.

Objective We adopted a policy of rapid-staged bilateral pulmonary artery banding (bPAB) before the Norwood (NW) procedure for all patients with hypoplastic left heart syndrome. We hypothesized that this strategy might mitigate some of the traditional risk factors and that postponing a major bypass procedure beyond the newborn period could have both short- and long-term benefits. The purpose of the present study was to evaluate the efficacy of this strategy with respect to the short-term outcomes. Methods From 2008 to 2010, 14 patients underwent bPAB and maintenance of ductal patency with prostaglandin E1 infusion before stage 1 NW. For reference, we also reviewed the data from patients who had undergone the primary NW procedure in the 2 years immediately before the study period. Results The bPAB was performed at a median age of 6 days (range, 2-39), gestational age of 38.5 weeks (range, 36-41), and weight of 2.75 kg (range, 2.3-3.6). The subsequent NW was performed at a gestational age of 43.5 weeks (range, 41-51) and weight of 3.2 kg (range, 2.2-4.9). When the NW procedure was eventually performed on the pBAB group, the maximum blood lactate levels within the first 24 hours after the NW were lower than those in the earlier primary NW group (2.8 ± 0.9 vs 10.1 ± 6.5 mmol/dL, P = .0002) and the urine output in the first 24 hours after the NW was greater in the pPAB group (4.1 ± 2.1 vs 2.2 ± 1.5 mL/kg/h; P = .0051). Conclusions These data suggest that rapid-staged bPAB before NW can reduce the challenge of postoperative management in the early postoperative period after the NW procedure and have potential to improve the outcomes.

Objective To develop and internally validate a preoperative nomogram for predicting stone-free status (SF) after flexible ureteroscopy (fURS) for renal stones, as there is a need to predict the outcome of fURS for the treatment of renal stone disease. Patients and Methods We retrospectively analysed 310 fURS procedures for renal stone removal performed between December 2009 and April 2013. Final outcome of fURS was determined by computed tomography 3 months after the last fURS session. Assessed preoperative factors included stone volume and number, age, sex, presence of hydronephrosis and lower pole calculi, and ureteric stent placement. Multivariate logistic regression analysis with backward selection was used to model the relationship between preoperative factors and SF after fURS. Bootstrapping was used to internally validate the nomogram. Results Five independent predictors of SF after fURS were identified: stone volume (P 50 fURS (P = 0.026), stone number (P = 0.075), and presence of hydronephrosis (P = 0.047). We developed a nomogram to predict SF after fURS using these five preoperative characteristics. Total nomogram score (maximum 25) was derived from summing individual scores of each predictive variable; a high total score was predictive of successful fURS outcome, whereas a low total score was predictive of unsuccessful outcome. The area under the receiver operating characteristics for nomogram predictions was 0.87. Conclusion The nomogram can be used to reliably predict SF based on patient characteristics after fURS treatment of renal stone disease.

High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs.

We evaluated possible changes in the function and expression of T-type and N-type Ca(2+) channels in the bladder of rats with bladder outlet obstruction.Female Sprague Dawley® rats were divided into a group with bladder outlet obstruction created by partial urethral ligation and a sham operated group. Six weeks postoperatively we determined the mRNA expression of T-type and N-type Ca(2+) channels in the bladder, dorsal root ganglion and spinal cord. We also cystometrically investigated expression by intravenous administration of the T-Ca blocker RQ-00311610 or the N-type Ca(2+) channel blocker ω-conotoxin GVIA. We then performed in vitro functional studies of detrusor strips using these blockers.mRNA expression of T-type Ca(2+) channels in the bladder detrusor and mucosa layers, and the spinal cord dorsal horn, and N-type Ca(2+) channels in the whole bladder and detrusor layer, and the spinal cord dorsal horn was greater in the obstructed group than the sham operated group. In obstructed rats bladder capacity and voided volume increased after RQ-00311610 administration but the number of nonvoiding contractions decreased after ω-conotoxin GVIA administration. Detrusor strips from obstructed rats showed weaker contractile responses to electrical field stimulation, particularly in regard to the purinergic component. ω-Conotoxin GVIA suppressed electrical field stimulation induced contractions only in the detrusor of obstructed rats, especially the cholinergic component.Blocking T-type Ca(2+) channels increased bladder capacity while N-type Ca(2+) channel blockade inhibited nonvoiding contractions in rats with bladder outlet obstruction. Decreased bladder efferent neurotransmission occurred after bladder outlet obstruction, predominantly in its purinergic component and detrusor contractions via cholinergic neurotransmission were activated in a compensatory manner, probably via N-type Ca(2+) channel up-regulation.

OBJECTIVES: Bicuspid aortic valve (BAV) is a common risk factor for valve-related problems and occurs more frequently in patients with an interrupted aortic arch (IAA) or coarctation of the aorta (CoA), combined with a ventricular septal defect (VSD), than in the general population. We have been using conventional repair for patients with IAA/CoA+VSD, including those with a very small aortic valve (AV). We retrospectively investigated the outcomes of these patients from the perspective of valve morphology. METHODS: Between 2000 and 2012, 50 consecutive patients underwent conventional repair for CoA/IAA with VSD [one-stage repair, 44 (88%); staged repair, 6 (12%)]. The criteria for conventional repair were as follows: an AV annulus diameter (AVD) z-score of >�6.0; mitral valve annulus diameter z-score of >�3.0; without retrograde flow in the proximal arch. Sixteen (32%) patients had BAV (Group B); the remaining 34 (68%) patients had a tricuspid AV (Group T). The surgical outcomes in both groups were investigated. RESULTS: No mortality occurred in the cohort. The median follow-up times were 6 years and 3 months (6 months to 11 years and 8 months) and 6 years and 2 months (4 months to 11 years and 4 months) in Groups B and T, respectively (P> 0.05). The preoperative data (median age at repair, median body weight and median AVD) were comparable in the two groups (P> 0.05). Two patients (4%) underwent reintervention in the aortic arch: 1 patient underwent balloon angioplasty for re-coarctation; the other removal of the interposed graft because of somatic growth. In both groups, the AVD became significantly larger at the 1-year follow-up, approximating the normal value. Three (6%) patients underwent a total of eight valve-related reinterventions (balloon angioplasty, 6; Ross operation, 1; valve replacement, 1). All three had BAV, and the AVD was 3.8–5.6 mm (z-score, �3.4 to �1.6). The 5-year valve-related reintervention-free survival rate was 76% and 100% in Groups B and T, respectively (P< 0.01). CONCLUSIONS: The long-term outcomes after conventional repair under our criteria were acceptable. BAV was a significant risk factor for valve-related reinterventions after conventional repair for IAA/CoAwith VSD.

Purpose The optimal treatment duration time and the causal relationship between neoadjuvant endocrine therapy and clinical response are not clear. Therefore, we conducted the present study to investigate the potential benefits of neoadjuvant exemestane therapy with the goal of identifying the optimal treatment duration. Methods This study was conducted at three hospitals, as a multicenter, randomized phase II trial(UMIN000005668) of pre-operative exemestane treatment in post-menopausal women with untreated primary breast cancer. Fifty-one post-menopausal women with ER-positive and/or PgR-positive invasive breast cancer were randomly assigned to exemestane for 4 months or 6 months. Clinical response, pathological response, and decisions regarding breast-conserving surgery were the main outcome measures. Results Of the 52 patients that enrolled, 51 patients underwent surgery. Of those, 26 and 25 patients had been treated with exemestane for 4 and 6 months, respectively. Treatments were performedat 3 hospitals in Japan between April 2008 and August 2010. The response rates as assessed by clinical examination were 42.3% and 48.0% for 4 and 6 months of treatment, respectively. Pathological responses (minimal response or better) were observed in 19.2% and 32.0% of patients, and breast-conserving surgery was performed on 50.0% and 48.0% of patients from the 4 and 6 month treatment groups, respectively. Conclusion The results of this study demonstrate that responses were equal to 4 or 6 months of exemestane treatment. Therefore, we propose that the rates of breast-conserving surgery could be maximized by 4 months of treatment. Furthermore, in addition to using exemestane as a preoperative treatment in post-menopausal women with ER-positive breast cancer, we envision administering the drug over the long term under careful clinical supervision.

Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and β-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.

We investigated the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of lower urinary tract symptoms using silodosin. In addition, the ability of the Core Lower Urinary Tract Symptom Score to detect overactive bladder in male patients with lower urinary tract symptoms was examined. The present study included 241 males with benign prostatic hyperplasia treated at 31 medical facilities between June 2009 and December 2010. All patients were given silodosin, and the effects of silodosin intake were measured using four questionnaires: the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score, Overactive Bladder Symptom Score and Quality-of-Life index. The efficacy of silodosin for treating lower urinary tract symptoms was validated according to the total scores of all four questionnaires weighted equally (P

Although pulmonary valve-sparing repair is preferable for patients with tetralogy of Fallot, the repair of very small pulmonary valves is challenging. The present study evaluates our modification for preserving severely hypoplastic pulmonary valves in patients with tetralogy of Fallot.Sixty-eight consecutive patients who underwent complete repair of a tetralogy of Fallot between 2005 and 2011 were retrospectively reviewed. Patients with pulmonary atresia, absence of a pulmonary valve, atrioventricular septal defect and/or subarterial ventricular septal defect were excluded. There were 19 (28%) patients with a severely hypoplastic pulmonary annulus determined by preoperative echocardiography (z-score-4). For these patients, we collected echocardiographic data and information about their postoperative course.Valve preserving was successful in 11 of 19 (58%) of the z-4 group, compared with 48 of 49 (98%) of the z-4 group. In the z-4 valve-sparing subgroup (n = 11), the preoperative pulmonary valve diameter z-score was -4.9 (range -6.3 to -4.3), and an approach involving ventriculotomy with no transannular patch was employed at a mean age of 6.9 (range 2.2-16.1) months. In this subgroup, residual right ventricular outflow tract velocity was 2.4 ± 0.6 m/s at discharge from the hospital. During a mean follow-up of 2.6 ± 2.4 years, no reintervention was necessary. Late right ventricular outflow tract velocity was 2.2 ± 0.6 m/s, and there was no severe pulmonary regurgitation. The pulmonary valve annulus grew in relation to the patient's body surface area (z = -0.51, range -4.2-0.24) without any aneurysmal changes in the right ventricular outflow tract.Although our modification of valve-sparing repair for severely hypoplastic pulmonary valves in patients with tetralogy of Fallot could not be applied in all patients, this strategy enabled acceptable growth of the valve annulus, with only mild stenosis during the early to mid-term follow-up. This modification seems to be an option, even for a very small pulmonary valve.

Purpose: Nephron sparing surgery is an effective surgical option in patients with renal cell carcinoma. Laparoscopic partial nephrectomy involves clamping and unclamping techniques of the renal vasculature. This study compared the postoperative renal function of partial nephrectomy using an estimation of the glomerular filtration rate (eGFR) for a Japanese population in 3 procedures; open partial nephrectomy in cold ischemia (OPN), laparoscopic partial nephrectomy in warm ischemia (LPN), and microwave coagulation using laparoscopic partial nephrectomy without ischemia (MLPN). Materials and Methods: A total of 57 patients underwent partial nephrectomy in Yokohama City University Hospital from July 2002 to July 2008. 18 of these patients underwent OPN, 17 patients received MLPN, and 22 patients had LPN. The renal function evaluation included eGFR, as recommended by The Japanese Society of Nephrology. Results: There was no significant difference between the 3 groups in the reduction of eGFR. eGFR loss in the OPN group was significantly higher in patients that experienced over 20 minutes of ischemia time. eGFR loss in LPN group was significantly higher in patients that experienced over 30 minutes of ischemia time. Conclusion: This study showed that all 3 procedures for small renal tumor resection were safe and effective for preserving postoperative renal function.

Background The neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response, has been demonstrated to correlate with patient outcomes for various solid malignancies. We investigated the utility of the pretreatment NLR as a prognosticator in patients who presented with penile cancer. Methods A total of 41 patients who underwent complete blood count with differential and subsequent radical penectomy from 1988 to 2014 were analyzed. We assessed the correlation between the NLR and the prognosis of penile cancer. Results The median and mean (± SD) NLRs in 41 penile cancer patients were 3.42 and 5.03 ± 4.99, respectively. Based on the area under receiver operator characteristic curve, the cut-off value of NLR was determined to be 2.82. Patients with a high NLR (≥2.82) showed a significantly poorer cancer-specific survival (p = 0.023) than those with a low NLR. Conclusions The pretreatment NLR may function as a biomarker that precisely predicts the prognosis in patients with penile cancer.

We evaluated aging related bladder dysfunctions and biological changes in the bladder and dorsal root ganglia in rats. We also investigated whether long-term caloric restriction may have preventive effects on these changes.Male Fischer 344 rats were divided into a young group (age 6 months) and an old group (age 25 to 28 months), each with free access to normal food, and an old group (age 25 to 28 months) with food restricted to 3 days per week. Conscious cystometry, cDNA microarray analysis, immunohistochemistry and oxidative stress measurements of the bladder and dorsal root ganglia were performed.The old group with free access to normal food showed higher threshold pressure, more nonvoiding contractions and lower bladder compliance than the young group with free access to food. Old rats with free access showed greater post-void residual volume and lower voiding efficiency than old rats with caloric restriction and young rats. In the old group with free access 83 genes in the bladder and 48 in the L6 dorsal root ganglia were up-regulated compared with old rats with caloric restriction and young rats. These genes were mostly related to immune and inflammatory responses. Immunohistochemistry showed stronger expression of the immune response protease Gzm (granzyme) B and the collagenase Mmp13 (matrix metalloproteinase-13) in the bladder of old rats with free access vs old rats with caloric restriction and young rats. The level of malondialdehyde, an oxidative stress marker, was higher in the bladder of old rats with free access than in young rats but there was no difference between old rats with caloric restriction and young rats with free access to food.In rats aging leads to storage and voiding dysfunctions associated with immune and inflammatory related responses in the bladder and dorsal root ganglia, and with increased oxidative stress in the bladder. Caloric restriction reduced these aging related changes.

Background There is no reliable biomarker for predicting the prognosis of patients who undergo radical cystectomy for bladder cancer. Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) could function as a useful prognostic factor in several types of malignancies. This study aimed to assess the usefulness of NLR in bladder cancer. Methods A total of 74 patients who underwent radical cystectomy in our institutions from 1999 to 2014 were analyzed. The NLR was calculated using the patients’ neutrophil and lymphocyte counts before radical cystectomy. An immunohistochemical analysis was also performed to detect tumor infiltrating neutrophils (CD66b) and lymphocytes (CD8) in bladder cancer specimens. Results A univariate analysis showed that the patients with a high NLR (≥2.38; HR = 4.84; p = 0.007), high C-reactive protein level (>0.08; HR = 10.06; p = 0.030), or pathological lymph node metastasis (HR = 4.73; p = 0.030) had a significantly higher risk of cancer-specific mortality. Kaplan-Meier and log-rank tests further revealed that NLR was strongly correlated with overall survival (p = 0.018), but not progression-free survival (p = 0.137). In a multivariate analysis, all of these were found to be independent risk factors (HR = 4.62, 10.8, and 12.35, respectively). The number of CD8-positive lymphocytes was significantly increased in high-grade (p = 0.001) and muscle-invasive (p = 0.012) tumors, in comparison to low-grade and non-muscle-invasive tumors, respectively. Conclusions The NLR predicted the prognosis of patients who underwent radical cystectomy and might therefore function as a reliable biomarker in cases of invasive bladder cancer.

Background The neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response in critical care patients, has been suggested as an independent prognostic factor for several solid malignancies. We investigated the utility of pretreatment NLR as a prognosticator in patients who presented with metastatic prostate cancer. Methods We first investigated the correlation between NLR and prostate-specific antigen (PSA) levels in 1464 men who had both tests and were found to have prostate cancer on their biopsies at our institution from 1999 to 2015. We then assessed the relationship between pretreatment NLR and the prognosis in 48 patients who were diagnosed with prostate cancer metastasized to the lymph node and/or bone. Results The NLR value was significantly elevated in men with higher PSA than in those with lower PSA (p