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Supplementary Data includes Supplementary Methods, Supplementary Results, Supplementary Table S1-S13, Supplementary Figure S1-S7, and Supplementary References.

Purpose: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. Experimental Design: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. Results: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24–5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60–8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. Conclusions: Detecting low-frequency ctDNA variants with a VAF

The present case study was conducted on a 74-year-old man who visited our department due to a left renal and retroperitoneal tumor on computed tomography (CT). The patient was diagnosed with left renal cancer lymph node metastasis and was hospitalized a few weeks prior to surgery due to fever, malaise, and severe appetite loss. Biochemical laboratory findings at admission showed markedly high levels of inflammation. The cause of high inflammatory response was paraneoplastic syndrome. Tumor resection was considered necessary, and left nephrectomy and lymphadenectomy were performed; however, it did not improve the inflammatory response. After operation, positron emission tomography-CT revealed hyperaccumulation of 18F-fluorodeoxyglucose in the bone marrow throughout the body. Pathological examination of the resected specimen and bone marrow aspiration revealed the coexistence of idiopathic multicentric Castleman disease (CD) and renal cancer. Prednisolone and tocilizumab were administered for idiopathic multicentric CD and a tyrosine kinase inhibitor for renal cancer; however, they had poor therapeutic effect, and the patient died. CD is characterized by systemic symptoms due to the overproduction of interleukin-6. Treatment for idiopathic multicentric CD involves steroid and anti-interleukin-6 therapy. The diagnostic criteria for CD require the exclusion of malignant tumors although there are some cases in which CD and malignant tumors coexist. The prognosis for CD is relatively good; however, as in this case, the prognosis of CD coexisting with uncontrollable renal cancer is insufficient due to poor improvement in the inflammatory response.

OBJECTIVE To evaluate the impact of cancer therapy on post-treatment ejaculation in patients with testicular cancer. METHODS A total of 74 testicular cancer survivors provided completed International Index of Erectile Function-15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." RESULTS Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post-treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function-15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P

Introduction Atypical femoral fractures are atraumatic or minimally traumatic fractures and rare side effects of bone resorption inhibitors. Bone resorption inhibitors are frequently used in the treatment of prostate cancer. Case presentation A 62-year-old man complained of difficulty in walking and left lower limb pain. Androgen deprivation and denosumab therapy for prostate cancer-induced bone metastasis was initiated 27 months ago. Even though the prostate-specific antigen level did not increase, imaging studies indicated the possibility of bone metastasis. The patient underwent bone biopsy; however, no malignancy was detected. Afterward, he had a fall, causing a complete fracture in his left femur. Conclusion Atypical femoral fractures occasionally mimic typical imaging findings and outcomes of bone metastasis. This case is important for recognizing such cases.

Background A spontaneous iliopsoas muscle hematoma is relatively rare and often associated with abnormal coagulation. Nafamostat mesilate is an anticoagulant agent that is sometimes used to treat hemodialysis patients at high risk of bleeding. Although severe drug allergy caused by nafamostat mesilate was previously reported, spontaneous iliopsoas muscle hematoma secondary to disseminated intravascular coagulation caused by nafamostat mesilate allergy has not yet been reported. Case presentation Severe nafamostat mesilate allergy occurred in a 78-year-old male patient with a 2-year history of hemodialysis. During hospitalization, disseminated intravascular coagulation occurred followed by a progressive iliopsoas muscle hematoma a few days later. Emergent transarterial lumbar artery embolization was successfully performed. Conclusion For dialysis patients, a detailed medical history including repeated nafamostat mesilate use and considering an allergy to nafamostat mesilate in differential diagnosis are critical. In addition to early diagnosis, when an iliopsoas hematoma occurs, early intravascular treatment is important.

A combination therapy of nivolumab and ipilimumab is effective for advanced renal cell carcinoma, but there are concerns about immune-related adverse events. A 46-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On days 16 and 49, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. A 70-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On day 44, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. Both patients were diagnosed with anaphylaxis due to the contrast agent.

We report a histologically pure stage 1 seminoma with an elevated human chorionic gonadotropin (hCG). A 38 year-old man was referred for the evaluation of the left testicular swelling. He showed an elevated serum hCG level of 25,265 mIU/ml with normal a fetoprotein and lactate dehydrogenase. Imaging showed heterogeneous tumor without any metastatic lesions. We conducted 4 courses of chemotherapy before detecting hCG nadir. The final pathological report showed pure seminoma with syncytiotrophoblastic cells but no choriocarcinoma components. The patient remains disease free until present time. The case raised several questions regarding diagnosis and treatment strategy for bulky testicular seminoma.

Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression. HOTAIR expression in tumors was significantly correlated with nuclear grade, lymph-node metastasis, and lung metastasis. High HOTAIR expression was associated with a poor prognosis in both our dataset and The Cancer Genome Atlas dataset. Migratory capacity was enhanced in RCC cell lines in a HOTAIR-dependent manner. HOTAIR overexpression accelerated tumorigenicity and lung metastasis in immunodeficient mice. Microarray analysis revealed that IGFBP2 expression was upregulated in HOTAIR-overexpressing cells compared with control cells. The enhanced migration activity of HOTAIR-overexpressing cells was attenuated by IGFBP2 knockdown. IGFBP2 and HOTAIR were co-expressed in clinical RCC samples. Our findings suggest that the HOTAIR-IGFBP2 axis plays critical roles in RCC metastasis and may serve as a novel therapeutic target for advanced RCC.

Case 1. A 48-year-old man with no history of hypertension was referred to our hospital with a 1 cm bladder tumor. According to cystoscopy, magnetic resonance imaging and 131I-MIBG scintigraphy, we diagnosed it as a paraganglioma of the bladder. Partial cystectomy was performed. The histological findings supported the diagnosis of paraganglioma of the bladder. Six years later, he was free of any evidence of recurrence. Case 2. A 64-year-old woman with hypertension was pointed out to have a 1cm bladder mass by ultrasound in a health examination. She was referred to our hospital for further examination. Cystoscopoy revealed a 1 cm intramural nodule covered by intact urothelium at the right posterior wall. Submucosal bladder tumor was not diagnosed as paraganglioma by cold punch biopsy. So, transurethral resection of the bladder tumor was performed for differential diagnosis. The tumor was hypervascular and involved the muscular layer of the bladder. Although a transient elevation of blood pressure occurred during the procedure, the tumor was resected as completely as possible. The histological diagnosis was paraganglioma of the bladder. She has been followed up for 27 months after operation without any evidence of recurrence.

Primary amyloidosis localized in the urinary bladder is comparatively rare,and 40% of the patients complain of lower urinary tract symptoms (LUTS). Although standard management for amyloidosis localized in the urinary bladder is not established,transurethral resection (TUR) is performed in most of the cases to diagnose the disease and to control bleeding. TUR is not considered as radical therapy for amyloidosis localized in the urinary bladder because of frequent recurrence. Dimethyl sulfoxide (DMSO) administered through intravenous,percutaneous or intravesical route has been shown to be effective for treating and preventing recurrence of the disease,but its effect on LUTS due to amyloidosis localized in the urinary bladder has not been demonstrated. We report a case showing improvement of LUTS and in which recurrence of amyloidosis localized in the urinary bladder was prevented for 18 months by intravesical DMSO therapy.

Renal cell carcinoma (RCC) during pregnancy is rare, and the treatment of this condition requires appropriate steps to treat both the patient and the fetus. To the best of our knowledge, this is the first report to describe a case of RCC with tumor thrombus in the inferior vena cava (IVC) occurring during pregnancy. The affected 46-year-old pregnant woman with placenta previa was clinically diagnosed with cT3bN0M0 RCC at 25 weeks gestation. Therapeutic considerations included risk of sudden pulmonary embolism, risk of thrombosis or intraoperative hemorrhage, and safe delivery of the fetus. After extensive consultation with obstetricians and pediatricians, the surgical management was divided into two steps. First, the patient underwent Caesarean section and simultaneous hysterectomy at 26 weeks gestation. Then, 16 days after delivery, when hemodynamics and hemostasis had improved due to termination of gestation, the patient underwent radical nephrectomy with concomitant IVC thrombectomy.

A 64-year-old man was referred to our hospital with chief complaints of gross hematuria and pollakisuria. Cystoscopic examination showed non-papillary broad basis tumor on the left lateral wall involving the left ureteral orifice. Computed tomography (CT) and magnetic resonance imaging revealed left hydronephrosis and urinary bladder tumor which extended outside of the bladder wall. Transurethral biopsy showed grade 3 urothelial carcinoma with glandular differentiation including signet ring cells. Radical cystectomy, left nephrureterectomy and right ureterocutaneostomy were performed. Pathological examination showed urothelial carcinoma; pT3aN0. Lymph node metastasis occurred five months later. Three courses of M-VAC chemotherapy (methotrexate, vinblastine, adriamycin, cisplatin) were done with little effectiveness. Sixteen months after the operation, he complained of anorexia and tenesmus, and CT showed annular thickening of the rectal wall. A fecal diversion was performed, but he died two months later.

Method for determination of mono- and diglycerides by gas liquid chromatography as their TMS derivatives or acetates were examined. Chromatograms which show completely separated and sharp peaks were obtained for the both derivatives.Calibration factors for glycerides of fatty acids of carbon numder 14, 16 and 18 were determined by using standard materials. Peak areas observed for diglycerides were relatively small in comparison with those for monoglycerides.Five sorts of commercial products of monoglycerides were used for investigation. Saponification value and hydroxyl value calculated from the GLC composition of the products well agreed with those values determined by chemical analysis, respectively. Contents of monoglyceride of the products determined by GLC and chemical analysis also showed good coincidence.