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Abstract Clostridioides difficile, a cause of healthcare-associated infections, poses a significant global health threat. This multi-institutional retrospective study focuses on epidemic dynamics, emphasizing minor and toxin-negative clinical isolates through high-resolution genotyping. The genotype of the C. difficile clinical isolates during 2005 to 2022 was gathered from 14 hospitals across Japan (N = 982). The total number of unique genotypes was 294. Some genotypes were identified in every hospital (cross-regional genotypes), while others were unique to a specific hospital or those in close geographic proximity (region-specific genotypes). Notably, a hospital located in a sparsely populated prefecture exhibited the highest prevalence of region-specific genotypes. The isolation rate of cross-regional genotypes positively correlated with the human mobility flow. A 6-month interval analysis at a university hospital from 2019 to 2021 revealed a temporal transition of the genotype dominance. The frequent isolation of identical genotypes over a brief timeframe did not always align with the current criteria for defining nosocomial outbreaks. This study highlights the presence of diverse indigenous C. difficile strains in regional environments. The cross-regional strains may have a higher competency to spread in the human community. The longitudinal analysis underscores the need for further investigation into potential nosocomial spread.

Abstract Germ cells preferentially induce apoptosis in response to DNA damage to avoid genomic mutations. Apoptosis of germ cells is closely related to cancer development and chemotherapy resistance; however, its regulatory mechanism is unclear. Here, we suggest that testis-specific lncRNA LINC03074 is involved in male germ cell apoptosis by regulating the expression of the proto-oncogene MDM2. LINC03074 is highly expressed in the sperm of healthy adult testes and cancer cells of testes with testicular germ cell tumors (TGCTs). LINC03074 binds to MDM2 mRNA via an Alu element, thereby reducing MDM2 protein levels. LINC03074 stimulates STAU1-mediated nuclear export of MDM2 mRNA by increasing STAU1 binding to MDM2 mRNA in the cell nucleus, thereby promoting PKR-mediated translational repression in the cytoplasm. The induction of apoptosis in TGCT cells and their responsiveness to the anticancer drug cisplatin is enhanced by LINC03074. Notably, LINC03074 increased E2F1 expression without increasing p53, the primary target of MDM2, and upregulated the apoptotic gene p73, the target gene of E2F1. LINC03074-mediated regulation of apoptosis contributes to the responsiveness of TGCTs to anticancer drug-induced DNA damage.

ABSTRACT Purpose: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). Materials and Methods: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Results: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Conclusions: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI

Introduction Histological outcome of the targeted focal therapy is in principle confirmed by targeted needle biopsy from the treated area in clinical trial. Herein, we report a rare case in which the MFT was followed by RARP. Case presentation A 68‐year‐old man with PSA 9.6 ng/mL and PI‐RADS 4 lesion in the right transition zone on multi‐parametric MRI underwent MR/ultrasound fusion‐guided targeted biopsy, which revealed grade‐group 1 cancer. Targeted focal therapy with microwave ablation was performed, resulting in disappearance of the PI‐RADS 4 lesion at post‐operative 4 months. However, PSA rose to 11.5 ng/mL, and a new PI‐RADS 4 lesion, was identified in the left peripheral zone. RARP was performed to reveal new grade‐group 3 cancer, and no viable cells in the previously treated area with MFT. Conclusion RARP was safely performed even after MFT and proved the pathological complete response of microwave ablation.

Abstract The objective of this study is to compare the efficacy of apalutamide and bicalutamide in combination with androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively collected the data of about 330 patients with metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and August 2023. Sixty-one patients were administered apalutamide (240 mg/day) with androgen deprivation therapy (group A), and 269 patients were administered bicalutamide (80 mg/day) with androgen deprivation therapy (group B). Propensity score matching was used to adjust for clinical background factors between the two groups. PSA progression-free survival and overall survival were significantly longer in group A than in group B among the matched patients. Apalutamide therapy was a significant independent factor for OS in matched patients. The second progression-free survival of group A was significantly longer than that of group B in matched patients. Patients treated with apalutamide achieved ≥ 90% PSA decline from baseline faster and in larger numbers than those with bicalutamide. Apalutamide combined with ADT may be superior to bicalutamide alone in terms of OS and PSA-PFS in patients with mHSPC.

Abstract Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before and after treatment in fourteen patients with metastatic bladder cancer who were indicated for systemic drug therapy. Patients were assessed via imaging before and after drug treatment, and cell-free DNA (cfDNA) analysis was performed to detect three parameters: cfDNA level, ERRB2 gene copy numbers, and telomerase reverse transcriptase (TERT) gene mutations. We hypothesized that decreased cfDNA levels, a normal copy number of ERB-B2 receptor tyrosine kinase 2 (ERBB2), and the absence of the TERT C228T mutation indicate cancer suppression. We found that a > 1.8-fold increase in cfDNA levels, increased copy number of ERBB2, or the existence of the TERT C228T mutation indicated disease progression. Stable cfDNA levels, normal ERBB2 copy number, and the absence of TERT C228T mutations indicate a stable cancer status. Collectively, our results show that the combination of cfDNA concentration, TERT mutation, and ERBB2 copy number may be useful for determining the efficacy of drug therapy in patients with metastatic bladder cancer.

Abstract SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level

Abstract Although recent clinical trials of new therapeutic agents for metastatic urothelial carcinoma have shown prolonged overall survival, there are few real-world evidence. To assess the impact of new therapeutic agents, we performed retrospective analysis for consecutive 158 metastatic urothelial carcinoma patients who performed systemic therapy in our institution between May 2008 and August 2023. We defined a period from May 2008 to December 2017, when pembrolizumab was first introduced to the clinical setting in the new therapeutic agents for metastatic urothelial carcinoma in Japan, as “pre new drug era” and a period from January 2018 to August 2023 as “post new drug era”. We compared overall survival between pre- and post- new drug era using Kaplan–Meier method with log rank test. Median overall survival of pre- and post- new drug era were 14.5 months (95% confidence intervals: 11.6–16.7) and 23.1 months (95% confidence intervals: 14.5-NA), respectively (p

BackgroundWith the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS).MethodsA 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement.ResultsFifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community.ConclusionsFT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS.

Abstract γ-Glutamylcyclotransferase (GGCT) is highly expressed in multiple types of cancer tissues and its knockdown suppresses the growth of cancer cells in vitro and in vivo. Although GGCT is a promising target for cancer therapy, the mechanisms underlying the antitumor effects remain unclear. The knockdown of GGCT inhibited the MEK-ERK pathway, and activated the tumor suppressor retinoblastoma gene (RB) at the protein level in cancer cell lines. c-Met was down-regulated by the knockdown of GGCT in cancer cells and its overexpression attenuated the dephosphorylation of RB and cell cycle arrest induced by the knockdown of GGCT in lung cancer A549 cells. STAT3 is a transcription factor that induces c-Met expression. STAT3 phosphorylation and its nuclear expression level were decreased in GGCT-depleted A549 and prostate cancer PC3 cells. The simultaneous knockdown of AMPK and GGCT restored the down-regulated expression of c-Met, and attenuated the dephosphorylation of STAT3 and MEK-ERK-RB induced by the knockdown of GGCT in PC3 cells. An intraperitoneal injection of a GGCT inhibitor decreased c-Met protein expression in a mouse xenograft model of PC3 cells. These results suggest that the knockdown of GGCT activates the RB protein by inhibiting the STAT3-c-Met-MEK-ERK pathway via AMPK activation.

Abstract In a world that seeks precision medicine, genetic testing is gaining importance in clinical decision making. We previously reported the utility of a novel tool for longitudinally dividing core needle biopsy (CNB) tissues into two filamentous tissues that can provide paired mirror image-like tissues (mirror-tissues) that spatially match each other. In this study, we investigated its application in gene panel testing in patients who underwent prostate CNB. Four hundred and forty-three biopsy cores were obtained from 40 patients. Of them, 361 biopsy cores (81.5%) were judged by a physician to be appropriate for dividing into two pieces using the new device, of which a histopathological diagnosis was successfully reached in 358 biopsy cores (99.2%). Among them, the quality and quantity of nucleic acid in 16 appropriately divided cores were assessed and found to be sufficient for gene panel testing, and histopathological diagnosis was successfully obtained from the remaining divided cores. The novel device for longitudinally-dividing CNB tissue provided mirror image-like paired-tissues for gene panel and pathology testing. The device might be a promising tool for obtaining genetic and molecular biological information, in addition to histopathological diagnosis, helping to advance personalized medicine.

Abstract To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073 observations of PSA values in Japanese men aged 18–98 years (2007–2017), including healthy men and those diagnosed with prostate cancer. Percentiles for 262,639 PSA observations in healthy men aged 18–70 years were calculated and plotted to elucidate the normal fluctuation range for PSA values by age. Univariable and multivariable logistic regression analyses were performed to develop a predictive model for prostate cancer incidence. PSA levels and PSA velocity increased with age in healthy men. However, there was no difference in PSA velocity with age in men diagnosed with prostate cancer. Logistic regression analysis showed an increased risk of prostate cancer for PSA slopes ranging from 0.5 to 3.5 ng/mL/year. This study provides age-specific normal fluctuation ranges for PSA levels in men aged 18–75 years and presents a novel and personalized prediction model for prostate cancer incidence. We found that PSA slope values of > 3.5 ng/mL/year may indicate a rapid increase in PSA levels caused by pathological condition such as inflammation but are unlikely to indicate cancer risk.

Background: Several reports are available regarding the treatment decision regret of patients receiving conventional treatments for localized prostate cancer (PCa); yet data on patients undergoing focal therapy (FT) are sparse. Objective: To evaluate the treatment decision satisfaction and regret among patients who underwent FT for PCa with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). Design, setting, and participants: We identified consecutive patients who underwent HIFU or CRYO FT as the primary treatment for localized PCa at three US institutions. A survey with validated questionnaires, including the five-question Decision Regret Scale (DRS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5), was mailed to the patients. The regret score was calculated based on the five items of the DRS, and regret was defined as a DRS score of >25. Outcome measurements and statistical analysis: Multivariable logistic regression models were applied to assess the predictors of treatment decision regret. Results and limitations: Of 236 patients, 143 (61%) responded to the survey. Baseline characteristics were similar between responders and nonresponders. During a median (interquartile range) follow-up of 43 (26–68) mo, the treatment decision regret rate was 19.6%. On a multivariable analysis, higher prostate-specific antigen (PSA) at nadir after FT (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.1–2, p = 0.009), presence of PCa on follow-up biopsy (OR 3.98, 95% CI 1.5–10.6, p = 0.006), higher post-FT IPSS (OR 1.18, 95% CI 1.01–1.37, p = 0.03), and newly diagnosed impotence (OR 6.67, 95% CI 1.57–27, p = 0.03) were independent predictors of treatment regret. The type of energy treatment (HIFU/CRYO) was not a predictor of regret/satisfaction. Limitations include retrospective abstraction. Conclusions: FT for localized PCa is well accepted by the patients, with a low regret rate. Higher PSA at nadir, presence of cancer on follow-up biopsy, bothersome postoperative urinary symptoms, and impotence after FT were independent predictors of treatment decision regret. Patient summary: In this report, we looked at the factors affecting satisfaction and regret in patients with prostate cancer undergoing focal therapy. We found that focal therapy is well accepted by the patients, while presence of cancer on follow-up biopsy as well as bothersome urinary symptoms and sexual dysfunction can predict treatment decision regret.

Introduction Metastasis to the bone marrow is rare in testicular germ cell tumor patients. We report a case of a patient with a non‐seminomatous testicular germ cell tumor who presented with bone marrow metastases after intensive chemotherapy. Case presentation A 36‐year‐old man was admitted to the hospital with pancytopenia. Previously, he had received intensive care for an advanced left testicular germ cell tumor. Although multidisciplinary treatments including several regimens of salvage chemotherapy, desperation retroperitoneal lymph node dissection, and focal radiotherapy were performed, the serum tumor marker alfa‐fetoprotein was not normalized and there were no findings of relapse by several imaging modalities. Bone marrow aspirate, conducted to diagnose a cause of pancytopenia, revealed metastatic germ cell tumors in the bone marrow. Conclusion Bone marrow metastasis should be considered as a differential diagnosis in patients with germ cell tumors whose serum tumor makers are not normalized without any radiographic finding of recurrence.

Introduction The presence of two different histologic types of renal cell carcinoma in the same kidney is rare in clinical practice. This report describes a patient with ipsilateral renal cell carcinomas, consisting of a clear cell renal cell carcinoma and a papillary type 1 renal cell carcinoma, who was successfully treated by robot‐assisted partial nephrectomy. Case presentation A 70‐year man was referred to our hospital for the treatment of two right mid‐pole renal tumors, measuring 51 mm and 31 mm in diameter. The two tumors, which differed in contrast enhancement on computed tomography, were removed simultaneously by robot‐assisted partial nephrectomy. Histopathological and immunohistochemical findings confirmed that one tumor was a clear cell renal cell carcinoma, pT1a, and the other was a papillary type1 renal cell carcinoma, pT1b. Conclusion This report describes a rare patient presenting with two ipsilateral renal cell carcinomas differing in histology. Robot‐assisted partial nephrectomy was the safe and effective nephron‐sparing surgery, even in patients with complex double renal tumors.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-β has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H₂O₂) and examined the effects of three TGF-β inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-β inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-β inhibitors. In our present study, TGF-β inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-β inhibitor.

Cushing’s syndrome and pheochromocytomas (PCCs) are associated with endocrine hypertension. Cortisol-producing adrenal adenomas are a major cause of Cushing’s syndrome. Simultaneous occurrence of cortisol-producing adrenal adenomas and PCCs is rare. Additionally, a PCC generally produces catecholamines in proportion to its size; therefore, micro-PCCs are rarely found in clinical practice. It is unknown whether micro-PCCs produce excess catecholamines during the pre-biochemical phase. Herein, we report the case of a 53-year-old woman who was referred to our hospital for further evaluation of left adrenal incidentaloma. She had been suffering from hypertension for 7 years. Endocrine tests indicated autonomous cortisol secretion, and she was diagnosed with cortisol-producing adrenal adenoma. A laparoscopic left adrenalectomy was performed. The final pathological examination revealed an adrenocortical adenoma measuring 26 × 24 mm. In addition, a micro-PCC measuring 3 × 2 mm was incidentally found near the cortisol-secreting adrenal adenoma in the ipsilateral adrenal gland. All catecholamine biosynthetic enzymes, tyrosine hydroxylase, aromatic l -amino acid decarboxylase, dopamine β-hydroxylase, and phenyl ethanolamine N-methyltransferase, were detected in this micro-PCC by immunohistochemical analyses. Although catecholamine levels were not biochemically elevated, the PCC expressed catecholamine biosynthetic enzymes. This is the first immunohistochemical report to show that a micro-PCC produces excess catecholamines in the pre-biochemical phase.

Introduction Ureteropelvic junction obstruction is a common congenital anomaly that causes hydronephrosis but rarely accompanies ipsilateral retrocaval ureter. Case presentation A 39‐year‐old woman, who visited to our hospital complaining of worsened right low back pain and fever, was diagnosed with right hydronephrosis due to ureteropelvic junction obstruction by contrast‐enhanced computed tomography. Intraoperatively before the planned robot‐assisted laparoscopic pyeloplasty, retrograde pyelography was performed to reveal concomitant ipsilateral retrocaval ureter. Laparoscopically, ureteropelvic junction obstruction due to aberrant blood vessel and coexisting retrocaval ureter was confirmed. Transposition of the ureter from posterior to anterior of the inferior vena cava and following dismembered pyeloplasty was performed. Two years after surgery, her right hydronephrosis improved and she had no complain of any symptom. Conclusion Retrocaval ureter is a rare abnormality; however, combination of preoperative retrograde pyelography and laparoscopic evaluation was important for management of this concomitant abnormality.

Objective Using a prospective observational design, we assessed adverse events (AEs) after COVID-19 vaccination in Japanese patients. Methods Two doses of the mRNA-1273 (SPIKEVAX®) or BNT162b2 (COMIRNATY®) vaccine were administered to participants aged 12 to 18 years, and AEs after each dose were recorded for 14 days. Data on the duration and nature (local vs. systemic) of AEs were collected using a questionnaire. Sex-based differences in AE frequency were also analyzed. Results After the first and second doses, 152 and 135 vaccinees were enrolled, respectively. After the first dose, fever (>37.1°C) occurred in 38.9% of males and 50.0% of females, whereas local pain occurred in 89.8% and 97.7% of males and females, respectively (only SPIKEVAX® was used as the first dose). After the second dose, fever (>37.1°C) occurred in 77.8% and 82.6% of males vaccinated with COMIRNATY® and SPIKEVAX®, respectively, and 82.6% of females (all received SPIKEVAX®). The local pain rates in these groups were 80.6%, 76.3%, and 100%, respectively. After the second dose, local pain, fever (>38.1°C) and headache were significantly more common in female participants, and the median symptom duration was 3 days. Conclusions AEs were more frequent after the second dose and in females.

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.

Abstract Bladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and HIF1α mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of NOS3 gene locus and upregulated NOS3 gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.

Abstract The objective of this study was to compare the efficacy of abiraterone acetate with that of bicalutamide in combination with gonadotropin-releasing hormone (GnRH) antagonist treatment for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). A total of 149 patients with mHSPC who underwent treatment at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) with a GnRH antagonist (degarelix) (group A), and 99 patients were administered bicalutamide (80 mg/day) with a GnRH antagonist (group B). The prostate-specific antigen (PSA) progression-free survival (PSA-PFS) was significantly longer in group A than in group B. Abiraterone acetate therapy and Gleason score were significant independent factors of PSA-PFS. Using propensity score matching, 56 matched patients were obtained. The PSA-PFS (p

Abstract This retrospective study was undertaken to identify predictors for the development of hypocalcaemia even with prophylactic administration of calcium and vitamin D, and to help guide future strategies to improve the safety, efficacy, and QOL of patients receiving denosumab. Between January 2016 and February 2020, a total of 327 advanced cancer patients at our hospital who were receiving denosumab were enrolled. Variables associated with the development of hypocalcaemia were extracted from the clinical records. The level of hypocalcaemia was evaluated using CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictors for the development of hypocalcaemia. Optimal cut off thresholds were determined using ROC analysis. Values of P

Background and purpose: Elongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years. Materials and methods: We compared 96 patients aged ≥80 years and 2333 younger patients (aged 60–79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT). Results: The 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%, p = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%, p = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%, p = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% (p

Introduction The remitting seronegative symmetrical synovitis with pitting edema syndrome primarily occurs in elderly individuals to represent symptoms of edema, pain, and joint swelling. It could be misdiagnosed in elderly maintenance hemodialysis patients, as hemodialysis patients often present with pain and joint swelling induced by hypervolemia, inflammation, amyloidosis, and/or chronic kidney disease. Here, we describe a maintenance hemodialysis patient with remitting seronegative symmetrical synovitis with pitting edema syndrome. Case presentation A 71‐year‐old man on maintenance hemodialysis who complained of continuous pain and swelling of joints was diagnosed with remitting seronegative symmetrical synovitis with pitting edema syndrome on his clinical findings that revealed tenosynovitis at the joint without joint erosions and no elevation of anti‐cyclic citrullinated peptide antibody and rheumatoid factor. After administration of prednisolone, systemic edema, and pain improved in 2 days. Conclusion Remitting seronegative symmetrical synovitis with pitting edema syndrome should be considered as a differential diagnosis in hemodialysis patients with edema and/or arthralgia.

Introduction Secondary bladder, colon, and rectal cancers are relatively common after prostate radiotherapy. However, secondary squamous cell carcinoma of the prostate is rare. Case presentation An 85‐year‐old man presented with dysuria and low‐serum prostate‐specific antigen levels. His medical history included localized prostate adenocarcinoma (Gleason score of 4 + 5) treated with combined three‐dimensional conformal radiotherapy and androgen deprivation therapy, 11 years ago. Urethroscopy and magnetic resonance imaging showed a bulging mass around the prostatic urethra. Transurethral resection of the prostate performed for histopathological diagnosis revealed squamous cell carcinoma. Conclusion Hereby, a rare case of secondary squamous cell carcinoma of the prostate after radiotherapy for adenocarcinoma was reported, which was found after 11 years of radiotherapy with symptom of dysuria including urinary hesitancy, difficulty, pain during urination, and low‐serum prostate‐specific antigen levels.

Nivolumab, a programmed death-1 checkpoint inhibitor, is worldwide available for metastatic renal cell carcinoma (mRCC). Limited data exist on the response to vascular endothelial growth factor receptor-tyrosine kinase inhibitor (TKI) therapy after administration of nivolu­mab. In this case study, we report on a patient with tumor lysis syndrome (TLS), which was induced by pazopanib after the administration of nivolumab. A 69-year-old woman with a primary diagnosis of mRCC received pazopanib as a fourth-line therapy, after sunitinib, axitinib, and nivolumab as first-, second-, and third-line therapies, respectively. Two weeks after the administration of pazopanib, she presented to the emergency room of our institution, complaining of fatigue associated with nausea and diarrhea. Her laboratory results showed hyperphosphatemia, hyperuricemia, hypocalcemia, and possible acute kidney injury; the results were consistent with TLS. Our case report highlights TLS as a potential reaction to pazopanib following nivolumab; and we consider careful observation is necessary when administering TKI after immune checkpoint inhibitors.

IntroductionInadequate vaccine response is a common concern among healthcare workers at the frontlines of the COVID-19 pandemic. We aimed to investigate if healthcare workers with history of weak immune response to HBV vaccination are more likely to have weak responses against the BioNTech/Pfizer's BNT162b2 mRNA SARS-CoV-2 vaccine.MethodsWe prospectively tested 954 healthcare workers for the Anti-SARS-CoV-2 spike (S) protein antibody titers prior to the first and second BNT162b2 vaccination doses and after four weeks after the second dose using Roche's Elecsys® assay. We calculated the percentage of patients who seroconverted after the first and second doses. We estimated the relative risk of non-seroconversion after the first BNT162b2 vaccine (defined as anti-SARS-CoV-2-S titer ResultsAmong 954 healthcare workers recruited between March 9 and March 24, 2021 at Osaka Medical and Pharmaceutical University, weak and normal HBV vaccine responders had comparable S-protein titers after the first BNT162b2 dose (51.4 [95% confidence interval 25.2-137.0] versus 59.7 [29.8-138.0] U/mL, respectively). HBV vaccine non-responders were more likely than normal responders to not seroconvert after a single dose (age and sex-adjusted relative risk 1.85 95% confidence interval [1.10-3.13]) although nearly all participants seroconverted after the second dose. After limiting the analysis to 382 patients with baseline comorbidity data, the comorbidity-adjusted relative risk of non-seroconversion among HBV vaccine non-responders to normal responders was 1.32 (95% confidence interval [0.59-2.98]).DiscussionLong term follow-up studies are needed to understand if protective immunity against SARS-CoV-2 wanes faster among those with history of HBV vaccine non-response and when booster doses are warranted for these healthcare workers.

Introduction Horseshoe kidney has unique anatomical features, such as a complex blood supply. We report a patient with renal cell carcinoma in a horseshoe kidney, who underwent tumor resection by robot‐assisted laparoscopic partial nephrectomy based on preoperative three‐dimensional computed tomography. Case presentation A 66‐year‐old man was referred to our hospital with a 2‐cm enhancing mid‐pole mass in the left moiety of a horseshoe kidney. The clinical diagnosis was renal cell carcinoma cT1aN0M0 (R.E.N.A.L. nephrometry score: 1 + 2 + 3 + 3 = 9p). Robot‐assisted laparoscopic partial nephrectomy was performed with selective clamping based on reconstructed three‐dimensional images. The warm ischemia time was 13 min. Pathologic examination confirmed a diagnosis of pT1a clear cell renal cell carcinoma with negative surgical margins. At 6 months postoperatively, computed tomography showed no local recurrence or metastasis and renal function was intact. Conclusion Robot‐assisted laparoscopic partial nephrectomy with preoperative three‐dimensional computed tomography may have advantages for resection of tumors in patients with horseshoe kidney.