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Abstract The purpose of this study is to investigate the relationship between chronic pain and the mortality rate of cerebrovascular disease (CVD) in cancer patients. Thus, we performed a case-control investigation was conducted by utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2019. Multiple demographics, pain rating and other clinical characteristics were extracted to assess predictors for the death from CVD in cancer patients. Different machine learning algorithms were applied to construct pain-related prediction model. The analysis involved 16,850 case patients and 710,729 controls. Among cancer patients, approximately 2.3% succumbed to subsequent CVD. Cancer pain (Pain rating II) was associated with a decreased risk of CVD. Univariate and multivariate COX analyses indicated that older age at cancer diagnosis, male gender, single marital status, Black or Other race, and lack of systemic therapy correlated with a higher risk of CVD-related death. Propensity score matching revealed a significantly lower proportion of Pain rating II in the case group. The logistic regression algorithm demonstrated superior predictive ability for 5-year and 10-year CVD risk in cancer patients. Notably, survival time, age, and pain rating emerged as the top three crucial variables. This study firstly investigated pain and various risk factors for CVD in cancer patients, highlighting pain as a novel and possible protective factor for CVD. The development of a risk model based on pain could aid in identifying individuals at high risk for CVD and may inspire innovative strategies for preventing CVD in cancer patients.

Abstract Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA–PFS was 8 months (IQR: 6.5–11.5), with a median follow-up duration of 39.0 months (IQR: 27.5–64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

Abstract Background The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers. Nevertheless, its specific function and underlying mechanism in bladder cancer (BCa) remain largely unexplored. Methods The expression levels of BHLHE41 in BCa tissues and cells were examined by qRT-PCR and western blot assays. BCa cells stably knocking down or overexpressing BHLHE41 were constructed through lentivirus infection. The changes of cell proliferation, cell cycle distribution, migration, and invasion were detected by CCK-8, flow cytometry, wound healing, transwell invasion assays, respectively. The expression levels of related proteins were detected by western blot assay. The interaction between BHLHE41 and PYCR1 was explored by co-immunoprecipitation analysis. Results In this study, we found that BHLHE41 was lowly expressed in bladder cancer tissues and cell lines, and lower expression of BHLHE41 was associated with poor overall survival in bladder cancer patients. Functionally, by manipulating the expression of BHLHE41, we demonstrated that overexpression of BHLHE41 significantly retarded cell proliferation, migration, invasion, and induced cell cycle arrest in bladder cancer through various in vitro and in vivo experiments, while silence of BHLHE41 caused the opposite effect. Mechanistically, we showed that BHLHE41 directly interacted with PYCR1, decreased its stability and resulted in the ubiquitination and degradation of PYCR1, thus inactivating PI3K/AKT signaling pathway. Rescue experiments showed that the effects induced by BHLHE41 overexpression could be attenuated by further upregulating PYCR1. Conclusion BHLHE41 might be a useful prognostic biomarker and a tumor suppressor in bladder cancer. The BHLHE41/PYCR1/PI3K/AKT axis might be a potential therapeutic target for bladder cancer intervention.

Abstract Objectives A considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa. Patients and methods We used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit. Results 4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p 0.05). Conclusions Based on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.

Abstract Cancer-directed surgeries (CDS) play a crucial role in prostate cancer (PCa) management along with possible survival and therapeutic benefits. However, barriers such as socioeconomic factors may affect patients’ decision of refusing recommended CDS. This study aimed to uncover risk factors and the impact on survival associated with CDS refusal. We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with PCa between 2000 and 2019. Multiple sociodemographic and clinical characteristics were extracted to assess predictors for physicians’ surgical recommendations and patients’ surgical refusal, respectively. Propensity score matching was performed to balance the covariates. The impact of surgical refusal on mortality risk was also investigated. A total of 185,540 patients were included. The physician’s recommendation of CDS was significantly influenced by the patient’s age, race, income, home location, diagnosis year, Gleason score, prostate-specific antigen (PSA), and TNM stage. About 5.6% PCa patients refused CDS, most of whom were older, non-White race, lack of partners, living outside of metropolitan areas, with higher PSA or lower clinical TNM stage. Patients who refused CDS had an increased risk of cancer-specific mortality and overall mortality than those who performed CDS. Physicians may weigh a host of sociodemographic and clinical factors prior to making a CDS recommendation. Patients’ refusal of recommended CDS affected survival and was potentially modifiable by certain sociodemographic factors. Physicians should fully consider the hindrances behind patients’ CDS refusal to improve patient-doctor shared decision-making, guide patients toward the best alternative and achieve better outcomes.

This population-based propensity score-matching study aimed to investigate the survival outcomes of patients with biopsy- and transurethral resection of the prostate (TURP)-diagnosed prostate cancer (PC). We obtained data from the Surveillance, Epidemiology and End Results (SEER) database, PC patients diagnosed by biopsy and TURP from 1975 to 2019 were enrolled. Cohort data were baseline-matched using a propensity score-matching (PSM) study. Compared with biopsy-confirmed PC (BPC) patients, prostate cancer-specific mortality (CSM) and overall mortality (OM) in patients with transurethral resection of the prostate (TURP)-diagnosed PC (TPC) were analyzed. A total of 26,027 cases were obtained for this study, of which 4770 cases (18.3%) were TPC patients and 21,257 cases (81.7%) were BPC patients. The proportion of TPC patients showed an increasing trend. The prognosis of TPC patients seemed worse, the ratios of CSM and OM were higher, and the median survival time was shorter (all p < 0.05). After PSM, TPC patients still had a worse prognosis. Compared with BPC patients, TPC patients’ CSM and OM risks increased by 42.0% and 43.0%, respectively (p < 0.001). The results of subgroup analysis indicated earlier the stage of TPC patients, the higher the risk of OM, while systemic treatment after surgery may bring declines of CSM and OM (all p for interaction < 0.001). To our knowledge, we first used a large sample size to find that clinically suspected PC patients with obstruction, directly TURP will increase the risk of CSM and OM.

ALK-positive Histiocytosis (ALK-HSs) is a recently identified rare clinical entity characterized by tissue histiocytic alterations associated with ALK gene rearrangement. Clinical presentations can be solitary, multifocal, or systemic (involving multiple sites and organs). Due to limited reported cases, there is inadequate understanding of this disease. This report presents a case of ALK-HSs in a 71-year-old male patient who presented with hematuria for one week. Imaging studies conducted at an external hospital showed multiple lesions in the penis, bilateral testes, back skin, and the third lumbar vertebra. Histopathological findings included spindle and histiocytic cell proliferation with mild or indistinct cellular atypia, interstitial infiltration of lymphocytes, plasma cells, foamy histiocytes, and fibrous tissue proliferation. Immunohistochemistry of the lesion cells revealed positivity for CD68, CD163, ALK1, ALK (D5F3), and Vimentin. FISH testing indicated ALK gene separation in the lesion cells. NGS testing identified the fusion genes KIF5B(NM_004521) and ALK(NM_004304) in the lesion cells. We combined the characteristics of this case with a review of the literature to enhance our understanding of this rare clinical entity.

Abstract Clear cell adenocarcinoma of the prostate (CCPC) is a rare entity compared to acinar carcinoma of the prostate (APC). The survival rate and prognostic factors of CCPC are still unclear and deserve further study. We downloaded data on prostate cancer from the Surveillance, Epidemiology, and End Results database for 1975–2019. After inclusion and exclusion criteria, we compared APC and analyzed cancer-specific mortality (CSM) and overall mortality (OM) in CCPC patients and prognostic risk factors using a propensity score matching (PSM) study and multivariate Cox regression. We included 408,004 cases of APC as a control group and 130 cases of CCPC as a case group. Compared with APC patients, the incidence of CCPC was extremely low, and the median age of diagnosis was older (72.00 years vs. 69.00 years, p

Abstract Objective To investigate the value of 3.0T MRI multi‐directional diffusion‐weighted imaging (DWI) combined with T2WI morphological features and lesion distribution in preoperative prediction of muscle layer invasion of bladder cancer (BC) and the correlation with postoperative Ki‐67. Materials and Methods This retrospective study enrolled patients with BC between 2019 and 2021. Patients with muscular invasive bladder cancer (MIBC) or non‐muscular invasive BC (NMIBC) were also analyzed by preoperative 3.0T MRI aFostic efficacy. Results A total of 186 patients were enrolled. About 27 patients with MIBC (35 lesions in total) and 62 with NMIBC (99 lesions in total). We found the tumor with a larger size, a wide base, and a smaller apparent dispersion coefficient (ADC) value and normalized ADC(nADC) value, without a stalk, presenting a greater risk of muscle invasion. ADC value, nADC value, maximum diameter, and stalk were independently associated with muscle invasion. Lesions located at the bladder fundus or involvement of multiple sites were independently associated with muscle invasion compared to the bladder body. In combination with morphological features, the AUCs of ADC and nADC showed accuracies of 0.925 and 0.947–0.951, respectively. TADC and nTADC showed the best diagnostic efficacy in multiple respects. KI‐67 LI was negatively correlated with ADC and nADC values. Conclusions This is the first report in which we found Multi‐directional DWI combined with T2WI in 3.0T MRI can be used to predict the muscle layer invasion of bladder cancer. ADC values reflect the muscular invasion of bladder cancer and show a moderate negative correlation with Ki‐67. It is especially suitable for bladder cancer patients with renal insufficiency or tumor recurrence.

Whether neoadjuvant therapy confers a survival benefit in advanced prostate cancer (PCa) remains uncertain. The primary endpoints of previous retrospective and phase II clinical studies that used neoadjuvant therapy, including androgen deprivation therapy combined with new-generation androgen receptor signaling inhibitors or chemotherapy, were pathological downstaging, progression-free survival, prostate-specific antigen relief, and local symptom improvement. To the best of our knowledge, no studies have explored the efficacy and safety of neoadjuvant therapy in improving the surgical resection rate in cases of unresectable primary tumors of PCa. We first designed this retrospective study to evaluate the potential value of apalutamide as neoadjuvant therapy in improving the resectability rate of radical prostatectomy (RP). We initially reported 7 patients with unresectable primary lesions who underwent neoadjuvant apalutamide treatment for a median of 4 months, and all of them successfully underwent RP treatment. Our study supported apalutamide as neoadjuvant therapy, which helped improve RP’s success rate and did not significantly increase perioperative complications, and the neoadjuvant therapy was controllable. Our findings’ clinical value and benefit for survival still need further clinical research to confirm.

(1) Background: This study investigates the early evaluation value of magnetic resonance imaging (MRI) and multidetector computed tomography (MDCT) in diagnosing the recurrence of bladder cancer (BC) after trans-urethral resection (TUR) alone or combined with intravesical perfusion chemotherapy. (2) Methods: This retrospective study enrolled 92 patients with BC who underwent MRI and MDCT after TUR. The time interval between MRI and MDCT was no more than 1 week. Tumor recurrence was recorded by two experienced radiologists who were double-blind. Recurrent patients were divided into nodular masses, irregular wall thickening and smooth wall thickening groups according to tumor morphology in cystoscopy and resected gross specimens. Inter- and intra-observer agreement was evaluated using the Kappa test. Imaging diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and McNemar’s test based on pathology. (3) Results: There were 56 relapsed and 36 non-relapsed patients. The intra-observer agreement for the imaging diagnosis was excellent (κ = 0.96 for MRI and κ = 0.91 for MDCT, both p < 0.001). The area under the ROC curve of MRI was higher than that for MDCT (0.91 vs. 0.74, p < 0.001) in identifying tumor recurrence and benign treatment-related changes. The sensitivity, specificity and accuracy of MRI (87.5%, 94.4% and 90.2%, respectively) were higher than those of MDCT (67.9%, 80.6% and 72.8%, respectively) in diagnosing tumor recurrence. Two observers missed 10 cases of small lesions (

Background: Ductal carcinoma of the prostate (DCP) is a rare type of prostate cancer (PCa) with a higher degree of infiltration and worse prognosis than acinar adenocarcinoma of the prostate (ACP). Previous reports comparing DCP and ACP have not been very reliable and involved small sample sizes. Objective: To assess differences in mortality between ACP and DCP in a large-scale study. Design, setting, and participants: Data were downloaded from the Surveillance, Epidemiology, and End Results database in June 2022. Data for 823 939 patients diagnosed with PCa from 2004 to 2019 were examined, excluding cases with survival data missing or pathological types other than DCP and ACP. Outcome measurements and statistical analysis: Prognostic and risk factors for DCP were analyzed by generating a propensity score–matched cohort of DCP and ACP cases (1:5). Adjusted Cox models were constructed to determine hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer-specific mortality (CSM) and overall mortality (OM) Results and limitations: A total of 822 607 cases (99.8%) has ACP and 1332 (0.2%) had DCP. In comparison to ACP, age at diagnosis was significantly lower for DCP (≤66 yr: 38.0% vs 50.7%; p

PurposeThis prospective study aimed to evaluate the difference between 99mTc-PSMA single-photon emission computed tomography (SPECT)/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of primary prostate cancer (PCa).Materials and methodsFifty-six men with suspected PCa between October 2019 and November 2022 were prospectively enrolled in this study. The median age of the patients was 70 years (range, 29-87 years). Patients were divided into high-(Gleason score>7, n=31), medium- (Gleason score=7, n=6) and low-risk groups (Gleason score < 7, n=6). All patients underwent 99mTc-PSMA SPECT/CT and mpMRI at an average interval of 3 days (range, 1-7 days). The maximum standardized uptake value (SUVmax), the minimum apparent diffusion coefficient (ADCmin), and their ratio (SUVmax/ADCmin) were used as imaging parameters to distinguish benign from malignant prostatic lesions.ResultsOf the 56 patients, 12 were pathologically diagnosed with a benign disease, and 44 were diagnosed with PCa. 99mTc-PSMA SPECT/CT and mpMRI showed no significant difference in the detection of primary PCa (kappa =0.401, P=0.002), with sensitivities of 97.7% (43/44) and 90.9% (40/44), specificities of 75.0% (9/12) and 75.0% (9/12), and AUC of 97.4% and 95.1%, respectively. The AUC of SUVmax/ADCmin was better than those of SUVmax or ADCmin alone. When SUVmax/ADCmin in the prostatic lesion was >7.0×103, the lesion was more likely to be malignant. When SUVmax/ADCmin in the prostatic lesion is >27.0×103, the PCa patient may have lymph node and bone metastases. SUVmax was positively correlated with the Gleason score (r=0.61, P=0.008), whereas ADCmin was negatively correlated with the Gleason score (r=-0.35, P=0.023). SUVmax/ADCmin was positively correlated with the Gleason score (r=0.59, P=0.023). SUVmax/ADCmin was the main predictor of the high-risk group, with an optimal cut-off value of 15.0×103.ConclusionsThe combination of 99mTc-PSMA SPECT/CT and mpMRI can improve the diagnostic efficacy for PCa compared with either modality alone; SUVmax/ADCmin is a valuable differential diagnostic imaging parameter.

Objective: Our study aims to assess the effectiveness and safety profile of Disitamab Vedotin (DV, RC48-ADC), an innovative humanized anti-HER2 antibody conjugated with tubulin-disrupting antimitotic drug monomethyl auristatin E (MMAE) via a cleavable peptide linker. This treatment combined immune checkpoint inhibitors as part of the bladder sparing approach for selected patients suffering from locally and locally advanced bladder urothelial carcinoma.Patients and methods: We conducted a two-center, real-world study involving locally advanced urothelial carcinoma (UC) patients. Patients were classified based on HER2 expression (IHC 3+/2+/1+) or lack of HER2 expression (IHC 0). The primary endpoint was the objective response rate (ORR), assessed by the investigator following the criteria of RECIST V1.1. Secondary endpoints encompassed the pathological complete response rate (pCR), pathological partial response rate (pPR), and pathological stable disease (pSD), along with recurrence-free survival (RFS), the pathological downstaging rate, and the safety profile of the treatment.Results: In this study, nine patients were enrolled, with a median follow-up duration of 12.0 months. The overall confirmed ORR was 88.9%, Five patients achieved a complete response (CR), and three patients achieved a partial response (PR). The radiological complete response (rCR) aligned perfectly with pCR. The median radiological progression-free survival (rPFS) spanned 12.0 months (range from 8.0 to 17.0 months). One patient diagnosed with disease progression (PD) underwent a radical cystectomy. The pathological stage evolved from T2N0M0 to T3aN2M0, followed by adjuvant chemotherapy with a gemcitabine-cisplatin (GC) combination radiotherapy. At the 9-month follow-up, neither recurrence nor metastasis was observed. The rate and intensity of complications were manageable among these patients, with no evidence of grade 4 and 5 adverse events.Conclusion: The combination of DV and PD-1 demonstrated considerable activity in the objective response rate (ORR) in patients with HER2 IHC 0/1+/2+/3+ muscle-invasive bladder cancer (MIBC), along with the longest reported median radiological progression-free survival (rPFS) to date. With an extended duration of treatment, the safety profile of DV plus PD-1 was also confirmed to be manageable.

Abstract The most common site of metastasis of prostate cancer (PCa) is bone. Skeletal-related events can increase the risk of death in patients with PCa by 28%. Due to the low detection rate of lesions in patients with low prostate-specific antigen (PSA) levels, the value of 99mTc methylene diphosphonate (99mTc-MDP) bone scintigraphy is limited. Prostate-specific membrane antigen (PSMA) is a small molecular probe that can efficiently and specifically detect PCa lesions. This prospective study aimed to evaluate the difference between 99mTc-PSMA single-photon emission computed tomography (SPECT)/CT and 99mTc-MDP SPECT/CT in the detection of bone metastasis in PCa. A total of 74 men with pathologically confirmed PCa from October 2019 to November 2021 were prospectively enrolled in this study. The median age was 70 (range, 55–87) years. All patients underwent both 99mTc-PSMA SPECT/CT and 99mTc-MDP SPECT/CT at an average interval of 12.1 (range, 1–14) days. The detected imaging-positive bone lesions were scored as “typical metastasis” or “equivocal metastasis” by a standard reporting schema. Subsequent therapy modality details were observed through follow-up. Twenty-five of the 74 patients were diagnosed with bone metastases. 99mTc-PSMA SPECT/CT and 99mTc-MDP SPECT/CT detected 20 and 18 bone metastases, with sensitivities of 80.0% (20/25) and 72.0% (18/25), specificities of 100.0% (49/49) and 81.3% (40/49), and AUCs of 88.0% and 84.9%, respectively. There was a significant difference in the AUC between the two imaging methods (P

ObjectiveThis study aimed to evaluate the awareness rate of prostate-specific antigen (PSA) among the general public in China and provide data about prostate cancer (PCa) for related scientific research.MethodsA cross-sectional survey of PSA awareness was conducted in multiple regional populations using an online questionnaire. The questionnaire included basic information, knowledge about PCa, the awareness rate and application of PSA, and future expectations toward applying PSA screening in clinical practice. The study applied the methods of Pearson chi-square analysis and Logistic regression analysis.ResultsA total of 493 valid questionnaires were included. Two hundred and nineteen respondents (44.4%) were males, and 274 (55.6%) were females. Of all respondents, 212 (43.0%) were under 20 years old, 147 (29.8%) were 20–30 years old, 74 (15.0%) were 30–40 years old, and 60 (12.2%) were over 40 years old. There are 310 people (62.9%) with medical educational background and 183 (37.1%) without. One hundred eighty-seven (37.9%) of the respondents were aware of PSA, and 306 (62.1%) were unaware of PSA. Statistically significant differences were obtained between the two groups regarding different ages, educational backgrounds, occupations, departments, and habits of knowing medical knowledge (all p < 0.05). In addition, the differences between the group of aware of PSA (AP) and the group unaware of PSA (UAP) in terms of whether they had been exposed to PSA screening and whether they had exposure to PCa patients or related knowledge were also observed (all p < 0.05). Age ≥30 years, medical educational background, understanding of medical knowledge, exposure to PCa patients or related knowledge, exposure to PSA screening, and status as a graduate student and above were independent factors for the occurrence of PSA awareness events (all p < 0.05). In addition, age ≥ 30 years, medical educational background, and awareness of PSA were independent factors for future expectations toward PSA (all p < 0.05).ConclusionsWe first analyzed the public awareness of PSA. Cognition degrees of PSA and PCa awareness vary among different populations in China. Therefore, we should designate corresponding widespread scientific educational programs for different populations to increase the awareness rate of PSA.

Langerhans cell sarcoma (LCS) is a rare malignancy of dendritic cells and usually results in a poor oncological outcome. Thus, LCS is usually given a positive administration. Herein, we presented the first case of primary LCS in the urinary bladder staged T1N0M0 and treated by TURBT and short-term local chemotherapy. Our experience in this unique case may suggest that LCS in the urinary bladder with a non-muscle-invasive stage may be managed according to the treatment model of non-muscle-invasive urothelial carcinoma of the urinary bladder.

Background: The genome-wide CRISPR-cas9 dropout screening has emerged as an outstanding approach for characterization of driver genes of tumor growth. The present study aims to investigate core genes related to clear cell renal cell carcinoma (ccRCC) cell viability by analyzing the CRISPR-cas9 screening database DepMap, which may provide a novel target in ccRCC therapy.Methods: Candidate genes related to ccRCC cell viability by CRISPR-cas9 screening from DepMap and genes differentially expressed between ccRCC tissues and normal tissues from TCGA were overlapped. Weighted gene coexpression network analysis, pathway enrichment analysis, and protein–protein interaction network analysis were applied for the overlapped genes. The least absolute shrinkage and selection operator (LASSO) regression was used to construct a signature to predict the overall survival (OS) of ccRCC patients and validated in the International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. Core protein expression was determined using immunohistochemistry in 40 cases of ccRCC patients.Results: A total of 485 essential genes in the DepMap database were identified and overlapped with differentially expressed genes in the TCGA database, which were enriched in the cell cycle pathway. A total of four genes, including UBE2I, NCAPG, NUP93, and TOP2A, were included in the gene signature based on LASSO regression. The high-risk score of ccRCC patients showed worse OS compared with these low-risk patients in the ICGC and E-MTAB-1980 validation cohort. UBE2I was screened out as a key gene. The immunohistochemistry indicated UBE2I protein was highly expressed in ccRCC tissues, and a high-level nuclear translocation of UBE2I occurs in ccRCC. Based on the area under the curve (AUC) values, nuclear UBE2I had the best diagnostic power (AUC = 1). Meanwhile, the knockdown of UBE2I can inhibit the proliferation of ccRCC cells.Conclusion: UBE2I, identified by CRISPR-cas9 screening, was a core gene-regulating ccRCC cell viability, which accumulated in the nucleus and acted as a potential novel promising diagnostic biomarker for ccRCC patients. Blocking the nuclear translocation of UBE2I may have potential therapeutic value with ccRCC patients.

BackgroundTo compare the middle-term efficacy and safety results between scrotoscope-assisted (SA) minimally invasive excision and traditional open excision (OE) for the treatment of epididymal mass.MethodsA total of 253 males with surgery excision of epididymal mass from 2012 to 2018 were included in this retrospective study. Patients were divided into two groups: the traditional OE group and the SA group. Patient demographics and intraoperative and postoperative outcomes were obtained and compared between these two groups.ResultsAbout 174 patients (68.8%) underwent SA, and the other 79 (31.2%) underwent OE. Demographic data were similar between the two groups. Compared with OE surgery, SA could significantly shorten the operating time (19.4 ± 4.1 vs. 53.8 ± 12.9 min), reduce blood loss (5.3 ± 1.5 vs. 21.3 ± 5.6 ml), and downsize the operative incision (1.5 ± 0.3 vs. 4.5 ± 0.8 cm). Additionally, postoperative complications were significantly less occurred in the SA group than those in OE (15.5% vs. 21.5%), in particular scrotal hematoma (1.7% vs. 12.7%) and incision discomfort (2.8% vs. 6.3%). Patients in the SA group had a significantly higher overall satisfaction score (94.8 ± 3.7 vs. 91.7 ± 4.9) and a significantly shorter length of hospital stay (4.1 ± 0.9 vs. 5.0 ± 1.5 days) than those in the OE group. No postoperative testicular atrophy occurred in the SA group.ConclusionSA is emerging as a novel and effective option with promising perspectives for epididymal mass therapy.

Ketamine is a glutamate N-methyl D-aspartate receptor antagonist and an anaesthetic agent that has been effectively used to treat depression. However, ketamine has also been increasingly used for recreational purposes. The dissociative side-effects of ketamine use, such as hallucinations, are the reason for abuse. Additionally, long-term ketamine abuse has been highly associated with liver-gallbladder and urinary symptoms. The present study reports the case of a 28-year-old young male adult with an 8-year history of daily inhalation of ketamine. We investigated the association between ketamine abuse and the mechanism of its adverse effects, particularly encephalatrophy, and attempted to find a link between these disorders. These results would help us to better understand ketamine usage, ketamine abuse effects and the addictive mechanism. To the best of our knowledge, the present case is the first report of severe brain atrophy related to ketamine abuse. Details of the patient are presented and the mechanism of the encephalatropy-associated ketamine abuse is discussed. Furthermore, organ dysfunction following chronic ketamine abuse may indicate that the side effects are the result of comprehensive action on multiple regions in the brain.

Bladder transitional cell carcinoma (BTCC) is highly fatal and generally has a poor prognosis. To improve the prognosis of patients with BTCC, it is particularly important to identify biomarkers related to the prognosis. In this study, differentially expressed messenger RNAs were obtained by analyzing relevant data of BTCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Next, hub genes that were suitable for correlation analysis with prognosis were determined through constructing a protein–protein interaction (PPI) network of differentially expressed genes and screening of major modules in the network. Finally, survival analysis of these hub genes found that three of them (CCNB1, ASPM, and ACTC1) were conspicuously related to the prognosis of patients with BTCC (p < 0.05). By combining the clinical features of BTCC and the expression levels of the three genes, univariate Cox and multivariate Cox regression analyses were performed and denoted that CCNB1 could be used as an independent prognostic factor for BTCC. This study provided potential biomarkers for the prognosis of BTCC as well as a theoretical basis for subsequent prognosis-related research.

Background. Prostate cancer is one of the most common malignancies in men. Protein ubiquitination is an important mechanism for regulating protein activity and level in vivo. We aimed to study the mechanism of SEPT6 and UBC action in prostate cancer to identify new targets. Methods. The ubiquitin-protein and the ubiquitin coding gene UBA52, UBA80, UBB, and UBC expressions were detected in clinical tissues and cells. Overexpression and knockdown of UBC were performed in prostate cancer DU145 cells. Cell Counting Kit 8 (CCK-8) assay was performed to detect cell proliferation. Cell cycle at 24 h was detected by flow cytometry. Clonal formation assay was used to measure cell clone number. Immunofluorescence (IF) was performed to detect the colocalization of SEPT6 and UBC in prostate cancer cells. Next, we overexpressed or knocked down SEPT6 expression in DU145 cells. Pearson correlation coefficient was applied to analyze the relationship between SEPT6 and UBC in prostate cancer tissue. oe-SEPT6+oe-UBC coexpressing cells were constructed to detect the upstream and downstream relationship between SEPT6 and UBC on prostate cancer cells. The tumor formation experiment was performed to explore SEPT6/UBC effect on prostate cancer. Results. UBC was upregulated in prostate cancer tissues and cells. Overexpression of UBC promoted cell survival and proliferation. IF revealed the colocalization of SEPT6 and UBC in prostate cancer cells. UBC expression decreased after oe-SEPT6, while increased after sh-SEPT6, indicating that UBC was downstream of SEPT6. Pearson correlation coefficient analysis showed that SEPT6 was negatively correlated with UBC in prostate cancer tissues. SEPT6 as an upstream gene of UBC regulated prostate cancer cell behavior through UBC. The tumor formation experiment showed that SEPT6 could inhibit tumor growth. Conclusion. In general, SEPT6 inhibited UBC expression, thereby reducing the overall ubiquitination level, affecting the expression level of downstream cell proliferation-related genes, and then affecting the progression of prostate cancer.

Dioscin possesses antioxidant effects and has anticancer ability in many solid tumors including prostate cancer (PCa). Nevertheless, its effect and mechanism of anti-PCa action remain unclear. The tyrosine protein phosphatase SHP1, which contains an oxidation-sensitive domain, has been confirmed as a target for multicancer treatment. Further studies are needed to determine whether dioscin inhibits PCa through SHP1. We performed in vitro studies using androgen-sensitive (LNCaP) and androgen-independent (LNCaP -C81) cells to investigate the anticancer effects and possible mechanisms of dioscin after administering interleukin-6 (IL-6) and dihydrotestosterone (DHT). Our results show that dioscin inhibited cell growth and invasion by increasing SHP1 phosphorylation [p-SHP1 (Y536)] and inhibiting the subsequent P38 mitogen-activated protein kinase signaling pathway. Further in vivo studies confirmed that dioscin promoted caspase-3 and Bad-related cell apoptosis in these two cell lines. Our research suggests that the anticancer effects of dioscin on PCa may occur through SHP1. Dioscin may be useful to treat androgen-sensitive and independent PCa in the future.

Background and objective: A scrotal wall mass is relatively rare in clinical practice, and very difficult to differentiate from a scrotal content lesion by a physical or ultrasound examination. In this study, we share our experience with the scrotoscope for diagnosing and treating scrotal wall masses. Methods: We retrospectively reviewed all clinical data of scrotal wall mass patients treated by our medical team between June 2015 and July 2019. Diagnostic value was evaluated by comparison with a Doppler ultrasound examination and therapeutic value was evaluated by comparison with traditional surgery. Suspected scrotal tuberculosis or malignant scrotal tumor patients were excluded. Results: Six patients with scrotal wall masses were diagnosed and treated with the scrotoscope. A preoperative ultrasound examination led to an ambiguous or incorrect diagnosis for the origin of the scrotal wall masses in all six cases. The location of all of the masses was confirmed by exploring with the scrotoscope. Three patients were diagnosed with scrotal wall cysts, and one was successfully resected during the procedure; the other two were resected through a small incision. Four scrotal wall solid masses were resected in the other three patients through small incisions after the diagnosis using the scrotoscope. No wound infection, scrotal edema, hematoma, chronic scrotal pain, or injury to the testicles or epididymis were observed. Conclusions: Scrotal wall masses are relatively rare, and it was very difficult to obtain a firm diagnosis of their origin using preoperative ultrasound. The scrotoscope confirmed localization of the tumor, and provided us important information for a minimally invasive resection. Endoscopic resection of a mass can be performed using a scrotoscope.

Purpose: This prospective study aimed to evaluate the difference between 99mTc-PSMA single-photon emission computed tomography (SPECT)/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of primary prostate cancer (PCa). Materials and Methods: Fifty-six men with suspected PCa between October 2019 and November 2022 were prospectively enrolled in this study. The median age of the patients was 70 years (range, 29-87 years). Patients were divided into high-(Gleason score>7, n=31), medium-(Gleason score=7, n=6) and low-risk groups (Gleason score < 7, n=6). All patients underwent 99mTc-PSMA SPECT/CT and mpMRI at an average interval of 3 days (range, 1-7 days). The maximum standardized uptake value (SUVmax), the minimum apparent diffusion coefficient (ADCmin), and their ratio (SUVmax/ADCmin) were used as imaging parameters to distinguish benign from malignant prostatic lesions. Results: Of the 56 patients, 12 were pathologically diagnosed with a benign disease, and 44 were diagnosed with PCa. 99mTc-PSMA SPECT/CT and mpMRI showed no significant difference in the detection of primary PCa (kappa =0.401, P=0.002), with sensitivities of 97.7% (43/44) and 90.9% (40/44), specificities of 75.0% (9/12) and 75.0% (9/12), and AUC of 97.4% and 95.1%, respectively. The AUC of SUVmax/ADCmin was better than those of SUVmax or ADCmin alone. When SUVmax/ADCmin in the prostatic lesion was >7.0×103, the lesion was more likely to be malignant. When SUVmax/ADCmin in the prostatic lesion is >27.0×103, the PCa patient may have lymph node and bone metastases. SUVmax was positively correlated with the Gleason score (r=0.61, P=0.008), whereas ADCmin was negatively correlated with the Gleason score (r=-0.35, P=0.023). SUVmax/ADCmin was positively correlated with the Gleason score (r=0.59, P=0.023). SUVmax/ADCmin was the main predictor of the high-risk group, with an optimal cut-off value of 15.0×103. Conclusions: The combination of 99mTc-PSMA SPECT/CT and mpMRI can improve the diagnostic efficacy for PCa compared with either modality alone; SUVmax/ADCmin is a valuable differential diagnostic imaging parameter. [ABSTRACT FROM AUTHOR]

Context: IDH1 is a pheochromocytoma/paraganglioma (PPGL) susceptibility gene; however, its role, especially in the Chinese population, has not been characterized. Objective: To determine the prevalence of somatic IDH1 hotspot variants in a large cohort of Chinese patients with PPGLs and to summarize associated phenotypes. Methods: This retrospective cross-sectional study was based on a main cohort of 1141 patients with PPGLs from 2 tertiary-care centers in China. We included 50 cases with urinary bladder paragangliomas (UBPGLs), of whom 29 were part of the main cohort and 21 were from other centers. Two additional cases with IDH1 hotspot variants not part of the main cohort were also included for summarizing IDH1- associated phenotypes. Next-generation sequencing of tumor DNA was used to analyze a customized panel of genes. Results: The overall prevalence of IDH1 hotspot variants in the main cohort was 0.5% (6/1141). Among those PPGLs without mutations in 15 common driver genes, the prevalence of IDH1 variants was 0.9% (4/455). When restricted to paraganglioma (PGL) without mutations, the prevalence reached 4.7% (4/86). Among UBPGLs, IDH1 hotspot variants accounted for 8% (4/50). Together, all 10 patients (9 PGLs and 1 pheochromocytoma) with IDH1 hotspot variants, including 3 females with concurrent EPAS1 hotspot variants, had apparently sporadic tumors, without metastasis or recurrence. There were 3 patients with biochemical data, all showing a non-adrenergic phenotype. Conclusions: The somatic IDH1 hotspot variants cause PPGL development in some Chinese patients, especially among those apparently sporadic PGLs with a non-adrenergic phenotype and without mutations in major PPGL driver genes. [ABSTRACT FROM AUTHOR]