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1.
Cancer Med ; 13(11): e7341, 2024 Jun.
Article En | MEDLINE | ID: mdl-38845479

BACKGROUND: This study evaluates the efficacy of a nomogram for predicting the pathology upgrade of apical prostate cancer (PCa). METHODS: A total of 754 eligible patients were diagnosed with apical PCa through combined systematic and magnetic resonance imaging (MRI)-targeted prostate biopsy followed by radical prostatectomy (RP) were retrospectively identified from two hospitals (training: 754, internal validation: 182, internal-external validation: 148). A nomogram for the identification of apical tumors in high-risk pathology upgrades through comparing the results of biopsy and RP was established incorporating statistically significant risk factors based on univariable and multivariable logistic regression. The nomogram's performance was assessed via the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). RESULTS: Univariable and multivariable analysis identified age, targeted biopsy, number of targeted cores, TNM stage, and the prostate imaging-reporting and data system score as significant predictors of apical tumor pathological progression. Our nomogram, based on these variables, demonstrated ROC curves for pathology upgrade with values of 0.883 (95% CI, 0.847-0.929), 0.865 (95% CI, 0.790-0.945), and 0.840 (95% CI, 0.742-0.904) for the training, internal validation and internal-external validation cohorts respectively. Calibration curves showed good consistency between the predicted and actual outcomes. The validation groups also showed great generalizability with the calibration curves. DCA results also demonstrated excellent performance for our nomogram with positive benefit across a threshold probability range of 0-0.9 for the training and internal validation group, and 0-0.6 for the internal-external validation group. CONCLUSION: The nomogram, integrating clinical, radiological, and pathological data, effectively predicts the risk of pathology upgrade in apical PCa tumors. It holds significant potential to guide clinicians in optimizing the surgical management of these patients.


Image-Guided Biopsy , Nomograms , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Prostatic Neoplasms/diagnostic imaging , Image-Guided Biopsy/methods , Middle Aged , Aged , Retrospective Studies , ROC Curve , Magnetic Resonance Imaging/methods , Prostate/pathology , Prostate/diagnostic imaging , Prostate/surgery , Neoplasm Grading , Neoplasm Staging
2.
Oncol Lett ; 28(1): 319, 2024 Jul.
Article En | MEDLINE | ID: mdl-38807677

Leuprorelin acetate microspheres, a common gonadotropin-releasing hormone agonist, have certain clinical benefits for prostate cancer (PCa). The present study aimed to compare the efficacy and safety of generic and branded leuprorelin acetate microspheres in patients with PCa. The present retrospective, observational study included 116 patients with PCa who received generic (Boennuokang®; Beijing Biote Pharmaceutical Co., Ltd.) or branded (Enantone®; Takeda Pharmaceutical Company, Ltd.) leuprorelin acetate microspheres via injection (commonly 3.75 mg once every 4 weeks), defined as the test (n=64) and reference (n=52) groups, respectively. The present study showed that testosterone levels at month (M) 3 (P<0.001), M6 (P=0.012) and M12 (P<0.001) were decreased in the test group compared with the reference group. However, prostate-specific antigen (PSA) levels at baseline, M1, M3, M6 and M12 were not significantly different between the test and reference groups (all P>0.05). The median (interquartile range) testosterone and PSA levels at M12 were 15.50 ng/dl (10.00-31.25 ng/dl) and 0.01 ng/ml (0.01-0.10 ng/ml), respectively, in the test group and 28.00 ng/dl (22.00-37.00 ng/dl) and 0.02 ng/ml (0.01-0.16 ng/ml), respectively, in the reference group. No significant differences were observed in the M1-baseline, M3-baseline, M6-baseline and M12-baseline changes of testosterone or PSA levels between the two groups (all P>0.050). Additionally, the incidence of all adverse events was not significantly different between the two groups (all P>0.050). Overall, Boennuokang® leuprorelin acetate microspheres exhibited a similar efficacy for suppression of testosterone and PSA levels with a comparable safety profile compared with Enantone® leuprorelin acetate microspheres in patients with PCa.

3.
Cell ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38744281

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

4.
Transl Cancer Res ; 13(2): 651-660, 2024 Feb 29.
Article En | MEDLINE | ID: mdl-38482427

Background: Without a pseudocapsule, prostate cancer is invasive in volume growth and has some regularity in spatial distribution. Our study aims to explore the specific origin location, invasive characteristics, and morphology of prostate cancer. Methods: Ninety-eight clinical specimens with tumor volume equal to or less than one-third of the organ volume and 111 autopsy specimens were retrospectively analyzed. The origin location and invasion of prostate cancer in four horizontal quadrants and 11 vertical slides were demonstrated. In addition, the median maximum anteroposterior, left-right, horizontal, and vertical diameters of lesions were compared, and the spatial morphology of lesions was described. Results: There were 335 lesions in the autopsy and clinical specimens. There was no significant difference in the distribution of lesions confined to the horizontal quarter quadrant (P=0.064). The number of lesions with a single positive slide above the apex 0.5-1.4 cm was 75 (49.7%). No significant difference was found when compared with the maximum vertical and horizontal diameters (P=0.421). However, the maximum left-right and horizontal diameters were longer than the maximum anteroposterior diameter (P=0.046 and P<0.001). The number of lesions with a tumor area that decreased from the center to both sides was 85 (46.2%) and decreased from the center to one side was 81 (44.0%). Conclusions: Approximately 50% of the lesions originated from the apex above 0.5-1.4 cm. The invasive tendency of prostate cancer was consistent in the horizontal and vertical dimensions but less so in the anteroposterior direction. About ninety percent of lesions with tumor area decreased from the center to both sides or one side.

5.
J Endocr Soc ; 8(5): bvae041, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38533349

Objective: Adrenal hemangioma (AH) is a rare, benign adrenal tumor often detected incidentally by imaging. This retrospective study aimed to investigate the clinical characteristics of AH, including clinical and diagnostic imaging features, to improve the recognition and understanding of AH. Methods: We retrospectively analyzed the medical records of patients diagnosed with AH at Peking Union Medical College Hospital between 2008 and 2022. Clinical manifestations, adrenal hormone levels, imaging findings, treatment approaches, and pathological results were collected and analyzed. Results: Of the 7140 adrenal tumor patients, 40 (0.56%) had AH confirmed postoperatively. The mean age at diagnosis was 53.9 years, with a female predominance. Most (70%) were asymptomatic and diagnosed incidentally. Misdiagnosis before surgery was common, most frequently as pheochromocytoma. Imaging characteristics, especially enhanced computed tomography, revealed distinct features based on tumor size. Surgery was the main treatment, with laparoscopic adrenalectomy preferred. Conclusion: This study elucidates the clinical characteristics of AH, including demographics, diagnostic challenges, and imaging features. AH often presents incidentally and is frequently misdiagnosed preoperatively. Recognizing distinct imaging characteristics and appropriate surgical management can enable accurate diagnosis and optimal treatment.

6.
Am J Cancer Res ; 14(1): 73-85, 2024.
Article En | MEDLINE | ID: mdl-38323293

This study aimed to construct nomograms for predicting the likelihood of clinically significant prostate cancer (csPCa) in patients with lesions rated as Prostate Imaging Reporting and Data System (PI-RADS) 3 on biparametric magnetic resonance imaging (bpMRI). We retrospectively analyzed a cohort of 457 patients from the Peking Union Medical College Hospital (January 2017-July 2021) to develop the model and externally validated it with a cohort of 238 patients from the Second Hospital of Tianjin Medical University (September 2017-September 2021). Univariate and multivariate logistic regression analyses identified significant predictors of csPCa, defined by tumor volumes ≥ 0.5 cm3, Gleason score ≥ 7, or presence of extracapsular extension. Diagnostic performance for the peripheral zone (PZ) and transitional zone (TZ) was compared using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Through univariate and multivariate logistic regression analyses, we identified age, prostate-specific antigen (PSA), and prostate volume (PV) as predictors of csPCa for the PZ, and age, serum-free to total PSA ratio (f/t PSA), and PSA density (PSAD) for the TZ. The nomograms demonstrated robust discriminative ability, with an area under the ROC curve (AUC) of 0.819 for PZ and 0.804 for TZ. The external validation corroborated the model's high predictive accuracy (AUC of 0.831 for PZ and 0.773 for TZ). Calibration curves indicated excellent agreement between predicted and observed outcomes, and DCA underscored the nomogram's clinical utility for both PZ and TZ. Overall, the nomograms offer high predictive accuracy for csPCa at initial biopsy, potentially reducing unnecessary biopsies in clinical settings.

7.
Innovation (Camb) ; 5(1): 100558, 2024 Jan 08.
Article En | MEDLINE | ID: mdl-38261840

Prostate cancer detected by autopsy is named latent prostate cancer. As the repertoire of clinical prostate cancer, latent cancer may better reflect the disease burden. Unlike clinical prostate specimens, which are obtained exclusively from biopsy-positive cases, prostate specimens obtained through autopsy provide information on biopsy-negative cases, helping calculate the true sensitivity of prostate biopsy. From 2014 to 2021, we collected autopsy specimens of the prostate from body donors in China and performed transperineal and transrectal biopsies on specimens before step-sectioning and pathological measurements. We found that the crude prevalence of latent prostate cancer in middle-aged and elderly men was 35.1% (81/231), which was higher than previous estimates for Chinese populations. The overall per-patient sensitivities of transperineal and transrectal biopsies were not significantly different (33.3% vs. 32.1%, p = 0.82), but the two approaches differed in preferential sampling area along the proximal-distal axis of the prostate. Transperineal biopsy had a higher sensitivity for detecting clinically significant lesions in the distal third (34.7% vs. 16.3%, p = 0.02) and distal half (30.6% vs. 18.1%, p = 0.04), while transrectal biopsy had a higher sensitivity for lesions in the proximal half (25.0% vs. 13.9%, p = 0.046). Both transperineal and transrectal methods of biopsy missed most small lesions (<0.1 mL) and 35.3% (6/17) of large lesions (>0.5 mL). In conclusion, the prevalence of latent prostate cancer in China has increased over the past 2 decades. Systematic transperineal and transrectal methods of biopsy had comparable sensitivities but had different preferential sampling areas. Both approaches miss one-third of large lesions.

8.
World J Urol ; 42(1): 29, 2024 Jan 12.
Article En | MEDLINE | ID: mdl-38214793

PURPOSE: To evaluate the diagnostic ability of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in detecting and localizing lesions, and further clarify the accuracy of these examinations in tumor staging. METHODS: Seventy patients who underwent mpMRI, 68Ga-PSMA PET/CT and radical prostatectomy were enrolled. The abilities to detect index and clinically significant lesions by three examinations were compared. We further evaluated the ability of these examinations to localize lesions to the superior, inferior, anterior, posterior, left and right halves of the prostate and analyzed their accuracy in local and lymph node staging. RESULTS: There were no significant differences among mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in their ability to detect index (p = 0.48, p = 0.23 and p = 0.07) and clinically significant lesions (p = 0.30, p = 0.29 and p = 0.06) or to localize lesions in six half divisions of the prostate. With postoperative pathology as reference, both mpMRI (p = 0.10) and mpMRI combined with 68Ga-PSMA PET/CT (p = 0.10) can accurately assess the local staging of prostate cancer. However, 68Ga-PSMA PET/CT underestimates the local staging of prostate cancer (p < 0.01). Regarding lymph node staging, the three types of examination showed no significant differences compared to postoperative pathology (p = 0.63, p = 0.51 and p = 0.14). CONCLUSIONS: With postoperative pathology as reference, 68Ga-PSMA PET/CT underestimates the local tumor staging. MpMRI combined with 68Ga-PSMA PET/CT has no obvious advantages in detecting, localizing or staging prostate cancer compared with mpMRI.


Gallium Radioisotopes , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Male , Humans , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Gallium Isotopes
9.
J Clin Invest ; 133(20)2023 10 16.
Article En | MEDLINE | ID: mdl-37843276

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and MST2 (MST1/2). WW45 interaction with MST1/2 was thereby enhanced, resulting in the activation of Hippo signaling to block YAP activity for cell contact inhibition. Importantly, low cell density led to SPTAN1 dephosphorylation and NUMB cytoplasmic location, along with MST1/2 inhibition and, consequently, YAP activation. Moreover, double KO of NUMB and WW45 in the liver led to appreciable organ enlargement and rapid tumorigenesis. Interestingly, NUMB isoforms 3 and 4, which have a truncated phosphotyrosine-binding (PTB) domain and are thus unable to interact with phosphorylated SPTAN1 and activate MST1/2, were selectively upregulated in liver cancer, which correlated with YAP activation. We have thus revealed a SPTAN1/NUMB1/2 axis that acts as a cell density sensor to restrain cell growth and oncogenesis by coupling external cell-cell contact signals to intracellular Hippo signaling.


Hippo Signaling Pathway , Protein Serine-Threonine Kinases , Humans , Protein Serine-Threonine Kinases/metabolism , Spectrin/metabolism , Adaptor Proteins, Signal Transducing/metabolism , YAP-Signaling Proteins , Transcription Factors/metabolism , Carcinogenesis/genetics
11.
Eur J Med Res ; 28(1): 181, 2023 Jun 02.
Article En | MEDLINE | ID: mdl-37268989

BACKGROUND: This study aims to compare the clinical outcomes after performing radical prostatectomy (RP) or low-dose-rate brachytherapy (LDR) for patients with intermediate-risk prostate cancer (IRPC). METHODS: We performed a retrospective analysis on 361 IRPC patients who underwent treatment in Peking Union Medical College Hospital from January 2014 to August 2021, of which 160 underwent RP and 201 underwent Iodine-125 LDR. Patients were followed in clinic monthly during the first three months and at three-month intervals thereafter. Univariate and multivariate regression analyses were conducted to predict biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS), and overall survival (OS). Biochemical recurrence was defined using the Phoenix definition for LDR and the surgical definition for RP. The log-rank test was applied to compare bRFS between the two modalities, and Cox regression analysis was performed to identify factors associated with bRFS. RESULTS: Median follow-up was 54 months for RP and 69 months for LDR. According to log-rank test, the differences of 5-year bRFS (70.2% vs 83.2%, P = 0.003) and 8-year bRFS (63.1% vs 68.9%, P < 0.001) between RP and LDR groups were statistically significant. Our results also indicated that there was no significant difference in terms of cRFS, CSS, or OS between the two groups. With multivariate analysis of the entire cohort, prostate volume ≤ 30 ml (P < 0.001), positive margin (P < 0.001), and percentage positive biopsy cores > 50% (P < 0.001) were independent factors suggestive of worse bRFS. CONCLUSIONS: LDR is a reasonable treatment option for IRPC patients, yielding improved bRFS and equivalent rates of cRFS, CSS and OS when compared with RP.


Brachytherapy , Laparoscopy , Prostatic Neoplasms , Male , Humans , Prostate/surgery , Retrospective Studies , Neoplasm Recurrence, Local , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prognosis , Prostatectomy/methods
15.
JAMA Surg ; 157(8): 693-700, 2022 08 01.
Article En | MEDLINE | ID: mdl-35793110

Importance: Focal therapy of prostate cancer must balance the oncologic outcome and functional outcome. High-frequency irreversible electroporation (H-FIRE) can destroy cancer cells while selectively preserving surrounding nerves and blood vessels, but no clinical trials have been conducted, to our knowledge. Objective: To evaluate the efficacy and safety of H-FIRE in the treatment of localized prostate cancer (PCa). Design, Setting, and Participants: This was a single-group, objective performance criteria, nonrandomized controlled trial. Recruitment began on May 2, 2018, and ended March 27, 2019. The follow-up duration was 6 months. This was a multicenter trial conducted at 4 tertiary teaching hospitals in China. Patients with low or intermediate risk of biochemical recurrence of localized and locally advanced PCa were eligible. Key inclusion criteria were serum prostate-specific antigen (PSA) level less than 20 ng/mL, clinical stage of T2c or less, and Gleason score of 7 or less. Data were analyzed from January 20 to February 20, 2021. Intervention: H-FIRE ablation of all lesions identified with biopsy. Main Outcomes and Measures: The primary end point was 6-month clinically significant PCa (csPCa), which was defined as any biopsy core with Gleason score of greater than or equal to 7, or Gleason score of 6 plus maximum cancer core length of greater than 3 mm or an increase from the original cancer burden. Secondary outcomes were calculated in patients who actually received H-FIRE treatment. Results: A total of 117 patients (median [IQR] age, 67 [62-73] years) were recruited from 4 centers, and 109 patients (27 [24.8%] low risk and 82 [75.2%] intermediate risk) actually received H-FIRE. Median (IQR) PSA level was 9.0 (6.0-12.7) ng/mL. Among the 100 patients who underwent biopsy at 6 months, the 6-month csPCa rate was 6.0% (95% CI, 2.2%-12.6%; P < .001; 1 in the treatment zone and 5 outside the treatment zone). Superiority criteria vs the historical control of 20% was achieved. PCa was detected in 14 patients, with a Gleason score of 7 in 2 patients and 6 in the remaining 12 patients. At 6 months, median (IQR) PSA level was 1.08 (0.4-3.2) ng/mL, median (IQR) International Prostate Symptom Score was 4.5 (2.0-9.5), and median (IQR) International Index of Erectile Function 5 score was 2.0 (0.5-12.5). Superiority vs the 20% historical control was also met in the subgroup analysis that only included the 57 patients with Gleason score of 7 at baseline (3.5% 6-month csPCa; 95% CI, 0.4%-12.1%). Conclusions and Relevance: The rate of 6-month csPCa with H-FIRE ablation was lower than the historical control using other energy platforms. Trial Registration: ClinicalTrials.gov Identifier: NCT03838432.


Prostate-Specific Antigen , Prostatic Neoplasms , Aged , Electroporation , Humans , Male , Neoplasm Grading , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Treatment Outcome
16.
J Transl Med ; 20(1): 91, 2022 02 15.
Article En | MEDLINE | ID: mdl-35168617

BACKGROUND: Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment. METHODS: In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown. RESULTS: The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed. CONCLUSIONS: In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.


Prostatic Neoplasms , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Male , Prostatic Neoplasms/pathology
17.
Prostate ; 82(5): 556-565, 2022 04.
Article En | MEDLINE | ID: mdl-35098557

OBJECTIVE: Prostate cancer (PCa) is the most prevalent cancer among males. This study attempted to develop a clinically significant prostate cancer (csPCa) risk nomogram including Prostate Imaging-Reporting and Data System (PI-RADS) score and other clinical indexes for initial prostate biopsy in light of the different prostate regions, and internal validation was further conducted. PATIENTS AND METHODS: A retrospective study was performed including 688 patients who underwent ultrasound-guided transperineal magnetic resonance imaging fusion prostate biopsy from December 2016 to July 2019. We constructed nomograms combining PI-RADS score and clinical variables (prostate-specific antigen [PSA], prostate volume (PV), age, free/total PSA, and PSA density) through univariate and multivariate logistic regression to identify patients eligible for biopsy. The performance of the predictive model was evaluated by bootstrap resampling. The area under the curve (AUC) of the receiver-operating characteristic (ROC) analysis was appointed to quantify the accuracy of the primary nomogram model for csPCa. Calibration curves were used to assess the agreement between the biopsy specimen and the predicted probability of the new nomogram. The χ2 test was also applied to evaluate the heterogeneity between fusion biopsy and systematic biopsy based on different PI-RADS scores and prostate regions. RESULTS: A total of 320 of 688 included patients were diagnosed with csPCa. csPCa was defined as Gleason score ≥7. The ROC and concordance-index both presented good performance. The nomogram reached an AUC of 0.867 for predicting csPCa at the peripheral zone; meanwhile, AUC for transitional and apex zones were 0.889 and 0.757, respectively. Statistical significance was detected between fusion biopsy and systematic biopsy for PI-RADS score >3 lesions and lesions at the peripheral and transitional zones. CONCLUSION: We produced a novel nomogram predicting csPCa in patients with suspected imaging according to different locations. Our results indicated that PI-RADS score combined with other clinical parameters showed a robust predictive capacity for csPCa before prostate biopsy. The new nomogram, which incorporates prebiopsy data including PSA, PV, age, and PI-RADS score, can be helpful for clinical decision-making to avoid unnecessary biopsy.


Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Male , Nomograms , Prostate-Specific Antigen , Prostatic Neoplasms/pathology , Retrospective Studies
18.
Front Oncol ; 11: 760003, 2021.
Article En | MEDLINE | ID: mdl-34858837

INTRODUCTION: The classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. An alternative pathway is to perform an ablation by some energy to the localized lesion, known as focal therapy. High-frequency irreversible electroporation (H-FIRE) is nonthermal energy that can be used in cancer ablation to deliver pulsed high-voltage but low-energy electric current to the cell membrane and to invoke cell death. An H-FIRE pathway has been reported to be tissue-selective, which leads to fewer side effects. METHODS AND ANALYSIS: This is a multicenter and single-arm objective performance criteria (OPC) study, in which all men with localized prostate cancer are allocated to H-FIRE ablation. This trial will assess the efficacy and safety of the H-FIRE ablation for prostate cancer. Efficacy will be assessed by prostate biopsy 6 months after treatment while safety will be assessed by adverse event reports and questionnaires. The main inclusion criteria are moderate to low-risk prostate cancer in NCCN risk classification and had no previous therapy for prostate cancer. A sample size of 110 participants is required. The primary objective is to determine whether the detection rate of clinically significant cancer by prostate biopsy is less than 20% after the H-FIRE ablation. ETHICS AND DISSEMINATION: This study has obtained ethical approval by the ethics committee of all participating centers. The results of the study will be submitted for dissemination and publication in peer-reviewed journals. CONCLUSIONS: This multicenter single-arm objective performance criteria trial will evaluate the efficacy and safety of the use of high-frequency irreversible electroporation in treating prostate cancer. STRENGTHS AND LIMITATIONS OF THIS STUDY: A comprehensive evaluation of imaging and histopathology is used to determine the effect of treatment. Questionnaires were used to assess the treatment side effects. Multicenter and pragmatic designs capacitate higher generalizability. A limitation of this trial is that the prostate biopsy as an endpoint may not be as accurate as of the specimen from prostate prostatectomy. Another limitation is the 6-month follow-up time, making this trial challenging to come to firm conclusions regarding the efficacy and safety of IRE in the long term. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03838432.

19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 944-948, 2021 Aug.
Article Zh | MEDLINE | ID: mdl-34590561

OBJECTIVE: To observe the effects of self-made Qingyuan Shenghua decoction on coagulation dysfunction in patients with sepsis, and to explore its possible mechanism. METHODS: Eighty patients with sepsis and coagulation dysfunction admitted to the department of critical care medicine of Chengdu First People's Hospital from March 2018 to April 2020 were enrolled. The patients were divided into control group and observation group according to random number table method, with 40 cases in each group. Patients in both groups received basic treatment for sepsis. On this basis, the observation group was administrated with self-made Qingyuan Shenghua decoction, one dose a day, 100 mL in the morning and 100 mL in the evening; the control group was given the same amount of normal saline. Both groups were treated for 7 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (Fib), D-dimer, platelet count (PLT), white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were measured before and after treatment, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were calculated. The length of intensive care unit (ICU) stay, the incidence of multiple organ dysfunction syndrome (MODS) and 28-day mortality was recorded. RESULTS: The indexes of coagulation function and inflammation in the two groups were significantly improved after treatment, the improvement of various indexes in the observation group were better than those in the control group [PT (s): 16.01±1.08 vs. 19.21±1.38, APTT (s): 55.33±15.29 vs. 79.41±12.69, INR: 1.30±0.21 vs. 1.65±0.22, Fib (g/L): 2.87±0.89 vs. 5.44±1.13, D-dimer (mg/L): 2.56±1.67 vs. 6.41±2.42, PLT (×109/L): 125.79±18.51 vs. 95.46±18.50, WBC (×109/L): 7.50±0.78 vs. 12.75±4.09, CRP (mg/L): 21.27±9.32 vs. 65.44±13.40, PCT (µg/L): 1.15±0.58 vs. 6.31±1.29], and the differences were statistically significant (all P < 0.05). After treatment, APACHE II and SOFA scores in the two groups decreased significantly compared with those before treatment, and the decrease in the observation group were more obvious than those in the control group (APACHE II score: 10.29±1.86 vs. 15.35±2.06, SOFA score: 5.51±1.08 vs. 7.65±1.58, both P < 0.05). The length of ICU stay was shortened in the observation group than that in the control group (days: 12.22±9.48 vs. 20.22±15.35, P < 0.05). The incidence of MODS [35.0% (14/40) vs. 47.5% (19/40)] and the 28-day mortality [45.0% (18/40) vs. 47.5% (19/40)] was lower than that of the control group, but there was no statistical difference (both P > 0.05). CONCLUSIONS: Self-made Qingyuan Shenghua decoction can effectively improve the prognosis of patients with coagulation dysfunction and sepsis, and its mechanism may be related to inhibition of inflammatory reaction and improvement of coagulation function.


Blood Coagulation Disorders , Drugs, Chinese Herbal , Sepsis , Blood Coagulation Disorders/drug therapy , Drugs, Chinese Herbal/therapeutic use , Humans , Retrospective Studies , Sepsis/drug therapy
20.
Urol Oncol ; 39(10): 730.e17-730.e22, 2021 10.
Article En | MEDLINE | ID: mdl-34175215

PURPOSE: This study aimed to investigate if preoperative assessments of multiparametric magnetic resonance imaging (mpMRI) and Magnetic resonance imaging /ultrasound (MRI/US) fusion-guided prostate biopsy could be used to guide focal therapy for prostate cancer. MATERIALS AND METHODS: A total of 101 prostate cancer patients undergoing radical prostatectomy were included. Preoperative findings included mpMRI and MRI/US fusion-guided prostate biopsy, while postoperative whole mount pathology was based on surgical specimen. RESULTS: Of the 101 patients preoperatively diagnosed with a unilateral tumor, postoperative whole mount pathology showed 73.27% were bilateral tumors, and 71.62% of bilateral lesions were clinically significant. Comparison between preoperative and postoperative findings, the correct rate of preoperative mpMRI on the lesion side (left or right) was only 20.79%. As for the Gleason score, the correct rate of preoperative MRI/US fusion-guided prostate pathology was 67.33%. Judging from postoperative whole mount pathology, 47.52% of patients had a unilateral clinically significant tumor, which is an indication for focal therapy. CONCLUSION: Preoperative examinations of mpMRI and MRI/US fusion-guided prostate biopsy cannot be used to guide focal therapy for prostate cancer.


Image-Guided Biopsy/methods , Multiparametric Magnetic Resonance Imaging/methods , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Aged , Humans , Male , Preoperative Period , Retrospective Studies
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