Prostate最新文献

Background: The diagnosis of treatment-related neuroendocrine prostate cancer (t-NEPC) often involves a pathological assessment and immunohistochemistry (IHC) for neuroendocrine markers. Genomic alterations in RB1 and TP53 are frequently observed in NEPC and are believed to play a crucial role in the transformation of adenocarcinoma to NEPC. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of patients with t-NEPC to better understand their prognosis and diagnostic utility.

Methods: This retrospective study reviewed the records of patients diagnosed with t-NEPC at Kobe University Hospital between October 2018 and December 2022. Clinical data, including age, serum neuroendocrine marker levels, and treatment history, were collected. IHC was performed for conventional neuroendocrine markers (synaptophysin, chromogranin A, and CD56) and RB1 and p53 expression. Next-generation sequencing (NGS) was conducted using FoundationOne® CDx to identify mutations in RB1 and TP53.

Results: This study included 20 patients with t-NEPC. The median time from ADT initiation to development was 42.8 months. IHC revealed RB1 loss in 75% of cases and p53 abnormalities in 75% of cases. NGS identified RB1 mutations in 55% and TP53 mutations in 75% of cases. The concordance between NGS and IHC results was high, with 70% (14/20) agreement for RB1/RB1 and 80% (16/20) for p53/TP53. The immunostaining and genomic analysis of RB1/RB1 and p53/TP53 showed abnormal findings for the four negative cases for conventional neuroendocrine markers.

Conclusions: This study indicated high concordance between IHC and NGS findings for RB1/RB1 and p53/TP53 in t-NEPC. We provide a comprehensive benchmark of NGS performance compared with IHC, and these findings may help increase the diagnostic sensitivity of t-NEPC.

Background: Prostate Cancer (PCa) increases the mortality rate of males worldwide and is caused by genetics, lifestyle, and age reasons. The existing automated PCa classification systems face difficulties with overfitting issues, and non-generalizability, leading to poor classification performance.

Objective: On this account, this study proposes an automated classification of PCa from MRI images using a hybrid weighted mean of vectors-optimized DarkNet53 classifier model.

Methodology: The proposed method suggests nonlocal mean filtering for noise reduction, N4ITK bias field correction to enhance image quality, and active contour-based segmentation for accurately identifying the disease region. The feature extraction utilizes the gray level run length matrix and shape features for effective feature extraction. A weighted mean of vectors optimization is used to optimize the feature selection process by hybridizing it with the DarkNet53 model for classification. Finally, the interpretation of achieving the classification has been demonstrated using the explainable AI Grad-CAM model.

Results: After comparing the proposed work with various state-of-the-art algorithms, the proposed model achieves 99.31% accuracy, 98.24% sensitivity, and 98.46% specificity, respectively, highlighting the model's accomplishment using the DarkNet53 classifier.

Background: The influence of testosterone on the prostate's immune microenvironment remains unclear. This study aims to elucidate the dynamics of immune cells in the prostate following androgen deprivation therapy (ADT).

Methods: We retrospectively compared prostate needle biopsy and radical prostatectomy specimens from 33 patients who underwent both procedures, along with neoadjuvant ADT at a single institution. Immune cell infiltration in the cancer and stroma areas was assessed using multiplex fluorescence immunohistochemistry.

Results: Post-ADT, all immune cells, including CD4⁺ T cells, CD8⁺ T cells, Foxp3⁺ regulatory T cells, CD204⁺ macrophages, and CD20⁺ B cells, significantly increased in the prostatectomy specimen. However, few immune cells were detected in the biopsy of the same patients (p < 0.001). The number of CD20⁺ B cells in the cancer area was significantly lower post-ADT in high-risk cases according to the NCCN classification (p = 0.020). This difference was significantly associated with the Gleason Grade Group, rather than PSA levels or T classification (p < 0.001). However, no significant difference was observed in the recurrence rate between Grade Groups 1, 2, 3 and 4, 5 (p = 0.991). There was no significant difference in immune cells other than CD20⁺ B cells when divided into NCCN classifications.

Conclusions: The marked increase in immune cells following ADT suggests an intensified immune response against prostate cancer.

Background: Lymph node (LN) metastasis is a poor prognostic factor in patients with prostate cancer. Elucidating the mechanisms underlying cancer progression in the metastatic microenvironment of LNs is crucial to establishing novel therapies. Adipocytes interact with cancer cells and regulate cancer progression. In this study, we aimed to clarify the clinicopathological significance of extranodal adipose tissue invasion in metastatic LNs and preoperative adipokine concentration in patients with prostate cancer exhibiting metastatic LNs.

Methods: We examined the pathological findings of primary and metastatic nodes and clinical information of 66 specimens from 46 patients with prostate cancer. A sub-analysis was performed to assess the relationship between preoperative adiponectin/leptin concentrations and clinical/pathological findings in the blood samples of 56 patients with prostate cancer who either did or did not show LN metastasis.

Results: The number of metastatic LNs in patients correlated with the involvement of adipose tissue and lymphovascular invasion (p = 0.039 and < 0.001, respectively). Preoperative adiponectin concentration was lower in patients with resected margin-positive and extraprostatic extension-positive primary cancers (p = 0.0071 and 0.02, respectively). Preoperative adiponectin concentrations were significantly lower in patients with metastatic LNs than in patients without LN metastasis (p < 0.001). Moreover, leptin concentrations were significantly higher in patients with metastatic LNs than in patients without LN metastasis (p < 0.001). In patients with metastatic LNs, preoperative adiponectin concentrations were significantly lower in patients with biochemical recurrence than in patients without biochemical recurrence (p = 0.031). There was no correlation between biochemical recurrence and pathological findings.

Conclusions: This is the first report on the detailed histopathological characteristics of prostate cancer with LN metastases and the significance of preoperative adiponectin concentration in predicting the pathological features of primary cancers. Also, adipokines are a significant prediction factor of LN metastases for prostate cancer patients. Adipose tissue and adipose-secreting factors may be involved in the progression of metastatic and primary prostate cancer.

Background: We aimed to assess the safety and effectiveness of TRUS guided betamethasone injections in refractory cases of chronic nonbacterial prostatitis.

Patients and methods: Forty-five patients with refractory CNP were included in a prospective cohort clinical trial. Six injections of betamethasone sodium sulfate were guided by TRUS. After injection: assessment of NIH-CPSI, IPSS, IIEF, GRA and VAS were performed 1, 4, and 12 weeks after injection. Prostatitis symptoms were measured by NIH-CPSI. We considered the minimal clinically important difference (MCID) as a 25% decrease or a six-point reduction from baseline. We considered the MCID of the IIEF to be at least an increase of 4 points. We considered the MCID of the IPSS score to be three points and the MCID for the VAS score to be a 25%-35% change of the initial score. Regarding the global response assessment (GRA), scores 5-7 means significant success rate of perceived treatment.

Results: According to total NIH CPSI score, the success rate of injected cases was 71% after 1 week, dropping to 55.6% after 4 weeks and 44.4% after 12 weeks. According to IPSS questionnaire, the MD (mean difference) is -4.09 ± 3.5, -3.8 ± 3.83 and -3.47 ± 3.92. According to the IIEF questionnaire, the success rate was 22% and 26.7% after 4 and 12 weeks respectively. According to GRA, successful pain control was reported in 82%, 71% and 64.4% after 1, 4 and 12 weeks, respectively.

Conclusion: Intraprostatic betamethasone injection is a simple, safe, and feasible procedure in refractory cases with CNP with predominant pain and urinary symptoms.

Introduction: Prostate cancer (PC) remains a significant global health concern, with prognostic assessments largely reliant on the Gleason Classification System. While it has proven effective, subjectivity in interpretation persists, prompting the need for complementary approaches. Reactive stroma (RS) has emerged as a potential candidate for enhancing PC characterization, as it reflects intricate interactions among stromal, epithelial, and extracellular matrix components. To shed light on this, we conducted a comprehensive study.

Methods: Two expert pathologists independently analyzed consecutive prostate biopsies (n = 120 patients), categorized into four groups based on Gleason scores. Four acinar patterns were described, denoted as A, B, C, and D. Our study uncovered a noteworthy presence of RS, predominantly within poorly differentiated tumors. Stromogenic tumors, characterized by high RS content, were particularly associated with Gleason scores of 4 + 3 and ≥ 8. Intriguingly, acinar patterns, including the distinctive B and D patterns, exhibited strong correlations with stromogenic tumors. Incorporating quantitative imaging techniques (Second Harmonic Generation and Two-Photon Excitation Fluorescence Microscopy), we examined collagen fiber density within the stroma.

Results: Our analysis revealed a direct relationship between RS intensity and collagen fiber counts, particularly prominent in patterns B and D. These findings suggest that the stromal reaction in PC is closely linked to acinar morphology and collagen deposition. Moreover, rudimentary microacini at the tumor periphery, associated with intense RS and patterns B and D, may signify an unfavorable prognosis.

Conclusion: Our study highlights the potential of RS as an additional prognostic factor in PC. It underscores the intricate interplay between acinar patterns, RS intensity, and collagen fiber density, providing valuable insights for future prognostic assessments and therapeutic strategies. Further exploration of these relationships is essential for a comprehensive understanding of PC progression and management.

Background: The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3^Tyr705) or serine at 727 (pSTAT3^Ser727). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway. However, not much is known about how androgen deprivation therapy (ADT) in advanced disease affects pSTAT3 expression. The aim of this study was to determine the influence of ADT on pSTAT3 expression in PCa tissue.

Methods: The study cohort came from a PCa tissue microarray resource containing prostate specimens from patients before and post-initiation of ADT. Tissue samples from 111 patients were immunostained for pSTAT3^Tyr705 and pSTAT3^Ser727. H-score was used to evaluate the intensity and the percentage of pSTAT3 expression in malignant epithelial and stromal compartments. Univariate and multivariable Cox regression analyses were used to assess pSTAT3^Tyr705 and pSTAT3^Ser727 as biomarkers of oncological outcome in patients undergoing ADT.

Results: Post-ADT PCa samples demonstrated increased nuclear and cytoplasmic levels of pSTAT3^Ser727 in the stroma compared to pre-ADT samples, whereas pSTAT3^Tyr705 expression was increased significantly in both stromal and malignant epithelial compartments except for stromal cytoplasm. High cytoplasmic pSTAT3^Ser727 in stromal compartments correlated with reduced overall survival, shorter time to castration-resistant PCa development, and decreased metastasis-free survival. An increase in nuclear and cytoplasmic pSTAT3^Ser727 expression within the stromal compartment of post-ADT samples corresponded to a shorter time to CRPC development, which was not observed for pSTAT3^Tyr705. Multivariable survival analysis using Cox's regression identified that high cytoplasmic pSTAT3^Ser727 expression in the stroma of post-ADT samples and pT3 or pT4-stage were associated with worse overall survival and 5-year metastasis-free survival (MFS).

Conclusions: This study presents novel insights into the impact of ADT on the expression levels of pSTAT3^Tyr705 and pSTAT3^Ser727 in PCa. Cytoplasmic pSTAT3^Ser727 status of cancer-associated stromal cells in post-ADT samples may serve as an independent prognostic marker for OS and 5-year MFS, identifying prostate cancer patients prone to developing resistance to ADT.

Objectives: To compare the detection rates for clinically significant prostate cancer (csPCa; grade group 2 or higher disease) using MRI-targeted biopsy (MRI-TB) versus systematic biopsy (SB) or their combination, and identify risk factors for detecting csPCa in MRI-TB with systematic transrectal (TR)/transperineal (TP) biopsies (sTR/TP-bx) and MRI-TB with sTP-bx.

Methods: We retrospectively analyzed 216 patients who underwent MRI-TB with SB at our hospital between September 2020 and December 2023 and compared clinical characteristics for patients with and without prostate cancer.

Results: csPCa was detected in 132 (61.1%) patients by MRI-TB with sTR/TP-bx, in 121 (56.0%) patients using MRI-TB with sTP-bx, and in 101 (46.8%) patients using MRI-TB. Older age, higher PSA density (PSAD), smaller prostate volume, region of interest in the peripheral zone, higher Prostate Imaging-Reporting and Data System (PI-RADS), and administration of dutasteride were more common in csPCa cases. A scoring system was constructed based on odds ratios for PSAD, PI-RADS ≥ 4, and administration of dutasteride; accordingly, the detection rate of csPCa was 20.3% (14/69) in the low-risk group (RG) and 95.5% (42/44) in high RG for MRI-TB with sTR/TP-bx, and 16.7% (12/72) in the low RG and 97.8% (45/46) in high RG for MRI-TB with sTP-Bx.

Conclusions: The addition of SB increased the detection rate of csPCa compared with MRI-TB alone. PSAD, PI-RADS ≥ 4, and administration of dutasteride significantly affect the detection of csPCa using MRI-TB with SB and can be used for deciding whether to perform a biopsy or include sTR-bx with MRI-TB.