Seminal Vesicle Research Articles

Commonality and heterogeneity of pacemaker mechanisms in the male reproductive organs.

During emission, the first phase of ejaculation, smooth muscle in organs of the male reproductive tract (MRT) vigorously contract upon sympathetic nerve excitation to expel semen consisting of sperm and seminal plasma. During inter-ejaculation phases, the epididymis, seminal vesicles and prostate undergo spontaneous phasic contractions (SPCs), this transporting and maintaining the quality of sperm and seminal plasma. Recent studies have revealed platelet-derived growth factor receptor α-expressing (PDGFRα+) subepithelial interstitial cells in seminal vesicles subserve the role of pacemaker cells that electrically drive SPCs in this organ. PDGFRα+ smooth muscle cells in the epididymis also appear to function as pacemaker cells implicating PDGFRα as a potential signature molecule in MRT pacemaking. The dominant mechanism driving pacemaking in these organs is the cytosolic Ca2+ oscillator. This operates through entrainment of the release-refill cycle of Ca2+ stores, the released Ca2+ ions opening Ca2+-activated chloride channels, including in some cases ANO1 (TMEM16A), with the resultant pacemaker potential activating L-type voltage-dependent Ca2+ channels in the smooth muscle causing contraction (viz. SPCs). A second pacemaker mechanism, namely the membrane oscillator also has a role in specific cases. Further investigations into the commonality and heterogeneity of MRT pacemakers will open an avenue for understanding the pathogenesis of male infertility associated with deterioration of seminal plasma.

Addressing racial disparities in prostate cancer pathology prediction models: external validation and comparison of four models of pathological outcome prediction before radical prostatectomy in the multiethnic SEARCH cohort.

Certain widely used pathological outcome prediction models that were developed in tertiary centers tend to overpredict outcomes in the community setting; thus, the Michigan Urological-Surgery Improvement Collaborative (MUSIC) model was developed in general urology practice to address this issue. Additionally, the development of these models involved a relatively small proportion of Black men, potentially compromising the accuracy of predictions in this patient group. We tested the validity of the MUSIC and three widely used nomograms to compare their overall and race-stratified predictive performance. We extracted data from 4139 (1138 Black) men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database of the Veterans Affairs health system. The predictive performance of the MUSIC model was compared to the Memorial-Sloan Kettering (MSK), Briganti-2012, and Partin-2017 models for predicting lymph-node invasion (LNI), extra-prostatic extension (EPE), and seminal vesicle invasion (SVI). The median PSA of Black men was higher than White men (7.8 vs. 6.8 ng/ml), although they were younger by a median of three years and presented at a lower-stage disease. MUSIC model showed comparable discriminatory capacity (AUC:77.0%) compared to MSK (79.2%), Partin-2017 (74.6%), and Briganti-2012 (76.3%), with better calibration for LNI. AUCs for EPE and SVI were 72.7% and 76.9%, respectively, all comparable to the MSK and Partin models. LNI AUCs for Black and White men were 69.6% and 79.6%, respectively, while EPE and SVI AUCs were comparable between races. EPE and LNI had worse calibration in Black men. Decision curve analysis showed MUSIC superiority over the MSK model in predicting LNI, especially among Black men. Although the discriminatory performance of all models was comparable for each outcome, the MUSIC model exhibited superior net benefit to the MSK model in predicting LNI outcomes among Black men in the SEARCH population.

Two new species of Achaeta (Enchytraeidae, Oligochaeta) from afforested post-mining and post-fire sites in Poland

Achaeta (Enchytraeidae, Oligochaeta, Clitellata) is a genus of small, soil-dwelling annelids, peculiar by the absence of chaetae in all species. Here two new species of this genus are described from afforestation sites in southern Poland. Descriptions are based on the investigation of living and preserved material. The species are also characterized at the DNA level, using fragments of the COI and ITS genes, sequenced from the holotypes and paratypes. The worms are not longer than 4–6 mm, with about 30 to 35 segments, and with medium-large male and female reproductive organs. Achaeta florens sp. nov., discovered at a post-mining site, has four segmental pyriform glands, an oesophageal appendage restricted to segment V, a clitellum with distinct transverse rows and dorsal and ventral interruption, and spermathecae with blossom-like fields of vesicular gland cell apices around the ventrally located ectal pores. The species is without peculiar characters but the combination of characters is diagnostic. Its morphological distinction from A. nurmineni, described from the Indian subcontinent, is difficult due to the poor description of that species; A. nurmineni is therefore considered a species inquirenda. Achaeta gemmata sp. nov., discovered in high abundance at a post-fire site, is without pyriform glands but with conspicuous, gem-like lateral papillae in all preclitellar segments. The papillae are modified and enlarged epidermal gland cells that protrude into the body cavity. The species is without oesophageal appendage and has a dorsally closed clitellum and lateral spermathecal pores. It is superficially similar to Achaeta camerani, found at the same site, but can be distinguished based on sexual and non-sexual characters. A comparison of COI sequences showed 100% identity with a specimen from Sweden, erroneously identified as A. cf. brevivasa. Genetic distance between the two new species based on COI differences is 20%, distances to other species of Achaeta with publicly available COI sequences range from 16% to 26%.

Knockout of phosphatidylethanolamine binding protein4 (PEBP4) promotes chronic non-bacterial prostatitis by mediating the activation of NF-κB signaling.

The etiology of chronic prostatitis remains unclear; consequently, this disease is associated with recurrence and ineffective clinical therapy. Therefore, there is an urgent need to investigate the underlying pathogenesis of chronic prostatitis in order to develop more efficacious treatments. The previous study found that knocking out of PEBP4 leads to chronic prostatitis in the male mice. This research aimed to identify the role of PEBP4 in prostatitis, determine the molecular pathogenic mechanisms associated with chronic prostatitis, and provide guidelines for the development of new treatment strategies for chronic prostatitis. A PEBP4 exon knockout strain (PEBP4-/-) was established in C57BL/6 mice via the Cre-loxP system. Hematoxylin-eosin (H&E) staining was used to investigate histological changes. RNA-sequencing was used to investigate the gene expression signature of the prostate and the levels of inflammatory cytokines were determined by real-time polymerase chain reaction (RT-PCR). The expression of PEBP4 protein in prostate tissue was determined by immunohistochemistry in specimens from patients with BPH and BPH combined with chronic prostatitis. Finally, we used a CRISPR-Cas9 plasmid to knockout PEBP4 in RWPE-1 cells; western blotting was subsequently used to measure the level of activation in the NF-κB signaling pathway after activating with TNF-α. Hemorrhage and inflammatory cell infiltration were incidentally observed in the seminal vesicles and prostate glands of PEBP4-/- mice after being fed with a normal diet for 1 year. In addition, we found significantly lower (p<0.001) expression levels of PEBP4 protein in prostate tissues from patients with benign prostate hyperplasia (BPH) and chronic and non-bacterial prostatitis (CNP)when compared to those with BPH only. The reduced expression of PEBP4 led to a higher risk of prostatitis recurrence in patients after 2 years of follow-up. Increased levels of NF-κB and IκB phosphorylation were observed in PEBP4-knockout RWPE-1 cells and prostate glands from PEBP4-/- mice. The knockout of PEBP4 in experimental mice led to chronic prostatitis and the reduced expression of PEBP4 in patients with higher risk of chronic and non-bacterial prostatitis suggested that PEBP4 might act as a protective factor against chronic prostatitis. The knockout of PEBP4 in RWPE-1 cells led to the increased activation of NF-κB and IκB, thus indicating that inhibition of PEBP4 faciliated the NF-κB signaling cascade. Our findings provide a new etiology and therapeutic target for chronic prostatitis.

Cascaded cross-attention transformers and convolutional neural networks for multi-organ segmentation in male pelvic computed tomography.

Segmentation of the prostate and surrounding organs at risk from computed tomography is required for radiation therapy treatment planning. We propose an automatic two-step deep learning-based segmentation pipeline that consists of an initial multi-organ segmentation network for organ localization followed by organ-specific fine segmentation. Initial segmentation of all target organs is performed using a hybrid convolutional-transformer model, axial cross-attention UNet. The output from this model allows for region of interest computation and is used to crop tightly around individual organs for organ-specific fine segmentation. Information from this network is also propagated to the fine segmentation stage through an image enhancement module, highlighting regions of interest in the original image that might be difficult to segment. Organ-specific fine segmentation is performed on these cropped and enhanced images to produce the final output segmentation. We apply the proposed approach to segment the prostate, bladder, rectum, seminal vesicles, and femoral heads from male pelvic computed tomography (CT). When tested on a held-out test set of 30 images, our two-step pipeline outperformed other deep learning-based multi-organ segmentation algorithms, achieving average dice similarity coefficient (DSC) of (prostate), (bladder), (rectum), (seminal vesicles), and (femoral heads). Our results demonstrate that a two-step segmentation pipeline with initial multi-organ segmentation and additional fine segmentation can delineate male pelvic CT organs well. The utility of this additional layer of fine segmentation is most noticeable in challenging cases, as our two-step pipeline produces noticeably more accurate and less erroneous results compared to other state-of-the-art methods on such images.

Three-dimensional ultrastructural and anatomical analysis of prostatic neuroendocrine cells in mice.

A few studies have examined the ultrastructure of prostatic neuroendocrine cells (NECs), and no study has focused on their ultrastructure in three dimensions. In this study, three-dimensional ultrastructural analysis of mouse prostatic NECs was performed to clarify their anatomical characteristics. Three 13-week-old male C57BL/6 mice were deeply anesthetized, perfused with physiological saline and 2% paraformaldehyde, and then placed in 2.5% glutaraldehyde in 0.1 M cacodylate (pH 7.3) buffer for electron microscopy. After perfusion, the lower urinary tract, which included the bladder, prostate, coagulation gland, seminal vesicle, upper vas deferens, and urethra, was removed, and the specimen was cut into small cubes and subjected to postfixation and en bloc staining. Three-dimensional ultrastructural analysis was performed on NECs, the surrounding cells, tissues, and nerves using focused ion beam/scanning electron microscope tomography. Twenty-seven serial sections were used in the present study, and 32 mouse prostatic NECs were analyzed. Morphologically, the NECs could be classified into three types: flask, flat, and closed. Closed-shaped NECs were always adjacent to flask-shaped cells. The flask-shaped and flat NECs were in direct contact with the ductal lumen and always had microvilli at their contact points. Many of the NECs had accompanying nerves, some of which terminated on the surface in contact with the NEC. Three-dimensional ultrastructural analysis of mouse prostatic NECs was performed. These cells can be classified into three types based on shape. Novel findings include the presence of microvilli at their points of contact with the ductal lumen and the presence of accompanying nerves.

Secondary infertility due to necrospermia in men with autosomal-dominant polycystic kidney disease: a report of two cases.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the formation of numerous cysts in organs other than the kidneys. Although female patients with ADPKD do not have direct fertility problems, infertility in male patients may arise following the formation of cystic lesions in the lower seminal tract, which impair the function of spermatozoa. Generally, the treatment strategy for necrospermia depends on the severity of sperm viability, and intracytoplasmic sperm injection may be offered to patients with necrospermia. We report two cases of secondary infertility in men with ADPKD. These men experienced an inability to reproduce naturally after the previous birth of a child, suggesting a progressive deterioration of semen quality. Semen analysis showed necrospermia in both patients, and transrectal ultrasound revealed marked dilatation of the seminal vesicles bilaterally. The main cause of secondary infertility in male patients with ADPKD is sperm death resulting from progressive dilatation of seminal vesicles. Further research is needed on the appropriate follow-up schedule for men with ADPKD who desire to reproduce naturally.

Ultrahypofractionated Radiation Therapy for Prostate Cancer Including Seminal Vesicles in the Target Volume: A Treatment-planning Study Based on the HYPO-RT-PC Fractionation Schedule

PurposeUltra-hypofractionated (UHF) radiation therapy (RT) has become a treatment alternative for patients with localized prostate cancer. In more advanced cases, seminal vesicles (SV) are routinely included in the target volume. The Scandinavian HYPO-RT-PC trial, which compared 42.7Gy in 7 fractions (fr) to conventional fractionation (CF), did not include SV in the CTV. The primary objective of the present work is to implement a UHF simultaneous integrated boost (SIB) for prostate cancer RT, incorporating SV into the target volume based on this fractionation schedule. A secondary objective is to analyze the unintentional dose coverage of SV from state-of-the-art VMAT treatments to the prostate gland only. Material and MethodsTwo different equi-effective UHF-SIB treatment schedules to SV were derived based on the CF clinical schedule (50.0Gy/25fr to elective SV and 70.0Gy/35fr to verified SV-invasion (SVI)) using the linear quadric model with α/β=2Gy and 3Gy. The dose to the prostate was 42.7Gy/7fr in both schedules with 31.2Gy/37.8Gy (α/β=2Gy) and 32.7Gy/40.1Gy (α/β=3Gy) to elective SV/verified SVI. VMAT plans to the proximal 10mm and 20mm were optimized and dose-volume-metrics for target volumes and organs at risk (OAR) evaluated. ResultsDose metrics were overall lower for UHF-SIB compared to CF. QUANTEC based volume-criteria are 2-7% lower for rectum and 2-4% lower for bladder in the UHF-SIB. D98% to elective SV were 7-12Gy3 lower with UHF-SIB and the corresponding data for verified SVI were about 2-3Gy3. The SV(10mm) V90%/(29.5Gy) for prostate only treatments (42.7Gy) were in median (IQR) 99% (87-100)/ 78% (58-99) for CTV/PTV. ConclusionUHF RT, based on the HYPO-RT-PC fractionation schedule, with a SIB technique to the prostate and the base of the SV can be planned with lower doses (EQD2) to OARs compared to CF. Unintentional dose to the proximal parts of SV in prostate only treatment can be substantial.

Dosimetric Features of Ultra-Hypofractionated Intensity Modulated Proton Therapy for Prostate Cancer

PurposeTo report clinical and dosimetric characteristics of five-fraction stereotactic ablative radiotherapy (SABR) using intensity modulated proton therapy (IMPT) for localized prostate cancer. Materials and MethodsAll patients receiving IMPT SABR from 2017 to 2021 for localized prostate cancer at our institution were included. Five fractions were delivered every other day to the prostate +/- seminal vesicles [clinical target volume (CTV)] with 3 mm/3% robustness. A four-field arrangement with two anterior oblique and two opposed lateral beams was used in most patients (97%), and most (99%) had a retroprostatic hydrogel spacer. ResultsA total of 534 patients with low (14%), favorable intermediate (45%), unfavorable intermediate (36%), high (4.0%), or very high-risk (0.6%) disease are evaluated. Prescription dose was 36.25 Gy (31%), 38 Gy (38%), or 40 Gy (31%) was prescribed. Median volume percentage of CTV receiving at least 100% of prescription dose [V100% (%)] was 100% [interquartile range: 99.99 - 100]. Rectum V50% (%), V80% (%), and V90% (%) were significantly lower in patients who had spacer, with a mean difference of -9.70%, -6.59%, and -4.42%, respectively, compared to those who did not have spacer. Femoral head dose was lower with a four-field arrangement. Mean differences in left and right femoral head V40% (%) were -6.99% and -10.74%, respectively. ConclusionWe provide a large, novel report of patients treated with IMPT SABR for localized prostate cancer. Four-field IMPT with hydrogel spacer provides significant sparing of rectum and femoral heads without compromising target coverage.

Comparative Proteomics Elucidates the Potential Mechanism of Sperm Capacitation of Chinese Mitten Crabs (Eriocheir sinensis).

Sperm capacitation is broadly defined as a suite of biochemical and biophysical changes resulting from the acquisition of fertilization ability. To gain insights into the regulation mechanism of crustacean sperm capacitation, 4D label-free quantitative proteomics was first applied to analyze the changes of sperm in Eriocheir sinensis under three sequential physiological conditions: seminal vesicles (X2), hatched with the seminal receptacle content (X3), and incubated with egg water (X5). In total, 1536 proteins were identified, among which 880 proteins were quantified, with 82 and 224 proteins significantly altered after incubation with the seminal receptacle contents and egg water. Most differentially expressed proteins were attributed to biological processes by Gene Ontology annotation analysis. As the fundamental bioenergetic metabolism of sperm, the oxidative phosphorylation, glycolysis, and the pentose phosphate pathway presented significant changes under the treatment of seminal receptacle contents, indicating intensive regulation for sperm in the seminal receptacle. Additionally, the seminal receptacle contents also significantly increased the oxidation level of sperm, whereas the enhancement of abundance in superoxide dismutase, peroxiredoxin 1, and glutathione S-transferase after incubation with egg water significantly improved the resistance against oxidation. These results provided a new perspective for reproduction studies in crustaceans.

Seminal vesiculitis in golden hamsters (Mesocricetus auratus): two cases (2022)

BackgroundSeminal vesiculitis is a disease characterized by inflammation of the seminal vesicles. It has been reported in stallions, bulls, rams, boars, rabbits, mice, and rats but has not been reported in golden hamsters. MethodsGolden hamsters (Mesocricetus auratus) with seminal vesiculitis diagnosed by histopathologic examination in a private animal hospital between February and December 2022 were eligible for inclusion. ResultsTwo golden hamsters were included in the study. Both patients presented with lethargy and hematuria. Ultrasonographic examination of the seminal vesicles showed less distinct lobulation, wall thickening, and hyperechoic fluid in one case. One patient was treated with trimethoprim-sulfamethoxazole. The hamster died 11 days after presentation. The other patient was treated with a seminal vesiculectomy and was euthanized 66 days after surgery due to congestive heart failure and a left atrial mass. Histopathologic examination of seminal vesicles from both patients showed dilation, transmural necrosis, and inflammation. Conclusions and clinical relevanceSeminal vesiculitis should be considered as a differential in male golden hamsters with hematuria. In the cases presented here, ultrasonography was useful to formulate a diagnostic suspicion. Treatment options require further investigation.

Comparison of Ga-68 PSMA PET/CT and Multiparametric MRI for Initial Detection and Staging of Prostate Cancer

Abstract Background Multiparametric magnetic resonance imaging (mpMRI) is widely used for the evaluation of prostate cancer and is known to have better accuracy. Gallium-68 prostate-specific membrane antigen (Ga-68 PSMA) is a radiotracer that shows high localization in prostate cancer cells. Purpose The purpose of this study was to assess the sensitivity and utility of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in comparison with mpMRI as a noninvasive imaging technique for the initial diagnosis and locoregional staging of prostate cancer using transrectal ultrasound (TRUS)-guided biopsy as gold standard. Materials and Methods This prospective observational study conducted from August 2017 to April 2020 evaluated 60 men (n = 60) with biopsy-proven prostate carcinoma. They underwent mpMRI and Ga-68 PSMA PET/CT scans within 14 days with TRUS biopsy being gold standard. T staging of disease, N staging of lymph nodes within the pelvis, and M staging of lesions in pelvic bones (within the imaging field of mpMRI) were compared using PSPP version 1.0.1 statistical software. Results All 60 men with a mean age of 69.9 ± 9.35 years showed Ga-68 PSMA avid disease, whereas 55 were detected by mpMRI. The sensitivity in detection of prostate lesions (with 95% confidence interval) was 99.08% for Ga-68 PSMA PET/CT and 84.40% for mpMRI. Ga-68 PSMA PET/CT detected greater number of patients with regional lymph nodal involvement (19/60) as compared with mpMRI (12/60). Ga-68 PSMA PET/CT showed PSMA avid pelvic skeletal lesions in nine patients, whereas mpMRI detected pelvic lesions in six patients. In addition, four other patients showed extrapelvic skeletal lesions on Ga-68 PSMA PET/CT. Conclusion Ga-68 PSMA PET/CT has superior sensitivity in detection of primary prostate tumor, as compared with mpMRI. Both modalities correlate well in detection of seminal vesicle involvement. Ga-68 PSMA PET/CT outperformed mpMRI in detection of lymph nodal and skeletal metastases. Hence, Ga-68 PSMA PET/CT should be considered as first-line diagnostic modality for carcinoma prostate. Summary Statement: Ga-68 PSMA PET/CT shows superior diagnostic performance than mpMRI in the evaluation of prostate cancer.

Tumor upgrading among very favorable intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy: how can it impact the clinical course?

We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression. A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses. Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2. Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment.

Impact of bias field correction on 0.35 T pelvic MR images: evaluation on generative adversarial network-based OARs' auto-segmentation and visual grading assessment.

Magnetic resonance imaging (MRI)-guided radiotherapy enables adaptive treatment plans based on daily anatomical changes and accurate organ visualization. However, the bias field artifact can compromise image quality, affecting diagnostic accuracy and quantitative analyses. This study aims to assess the impact of bias field correction on 0.35 T pelvis MRIs by evaluating clinical anatomy visualization and generative adversarial network (GAN) auto-segmentation performance. 3D simulation MRIs from 60 prostate cancer patients treated on MR-Linac (0.35 T) were collected and preprocessed with the N4ITK algorithm for bias field correction. A 3D GAN architecture was trained, validated, and tested on 40, 10, and 10 patients, respectively, to auto-segment the organs at risk (OARs) rectum and bladder. The GAN was trained and evaluated either with the original or the bias-corrected MRIs. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95th) were computed for the segmented volumes of each patient. The Wilcoxon signed-rank test assessed the statistical difference of the metrics within OARs, both with and without bias field correction. Five radiation oncologists blindly scored 22 randomly chosen patients in terms of overall image quality and visibility of boundaries (prostate, rectum, bladder, seminal vesicles) of the original and bias-corrected MRIs. Bennett's S score and Fleiss' kappa were used to assess the pairwise interrater agreement and the interrater agreement among all the observers, respectively. In the test set, the GAN trained and evaluated on original and bias-corrected MRIs showed DSC/HD95th of 0.92/5.63mm and 0.92/5.91mm for the bladder and 0.84/10.61mm and 0.83/9.71mm for the rectum. No statistical differences in the distribution of the evaluation metrics were found neither for the bladder (DSC: p = 0.07; HD95th: p = 0.35) nor for the rectum (DSC: p = 0.32; HD95th: p = 0.63). From the clinical visual grading assessment, the bias-corrected MRI resulted mostly in either no change or an improvement of the image quality and visualization of the organs' boundaries compared with the original MRI. The bias field correction did not improve the anatomy visualization from a clinical point of view and the OARs' auto-segmentation outputs generated by the GAN.

Histogram analysis of MR quantitative parameters: are they correlated with prognostic factors in prostate cancer?

To investigate the correlation between quantitative MR parameters and prognostic factors in prostate cancer (PCa). A total of 186 patients with pathologically confirmed PCa who underwent preoperative multiparametric MRI (mpMRI), including synthetic MRI (SyMRI), were enrolled from two medical centers. The histogram metrics of SyMRI [T1, T2, proton density (PD)] and apparent diffusion coefficient (ADC) values were extracted. The Mann‒Whitney U test or Student's t test was employed to determine the association between these histogram features and the prognostically relevant factors. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the differentiation performance. Spearman's rank correlation coefficients were calculated to determine the correlations between histogram parameters and the International Society of Urological Pathology (ISUP) grade group as well as pathological T stage. Significant correlations were found between the histogram parameters and the ISUP grade as well as pathological T stage of PCa. Among these histogram parameters, ADC_minimum had the strongest correlation with the ISUP grade (r = -0.481, p<0.001), and ADC_Median showed the strongest association with pathological T stage (r = -0.285, p=0.008). The ADC_10th percentile exhibited the highest performance in identifying clinically significant prostate cancer (csPCa) (AUC 0.833; 95% CI 0.771-0.883). When discriminating between the status of different prognostically relevant factors, a significant difference was observed between extraprostatic extension-positive and -negative cancers with regard to histogram parameters of the ADC map (10th percentile, 90th percentile, mean, median, minimum) and T1 map (minimum) (p=0.002-0.032). Moreover, histogram parameters of the ADC map (90th percentile, maximum, mean, median), T2 map (10th percentile, median), and PD map (10th percentile, median) were significantly lower in PCa with perineural invasion (p=0.009-0.049). The T2 values were significantly lower in patients with seminal vesicle invasion (minimum, p=0.036) and positive surgical margin (10th percentile, 90th percentile, mean, median, and minimum, p=0.015-0.025). Quantitative histogram parameters derived from synthetic MRI and ADC maps may have great potential for predicting the prognostic features of PCa.

Safety of Docetaxel in a Patient with Metastatic Castration-Resistant Prostate Cancer After Kidney Transplantation: A Case Report

There are limitations in treating advanced prostate cancer (PC), especially castration-resistant (CR) cases, in renal transplant recipients (RTRs). We describe the case of RTR with metastatic CRPC (mCRPC) treated with docetaxel. A 60-year-old man with end-stage renal disease due to autosomal-dominant polycystic kidney disease (ADPKD) underwent living-related kidney transplantation. A year later, he was diagnosed with PC (prostate-specific antigen level: 998 ng/mL). Prostate biopsy revealed prostatic adenocarcinoma with a Gleason score of 4 + 4 = 8. Radiographic examination revealed seminal vesicle invasion and multiple bone and lymph node metastases. Combined androgen blockade therapy was initiated; however, the patient was diagnosed with CRPC 6 months later. Triweekly docetaxel therapy was administered 28 months after diagnosis. The patient successfully completed 7 cycles of this therapy without major adverse events. However, after the 7th cycle, he developed a high fever caused by an infection of ADPKD-associated renal cysts. Therefore, docetaxel was discontinued, and enzalutamide was started, followed by abiraterone, but without any effect. We then introduced cabazitaxel but discontinued it because of hepatic dysfunction. Hence, the patient underwent a docetaxel rechallenge. He was administered the PEGylated form of the recombinant human granulocyte colony-stimulating factor for neutropenia prophylaxis. After 6 cycles of rechallenge docetaxel therapy, the patient accidentally fell, resulting in a cervical spine fracture and subsequent death due to respiratory failure. Docetaxel can be safely delivered to patients with CRPC after renal transplantation who are taking oral immunosuppressants. It can be a good treatment option for them.

Anatomy and histology of the male reproductive tract of the parasitoid wasp Hymenoepimecis bicolor (Brullé, 1846) (Hymenoptera: Ichneumonidae)

AbstractHymenoepimecis wasps (Hymenoptera: Ichneumonidae) are ectoparasitoids of spiders that modify the hosts’ behaviour by inducing changes in webs. Variations in the male reproductive tract contribute to enhancing our understanding of the reproductive behaviour of these insects. This study describes the morphology of the male reproductive tract of Hymenoepimecis bicolor (Brullé, 1846) using light microscope. The male reproductive tract of H. bicolor consists of a pair of testes, each containing a single follicle, two vasa deferentia, one ejaculatory duct and two accessory glands. The testis follicle has cysts at various stages of spermatogenesis, indicating ongoing sperm cell development and maturation. The vasa deferentia are elongated, with a coiled distal portion, whereas the proximal regions are laterally associated with a pair of accessory glands. The wall of the vasa deferentia has simple cuboidal epithelium. The accessory glands had a simple columnar epithelium with the lumen filled with heterogeneous content. The seminal vesicle is absent. The similarity in the anatomy and histology of the male reproductive tract of H. bicolor with other Hymenoptera suggests that the parasitoid behaviour does not result in significant alteration to their reproductive organs, indicating that the reproductive tract is conserved in Hymenoptera, regardless of their behaviours.

Combined effects of polyethylene microplastics and carbendazim on Eisenia fetida: A comprehensive ecotoxicological study

Microplastic (MP) pollution is becoming an emerging environmental concern across aquatic and terrestrial ecosystems. Plastic mulching and the use of pesticides in agriculture can lead to microplastics and agrochemicals in soil, which can result in unintended exposure to non-target organisms. The combined toxicity of multiple stressors represents a significant paradigm shift within the field of ecotoxicology, and its exploration within terrestrial ecosystems involving microplastics is still relatively limited. The present study investigated the combined effects of polyethylene MP (PE-MP) and the agrochemical carbendazim (CBZ) on the earthworm Eisenia fetida at different biological levels of organization. While E. fetida survival and reproduction did not exhibit significant effects following PE-MP treatment, there was a reduction in cocoon and hatchling numbers. Notably, prolonged exposure revealed delayed toxicity, leading to substantial growth impairment. Exposure to CBZ led to significant alterations in the endpoints mentioned above. While there was a decrease in cocoon and hatchling numbers, the combined treatment did not yield significant effects on earthworm reproduction except at higher concentrations. However, lower concentrations of PE-MP alongside CBZ induced a noteworthy decline in biomass content, signifying a form of potentiation interaction. In addition, concurrent exposure led to synergistic effects, from oxidative stress to modifications in vital organs such as the body wall, intestines, and reproductive structures (spermathecae, seminal vesicles, and ovarian follicles). The comparison of multiple endpoints revealed that seminal vesicles and ovarian follicles were the primary targets during the combined exposure. The research findings suggest that there are variable and complex responses to microplastic toxicity in terrestrial ecosystems, especially when combined with other chemical stressors like agrochemicals. Despite these difficulties, the study implies that microplastics can alter earthworms' responses to agrochemical exposure, posing potential ecotoxicological risks to soil fauna.

Human Seminal Extracellular Vesicles Enhance Endometrial Receptivity Through Leukemia Inhibitory Factor.

Seminal extracellular vesicles (EVs) contain different subgroups that have diverse effects on sperm function. However, the effect of seminal EVs-especially their subgroups-on endometrial receptivity is largely unknown. Here, we found that seminal EVs could be divided into high-density EVs (EV-H), medium density EVs, and low-density EVs after purification using iodixanol. We demonstrated that EV-H could promote the expression and secretion of leukemia inhibitor factor (LIF) in human endometrial cells. In EV-H-treated endometrial cells, we identified 1274 differentially expressed genes (DEGs). DEGs were enriched in cell adhesion and AKT and STAT3 pathways. Therefore, we illustrated that EV-H enhanced the adhesion of human choriocarcinoma JAr cell spheroids to endometrial cells through the LIF-STAT3 pathway. Collectively, our findings indicated that seminal EV-H could regulate endometrial receptivity through the LIF pathway, which could provide novel insights into male fertility.

Abstract 6450: High mobility group protein 2 (HMGA2) is highly expressed in a broad range of human cancers

Abstract The high mobility group protein 2 (HMGA2) is an essential component of the enhanceosome. It can attach to AT-rich binding sites in the DNA minor groove, affect the conformation of the DNA, and thereby modify the transcription of numerous genes. HMGA2 is preferentially expressed during organogenesis. Aberrant expression of HMGA2 in adult tissues is commonly associated with tumor formation and cancer aggressiveness. Accordingly, HMGA2 represents a potential drug target. To better comprehend the role of HMGA2 expression in cancer, a tissue microarray containing 8,344 samples from 115 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. In normal tissues, a strong nuclear HMGA2 staining was limited to few cell types from the amnion, placenta, seminal vesicle, endocervix, fallopian tube, and respiratory epithelium. HMGA2 expression was generally markedly higher in cancer than in corresponding normal tissues. HMGA2 staining was found in 2,695 (42.7%) of the 6,313 interpretable tumor samples, including 701 (11.1%) with weak, 769 (12.2%) with moderate, and 1,225 (19.4%) with strong positivity. A total of 93 of 115 tumor categories showed HMGA2 expression in at least one case, and 69 tumor categories included at least one case with strong HMGA2 staining. The frequency of HMGA2 positivity was particularly high in cancers of the ovary and the endometrium (52.6-92.6%), pancreatico-biliary cancers (48.1-75.5%), thyroidal neoplasms (53.4-95%), salivary gland neoplasms (66.7-98%), nonseminomatous testicular germ cell tumors (73.5-93.5%), colorectal adenocarcinoma (81.6%), papillary renal cell carcinoma (68.2%), and in squamous cell carcinomas (36-81.5%). Tumor entities with a particularly low expression of HMGA2 included prostatic adenocarcinomas (1.3-4%), non-invasive urothelial carcinomas (1.8-4.3%), hepatocellular carcinoma (3.2%), and non-Hodgkin’s lymphomas (0%) It is concluded, that HMGA2 is highly expressed in a very broad range of tumor entities. These findings emphasize a potential role of HMGA2 as a drug target and demonstrate utility for HMGA2 IHC for the distinction of neoplastic from non-neoplastic tissues in several organs. Citation Format: Katharina Möller, Florian Lutz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Stefan Steurer, Christoph Fraune, Sarah Minner, Natalia Gorbokon, Maximilian Lennartz, Eike Burandt, Anne Menz. High mobility group protein 2 (HMGA2) is highly expressed in a broad range of human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6450.