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Frontiers in Pharmacology 2024One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its...
BACKGROUND
One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated.
METHODS
Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub).
RESULTS
113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa.
CONCLUSION
We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.
PubMed: 38957390
DOI: 10.3389/fphar.2024.1383304 -
Frontiers in Oncology 2024Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel...
INTRODUCTION
Precise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer.
MATERIALS AND METHODS
Prior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared.
RESULTS
140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators.
CONCLUSIONS
For precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.
PubMed: 38957327
DOI: 10.3389/fonc.2024.1386058 -
Cureus Jun 2024Adenocarcinoma, while constituting the predominant variant among small bowel cancers, is a component of the broader category of primary small bowel malignancies, which...
An Unexpected Challenge: Marked Small Bowel Obstruction Arising From a Poorly Differentiated Metastatic Mucinous Adenocarcinoma of the Distal Ileum in a Risk-Free Healthy Patient.
Adenocarcinoma, while constituting the predominant variant among small bowel cancers, is a component of the broader category of primary small bowel malignancies, which are notably infrequent in occurrence. The diagnosis of such malignancies is often markedly delayed, a consequence of their insidious onset and the nonspecific nature of the abdominal symptoms presented. A 69-year-old Caucasian male presented to the emergency department manifesting acute, sharp, and colicky abdominal pain accompanied by a single episode of vomiting, all developing over one day. His medical history was notable for gastroesophageal reflux disease (GERD) and regionally confined prostate adenocarcinoma, which was under meticulous surveillance by the urological team. The patient's lifestyle was characterized by abstention from alcohol and tobacco, adherence to a nutritious diet, and a commitment to regular physical activity. Subsequent examination and surgical excision of an abnormal mass, as delineated on computed tomography (CT), culminated in the diagnosis of a stage IV, poorly differentiated adenocarcinoma. We have reported this case to spark research regarding early diagnostic techniques for small bowel adenocarcinoma (SBA). In this case, a healthy individual presented with vague abdominal pain and a single episode of vomiting. Diagnosis required the surgical resection of the tumor, where metastasis was also visualized. Due to the rare nature of SBA, we believe different diagnostic measures and adjuvant therapy should be researched for earlier diagnosis and subsequently better patient outcomes.
PubMed: 38957234
DOI: 10.7759/cureus.61528 -
International Journal of Urology :... Jul 2024New indices of dyslipidemia, such as the Atherogenic Index of Plasma (AIP) or Castelli Risk Index I and II (CR-I/II), have been tested to predict erectile dysfunction...
OBJECTIVE
New indices of dyslipidemia, such as the Atherogenic Index of Plasma (AIP) or Castelli Risk Index I and II (CR-I/II), have been tested to predict erectile dysfunction (ED). The aim of this study was to assess the role of these lipidic scores in predicting severe ED and erectile function (EF) worsening in patients who underwent robot-assisted radical prostatectomy (RARP).
METHODS
Data from 1249 prostate cancer patients who underwent RARP at our single tertiary academic referral center from September 2021 to April 2023 were reviewed. RARP patients with a complete lipid panel were included in the final analysis. Two independent multivariable logistic regression models (LRMs) were fitted to identify predictors of ED severity and worsening in RARP patients.
RESULTS
Among the 357 RARP patients, the median age was 70 (interquartile range [IQR]: 65-74), and the median BMI was 28.4 (IQR: 26-30.4). According to the preoperative IIEF5, 115 (32.2%), 86 (24.5%), 26 (7.3%), and 40 (11.2%) were mild, mild-moderate, moderate, and severe ED patients, respectively. After multivariable LRMs predicting severe ED, only the nerve-sparing (NS) approach (odds ratio [OR]: 0.09) as well as the preoperative IIEF5 score (OR: 0.32) were independent predictors (p < 0.001). After LRMs predicting EF worsening, only preoperative IIEF5 was an independent predictor (OR: 1.42, p < 0.001).
CONCLUSION
The power of novel lipidic scores in predicting severe ED and EF worsening in RARP patients was low, and they should not be routinely applied as a screening method in this patient subgroup. Only preoperative IIEF5 and nerve-sparing approaches are relevant in EF prediction after RARP.
PubMed: 38957091
DOI: 10.1111/iju.15516 -
Lower Urinary Tract Symptoms Jul 2024This study aimed to evaluate the efficacy and safety of Vibegron for the treatment of residual overactive bladder (OAB) symptoms after laser vaporization of the prostate... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of Vibegron for the treatment of residual overactive bladder symptoms after laser vaporization of the prostate: A single-center prospective randomized controlled trial (VAPOR TRIAL).
OBJECTIVES
This study aimed to evaluate the efficacy and safety of Vibegron for the treatment of residual overactive bladder (OAB) symptoms after laser vaporization of the prostate (photo-selective vaporization of the prostate, contact laser vaporization of the prostate, and thulium laser vaporization).
METHODS
This randomized, open-label, parallel-group, single-center superiority trial with a 12-week observation (jRCTs071190040) enrolled male patients with OAB aged 40 years or older who had undergone laser vaporization of the prostate for not less than 12 weeks and not more than 1 year earlier. Patients were allocated to receive Vibegron 50 mg once daily or follow-up without treatment for 12 weeks.
RESULTS
Forty-seven patients were enrolled between January 2020 and March 2023. The median age (interquartile range) was 75.5 (72.5-78.5) years for the Vibegron group and 76.5 (71.0-81.0) years for the control group. The intergroup difference in the mean change (95% confidence interval) in the 24-hour urinary frequency at 12 weeks after randomization was -3.66 (-4.99, -2.33), with a significant decrease for the Vibegron group. The Overactive Bladder Symptom Score, International Prostate Symptom Score, IPSS storage score, and Overactive Bladder Questionnaire score significantly improved for the Vibegron group. Voided volume per micturition also increased for the Vibegron group.
CONCLUSIONS
The administration of 50 mg of Vibegron once daily for 12 weeks showed significant improvement compared with follow-up without treatment in bladder storage (OAB) symptoms after laser vaporization of the prostate for symptomatic benign prostatic hyperplasia.
Topics: Humans; Male; Aged; Urinary Bladder, Overactive; Prospective Studies; Laser Therapy; Prostatic Hyperplasia; Treatment Outcome; Aged, 80 and over; Pyrimidinones; Pyrrolidines
PubMed: 38956950
DOI: 10.1111/luts.12529 -
International Neurourology Journal Jun 2024We aimed to evaluate the effect of self-training using a virtual reality head-mounted display simulator on the acquisition of surgical skills for holmium laser...
PURPOSE
We aimed to evaluate the effect of self-training using a virtual reality head-mounted display simulator on the acquisition of surgical skills for holmium laser enucleation surgery.
METHODS
Thirteen medical students without surgical skills for holmium laser enucleation of the prostate were trained using multimedia to learn the technique via simulator manipulation. Thereafter, participants performed the technique on a virtual benign prostatic hyperplasia model A (test A). After a 1-week wash-out period, they underwent self-training using a simulator and performed the technique on model B (test B). Subsequently, participants were asked to respond to Training Satisfaction Questions. Video footage of hand movements and endoscope view were recorded during tests A and B for later review by 2 expert surgeons. A 20-step Assessment Checklist, 6-domain Global Rating Scale, and a Pass Rating were used to compare performance on tests A and B.
RESULTS
Thirteen participants completed both tests A and B. The 20-step Assessment Checklist and 6-domain Global Rating Scale evaluation results showed significantly improved scores in test B than in test A (P<0.05). No evaluator rated participants as passed after test A, but 11 participants (84.6%) passed after test B. Ten participants (76.9%) indicated that the simulator was helpful in acquiring surgical skills for holmium laser enucleation of the prostate.
CONCLUSION
The virtual reality head-mounted display holmium laser enucleation of the prostate simulator was effective for surgical skill training. This simulator may help to shorten the learning curve of this technique in real clinical practice in the future.
PubMed: 38956773
DOI: 10.5213/inj.2448042.021 -
International Neurourology Journal Jun 2024Transurethral resection of the prostate, or other methods to decrease outlet resistance usually leads to relief of symptoms in patients with bladder outlet obstruction...
Transurethral resection of the prostate, or other methods to decrease outlet resistance usually leads to relief of symptoms in patients with bladder outlet obstruction (BOO). If symptoms of underactivity persist after normalization of outflow conditions, treatment options are limited. In this review, we hypothesize, based on results from basic research, what might become treatment options for such patients in the future. The primary local treatment will still aim at reducing outlet obstruction. We speculate that local secondary treatment in the future might include transplantation of stem cells or mature bladder ganglion cells into the bladder wall. There has been some success in transplanting ganglion cells into the rat bladder. The ganglion cells will sprout into the surrounding tissue but functional connections between the axons of the transplanted neurons, and the detrusor smooth muscle have so far not been demonstrated. Neurotrophins or neurotrimin might be injected into the bladder wall to increase the sprouting of existing or transplanted neurons. Stem cell transplantation has been performed and improves detrusor function, but it has so far, been difficult to demonstrate transplanted stem cells. BOO, persisting detrusor underactivity, and decreased nerve density are often combined with inflammatory activity of the lower urinary tract. NLR family pyrin domain containing 3 (NLRP3) and its messenger RNA (mRNA) as well as cyclooxygenase-2 (Cox-2) mRNA are increased in obstructed bladders. Systemic treatment with the NLRP3 inhibitor glyburide normalized nerve density in rat bladder, and, to some extent, bladder function. It is unclear whether Cox-2 is involved in the decreased nerve density following obstruction, but Cox-2 mRNA increases 5-fold in obstructed bladder. Future therapy against bladder underactivity remaining following relief of obstruction includes either systemic treatment, perhaps by anti-inflammatory drugs, or local treatment by injection of stem cells, mature ganglion cells, and/or neurotrophins or neurotrimin into the bladder wall.
PubMed: 38956767
DOI: 10.5213/inj.2448134.067 -
Cancer Imaging : the Official... Jul 2024Numerous studies have shown that magnetic resonance imaging (MRI)-targeted biopsy approaches are superior to traditional systematic transrectal ultrasound guided biopsy...
BACKGROUND
Numerous studies have shown that magnetic resonance imaging (MRI)-targeted biopsy approaches are superior to traditional systematic transrectal ultrasound guided biopsy (TRUS-Bx). The optimal number of biopsy cores to be obtained per lesion identified on multiparametric MRI (mpMRI) images, however, remains a matter of debate. The aim of this study was to evaluate the incremental value of additional biopsy cores in an MRI-targeted "in-bore"-biopsy (MRI-Bx) setting.
PATIENTS AND METHODS
Two hundred and forty-five patients, who underwent MRI-Bx between June 2014 and September 2021, were included in this retrospective single-center analysis. All lesions were biopsied with at least five biopsy cores and cumulative detection rates for any cancer (PCa) as well as detection rates of clinically significant cancers (csPCa) were calculated for each sequentially labeled biopsy core. The cumulative per-core detection rates are presented as whole numbers and as proportion of the maximum detection rate reached, when all biopsy cores were considered. CsPCa was defined as Gleason Score (GS) ≥ 7 (3 + 4).
RESULTS
One hundred and thirty-two of 245 Patients (53.9%) were diagnosed with prostate cancer and csPCa was found in 64 (26.1%) patients. The first biopsy core revealed csPCa/ PCa in 76.6% (49/64)/ 81.8% (108/132) of cases. The second, third and fourth core found csPCa/ PCa not detected by previous cores in 10.9% (7/64)/ 8.3% (11/132), 7.8% (5/64)/ 5.3% (7/132) and 3.1% (2/64)/ 3% (4/132) of cases, respectively. Obtaining one or more cores beyond the fourth biopsy core resulted in an increase in detection rate of 1.6% (1/64)/ 1.5% (2/132).
CONCLUSION
We found that obtaining five cores per lesion maximized detection rates. If, however, future research should establish a clear link between the incidence of serious complications and the number of biopsy cores obtained, a three-core biopsy might suffice as our results suggest that about 95% of all csPCa are detected by the first three cores.
Topics: Humans; Male; Prostatic Neoplasms; Retrospective Studies; Aged; Image-Guided Biopsy; Middle Aged; Prostate; Magnetic Resonance Imaging; Biopsy, Large-Core Needle; Neoplasm Grading; Magnetic Resonance Imaging, Interventional; Multiparametric Magnetic Resonance Imaging
PubMed: 38956721
DOI: 10.1186/s40644-024-00734-3 -
Radiation Oncology (London, England) Jul 2024Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a...
BACKGROUND
Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling.
METHODS
Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis.
RESULTS
Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified.
CONCLUSION
Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle.
Topics: Humans; Male; Prostatic Neoplasms; Receptors, Androgen; Tumor Suppressor Protein p53; Photons; Transcriptome; Signal Transduction; DNA Damage; Heavy Ion Radiotherapy; DNA Repair; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Carbon
PubMed: 38956684
DOI: 10.1186/s13014-024-02480-z -
BMC Urology Jul 2024In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on... (Comparative Study)
Comparative Study
BACKGROUND
In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk.
METHODS
As the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS).
RESULTS AND CONCLUSIONS
We used 26 SNPs to establish GRS models to predict the risk of biochemical recurrence (BCR) after radical prostatectomy. Combining clinical variables such as age at diagnosis, body mass index, prostate-specific antigen, Gleason score, pathologic T stage, and surgical margin and GRS models has better predictive power for BCR. The results of simulation data (statistical power = 0.707) and prostate cancer data (area under curve = 0.8462) show that DL-GRS has the best prediction performance. The rs455192 was the most relevant locus for BCR (p = 2.496 × 10) in our study.
Topics: Prostatic Neoplasms; Male; Humans; Prostatectomy; Neoplasm Recurrence, Local; Risk Assessment; Middle Aged; Aged; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Predictive Value of Tests; Genetic Risk Score
PubMed: 38956663
DOI: 10.1186/s12894-024-01524-6