prostate

Prostate cancer (PCa) is the most common cancer among men, and type 2 diabetes mellitus (T2DM) increases the risk of PCa. This meta-analysis aimed to investigate the association between metformin administration, PCa incidence, and mortality rates.

The inquiry included databases PubMed, Cochrane, Scopus, Web of Science, and Google Scholar search engine and was updated until June 9, 2024. The primary outcome was the effect of metformin on the risk of PCa. Data were analyzed using STATA version 14 software, and statistical significance was determined at P<0.05.

The results of 30 studies containing 1655591 men showed no significant relationship between metformin use and prostate neoplasm (OR: 0.94; 95% CI: 0.79-1.11). Additionally, the use of metformin in men aged 60 to 69 (OR: 0.97; 95% CI: 0.86-1.09) and men aged 70 to 79 (OR: 1.11; 95% CI: 0.91-1.35) was not associated with the risk of prostate carcinoma. Metformin use was not related to PCa in cohort studies (OR: 0.88; 95% CI: 0.71-1.08) and case-control studies (OR: 1.07; 95% CI: 0.92-1.25). Moreover, no significant relationship was found between metformin use and prostate carcinoma in Asia (OR: 0.78; 95% CI: 0.52-1.17), Europe (OR: 1.13; 95% CI: 0.96-1.32), or America (OR: 0.94; 95% CI: 0.74-1.20). However, metformin use reduced PCa mortality (HR: 0.83; 95% CI: 0.71-0.98).

Although the use of metformin did not reduce the risk of prostate carcinoma, it was associated with a 17% reduction in prostate carcinoma cancer mortality.

One of the common diseases among men is prostate problems, which include benign prostatic hyperplasia and prostate cancer. For centuries, medicinal plants have served as integral components in the management of prostate disorders, providing natural alternatives to conventional therapies. In this regard, using local and ethnobotanical knowledge in a region like Ilam can help to identify effective medicinal plants for these diseases. This research was conducted with the aim of identifying and investigating medicinal plants effective on the prostate in Abdanan city from an ethnobotanical point of view.

This study was conducted using a qualitative method and through semi-structured interviews with 25 traditional healers in Abdanan city (Ilam province, western Iran). The collected information included the names of the plants, how to use them, the parts of the plant used and their therapeutic effects on the prostate. Data analysis was done using quantitative analysis and qualitative content.

The results showed that 10 types of medicinal plants in Abdanan city are known to be effective on prostate problems. Among the identified plants, we can mention clover, rose hip, chicory, yarrow, stinging nettle, camelthorn, flaxseed, puncture vine, borage, and hollyhock. Clover and rose hip plant with UR (usage report index) equal to 9, RFC (relative frequency of citation) equal to 0.62 and PFU (percentage of frequency of use) equal to 34.6% are the most medicinal plants used for prostate in Abdanan region.

The indigenous and ethnobotanical knowledge of Abdanan city shows that medicinal plants can be used as effective therapeutic supplements in the management of prostate problems. The findings suggest a potential for developing herbal-based treatments as complementary approaches.

Prostatitis, characterized by inflammation of the prostate gland, is a common condition among men, especially those in middle age, and is associated with painful symptoms and urinary complications. While bacterial infections are the primary cause, non-infectious factors can also contribute to the disease. Treatment of prostatitis typically involves the administration of anti-inflammatory drugs, analgesics, and antibiotics, which may be associated with adverse effects. This study aims to identify medicinal plants used in traditional Iranian medicine for the treatment of prostatitis. In this review, keywords such as "medicinal plants," "prostate," "bladder infection," "traditional medicine," and "Iran" were used to search for relevant articles. The databases used for this search included Google Scholar, SID, Magiran, PubMed, and Scopus. Articles related to ethnobotany were selected for the literature review. Plants such as green tea, flaxseed, pumpkin, turmeric, pomegranate, tomato, licorice, nettle, apple, red clover, horsetail, carrot, beetroot, turnip, artichoke, cabbage, tribulus, red pepper, soybean, onion, garlic, strawberry, raspberry, and blackberry are among the most important medicinal plants effective in the treatment of benign prostatic hyperplasia. The results of this review suggest that the use of medicinal plants is a low-risk and effective approach to the treatment of prostatitis.

Considering the non-invasiveness, sensitivity, and specificity of magnetic resonance spectroscopy (MRS), as well as its ability to diagnose prostate lesions in the early stages, this study aimed to determine the value of the MRS method compared to the standard method (pathology) for diagnosing prostate cancer.

This analytical cross-sectional study was conducted on 35 male patients. Individuals with indications for prostate biopsy were first subjected to a prostate-specific antigen (PSA) test and a finger examination. It should be noted that the negative or positive result of MRS, in terms of the imaging method used for the patients did not affect the biopsy. After evaluating the patients using the MRS method, the MRS and prostate biopsy results were assessed for each patient separately and compared with the pathological results of the biopsy. To determine the diagnostic value of the test, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated.

The sensitivity, specificity, positive, and negative predictive value of MRS in the left prostate region were calculated as 100%, 66.7%, 33.3%, and 100%, respectively. On the right side of the prostate, these values were 50%, 93%, 50%, and 93%, respectively. The diagnostic accuracy of MRS was 71.4% in the diagnosis of prostate cancer in the left area and 88.57% in the right area. On both sides, the test’s sensitivity, specificity, and positive and negative predictive value were 87.5%, 59.3%, 38.9%, and 94.1%, respectively, and the diagnostic accuracy of neoadjuvant systemic therapy was 65.7%.

MRS, as a non-invasive method, demonstrates optimal sensitivity, specificity, and accuracy compared to other pathological and clinical methods.

Single agent use of chemotherapy in prostate cancer is very limiting, as large doses are often required for tumour control and can lead to elevated systemic toxicity. Targeting of survival proteins of the epidermal growth factor receptor (EGFR), phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR) and androgen receptor (AR) pathways with cocktails of specific inhibitors might yield optimum therapeutic benefit with minimal toxicity. 

The modes of interaction of the dual inhibitor of PI3K and mTOR (NVP-BEZ235), EGFR inhibitor (AG-1478), and AR inhibitor (MDV3100) in in vitro cultures of four human prostate cell lines (DU145, LNCaP, BPH-1 and 1542N) were evaluated as cocktails, using clonogenic cell survival, subsequent to validation of the androgen dependency. Components of cocktails (Cocktail 1 (AG-1478 and NVP-BEZ235), Cocktail 2 (NVP-BEZ235 and MDV3100), and Cocktail 3 (MDV3100 and AG-1478)) were used at equivalent concentrations for 50% cell killing. Combination indices (CI) for the cocktails were determined and used as descriptors of inhibitor interaction. Radiomodulatory effects of inhibitor cocktails were also evaluated.

Inhibitor cocktails selectively showed strong to very strong synergism and radiosensitization. Concurrent inhibition of PI3K/mTOR and AR could potentially be of better therapeutic benefit than inhibition of EGFR and PI3K/mTOR or AR and EGFR, as the potential benefit of EGFR targeting was found to be limited.

These data may guide the design of potent treatment approaches for prostate cancer.

Volumetric modulated arc therapy (VMAT) is mostly considered due to its superior tumor coverage and sparing of organs at risk (OAR) with shorter treatment delivery time. This study aimed to explore the feasibility and potential benefits of VMAT with a constant dose rate (CDR). In this analytical study, 75 cancer patients (15 from each cancer) were selected. Step and shoot intensity-modulated radiation therapy (S&S IMRT), CDR, and VDR VMAT (variable dose rate VMAT) plans were generated for each patient using the Monte Carlo algorithm on the Monaco treatment planning system for 6 MV photon energy. For dosimetric comparison, some variables were compared, including doses to the planning target volume (PTV), OAR, homogeneity index, conformity index (CI), treatment delivery time, and monitor units. CI was higher in CDR and VDR VMAT plans compared to IMRT without any significant variation for PTV coverage V95 and PTV mean dose. In the sparing of OAR, no significant variation was found between CDR, VDR, and IMRT for the brain, head-neck, oesophagus, lung, and prostate. The treatment delivery time was reduced more, i.e., by up to 72-80% in the CDR VMAT technique compared to IMRT.  CDR VMAT technique generates a clinically acceptable plan in terms of PTV coverage, dose conformity, and OAR sparing as IMRT and VDR VMAT in all five cancer sites.

Erectile dysfunction (ED) is a common issue in men, often associated with various factors, such as obesity, diabetes, and more. This case study examines the impact of friction massage combined with pelvic floor exercises on ED in three patients, linked to prostatic adenectomy, aging, and diabetes.

Case Description:

 Patients followed a one-month regimen of pelvic floor exercises and techniques. The technique’s progress was monitored via video calls twice a week. Exercises lasted for 10 min daily, along with a 10-min massage. We assessed improvement using the international index of erectile function 15 (IIEF15) questionnaire and erection hardness score (EHS), as well as ultrasound scans.

Following treatment, all three patients showed increased EHS and IIEF15 15 scores. Muscular thickness increased in the ischiocavernosus and bulbospongiosus muscles, while the cavernosal artery exhibited higher systolic velocity and lower diastolic velocity, although maximum blood flow velocity in the posterior vein decreased. Treatment had the most significant impact on the adenectomy patient, followed by the elderly patient and then the diabetic patient.

Combining friction massage and pelvic floor exercises led to improved erection-related indicators and increased patient satisfaction.

 To analyze the perioperative factors that influence the risk of biochemical recurrence (BCR) in patients with localized PCa undergoing radical prostatectomy

 A total of 457 patients, operated by 2 surgeons in our high-volume oncological center were included in the initial database. Patients who underwent RP for clinically localized PCa in our clinic from 2016 to 2021 were included in the study. Perioperative data were retrospectively reviewed for this study. Follow-up data including post-operative PSA and adjuvant treatment was prospectively gathered by contacting the patients or from the follow-up consultation. Final database was composed of 366 patients who underwent open or 3D laparoscopic RP. Statistical analysis was performed to emphasize the most powerful parameters that influence the BCR. 

 Accounting for multivariable analysis, 4 parameters were statistically significant: initial PSA (iPSA), Gleason score, vascular involvement and positive surgical margins. For the group of patients with no positive margins, 3 parameters were statistically significant: iPSA above 10,98 ng/mL (AUC=0,71); lymph node involvement and Gleason score. Multivariable Cox regression showed that positive margins and iPSA had a significant impact on the time to BCR. Patients that received adjuvant therapy were excluded from the study. Out of the whole cohort, 27,3% of patients presented BCR.

Perioperative factors need to be carefully analyzed and a detailed follow-up needs to be conducted in order to assess the risk of biochemical recurrence, resulting in the optimal time for adjuvant treatment implementation.

Patient repositioning in treatment radiotherapy is one of the main factors that increase error of target irradiation. However additional margin is necessary to consider the uncertainties created along and around X, Y and Z-axis. Set-up and random errors were calculated in translational and rotational axis for a sample of 20 prostatic patients; using daily IGRT-CBCT method. The aim of this study was to determine the additional margin that should be added from clinical target volume (CTV) to prevent toxicity and increase the irradiation precision in radiotherapy. The van Hark formula (PTV margin =2.5Σ +0.7σ) was used for all patients to perform PTV margin for prostatic localization. The research performed for a sample of 20 consecutive patients. With respect to systematic error along the lateral axis, longitudinal and anterior-posterior was 2.32, 2.42 and 3.54 respectively. The Random error was 1.82, 2.19 and 1.76° along lateral axis, longitudinal and anterior-posterior respectively. The rotational systematic error was 1.49, 2.04 and 2.14° around lateral, longitudinal and anterior-posterior axis respectively. The Random error was 1.78, 1.75 and 1.63° around lateral, longitudinal and anterior-posterior axis respectively. The calculated safety margin to cover clinical target volume (CTV) taking the prostate variability into account measured 7.55, 8.08 and 10.79 mm for lateral, longitudinal and anterior posterior respectively and 7mm would be enough in the posterior side. Rotational set-up errors for almost 95% of patients were between -2° and 2°. The calculated safety margin in all direction was smaller than 1 cm except in anterior side that was 1 cm or more.

Accurate and non-invasive diagnostic and prognostic markers are necessary to improve patient outcomes. MicroRNAs have been proposed as relatively non-invasive and pertinent biomarkers. miR-93 has been studied for its potential as a diagnostic and prognostic marker in prostate cancer (PCa), but findings from individual studies are inconsistent. We conducted a meta-analysis of its overall differential expression in 13 PCa studies and a bioinformatics analysis to provide a comprehensive appraisal of its diagnostic and prognostic role.

We searched all published papers on miR-93 expression in PCa up to Nov 30, 2022 using PubMed, Science Direct, Web of Science, Cochrane Central Register of Controlled Trials databases. We used RevMan software to Meta-analyze the included literature. A bioinformatics analysis of genes and pathways that might be target to the effect of the mature miR-93-5p was carried out.

The pooled standardized mean difference (SMD) of miR-93 expression in PCa, its area under the curve (AUC) and hazard ratio (HR) were 1.26, 95% CI [-0.34–2.86], 0.84, 95% CI [0.76 –0.93] and 1.67, 95% CI [0.98, 2.84] respectively. Bioinformatics analysis revealed that mature miR-93-5p may regulate genes such as SMAD1, SMAD7 and MAPK and the PI3K-Akt signaling pathways.

miR-93 has significant diagnostic and prognostic value in PCa. These findings highlight the potential of miR-93 as a non-invasive biomarker for PCa and may contribute to earlier detection and prognostic assessment. The target genes and signaling pathways regulated by miR-93 may provide insights into the underlying molecular mechanisms of PCa.

 Transperineal template prostate biopsies (TPTPB) are now increasingly commonly performed for the diagnosis of prostate cancer. TPTPB are traditionally performed under general anaesthetic. However, this poses a significant strain on hospital theatre capacity. As such, local anaesthetic (LA) TPTPB are becoming more popular. We describe a novel technique in performing the standard TPTPB under LA in the outpatient setting.

 Between February 2019- February 2021, 254 consecutive men (median age 69; range: 44-80 years) with a median PSA of 8.7 ng/ml (range: 2.2-76) underwent L/A TPTPB using our novel technique. This is whereby 50mls of 1% prilocaine was injected partially around the perineal skin and partially deep bilateral periprostatic areas. Multiple simultaneous prostate biopsies were then taken with the standard template grid and stepper.

 A total of 250/254 (98.4%) men underwent successful L/A TPTPB with a median visual analogue pain score of 4 (range: 2-8). The median prostate volume was 49cc (range: 14-240cc). The median number of cores taken were 18 (range: 14-24). A total of 163/250 men (65.2%) had a positive histology for prostate cancer with a median of 5 cores being involved with prostate cancer (range: 1-18). In addition, 101/163 men (62.0%) diagnosed with prostate cancer had either Gleason score 3+4=7 or greater. None experienced urosepsis and only 2/250 men (0.8%) had temporary urinary retention.

 Our novel LA technique in performing the standard TPTPB is safe, feasible and well tolerated and associated with a high rate of prostate cancer detection.

This study aims to use the Intensity Modulated Radiation Therapy (IMRT) technique for prostate cancer patients to evaluate the effectiveness of four different commercial Treatment Planning Systems (TPS): (Eclipse, Monaco, Ray plan, and Prowess). In terms of Conformality Index, Homogeneity Index, the dose distributions, the mean dose, the maximum dose, number of segments in each plan for each TPS, Monitor Units per fraction for each treatment plan for each TPS, coverage of the PTVs, and avoidance of Organs At Risk (OARs) for Simultaneous Integrated Boost (SIB) for cancer prostate treatment plans.
CT images and volumes structure of 10 patients were used to make IMRT plans. The target volume’s structure was contoured according to RTOG 0534 protocol. Fixed beam geometry and clinical goals were set for all individual patient plans. The results were analyzed in terms of dosimetric parameters, the number of segments, and monitor units per segment.
All TPSs achieve similar coverage, and dose distributions to the PTVs. For PTV60 Eclipse achieved the lowest coverage relative to other planning and the nearest mean dose to prescription dose and significant difference relative to other planning. For PTV 44: the Ray plan achieved the best coverage with a significant difference relative to other systems, but Eclipse achieved the nearest mean dose to the prescribed dose with a significant difference relative to the ray plan. Prowess achieved the lowest MU/fraction with a significant difference relative to Monaco the highest in Mus and the lowest possible number of segments.
The four planning systems achieve close dose distributions and confirmation numbers but there is a significant difference in total segments per fraction and total monitor units per fraction which affect the long life of the machine and the session treatment time.

Expression of CD44 variant 6 (CD44v6) as a homing-associated cell adhesion molecule (HCAM),hasproved to change most cancer cells. Aim of the study is the effect of mutant allele of CD44 (rs8193C>T),Pum2regulatory element as a prognosis factor of prostate neoplasms: a case-control,in silico studies in the Mazandaranprovince-Iran.

In a case-control study,CD44-rs8193C>T genotyping of the 420 prostate neoplasms (210benign prostatic hyperplasia (BPH) patients,210 prostate cancer patients),150 healthy samples are performedby the touchdown polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. The T mutantallele effects on the mRNA structure,cell pathways were also investigated in silico methods.

Our results showed that the increase of T mutant allele frequency was significantly associated with BPHcompared with prostate cancer. Furthermore,results showed TT genotype was significantly associated with BPH[odds ratio (OR),0.572,P,0.015],and also influenced the CD44v6 transcript secondary structure,miRNA binding,and regulatory element-binding site for Pum2 protein. Attachment of Pum2 to standard CD44 transcript may lead totranscript isoform-switching,shift-expression to a variety of CD44 isoforms,which can trigger some of the cellsignaling pathways,such as Nanog-Stat,PKC-Nanog,and PKC-Twist.

Based on this,the presence of the T mutant allele of CD44 (rs8193C>T) in the populations may createa regulatory element-binding site for Pum2. So,it could be known as a prognosis factor,prediction of prostateneoplasms. However,more comprehensive studies in different populations (with various ethnicities,large populationsizes),and also CD44v6 gene expression studies in protein,transcript levels are required to confirm our data.

Respiratory movement and the motion range of the diaphragm can affect the quality and quantity of prostate images. This study aimed to investigate the magnitude of respiratory-induced errors to determine Dominant Intra- prostatic Lesions (DILs) in positron emission tomography (PET) images. In this simulation study, we employed the 4D NURBS-based cardiac-torso (4D-NCAT) phantom with a realistic breathing model to simulate the respiratory cycles of a patient to assess the displacement, volume, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), signal to noise ratio (SNR), and the contrast of DILs in frames within the respiratory cycle. Respiration in a diaphragm motion resulted in the maximum superior-inferior displacement of 3.9 and 6.1 mm, and the diaphragm motion amplitudes of 20 and 35 mm. In a no-motion image, the volume measurement of DILs had the smallest percentage of errors. Compared with the no-motion method, the percentages of errors in the average method in 20 and 35 mm- diaphragm motion were 25% and 105%, respectively. The motion effect was significantly reduced in terms of the values of SUVmax and SUVmean in comparison with the values of SUVmax and SUVmean in no- motion images. The contrast values in respiratory cycle frames were at a range of 3.3-19.2 mm and 6.5-46 for diaphragm movements’ amplitudes of 20 and 35 mm.  The respiratory movement errors in quantification and delineation of DILs were highly dependent on the range of motion, while the average method was not suitable to precisely delineate DILs in PET/CT in the dose-painting technique.