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Type-2 diabetes mellitus (T2DM), the predominant form of diabetes in adults, is a co-morbid condition that exacerbates the severity of many other diseases, including cardiovascular disease, obesity, dyslipidemia, hypertension, and cancer. Among these, cancer is particularly concerning due to elevated mortality rates and a distinct lack of cost-effective therapeutic interventions. Identifying novel biomarkers for improved early cancer detection is imperative. Therefore, an integrated bioinformatics analysis was conducted to elucidate the co-morbid relationship between T2DM and five different types of cancer, namely bladder (BLCA), breast (BRCA), colon (CRC), liver (HCC), and prostate cancer (PRAD) and identification of novel biomarkers for early cancer detection in individuals with T2DM. A significant comorbid relationship was observed among T2DM, BLCA, and BRCA through gene expression and pathway enrichment analysis, while a moderate association was observed for between T2DM, and PRAD. Notably, we identified 18 significant hub proteins in the context of cancer and T2DM, along with 16 transcription factors and 5 miRNAs. Among these, the hub proteins ESR1, PIK3CA, GNAI1, ERBB2, NR3C1, SNCA, TGFBR2, as well as the micro RNAs hsa-mir-335-5p, hsa-mir-16-5p, and hsa-mir-93-5p hold promise for understanding the comorbidities of T2DM and cancers; and could serve as valuable disease biomarkers for clinical diagnosis and prognosis. This study, centred on bioinformatics analysis for biomarker identification in comorbidities, paves the way for future research encompassing wet lab experimentation and translational studies. These endeavours are poised to validate and facilitate the integration of these findings into the realm of personalized medicine. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has posed daunting challenges when conducting clinical research. Adopting new technologies such as remote electronic consent (e-Consent) can help overcome them. However, guidelines for e-Consent implementation in ongoing clinical trials are currently lacking. The NeuroSAFE PROOF trial is a randomized clinical trial evaluating the role of frozen section analysis during RARP for prostate cancer. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this paper is to describe the process of implementation, impact on recruitment rate, and patients' experience using e-Consent.Methods: A substantial amendment of the protocol granted the creation of a remote e-Consent framework based on the REDCap environment, following the structure and content of the already approved paper consent form. Although e-Consent obviated the need for in-person meeting, there was nonetheless counselling sessions performed interactively online. This new pathway offered continuous support to patients through remote consultations. The whole process was judged to be compliant with regulatory requirements before implementation.Results: Before the first recruitment suspension, NeuroSAFE PROOF was recruiting an average of 9 patients per month. After e-Consent implementation, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. Limited troubleshooting has been required after implementation.Conclusion: Remote e-Consent-based recruitment was critical for the continuation of the NeuroSAFE PROOF trial during the COVID-19 pandemic. The described pathway complies with ethical and regulatory guidelines for informed consent, while minimizing face-to-face interactions that increase the risk of COVID-19 transmission. This guide will help researchers integrate e-Consent to ongoing or planned clinical trials while uncertainty about the course of the pandemic continues.Trial Registration: NeuroSAFE PROOF trial NCT03317990 . Registered on 23 October 2017. Regional Ethics Committee reference 17/LO/1978. [ABSTRACT FROM AUTHOR]

• HDR single fraction 19 Gy brachytherapy provides insufficient rates of biochemical and local control, in patients with localized prostate cancer. • The pattern of relapse is predominantly local. • HDR single fraction 19 Gy should not be used to treat favorable localized prostate cancer. To report the pattern of relapse within the prostate with reference to the initial site of disease in patients treated with single fraction 19-Gy. Forty-four patients were treated according to a prospective study of single-fraction HDR-brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate. Patients who experienced a biochemical failure underwent a re-staging multiparametric MRI (mpMRI) and MRI-TRUS fusion biopsy to rule-out local recurrence. In patients with visible Dominant intraprostatic lesions (DIL) on pretreatment mpMRI, the site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated. The median follow-up period was 48 months (range 29–63). The PSA nadir was reached at 24 months follow-up, with a median value of 1.07 ng/mL. To date, 14 patients (32%) have experienced biochemical failure (4 patients low-risk and 10 intermediate-risk; p = 0.013). Re-staging mpMRI was performed in 11/14 patients. Eleven patients underwent MRI-TRUS fusion biopsy confirming local relapse in all patients. The analysis of DVH of all 44 patients revealed that patients with biochemical failure had received significantly lower doses in terms of V100, V125 and D90 (p = 0.032, p = 0.018 and p = 0.018 respectively). In patients with DILs on diagnostic mpMRI, the mean D90 and D98 on DIL were lower for patients with biochemical failure. This dosimetric analysis demonstrates a dose-response relationship in patients treated with single fraction 19 Gy. Patients with intermediate risk disease, with visible DIL on mpMRI and patients treated with cooler implants have higher incidence of biochemical and local failure. [ABSTRACT FROM AUTHOR]

Background: By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore, PSMA-PET is increasingly used for planning of radiotherapy treatment; however, any data on intermediate-term outcome is missing so far.Methods: Patients with high-risk or very high risk prostate cancer, referred for salvage radiotherapy (SRT, n = 22) between 2013 and 2015, underwent PSMA-PET prior to therapy. Irradiation was planned on PET data with boost to macroscopic tumors/metastases. Treatment related toxicity was measured using Common Terminology Criteria for Adverse Events (CTCAE, v4.0).Result: Findings in PSMA-PET led to treatment modifications in 77% of SRT patients compared to available CT information. One patient did not receive irradiation due to disseminated disease, the other patients received increased boost doses to macroscopic disease and/or inclusion of additional target volumes. Toxicity was low as only 2 patients reported toxicities > grade 1. With a Median follow-up time of 29 in patients that were not lost to follow-up, prolonged PSA responses below baseline were observed in the majority of patients (14 of 20). In hormone-naïve SRT patients (n = 11), radiotherapy led to prolonged PSA decrease in 8/11 patients, however with 3 of these 8 patients receiving repeated PSMA based irradiation of novel lesions during follow-up.Conclusion: PSMA-PET guided planning of radiotherapy led to change of treatment in the majority of patients. Treatment related toxicity was well tolerated and promising results regarding intermediate-term PSA decrease were observed.Trial Registration: No trial registration was performed due to retrospective evaluation. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is the most suitable method for early detection of prostate cancer. It is very difficult to distinguish benign and malignant nature of the affliction in the early stage of cancer. This is reflected in the high percentage of unnecessary biopsies that are performed and many deaths caused by late detection or misdiagnosis. A computer based classification system can provide a second opinion to the radiologists. Generally, objects are described in terms of a set of measurable features in pattern recognition. The selection and quality of the features representing each pattern will have a considerable bearing on the success of subsequent pattern classification. Feature selection is a process of selecting the most wanted or dominating features set from the original features set in order to reduce the cost of data visualization and increasing classification efficiency and accuracy. The region of interest (ROI) is identified from transrectal ultrasound (TRUS) images using DBSCAN clustering with morphological operators after image enhancement using M3-filter. Then the 22 grey level co-occurrence matrix features are extracted from the ROIs. Soft computing model based feature selection algorithms genetic algorithm (GA), ant colony optimization (ACO) and QR are studied. In this paper, QR-ACO (hybridization of rough set based QR and ACO) and GA-ACO (hybridization GA and ACO) are proposed for reducing feature set in order to increase the accuracy and efficiency of the classification with regard to prostate cancer. The selected features may have the best discriminatory power for classifying prostate cancer based on TRUS images. Support vector machine is tailored for evaluation of the proposed feature selection methods through classification. Then, the comparative analysis is performed among these methods. Experimental results show that the proposed method QR-ACO produces significant results. Number of features selected using QR-ACO algorithm is minimal, is successful and has high detection accuracy. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the feasibility and efficacy of docetaxel-based chemotherapy in patients with hormone-refractory prostate cancer (HRPC). Methods: Forty-six consecutive HRPC patients treated between January 2003 and March 2008 were included in this analysis. Docetaxel was given at a dose of 35 mg/m2 twice every 3 weeks and oral estramustine concurrently for three consecutive days during weeks 1 and 2 of each cycle. During each treatment week, the dose of estramustine was 1260 mg on the first day, 980 mg on the second day and 840 mg on the third day. Patients were premedicated with 4 mg twice a day of oral dexamethasone for three consecutive days. Treatment was continued until evidence of disease progression or unacceptable toxicity. Prostate-specific antigen (PSA) levels were evaluated at least once every 4 weeks. Results: Patients received a median of three cycles of chemotherapy. Of the evaluable 46 patients, 25 (54%) had a ≥50% PSA decline and 12 (26%) had a ≥75% PSA decline. Median time to PSA progression and overall survival time were 10.1 and 27.0 months, respectively. Median follow-up was 15.0 months. Major severe toxicities were grade 3 or 4 leukopenia in five (11%) patients. Mild toxicities included grade 1 or 2 nausea in eight (17%) patients. Two patients could not continue the treatment because of interstitial pneumonitis and a gastric hemorrhage, respectively. Conclusions: Docetaxel plus estramustine chemotherapy represents an active and well tolerated treatment for Japanese HRPC patients. [ABSTRACT FROM AUTHOR]

During radical retropubic prostatectomy, hemostasis of the venous vascular plexus is of the utmost importance for avoiding excessive blood loss and ensuring optimal preservation of urethral length, complete extirpation of all apical prostatic notches and careful preservation of the parasympathetic nerves ('neurovascular bundles'). We have developed a careful bipolar coagulation of the venous plexus that results in a significant reduction of intra-operative blood loss, and the consequent need for transfusion, compared to the standard approach. Furthermore, this coagulation approach results in improved visibility, allowing maximum preservation of urethral length, complete extirpation of all apical prostatic notches and improved application of the nerve sparing technique compared to the standard approach. Follow-up after a mean of 14 months suggests that postoperative continence and potency is at least comparable to the standard approach. However, long-term follow-up and multicenter studies will show if this modification results in equally effective cancer control and equivalent functional results compared to the standard approach. [ABSTRACT FROM AUTHOR]

A question-and-answer booklet about early-stage prostate-cancer was created for patients and their family members. Two sequential studies were conducted to determine if the single source of information would be useful to both patients and their families. The first study used 1:1 interviews with 11 readers (6 patients and 5 family members) to identify features of the booklet that may be problematic. In all, six features were identified as either irrelevant or problematic in their design. The second study was a survey of 54 patients (79% response rate) and 33 family members (49% response rate); the study was designed to obtain an overall evaluation of the booklet, to clarify the proportion of readers for whom the features identified in the first study were problematic, to provide insight into how and why readers were reading the booklet, and to determine if patients and family differed on any of the outcomes. Results showed that 85% of readers liked the booklet; most (81.6%) read it from beginning to end. Most readers in both groups wanted the information to help them understand (85.2% patients; 87.9% family); more patients than family wanted it for treatment decision making (44.4% patients; 27.3% family) and for planning (35.2% patients; 9.1% family); more family (42.4%) than patients (20.4%) wanted the information to help them provide support. We conclude that even though patients and family differ in why they want information, the booklet appears to be considered useful by both groups. [Copyright &y& Elsevier]

Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or ‘pure’ antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have ‘learned’ to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens, bicalutamide offers some advantages over flutamide as it possesses a much longer half-life, allowing a once daily regimen, and has advantages over nilutamide in terms of fewer adverse effects. [ABSTRACT FROM AUTHOR]

68Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative intended therapy. Owed to the novelty of the PSMA-targeting tracers, clinical evidence on the value of PSMA-PET is moderate but rapidly increasing. State of the art imaging is pivotal for radiotherapy treatment planning as it may affect dose prescription, target delineation and use of concomitant therapy.This review summarizes the evidence on PSMA-PET imaging from a radiation oncologist's point of view. Additionally a short survey containing twelve examples of patients and 6 additional questions was performed in seven mayor academic centers with experience in PSMA ligand imaging and the findings are reported here. [ABSTRACT FROM AUTHOR]