Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Proteomics Analysis of Formalin Fixed Paraffin Embedded Tissues in the Investigation of Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of death in men worldwide. The molecular features, associated with the onset and progression of the disease, are under vigorous investigation. Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources for large-scale studies; however, their application in proteomics is limited due to protein cross-linking. In this study, the adjustment of a protocol for the proteomic analysis of FFPE tissues was performed which was followed by a pilot application on FFPE PCa clinical samples to investigate whether the optimized protocol can provide biologically relevant data for the investigation of PCa. For the optimization, FFPE mouse tissues were processed using seven protein extraction protocols including combinations of homogenization methods (beads, sonication, boiling) and buffers (SDS based and urea-thiourea based). The proteome extraction efficacy was then evaluated based on protein identifications and reproducibility using SDS electrophoresis and high resolution LC-MS/MS analysis. Comparison between the FFPE and matched fresh frozen (FF) tissues, using an optimized protocol involving protein extraction with an SDS-based buffer following beads homogenization and boiling, showed a substantial overlap in protein identifications with a strong correlation in relative abundances (rs = 0.819, p < 0.001). Next, FFPE tissues (3 sections, 15 µm each per sample) from 10 patients with PCa corresponding to tumor (GS = 6 or GS ≥ 8) and adjacent benign regions were processed with the optimized protocol. Extracted proteins were analyzed by GeLC-MS/MS followed by statistical and bioinformatics analysis. Proteins significantly deregulated between PCa GS ≥ 8 and PCa GS = 6 represented extracellular matrix organization, gluconeogenesis, and phosphorylation pathways. Proteins deregulated between cancerous and adjacent benign tissues, reflected increased translation, peptide synthesis, and protein metabolism in the former, which is consistent with the literature. In conclusion, the results support the relevance of the proteomic findings in the context of PCa and the reliability of the optimized protocol for proteomics analysis of FFPE material.

Isolated corpus spongiosum injury after sexual intercourse.

Penile fractures are generally rare and underreported. The mechanism of injury is due to a rupture of the corpora cavernosa following blunt or sexual trauma to the penis when fully erect. Penile fractures usually present with a 'popping' sound with concomitant sudden swelling and ecchymosis of the penis followed by rapid detumescence. Urethral involvement occurs only in a small part of the cases. Isolated spongiosal injury after sexual intercourse is also extremely rare. The cardinal sign of urethral injury is blood at the meatus. A small laceration can be repaired by simple closure with absorbable sutures, while a complete rupture requires a more complex anastomotic repair. We report a case of a typically presenting penile fracture that was eventually proven to be an isolated corpus spongiosum injury, with no corpora cavernosa involvement.

Novel Concept Enabling an Old Idea: A Flexible Electrode Array to Treat Neurogenic Erectile Dysfunction.

INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement. AIM: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively. METHODS: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system. MAIN OUTCOME MEASURE: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array. RESULTS: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01). CLINICAL IMPLICATIONS: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury. STRENGTH & LIMITATIONS: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice. CONCLUSION: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569.

Conservative management of a bladder leiomyosarcoma in a 43-year-old patient.

Leiomyosarcoma of the bladder is an aggressive and rare tumor, with less than 200 reported cases. The treatment of bladder leiomyosarcoma is controversial although in most cases an aggressive surgical therapy is preferred. Usually, a radical cystectomy is performed, as it is considered to have a better disease-specific survival rate. A 43-year-old man presented to our Urology Department with painless macroscopic hematuria. He was submitted to transurethral resection of the tumor. The transurethral resection was complete and revealed only this small single lesion and the rest of the bladder was normal with no other lesion or suspicious lesion. The final histology revealed leiomyosarcoma of the bladder. Due to his age and the aggressiveness of the tumor after a thorough and detailed discussion with the patient a conservative management with aggressive follow up was decided. The patient a year after the diagnosis is in perfect condition without sign of a recurrence or metastastes.

Role of coagulation factors in urological malignancy: A prospective, controlled study on prostate, renal and bladder cancer.

OBJECTIVES: To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. METHODS: This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal (n = 44), prostate (n = 56) and bladder cancer (n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. RESULTS: Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). CONCLUSIONS: The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events.

B-lymphocytic infiltration of the prostate to a patient with chronic lymphocytic leukemia. A case report.

Involvement of the prostate gland, as an early extra-nodal manifestation of a hematologic disease, or as a secondary infiltration is rare. Even rarer is the acute urinary retention due to infiltration by lymphocytes and simultaneously enlarged prostate. We present a case of a 61 years old male patient with a history of chronic lymphocytic leukemia, who was under oncological follow-up with no active treatment and had typical lower urinary tract symptoms due to benign prostatic hyperplasia and was receiving 5-alpha reductase inhibitor. After an acute urinary retention episode which was managed with a suprapubic catheter due to urethral catheter insertion failure, the patient was submitted to a transurethral prostatectomy. Histological examination revealed lymphocytic infiltration of the prostatic parenchyma by mostly small B cells. B-lymphocytic infiltration of the prostate gland, causes symptoms similar to benign prostatic hyperplasia. Acute urinary retention due to B-lymphocytic infiltration of the prostate is rare and the diagnosis is always histological and an oncological re-evaluation is necessary. The prognosis of these patients is related to the generalized disease rather than to the prostatic involvement.

Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

Primary adenocarcinoma of the seminal vesicles. A review of the literature.

Primary adenocarcinoma of the seminal vesicles (SV) are extremely rare and approximately only 60 cases have been reported in the literature. Due to the lack of specific symptoms the patients often present in an advanced stage of their disease. The only clinical examination that can indicate the presence of a neoplasm in the SVs is the digital rectal examination (DRE). Serum prostatic specific antigen (PSA) and prostate specific acid phosphatase (PAP) are usually normal in patients with primary adenocarcinoma of the SV and only CA-125 can be proved a useful blood biomarker contributing to the diagnosis and the follow up of the SV adenocarcinoma. Computed tomography (CT) and magnetic resonance imaging (MRI) and FDG-PET/CT have been used for the diagnosis and the staging of the SV adenocarcinoma. Various combinations of radical surgery, radiotherapy androgen deprivation therapy and chemotherapy have been proposed for the management of the disease but the prognosis is poor and the mean survival is two years after the diagnosis.

In the search of novel urine biomarkers for the early diagnosis of prostate cancer. Intracellular or secreted proteins as the target group? Where and how to search for possible biomarkers useful in the everyday clinical practice.

OBJECTIVE: To search which category of proteins can be detected in urine in order to examine subsequently its ability to improve our accuracy for the diagnosis of Prostate Cancer (PCa) as biomarkers in clinical useful fluids like urine and serum. Material and method(s): Urine samples of 127 patients were obtained after a vigorous transrectal prostatic massage to both lobes. The patients were considered to have a high risk for PCa according to their PSA (> 4 ng/ml), their digital rectal examination (DRE) (positive for suspicious prostatic lesions) or to their abnormal PSA kinetics (PSA velocity (PSAV > 0.75 ng/mL). All patients subsequently were subjected to an extended 10-core per prostatic lobe TRUS-b (total 20 prostatic samples). The proteins that were chosen to be detected in the urine samples with Western-blot, as possible biomarkers, were Glutathione peroxidase 3 precursor (GPx3), Cofilin-1 (CFL1), Heat shock protein-90ß (HSP 90ß), Zinc alpha 2-glycoprotein (ZAG) and secreted protein acidic and rich in cysteine (SPARC).These proteins have been detected previously in the prostatic tissue by proteomics proving their discriminative ability between patients with prostate cancer and benign prostatic hyperplasia. RESULT(S): From the five proteins, only the secreted Zinc alpha 2-glycoprotein was detected in urine showing a promising ability in the improvement of our diagnostic accuracy for the early diagnosis of prostate cancer. CONCLUSIONS: From various categories of proteins that have already been detected in the tissue of prostate by proteomics, only secreted protein Zinc alpha 2-glycoprotein showed a clear signal in the urine, proving its discriminative potential for the early diagnosis of PCa.

A two staged treatment procedure for the difficult to treat bladder neck contractures with concomitant incontinence. In the search of a solution to a complex problem.

OBJECTIVE: To examine the efficacy of a two staged treating strategy with the use of a non-permanent urethral ALLIUM(®) stent for the management of recurrent bladder neck stenosis and subsequently the use of an artificial sphincter AUS800(®) by AMS for the management of the incontinence. MATERIALS AND METHODS: We progressively identified patients eligible for the study creating a population of cases with recurrent bladder neck stenosis and concomitant incontinence occurring after the last intervention for the stenosis. Efficacy for the treatment of the stenosis was defined as no recurrence both prior and post to the sphincter placement and efficacy for the treatment of the incontinence was defined as continence (0-1pads) after the sphincter placement. RESULTS AND LIMITATIONS: 14 white males with a mean age of 66.21, ranging from 59 to 73 years consisted the population of the study. All patients had severe stress incontinence following the last transurethral resection. The efficacy of the treatment of the bladder neck stenosis was 93% (13/14) while the efficacy for the treatment of the incontinence was 100%. A single patient had a recurrent bladder neck stenosis after the artificial sphincter placement and was treated with transurethral resection using a long pediatric 13 F resectoscope at 12 months. Our limitations is the absence of a control group and the small number of patients enrolled, with a relatively short time of follow up. CONCLUSIONS: In our series we propose the use of a non-permanent urethral ALLIUM(®) stent for 6 months in order to control the growth of fibrotic scar tissue, a further 6 months follow up for recurrence, and then placement of an artificial sphincter. The results are very promising both on stabilizing the vesicourethral stenosis, and on patient safety and tolerability.

Correcting and sharing our complications. Misplacement of pigtail catheter, during a Robot Assisted Pyeloplasty. Clinical findings, diagnosis, possible causes and endoscopic treatment.

OBJECTIVE: Robotic assisted pyeloplasty (RAP) is rapidly adopted by surgeons around the world. We present a unique complication of the technique, consisting of pigtail misplacement, which was endoscopically resolved. We discuss the clinical findings, differential diagnosis and principles of endoscopic treatment. MATERIALS AND METHODS: A 41 years old female patients underwent transperitoneal right side RAP with the Hynes-Anderson technique for ureteropelvic junction obstruction. Pigtail was placed intraoperatively in an antegrade fashion. Post operative course appeared normal but Kidney-Ureterer-Bladder(KUB) X-ray, revealed a misplaced pigtail. Patient underwent a semirigid ureterorenoscopy demonstrating that the pigtail was exiting the collecting system in the rear line of suturing between continuous sutures. Pigtail was retrieved with a stone retrieval forceps with short upward motions in the renal pelvis under fluoroscopy and then removed from patient, in order to avoid stressing the anastomosis. No leakage was noted in fluoroscopy, a pigtail was correctly placed and patient recovery was uneventful. RESULTS: Retrograde pyelography was the key to accurate diagnosis and endoscopic treatment, because the exact point of exit and anastomosis integrity were established. Retrieval of the pigtail was the most challenging part. Lack of proper visualization and mobilization of the rear part of the anastomosis during surgery, combined with lack of tactile feedback, because of robotic instrumentation, were of critical importance in the manifestation of such a mishap. Endoscopy facilitated case resolve, but proper handling is required to protect the anastomosis. CONCLUSIONS: The introduction of novel techniques can carry the burden of novel complications. A surgeon must always keep in mind the complications inherent to the technique and at the same time the limitations of the equipment used, especially the lack of tactile feedback in robotic instrumentation.

Assessing the association between global structural brain age and polygenic risk for schizophrenia in early adulthood: A recall-by-genotype study.

Neuroimaging studies consistently show advanced brain age in schizophrenia, suggesting that brain structure is often 'older' than expected at a given chronological age. Whether advanced brain age is linked to genetic liability for schizophrenia remains unclear. In this pre-registered secondary data analysis, we utilised a recall-by-genotype approach applied to a population-based subsample from the Avon Longitudinal Study of Parents and Children to assess brain age differences between young adults aged 21-24 years with relatively high (n = 96) and low (n = 93) polygenic risk for schizophrenia (SCZ-PRS). A global index of brain age (or brain-predicted age) was estimated using a publicly available machine learning model previously trained on a combination of region-wise gray-matter measures, including cortical thickness, surface area and subcortical volumes derived from T1-weighted magnetic resonance imaging (MRI) scans. We found no difference in mean brain-PAD (the difference between brain-predicted age and chronological age) between the high- and low-SCZ-PRS groups, controlling for the effects of sex and age at time of scanning (b = -.21; 95% CI -2.00, 1.58; p = .82; Cohen's d = -.034; partial R2 = .00029). These findings do not support an association between SCZ-PRS and brain-PAD based on global age-related structural brain patterns, suggesting that brain age may not be a vulnerability marker of common genetic risk for SCZ. Future studies with larger samples and multimodal brain age measures could further investigate global or localised effects of SCZ-PRS.

P53/MDM2 Complex-Based Targeted Strategies in Colon Adenocarcinoma.

In the current molecular review, we describe the mechanisms of TP53/MDM2 deregulation and their impact on the colon adenocarcinoma molecular substrate and phenotype. Among the genes that are critically altered in carcinogenesis, the TP53 tumor suppressor gene is of major importance. The TP53 gene (gene locus: 17p13.1) regulates the cell cycle by controlling the G1/S and G2/M checkpoints securing the normal sequence of cell cycle phases. Furthermore, it is involved in apoptosis programmed cell death. The gene is mutated or epigenetically altered in all epithelial malignancies, including colon adenocarcinoma. Additionally, Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3), acts as a major negative regulator for p53 expression in the p53-MDM2 auto-regulatory pathway. MDM2 binds directly to p53 and represses its transcriptional activity, promoting p53 degradation. CONCLUSION: In colon adenocarcinoma, MDM2 oncogene overexpression directly influences p53 oncoprotein expression levels.

All you need to know about urethrovesical anastomotic urinary leakage following radical prostatectomy.

PURPOSE: Radical prostatectomy is a challenging operation demanding a high level of surgical expertise and experience. Urinary leakage at the urethrovesical anastomosis is one of the most common short-term complications of radical prostatectomy, reaching an incidence of 0.3% to 15.4%. In this review we investigate and discuss all matters directly related to urethrovesical anastomotic leak, specifically how to diagnose it properly, how to determine when it is clinically significant and when intervention is required, how to prevent or predict it and, finally, the possible long-term sequelae. MATERIALS AND METHODS: We conducted a systematic analysis of the literature searching for English and nonEnglish language publications from a preidentified time frame (1985 to 2011) using primary search databases (PubMed®, Web of Science®). Manual selection was performed by 2 authors and the third reviewed the final common selection. We also created an algorithm for the diagnosis and management of urethrovesical anastomotic leak. RESULTS: A total of 72 studies were finally selected, including 48 (67%) observational case series, 16 (22.2%) prospective trials, 1 letter to the editor, 1 review and 1 systematic review which was focused only on laparoscopic radical prostatectomy. We also found 2 experimental studies performed in animal models and 3 case reports. Of these studies 7 reported results from fewer than 20 patients. No consensus was recorded on a strict definition of urethrovesical anastomotic leak. The factors determining possible definitions included postoperative day of urethrovesical anastomotic leak, amount of extravasation on cystography and the need for intervention. Urethrovesical anastomotic leak should be classified according to the Clavien classification system, depending on severity and the need for intervention. To our knowledge the role of the open, laparoscopic or robotic approach in the incidence of urethrovesical anastomotic leak has not been systematically investigated. Risk factors for urethrovesical anastomotic leak include obesity, prostate size, previous prostatic surgery, type of anastomosis technique, suture number and type, eversion of the mucosa, a difficult anastomosis or an anastomosis under tension, reconstruction of the musculofascial plate, blood loss, intraoperative flush test result and postoperative urinary tract infection. Diagnosis can be determined primarily by establishing the nature of the drain output. Retrograde cystography, computerized tomography cystography, transrectal ultrasound, contrast enhanced ultrasound and excretory urography are the indicated imaging modalities, and are not always necessary. Finally, the development of anastomotic stricture and incontinence due to urethrovesical anastomotic leak are additional complications. CONCLUSIONS: We gathered all relevant critical information concerning urethrovesical anastomotic leak to encourage standardization in the diagnosis and management of this common complication. Systematic meta-analysis of each debatable issue is required to provide definite answers.

L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. OBJECTIVE: To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). PATIENTS AND METHODS: The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. RESULTS: DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015). CONCLUSIONS: This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted.

Implementation and external validation of Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score for predicting complications in 74 consecutive partial nephrectomies.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Partial nephrectomy (PN) is the gold standard operation for small renal tumours. The decision for or against a PN has been based mostly on preoperative radiological evaluation of the tumour. Three nephrometry scoring systems have been recently proposed for prediction of postoperative complications of PN (RENAL, C-index and PADUA). We validate externally the accuracy of the PADUA system and suggest for the first time a novel scoring system, based on the original PADUA system, which implements three other significant factors for the postoperative course of a partial. OBJECTIVE: • To externally validate the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours managed by partial nephrectomy (PN). PATIENTS AND METHODS: • Seventy-four consecutive patients in a single academic tertiary institution underwent open PN. • Incidence of 90-day complications was stratified by several clinicopathological variables, such as gender, age of the patient, hospital stay, pathology report, tumour characteristics and positive surgical margins. PADUA scores were given to each case. • The severity of complications was also categorized with the Clavien system. RESULTS: • The optimal threshold of PADUA for the prediction of complications was 8 with a sensitivity equal to 90.9% and a specificity equal to 77.8% (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.73-1.00). • Multivariate analysis revealed that that PADUA is an independent predictor for the risk of complications. • Also, PADUA score ≥ 8 identified a group of patients with almost 20-fold higher risk of complications (hazard ratio [HR]= 19.82; 95% CI, 1.79-28.35; P= 0.015). • Patients with papillary histology had greater risk for complications than those with clear-cell tumours (HR = 4.88; 95% CI, 1.34-17.76; P= 0.016). CONCLUSIONS: • The PADUA score is a simple anatomical system that predicts the risk of postoperative complications. This is the first external validation of this system for open PN from a single centre. • The authors believe that PADUA is an efficient tool, since the only variable of the present study that predicted a higher incidence of complications was the histology type, which is determined after surgery. • However, it should be applied to laparoscopic and robot-assisted series and it could also include the ischaemia time and surgeon experience in the overall scoring to be complete.

Zinc α2-glycoprotein as a potential novel urine biomarker for the early diagnosis of prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? The use of biomarkers to detect a cancer early, especially prostate cancer, is not a new idea and PSA has been proved to be the best biomarker for the early diagnosis of prostate cancer. Since the introduction and wide use of PSA various efforts have been made to find novel biomarkers in both serum and urine of individuals at high risk for prostate cancer. The best example of a biomarker detected in the urine after a vigorous digital rectal examination is PCA3, which is used mainly in the subgroup of patients with PSA 4-10 ng/mL whose prostate biopsy was repeatedly negative for prostate cancer in order to decide the performance or not of a new biopsy. Proteomics is a state of the art new biotechnology used to identify the proteome of a certain tissue meaning the whole group of proteins related to the anatomy and biochemistry of the tissue. Using proteomics can effectively and more specifically identify proteins that can be used as potential biomarkers for the early diagnosis of prostate cancer. Zinc α2-glycoprotein has been studied in the past as a protein related to cancer cachexia and it has been measured in both prostate tissue and serum in patients with prostate cancer. Zinc α2-glycoprotein has also been recently identified by proteomics in prostate tissue showing different values in patients with prostate cancer and benign prostate hyperplasia. It is the first time that zinc α2-glycoprotein has been systematically measured and studied in an easily obtained biological fluid such as urine showing a very optimistic potential both as a novel solo biomarker and as an adjunct to PSA for the early diagnosis of prostate cancer. PSA has revolutionized the way we approximate prostate cancer diagnosis. Even though PSA is still the best biomarker for the diagnosis of prostate cancer it constitutes an organ-specific and not a disease-specific biomarker and diagnostic dilemmas are often raised concerning the performance or not of a prostate biopsy. Thus novel biomarkers are required in order to improve the diagnostic ability of PSA. Increasingly in the literature it is stated that the future of prostate cancer diagnosis could be not a single biomarker but a band of different biomarkers that as a total could give the possibility of an individual having prostate cancer. By detecting and measuring zinc α2-glycoprotein in the urine we believe that interesting conclusions can be made: first that proteomics is the way to detect with accuracy proteins that could be proved to be valuable novel biomarkers; second that zinc α2-glycoprotein detected in the urine could be used both as a solo biomarker and as an adjunct to PSA for the early diagnosis of prostate cancer. OBJECTIVE: • To examine the potential utility as a novel biomarker in the urine of zinc α2-glygoprotein (ZAG) for the early diagnosis of prostate cancer. PATIENTS AND METHODS: • The urine of 127 consecutive candidates for a transrectal ultrasound prostatic biopsy with a mean age of 65.7 ± 8.7 years and mean PSA 9.1 ± 5.3 ng/mL was collected. • Western blot analysis and immunohistochemistry for ZAG were performed. • Receiver operating characteristic curves and logistic regression models were used to estimate the predictive ability of ZAG and to determine the optimal sensitivity and specificity by using various cut-off values for the prediction of prostate cancer. RESULTS: • In all, 42 patients had prostate cancer, 29 showed high grade prostatic intraepithelial neoplasia and 56 were negative. • Receiver operating characteristic curve analysis showed a significant predictive ability of ZAG for prostate cancer. The area under the curve (AUC) for the prediction of prostate cancer was 0.68 (95% CI 0.59-0.78). • The combination of ZAG with PSA showed a significant improvement in the predictive ability (P= 0.010), with AUC equal to 0.75 (95% CI 0.66-0.85). Separate analysis in patients with PSA levels of 4-10 ng/mL (70.1%) showed that ZAG had a discriminative power with AUC equal to 0.68. • The optimal cut-off was 1.13 for ZAG, which corresponded to 6.88 times greater odds for prostate cancer. CONCLUSIONS: • Urine detected ZAG showed promising results in the prediction of prostate cancer. • Further validation is required to establish ZAG as a novel biomarker.

Radical cystectomy over the age of 75 is safe and increases survival.

BACKGROUND: Radical cystectomy (RC) is probably underused in elderly patients due to a potential increased postoperative complication risk, as reflected by their considerable comorbidities. Our objective was to estimate the overall complication rate and investigate a potential benefit to patients over the age of 75 subjected to RC in terms of disease-free survival. METHODS: A total of 81 patients, 61 men and 20 women, from two urological departments, with a mean age of 79.2 ± 3.7 years, participated in the study. The mean follow-up period was 2.6 ± 1.6 years. All patients underwent RC with pelvic lymphadenectomy. An ileal conduit, an orthotopic ileal neobladder and cutaneous ureterostomies were formed in 48.1%, 6.2% and 45.7% of the patients, respectively. The perioperative and 90-day postoperative complications were recorded and classified according to the modified Clavien classification system. Survival plots were created based on the oncological outcome and several study parameters. RESULTS: The perioperative morbidity rate was 43.2%; the 90-day morbidity rate was 37%, while the 30-day, 90-day and overall mortality rates were 3.7%, 3.7% and 21%, respectively. Overall mortality rates were recorded at the final year of data gathering (2009). Increased age, increased body mass index (BMI), longer hospitalization and age-adjusted Charlson comorbidity index (ACCI) more than six, were associated with greater hazard for 90-day morbidity. The cumulative mortality / metastasis-free rates for one, two, three and five years were 88.7%, 77.5%, 70.4%, and 62.3%, respectively. Tumour stage and positive nodes were prognostic predictors for oncological outcome. CONCLUSIONS: RC in patients over 75 is justified and feasible, due to acceptable complication rates and high 5-year cancer-specific survival, which support an aggressive approach. Prospective studies are needed for the verification of the above results.

Quality of life, physical functioning, and psychosocial function among patients with achondroplasia: a targeted literature review.

PURPOSE: Achondroplasia (ACH) is the most common form of skeletal dysplasia, resulting in disproportionate short stature and medical complications. We review the literature on physical functioning, psychosocial function, and quality of life (QoL) in ACH individuals compared to average stature individuals or other short stature conditions. Studies that assess the association between these outcomes and height, limb length/lengthening surgery in ACH patients are also summarized. MATERIALS AND METHODS: PubMed/MEDLINE and Embase were searched through April 2021. Study inclusion criteria were: (1) quantitative design; (2) study population consisting solely/mainly of ACH patients; (3) reports of physical functioning, psychosocial functioning, and/or QoL. Included studies were summarized separately for pediatric and adult populations. RESULTS: Of 1664 records identified, 23 primary studies (sample size 8-437 participants) were included. Multiple tools were used across studies, including the generic PedsQL and SF-36 and height-specific QoLISSY. CONCLUSIONS: The literature demonstrates that ACH patients experience limitations in physical functioning and poorer QoL outcomes compared to average stature people across the life span. This appeared to be at least in part due to disproportionate short stature. Future research to better characterize QoL in ACH patients will assist clinicians to better evaluate the effectiveness of management programs including novel interventions.IMPLICATIONS FOR REHABILITATIONPatients with achondroplasia experience limitations in physical functioning and poorer quality of life throughout their life course when compared to average statured individuals.Psychosocial issues are also heightened in adults with achondroplasia compared to average statured peers but are observed less frequently in children and adolescents with achondroplasia.The overall impact that limb lengthening has on physical functioning and QoL remains unclear, although there is some evidence that greater height or upper limb length may lead to an improvement in these parameters.Rehabilitation professionals should regularly assess physical functioning, psychosocial wellbeing, and quality of life in individuals with achondroplasia using condition-specific tools.