A Liquid Biopsy in Bladder Cancer-The Current Landscape in Urinary Biomarkers.

The non-muscle invasive bladder cancer tends to recur and progress. Therefore, it requires frequent follow-ups, generating costs and making it one of the most expensive neoplasms. Considering the expensive and invasive character of the current gold-standard diagnostic procedure, white-light cystoscopy, efforts to find an alternative method are ongoing. Although the last decade has seen significant advancements in urinary biomarker tests (UBTs) for bladder cancer, international guidelines have not recommended them. Currently, the paramount urgency is to find and validate the test with the best specificity and sensitivity, which would allow for the optimizing of diagnosis, prognosis, and a treatment plan. This review aims to summarise the up-to-date state of knowledge relating to UBTs and new developments in the detection, prognosis, and surveillance of bladder cancer and their potential applications in clinical practice.

Diagnostic and Prognostic Potential of Biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in Bladder Cancers.

The high occurrence of bladder cancer and its tendency to recur in combination with a lifelong surveillance make the treatment of superficial bladder cancer one of the most expensive and time-consuming. Moreover, carcinoma in situ often leads to muscle invasion with an unfavorable prognosis. Currently, invasive methods including cystoscopy and cytology remain a gold standard. The aim of this study was to explore urine-based biomarkers to find the one with the best specificity and sensitivity, which would allow optimizing the treatment plan. In this review, we sum up the current knowledge about Cytokeratin fragments (CYFRA 21.1), Excision Repair Cross-Complementation 1 (ERCC1), Tumour Protein p53 (Tp53), Fibroblast Growth Factor Receptor 3 (FGFR3), Tumor-Associated Trypsin Inhibitor (TATI) and their potential applications in clinical practice.

Suture techniques during laparoscopic and robot-assisted partial nephrectomy: a systematic review and quantitative synthesis of peri-operative outcomes.

OBJECTIVE: To summarize the available evidence on renorrhaphy techniques and to assess their impact on peri-operative outcomes after minimally invasive partial nephrectomy (MIPN). MATERIALS AND METHODS: A systematic review of the literature was performed in January 2018 without time restrictions, using MEDLINE, Cochrane and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement recommendations. Studies providing sufficient details on renorrhaphy techniques during laparoscopic or robot-assisted partial nephrectomy and comparative studies focused on peri-operative outcomes were included in qualitative and quantitative analyses, respectively. RESULTS: Overall, 67 and 19 studies were included in the qualitative and quantitative analyses, respectively. The overall quality of evidence was low. Specific tumour features (i.e. size, hilar location, anatomical complexity, nearness to renal sinus and/or urinary collecting system), surgeon's experience, robot-assisted technology, as well as the aim of reducing warm ischaemia time and the amount of devascularized renal parenchyma preserved represented the key factors driving the evolution of the renorrhaphy techniques during MIPN over the past decade. Quantitative synthesis showed that running suture was associated with shorter operating and ischaemia time, and lower postoperative complication and transfusion rates than interrupted suture. Barbed suture had lower operating and ischaemia time and less blood loss than non-barbed suture. The single-layer suture technique was associated with shorter operating and ischaemia time than the double-layer technique. No comparisons were possible concerning renal functional outcomes because of non-homogeneous data reporting. CONCLUSIONS: Renorrhaphy techniques significantly evolved over the years, improving outcomes. Running suture, particularly using barbed wires, shortened the operating and ischaemia times. A further advantage could derive from avoiding a double-layer suture.

Perioperative and Oncological Outcomes of Percutaneous Radiofrequency Ablation versus Partial Nephrectomy for cT1a Renal Cancers: A Retrospective Study on Groups with Similar Clinical Characteristics.

Over the recent years, progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the results of US-guided percutaneous radiofrequency ablation (RFA) and partial nephrectomy (PN) in the treatment of cT1a renal cancers. Between August 2016 and February 2022, 271 patients with renal tumours underwent percutaneous RFA as initial treatment in our institution. In the same period, 396 patients with renal tumours underwent surgical tumour excision. For the purpose of this study, only patients with confirmed renal cancer with matched age and tumour characteristics (size, location) were selected for both groups. Thus, a group of 44 PN patients and 41 RFA patients were formed with the same qualification criteria for both groups. Parameters such as procedure length, blood loss, hospital stay, analgesics used, and pre- and post-procedural serum creatinine were compared between these groups. Patients followed up with contrast-enhanced CT. There was no significant difference in age, tumour size, tumour location, and creatinine levels between these groups. All procedures were generally well tolerated. During a median follow-up of 28 months, two cases of recurrence/residual disease were found in each group. The overall survival was 100% in both groups, and all patients were disease-free at the end of observation. Percutaneous RFA was associated with a significantly shorter procedure length and hospital stay, lower blood loss, and lower analgesics used than PN. In the selected group of renal cancer patients, US-guided percutaneous RFA was associated with a shorter hospital stay, less analgesics used, and a shorter procedure length than PN, without differences in the oncological results or kidney function.

High-resolution ERG-expression profiling on GeneChip exon 1.0 ST arrays in primary and castration-resistant prostate cancer.

OBJECTIVE: To assess whether oestrogen-regulated gene (ERG) expression analysis using GeneChip arrays can predict transmembrane protease, serine 2 (TMPRSS2)-ERG fusion. The expression level of the TMPRSS2-ERG gene was studied in various histological grades of prostate cancer and castration-resistant prostate cancer (CPRC). PATIENTS AND METHODS: GeneChip Affymetrix exon 1.0 ST arrays were used for expression profiling of ERG, erythroblast transformation-specific (ETS) variant gene 1 (ETV1), ETV4 and ETV5 genes in 67 prostate cancer tissue specimens. Real-time quantitative polymerase chain reaction analysis and in some cases DNA sequencing was used to validate the presence and the expression levels of TMPRSS2-ERG gene fusions. RESULTS: In our series of patients with prostate cancer over expression of the ERG gene predicted the presence of TMPRSS2-ERG rearrangements in almost all cases. ETS expression by itself outmatched the diagnostic performance of the ERG exons ratioing allowing equal detection of the less frequent ETS gene fusion transcripts. The gene fusions were expressed at significantly lower levels in CPRC but occurred more frequently than in primary prostate cancer. CONCLUSIONS: ERG expression analysis using GeneChip arrays appears to be an excellent diagnostic tool for identifying gene rearrangements. In coming years, measuring expression of the ETS gene family by itself might become a clinically relevant surrogate test to identify patients with fusion-positive prostate cancer. The variation of gene fusion expression levels, particularly in CPRC, needs to be taken into account when using quantitative molecular diagnosis of prostate cancer.

Surgical Approach in Metastatic Renal Cell Carcinoma: A Literature Review.

The treatment of metastatic renal cell carcinoma has undergone considerable advances in the last two decades. Cytoreductive nephrectomy and metastasectomy retains a role in patients with a limited metastatic burden. The choice of optimal treatment regimen remains a matter of debate. The article summarises the current role of surgery in metastatic kidney cancer.

Ultrasound-Guided Percutaneous Thermal Ablation of Renal Cancers-In Search for the Ideal Tumour.

Over the recent years, the progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the success of percutaneous radiofrequency ablation (RFA) in relation to kidney tumour diameter and location. Between August 2016 and September 2021, 253 patients with 259 renal tumours underwent US-guided RFA as a primary treatment in our institution. A total of 67 patients were excluded from this study. Abdominal computed tomography (CT) and tumour biopsy were performed before the procedure. Patients were followed with contrast-enhanced CT, the average follow-up time was 28 months. The studied group was composed of 186 patients with 191 renal tumours-only biopsy-confirmed renal cancers were included. During the follow-up, 46 cases of residual disease and 4 cases of local progression were found. There was a significant correlation between tumour size and the ablation success rate. The success rate was 73.5% and 87.6% for lesions ≤25 mm, 94.6% for lesions ≤25 mm and exophytic, 79.1% for lesions 26-30 mm and 84.4% for lesions 26-30 mm and exophytic, respectively. Four Clavien-Dindo grade ≥2 complications were observed. US-guided percutaneous RFA of T1a renal cancers is safe and well-tolerated. Its effectiveness depends on tumour size, with best results for exophytic lesions smaller than 3 cm. Most of the recurrent or residual tumours can be successfully re-treated with US-guided percutaneous RFA.

Molecular diagnosis of prostate cancer: PCA3 and TMPRSS2:ERG gene fusion.

PURPOSE: Widespread prostate specific antigen screening together with the increase in the number of biopsy cores has led to increased prostate cancer incidence. Standard diagnostic tools still cannot unequivocally predict prostate cancer progression, which often results in a significant overtreatment rate. We present recent findings on PCA3 and TMPRSS:ERG fusion, and describe their clinical implications and performance. MATERIALS AND METHODS: The PubMed® database was searched for reports on PCA3 (130 articles), TMPRSS:ERG and ETS fusion (180 publications) since 1999. RESULTS: In recent years advances in genetics and biotechnology have stimulated the development of noninvasive tests to detect prostate cancer. Serum and urine molecular biomarkers have been identified, of which PCA3 has already been introduced clinically. The identification of prostate cancer specific genomic aberrations, ie TMPRSS2:ERG gene fusion, might improve diagnosis and affect prostate cancer treatment. CONCLUSIONS: Although several recently developed markers are promising, often showing increased specificity for prostate cancer detection compared to that of prostate specific antigen, their clinical application is limited. The only 2 true prostate cancer specific biomarkers identified to date remain PCA3 and TMPRSS2:ERG gene fusion.

Can we lower the rates of cystectomy complications by modifying risk factors? A review of the literature.

Introduction: Radical cystectomy (RC), beyond its therapeutic effect, is associated with significant rates of complications, hospital readmissions and mortality. In recent years much research has been made in order to clarify the main reasons of these events. This article, based on a literature review, presents the impact of risk factors on RC complications and highlights possible modifications of these factors to reach better RC outcome. Material and methods: PubMed, Science Direct, Google Scholar databases were searched using key-words to identify studies about risk factors and RC complications between 2010 and 2021. A total of 96 articles were retrieved and studied as full-text versions. The most significant data was targeted, analysed and categorized according to the article's design. Results: All the most valuable risk factors of RC complications were grouped in patient-related, treatment-related risk factors and subgrouped in nonmodifiable, modifiable and potentially modifiable categories. All the modifiable and potentially modifiable risk factors were found to have considerable value, as their adjustment lowers the rates of morbidity and mortality. Conclusions: Proper identification and adjustment of the risk factors present the possibility of better RC results. Although, in advanced disease and highly morbid cases, complications are not fully omit-table. Management of bladder cancer (BC) in high-volume centres using new technologies offers lower rates of complications. To sum up, rigorous interdisciplinary presurgical patient preparation should be implemented in BC management.

The Role of Focal Therapy and Active Surveillance for Small Renal Mass Therapy.

Small and low-grade renal cell carcinomas have little potential for metastasis and disease-related mortality. As a consequence, the main problem remains the use of appropriately tailored treatment for each individual patient. Surgery still remains the gold standard, but many clinicians are questioning this approach and present the advantages of focal therapy. The choice of treatment regimen remains a matter of debate. This article summarizes the current treatment options in the management of small renal masses.

Can We Identify Patients in Danger of Complications in Retrograde Intrarenal Surgery?-A Retrospective Risk Factors Analysis.

Retrograde intrarenal surgery (RIRS) is an innovative and effective method of kidney stones treatment, as it had great influence on the development of endoscopy in urology. The increasing prevalence of urolithiasis together with the rapid development of endourology leads to a rise in the number of procedures related to the disease. Flexible ureteroscopy is constantly being improved, especially regarding the effectiveness and safety of the procedure. The purpose of this study is to evaluate intraoperative and early post-operative complications of RIRS in the treatment of kidney stones. A retrospective analysis of medical records was performed. A series was comprised of 207 consecutive operations performed from 2017 to 2020. Complications occurred in 19.3% (n = 40) of patients. Occurrence according to the Clavien-Dindo scale was: 11.1% for grade I, 5.8% for grade II and 2.4% for grade IV. Infectious complications included SIRS (5.3%, n = 11) and sepsis (2.4%, n = 5). Statistical analysis revealed a correlation between acute post-operative infections and positive midstream urine culture, history of chronic or recurrent urinary tract infections, and increased body mass index (BMI). Furthermore, a significant correlation was observed between pain requiring the use of opioids with BMI over 25. Consequently, history of urinary tract infections, positive pre-operative urine culture, and increased BMI are considered risk factors and require appropriate management.

Prostate Cancer Liquid Biopsy Biomarkers' Clinical Utility in Diagnosis and Prognosis.

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker's low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

Calcified Urachal Cancer Managed by Partial Cystectomy: A Case Report.

This report presents the case of a rare and aggressive cancer originating from the urachus in a 73-year-old female. After 12 years of observation due to a cystic lesion in the bladder dome, the patient rapidly developed haematuria and mucinuria. The use of multiple diagnostic measures suggested urachal malignancy. Partial cystectomy and urachal excision along with pelvic lymphadenectomy were performed. Urachal adenocarcinoma with negative surgical margins and lymph nodes was reported in pathology. Follow-up after 12 months did not reveal any cancer relapse. Epidemiological, clinical and therapeutic features of this disease are also discussed.

Active surveillance in prostate cancer management: where do we stand now?

Prostate cancer (PCa) is the most common cancer in men, with a steadily rising incidence, affecting on average one in six men during their lifetime. The increase in morbidity is related to the increasing overall life expectancy, prostate-specific antigen testing, implementation of new molecular markers for cancer detection and the more frequent application of multiparametric magnetic resonance imaging. There is growing evidence demonstrating that active surveillance (AS) is an alternative to immediate intervention in patients with very low- and low-risk prostate cancer. Ongoing reports from multiple studies have consistently demonstrated a very low rate of metastases and prostate cancer specific mortality in selected cohorts of patients. As a matter of fact, AS has been adopted by many institutions as a safe and effective management strategy. The aim of our review is to summarize the contemporary data on AS in patients affected with PCa with the intention to present the most clinically useful and pertinent AS protocols.

Is ERCC1 a prognostic biomarker for urothelial cancer following radical cystectomy? A long-term analysis.

INTRODUCTION: Excision repair cross-complementation 1 protein (ERCC1) plays a vital role in cancer cells enabling DNA repair via nucleotide excision repair. Thus, we hypothesized whether expression of this protein may be utilized as a prognostic marker in patients after radical cystectomy. MATERIAL AND METHODS: The final analysis involved 123 patients with urothelial bladder carcinoma who underwent radical cystectomy with bilateral lymphadenectomy. The median follow-up time was equal to 853 days. ERCC1 status was evaluated immunohistochemically with the application of tissue microarrays. RESULTS: Positive ERCC1 expression was noted in 46% of the studied cases. Among the analyzed clinical and pathological factors, we could not establish a statistically significant correlation with ERCC1. Similarly, survival curves were statistically indifferent in patients with tumors categorized according to both expression categories. We did not confirm a prognostic value of ERCC1 in the multivariate regression analysis. CONCLUSIONS: ERCC1 expression does not influence the overall survival of patients with urothelial bladder carcinoma after radical cystectomy.

Angiomyolipoma rupture: does size always matter?

Angiomyolipoma (AML) is the most common benign renal neoplasm. Although asymptomatic lesions rarely lead to clinical dilemma, the management of ruptured tumours can become challenging. The size of the tumour has been widely accepted as a prognostic factor for intervention but there exists some evidence against considering the size as the only prognostic factor for intervention in AML. In our study, we described three recent cases of ruptured AML which were treated with different approaches - in two cases radical nephrectomy was performed, and in one patient a minimally invasive approach was adopted.

Differential expression of PCA3 and its overlapping PRUNE2 transcript in prostate cancer.

BACKGROUND: PCA3 is one of the most prostate cancer (PrCa)-specific markers described so far. Recently, a new genomic structure of PCA3 as well as new flanking and overlapping gene transcripts has been identified. Furthermore, a co-regulation of PCA3 and its overlapping gene PRUNE2(BMCC1) has been suggested. Our aim was to assess the diagnostic performance of a new PCA3 isoform (PCA3-TS4) and to study the interactions between PCA3 and BMCC1 in PrCa. METHODS: We used SYBR Green quantitative (q)PCR with specific primers to compare PCA3 and BMCC1 expression of normal versus tumor tissue of human prostate. PCA3-TS4 plasmid was created to calculate the absolute amounts of PCA3 transcripts. The androgen regulation of PCA3 and BMCC1 expression was studied in LNCaP and 22Rv1 cells stimulated with 5alpha-dihydrotestosterone. RESULTS: We have not found any relevant diagnostic advantage of the PCA3-TS4 isoform over the "classical" PCA3 isoform in our group of PrCa patients. Additionally, PCA3-TS4 appears to be only a minor PCA3 transcript. We were also unable to confirm the hypothesis that BMCC1 isoforms are androgen-induced in vitro. CONCLUSIONS: Despite the presence of the recently identified marginal PCA3 transcripts in human PrCa, the previously described major PCA3 isoform still constitutes the best target for diagnostic purposes. PCA3 and BMCC1 are overlapping genes in reverse orientation that do not appear to be co-regulated.

Radiofrequency ablation in kidney tumour management: a method of real-time monitoring.

OBJECTIVE: Radiofrequency ablation (RFA) is an alternative to surgery in kidney tumour management. The aim was to describe a method of real-time temperature monitoring during ultrasound-guided RFA and establish the related efficacy and safety. MATERIAL AND METHODS: Over a 6-year period 110 radiofrequency ablations in patients with kidney tumours and in most cases contraindications to surgery were performed. For the real-time temperature-monitored intervention 42 larger renal lesions exceeding 30 mm (range 31-59 mm) were selected. The monopolar Cool-tip RFA system was applied. The procedure involved the placement of up to three single radiofrequency probes within the tumour before starting the ablation session. Then, while ablating a tumour with one of the probes the remaining non-active electrode(s) served as real-time thermometer(s) to monitor simultaneously the temperature within the ablation zone. The average ablation time was between 10 and 15 min. The absence of contrast enhancement on computed tomography (CT) was considered to be a successful treatment. RESULTS: At a mean follow-up of 24 months (range 6-60 months), 38 tumours (90%) showed no contrast enhancement on CT. Four incompletely ablated tumours (10%) were successfully treated with the second ablation session. Two major and two minor complications occurred. At the time of writing, no local progression has been observed. CONCLUSION: RFA with the use of non-active probes as thermal probes to monitor the temperature within the tumour results in high efficacy and is associated with low complication rates.

Active surveillance and focal ablation for small renal masses: a better solution for comorbid patients.

The natural history of small renal masses (SRM) is still not well understood and they are frequently incidentally diagnosed in elderly patients. Therefore, there is a need for less invasive options sparing the patient from the side-effects related to conventional surgical treatment. PubMed and Medline database search was performed to look for new findings on active surveillance and focal therapy for SRM. Sixty-one articles published between 2002 and 2018 were selected for the purpose of the review. There is growing evidence confirming the safety of active surveillance in patients at surgical risk and there appears to be a satisfactory intermediate-term outcome of focal treatment of SRM. In the group of elderly patients with a decreased life expectancy active surveillance appears to be the most appropriate approach. The future of minimally invasive therapy appears bright, especially with the improvement of new imaging modalities.

The application of prostate artery embolization in the management of intractable prostate bleeding.

INTRODUCTION: Prostate cancer is one of the most common malignancies affecting European men. Sequelae of the advanced malignancy require invasive procedures which may not be eligible especially for old, debilitated patients. The aim of this manuscript is to review the outcomes of prostate artery embolization in the management of refractory bleeding. MATERIAL AND METHODS: A PubMed database search was done for all English language articles on prostate artery embolization in prostate cancer, published between 2003 and 2019. For current review, information related to number, age of the patients, aetiology of the hematuria, bilateral or unilateral procedure, type of embolic material, technical and clinical success, complications, recurrent hematuria, hematocrit and hemoglobin levels were analyzed. RESULTS: A total of 10 original full-text comparative and non-comparative (case series) studies were reviewed. Minor complications described in the literature ranged from 10-50%. After prostate artery embolization, the recurrence of the haematuria occurred in 10-57% of the patients. Moreover, prostate artery embolization successfully treated lower urinary tract symptoms and urinary retention in prostate cancer patients. CONCLUSIONS: The procedure appears safe, burdened with low risk of complications and accomplishes technical and clinical success. It is a promising option for patients with hemorrhage, but due to the scarcity of data further investigations are needed.