Bilateral Nephrectomy in Patients with Autosomal Dominant Polycystic Kidney Disease and End-Stage Chronic Renal Failure.

BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD) and end-stage kidney disease, bilateral nephrectomy (BN) is currently performed predominantly via the laparoscopic approach. We analysed the results of BN depending on the approach and preoperative and perioperative factors. PATIENTS AND METHODS: This was a single-centre retrospective study carried out from April 2010 to March 2020, including a total of 142 patients presenting with ADPKD who were treated by BN. Of these, 108 patients meeting the inclusion criteria were selected to analyse the results. We compared therapeutic outcomes depending on the surgical approach (laparotomy or laparoscopy) and the type of the operation (emergent or elective). RESULTS: Of the 108 eligible patients, 36 (group I) underwent laparoscopic BN and the remaining 72 patients (group II) were subjected to midline laparotomy. Sixty-nine patients underwent elective surgery and 39 endured emergent operations. The most frequent indications (87 patients, 80.6%) for surgical treatment were urinary tract infection and infected cysts. The median length of hospital stay for group I and group II patients amounted to 8 days (IQR: 7.5-9) and 12.5 days (IQR: 9-16.5), respectively (p < 0.001). However, comparing the patients operated on electively, the actual difference in the length of hospital stay was inconsiderable: median 8 days (IQR: 7-9) in group I and 9 days (IQR: 9-11.5) in group II. The median duration of the operation was significantly (p < 0.001) longer in group I amounting to 217.5 min (IQR: 197.5-305) than in group II equalling 115 min (IQR: 107.5-145). The frequency of postoperative complications, lethal outcomes, and blood loss volume did not statistically significantly differ depending on the surgical approach. Only patients operated on emergency underwent releparotomy due to intraoperative large bowel injury. Lethal outcomes (n = 18, 16.7%) after surgery were observed only in emergent patients. Sepsis prior to surgery, systemic inflammation response syndrome (SIRS) with the CRP level above 173 mg/mL, prolonged preoperative antibacterial therapy, and undiagnosed large bowel injury were associated with a lethal outcome after BN. CONCLUSION: The results of open and laparoscopic BN in elective surgery were comparable. Emergency operations for infected renal cysts and SIRS were associated with increased incidence of large bowel injury and lethal outcomes.

Primary Undifferentiated Pericardial Sarcoma after Radiоtherapy for Hodgkin Lymphoma.

Various types of sarcomas arise as a result of postradiation chronic fibrous pericarditis. A primary undifferentiated spindle cell pericardial sarcoma is a rare type of sarcoma after radiotherapy. The risk of sarcoma increases with time after treatment of cancer. A 55-year-old woman underwent successful radiation and chemotherapy for Hodgkin lymphoma 20 years ago. She was hospitalized with typical manifestations of severe heart failure. Echocardiography, сomputed tomography of the chest and magnetic resonance imaging scan of the heart detected neoplastic formations of the pericardium. A biopsy of the pericardium was performed. Histological, immunohistochemical, and genetic studies showed a primary undifferentiated spindle cell pericardial sarcoma (an extremely rare type of sarcoma).

The prognostic value of the urokinase-plasminogen activator system (uPA) in bladder cancer patients treated with radical cystectomy (RC).

PURPOSE: Urokinase-plasminogen activator (uPA), its receptor (uPAR), and the plasmin-activator inhibitor type 1 (PAI-1) have been associated with oncologic outcomes in various malignancies and could help identify bladder cancer (BC) patients treated with radical cystectomy (RC) who are likely to benefit from intensification of therapy to prevent disease progression. Our aim was to assess the value of uPA, uPAR, and PAI-1 for prognosticating survival outcomes of patients treated with RC for BC. MATERIALS AND METHODS: Tumor specimens from 272 consecutive patients treated with RC for advanced BC were assessed with immunohistochemical staining for uPA, uPAR, and PAI-1. Overexpression was assessed by pathological image analysis. Kaplan-Meier estimates and multivariable Cox-regression were used to analyze survival. Harrell's C-index was used to assess for clinical impact of the uPA system. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 48.2%, 51.1%, and 52.2% of patients, respectively. uPA overexpression was associated with lymphovascular invasion (P = 0.034) and nodal status (P = 0.013); PAI-1 overexpression was associated with primary muscle-invasive BC (P = 0.015) and lymphovascular invasion (P = 0.024). uPA, uPAR, and the number of overexpressed markers were all 3 significantly associated with shorter overall recurrence-free-, distant recurrence-free-, and cancer-specific survival. In multivariable analyses, uPA overexpression remained associated with shorter recurrence-free survival (hazard ratio [HR] = 1.79; P = 0.036) in the entire cohort, in patients without lymph node metastasis (HR = 1.98; P = 0.018) and those with nonorgan-confined disease (HR = 1.98; P = 0.022). uPAR overexpression was associated with shorter recurrence-free survival in patients without lymph node metastasis (HR = 2.01; P = 0.021) and those with organ-confined disease (HR = 4.11; P = 0.037). CONCLUSION: Members of the uPA system are associated with features of biologically aggressive BC and oncologic outcomes. However, their value beyond currently available information remains limited.

The prognostic impact of tumour NSD2 expression in advanced prostate cancer.

Purpose: To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa).Methods: We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression.Results: Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival (p = 0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints.Conclusions: NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.

Prognostic value of the systemic inflammation modified Glasgow prognostic score in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy: Results from a large multicenter international collaboration.

INTRODUCTION AND OBJECTIVES: To evaluate the prognostic role of modified Glasgow prognostic score (mGPS) for the prediction of oncological outcomes in a retrospective large multicenter cohort of upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed a multicenter cohort of patients treated with RNU for clinically nonmetastatic UTUC. Multivariable logistic regression analyses were performed to evaluate the ability of mGPS to predict nonorgan confined (NOC) disease and lymph-node involvement (LNI) at RNU. Multivariable Cox-regression models were performed to evaluate the preoperative and postoperative prognostic effect of mGPS on survival outcomes. RESULTS: Overall, 2,492 patients were included in the study. Of these, 1,929 (77%), 530 (21%), and 33 (1%) had a mGPS of 0, 1, and 2, respectively. mGPS was associated with characteristics of tumor aggressiveness and independently predicted LNI and NOC at RNU (both P < 0.05). On univariable and multivariable Cox-regression analyses, higher mGPS was independently associated with recurrence-free, cancer-specific, and overall survival, both in a preoperative and in a postoperative setting. The inclusion of mGPS significantly improved the discrimination of a preoperative model for the prediction of oncologic outcomes compared to standard prognosticators. CONCLUSIONS: We found that mGPS is independently associated with clinicopathologic features and survival outcomes after RNU. Future studies should investigate the role of mGPS in a panel of preoperative markers for the prediction of NOC and LNI in UTUC patients, thus possibly improving the selection for perioperative systemic therapy.

Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis.

PURPOSE: To evaluate the prognostic value of substaging on oncological outcomes in patients with T (or pT1) urothelial carcinoma of the bladder. METHODS: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on March 2019 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The pooled disease recurrence (DR) and disease progression (DP) rate in T1(or pT1) patients were calculated using a fixed or random effects model. RESULTS: Overall 36 studies published between 1994 and 2018 including a total of 6781 bladder cancer patients with T1(or pT1) stage were selected for the systematic review and meta-analysis. Twenty-nine studies reported significant association between tumor infiltration depth or muscularis mucosa (MM) invasion and oncological outcomes. Totally 12 studies were included in the meta-analysis. MM invasion (T1a/b/c [or pT1a/b/c] or T1a/b [or pT1a/b] substaging system) was associated with DR (pooled HR: 1.23, 95%CI: 1.01-1.49) and DP (pooled HR: 2.61, 95%CI: 1.61-4.23). Tumor infiltration depth (T1 m/e [or pT1 m/e] substaging system) was also associated with DR (pooled HR: 1.49, 95%CI: 1.11-2.00) and DP (pooled HR: 3.29, 95%CI: 2.39-4.51). CONCLUSIONS: T1(or pT1) substaging in patients with bladder cancer is of prognostic value as it is associated with oncologic outcomes. Inclusion of this factors into the clinical decision-making process of this heterogeneous tumor may improve outcomes, while avoiding over- and under-treatment for T1(or pT1) bladder cancer.

Diagnostic performance of multidetector computed tomographic (MDCTU) in upper tract urothelial carcinoma (UTUC): a systematic review and meta-analysis.

PURPOSE: To systematically review the literature evaluating the performance of MDCTU for the diagnosis of UTUC and meta-analyse available data. We also compared the diagnostic accuracy of MDCTU to other radiologic modalities. METHODS: This systematic review and meta-analysis was conducted according to the PRISMA statement. A systematic research using Pubmed, Scopus, Cochrane, and Web of Science libraries was performed on November 1st, 2018. We included all original articles investigating the performance of MDCTU for the diagnosis of UTUC using histopathology as the reference standard for true positives and an unsuspicious clinical follow-up of at least 1 year for true negatives. RESULTS: Overall, 13 studies comprising 1233 patients were eligible and included in this systematic review and meta-analysis. In patient-based analyses, the pooled sensitivity and specificity were 92% (CI 0.85-0.96) and 95% (CI 0.88-0.98), respectively. The reported sensitivity in the per-lesion analysis ranged between 91 and 97%. All studies reporting segment-based analysis demonstrated high diagnostic accuracy (> 90%). While one study reported higher accuracy of retrograde ureteropyelography than MDCTU (97% vs. 94%), another study demonstrated an inferior accuracy of intravenous pyelogram compared to MDCTU. Findings on the accuracy of diffusion-weighted magnetic resonance imaging compared to MDCTU were inconsistent. CONCLUSION: MDCTU has excellent diagnostic performance in detecting UTUC and ruling-out suspicious upper urinary tract lesions in per-patient and per-lesion-based analyses. We confirm the choice of MDCTU as the radiologic diagnostic modality of choice for work-up of suspicious upper urinary tract lesions providing valuable information in patient counseling, decision-making, and treatment planning.

Impact of Patients' Gender on Efficacy of Immunotherapy in Patients With Metastatic Kidney Cancer: A Systematic Review and Meta-analysis.

Recent meta-analyses on checkpoint inhibitors in cancer report conflicting data regarding the association of patient gender with inhibitor efficacy. In advanced kidney cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared with standard of care, but the role of patient gender on treatment outcome is unclear. We aimed to assess the efficacy of immunotherapy according to patient gender in advanced kidney cancer. We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Scopus, Web of Science, and The Cochrane Library to identify eligible studies published through February 16, 2019. Studies were included if they reported on the differential outcomes of male and female patients with metastatic kidney cancer receiving immunotherapy. Our outcomes of interest were overall survival (OS) or progression-free survival (PFS). Four randomized controlled trials comprising a total of 3664 patients (2715 males and 949 females) met our inclusion criteria. Both men and women with metastatic kidney cancer had an OS and PFS advantage with immunotherapy compared with standard-of-care, but no statistically significant difference between the genders was observed (OS hazard ratio [HR] for men, 0.69; 95% confidence interval [CI], 0.59-0.8; P = .40; HR for women, 0.62; 95% CI, 0.48-0.81; P = .13; PFS HR for men, 0.7; 95% CI, 0.59-0.82; P = .24; HR for women, 0.68; 95% CI, 0.52-0.90; P = .105). In patients with advanced kidney cancer receiving checkpoint inhibitors, there seems to be no association of patient gender with treatment outcome.

Comparative Effectiveness of Intravesical BCG-Tice and BCG-Moreau in Patients With Non-muscle-invasive Bladder Cancer.

BACKGROUND: The purpose of this study was to compare the efficacy of 2 bacillus Calmette-Guérin (BCG) strains, BCG-Tice and BCG-Moreau, in the treatment of non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively reviewed clinical data from patients treated with BCG for NMIBC at 3 academic centers. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare recurrence-free (RFS) and progression-free survival (PFS) of patients in the 2 treatment groups. In addition, we performed exploratory analyses of treatment effect according to the receipt of adequate BCG treatment, high-risk disease, age, gender, smoking status, pathologic stage, and pathologic grade. RESULTS: A total of 321 (48.6%) patients were treated with BCG-Tice and 339 (51.4%) with BCG-Moreau. IPTW-adjusted Cox proportional hazard regression analysis did not show a difference in RFS (hazard ratio, 0.88; 95% confidence interval, 0.56-1.38; P = .58) or PFS (hazard ratio, 0.55; 95% confidence interval, 0.25-1.21, P = .14) between BCG-Tice and BCG-Moreau. On subgroup analyses, we could not identify an association of BCG strain with outcomes. CONCLUSIONS: There was no difference in RFS and PFS between BCG-Tice and BCG-Moreau strains in the adjuvant treatment of NMIBC. However, we confirmed the importance of maintenance therapy for achieving a sustainable response in patients with intermediate- and high-risk NMIBC.

Assessment of body composition in the advanced stage of castration-resistant prostate cancer: special focus on sarcopenia.

PURPOSE: To assess the prevalence of sarcopenia and whether body composition parameters are associated with disease progression and overall survival (OS) in castration-resistant prostate cancer (CRPC) patients. MATERIALS AND METHODS: This single-centre retrospective study evaluated data of 186 consecutive patients who underwent chemohormonal therapy between 2005 and 2016 as first-line systemic treatment for CRPC. Skeletal muscle and fat indices were determined using computerized tomography data before initiation of chemotherapy. Sarcopenia was defined as SMI of <55 cm2/m2. Visceral-to-subcutaneous fat ratio and skeletal muscle volume were calculated with body composition specific areas. Harrell's concordance index was used for predictive accuracy. RESULTS: A total of 154 (82.8%) patients met the criteria for sarcopenia; 139 (74.7%) individuals completed at least six cycles of docetaxel. Within a median follow-up of 24.1 months, age (HR 1.03, 95% CI 1.01-1.06, p = 0.02), high PSA (1.55, 95% CI 1.07-2.25, p = 0.02) and low skeletal muscle volume (HR 1.61, 95% CI 1.10-2.35, p = 0.02) were the only independent prognostic factor for tumor progression. Overall, 93 (50%) patients died during the follow-up period. The established prognosticator, the prechemotherapy presence of liver metastases (HR 1.32, 95% CI 1.08-1.61, p < 0.01) was associated with shorter OS. Moreover, we noted that patients with an elevated visceral-to-subcutaneous fat ratio tended to have a shorter OS (p = 0.06). CONCLUSION: The large majority of men with CRPC suffers from sarcopenia. In our cohort, low skeletal muscle volume was an independent adverse prognosticator for progression of disease. We could not detect a statistically significant body composition parameter for OS, although patients with a high proportion of visceral fat had a trend for shorter OS. However, we suggest that body composition parameters determined by CT data can provide useful objective prognostic factors that may support tailored treatment decision-making.

Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.

The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor-axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.

Risk stratification of upper tract urothelial carcinoma: A Review of the Current Literature.

Introduction: Several prognostic factors have been identified to risk stratify patients with upper tract urothelial carcinoma (UTUC). However, due to the heterogeneity of these prognosticators and the presence of different therapeutic modalities for this rare and heterogeneous disease, decision-making and patient consulting remains challenging. Areas covered: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted in January 2019 to find relevant English-language studies identifying prognostic factors that can help risk stratify patients and select proper therapeutic modality. Expert opinion: Several studies confirmed the value of patient and tumor-related factors for prognosticating oncological outcomes in UTUC patients. However, due to the retrospective nature of these studies, the true clinical impact needs to be assessed in well-designed prospective-controlled studies to increase the accuracy and fortify the evidence-driven clinical decision-making process. More biomarkers studies for stratifying risks of UTUC patients are needed to capture their biologic and clinical potentials of each individual tumor.

3D reconstruction of CT scans aid in preoperative planning for sarcomatoid renal cancer: A case report and mini-review.

Contrast-enhanced multi-slice computed tomography (MSCT) is commonly used in the diagnosis of complex malignant tumours. This technology provides comprehensive and accurate information about tumour size and shape in relation to solid tumours and the affected adjacent organs and tissues. This case report demonstrates the benefit of using MSCT 3D imaging for preoperative planning in a patient with late-stage (T4) sarcomatoid renal cell carcinoma, a rare renal malignant tumour. The surgical margin on the liver was negative, and no metastases to veins, lungs or other organs were detected by abdominal and chest contrast-enhanced CT. Although sarcomatoid histology is considered to be a poor prognostic factor, the patient is alive and well 17 months after surgery. The MSCT imaging modality enables 3D rendering of an area of interest, which assists surgical decision-making in cases of advanced renal tumours. In this case, as a result of MSCT 3D reconstruction, the patient received justified surgical treatment without compromising oncological principles.

Evaluation of Prostate HistoScanning as a Method for Targeted Biopsy in Routine Practice.

BACKGROUND: Prostate HistoScanning (PHS) is a tissue characterization system used to enhance prostate cancer (PCa) detection via transrectal ultrasound imaging. OBJECTIVE: To assess the impact of supplementing systematic transrectal biopsy with up to three PHS true targeting (TT) guided biopsies on the PCa detection rate and preclinical patient assessment. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective study involving a cohort of 611 consecutive patients referred for transrectal prostate biopsy following suspicion of PCa. PHS-TT guided cores were obtained from up to three PHS lesions of ≥0.5cm3 per prostate and only one core per single PHS lesion. Histological outcomes from a systematic extended 12-core biopsy (Bx) scheme and additional PHS-TT guided cores were compared. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Comparison of PHS results and histopathology was performed per sextant. The χ2 and Mann-Whitney test were used to assess differences. Statistical significance was set at p<0.05. RESULTS AND LIMITATIONS: PHS showed lesions of ≥0.5cm3 in 312 out of the 611 patients recruited. In this group, Bx detected PCa in 59% (185/312) and PHS-TT in 87% (270/312; p<0.001). The detection rate was 25% (944/3744 cores) for Bx and 68% (387/573 cores) for PHS-TT (p<0.001). Preclinical assessment was significantly better when using PHS-TT: Bx found 18.6% (58/312) and 8.3% (26/312), while PHS-TT found 42.3% (132/312) and 20.8% (65/312) of Gleason 7 and 8 cases, respectively (p<0.001). PHS-TT attributed Gleason score 6 to fewer patients (23.4%, 73/312) than Bx did (32.4%, 101/312; p=0.0021). CONCLUSIONS: Patients with a suspicion of PCa may benefit from addition of a few PHS-TT cores to the standard Bx workflow. PATIENT SUMMARY: Targeted biopsies of the prostate are proving to be equivalent to or better than standard systematic random sampling in many studies. Our study results support supplementing the standard schematic transrectal ultrasound-guided biopsy with a few guided cores harvested using the ultrasound-based prostate HistoScanning true targeting approach in cases for which multiparametric magnetic resonance imaging is not available.

Holmium laser enucleation of the prostate (HoLEP) for small, large and giant prostatic hyperplasia: tips and tricks.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) allows to treat extremely large prostates (>200 cm3). The aim of the study was to compare the efficiency of HoLEP for prostates of different sizes. METHODS: Four hundred and fifty-nine patients were divided into three groups: group 1 included 278 patients (<100 cm3); group 2 included 169 patients (100-200 cm3); group 3 included 12 patients (>200 cm3). RESULTS: The duration of enucleation in group 1 was 56.5 ± 10.7 min; in group 2 was 96.4 ± 24.9 min; in group 3 was 120.9 ± 35 min. The duration of morcellation in group 1 was 37.5 ± 7.3 min; in group 2 was 63.3 ± 11.2 min; in group 3 was 84.0 ± 25.6 min. The enucleation efficiency in group 3 (1.70 g/min) was higher (p<0.05) than in group 1 (1.05 g/min) and group 2 (1.23 g/min). Morcelation efficiency was lower in groups 1 and 2 (1.58 and 1.87 g/min, respectively) than in group 3 (2.45 g/min) (p<0.05).Follow-up period lasted 18 months. There were no significant differences (p>0.05) in International Prostate Symptom Score, Qmax, quality of life and postvoid residual volume for 1, 3, 6, 12 and 18 months after surgery. CONCLUSIONS: HoLEP is a safe, highly efficacious and a size-independent procedure.