Comparison of the performances of the ADXBLADDER test and urinary cytology in the follow-up of non-muscle-invasive bladder cancer: a blinded prospective multicentric study.

OBJECTIVE: To compare directly the performance of the ADXBLADDER test with that of cytology in the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences. BACKGROUND: ADXBLADDER is a urine test based on the detection of MCM5, a DNA licensing factor expressed in all cells capable of dividing. Expression is usually restricted to the basal stem cell compartment; however, in malignancy, MCM5-expressing cells can be found throughout the epithelium. Detection of MCM5 in urine sediment can be indicative of the presence of a bladder tumour. PATIENTS AND METHODS: A multicentre prospective, blinded study was carried out from August 2017 and July 2019 at 21 European Union centres, 14 of which collected matching cytology data. Urine was collected from patients prior to cystoscopy. Urine cytology and ADXBLADDER were performed and compared to the diagnosis obtained by cystoscopy. The performance of cytology and ADXBLADDER were then compared. RESULTS: The overall performance of ADXBLADDER demonstrated a sensitivity of 51.9%, a specificity of 66.4%, and a negative predictive value (NPV) of 92%. The sensitivity of ADXBLADDER for low- and high-grade recurrences was 44.1% and 58.8%, respectively. By contrast, cytology sensitivity was 16.7%, specificity was 98% and NPV was 90.7%. Cytology sensitivity for both low- and high-grade disease was 17.6%. CONCLUSIONS: ADXBLADDER detection of both low- and high-grade NMIBC recurrence is superior to that of cytology, with ADXBLADDER able to exclude the presence of high-grade recurrence in 97.8% of cases compared to 97.1% with cytology. These results show that ADXBLADDER has promise as a more reliable alternative to urine cytology in the follow-up of NMIBC.

Diagnostic Accuracy of MCM5 for the Detection of Recurrence in Nonmuscle Invasive Bladder Cancer Followup: A Blinded, Prospective Cohort, Multicenter European Study.

PURPOSE: Detection of MCM5 containing cells in urine has been shown to be indicative of the presence of a bladder tumor on primary diagnosis. In this study we evaluate diagnostic performance of ADXBLADDER in patients undergoing cystoscopic surveillance in nonmuscle invasive bladder cancer followup. MATERIALS AND METHODS: A multicenter prospective blinded study was performed at 21 European centers with patients undergoing cystoscopy for nonmuscle invasive bladder cancer surveillance, diagnosed in the preceding 2 years. Urine was collected from all eligible patients and ADXBLADDER-MCM5 testing was performed. Performance characteristics were calculated by comparing MCM5 results to the outcome of cystoscopy plus pathological assessment. RESULTS: Of 1,431 eligible patients enrolled 127 were diagnosed with a bladder cancer recurrence. The overall sensitivity for the ADXBLADDER-MCM5 test in detecting bladder cancer recurrence was 44.9% (95% CI 36.1-54) with a 75.6% sensitivity for nonpTaLG tumors (95% CI 59.7-87.6). Specificity was 71.1% (95% CI 68.5-73.5). The overall negative predictive value was 93% (95% CI 91.2-94.5). However, ADXBLADDER was able to rule out the presence of a nonpTaLG recurrent tumor with a negative predictive value of 99.0% (95% CI 98.2-99.5). No statistically significant differences in the performance of ADXBLADDER were observed as a result of age or sex. CONCLUSIONS: This large blinded prospective study demonstrates that in the followup of patients with nonmuscle invasive bladder cancer ADXBLADDER is able to exclude the presence of the most aggressive tumors with a negative predictive value of 99%. These results indicate that ADXBLADDER could be incorporated in the followup strategy of nonmuscle invasive bladder cancer.

MMP23B expression and protein levels in blood and urine are associated with bladder cancer.

Urothelial bladder cancer (UBC) represents a public health problem because of its high incidence/relapse rates. At present, there are no suitable biomarkers for early diagnosis or relapse/progression prognosis. To improve diagnostic accuracy and overcome the disadvantages of current diagnostic strategies, the detection of UBC biomarkers in easily accessible biofluids, such as urine, represents a promising approach compared with painful biopsies. We investigated the levels of MMP23 genes (microarray and qPCR) and protein (western blot and enzyme-linked immunosorbent assay) in a set of samples (blood, plasma and urine) from patients with UBC and controls as biomarkers for this cancer. MMP23B and its pseudogene MMP23A resulted downregulated in blood cells from UBC compared with controls (66 cases, 70 controls; adjusted P-value = 0.02 and 0.03, respectively). In contrast, MMP23B protein levels in plasma (53 UBC, 49 controls) and urine (59 UBC, 57 controls) increased in cases, being statistically significant in urine. MMP23B dosage observed in urine samples was related to both tumor risk classification and grading. As the lack of correlation between mRNA and protein levels could be due to a posttranscriptional regulation mediated by microRNAs (miRNAs), we investigated the expression of urinary miRNAs targeting MMP23B. Five miRNAs resulted differentially expressed between cases and controls. We reported the first evidence of MMP23B secretion in plasma and urine, suggesting a role of this poorly characterized metalloproteinase in UBC as a potential non-invasive biomarker for this cancer. Further analyses are needed to elucidate the mechanism of regulation of MMP23B expression by miRNAs.

Retreatment after focal therapy for failure: a bridge too far?

PURPOSE OF REVIEW: To summarize the current knowledge about the evaluation of disease persistence and recurrence after focal therapy ablation (FTA) for small renal masses and to assess the outcomes and complications of related treatment options. RECENT FINDINGS: FTA procedures continuously increased over the last 20 years, being now performed in more than one on 10 patients with T1a renal cell carcinoma. Disease recurrence seems to occur more often following radiofrequency ablation (RFA) compared with cryoablation. Evidence about the management of disease recurrence is scarce. Treatment options are similar to those available for de novo renal cell carcinomas, and include reablation, partial or radical nephrectomy and observation. Reablation is feasible, safe and can be easily done in the majority of cases. Oncological outcomes of repeated ablation, although encouraging, remain mostly uninvestigated and unreported. SUMMARY: In case of disease persistence or recurrence after FTA, observation may be an acceptable approach, reserving repeated ablation or surgery only in those exhibiting significant tumor growth. In these patients repeated ablation with RFA is safe and noninvasive. Surgery after FTA presents technical difficulties related to perinephric scarring, especially with regards to nephron-sparing surgery. This should be taken into consideration in patients' counseling as well as in decision-making process.

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel-Lindau patients.

CONTEXT: Von Hippel-Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death. OBJECTIVE: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients. MATERIALS AND METHODS: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers. RESULTS: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC. DISCUSSION AND CONCLUSION: A1AT and APOH could be promising non-invasive biomarkers.

Radical Prostatectomy for Nonmetastatic Prostate Cancer in Renal Transplant Recipients: Outcomes for a Large Contemporary Cohort and a Matched Comparison to Patients Without a Transplant.

BACKGROUND AND OBJECTIVE: It is unknown whether renal transplant receipt (RTR) status can affect perioperative and oncological outcomes of radical prostatectomy (RP). Our aim was to evaluate oncological and functional outcomes of RTR patients treated with RP for cN0M0 prostate cancer (PCa) via comparison with a no-RTR cohort. METHODS: RTR patients who had undergone RP at seven European institutions during 2001-2022 were identified. A multi-institutional cohort of no-RTR patients treated with RP during 2004-2022 served as the comparator group. Propensity score matching (PSM) at a ratio of 1:4 was used to match no-RTR patients to the RTR cohort according to age, prostate-specific antigen, and final pathology features. We used Kaplan-Meier plots and multivariable Cox, logistic, and Poisson log-linear regression models to test the outcomes of interest. KEY FINDINGS AND LIMITATIONS: After PSM, we analyzed data for 102 RTR and 408 no-RTR patients. RTR patients experienced higher estimated blood loss (EBL), longer length of hospital stay (LOS) and time to catheter removal, higher postoperative complication rates, and a lower continence recovery rate (all p < 0.001). On multivariable analyses, RTR independently predicted unfavorable operative time (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.18-1.25), LOS (OR 1.57, 95% CI 1.32-1.86), EBL (OR 2.24, 95% CI 2.18-2.30), and time to catheter removal (OR 1.93, 95% CI 1.68-2.21), but not complications or continence recovery. There were no significant differences for any oncological outcomes (biochemical recurrence, local or systemic progression) between the RTR and no-RTR groups. While no PCa deaths were recorded, the overall mortality rate was significantly higher in the RTR group (17% vs 0.5%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although RP is feasible for RTR patients, the procedure poses non-negligible surgical challenges, with longer operative time and LOS and higher EBL, but no major differences in terms of complications and continence recovery. The RTR group had similar oncological outcomes to the no-RTR group but significantly higher overall mortality related to causes other than PCa. Therefore, careful selection for RP is required among candidates with previous RTR. PATIENT SUMMARY: Removal of the prostate for prostate cancer is possible in patients who have had a kidney transplant, and cancer control outcomes are comparable to those for the general population. However, transplant patients have a higher risk of death from causes other than prostate cancer and the prostate surgery is likely to be more challenging.

Awake Da Vinci robotic partial nephrectomy: First case report ever in a situation of need.

We report a unique case of a robotic partial nephrectomy performed under continuous spinal anesthesia (CSA). A 63-year-old woman, active smoker with mild obesity and previous right pneumonectomy, was diagnosed with a growing 5.5-cm renal right cystic tumor. Being at high risk for general anesthesia, a loco-regional approach was indicated. Therefore, after multidisciplinary discussion, a robotic-assisted partial nephrectomy under CSA was considered mandatory. After T4-T5 sensory and motor block, retroperitoneoscopic robot-assisted surgery was successfully performed. Postoperative period was uneventful, with optimal pain control. This unique case demonstrates the feasibility of robotic surgery under CSA, for imperative indications.

Reducing the Frequency of Follow-up Cystoscopy in Low-grade pTa Non-muscle-invasive Bladder Cancer Using the ADXBLADDER Biomarker.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is one of the most expensive cancers owing to frequent follow-up cystoscopies for detection of recurrence. OBJECTIVE: To assess if the noninvasive ADXBLADDER urine test could permit a less intensive surveillance schedule for patients with low-grade (LG) pTa tumor without carcinoma in situ (CIS) at the previous diagnosis. DESIGN, SETTING, AND PARTICIPANTS: In a prospective, double-blind, multicenter study, 629 patients underwent follow-up cystoscopy, transurethral resection of bladder tumor/biopsy of suspect lesions, and ADXBLADDER testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Diagnostic test accuracy and decision curve analysis were used to evaluate the impact of ADXBLADDER on decision-making on whether to perform follow-up cystoscopy. The primary endpoint was the negative predictive value (NPV) of ADXBLADDER for detection of high-grade and/or CIS (HG/CIS) recurrence and its impact on reducing unnecessary cystoscopies. RESULTS AND LIMITATIONS: ADXBLADDER had sensitivity of 66.7% (95% confidence interval [CI] 34.9-90.1%) and an NPV of 99.15% (95% CI 97.8-99.8%) for detection of HG/CIS recurrence. The probability of HG/CIS recurrence was 5.0% for ADXBLADDER-positive patients and 0.85% for ADXBLADDER-negative patients. For HG/CIS recurrence threshold probabilities between 0.85% and 5.0%, ADXBLADDER yields a net benefit with omission of cystoscopy for ADXBLADDER-negative patients. The corresponding net reduction in unnecessary cystoscopies ranges from 11 to 62 per 100 patients. CONCLUSIONS: Patients with LG pTa tumor at the previous diagnosis, for which the risk of HG/CIS recurrence is low and the ADXBLADDER NPV for ruling out HG/CIS recurrence is 99.15%, are ideally suited for a less intensive, personalized follow-up surveillance strategy using ADXBLADDER, with omission of cystoscopy for ADXBLADDER-negative patients. PATIENT SUMMARY: ADXBLADDER is a urine test that can predict the probability of recurrence of bladder cancer. Patients diagnosed with low-grade cancer confined to the bladder mucosa are ideally suited for less intensive follow-up using this test, which could reduce unnecessary cystoscopy procedures for those with a negative result, potentially improve quality of life, and reduce overall health care costs.

Combination of urinary fibrinogen ß-chain and tyrosine-phosphorylated proteins for the detection of bladder cancer.

AIM: To evaluate the performance of urinary fibrinogen ß-chain (FBC) - either alone or associated with urinary tyrosine-phosphorylated proteins (UPY) - as bladder cancer (BCa) diagnostic biomarker. MATERIALS & METHODS: 164 subjects were tested. RESULTS: Significantly different FBC and UPY levels were found between BCa patients and controls, as well as between low-grade and high-grade cancers. The diagnostic accuracy was 0.84 for FBC and 0.87 for UPY. The combination of FBC and UPY improved the accuracy to 0.91. The addition of clinical variables (age, gender, and smoking habit) to FBC and UPY into a model for BCa prediction significantly improved the accuracy to 0.99. The combination of FBC and UPY adjusted for clinical variables associates with the highest sensitivity and good specificity. CONCLUSION: Urinary FBC and UPY could be used as biomarkers for BCa diagnosis.

Is partial nephrectomy safe and effective in the setting of frail comorbid patients affected by renal cell carcinoma? Insights from the RECORD 2 multicentre prospective study.

BACKGROUND: To investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project). METHODS: Clinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared. RESULTS: Overall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6-8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery. Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74). CONCLUSION: In selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease.

Small Non-Coding RNA Profiling in Plasma Extracellular Vesicles of Bladder Cancer Patients by Next-Generation Sequencing: Expression Levels of miR-126-3p and piR-5936 Increase with Higher Histologic Grades.

Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine as possible biomarkers for BC, but in plasma their potential has not yet been defined. The expression levels of sncRNAs contained in plasma extracellular vesicles (EVs) from 47 men with BC and 46 healthy controls were assessed by next-generation sequencing. The sncRNA profiles were compared with urinary profiles from the same subjects. miR-4508 resulted downregulated in plasma EVs of muscle-invasive BC patients, compared to controls (adj-p = 0.04). In World Health Organization (WHO) grade 3 (G3) BC, miR-126-3p was upregulated both in plasma EVs and urine, when compared to controls (for both, adj-p < 0.05). Interestingly, two sncRNAs were associated with the risk class: miR-4508 with a downward trend going from controls to high risk BC, and piR-hsa-5936 with an upward trend (adj-p = 0.04 and adj-p = 0.05, respectively). Additionally, BC cases with low expression of miR-185-5p and miR-106a-5p or high expression of miR-10b-5p showed shorter survival (adj-p = 0.0013, adj-p = 0.039 and adj-p = 0.047, respectively). SncRNAs from plasma EVs could be diagnostic biomarkers for BC, especially in advanced grade.

A Review on the Management of Small Renal Masses: Active Surveillance Versus Surgery.

Despite the rise of small renal tumour (SRMs) diagnosis and related surgeries, death rate of kidney cancer is increasing, suggesting a non-optimal management of SRMs. Active Surveillance (AS) for kidney cancer was introduced to deal with this paradox. However, incertitude remains on whether and when AS can replace surgery in selected patients. We performed a literature search, reviewed and discussed the evidence in favour of AS or surgery for SRMs. Histopathology and natural history of SRMs, including the percentage of benign tumours amongst SRMs, tumour growth rate, life expectancy of SRMs patients being generally older, and current results of AS series seem to support its use in selected groups. However, kidney cancer is a heterogeneous entity, metastasis and ≥T3a status can be found also for SRMs and no biomarkers or other parameters are available to identify lethal SRMs. Despite the recent improvement in the diagnostic and prognostic work through imaging modalities, renal biopsies and nomograms, the interpretation of a survival plot subjectively is still not possible. The majority of AS studies are retrospective and extensive level 1 evidence cohorts with long term follow up are lacking. No unanimity is present regarding inclusion and exclusion criteria to undergo AS, follow up timings and AS exit criteria. Surgery is the only definitive treatment and remains the current standard. A better understanding of kidney cancer biology and SRMs behaviour is needed to clarify the role of AS and its indications.

The prognostic value of basal DNA damage level in peripheral blood lymphocytes of patients affected by bladder cancer.

BACKGROUND: Bladder cancer (BC) is one of the most aggressive malignancies of the urinary tract, with the highest lifetime treatment costs per patient of all cancers, due to the high rate of recurrences requiring continuous surveillance. An early diagnosis is essential to improve survival of patients with BC. Noninvasive and sensitive molecular biomarkers are needed to improve current strategies for the detection and monitoring of BC. Previous studies suggested that elevated DNA damage levels and suboptimal nucleotide excision DNA repair (NER) may be associated with BC. METHODS: In the present study, we investigated basal DNA damage and DNA repair capacity in peripheral blood mononuclear cells (PBMCs) from 146 newly diagnosed patients with BC and 155 controls using a modified comet assay able to evaluate NER activity after challenging cells by benzo(a)pyrene diolepoxide (BPDE). RESULTS: We found an association between DNA damage levels in PBMCs of BC cases and patients' outcomes. Basal DNA damage at diagnosis was significantly increasing with tumor grades (trend test, P = 0.02) and risk classes (trend test, P = 0.02). The overall survival analysis showed that DNA damage in patients at BC diagnosis was significantly higher in subjects with a shorter survival time (hazard ratio = 3.7; 95% CI: 1.3-10.6; P = 0.02). CONCLUSIONS: Based on these data, we suggest that DNA damage levels measured in PBMCs of patients with BC may potentially represent a prognostic marker associated with poor survival; further validation is needed to better stratify patients with BC for clinical trials.

Small non-coding RNA profiling in human biofluids and surrogate tissues from healthy individuals: description of the diverse and most represented species.

The role of non-coding RNAs in different biological processes and diseases is continuously expanding. Next-generation sequencing together with the parallel improvement of bioinformatics analyses allows the accurate detection and quantification of an increasing number of RNA species. With the aim of exploring new potential biomarkers for disease classification, a clear overview of the expression levels of common/unique small RNA species among different biospecimens is necessary. However, except for miRNAs in plasma, there are no substantial indications about the pattern of expression of various small RNAs in multiple specimens among healthy humans. By analysing small RNA-sequencing data from 243 samples, we have identified and compared the most abundantly and uniformly expressed miRNAs and non-miRNA species of comparable size with the library preparation in four different specimens (plasma exosomes, stool, urine, and cervical scrapes). Eleven miRNAs were commonly detected among all different specimens while 231 miRNAs were globally unique across them. Classification analysis using these miRNAs provided an accuracy of 99.6% to recognize the sample types. piRNAs and tRNAs were the most represented non-miRNA small RNAs detected in all specimen types that were analysed, particularly in urine samples. With the present data, the most uniformly expressed small RNAs in each sample type were also identified. A signature of small RNAs for each specimen could represent a reference gene set in validation studies by RT-qPCR. Overall, the data reported hereby provide an insight of the constitution of the human miRNome and of other small non-coding RNAs in various specimens of healthy individuals.

Robot-assisted laparoscopic pyeloplasty in a pediatric patient with horseshoe kidney: surgical technique and review of the literature.

OBJECTIVE: The aim of this study was to describe the technical aspects of a robotic pyeloplasty in pediatric patients with uretero-pelvic junction obstruction (UPJO) in horseshoe kidney (HSK) through the report of our recent case, and to outline the state of the art of minimally invasive pyeloplasty (MIP) with a systematic review of the literature. METHODS: We describe all the steps of our surgery performed on an 11-year-old patient with left UPJO in HSK in detail. All the anatomic landmarks are clearly showed, with particular attention to trocar placement in a pediatric patient. A systematic review of the literature on the outcomes of MIP in HSK patients has been performed, including 16 articles. RESULTS: Our surgery was successful following a standardized approach. However, we recorded a rare complication, the herniation of a small portion of omentum through the 8 - mm defect used for the caudal robotic port. The evidence synthesis shows excellent postoperative outcomes for both laparoscopic and robot-assisted laparoscopic pyeloplasties in HSK patients. Probably, MIP should be preferred to the traditional open approach in these patients, when feasible. CONCLUSIONS: Transperitoneal robotic pyeloplasty is an excellent minimally invasive choice for the treatment of UPJO in HSK pediatric patients. The pediatric setting should prompt attention to every detail to avoid unfortunate complications.

Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a "de novo" Von Hippel-Lindau syndrome.

INTRODUCTION: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. CASE PRESENTATION: A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. CONCLUSIONS: This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria.RFA appears to be safe in terms of oncological radicalism and in renal function preservation.In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

Radiofrequency Ablation for Renal Cancer in Von Hippel-Lindau Syndrome Patients: A Prospective Cohort Analysis.

INTRODUCTION: Management of renal-cell carcinoma (RCC) in patients with Von Hippel-Lindau syndrome (VHL) represents a clinical dilemma: the oncologic outcomes must be weighed against preservation of renal function. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small-size RCC. The aim of this study was to evaluate the safety, complications, and functional and oncologic outcomes of RFA in the treatment of RCC in VHL patients. PATIENTS AND METHODS: RCCs were treated with ultrasound-guided RFA or with laparoscopic RFA. Clinical and radiologic response, disease recurrence, and survival outcomes were evaluated during follow-up. Early and late complications were recorded and graded. RESULTS: Nine RCC patients underwent RFA. The median number of RCCs per patient was 3 (interquartile range, 2-4). Among these 9 patients, a total of 20 RCCs were treated by RFA (19 ultrasound-guided RFA and 1 laparoscopic procedure). Median RCC size was 2.5 cm (interquartile range, 2.0-3.0). RFA did not impair renal function (P = .35). In 2 cases disease persisted, and in 1 case disease recurred after 18 months. These patients were retreated with ultrasound-guided RFA with complete response and no renal function impairment. RFA treatment was overall well tolerated and safe. No complications were recorded. Postoperative stay was no longer than 1 day. CONCLUSION: RCC occurred in about two-thirds of VHL patients, who had young age at presentation; it was frequently multifocal and recurrent. The use of RFA, with extended indications, could represent a tailored treatment for VHL patients, reducing the risk of renal failure and resulting in satisfying oncologic results.

Hyperthermia for non-muscle invasive bladder cancer.

Recurrent non muscle invasive bladder cancer (NMIBC) represents a therapeutic challenge, especially in the case of Bacillus Calmette Guerin (BCG)-failures. Chemohyperthermia (CHT) has been tested as adjuvant therapy in selected categories of patients with promising results. The aim of this systematic review is to explore the current role of CHT and its future perspectives. The review process was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. After the selection process, 30 articles were used in this review. Treatment with CHT is safe and quite well tolerated. CHT seems to be effective in low and intermediate risk bladder cancer. Moreover CHT could be offered to selected categories of high risk patients and BCG failures NMIBC. Further trials are needed in order to better identify the categories of patients which could benefit from this therapy and to standardise the right schedule of treatment.

Proteomic identification of Reticulocalbin 1 as potential tumor marker in renal cell carcinoma.

Renal cell carcinoma (RCC) biomarkers are necessary for diagnosis and prognosis. They serve to monitor therapy response and follow-up, as drug targets, and therapy predictors in personalized treatments. Proteomics is a suitable method for biomarker discovery. Here we investigate differential protein expression in RCC, and we evaluate Reticulocalbin 1 (RCN1) use as a new potential marker. Neoplastic and healthy tissue samples were collected from 24 RCC patients during radical nephrectomy. Seven specimens were firstly processed by proteomic analysis (2-DE and MALDI-TOF) and 18 differentially expressed proteins from neoplastic and healthy renal tissues were identified. Among them, RCN1 was over-expressed in all cancer specimens analyzed by proteomics. Consequently RCN1 use as a potential marker was further evaluated in all 24 donors. RCN1 expression was verified by Western blotting (WB) and immunohistochemistry (IHC). WB analysis confirmed RCN1 over-expression in 21 out of 24 tumor specimens, whereas IHC displayed focal or diffuse expression of RCN1 in all 24 RCC tissues. Thus RCN1 appears as a potential marker for clinical approaches. A larger histopathological trial will clarify the prognostic value of RCN1 in RCC. BIOLOGICAL SIGNIFICANCE: The present work aimed at finding new biomarkers for RCC - a life-threatening disease characterized by high incidence in Western countries - by performing differential proteomic analysis of neoplastic and normal renal tissues obtained from a small cohort of RCC patients. Some of the identified proteins have been previously associated to renal cancer however data confirming the possible use of these proteins in clinical practice are not available to date. By IHC we demonstrated that RCN1 could be easily employed in clinical practice, confirming RCN1 over-expression in RCC tissues of all examined patients, and weak protein expression in healthy renal tissues only in correspondence to the renal tubule section. These data indicate a promising role of RCN1 as a possible marker in RCC and indicate the proximal convoluted renal tubule as a putative origin point for RCC. Since IHC staining displayed different grades of intensity in tested tissues, we hypothesized that RCN1 could also be employed as a prognostic marker or as a response predictor for RCC-targeted therapy. To test such a hypothesis, a larger retrospective trial on paraffin-embedded tissues obtained from radical or partial nephrectomy of RCC patients is planned to be performed by our group.

CT findings in primary pulmonary lymphomas.

PURPOSE: To describe the CT findings of pathologically confirmed primary pulmonary lymphomas. MATERIALS AND METHODS: The CT examinations of 11 patients with pathologically proven primary pulmonary lymphoma (9 BALT lymphomas and 2 non-BALT lymphomas) were retrospectively reviewed by three radiologists. Evaluated findings included morphology (consolidation, mass, nodule), number and distribution of lesions. Other CT findings such as air bronchogram, lymphadenopathy, atelectasis and pleural effusion were also assessed. RESULTS: Pulmonary lesions were depicted as airspace consolidation (pneumonia-like) in 5 patients (45%), tumour-like rounded opacity in 4 (36%), and nodules in 4 (36%). Multiple and bilateral lung lesions were seen in 3 patients (27%). Air bronchogram was present in 7 patients (63%), lymphadenopathy in 3 (27%), atelectasis in 4 (36%) and pleural effusion in only 1 (9%). CONCLUSIONS: Our results agree with previous studies regarding lesion patterns and their relative frequency. A smaller number of nodules and multiple lesions were found compared with some previous studies. The most frequent pattern was airspace consolidation.