Impact of a delayed presentation to the emergency department for acute renal colic on biochemical and clinical outcomes.

INTRODUCTION AND OBJECTIVE: To verify the impact of delay on biochemical and clinical outcomes for patients presenting to the emergency department (ED) with acute renal colic. MATERIALS AND METHODS: Data were retrospectively collected from three institutions of two European countries between 01 January and 30 April 2020. Patients who presented to the ED with unilateral or bilateral renal colic caused by urolithiasis confirmed by imaging tests during the study period were included. A presentation after 24 h since the onset of symptoms was considered a delay. Patients presenting before 24 h from the symptom onset were included in Group A, while the patients presenting after 24 h in Group B. Clinical and biochemical parameters and management were compared. RESULTS: A total of 397 patients who presented to ED with confirmed urolithiasis were analyzed (Group A, n = 199; Group B, n = 198. The median (IQR) delay in presentation was 2 days (1,5-4). At presentation, no statistically significant differences were found amongst the two groups of patients regarding presenting symptoms such as fever and flank pain, and the median serum levels of creatinine, C reactive protein and white blood cells. No differences were found in terms of conservative or operative management. CONCLUSION: Delay in consultation >24 h is not associated with worsening biochemical parameters and clinical outcomes. Most patients with acute loin pain do not necessarily need urgent attendance to the ED and may be managed in the outpatients.

Impact of COVID-19 on birth rate trends in the Italian Metropolitan Cities of Milan, Genoa and Turin.

OBJECTIVES: The COVID-19 pandemic has led to major changes in the lives of people worldwide, including changes in personal and social habits. Faced with this global health emergency, governments have imposed strict mitigation measures. Within this context, and considering data from previous epidemics, it has been proposed that birth rates may have been negatively impacted. This study aimed to assess the trends in birth rates in three main industrial cities in Northern Italy during the COVID-19 pandemic. STUDY DESIGN: This was a retrospective and observational study. METHODS: Data on birth rates were collected and compared for the cities of Milan, Genoa and Turin from November 2019 to January 2020 (i.e. before the COVID-19 pandemic) and during the same period of the following year (i.e. during the COVID-19 pandemic). RESULTS: Birth rates in the cities of Milan, Genoa and Turin decreased by 55%, 12% and 33%, respectively. CONCLUSIONS: The decrease in birth rates during the COVID-19 pandemic in these three industrialised cities is in line with the demographic effects of previous pandemics. The negative impact of COVID-19 on conception may be a result of various underlying factors. Further studies are required to verify how social and demographic factors may influence birth rates during pandemics.

Assessment of trends and clinical presentation in the emergency department of patients with renal colic during the COVID-19 pandemic era. / Evaluación de las tendencias y presentación clínica de pacientes con cólico nefrítico que acuden al servicio de urgencias durante la era pandémica del COVID-19.

INTRODUCTION: We hypothesized that the recent COVID-19 pandemic may lead to a delay in renal colic patients presenting to the Emergency Department due to the fear of getting infected. This delay may lead to a more severe clinical condition at presentation with possible complications for the patients. MATERIAL AND METHODS: Retrospective review of data collected from three institutions from Spain and Italy. Patients who presented to Emergency Department with unilateral or bilateral renal colic caused by imaging confirmed urolithiasis during the 45 days before and after each national lockdown were included. Data collected included patients' demographics, biochemical urine and blood tests, radiological tests, signs, symptoms and the therapeutic management. Analysis was performed between two groups, Group A: patients presenting prior to the national lockdown date; and Group B: patients presenting after the national lockdown date. RESULTS: A total of 397 patients presented to Emergency Department with radiology confirmed urolithiasis and were included in the study. The number of patients presenting to Emergency Department with renal/ureteric colic was 285 (71.8%) patients in Group A and 112 (28.2%) patients in Group B (p<0.001). The number of patients reporting a delay in presentation was 135 (47.4%) in Group A and 63 (56.3%) in Group B (p=0.11). At presentation, there were no statistical differences between Group A and Group B regarding the serum creatinine level, C reactive protein, white blood cell count, fever, oliguria, flank pain and hydronephrosis. In addition, no significant differences were observed with the length of stay, Urology department admission requirement and type of therapy. CONCLUSION: Data from our study showed a significant reduction in presentations to Emergency Department for renal colic after the lockdown in Spain and Italy. However, we did not find any significant difference with the length of stay, Urology department admission requirement and type of therapy.

Treatment options and predictive factors for recurrence and cancer-specific mortality in bladder cancer after renal transplantation: A multi-institutional analysis. / Opciones terapéuticas y factores predictivos de recurrencia y mortalidad cáncer-específica en pacientes con tumor vesical después de trasplante renal: análisis multiinstitucional.

OBJECTIVES: Bladder cancer (BC) in the transplanted population can represent a challenge owing to the immunosuppressed state of patients and the higher rate of comorbidities. The objective was to analyze the treatment of BC after renal transplant (RT), focusing on the mode of presentation, diagnosis, treatment options and predictive factors for recurrence. MATERIAL AND METHODS: We conducted an observational prospective study with a retrospective analysis of 88 patients with BC after RT at 10 European centers. Clinical and oncologic data were collected, and indications and results of adjuvant treatment reviewed. The Kaplan-Meier method and uni- and multivariate Cox regression analyses were performed. RESULTS: A total of 10,000 RTs were performed. Diagnosis of BC occurred at a median of 73 months after RT. Median follow-up was 126 months. Seventy-one patients (81.6%) had non-muscle invasive bladder cancer, of whom 29 (40.8%) received adjuvant treatment; of these, six (20.6%) received bacillus Calmette-Guérin and 20 (68.9%) mitomycin C. At univariate analysis, patients who received bacillus Calmette-Guérin had a significantly lower recurrence rate (P=.043). At multivariate analysis, a switch from immunosuppression to mTOR inhibitors significantly reduced the risk of recurrence (HR 0.24, 95% CI: 0.053-0.997, P=.049) while presence of multiple tumors increased it (HR 6.31, 95% CI: 1.78-22.3, P=.004). Globally, 26 patients (29.88%) underwent cystectomy. No major complications were recorded. Overall mortality (OM) was 32.2% (28 patients); the cancer-specific mortality was 13.8%. CONCLUSIONS: Adjuvant bacillus Calmette-Guérin significantly reduces the risk of recurrence, as does switch to mTOR inhibitors. Multiple tumors increase the risk.

European temporal trends in the use of lymph node dissection in patients with renal cancer.

BACKGROUND: The role of lymph node dissection (LND) in renal cell carcinoma (RCC) is still under debate. We aimed to assess the utilization rates of LND over time in Europe. METHODS: A multi-institutional database of 13,581 RCC patients who underwent radical nephrectomy (RN) or nephron sparing surgery (NSS) between 1988 and 2014 was created within an European consortium. We analysed temporal trends in the frequency of LND by using Joinpoint regression. Logistic regression models were used to identify predictors of LND. RESULTS: Overall, 5114 patients (42.7%) underwent LND. Lymph node invasion was recorded in 566 cases (11% of LND patients) which represents 4.7% of the whole study cohort. A gradual decline in the use of LND started in the 1990s. After 2008 LND decreased significantly by 21.5% per year (95%CI -33.3 to -7.5, p < 0.01) until 2011 and stabilized thereafter (Annual Percentage Change 4.9%, 95%CI -3.4 to 13.8, p = 0.2). At multivariable analyses, patient age (OR 0.98, p < 0.0001), type of surgery (RN vs. NSS: OR 5.46, p < 0.0001), surgical approach (open vs. minimally invasive: OR 1.75, p < 0.0001), T stage (T2 vs. T1: OR 1.57; T3-4 vs. T1: OR 1.44, p < 0.0001), clinical tumour size (OR 1.14, p < 0.0001), and year of surgery (OR 0.95, p < 0.0001) were associated with higher probability of LND at nephrectomy. CONCLUSIONS: A trend towards lower LND was observed over time for RCC patients who underwent RN or NSS. LND is more frequently performed in younger patients, locally advanced diseases and in case of open surgery.

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. RESULTS: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. CONCLUSION: Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

PURPOSE: According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. METHODS: To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. RESULTS: CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. CONCLUSIONS: According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.

A snapshot of nephron-sparing surgery in Italy: a prospective, multicenter report on clinical and perioperative outcomes (the RECORd 1 project).

INTRODUCTION: Nephron-sparing surgery (NSS) has become the standard of care for the surgical management of small and clinically localized renal cell carcinoma (RCC). The conservative management of those RCCs is increasing over time. Aim of this study was to report a snapshot of the clinical, perioperative and oncological results after NSS for RCC in Italy. MATERIAL AND METHODS: We evaluated all patients who underwent conservative surgical treatment for renal tumours between January 2009 and December 2012 at 19 urological Italian Centers (RECORd project). Perioperative, radiological and histopathological data were recorded. Surgical eras (2009 vs 2012 and year periods 2009-2010 vs 2011-2012) were compared. RESULTS: Globally, 983 patients were evaluated. More recently, patients undergoing NSS were found to be significantly younger (p = 0.05) than those surgically treated in the first study period, with a significantly higher rate of NSS with relative and imperative indication (p < 0.001). More recently, a higher percentage of procedures for cT1b or cT2 renal tumours was observed (p = 0.02). Utilization rate of open partial nephrectomy (OPN) constantly decreased during years, laparoscopic partial nephrectomy (LPN) remained almost constant while robot-assisted partial nephrectomy (RAPN) increased. The rate of clampless NSS constantly increased over time. The use of at least one haemostatic agent has been significantly more adopted in the most recent surgical era (p < 0.001). CONCLUSIONS: The utilization rate of NSS in Italy is increasing, even in elective and more complex cases. RAPN has been progressively adopted, as well as the intraoperative utilization of haemostatic agents and the rate of clampless procedures.

Middle and long-term outcomes of dual kidney transplant: a multicenter experience.

INTRODUCTION: Dual kidney transplantation (DKTx) to reduce the disparity between demand and supply of organs was evaluated in two Italian centers (Bari and Novara). MATERIALS AND METHODS: Between October 2000 and October 2011, we performed 97 DKT (26 ipsilateral/71 bilateral) following routine biopsy of all kidneys obtained from expanded criteria donors by Remuzzi-Karpinsky scores. The reference group was 379 single grafts from donors older than 60 years single kidney transplantation ([SKT] × > 60). RESULTS: Good postoperative renal function was observed in 56 DKTx (57.7%); whereas acute tubular necrosis requiring dialysis was observed in 41 (42.3%) patients. After a mean follow-up of 60 months, DKTx graft survivals were 96%, 93%, and 90% and patient survivals, 96%, 91%, and 91% at 1, 3, and 5 years, respectively. Complications in expanded criteria donor kidney transplantations included a high rate of cytomegalovirus (CMV) disease especially dual kidney cases. DKTx represented the only independent risk factor for CMV disease upon multivariate analysis (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.28-4.2; P = .006). We did not observe any significant difference in graft or patient survival between DKTx and SKTx > 60 years. CONCLUSIONS: We observed good outcomes up to 5 years after transplantation in terms of graft and patient survival despite the use of inferior grafts. Comparing DKTx and SKT > 60, we noted that the mean Karpinski score for SKTx was significantly better than DKTx, although patient and graft survivals were similar. This trend confirms that the use of a biopsy to allocate expanded criteria donor kidneys may be too protective; therefore, the criteria to select DKTx require further refinement.

The current TNM staging system of renal cell carcinoma: are further improvements needed?

Objective of the study is to review the current 7th edition of the TNM classification of renal tumors and to perform a critical analysis of the recent evidence in order to identify the limitations of this new staging system. A search of the english literature was performed through the Medline and Pubmed database using the following keywords: renal cell carcinoma, staging system and TNM. Overall, 2600 references were initially scrutinized. Forty papers were selected based on their pertinence with the topic of the review, level of evidence provided and overall contribution to the field. Few changes have been made in the current version of the TNM staging system of renal tumors. pT2 tumors have been divided in 2 subgroups based on tumor size with a cut-off at 10 cm; the invasion of the renal vein was classified as pT3a; finally, the invasion of the ispsilateral adrenal gland was classified as pT4. However, other changes were suggested by the analysis of the recent literature and have not been introduced in this new version. Further improvements of the TNM classification for renal tumors are needed especially with regard to locally advanced tumors and node-positive disease, in order to improve the accuracy of this important prognostic tool in renal oncology.

Sexual function in women undergoing hemodialytic treatment assessed using the female sexual function index (FSFI) and the somatic inkblot series (SIS) test.

AIMS: Female sexuality in end-stage renal disease has so far only been explored using non-validated tools. The aim of this study was to compare sexual function among hemodialyzed (HD) patients and healthy controls using validated questionnaires. MATERIAL: Two internationally validated tests have been administrated: the female sexual function index (FSFI) questionnaire and a set of tables from the somatic inkblot series (SIS) test which focus specifically on the area of sexuality. METHODS: 25 consecutive HD patients were assessed for sexual function using the FSFI. Nine SIS inkblots concerning sexuality were also administered to obtain more detailed information about the psychological component of sexuality. An equal number of control healthy volunteers perfectly matched for age, marital status and educational level underwent the same evaluations, and the results of the two groups were compared. RESULTS: HD patients had significantly lower scores than the controls for all FSFI domains except sexual desire even when stratified by age and marital status. All sexually related thematic areas of the SIS except body perception were significantly affected in the HD group compared to the control group. CONCLUSIONS: Chronic renal failure requiring HD treatment adversely affects female sexual function. The psychological impact on patients is significant when compared to an age-matched control group. Both the FSFI questionnaire and the SIS test may be considered useful tools for an integrated medical and psychological screening of FSD.

Proposal of an improved prognostic classification for pT3 renal cell carcinoma.

PURPOSE: The prognostic accuracy of the current TNM 2002 staging system for locally advanced renal cell carcinoma has been questioned. To contribute to the development of a more accurate classification for this stage of disease we assessed the correlation between patterns of invasion in the pT3 category and outcomes in a large multi-institutional series. MATERIALS AND METHODS: Pathological data and clinical followup on 513 pT3 renal cell carcinoma cases treated with radical nephrectomy between 1983 and 2005 at 3 Italian academic centers were retrospectively reviewed. Cause specific survival rates were calculated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Estimated overall 5-year cause specific survival was 50.1% at a median followup of 61.5 months in survivors. The current TNM classification was not a significant outcome prognosticator. Patients with a tumor invading only the perirenal or sinus fat were at lowest risk for death from the disease. Patients at intermediate risk had tumors with invasion of the venous system alone. Simultaneous perirenal fat and sinus fat invasion or perirenal fat and vascular invasion as well as adrenal gland involvement characterized high risk tumors. Low risk tumors could be further divided into 2 groups with different outcomes based on a size cutoff of 7 cm. Our classification was a significant predictor of survival on multivariate analysis as well as M stage, N stage, Fuhrman grade and tumor size. CONCLUSIONS: We confirm that the prognostic usefulness of the current 2002 TNM system for pT3 renal cell carcinoma is limited. We have identified 4 groups of tumors with distinct patterns of invasion and significantly different survival probabilities in this category. Large prospective series are needed to validate these findings.

Radical prostatectomy.

The management of prostate cancer is one of the core tasks for urologists today. Radical prostatectomy represents a valid therapeutic option for the curative treatment of localised prostate cancer. Urologists are on a continuous search for development of technical modifications and refinements, to reduce morbidity and ameliorate clinical and quality of life outcome. This review focuses on the clinical aspects of preoperative patient selection, the current trends of different surgical techniques and the indication of an adequate lymphadenectomy.

Immune response in prostate cancer.

Surprisingly perhaps for a tumor where there is such clear proof of a primary hormonal basis to its development, there is emerging evidence that all elements playing a key role in prostate cancer somehow affect the host immune system. This review turns the spotlight on some previously unsuspectable aspects, able to interact with the immune system in prostate cancer patients PSA, sex hormones, inflammatory infiltrates, cytokines, growth factors, neoformed blood vessels, neurotransmitters and neurotrophins, cigarette smoking, diet, therapeutic approaches. The concept of exploiting the immune system to combat cancer is not new, but only nowadays immunotherapy is a reality. Prostate cancer is an excellent target, involved in an increasing number of clinical immunotherapeutic trials. The main current purpose is to overcome the host immune tolerance of tumor cells. The most recent progresses in gene, monoclonal antibody and vaccine therapies are reported.

Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease.

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07-1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06-1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials.

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.