Renal cell carcinoma: the population, real world, and cost-of-illness.

BACKGROUND: The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC's cost-of-illness for this tumour's clinical pathway. METHODS: This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis. RESULTS: The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages. CONCLUSIONS: This observational study provides real-world and valuable estimates of RCC's cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs' evaluation.

Peripheral primitive neuroectodermal tumor of seminal vesicles: is there a role for relatively aggressive treatment modalities?

A 50 year old white man received an incidental ultrasound diagnosis of hypoechoic mass interesting the right seminal vesicle. A CT scan showed the presence of a 7.8 cm roundish cyst, originating from the right seminal vesicle. He had been followed by the removal of the right seminal vesicle and both the cystic lesion. The histological findings of the specimen documented the presence of small round cells compatible with Ewing's sarcoma/PPNET. The patient received also adjuvant chemotherapy and radiation treatment. After 10 years, the follow-up is still negative.

Estimated Direct Costs of Renal Cancer by Stage of Disease at Diagnosis and Phase of Its Management: A Whole-Disease Model.

BACKGROUND: Renal cell carcinoma (RCC) is the seventh most common neoplasm in high-income countries. New clinical pathways have been developed to deal with this tumor, which includes costly drugs that pose an economic threat to the sustainability of healthcare services. This study provides an estimate of the direct costs of care for patients with RCC by stage of disease (early vs. advanced) at diagnosis, and disease management phase along the pathway recommended by local and international guidelines. MATERIALS AND METHODS: Considering the clinical pathway for RCC adopted in the Veneto region (north-east Italy) and the latest guidelines, we developed a very detailed "whole-disease" model that covers the probabilities of all potentially necessary diagnostic and therapeutic actions involved in the management of RCC. Based on the cost of each procedure according to the Veneto Regional Authority's official reimbursement tariffs, we estimated the total and average per-patient costs by stage of disease (early or advanced) and phase of its management. RESULTS: In the first year after diagnosis, the mean expected cost of a patient with RCC is €12,991 if it is localized or locally-advanced and reaches €40,586 if it is advanced. For early disease, the main cost is incurred by surgery, whereas medical therapy (first and second line) and supportive care become increasingly important for metastatic disease. CONCLUSION: It is crucially important to examine the direct costs of care for RCC, and to predict the burden on healthcare services of new oncological therapies and treatments, as the findings could be useful for policy-makers planning the allocation of resources.

Phosphatidylethanol in Maternal or Neonatal Blood to Detect Alcohol Exposure during Pregnancy: A Systematic Review.

BACKGROUND: Alcohol consumption during pregnancy, even at low doses, may damage the fetus. Pregnant women tend to underreport their alcohol consumption generating the need for sensitive and specific biomarkers, among which PEth has emerged due to its high specificity and possibility to be measured in both maternal and neonatal blood. The aim of this study is to systematically review the latest 20 years of literature for depicting the state of the art, the limitations, and the prospects of PEth for estimating alcohol consumption during pregnancy. MATERIALS AND METHODS: A systematic search, adhering to PRISMA guidelines, of the latest 20 years of literature through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science, with time limits 1 January 2002-1 March 2022, was performed. The inclusion criteria were as follows: PEth used for detecting alcohol consumption during pregnancy, quantified in blood through liquid chromatography coupled to mass spectrometry, and full texts in the English language. Opinion papers, editorials, and narrative reviews were excluded. RESULTS: Sixteen (16) papers were included in the present review (0.81% of total retrieved records). All the included records were original articles, of which there were seven prospective cohort/longitudinal studies, six cross-sectional studies, two observational-descriptive studies, and one retrospective study. All studies assayed PEth in at least one biological matrix; seven (7) studies quantified PEth in maternal blood, seven studies in newborn blood, and only two studies in both maternal and neonatal blood. In several included papers, PEth proved more sensitive than self-reports for identifying pregnant women with an active alcohol intake with the diagnostic efficiency improving with the increase of the maternal alcohol intake. CONCLUSIONS: Further studies, performed on wider and well-stratified populations, are needed to drive any definitive conclusion. PEth is a promising marker for monitoring alcohol use in pregnancy; however, at the present time, its use is still limited mainly by the absence of a globally agreed interpretative cut-off, the paucity of data regarding its specificity/sensitivity, and the lack of standardization on the diagnostic efficiency of the different isoforms.

Metastasis to the renal hilum from malignant melanoma of the anterior trunk: an unusual finding.

A retroperitoneal metastasis from malignant melanoma is an uncommon event and mostly secondary to a primary lesion of the posterior trunk. We report on a 38-year-old patient with malignant melanoma of the anterior trunk who presented a symptomatic metastatic mass of the left renal hilum not originating from the retroperitoneal lymph nodes of the renal hilum, surrounding and infiltrating the renal pelvis, treated with left nephrectomy, complete mass excision and regional lymph node dissection. The patient later developed also brain metastases and is now undergoing immunotherapy.

Disseminated intravascular coagulation secondary to metastatic prostate cancer: case report and review of the literature.

Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with metastatic prostate cancer. We report a case of a 60-year-old white man who was admitted in our department with ecchymoses and haematuria secondary to a DIC associated with metastatic prostate cancer. A review of this clinical scenario is also reported.

Progression, risk factors and subsequent medical management of symptomatic benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a chronic common disease in many men and is often associated with bothersome lower urinary tract symptoms (LUTS). In many men the disease presents with a progressive course that can result in complications such as acute urinary retention (AUR) and BPH-related surgery. Several factors have been associated with progression such as age and prostate volume (PV). Serum prostate-specific antigen (PSA) level, closely correlated with PV is another useful parameter for determining the risk of BPH progression. Medical therapy is the first and the most frequently used treatment for BPH; surgical treatments represent a second-line option when medical therapy is non effective or when complications are associated. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. 5alpha-reductase inhibitors (5ARIs) display their effectiveness at long distance decreasing PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of dutasteride and Tamsulosin (CombAT), at a pre-planned 2-year analysis, has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment. PubMed database has been used to identify publications on the epidemiology of BPH, risk factors for BPH progression and drug treatment options for the management of BPH.

Immunotherapy and urothelial carcinoma: An overview and future prospectives.

BACKGROUND: Urothelial carcinoma (UC) is a common malignancy with a high mortality rate when metastatic. Traditionally, systemic therapy consisted in platinum-based regimens as first-line, with Taxanes or Vinflunine as further lines. Recently, checkpoint inhibitors (CPIs) immunotherapy has emerged as a new therapeutic option. METHODS: We searched in Medline, Pubmed and ClinicalTrial.gov databases for the relevant literature, reviewing the results of published trials and the design of ongoing studies involving CPIs in UC. RESULT: Strong evidence supports the use of CPIs after failure of Cisplatin-based chemotherapy, although no predictive parameter is available so far. Expression of Programmed-Death-1-Ligand has given conflicting results, and is currently indicated only for the selection of Cisplatin-ineligible patients who should receive CPIs. CONCLUSION: The therapeutic landscape of UC is rapidly changing due to the availability of CPIs. Neoadjuvant trials with CPIs and trials combining two CPIs are promising and will further expand the use of immunotherapy.

Inhibition of prostate efferent neurotransmission by amikacin.

BACKGROUND: It has been suggested that manipulation of the autonomic nerve supply to the prostate leads to loss of functional and structural integrity of the gland, and that these changes may be useful in treating prostatic diseases. This study investigates the effect of amikacin on prostate efferent neurotransmission in vitro, in both rat and human prostate samples. METHODS: Prostate samples, obtained from male Wistar rats and 8 patients undergoing endoscopic surgery for benign prostatic hyperplasia, were studied by measurement of isometric contraction induced by electrical field stimulation (EFS), noradrenalin, carbachol, serotonin and ATP, in the presence or absence of amikacin 10(-3) M in a low-Ca medium. RESULTS: Amikacin significantly reduced EFS-induced contraction of isolated rat and human prostate samples by 45 +/- 6.5% (P < 0.01) and 47 +/- 6% (P < 0.01), respectively. Contraction was restored after addition of calcium chloride 2 x 10(-3) M. Amikacin-induced relaxation in rat prostate samples was greater than the effect of magnesium and weaker than those of prazosin and verapamil, but comparable in extent with the latter. No significant effect was observed on rat prostate contractile response to noradrenaline as to ATP in the presence of amikacin. Rat prostate contraction to carbachol and serotonin was inhibited by 35 +/- 11% (P < 0.05) and 59 +/- 11.7% (P < 0.01), respectively, after addition of amikacin 10(-3) M. CONCLUSIONS: Amikacin reduces in vitro both rat and human prostate contraction elicited by pre-junctional stimulation, but does not affect prostate contraction evoked by post-junctional stimulation. Our results indicate that amikacin affects prostatic efferent neurotransmission.

New therapeutical approaches for non muscle invasive bladder cancer.

Non muscle invasive bladder cancer, given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical and histology features. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo-immunotherapies are obtaining new vitality as optimization strategies, while new drugs and rational drug combinations provide the potential for improved efficacy with reduced toxicity. Novel therapeutic modalities under investigation include activation of the host immune system and enhancement of the cytotoxic effects of chemotherapeutic agents. New technological advances such as microwave chemothermotherapy offer further hope for better outcomes even for disease previously refractory to conservative measures. While much of this research is in the preclinical phase, the encouraging results of many of the studies discussed here suggest that testing in human trials should follow in the coming years. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures. Although great strides continue to be made each year in the diagnosis and management of bladder cancer considerably more work needs to be done in order to improve the lives of our patients with this disease.

Oligometastatic recurrent prostate cancer detects by fluorine-18-choline positron emission tomography/computed tomography in patients with prostate-specific antigen levels of up to 5 ng/ml.

PURPOSE: The aim of this study was to assess the ability of fluorine-18-fluorocholine (F-FCH) PET/computed tomography (CT) to detect oligometastatic disease (OMD) in patients with early recurrence of prostate cancer (PC) [prostate-specific antigen (PSA)≤5 ng/ml]. PATIENTS AND METHODS: Between 2010 and 2016, 324 patients with PC and PSA levels of less than or equal to 5 ng/ml were recruited. The mean (SD) age of the patients was 71 (10) years. All patients were treated with a radical prostatectomy±lymphadenectomy. One-hundred and twenty-one patients were under hormonal therapy at the time of PET/CT, whereas 203 were not. The mean (SD) PSA at the time of PET/CT was 1.33 (1.19) ng/ml, the mean (SD) PSA doubling time (PSAdt) was 10 (12) months, and the mean (SD) PSA velocity (PSAvel) was 1.94 (3.31) ng/ml/year. The correlation between continuous and categorical data was assessed using Student's t-test or by analysis of variance and by the χ-test, respectively. Univariate and multivariate analysis was carried out for the identification of clinical variables able to predict the presence of OMD. RESULTS: One-hundred and ninety-three patients had a negative F-FCH PET/CT, whereas 131 (40.4%) had a positive scan. Of these latter patients, 35 had a significant F-FCH uptake in the prostatic fossae, 59 in the lymph nodes, and 37 in bone. PSA levels were significantly different between patients with a positive than those with a negative scan (P<0.001). F-FCH PET/CT was negative in the majority of patients with a PSA of less than or equal to 1 (63.2%) ng/ml. More than 60% of patients with a PSAdt of less than or equal to 6 months had a positive F-FCH PET/CT scan for OMD. PSAvel was higher in patients with a positive scan than those with a negative finding. At univariate analysis, PSA level, PSAdt, and PSAvel were predictors of a positive F-FCH PET/CT for OMD, whereas on multivariate analysis, only PSA level and PSAdt were independent predictors (both P<0.01). Furthermore, PSAdt was the only independent predictor of OMD at the lymph node level. CONCLUSION: In patients with early recurrence of PC, F-FCH PET/CT is able to detect OMD in 40% of cases. This finding has an important impact on the detection of PC recurrent lesions that could be treated by local therapy to achieve long-term survival or cure.

Von Hippel-Lindau disease: an evaluation of natural history and functional disability.

BACKGROUND: Although many studies have been published about specific lesions characterizing von Hippel-Lindau(VHL) disease, none have dealt with the natural history of the whole disease and the consequent disabilities. We aim to define the comprehensive natural history of VHL disease and to describe the functional disabilities and their impact upon patients' quality of life, thereby tailoring the follow-up schedule accordingly. METHODS: We performed a prospective analysis on 128 VHL-affected patients beginning in 1996. For each affected organ, we defined intervals between the first and subsequent VHL-related manifestations and compared them with current VHL surveillance protocols. We looked for any association of the number of involved organs with age, sex, type of VHL gene mutation, and functional domain mutation. Ultimately, we assessed the organ-specific disabilities caused by VHL disease. RESULTS: Hemangioblastomas show different patterns of progression depending on their location, whereas both renal cysts and carcinomas have similar progression rates. Surgery for pheochromocytoma and CNS hemangioblastoma is performed earlier than for pancreatic or renal cancer. The number of involved organs is associated with age but not with sex, type of VHL gene mutation, or functional domain mutation. A thorough analysis of functional disabilities showed that age is related to the first-appearing functional impairment, but it is not predictive of the final number of disabilities. CONCLUSIONS: Our study defines the disease progression and provides a comprehensive view of the syndrome over time. We analyzed for the first time the functional disability of VHL patients, assessing the progression for each function.

Recurrent nephrogenic adenoma in bladder diverticulum: Case report and literature review.

Nephrogenic adenoma is an uncommon benign lesion of the urinary tract induced by chronic irritation of the vesical mucosa, due to infection, trauma, surgery, calculi, foreign bodies and chemical agents. A 68-year-old male was admitted to our linic for a periodical cystoscopic evaluation as part of a follow-up initiated due to a past transitional cell carcinoma. The scheduled cystoscopy revealed, within a bladder diverticulum, an unexpected and completely asymptomatic nephrogenic adenoma that we removed by transurethral resection. We followed up the patient at 24 months, then later we made the diagnosis of nephrogenic adenoma. During this time, the patient experienced three relapses within the same diverticulum, always involving a nephrogenic adenoma we persistently treated by transurethral resections. As the nephrogenic adenoma is considered a benign lesion without any direct evidence of a possible evolution to an overt cancer, we successful attempted a half-yearly cystoscopic follow-up to control the growth of a highly recurrent benign entity, interposing between controls a periodical imaging. This paper represents the second report of a nephrogenic adenoma within a bladder diverticulum, but the first case of a nephrogenic adenoma highly recurrent within the same diverticulum and managed conservatively by regular transurethral resection scheduled over the time.

Postoperative nomogram for invasive bladder cancer: does it really work? A multicenter cohort study.

OBJECTIVES: Nomograms are statistical models designed to maximize predictive accuracy. We have tested the statistical correlation between the predictions of International Bladder Cancer Nomogram Consortium and the clinical outcomes in a multicenter Italian cohort of patients treated with radical cystectomy (RC) and pelvic lymph-nodes dissection. METHODS AND MATERIALS: Two hundred four patients who underwent RC were selected for multiple variable and then enrolled in the study. Patients were tested by the "online tool" based on the nomogram, then stratified and risk grouped for 5-year predicted disease-free survival (pDFS): low risk (67%-100%), intermediate risk (34%-66%), and high risk group (0%-33%). Receiving operating characteristic curve (ROC) quantified the area under curve (AUC) as predictive accuracy. Actual overall survival (aOS) and actual disease-free survival (aDFS) were calculated with Kaplan-Meyer analysis. Median of pDFS was compared with 5-year aDFS. RESULTS: AUC was 0.69 (P < 0.001). The aOS is 50% (95% confidence interval (95% CI, -7.68/+8.23) at 5-years after RC, the aDFS is 65.5% (95% CI, -7.56/+8.98). The 5-year aDFS is 75.3% (-8.82/+12.53) in low risk group; 67.3% (-12/+16.4) in intermediate risk group; 28.3% (-20/+17.2) in high risk group. The 5-year aDFS was well calculated by the nomogram but in all groups the nomogram slightly underestimated the prediction. In intermediate risk group, 5-year aDFS overscored both the nomogram pDFS and the pDFS range of this group (34%-66%). In all patients investigated, the pDFS was 65%, a value close to the 5-year aDFS found (65.6%). CONCLUSION: Statistical correlation between postoperative nomogram prediction and the clinical reality was observed.

Renal hemangiopericytoma: case report and review of the literature.

Hemangiopericytoma is an uncommon perivascular tumor that occurs most frequently in the pelvis, head and neck, and meninges; it is extremely rare in the kidney. We report a kidney hemangiopericytoma in a 43-year-old woman who was treated with a nephron-sparing surgery and review the literature.

Histotopographic study of the rectourethralis muscle.

Radical perineal prostatectomy, relative to retropubic prostatectomy, has become an increasingly used surgical technique for prostate cancer, following advances in laparoscopic methods for pelvic lymph node dissection. Recent protocols of risk stratification may even obviate the need for lymph node dissection. Section of the rectourethralis muscle (RUM) is necessary for access to the retroprostatic space, however, during this procedure rectal injuries may be produced. In this work, we studied the topography and morphology of the RUM, which, despite its importance in perineal surgery, has not been univocally described in the literature. After in situ formalin fixation, the pelvic viscera were removed from 16 male cadavers (age: 54-72 years) and from 4 full-term infants (gestational age: 37-38 weeks). Serial macrosections of the bladder base, prostate gland, and lower rectum cut in horizontal (6 adults and 2 infants) and sagittal (6 adults and 2 infants) planes underwent histological (hematoxylin and eosin, azan-Mallory, and Weigert's staining) and immunohistochemical (anti-smooth muscle actin and anti-sarcomeric actin) study. The remaining 4 adult specimens were cut in horizontal and sagittal planes and plastinated using the epoxy resin E12 sheet procedure. RUM was identified in 10 of 12 (83%) adult specimens and in 4 of 4 (100%) infant specimens. In both sagittal and transverse sections, it showed a triangular-shaped configuration. In all cases, at the level of its posterior portion, fibers continuing with the longitudinal muscular layer of the rectum were visible. In the majority of adult and infant cases, attachment of muscle fibers into the anterior wall of the anal canal was also observed. Anteriorly, the mean (+/-SD) distance between the RUM and the membranous urethra was 5.3 (+/-1.25) mm in adults and 1.0 (+/-0.41) mm in infants. Location of RUM in the prerectal space and the absence of urethral attachment makes the original name of this muscle, "prerectal," by Henle, more correct. In 7 of 10 (70%) adult cases and in 1 of 4 (25%) infant cases, muscle fibers were densely packed along the lateral portions of the RUM, while in its central portion connective tissue was prevalent, with sparse numbers of smooth muscle fibers. Immunohistochemical staining showed that this muscle consists almost entirely of smooth fibers. In all the infant specimens, the RUM was clearly separated from the levator ani, while in 8 of 10 (80%) adult cases, striated fibers of the levator ani and smooth fibers of the RUM intermingled. These structural associations suggest a functional cooperation between the two muscles, particularly in determining the anorectal flexure.

Histotopographic study of the rectovaginal septum.

The rectovaginal septum (RVS) is described as a strong connective tissue between the rectum and the vagina. The aim of the present study was to investigate the topography and histological structure of the RVS in 20 cadavers (age range: 54-72 years). After in situ formalin fixation, the pelvic viscera and the surrounding connective tissue were removed, together with the pelvic floor. In 8 cases, the topographical relationships of the septum with the vagina and rectum were studied during dissection. In 8 other cases, serial macrosections of the bladder base, vagina, lower rectum and pelvic floor complex were stained with hematoxylin-eosin, azan-Mallory and Weigert Van Gieson. RVS thickness was evaluated on transverse sections collected at the cranial and caudal levels of the middle third of the vagina (level II) and inferior third (level III). In the other 4 cases, specimens were cut with a slicer in 2-3 mm thick axial slices and plastinated using the von Hagens E12 technique. The RVS is located in an oblique coronal plane, close to the posterior vaginal wall, and is formed of a network of collagen, elastic fibres, smooth muscle cells with nerve fibres, emerging from the autonomic inferior hypogastric plexus, and variable numbers of small vessels. The RVS was thicker at cranial levels II and III, with respect to caudal level II, both in the midline (1.75 and 1.70 vs 0.2 mm, p<0.05) and lateral portions of the septum (2.67 and 2.64 vs 0.17 mm, p<0.05). At caudal level II, there was no statistically significant difference between the thicknesses of the lateral portions and the midline (0.17 vs 0.2 mm, P>0.05). The RVS resembles an hourglass, with a flattened central portion in the frontal plane. Given its position in the centre of the pelvis, the RVS plays a connecting role between the perineal body and the overlying portions of the endopelvic fascia, and may also play an active role in modulating the tone of the musculature of the pelvic walls during variations in endorectal pressure.