Urologic surgery in a safe hospital during the COVID-19 pandemic scenario.

BACKGROUND: The COVID-19 pandemic induced a global emergency that overwhelmed most hospitals around the world. Access to hospitals has been restricted to selective oncological and urgent patients to minimize surgeries requiring Intensive Care Unit care. All other kind of non-urgent and benign surgeries have been rescheduled. The burden of oncological and urgent cases on the healthcare system has increased. METHODS: We have been asked to become the referral center for major oncological and urgent urological surgeries, increasing our surgical volume. Through meticulous hospital protocols on PPE, use of nasopharyngeal swabs, controlled hospital access and the prompt management of suspected/positive cases, we were able to perform 31% more urological surgical procedures during the COVID-19 pandemic compared to the same period in 2019. RESULTS: We observed a 72% increase in oncological surgical procedures and 150% in urgent procedures. CONCLUSIONS: Our experience shows how the management of oncological and urgent cases can be maintained during unexpected, global emergencies, such as COVID-19.

A protein corona sensor array detects breast and prostate cancers.

Following exposure to human plasma (HP), nanoparticles (NPs) are coated with a biomolecular layer referred to as a protein corona. We recently revealed that characterizing the protein coronas of various NPs may provide a unique opportunity for cancer identification and discrimination. In other words, protein corona profiles of several NPs, when being analyzed using classifiers, would provide a unique "fingerprint" for each type of disease. Here, we probed the capacity of the protein corona for the identification and discrimination of breast and prostate cancer patients from healthy individuals. Using three lipid NP formulations with distinct physical-chemical properties as a cross-reactive sensor array and a supervised random forest classifier, we identified a set of proteins that showed a significant difference in cancer patients and control subjects. Our data show that many of the corona proteins with the highest discrimination ability between oncological patients and healthy individuals are related to cellular and molecular aspects of breast and prostate cancers.

Endoscopic Intravesical Fibrin Glue Application in the Treatment of Refractory Hemorrhagic Radiation Cystitis: A Single Cohort Pilot Study.

OBJECTIVE: To evaluate the clinical value of endoscopic fibrin glue (FG) application therapy in treating hemorrhagic radiation cystitis (HRC). PATIENTS AND METHODS: This is a single-cohort, prospective pilot study. We collected data from patients with HRC who were treated at our urology unit from May 2014 to December 2016. Patients with grade ≥2 HRC for whom conventional therapy and transurethral endoscopic electrocoagulation had failed were treated with endoscopic intravesical FG. The mean follow-up was 26.2 ± 9.78 months. Our analysis included data on patient demographics, pelvic malignancies, radiotherapy regimens, total dose of radiation received, time of onset and severity of hematuria, and previous intravesical management. Following FG intervention, patients' clinical status was defined as: (1) clinical response; absence of dysuria, urgency, and frequency; discontinuation of analgesic medication; and Foley catheter removal, but with ongoing hematuria grade <2; (2) complete response, clinical response, and no further hematuria; or (3) no response, no clinical response, and sustained hematuria. RESULTS: A total of 20 patients (12 women and 8 men; mean age, 69 ± 7.5 years) were treated with 12 mL FG intravesically, using endoscopic application. Of the 20 patients, 16 (80%) had a complete response and 4 (20%) had a clinical response. In the case of four patients (20%), treatment was carried out twice. Mean hospital stay was 6 ± 2.5 days. The intervention showed good tolerability in all patients. No major adverse events were reported. Bladder spasms were the only minor adverse events reported in six patients (30%). CONCLUSION: Application of FG is an effective, practical, affordable, and repeatable procedure for the treatment of grade ≥2 HRC.

Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma.

The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma).A tumor-specific DNA methylation of the KEAP1 gene promoter region was found as a specific feature of the ccRCC subtype (18/37, 48.6%) and a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment. Analysis of an independent data set of 481 ccRCC and 265 PRCC tumors corroborates our results and multivariate analysis reveals a significant correlation among ccRCCs epigenetic KEAP1 silencing and staging, grading and overall survival.Our molecular results show for the the first time the epigenetic silencing of KEAP1 promoter as the leading mechanism for modulation of KEAP1 expression in ccRCCs and corroborate the driver role of Keap1/Nrf2 axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma.

Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation.

Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting.

PURPOSE: Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. METHODS: Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samples were collected at the following times: T0 (before the first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and CEC/CEP levels were directly quantified by flow cytometry at all these time points. RESULTS: Our analyses highlighted a significant reduction of mean percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day 3) and p = 0.012 (at day 84), respectively]. CONCLUSION: These preliminary results demonstrate that ZOL could exert an antiangiogenic effect in early prostate cancer through CEP and CEC modulation.

Surgical treatment of locally advanced anal cancer after male-to-female sex reassignment surgery.

We present a case of a transsexual patient who underwent a partial pelvectomy and genital reconstruction for anal cancer after chemoradiation. This is the first case in literature reporting on the occurrence of anal cancer after male-to-female sex reassignment surgery. We describe the surgical approach presenting our technique to avoid postoperative complications and preserve the sexual reassignment.

Early and late urodynamic assessment of Padua ileal bladder.

OBJECTIVES: To report the data from a single series of 46 patients who underwent cystectomy and Padua ileal bladder (PIB) substitution during a 48-month period. Data are lacking concerning the changes in urodynamic characteristics of the orthotopic ileal neobladder. METHODS: From January 2002 to April 2003, 46 consecutive male patients underwent radical cystectomy and PIB substitution for muscle-invasive bladder cancer. Uroflowmetry, cystometry, and urethral pressure profilometry were analyzed at 12 and 48 months after surgery. All patients were asked to complete a questionnaire regarding quality of life (the European Organization for Cancer Research and Treatment of Cancer Quality of Life Questionnaire and the bladder cancer-specific module). RESULTS: Of the 46 patients, 8 were lost to follow-up because of cancer-related death. When comparing the 12- and 48-month urodynamic characteristics, no significant changes were observed in cystometric capacity or urethral closing pressure. However, the end-filling pressure, peak flow pressure, and postvoid residual urine volume were significantly lower at the 48-month evaluation (P = .0005, P = .0007, and P = .013, respectively). The number of involuntary contractions at 48 months had increased significantly (P = .0012), and the amplitude of the contractions was comparable (P = .084). The daytime continence rate was 96% and 90% at 12 and 48 months, respectively. The nighttime continence rate was 60% at the 48-month evaluation. The questionnaires about the quality of life highlighted the excellent results. CONCLUSIONS: An ileal tone is maintained despite detubularization and most likely prevents enlargement of the neobladder. PIB was revealed to maintain an adequate capacity and low pressure during a 48-month period. The urodynamics results and quality of life support this urinary diversion as a valid treatment option for muscle-invasive bladder cancer.

Fibrin glue for refractory hemorrhagic cystitis after unrelated marrow, cord blood, and haploidentical hematopoietic stem cell transplantation.

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) are particularly exposed to the risk of developing hemorrhagic cystitis (HC), which is characterized by symptoms ranging from macroscopic hematuria to renal failure. Although HC significantly affects the quality of life and in a few cases becomes intractable leading to patient death, its therapeutic management has not been established. Fibrin glue (FG), a hemostatic agent derived from human plasma, has been largely employed in different surgical settings including urologic procedures. STUDY DESIGN AND METHODS: In this pilot study we used FG to treat refractory HC. During cystoscopy, bladder distension was maintained at a constant pressure of 12 mmHg by a carbon dioxide insufflator. An endoscopic applicator allowed spraying FG on the bleeding and raw surfaces of bladder mucosa. RESULTS: Five of 221 patients undergoing an HSCT developed a very severe, refractory HC and have been treated with endoscopic FG. The treatment was successful in 3 patients; the response was partial in 1 patient and transient in the last one, whose clinical course was severely complicated by acute graft-versus-host disease and multiple organ failure. CONCLUSIONS: FG therapy is a feasible procedure and this pilot study suggests that it may be an effective treatment for refractory HC. Its application could be considered also in Grade 1 or 2 HC to prevent progression of damaged mucosa. The use of FG for HC should be prospectively investigated in terms of therapeutic efficacy, transfusion support, length of hospitalization, quality of life, and costs.

Bacteriuria in patients with an orthotopic ileal neobladder: urinary tract infection or asymptomatic bacteriuria?

OBJECTIVE: To investigate the prevalence of asymptomatic bacteriuria (ABU) and urinary tract infection (UTI), and the local and systemic inflammatory response, in patients with ileal neobladder. PATIENTS AND METHODS: The study included 40 patients who had a radical cystectomy and ileal neobladder. Two urine samples, one for chemical and physical analysis, and cytofluorimetry, and one for urine culture, were collected every 3 months for 9 months after surgery. RESULTS: Of 119 urine cultures, 69 (57%) were positive for bacteria. Only nine of the 40 patients had no bacteriuria on urine culture. Escherichia coli strains were cultured from eight of 10 patients with persistently positive urine. The incidence of bacteriuria was different according to gender. There was a high concentration of leukocytes (0-6 microL) in 118 of 119 samples. The mean concentration of leukocytes in sterile urine culture was 1181/microL, while in patients with ABU the mean was 491 (P < 0.05). CONCLUSION: A positive urine culture is a very common finding in patients with an orthotopic bladder. The most interesting results was the absence of elevated inflammatory indices and/or symptoms, even in those patients with high levels of bacteriuria. Probably this is due to the completely different inflammatory response of ileal mucosa against bacteria than has bladder mucosa. Indeed, the leukocyte concentration detected in urinary sediment was inversely association with bacterial growth in urine cultures. These findings suggest a redefinition of ABU and UTI in patients with an orthotopic neobladder.

Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade.

Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P=0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 pattern did not show reelin immunoreactivity, reelin expression was found in 35% Gleason 4 patterns and 45% Gleason 5 patterns (P<0.001). Our results demonstrated for the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may behave as a specific histological marker and may represent a useful biomarker to predict aggressive phenotypic behavior of prostatic cancer cells.

Collagen changes in the ureteropelvic junction after failed antegrade endopyelotomy.

PURPOSE: We evaluated the collagen content and differentiation of the ureteropelvic junction (UPJ) of patients who underwent Anderson-Hynes dismembered pyeloplasty after failure of antegrade endopyelotomy. MATERIALS AND METHODS: A total of 12 UPJ obstructions were examined more than 12 months after endopyelotomy with both histochemical staining to analyze total collagen content and immunohistochemical staining to analyze collagen types I and III. The specimens were compared with 12 primary UPJ obstructions and 6 normal UPJs. Statistical analysis was performed using Fisher's test and Wilcoxon matched-pairs signed-rank test. RESULTS: Immunohistochemical staining revealed that collagen type I was located in the interfascicular space and collagen type III in the intrafascicular space in all UPJs. We found more collagen in obstructed than in normal UPJs. Collagen type III was more abundant in secondary than in primary UPJ obstructions (P < 0.01). In obstruction after endopyelotomy, the staining intensity of collagen type III was greater than the intensity of collagen type I (P < 0.01). CONCLUSION: Our results suggest that the success of antegrade endopyelotomy was impaired by an inflammatory process. This condition determined a shift of collagen differentiation toward type III, which is more fibrous than type I.

Liver harvesting surgical technique for the treatment of retro-hepatic caval thrombosis concomitant to renal cell carcinoma: perioperative and long-term results in 15 patients without mortality.

OBJECTIVE: Radical surgical treatment improves the prognosis of patients affected by Inferior Vena Cava (IVC) thrombosis concomitant to renal carcinoma. However, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable haemorrhages and tumor fragmentation. We report the results of an innovative surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. In the presence of retro-hepatic IVC thrombosis, this technique improves vascular control and allows to perform a large cavotomy with an en-bloc removal of the thrombus and the tumor. METHODS: From January 1995 through June 2003, 15 patients with renal cancer and caval thrombosis were treated at our Institution. Four, ten and one patients were respectively affected by an infrahepatic (Level I), retro-hepatic (Level II) and atrial (Level III) IVC thrombosis. RESULTS: All patients underwent radical surgical treatment. In presence of Level II caval thrombosis, the patients underwent the above reported surgical technique. Perioperative mortality was absent; major morbidity occurred in one patient (6.7%). The thrombus was radically removed in all cases. After a mean follow-up of 53.9 months (5-100 months) all patients but one are still alive. One patient died 9 months after surgery with multiple bilateral pulmonary metastases. CONCLUSIONS: Isolation of the retro-hepatic IVC is a safe and effective manoeuvre to significantly reduce perioperative mortality and morbidity in patients affected by Level II caval thrombosis concomitant to renal carcinoma.

Mutations of the D310 mitochondrial mononucleotide repeat in primary tumors and cytological specimens.

A mononucleotide repeat (D310) in mitochondrial DNA has been recently identified as a mutational hot spot in primary tumors. We analyzed 56 tumors for insertion/deletion mutations in the D310 repeat. A total of 13 mutations were detected. The highest frequency of mutations was found for cervical cancer, followed by bladder tumors, breast cancer and endometrial neoplasia. No alterations were observed in four patients suspected of malignancy but without evidence of malignant tumor. We detected identical changes in four of four urine sediments from patients with bladder cancer and in three of three fine needle aspirates of patients with breast cancer. Our results indicate that D310 abnormalities are detectable in cytology specimens from patients with cancer and support the notion that D310 analysis may represent a new molecular tool for cancer detection.