Natural History and Outcome of Hepatic Vascular Malformations in a Large Cohort of Patients with Hereditary Hemorrhagic Teleangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality. AIM: This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients. METHODS: We analyzed 16 years of surveillance data from a tertiary hereditary hemorrhagic telangiectasia referral center in Italy. We considered for inclusion in this study 502 consecutive Italian patients at risk of hereditary hemorrhagic telangiectasia who presented at the hereditary hemorrhagic telangiectasia referral center and underwent a multidisciplinary screening protocol for the diagnosis of hereditary hemorrhagic telangiectasia. Of the 502 individuals assessed in the center, 154 had hepatic vascular malformations and were the subject of the study; 198 patients with hereditary hemorrhagic telangiectasia and without hepatic vascular malformations were the controls. Additionally, we report the response to treatment of patients with complicated hepatic vascular malformations. RESULTS: The 154 patients were included and followed for a median period of 44 months (range 12-181); of these, eight (5.2%) died from VM-related complications and 39 (25.3%) experienced complications. The average incidence rates of death and complications were 1.1 and 3.6 per 100 person-years, respectively. The median overall survival and event-free survival after diagnosis were 175 and 90 months, respectively. The rate of complete response to therapy was 63%. CONCLUSIONS: This study shows that substantial morbidity and mortality are associated with liver vascular malformations in hereditary hemorrhagic telangiectasia patients

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Indication to Open Anatrophic Nephrolithotomy in the Twenty-First Century: A Case Report

Introduction. Advances in endourology have greatly reduced indications to open surgery in the treatment of staghorn kidney stones. Nevertheless in our experience, open surgery still represents the treatment of choice in rare cases. Case Report. A 71-year-old morbidly obese female patient complaining about occasional left flank pain, and recurrent cystitis for many years, presented bilateral staghorn kidney stones. Comorbidities were obesity (BMI 36.2), hypertension, type II diabetes, and chronic obstructive pulmunary disease (COPD) hyperlipidemia. Due to these comorbidities, endoscopic and laparoscopic approaches were not indicated. We offered the patient staged open anatrophic nephrolithotomy. Results. Operative time was 180 minutes. Blood loss was 500 cc. requiring one unit of packed red blood cells. Hospital stay was 7 days. The renal function was unaffected based on preoperative and postoperative serum creatinine levels. Stone-free status of the left kidney was confirmed after surgery with CT scan. Conclusions. Open surgery can represent a valid alterative in the treatment of staghorn kidney stones of very selected cases. A discussion of the current indications in the twenty-first century is presented

Retroperitoneal Urinoma Spontaneously Drained in the Scrotum Repaired with Gracilis Muscle Flap: A Case Report

Aim. To report a unique case of retroperitoneal urinoma extending to the scrotum through the spermatic cord and successfully treated with nephrostomy, drainage, and gracilis muscle flap

Adenoviral receptor expression of normal bladder and transitional cell carcinoma of the bladder

The insertion of absent or underexpressed genes into cancer cells to alter their malignant phenotype is an important potential application of available gene therapy technology. One of the more common viral vector systems that has been extensively studied for this purpose are the replication-deficient adenoviruses (Ad). Adenoviral infection of cells is mediated through a complex pathway, initiated following viral-cell attachment. Adenoviral-cell attachment occurs following interactions with a 46-kDa transmembrane protein with high affinity for both the Coxsackie and adenovirus, designated the CAR (Coxsackie and adenoviral receptor). Additional important cell-viral interactions that occur involve the alpha(v)-based integrins, specifically alpha(v)beta3 and alpha(v)beta5. The purpose of the present study was to determine the extent of expression and localization of the known Ad receptor proteins (CAR, alpha(v)beta3, and alpha(v)beta5) in normal and cancerous human bladders. Frozen tissue samples of normal bladder and invasive transitional cell cancers of the bladder were evaluated. Tissue blocks containing muscle-invasive transitional cell carcinoma (TCC) were obtained following radical cystectomy, which were performed at our institution. Thirty-two invasive transitional cell bladder tumors were evaluated, each with a matched sample of histologically normal-appearing bladder used as a control. Four additional samples of normal bladder were obtained from patients with no evidence of disease of the bladder and served as further controls. Three additional cases of invasive bladder cancer with no matching normal tissue were also evaluated. Identification of the CAR receptor was performed using the anti-CAR mouse monoclonal antibody designated RmBC. The integrins alpha(v)beta3 and alpha(v)beta5 were identified using the mouse monoclonal antibodies designated LM609 and P1F6 respectively. All slides were evaluated by two of the authors (M.B., B.B.) without knowledge of the clinical and pathological data. Normal bladder: Normal bladder mucosa demonstrated a marked positivity for CAR in 29/35 (82.8%) cases. In contrast, normal transitional epithelial cells were uniformly negative when tested for the integrins alpha(v)beta3 and alpha(v)beta5. Subepithelial tissues, specifically the connective tissue components of the lamina propria and deep muscle wall of the bladder, were positive for alpha(v)beta3 and for alpha(v)beta5 in 61 and 75% of samples, respectively. Endothelial cells associated with the various layers throughout the bladder uniformly expressed both integrins and served as a consistent internal control for both antibodies. An almost identical staining pattern of the endothelium was observed using LM609 and P1F6 in all samples tested. Bladder transitional cell carcinoma: CAR immunoreactivity against TCC cells was uniformly decreased compared to normal transitional cells. Nine tumors exhibited a weak positivity for CAR while the remaining samples were negative. In some cases, the absence of CAR positivity was associated with histological evidence of carcinoma in situ. In 6 cases, it led to the identification of small regions of carcinoma in situ that were not noted on primary pathological evaluation. Peritumoral connective tissue expressed both integrins in the majority of cases, similar to the pattern described above for normal bladder. Transitional cell cancers demonstrated a similar pattern of expression of alpha(v)beta5, in which all tumor cells exhibited minimal or no staining. The success of all viral-mediated gene therapy strategies relies on the ability of the vector to efficiently deliver its genetic material to a target cell population. In the current study, we demonstrate that the bladder epithelial layer consistently expresses high levels of CAR. Deeper layers of the epithelium also express CAR, including the basal layer cells. A decrease in the expression of CAR appears as an early event in bladder carcinogenesis. We observed that both alpha(v)beta3 and alpha(v)beta5 are strongly expressed in muscle cells surrounding the neoplastic cells, as well as within the peritumoral connective tissue. In cases of invasive bladder cancer that have lost CAR expression, an adenoviral vector may still be utilized through the less efficient interactions with the integrins. Bladder tumor tissue may be less susceptible to an adenoviral-mediated gene therapy approach in which a significant percentage of tumor cells require transduction. Adenoviral uptake by tumor or peritumoral cells with subsequent gene transfer could be predicted by the level of CAR and alpha(v)-based integrin expression. This would enhance our ability to identify those patients whose tumors would be more susceptible to Ad-mediated gene delivery as part of an antitumor treatment

Retrograde placement of ureteral stent and ureteropelvic anastomosis with two running sutures in transperitoneal laparoscopic pyeloplasty: Tips of success in our learning curve

Purpose: We report our experience of transperitoneal laparoscopic dismembered pyeloplasties describing our step-by-step surgical technique, and we retrospectively analyze the impact on operative times of technical modifications that were introduced during the learning curve. Patients and Methods: From November 2002 to May 2008, 84 consecutive patients with ureteropelvic junction (UPJ) obstruction were selected for laparoscopic pyeloplasty (LP). The main steps of the surgical procedure are described. In the initial 14 patients who underwent LP, we performed intraoperative antegrade stenting, and we configured the ureteropelvic anastomosis with interrupted sutures; in the 25 following patients, anastomosis was performed with running sutures. In the latest 45 patients, the ureteral stent was positioned retrograde, and ureteropelvic anastomosis was performed with two running sutures. We evaluated the impact of technical modifications on the operative times, dividing patients into three groups (group A, first 14 patients; group B, following 25 patients; and group C, last 45 patients). Median operative times of each group were compared with the Student t test. Results: No major complications ccurred, while postoperative urinary leakage was seen in three patients at bladder catheter removal (two in group A and one in group B). Mean operative blood loss was 70mL, and mean hospital stay was 1.6 days. Median operative time was 115min (range 110-125min) for group A, 100min (range 95-115min) for group B, and 85min (range 65-95min) for group C; differences between operative times of groups A and B and between groups B and C were statistically ignificant (both P<0.001). At a median follow-up of 38 months, recurrent symptoms developed in three patients. Overall, the success rate of the procedure was 96.5%. Conclusion: In a retrospective analysis of our series, the retrograde placement of the ureteral stent and the ureteropelvic anastomosis with two running sutures seemed to be tips of success in reducing operative times. © 2009 Mary Ann Liebert, Inc

Endovesical instillation of platelet rich fibrin for treatment of interstitial cystitis: case report of two patients

Interstitial cystitis, also called painful bladder syndrome, is a chronic condition causing bladder pain and sometimes pelvic pain. The exact cause of interstitial cystitis is not known. Often, signs and symptoms are hard to elucidate and no single treatment works for everyone. We report two cases of patients affected by interstitial cystitis treated with endovesical instillation of platelets rich fibrin (PRF). PRF is an autologous component that promotes angiogenesis, tissue growth and repair. This report presents the safety and the efficacy of PRF instillations in controlling clinical symptoms and restoring quality of life

Can re-cTURBT be useful in pT1HG disease as a risk indicator of recurrence and progression? A single centre experience

Introduction: Understaging after initial transurethral resection is common in patients with high-risk non muscle infiltrating bladder cancer (NMIBC) and can delay accurate diagnosis and definitive treatment. The rate of upstaging from T1 to T2 disease after repeated transurethral resection ranges from 0 to 28%, although the rate of upstaging may be even higher up to 49% when muscularis propria is absent in the first specimen. A restaging classic transurethral resection of bladder tumour (re-cTURBT) is the better predictor of early stage progression. According to some reports, the rate of positivity for tumor in re-cTURBT performed within eight weeks after initial cTURBT was as high as 18-77%, and in about 40% of the patients a change in tumor stage was reported. We aimed to investigate, in high risk group, the presence of residual tumor following white light classical transurethral resection of bladder tumor (WLre-cTURBT) and the different recurrence and progression rate between patients with persistent or negative (pT0) oncological disease after WLre-cTURBT. Materials and methods: A cohort of 285 patients presenting with primitive bladder cancer underwent to WLcTURBT from January 2011 to December 2015; out of them 92 (32.28%) were T1HG. In according to EAU guidelines 2011, after 4-6 weeks all HG bladder cancer patients underwent a WL recTURBT . All patients were submitted to a subsequent followup including cystoscopy every 3 months with multiple biopsies, randomly and in the previous zone of resection; urinary citology on 3 specimens and kidney/bladder ultrasound every 6 months. The average follow-up was 48 months. Results: Following WLre-cTURBT we observed a persistent disease in 18 (15.2%) patients: 14 (77.7%) with a HG-NMIBC and 4 (22.2%) with a high grade (HG) muscle invasive bladder cancer (pT2HG). After follow up of all 92 patients according to the guidelines EAU, we observed recurrence in 36/92 (39.1%) and progression in 14/92 (15.2%). Of 14 NMIBC with persistent disease, 10 patients (71.4%) showed recurrence: 4 patients (40%) were pT1HG with concomitant carcinoma in situ (CIS), 3 patients (30%) multifocal pTaHG, 2 (20%) patients CIS and one patient (10%) a muscle invasive neoplasm (pT2HG). Instead of the group of 48 patients pT0 following WL recTURBT, we observed recurrence in 26 patients (54.1%) and in two patients (4.1%) progressions, who presented after 3 months in association with CIS. The remaining 22 patients (45.9%) with initial pT1HG are still progression free. Multivariate analysis showed that the most important variable of early progression were persistent neoplasm and histopathological findings at WLre-cTURBt (p = 0.01), followed by the Summary No conflict of interest declared. INTRODUCTION Bladder cancer is a common genito-urinary malignancy, with transitional cell carcinoma comprising nearly 90% of all primary bladder tumours. At the first diagnosis 70% to 80% of urothelial tumours are confined to the epithelium, the remainder is characterized by muscle invasion. A significant number of patients with high risk non-muscle invasive bladder tumours (HG-NMIBT) treated with white light classic transurethral resection of bladder tumours (WLcTURBT) and intravesical BCG will progress to invasive disease (1-3). Progression to muscle invasion (pT2) mandates immediate radical cystectomy (4). WLcTURBT is the standard initial therapy for NMIBT, but the high percentage of recurrence after surgery is still an unresolved problem (5). High grade pT1 bladder neoplasm (pT1HG) really represents a therapeutic challenge due to the high risk of progression (about 15-30%) to muscle-invasive disease, usually within 5 years (6). However, no consensus exists regarding the treatment of patients with recurrent bladder tumours that invade the lamina propria (pT1) (7-9). Recent studies suggested that the first cTURBT may be incomplete in a significant number of cases (10). Understaging at the time of the initial transurethral resection is common for patients with high-risk NMIBC and can delay accurate diagnosis and definitive treatment. It is therefore recommended for patients with high-risk disease and in those with large or multiple tumors or when the initial transurethral resection is incomplete, to repeat WLre-cTURBT within 2-6 DOI: 10.4081/aiua.2017.4.272 result of the first cystoscopy (p = 0.002) and presence of CIS (p = 0.02). Discussion: Following WLre-cTURBt in HG-NMIBC patients we identified in 15% of cases a persistent disease with a 4.3% of MIBC. In the high risk persistent bladder neoplasms group we observed recurrent and progression rate higher than in T0 bladder tumours group (Δ = + 17.3% and = Δ + 62.5%, p < 0.0