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Hepatocellular carcinoma (HCC) is the seventh most common cancer worldwide and the second leading cause of cancer-related mortality. HCC typically arises within a cirrhotic liver, but in about 20% of cases occurs in absence of cirrhosis. Among non-cirrhotic risk factors, non-alcoholic fatty liver disease (NAFLD) currently represents the most important emerging cause of HCC in developed countries. It has been estimated that annual incidence of HCC among patients with non-cirrhotic NAFLD is approximately 0.1–1.3 per 1000 patients/year and ranges from 0.5% to 2.6% among patients with non-alcoholic steatohepatitis (NASH) cirrhosis. However, only a few clinical trials enrolling HCC patients actually distinguished NAFLD/NASH-related cases from other non-cirrhotic causes and therefore evidence is still lacking in this subset of patients. This review aims to describe the biology underpinning NAFLD development, to investigate the main molecular pathways involved in its progression to NASH and HCC and to describe how different pathogenetic mechanisms underlying the onset of HCC can have an impact in clinical practice. We hereby also provide an overview of current HCC treatment options, with a particular focus on the available data on NAFLD-related cases in practice-changing clinical trials.

Atopic dermatitis (AD) is characterized by itching or pruritus, erythematous lesions, pruritus, and a skin barrier defect. Repeated scratching can trigger the itch-scratch cycle. Itching is associated with an adverse impact on quality of life. The first-line treatment of AD includes the use of topical corticosteroids for atopic dermatitis. However, parents of children with atopic dermatitis are often reluctant to accept the use of topical corticosteroids due to their concern of adverse effects flare-up. Relizema™ cream is a prescription emollient device (PED) multi-ingredients moisturizer formulation that has been indicated for the treatment of signs and symptoms of dermatitis. It is approved as medical device (MD) class IIa in Europe and it is registered as a topical medical device in countries of Asia Pacific. A consensus meeting of 9 dermatologists from multiple countries in Asia Pacific region treating atopic dermatitis was conducted. The dermatologists presented their cases of atopic dermatitis. PED was reported by patients to offer good relief of symptoms and improve skin softness unlike other moisturizers. In fact, a few patients reported relief with Relizema™ cream after using other moisturizers which were not demonstrating clinical effectiveness. Patients reported they noticed a softness in their skin after the application of the PED. PED was effective even in patients with lichenified skin. The formulation which is enriched with antioxidants helped relieve eczema. Due to its steroid-free formulation, the PED can be continued as a part of long-term maintenance treatment to maintain healthy skin conditions, prolong remission, and prevent recurrence.

Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials.

Background Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. Conclusion Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines., Highlights • To define the best treatment strategy for 1st and 2nd L is crucial for luminal mBC. • 1st L CDK4/6i-based therapies represent the standard treatment in luminal mBC. • This study confirmed the key role of 1st L CDK4/6i on a real-world cohort. • This study suggested a preeminent role for ET after first-line CDK4/6i. • The 2nd line ET with other molecules could allow to further postpone CT.

La bronquiolitis es una patología frecuente en la práctica clínica pediátrica. Constituye una de las principales entidades clínicas dentro de las infecciones respiratorias agudas bajas (IRAB). Se define como el primer episodio de sibilancias con manifestaciones clínicas de infección viral en un niño menor de dos años y afecta principalmente a lactantes menores de 6 meses. El tratamiento es fundamentalmente de soporte con oxigenoterapia e hidratación, quedando el resto de las terapéuticas bajo una profunda controversia acerca de su real efectividad. Metodología: Desde la exposición de un escenario clínico se planteó una pregunta estructurada para luego realizar una búsqueda bibliográfica con el fin de dar respuesta a la pregunta sobre la efectividad en el tratamiento del bronquiolitis con broncodilatadores. Se realizó una búsqueda en PubMed utilizando los Mesh (Medical Subject Headings) "bronchodilators AND bronchiolitis", se aplicaron distintos filtros, tras lo cual se llegó al número final de 23 artículos. Tras una lectura de los títulos y resúmenes de los artículos, se escogió el artículo "Bronchodilators for bronchiolitis". Análisis del artículo: Nos hemos centrado las siguientes variables con el fin de responder a la pregunta clínica: la mejoría en el score clínico, la reducción de la tasa de internación y la saturometría de oxígeno. Realizamos luego un análisis secundario de los datos de las distintas variables con el fin de definir los valores de riesgo relativo (RR), reducción de riesgo absoluto (RRA), reducción del riesgo relativo (RRR) y el número necesario a tratar (NNT) con sus respectivos intervalos de confianza del 95% (IC 95%). También se llevó a cabo un análisis estadístico para evaluar la variable de saturación de oxígeno. Recomendación final: No está recomendado el uso de broncodilatadores en el manejo del bronquiolitis, ya que no mejoran ninguna de las variables analizadas. Los broncodilatadores no sólo no tienen eficacia, sino que suponen un gasto y presentan efectos adversos indeseables

e13008 Background: Liquid biopsy-based biomarkers, including circulating tumor DNA (ctDNA), are increasingly important for the characterization of metastatic breast cancer (MBC). Currently, CA15.3 is the most commonly used serum marker for monitoring disease burden. To date, no liquid biopsy-based biomarkers have been proposed for this scope in clinical practice. Methods: The CRO-2018-56 multicenter study prospectively enrolled 83 patients (pts) with luminal-like MBC treated with first line endocrine therapy (ET) and CDK4/6 inhibitors. All pts were characterized for ctDNA through droplet digital PCR (ddPCR) in from 2018 to 2021. Clinicopathological and laboratory characteristics at baseline were tested for associations with tumor markers, ACTB fragments lengths, methylation status of ESR1 main promoters (expressed as promA and promB ratio, i.e., met_ratio) and ESR1/PIK3CA mutational status through Kruskal-Wallis test and Chi-square test. Prognosis was tested in terms of Progression Free Survival (PFS) and Overall Survival (OS) through log-rank test. Results: At baseline, in 26 (31%) pts disease was diagnosed as de novo metastatic, 66 (80%) pts had < 3 of metastatic sites, and 41 (49%) pts had < 5 of metastatic lesions. Bone metastases were detected in 53 (64%) pts, liver metastases in 21 (25%) pts, and lung lesions in 30 (36%) pts. A ctDNA-detected ESR1 mutation and a PIK3CA mutation were found in 15% of pts and in 34% pts, respectively. Met_ratio was > 1.5 in 35 (42%) of pts. Median CA15.3 was 48.2 U/mL and median CEA was 3.8 U/mL. Number of liver metastases and number of metastatic sites were significantly higher in pts with ESR1 mutation (respectively, P = 0.0055 and P = 0.0208). CA15.3 and ctDNA yield were significantly higher in pts with number of metastatic sites ≥ 3, (respectively, P = 0.0164, and P = 0.0239), while number of metastatic sites ≥ 3 and number of metastatic lesions ≥ 5 were significantly associated with CEA > 3.8 U/mL (respectively, P = 0.039, and P = 0.029). Presence of bone metastases was significantly associated with PIK3CA mutation (P = 0.040), while number of metastatic sites ≥ 3 was significantly associated with ESR1 mutation (P = 0.022). No association with tumor burden was observed for different ACTB DNA fragments lengths. Met_ratio > 1.5 was significantly associated with lower number of metastatic lesions (P = 0.031). Number of metastatic sites ≥ 3, high ctDNA yield and CEA were associated with worse OS (respectively P = 0.0465, P = 0.0250 and P = 0.0474), while only CEA impacted on PFS (P = 0.0097). Conclusions: In pts with luminal-like MBC, some liquid biopsy-based biomarkers (i.e., ctDNA-detected ESR1 and PIK3CA mutations, ctDNA yield) were significantly associated with the burden of disease. The potential clinical validity and utility of these results deserve to be tested in an expansion cohort.

1027 Background: The combination of ET and CDK4/6i is the current standard of care for hormone receptor (HR)-positive/HER2-negative MBC (luminal MBC), with neutropenia being the main dose limiting toxicity. We previously observed the potential association between leucocyte count (WBC) and different fractions of cell free circulating DNA (cfDNA) (Bortot et al 2020). The present study aimed to evaluate the feasibility of a cfDNA-based workflow as a new tool to assess the risk of treatment induced neutropenia. Methods: The study analyzed a prospective cohort 83 luminal MBC patients (pts) treated with first line ET and CDK4/6i in the CRO-2018-56 multicenter study from 2018 to 2021. cfDNA was characterized through droplet digital PCR (ddPCR) based on different ACTB DNA fragments lengths: short (s), medium (m) and long (l). Blood samples were collected before treatment start (BL) and at the first clinical evaluation after 3 months (E1). Associations between clinical characteristics, neutropenia and cfDNA were explored through Kruskal Wallis, time to G3 neutropenia (NG3) (TTN) was analyzed through log-rank and Cox regression. Results: Neutropenia was G3 in 44 out of 83 pts (53%) and G4 in 2 pts (2%). Median TTN was 1.8 months, 60% of NG3 occurred within 3.7 months. Overall, 74 pts (89%) resolved toxicity within 7 days, 10 pts (12%) reduced CDK4/6i dose after NG3. BL neutrophils count (Neu) and WBC were significantly lower in pts that developed NG3 (P = 0.0013 and P = 0.0020 respectively). De novo metastatic pts had numerically higher Neu (median 4825 vs 3895), but only a numerically lower risk of NG3 was observed (HR 0.53 P = 0.064). Although bone involvement was not associated with risk of developing NG3, the total number of metastatic lesions was associated with higher NG3 (P = 0.0016). In particular, > 5 metastatic lesions were associated with higher NG3 risk (p = 0.013). E1 ACTB_m was significantly lower with respect to BL in pts that experienced NG3 (median 100% vs 16%, P = 0.0136 in NG3 no vs yes) with a consistent impact on the risk of NG3 (HR: 2.81, P = 0.025). No associations were observed for the other ACTB fragment length fractions. BL Neu and ACTB_m dichotomized at the median were then combined to describe 4 distinct TTN risk groups (P = 0.0006). Interestingly, pts with low BL Neu and low E1 ACTB_m had a median TTN of 0.9 months, while pts with high BL Neu and high E1 ACTB_m have not experienced NG3 after a median follow-up of 16.1 months. Conclusions: The present study proofed the concept of using cfDNA to provide clinically meaningful data not only about tumor biology, but also for a comprehensive patient assessment. Based on these results, a prospective study focused on a multiparametric neutropenia risk assessment will be started.

This study determined the factors that influenced purchase intention of young consumers in the BPO industry specifically on organic local food. The participants were 18-30 years old in selected cities in the National Capital Region (NCR). The study applied the Theory of Planned Behavior (TPB) and Self-Determination Theory (SDT) as its theoretical framework wherein the researcher extended the TPB by adding (1) value for money and willingness to pay (VM-WP); and (2) consciousness and environmental knowledge (CEK). Purposive sampling method was used in the selection of 5 participants for the in-depth interview which was based on the total sample size of 725 who responded on the online survey using stratified random sampling. Quantitative data were analyzed using PLS-SEM model and Spearman correlation analysis in support of the qualitative data. The findings of the study showed that young consumers in the BPO industry considered purchase intention as an important factor towards green purchasing. The integration of the two theories identified the influence of each factors, the additional variables: VM-WP and CEK has a positive and significant influence towards purchase intention however showed a weak coefficient value. Lastly, young consumers viewed environmental concern, health, and social responsibility as key points why it is essential to practice this mode of purchasing. Keywords: BPO Industry; Green Purchasing; Organic Local Food; Purchase Intention; Self-determination Theory; Theory of Planned Behavior; Young Consumers.

279 Background: In the last years, the introduction of immune checkpoint inhibitors (ICI) in clinical practice translated into major changes in oncology workload. We conducted a study aimed to estimate the shift in workload generated, within 1 year of first consultation, by any new metastatic cancer patient receiving ICI at the Oncology Department of the Academic Hospital of Udine, Italy. Methods: We collected from our electronic accountability system data all new cases of metastatic cancer between 01.01.2017 and 31.12.2018, leading to at least a second clinical episode (treatment sessions, unplanned presentations, hospitalizations, re-evaluations, follow-up, and inpatient oncology advices) during the following year. Patients (pts) were divided into those receiving ICI (anti-CTLA4/PD1/PDL1) versus pts receiving other treatments. Mean number per patient and standard deviation were calculated for clinical episodes, and the mean numbers in each group were compared using Student’s t-test (significance p

Background: The recent COVID-19 outbreak in Italy required timely adoption of efficient triage procedures (TPs) with the aim to minimize the risk of infection spreading in the hospitals We developed a written questionnaire (items explored: fever, respiratory symptoms, previous contacts or personal positivity for COVID-19) together with body temperature (BT) measurement, to intercept patients (pts) with suspect of COVID-19 infection Methods: We conducted a monocentric observational study of a consecutive series of outpatients with diagnosis of solid tumor, accessing the Day Unit of Oncology Department at Udine Academic Cancer Center (Northern Italy) from 30 March 2020 to 30 April 2020 In this abstract we present the preliminary results of the TPs performed until 10 April 2020 Results: 1054 TPs were performed out of 586 pts, with a median of 2 TPs per pt Median age was 64 9 years, males were 35 4% Overall, 82 5% of TPs were made because of access for therapy, 10 7% for programmed procedures, radiological exams or non-oncological consultations, 1 2% for unplanned presentation (e g urgencies) The stage of neoplasm was early in 30 7% and advanced in 69 3% of pts TPs were made in pts receiving chemotherapy (58 2%), immunotherapy (10 8%), targeted therapy (18 9%), other therapies (5 2%) and in pts without active oncological therapy (6 9%) The questionnaires resulted positive in 5 5% of cases;2 9% were positive for fever, 2 9% for respiratory symptoms, 0 1% for previous contact with a case of COVID-19 Concomitant presence of 2 or more items was observed in 0 5% of questionnaires Of note, 6 TPs required medical evaluation despite a negative questionnaire and were considered to be clinically suspect BT≥37°C was observed in 7 TPs Overall, the oncologic program was postponed in 0 9% of the TPs, while in 0 5% a test for SARS-CoV-2 was performed for clinical suspect: no one resulted positive At multivariate analysis, factors associated with positive triage were diagnosis of thoracic cancer (OR 2 06;95%CI 1 02-4 12;p=0 04) and prior test for SARS-CoV-2 (OR 2 81;95%CI 1 46-5 41;p=0 001) Conclusions: A well-structured triage for COVID-19 could reduce the risk for further spreading of infection in Oncology facilities with limited impact on scheduled activities Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: F Puglisi: Honoraria (self): MSD;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Eli Lilly;Honoraria (self): Takeda;Pfizer;Advisory/Consultancy: Amgen;Novartis;Pierre Fabre;Research grant/Funding (self): Astrazeneca;Eisai;Travel/Accommodation/Expenses: Celgene;Servier C Andreetta: Advisory/Consultancy: AstraZeneca;GlaxoSmithKline;MSD A M Minisini: Advisory/Consultancy: Novartis;MSD;Pierre Fabre G Fasola: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb srl;Eli Lilly SpA ;Servier Italia SpA ;Speaker Bureau/Expert testimony: Astrazeneca;Travel/Accommodation/Expenses: Merck Sharp and Dohme S p A ;Boehringer-Ingelheim S p A All other authors have declared no conflicts of interest

e15163 Background: Immune checkpoint inhibitors (ICI), anti CTLA-4 and anti PD-1/PD-L1 agents, have demonstrated an improvement in survival outcome in several malignancies. Therapy with ICI is characterized by immune-related adverse events (irAEs) as a result of exuberant immune system activation. Despite good tolerance for ICI, the potentially severe and life-threatening irAEs underscore the importance of investigating optimal management strategies. Methods: A retrospective series of 130 consecutive patients (pts) treated with ICI from Jan 2012 to Dec 2017 was analyzed. Adverse events with a potential immunological etiology were defined as irAEs and graded according to CTCAE v.4.0. The aim of the study was to evaluate irAEs management in an academic hospital center. Results: Pts with a diagnosis of NSCLC n = 64 (49%), melanoma n = 55 (42%), kidney n = 9 (7%) and others n = 2 (2%) were investigated. Baseline ECOG PS was ≤ 1 in 96% of the pts. ICI represented first line treatment for 27% pts, second line for 57% and third or further line for the remaining 16%. 18% were treated with ipilimumab and 82% with anti PD-1/PD-L1 agents (nivolumab 60%, pembrolizumab 21%, atezolizumab 1%). Overall, 50 (38% of pts) developed an irAE.42% of irAEs were grade 1, 38% grade 2, 14% grade 3 and 6% grade 4. The most frequent irAEs were endocrinopathies in 17 pts (34%), followed by cutaneous toxicity in 9 pts (18%) and colitis and diarrhea in 7 pts (14%). A total of 373 unscheduled accesses were observed, 89 (24%) of them were due to irAEs: 78 were unplanned consultations in the oncology department and 11 in the emergency department. irAEs led to hospitalization in 14 pts for 118 days, cumulatively. Grade ≥ 2 colitis was the most frequent irAE associated with hospitalization, it occurred in 4 pts (29%). Colitis and diarrhea required the longest hospitalization (range 4-31 days). 48% (24 pts) required immunosuppressive treatment. Systemic steroids were the most common immunosuppressive agents used. Only one patient received infliximab as second line immunosuppressive treatment after steroid failure. Totally, irAEs required 67 specialist consultancies and additional diagnostic examinations. 15 pts required ICI discontinuation because of irAEs. Conclusions: In our center prevalence and severity of irAEs were similar to literature data. Considered the complexity of irAEs management, multidisciplinary approach and a trained hospital network plays a key role for a more efficient diagnostic and treatment work-up in pts who received ICI therapy and experienced irAEs.

Resumen Caso clinico Mujer de 38 anos con perdida visual en ojo izquierdo y papiledema bilateral. La resonancia magnetica nuclear (RMN) mostraba engrosamiento de la duramadre y la presion intracraneal estaba elevada. Se descarto enfermedad infecciosa, tumoral y autoinmune. Discusion La respuesta inicial a corticoides fue satisfactoria con desaparicion del edema de disco optico, mejoria de la agudeza visual y mejoria radiologica. Despues de un ano sin tratamiento presento un nuevo brote, desarrollando una neuropatia optica izquierda con perdida irreversible de vision a pesar del retratamiento con corticoides y azatioprina.

Case report A 38-year-old female patient with bilateral papilledema who presented with loss of vision in her left eye. The Magnetic Resonance Imagining (MRI) showed thickening of the dura mater, and the intracranial pressure was elevated. A cancer, infectious origin, and autoimmune origin were ruled out. Discussion The initial response to high doses of corticoids was satisfactory, with disappearance of the optic disk enema, with visual acuity and an improvement in the MRI. However, after one year without treatment she had a new outbreak of the disease. Despite renewed treatment with corticoids and azathioprine, the patient developed a left optic neuropathy and irreversible visual loss.

Thulium laser vaporization of the prostate (TL-PVP) has been performed for almost 10 years. However, there are very few studies focused on high power (150 W) applications. Published sources have short follow-up periods, few cases and small prostatic volumes. In this study, we present an analysis of the safety and efficacy of this technique in the mediumterm (42 months follow-up) perspective.Data from 235 patients that underwent TL-PVP from March 2011 to November 2013 has been collected, including prostatic size, intraoperative variables, IPSS, Qmax, and PSA, among others.Mean age was 69±9 years. Mean prostatic size was 62±28 ml. The average IPSS score and Qmax were 18±16 and 7.6 ± 3.5 ml/s, respectively. Mean hospital stay was 24±17 h. Mean time with urethral catheter was 38 h. Only 26.1% of the patients had perioperative complications but none of the cases was higher than a Clavien III. From this population, no more than 1.7% required readmission. Mean postoperative Qmax after 3 and 24 months was 19±6 ml/s and 17±8 ml/s. IPSS was 5±5 points. A successful outcome was achieved in 81.3% of the patients. Obstructive symptoms persisted in 15.7% of the population and 3% resulted in filling-phase dysfunction. Reoperation rate was 5%. The only statistically significant difference (p=0.008) between successful and unsuccessful outcomes occurred in prostatic size, where mean values calculated were 59.73 ml and 71.82 ml, respectively.In this study, high power TL-PVP is a safe and effective alternative with subjective and objective functional results that are comparable to the "gold standard" technique. It also offers a shorter hospital stay and a lower complication rate.

International audience; PurposeWe evaluated a new single-use digital flexible cystoscope with an integrated grasper designed for double-J stent removal, Isiris™, addressing success rate, image quality, deflection, maneuverability and grasper functionality.MethodsIn September 2015, a prospective cohort study was conducted in six tertiary European reference centers. All consecutive patients included underwent double-J stent removal and were 18 years or older. Success rate was defined by complete stent removal. Image quality, deflection, maneuverability and grasper functionality were rated with a Likert scale.ResultsA total of 83 procedures were performed. 82% of procedures were performed in the endoscopy room, while the others were in the operating room since a consecutive endourological intervention was planned. The median duration of stent implantation was 28 days [14; 60]. In five patients, stent removal was not possible. Four patients had an incrusted double-J stent, and in one patient, the stent migrated into the ureter. After unsuccessful attempts of stent removal with conventional flexible cystoscope and grasper, the five patients had to be scheduled for an ureterorenoscopy procedure to remove the stent. In the other 78 patients, all double-J stents were removed successfully. Image quality, deflection, maneuverability and grasper functionality were rated as “very good” in 72.3, 78.3, 72.3 and 73.5%, respectively.ConclusionThis multicenter clinical evaluation of Isiris™ displayed good image quality, active deflection, maneuverability and grasper functionality. Further evaluation of stent removal outcomes, cost analysis and microbiology will help to delineate the possible place of Isiris™ in the current practice.

Case report An alcoholic patient with loss of vision in his right eye and a peripapillar hemorrhage, who then presented with a venous thrombosis. Blood analysis revealed hyperhomocysteinemia with coagulation parameters within the normal range. In the follow-up he developed a bilateral optic neuropathy. Discussion An increase in homocysteine levels is common in alcoholics, and it has been considered a vascular risk factor. Folic acid and vitamins B 6 and B 12 deficiency may lead to hyperhomocysteinemia, as they participate in its metabolism. Conclusions When presented with a retinal occlusive disease or ischemic optic neuropathy in young patients, coagulation disorders and elevated levels of homocysteine should be ruled out.

Resumen Caso clinico Paciente alcoholico con disminucion de agudeza visual en el ojo derecho, presentando una hemorragia peripapilar temporal superior y, posteriormente, trombosis de subrama venosa. La analitica mostro hiperhomocisteinemia con coagulacion normal. En la evolucion desarrollo una neuropatia optica bilateral. Discusion La elevacion de homocisteina es comun en alcoholicos, considerandose un factor de riesgo cardiovascular. El acido folico y las vitaminas B6 y B12 participan en el metabolismo y su deficit puede incrementar sus niveles. Conclusiones Ante la observacion de fenomenos vasculares oclusivos retinianos y neuropatia optica isquemica en pacientes jovenes, se deben descartar alteraciones en la coagulacion y aumento de homocisteina.

Background Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance. Methods We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. Results Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2-positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing. Conclusions The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background High BMI is associated with better survival in metastatic melanoma patients (MM pts), while sarcopenia is linked to poorer outcome in pts with stage III. The aim of this study was to examine the prognostic impact of body-mass index (BMI), baseline sarcopenia, loss of skeletal muscle mass (LSMM) on overall survival (OS) in MM pts who received immunotherapy (IT). Methods The retrospective series included 42 consecutive MM pts (Jan 2011-Dec 2018) treated with IT in a single referral center. Sarcopenia was defined according to Prado’s criteria. Skeletal muscle index (SMI) was calculated as cross-sectional-area of muscle (cm2), using CT-scan, at the L3 level divided by the square of the height (m2). Early LSMM, during IT, was defined as a decrease in SMI > =10% from baseline at first evaluation. BMI was calculated as weight (kg) divided by the square of height (m2) and categorized according to standard WHO definitions. Weight loss was analyzed as continuous variable. Results At baseline, 27 pts (64,3%) were male, 26 pts (61.9%) were =25. Out of 42 pts, 30 (71.4%) had a CT-scan at first evaluation, and 30% of them had an early LSMM. Median OS was 11.38 months. Both in univariate and multivariate analysis, ECOG PS > =1, and early LSMM > =10% were significantly associated with worse OS. Conversely, pts with weight loss had better OS (Table). Table . 1367P OS univariate analysis OS multivariate analysis Factors HR p 95% Confidence Interval HR p 95% Confidence Interval PS ECOG³1 3.02 0.01 (1.29-7.08) 3.99 0.043 (1.04-15.31) Weight loss 0.88 0.03 (0.78-0.98) 0.85 0.02 (0.74-0.97) Early LSMM > =10% 4.24 0.006 (1.50-11.97) 3.09 0.04 (1.04-9.22) Conclusions Early LSMM > =10% and ECOG PS > =1 may negatively influence the outcome of MM pts treated with IT. Further prospective studies are needed to confirm these data. Legal entity responsible for the study Maria Grazia Vitale. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Patients (pts) with melanoma brain metastases (BM) have a historically poor prognosis, with a reported median overall survival (mOS) of 4-6 months. Aim of this study is to evaluate predictive factors of survival in pts with melanoma BM. Secondly, a multivariate model was used to define groups with distinct prognosis. Methods Consecutive pts with melanoma BM treated in two Italian cancer centers were included in this 10-year retrospective cohort study (2008-2018). Baseline clinicopathological factors, systemic and loco-regional treatments were registered. The Kaplan-Meier method and the Cox model were used to analyze the association of prognostic factors and OS. Results 150 pts with melanoma BM were enrolled in this study: 42% with a single BM, 51.3% with ≥ 3 extracranial metastatic sites and 38% with an ECOG performance status (PS) of 0. About 50.7% of pts had a BRAF mutation. Notably, 56% of pts were asymptomatic at BM diagnosis, and 40% presented high LDH levels at baseline. Overall, mOS after BM diagnosis was 5.78 months (95% CI 4.80-6.67), and median intracranial progression-free survival was 4.63 months (95% CI 3.81-5.12). According to treatment modality, stereotactic radiosurgery/neurosurgery plus systemic therapy showed the best outcome (mOS 12.32 months, 95% CI 7.92-25.30). A multivariate model was used to identify baseline prognostic factors independently associated with OS (Table). Conversely, sex and symptomatic BM did not significantly impact on OS. Predicted survival functions defined 3 distinct prognostic groups (P Table . 1363P Covariates HR 95% CI P Points BRAF wild type 1.95 1.22-3.12 1 BM > 1 2.20 1.35-3.59 1 LDH ≥ 2 x upper normal limit 1.83 1.07-3.11 0.026 1 ECOG PS > 0 2.68 1.62-4.43 0.0001 1 Extracranial metastatic sites ≥ 3 1.91 1.17-3.1 1 Age ≥ 65 1.86 1.15-3.02 0.012 1 Conclusions This score can be useful for stratifying prognosis in pts with melanoma BM. Prospective studies are needed to validate this score and to explore how it may guide treatment strategy. Legal entity responsible for the study Dipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata di Udine. Funding Has not received any funding. Disclosure F. Puglisi: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self): Pierre Fabre; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Takeda; Research grant / Funding (self): Astrazeneca. All other authors have declared no conflicts of interest.

Resumen Caso clinico Mujer de 80 anos intervenida mediante trabeculectomia por glaucoma primario de angulo abierto en la que, debido al incremento tensional, se inicio tratamiento con latanoprost. La monitorizacion de la tension arterial (TA) demostro un incremento estadisticamente significativo de la TA tanto sistolica como diastolica coincidiendo con el uso del hipotensor topico, que se resolvio al suspender voluntariamente el tratamiento, volviendo a elevarse al reintroducir la prostaglandina. Discusion Los analogos de las prostaglandinas disminuyen la presion intraocular al producir vasodilatacion de las arterias ciliares y epiesclerales, aumentando el drenaje del humor acuoso. Los efectos cardiovasculares son poco frecuentes pero se han descrito por el efecto vasoconstrictor que puede desencadenarse como el incremento reversible de la TA de este caso.

Case report An 80 year old woman operated on by trabeculectomy for primary open-angle glaucoma due to increased pressure, who started treatment with latanoprost. Monitoring of blood pressure (BP) showed a statistically significant increase in both systolic and diastolic BP, coinciding with the use of topical hypotensive, which resolved by voluntarily suspending treatment, thus increasing again to reintroduce the prostaglandin. Discussion Prostaglandin analogues reduce intraocular pressure to produce vasodilation of the episcleral and ciliary arteries, increasing the outflow of aqueous humour. Cardiovascular effects are rare, but have been described by the vasoconstrictor effect that can trigger the reversible increase in BP, as in this case.

Resumen Introduccion y Objetivos: el tumor vesical t1g3 constituye el grupo de tumores superficiales mas agresivo. Nuevos factores pronosticos en el campo de la citogenetica y la biologia molecular han sido analizados, con resultados a menudo contradictorios, siendo escasos los trabajos especificos en tumores t1g3. Nuestro objetivo es determinar si en este grupo de tumores los marcadores inmunohistoquimicos presentan valor predictivo de progresion clinicamente util, y por tanto con validez para indicar una actitud terapeutica precoz mas idonea. Material y metodos Estudio retrospectivo de una serie de 83 pacientes afectos de tumor vesical t1g3, sobre los que analizamos un total de 14 variables; entre los nuevos factores predictivos: la determinacion inmunohistoquimica de las proteinas reguladoras del ciclo celular: p53, p21 y bcl-2, asi como la proteina Ki-67 como marcador de proliferacion celular. Mediante analisis de regresion logistica establecemos las variables pronosticas independientes para progression tumoral. Resultados El punto de corte establecido para Ki67 y p53 fue el 40% de celulas inmunomarcadas, 20% para p21 y 10% para Bcl-2. El analisis univariante puso de manifiesto diferentes tasas de progresion y tiempos libres de progression en funcion de la inmunotincion de Ki67 y p53; sin embargo, la regresion logistica demostro que solo la inmunohistoquimica de p53 presentaba valor predictivo independiente. Conclusiones La determinacion inmunohistoquimica de p53 presenta valor predictivo de progresion clinicamente util en tumors vesicales t1g3, de manera que su determinacion puede constituir un factor fundamental en las estrategias de tratamiento de estos tumores.

Objectifs L’objectif de cette etude a ete d’evaluer un nouveau dispositif a usage unique (Isiris®, Coloplast-Porges) concu pour l’ablation des sondes JJ. Methodes Ce dispositif a usage unique consiste en un cystoscope numerique comprenant une pince integree et actionnee par l’operateur afin de saisir la sonde JJ. L’endoscope se connecte a un moniteur portable ( Fig. 1 , Fig. 2 ). Six centres europeens ont participe a cette evaluation prospective. Seize urologues experimentes en endo-urologie ont realises les interventions. Le critere de jugement principal a ete d’evaluer le taux de succes d’ablation des sondes JJ. Les criteres secondaires ont ete d’evaluer la qualite d’image, la manipulation, la deflection, la prehension de la pince et la satisfaction globale (echelle de Likert). Resultats Quatre-vingts ablations de sondes JJ ont ete realisees ( Tableau 1 ). Cinq cas ont ete exclus de l’analyse pour les raisons suivantes : quatre cas de sonde JJ incrustee, un cas ou la sonde avait migre dans l’uretere. Hormis ces derniers cas necessitant une intervention chirurgicale, le taux de reussite a ete de 100 %. Criteres secondaires : – ualite de l’image evaluee comme « tres bonne » dans 72,3 % et « bonne » dans 22,9 % des cas ; – manipulation evaluee comme « tres bonne » dans 72,3 % et « bonne » dans 25,3 % des cas ; – deflection evaluee comme « tres bonne » dans 78,3 % et « bonne » dans 20,5 % des cas ; – prehension de la pince evaluee comme « tres bonne » dans 73,2 % et « bonne » dans 23,2 % des cas ; – satisfaction globale evaluee comme « tres bonne » dans 70,4 % et « bonne » dans 21 % des cas. Conclusion Ce dispositif a usage unique d’ablation des sondes JJ apparait comme une solution satisfaisante et pouvant faire partie de l’arsenal therapeutique de l’urologue.

[EN] There are numerous passive strategies for reducing energy consumption in Spanish traditional vernacular architecture, depending on external conditions and also on the intended use of the interior of these constructions. In the case study analyzed, localized in an interior area of Spain, known as La Mancha, a set of vernacular buildings have been studied. Solar protection and solar gain, for example, are the key resources related to solar control. While cross ventilation, self-ventilation, or induced ventilation are related to the energy efficiency of the airflow. Other mechanisms identified are, for example, thermal insulation and thermal inertia of the materials. All these K-factors have been checked and parameterized in order to understand these vernacular strategies. Finally, thanks to a comparison of such resources, the study achieved a set of criteria for the use of these solutions in contemporary local architecture., The authors would like to thank the European Union framework 7th program for making this work possible via the LIMA project as well as to the following fellowships: The R&D FPI-UPV (P.A.I.D. program of the Universitat Politecnica de Valencia) and the FPU by the Spanish Ministerio de Educacion, Cultura y Deporte.

A 38-year-old female patient with bilateral papilledema who presented with loss of vision in her left eye. The Magnetic Resonance Imagining (MRI) showed thickening of the dura mater, and the intracranial pressure was elevated. A cancer, infectious, and autoimmune origin was ruled out.The initial response to high doses of corticoids was satisfactory, with disappearance of the optic disc enema, with visual acuity and an improvement in the MRI. However, after one year without treatment she had a new outbreak of the disease. Despite renewed treatment with corticoids and azathioprine, the patient developed a left optic neuropathy and irreversible visual loss.

To analyze the results of retrograde intrarenal surgery (RIRS) in patients with ≥2 cm stones treated in our center.A retrospective review of 106 patients with renal calculi underwent RIRS ≥2 cm (period January 2009-December 2011). The procedures were performed under general anesthesia as a source of fragmentation using the holmium laser (30 W Litho Quantasystem) and flexible ureteroscopes (X2 Flex Storz, Olympus P5) through ureteral access sheaths. It discusses demographic variables (age, medical history, antiplatelet or anticoagulant treatment, treatment of urolithiasis, BMI, ASA), treated stones variables (size, number, Hounsfield units, biochemical composition) and intra-and postoperative variables (operative time, number of pulses, hospital stay, complications) with the completion of a descriptive analysis of the same. To define our results we consider success to the complete absence of fragments or residual5 mm posterior imaging tests.The mean stone size was 2.46 cm treated, being the only stone in 87.7% of cases. The most frequent location was the renal pelvis stones (44%) followed by the lower calyx (39%). The postoperative complication rate was 6.7%, with all of little relevance. The success rate with a single procedure was 79.4% to 94.1% with retreatment.RIRS is a valid alternative for the treatment of kidney stones ≥2 cm for its high success rate and few complications if performed in specialized centers.

An 80 year old woman operated on by trabeculectomy for primary open-angle glaucoma due to increased pressure, who started treatment with latanoprost. Monitoring of blood pressure (BP) showed a statistically significant increase in both systolic and diastolic BP, coinciding with the use of topical hypotensive, which resolved by voluntarily suspending treatment, thus increasing again to reintroduce the prostaglandin.Prostaglandin analogs reduce intraocular pressure to produce vasodilation of the episcleral and ciliary arteries, increasing the outflow of aqueous humor. Cardiovascular effects are rare, but have been described by the vasoconstrictor effect that can trigger the reversible increase in BP, as in this case.

To compare the results obtained in percutaneous nephrolithotomy after introduction of flexible ureteroscopy/nephroscopy (endoscopic combined intrarenal surgery - ECIRS) with nephrolitomies with only rigid nephroscopy (standard percutaneous nephrolithotomy; sPCNL).A retrospective study of 171 sPCNL in Galdakao position performed between January 2005 and December 2011 was conducted. We compared the results obtained in those procedures in which endoscopic combined intrarenal surgery (ECIRS) was performed with those in which only the rigid nephroscopy (sPCNL) was used. Specific and global success, percentage of lithiasic load eliminated, days of hospital stay and complications derived were calculated. We defined success by complete absence of lithiasis or residual presence of5mm. We differentiated specific success, that only achieved with percutaneous surgery, from global success, or that achieved after a second line of treatment.In 73 procedures (42.4%) ECIRS was performed with flexible endoscopy while in 98 (57.6%) it was done with sPCNL. Both groups were comparable in regards to demographic parameters and characteristics of the lithiasis. The success rates in the first procedure and global success were superior for the ECIRS group (75.3% vs 40.8% and 93.1% vs 74.5%), the differences being statistically significant (P.05). No statistically significant differences were found in regards to the complications (28.8% vs 28.3% P=.86) or days of hospital stay (4.5 vs 5.0 P=.18).Use of the flexible ureteroscopy/nephroscopy in sPCNL (ECIRS) improves the success rates and elimination of lithiasic load, making it possible to perform the surgery with a single access in most of the cases.

An alcoholic patient with loss of vision in his right eye and a peripapillar haemorrhage, who then presented with a venous thrombosis. Blood analysis revealed hyperhomocysteinemia with coagulation parameters within the normal range. In the follow-up he developed a bilateral optic neuropathy.An increase in homocysteine levels is common in alcoholics, and it has been considered a vascular risk factor. Folic acid and vitamins B6 and B12 deficiency may lead to hyperhomocysteinemia, as they participate in its metabolism.When presented with a retinal occlusive disease or ischemic optic neuropathy in young patients, coagulation disorders and elevated levels of homocysteine should be ruled out.

Set predictors of complications in percutaneous nephrolithotomy (PCNL) using the modified Clavien system.Retrospective study included 172 PCNL in Galdakao position made in the La Ribera Hospital between January 2005 and December 2011. They classified the complications of these procedures using the modified Clavien system. We performed a univariate analysis (Chi(2) Test and Cramer's V) and multivariate (logistic regression) of predictors of these complications (P.05).In 49 of the 172 procedures complications were detected (28.5%).The most frequent complications were grade 1 (9.9%), 12 complications (6.9%) were classified as grade 2 by requiring additional medical treatment, 6 as grade 3A (3.5%), 7 as grade 3B (4.1%), 2 and 4A (1.1%), 4 and 4B (2.3%) and one and 5 (0.6%). In the univariate analysis, positive urine culture before surgery, the stones complex and larger than 40 mm of the same, showed a statistically significant association with the occurrence of complications (P.05). The positive culture (OR: 2.96) and complex stones (OR: 3.03) proved to be independent variables predicting complications in multivariate analysis.Clavien system allows a common language for classifying complications, expressing the degree of the same as the complexity of treatment required for resolution. The preoperative urine culture positivity and complex stone proved predictors of these complications in our serie.

Percutaneous Nephrolithotomy (PCNL) is a technique with good results for the treatment of kidney stones, however, bleeding complications derived can be serious if not diagnosed and treated effectively. The aim of this study is to assess bleeding complications resulting from PCNL in Galdakao position and therapeutic management.Retrospective-longitudinal study of 172 PCNL performed in La Ribera Hospital between January 2005 and December 2011, analyzing their bleeding complications and the treatment provided for resolution.Had bleeding complications 20 patients (11.6%). The need for transfusion in this series was 8.1% and the most common cause of blood transfusion the presence of postoperative retroperitoneal (7.5%). There were 6 arterial injuries (3.5%), 5 of them successfully treated with angiography and arterial selective embolization.The arterial injuries following PCNL are rare but can be serious. The possibility of an urgent arteriography and selective embolization to the diagnosis permits an effective and safe treatment of bleeding without risk to the affected renal unit.