Vismodegib for treatment of periocular basal cell carcinoma - 6-year experience from a tertiary cancer center

Abstract Background: The treatment of advanced periocular basal cell carcinomas becomes a challenge as surgery may involve highly mutilating procedures. Vismodegib is the first selective hedgehog inhibitor approved for the treatment of locally advanced tumors or metastatic disease. Objective: Analyze the results of treatment with vismodegib for advanced periocular basal cell carcinomas in a real-life setting of a reference center between 2014 and 2020. Methods: Retrospective longitudinal study. The patient's demographic profile, comorbidities, tumor characteristics, and treatment outcomes were analyzed. Results: A total of 13 patients were included. Median follow-up and treatment duration were 15.9 and 10.5 months, respectively. Objective clinical response rate was 76.9%: 30.8% had a complete response and 46.2% a partial response. The median duration of response was 13 months. Progressive disease was observed in 38.5% of cases, with a median of 19 months after the beginning of treatment. Eighty-four percent of the patients had at least one adverse event, and 61.54% needed to interrupt treatment temporarily or permanently to increase tolerability. Study limitations: Being a retrospective study in a real-life setting, the evaluation of objective clinical response was subjective to physician appreciation. Conclusion: Vismodegib is a safe and effective treatment for locally advanced basal cell carcinoma. To prevent recurrences, the drug should be used continually when tolerated. The role of neoadjuvant vismodegib before surgery is being investigated and might add an important step in searching for a definitive treatment for these cases.

Análise da composição e disposição espacial de placas ateroscleróticas localizadas em bifurcaçöes das artérias coronárias epicárdicas de adultos / Analysis of the Composition and Spatial Disposition of Atherosclerotic Plaques Located in Bifurcation of Epicardical Coronary Arteries in Adults

PURPOSE--To analyze macro and microscopic features of atherosclerotic plaques located in bifurcation of coronary arteries, defining their spatial disposition in those sites. METHODS--We studied 38 bifurcations of coronary arteries of patients whose cause of death was related to coronary artery disease. Histologic sections of 0.5mm were sequentially made from the main artery to the secondary branches. They were stained with hematoxilin-eosin technique. Histological analysis evaluated: a) morphologic composition of the plaques, b) degree of obstruction and c) plaque's disposition. RESULTS--a) Plaque's composition: fibrolipid plaques constituted 80 per cent of the cases and mingled focal atrophy of the media at the base of the plaque in 61 per cent with spots of total destruction and rupture of the elastic layers in 30 per cent ; b) degree of obstruction: ranged from 20 per cent to 95 per cent , with average 60 +/- 28 per cent ; c) disposition of plaques: we verified morphologic variation along the plaque, most of them (71 per cent ) being eccentric at bifurcation and not reaching the beginning of flow divider walls. CONCLUSION--Atherosclerotic plaques located in bifurcation of coronary arteries of adults are often fibrolipid plaques, eccentric, and their spatial disposition on those sites spare the beginning of the inner walls, reaching the outer walls

Infarto do miocárdio: comparaçäo dos achados anátomo-patológicos em coraçäo com e sem aterosclerose coronária grave em 194 casos de necrópsia / Myocardial infarction: comparison of pathological findings from hearts with and without severe coronary atherrosclerosis in 194 necropsy cases

Objetivo ­ Comparar as características morfológicas do infarto do miocárdio (IM) de pacientes com aterosclerose coronária causando obstrução da luz superior (com aterosclerose grave ­ AG) e inferior a 70% (sem AG). Métodos ­ 194 corações obtidos em necrópsia consecutivas de pacientes gue morreram por IM com idade entre 21 e 82 (média 60) anos, sendo 174 com e 20 sem AG. Resultados ­ A idade média no grupo com Ag foi 56 e a mediana 59 anos; no outro grupo, a média foi de 60 e a mediana 61 anos, havendo diferença significativa na distribuição etária (p = 0,023), com maior quantidade de pacientes abaixo de 40 anos no grupo sem AG. Não houve diferença significativa quanto ao sexo (31,0% de mulheres no grupo com AG e 35,0% no grupo sem AG, p = 0,718), peso médio do coração (com AG 500 g, sem AG 560 g), distribuição dos casos conforme tendo infarto recente apenas, infarto antigo apenas ou ambos (com AG - 36,2%, 28,2% e 35,6% respectivamente; sem AG - 45,0%, 20,0% e 35,0% respectivamente; p = 0,666), paredes acometidas pelos IM (p = 0,715), incidência de infarto hemorrágico (com AG­8,6%, sem AG - 15,0%, p = 0,406), de ruptura de ventrículo esquerdo (com Ag­5,2%, sem AG­10,0%, p = 0,719) e de aneurisma dessa câmara (com AG - 12,1%, sem AG - 15%, p = 0,316). Encontrouse associação entre AG e trombose coronária (trombose antiga recanalizada­p < 0,0001; trombose recente­p = 0,046), que todavia existia quando se restringiu a comparação à trombose recente nos casos não-operados de IM agudo (p = 0,091). Conclusão O grau de obstrução coronária superior ou não a 70% não condicionou diferenças morfológicas significativas em casos fatais de IM. Este dado sugere que esse fator não altera de maneira importante a história natural do IM.

Purpose ­ To compare morphological features of myocardial infarction (MI) from patients with any epicardial coronary artery narrowed at some point more then 70% (severe coronary atherosclerosis­SCA) with those from patients with either no coronary atherosclerosis or only mild (less than 70%) atherosclerosis. Methods ­ Necropsy findings from 194 patients who died due to MI, 174 patients with and 20 without SCA. Ages ranged from 21 to 82 (mean 60) years. Results ­ Mean age was 60 years in the cases with SCA and 56 in the case without it; nevertheless, age distribution was different (p = 0,023), due to the existence of more patients under age 40 in the group without SCA. There was no significant difference concerning sex (31.0% of female patients in the group with SCA and 35,0% in the other group, p = 0.718), mean heart weight (500 g and 506 g), distibution of cases according to time of evolution of MI in recent only, old only or both (cases with SCA - 36.2%, 28.2% and 35.6%; cases without SCA - 45.0% and 20%; p = 0,666), left ventricular wall commited by the MI (p=0.715), incidence of hemorrhagic infarction (with SCA - 8.6%; without SCA - 15.0%; p = 0.406), left ventricular rupture (with SCa - 5.17%, without SCA - 10.0%; p = 0.719) and left ventricular aneurysms (with SCA­12.1%, without SCA - 15.0%; p = 0,316). An association was found between coronary ahterosclerosis and recent (p=0,046) and recanalized (p<0.001) thrombosis, but absent when only recent thrombosis and non-operated cases with recent MI were considered (p = 0.091). Conclusion Necropsy of fatal cases of MI were not signifícantly different in the presence or absence of severe atherosclerotic narrowing (>70%) of epicardial coronary arteries, suggesting that this factor does not modify the natural history of MI.