Terapêutica do sarcoma de Kaposi : uma revisão da literatura

Trabalho final de mestrado integrado em Medicina área científica de Infecciologia, apresentado á Faculdade de Medicina da Universidade de CoimbraIntrodução: O Sarcoma de Kaposi (SK) é uma neoplasia de origem vascular, de localização cutânea, mucosa ou visceral. Com o diagnóstico dos primeiros casos de SIDA (síndrome de imunodeficiência adquirida), foi identificado como uma das suas manifestações mais frequentes. Na década de 90, o advento de anti-retrovíricos eficazes diminuiu a sua incidência nos países desenvolvidos. Objectivos: Identificar e caracterizar as diversas variantes de SK; esclarecer a sua etiologia e patogénese; identificar os modos de transmissão do vírus VHH-8 (vírus herpes humano tipo 8); sistematizar os dados epidemiológicos relativos à sua prevalência geográfica e em grupos populacionais particulares; analisar as diferentes alternativas terapêuticas já encontradas e a sua aplicação em casos particulares; indicar algumas terapêuticas inovadoras actualmente em investigação. Desenvolvimento: Existem 4 tipos de SK: clássico; endémico; relacionado com a SIDA e associada a imunossupressão. Todas partilham o mesmo agente etiológico - o VHH-8, pertencente à subfamília gama dos vírus herpes. Provoca uma proliferação de células fusiformes de origem endotelial, originando lesões cutâneas, mucosas ou viscerais de diferente extensão e gravidade. Os doentes com SK associado a VIH devem efectuar terapêutica anti-retrovírica. No caso de persistência das lesões ou impossibilidade de controlo da virémia VIH, são vários os agentes disponíveis. Na presença de lesões superficiais localizadas, pode recorrer-se a radioterapia, crioterapia, injecção intra-lesional ou excisão cirúrgica. Perante doença disseminada, rapidamente progressiva ou atingindo órgãos internos, torna-se necessária terapêutica sistémica com interferão , antraciclinas liposomais ou paclitaxel. Conclusão: A incidência do SK em doentes com SIDA tem vindo a diminuir fundamentalmente devido à introdução da terapêutica anti-retrovírica combinada (TARVc). No entanto, o risco de desenvolvimento de SK permanece substancialmente elevado nos indivíduos infectados por VIH, podendo surgir em qualquer etapa da infecção. A resposta ao tratamento é variável, dependendo da gravidade das lesões e do perfil imunitário do doente. O SK permanece, no entanto, uma doença incurável. O esclarecimento dos mecanismos patogénicos subjacentes ao SK permitirá o desenvolvimento de novas modalidades terapêuticas.Introduction: Kapois’s sarcoma (KS) is a neoplasm of vascular origin involving skin, mucous membranes and internal organs. In the initial period of AIDS (acquired immunodeficiency syndrome) epidemic, it was identified as one of its prominent clinical features. Its incidence has decreased dramatically in the mid 90s, after the introduction of highly active antiretroviral therapy (HAART). Objectives: To distinguish and describe the various types of KS; to elucidate its origin and pathogenesis; to identify the various modes of HHV-8 (human herpesvirus 8) transmission; to present epidemiological data concerning its geographic prevalence and among specific populational groups; to compare the different treatments employed and their use in specific indications; to point out several innovative therapeutic approaches under investigation. Development: There are four types of KS: classic; endemic; AIDS-related; and immunosuppression-associated. HHV-8 belongs to the subfamily of gamma herpesvirus and is implied in all forms of KS. It promotes a proliferation of spindle cells of endothelial origin, causing cutaneous, mucous or visceral lesions with a wide range of presentation. Patients with AIDS-related KS often respond well to HAART (Highly Active Antiretroviral Therapy) alone. If lesions persist or in case of uncontrolled HIV viremia, there are several other options. Localized, skin lesions can be treated by radiotherapy, criotherapy, intra-lesional injection or surgical excision. Widespred disease or with internal organ involvement can be treated with interferon , liposomal anthracyclines or paclitaxel. Conclusion: The risk of AIDS-related KS has declined since the introduction of HAART in the mid-1990s. However, it remains highly prevalent in HIV-infected patients and can arise at any stage of the disease. Response to treatment is variable according to lesion extension and patient immunity status. SK remains an incurable disease. The knowledge of pathogenic mechanisms involved in KS will allow the discovery of new therapeutic approache

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research