Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Immunohisthochemical expression of ErbB family receptors and their prognostic role in patients with colorectal cancer with high risk of recurrence after radical surgery

INTRODUÇÃO: Deve-se considerar que cerca de 70 a 80% dos pacientes portadores de carcinoma colorretal estádio II podem ser curados apenas com cirurgia. Por outro lado, a despeito do tratamento empregado e dos benefícios alcançados com a evolução dos tratamentos adjuvantes, cerca de 20 a 35% dos pacientes tratados com doença em estádio III vêm a falecer por recidiva tumoral. É provável que existam características biomoleculares intrínsecas que possam conferir maior agressividade e resistência ao tratamento adjuvante. A família de proteínas ErbB formam um grupo de receptores de membrana, cuja função é ativar a via de sinalização intracelular em resposta ao sinal extracelular e é formada por quatro receptores: EGFR/ErbB1, ErbB2/HER2, ErbB3/HER3 e ErbB4/HER4. O complexo de receptores ErbB é uma das vias de transmissão de sinal celular mais amplamente estudada, porém poucos estudos interessados em avaliar a expressão dos quatro receptores da família ErbB e sua correlação prognóstica no câncer de cólon e reto foram realizados até o momento. Nosso objetivo foi avaliar a expressão imunoistoquímica de EGFR, ErbB2, ErbB3 e ErbB4 e seu papel como fator prognóstico para sobrevida livre de doença e sobrevida global em carcinoma de cólon e reto estádio II de alto risco e estádio III submetidos a tratamento cirúrgico radical. CASUÍSTICA E MÉTODOS: vi Trata-se de um estudo retrospectivo que avaliou uma série de 118 indivíduos portadores de adenocarcinoma de colón e reto alto estádio II com fatores de alto risco ou estádio III. Foram analisadas variáveis clínicopatológicas e as expressões de EGFR, ErbB2, ErbB3 e ErbB4 foram determinadas através de imunoistoquímica pelo dispositivo técnico Tissue Microarray (TMA). RESULTADOS: O tempo de seguimento mediano foi de 58,8 meses. A sobrevida global da amostra foi de 71,2% em 5 anos. A sobrevida livre de doença foi de 67,8% em 5 anos. As expressões imunoistoquímicas positivas de EGFR, ErbB2, ErbB3, em membrana de ErbB4 e em citoplasma de ErbB4 foram encontradas em respectivamente 59,3%, 7,6%, 71,2%, 10,2% e 20,3% dos casos. Houve diferença significativa na expressão de EGFR em relação à localização da neoplasia, onde 75% dos pacientes com tumor em reto apresentaram expressão positiva, contra 52,4% entre os tumores de cólon (p=0,02). Em relação à expressão ErbB2, houve diferença significativa no que refere ao estadiamento, onde 1,8% dos pacientes com estádio II apresentavam expressão positiva, contra 12,7% entre os pacientes com estádio III (p=0,03). A expressão de ErbB3 teve diferença significativa em relação à presença de embolização linfática, com expressão positiva em 79,5% dos pacientes com ausência de embolização linfática frente a 46,7% dos com presença de embolização linfática (p=0,001). Em relação à expressão de ErbB4, não houve diferença significativa entre todas as variáveis estudadas, tanto para expressão em membrana quanto em citoplasma. Observamos que presença de embolização vascular linfática, presença de invasão perineural, expressão imunoistoquímica negativa de ErbB3 e positiva de ErbB4 em membrana influenciaram negativamente a sobrevida livre de doença em cinco anos na análise univariada. No modelo multivariado, a expressão negativa de ErbB3 (RR: vii 2,43; IC 95%: 1,26 4,66) e a expressão positiva de ErbB4 em membrana (RR: 3,03; IC 95%: 1,31 6,98) mantiveram-se como fator independente para risco de recaída. Observamos ainda que idade igual ou maior que 65 anos, presença de embolização linfática e expressão negativa de ErbB3 influenciaram negativamente a sobrevida global em 5 anos na análise univariada. No modelo multivariado, a idade igual ou maior que 65 anos (RR 2,83; IC 95%: 1,36 5,90) e a expressão negativa de ErbB3 (RR: 2,52; IC 95%: 1,28 4,97) mantiveram-se como fator independente para risco de óbito. CONCLUSÕES: A expressão positiva de ErbB4 em membrana foi variável de risco independente para recidiva e a expressão negativa de ErbB3 foi variável de risco independente para recidiva e óbito. As expressões imunoistoquímicas de ErbB3 e de ErbB4 em membrana podem selecionar pacientes portadores de câncer colorretal estádios II e III submetidos a tratamento cirúrgico radical que tenham maior risco de recidiva e óbitoINTRODUCTION: In spite of multidisciplinary treatment, survival after 5 years in these subgroups is under 60 and 70%. Probably, some patients have recurrence due to microscopic residual disease resistant to the adjuvant treatment received. However, other patients do not have recurrent disease even without adjuvant treatment as they have already been cured by surgery alone. Thus, there is a need to identify biological tumoral characteristics that may predict poor outcome and guide the development of new adjuvant treatments. The epidermal growth factor receptor (EGFR/ErbB1), ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4 are a group of subtype I tyrosine-kinases sharing structural homologies, especially at the intracellular domain. Protein kinases are enzymes that play a key regulation role in nearly every aspect of cell biology. There have been only a few studies that explored the expression of ErbB family in colorectal cancers. The present study was designed to investigate the expression of ErbB family in high risk colorectal cancer (high risk stage II and stage III) submitted to radical surgery and their role as a prognostic factor to recurrence and survival. MATERIALS AND METHODS: We studied 118 individuals with high risk stage II and stage III colorectal cancer submitted to radical surgery. Clinico-pathological data were reviewed. ErbB family protein expression in ix tumor tissue was assessed by immunohistochemistry using Tissue Microarray technique. RESULTS: The median follow-up time was 58,8 months. The five-year overall survival was 71,2% and five-year disease free survival was 67,8%. The immunohistochemical expression was considered positive for EGFR, ErbB2, ErbB3, ErbB4 membrane and ErbB4 cytoplasmic in respectively 59,3%, 7,6%, 71,2%, 10,2% and 20,3% of the patients. EGFR expression was associated with tumor localization, ErbB2 expression with stage III and ErbB3 negative expression with lymphovascular invasion. Membranous positive ErbB4 expression was an independent prognostic factor only for recurrence. ErbB3 negative expression was an independent prognostic factor for recurrence and survival in the multivariate analysis. EGFR, ErbB2 and cytoplasmic ErbB4 expression was not associated with prognosis. CONCLUSIONS: Membranous positive ErbB4 expression was an independent prognostic factor for recurrence and ErbB3 negative expression was an independent prognostic factor for recurrence and survival. The immunohistochemical expression of ErbB3 and ErbB4 may be used to identify a subgroup of patients with stage II and III colorectal tumors at higher risk of recurrence and deat

Immunohistochemical expression of HER-2, NF-B and IKK in patients with cervical cancer treated with radiation therapy

INTRODUÇÃO: O tratamento padrão do câncer do colo uterino é a histerectomia radical para doença inicial e quimio-radioterapia para doença avançada. A radioterapia após a histerectomia radical tem impacto em ganho de sobrevida caso hajam fatores de risco histopatológicos para recidiva. Portanto, a busca de marcadores preditores de radiossensibilidade torna-se importante para a individualização do planejamento terapêutico. O HER-2/ErbB-2 faz parte da família de proteínas ErbB que formam um grupo de receptores de membrana e tem um papel crítico no controle de diversas funções celulares básicas como diferenciação, proliferação, migração e sobrevida celular. A ação do NF-B na carcinogênese pode ocorrer através da regulação da apoptose e controle do ciclo celular. Para ativação do NF-B é necessário a enzima quinase IKK e a atividade do NF-B foi relacionada com resistência tumoral a quimioterapia e radioterapia. A via PI3K/Akt mediada pela hiperexpressão de HER-2 pode estar envolvida na ativação do NF-B. Os objetivos foram: a) avaliar os padrões de expressão imunoistoquímica de HER-2, NF-B-p65, NF-B-p50 e IKK em pacientes portadores de câncer do colo uterino submetidos à radioterapia; b) avaliar o status do gene HER2 através de FISH; c) avaliar o papel da expressão imunoistoquímica de NF-B-p65, NF-B-p50, IKK e HER-2 como fator prognóstico para sobrevida livre de doença e sobrevida global. MATERIAIS E MÉTODOS: Trata-se de estudo retrospectivo que avaliou uma série de 32 pacientes portadores de câncer do colo do útero submetidos a tratamento com radioterapia seguido de histerectomia no período de janeiro de 1992 a junho de 2001. RESULTADOS: A idade mediana foi 45 anos (22-67). Um paciente apresentava-se no estádio IB2 (FIGO) e 31 (96,9%) estádio IIB. Todos os pacientes foram submetidos à teleterapia e braquiterapia com alta taxa de dose com caráter neoadjuvante à histerectomia radical (HR). Dezesseis (50%) pacientes apresentaram doença residual após radioterapia. O tempo de seguimento mediano foi de 73,5 meses. A sobrevida global da amostra foi de 66,5% em 5 anos. As expressões imunoistoquímicas de NF-B-p65 e NF-B-p50 em citoplasma nos tumores primários foram encontradas em respectivamente 90,6% e 96,9% dos casos. As expressões de NF-B-p65 e NF-B-p50 em núcleo nos tumores primários 59,4% dos casos em ambos. As expressões de NF-B-p65 e NF-B-p50 em citoplasma nos tumores residuais após tratamento com radioterapia foram encontradas 50% dos casos em ambos. A expressão em núcleo de NF-B-p50 nos tumores residuais após tratamento com radioterapia foi encontrada em 75% dos casos. Não houve expressão em núcleo de NF-B-p65 nos tumores residuais. A expressão imunoistoquímica de HER-2 nos tumores primários foi de encontrada em 21,9% dos casos. Não houve expressão imunoistoquímica de HER-2 nos tumores residuais do colo uterino. A amplificação gênica de HER-2 nos tumores primários foi encontrada em 1 (3,1%) caso. Não houve expressão imunoistoquímica de IKK nos tumores primários ou residuais. As expressões imunoistoquímicas de HER-2, NF-B-p65 e NF-B-p50 não se correlacionaram com a resposta ao tratamento radioterápico pré-operatório. As expressões imunoistoquímicas positivas de NF-B-p65, NF-B-p50, IKK e HER-2 não se associaram a piores taxas de sobrevida livre de doença e sobrevida global. CONCLUSÕES: Nossos dados sugerem que as expressões imunoistoquímicas de NF-B e HER-2 não são capazes de predizer resposta à radioterapia e não estão relacionadas com pior prognóstico. O NF-B parece ser constitutivamente ativado no câncer do colo uterinoINTRODUCTION: The standard treatment of early cervical cancer is radical hysterectomy and concomitant radiation therapy and chemotherapy for advanced stages. After radical hysterectomy, adjuvant radiation therapy is indicated if risk factors are present. HER-2 is part of protein membrane family that has a critical role in cellular differentiation, proliferation and survival. The NF-B regulates apoptosis, cellular cycle, adhesion and cellular migration. NF-B is activated by IKK kinase. NF-B activation is related to resistance to radiotherapy and chemotherapy. The overexpression of HER-2 may activate the NF-B pathway through PI3K/Akt. Our aims were: a) analyze the immunohistochemical expression of HER-2, NF-B-p50, NF-B-p65 and IKK in patients with cervical cancer treated with radiation therapy followed by radical hysterectomy; b) analyze the HER-2 amplification gene with FISH; c) evaluate the immunohistochemical expression of HER-2, NF-B-p50, NF- B-p65 and IKK as a prognostic factor to recurrence and death. MATERIALS AND METHODS: A retrospective analysis was carries out on 32 patients with cervical cancer submitted to radical hysterectomy after neoadjuvant radiotherapy from January 1992 to June 2001. RESULTS: The median age was 45 years (22-67). One patient was stage IB2 (FIGO) and 31 IIB (96,9%). All patients received external beam radiotherapy and high dose vaginal brachytherapy. Sixteen (50%) patients had residual pathological disease after radical hysterectomy. Median follow-up time was 73.5 months and overall 5-year survival was 66.5%. Immunohistochemical cytoplasmic expression of NF-B-p65 e NF-B-p50 before radiotherapy was found in respectively 90.6% and 96.9% of cases. Immunohistochemical nuclear expression of NF-B-p65 and NF-B-p50 before radiotherapy was found in both 59.4% of cases. Immunohistochemical cytoplasmic expression of NF-B-p65 and NF-B-p50 in the residual tumors after radiotherapy was found in both 50% of cases. Immunohistochemical nuclear expression of NF-B-p50 in the residual tumors was found in 75% of cases. There was no nuclear expression of NF-B-p65 in the residual tumors. Immunohistochemical expression of HER-2 was found in 21.9% of cases. However, gene amplification was found in one case (3.1%). There was no expression of IKK in neither primary nor residual tumors. HER-2 and NF-B were not correlated to the risk of residual tumor after radiotherapy. Immunohistochemical expression of HER-2 and NF-B were not correlated to risk of recurrence or death. CONCLUSIONS: Our data suggest that NF-kB is constitutively activated in advanced cervical cancer. NF-kB and HER-2 may not predict response to radiotherapy and do not correlate to poor outcom

Vulvar melanoma: report on eleven cases and review of the literature

CONTEXT AND OBJECTIVE: Vulvar melanoma is a rare disease. We describe the experience of a single institution and review the literature. DESIGN AND SETTING: Retrospective study at the Department of Gynecology, Hospital do Cancer A. C. Camargo. METHODS: Eleven patients with vulvar melanoma attended between January 1987 and December 2006 were reviewed regarding clinicopathological characteristics, surgical therapy and follow-up. RESULTS: The initial symptoms were vulvar lesions, pruritus, pain and bleeding. The median age was 64.8 years. The median depth of invasion was 3.08 mm. The staging ranged from IB to IIIC (American Joint Committee on Cancer, 2002). All the patients underwent vulvectomy. Two patients did not undergo primary elective lymphadenectomy. Bilateral inguinal lymphadenectomy was performed on five patients, and one had unilateral inguinal lymphadenectomy. Sentinel lymph node investigation was performed on three patients. Five patients had locoregional recurrence. Prolonged survival was only achieved in the absence of lymph node involvement. The median follow-up was 56 months. The median disease-free survival was 15 months and the median overall survival was 29 months. CONCLUSIONS: The prognosis for patients with vulvar melanoma is generally poor, with a high tendency towards regional and distant recurrence. Depth of invasion and lymph node involvement are the most important prognostic factors. In most cases, resection of the lesion with adequate margins may replace vulvectomy. Elective inguinal femoral lymphadenectomy remains the standard lymph node staging procedure. Sentinel lymph node investigation is feasible and should be performed by a multidisciplinary team with experience of this method

Prognostic significance of c-KIT in vulvar cancer: bringing this molecular marker from bench to bedside

Abstract Background Vulvar carcinomas are rare tumors, and there is limited data regarding molecular alterations. To our knowledge there are no published studies on c-KIT and squamous cell carcinomas of the vulva (VSCC). Although there are a significant number of other tumor types which express c-KIT, there remains controversy as to its relationship to patient outcome. Thus, we wished to investigate such controversial findings to determine the prognostic importance of c-KIT by evaluating its protein and mRNA expression in VSCCs, correlating these findings with clinicopathological features and Human Papillomavirus (HPV) infection. Methods c-KIT expression was scored by immunohistochemistry (IHC) as positive or negative in 139 formalin-fixed paraffin-embedded (FFPE) cases of vulvar carcinomas arrayed in a tissue microarray (TMA) using the DAKO® A4502 rabbit polyclonal c-KIT antibody (diluted 1:100). c-KIT mRNA was evaluated by qRT-PCR in 34 frozen samples from AC Camargo Hospital Biobank (17 tumoral and 17 non-tumoral samples) using TaqMan probes–Applied Biosystems [Hs00174029_m1]. HPV genotyping was assessed in 103 samples using Linear Array® HPV Genotyping Test kit (Roche Molecular Diagnostics, Basel, Switzerland). All results obtained were correlated with clinical and pathological data of the patients. Results c-KIT protein was positive by immunohistochemistry in 70.5% of the cases and this was associated with a higher global survival (p = 0.007), a higher recurrence-free survival (p c-KIT mRNA quantitation revealed higher levels of transcripts in normal samples compared to tumor samples (p = 0,0009). Conclusions Our findings indicate that those vulvar tumors staining positively for c-KIT present better prognosis. Thus, positivity of c-KIT as evaluated by IHC may be a good predictor for use of more conservative surgery techniques and lymph node dissection in vulvar cancer. So part of the essence of our study is to see the possibility of translating our current results from the bench to the bedside. This will help provide patients a more appropriate, less mutilating treatment, in order to keep the maximum physical and psychic quality as possible to these women.</p