Neoadjuvant chemotherapy or upfront surgery in localized pancreatic cancer: a contemporary analysis.

Neoadjuvant chemotherapy is considered a new treatment option for potentially resectable pancreatic cancer. However, data are not well established on overall survival and delaying surgery in resectable pancreatic cancer, as well as on those patients that ultimately cannot undergo surgery. We analyzed pancreatic cancer patients treated in a tertiary hospital from January 2016 to December 2020. Patients with resectable stage I and II pancreatic cancer were evaluated regarding surgery, neoadjuvant treatment, and other clinical demographics. The survival function was estimated using the Kaplan-Meier method, and the relationship between the variables of interest and the overall survival (OS) was assessed by adopting the proportional regression Cox models. A total of 216 patients were evaluated. 81 of them with resectable/borderline resectable disease and 135 with unresectable /metastatic disease at diagnosis. Median OS for stage I and II disease were 36 and 28 months, respectively. For resectable pancreatic cancer median OS was 28 months, for borderline resectable pancreatic cancer median OS was 11 months. Median OS for stage III (locally advanced) and stage IV (metastatic) were 10 and 7 months, respectively (p < 0.0001). Median OS of 9 months were obtained for patients with stage I and II that did not undergo surgery compared to 25 months in patients that underwent surgery in any time (p < 0.001). Comparing patients with localized disease, median OS for patients treated with upfront surgery was 28 months, compared to 15 months in patients treated with neoadjuvant approach (p = 0.04). Most patients that did not undergo surgery have decline of performance status or disease progression on neoadjuvant treatment. On multivariable analysis in pancreatic cancer stages I and II, including age, sex, borderline or resectable disease, CA 19-9, positive lymph nodes and neoadjuvant treatment, the surgery was the only factor associated with improved overall survival (p = 0.04). Upfront surgery should still be considered a standard of care approach for resectable pancreatic cancer. Biomarker driven studies and randomized trials with combination therapies are necessary to address neoadjuvant chemotherapy and delaying surgery in purely resectable pancreatic cancer.

Management of metastatic cutaneous melanoma: updates in clinical practice.

In recent years, several drugs have been approved for the treatment of patients with metastatic cutaneous melanoma, completely reshaping the landscape of this aggressive disease. Immune therapy with cytotoxic T-lymphocyte antigen 4 and programmed cell death-1 inhibitors yielded significant and durable responses, achieving long-term disease control in up to 40% of the patients. BRAF inhibitors (BRAFi), in combination with MEK inhibitors, also resulted in improved overall survival compared with single-agent BRAFi in patients with BRAFV600-mutated metastatic melanoma. The optimized sequencing and duration of treatment, however, is yet to be found. In this article, we thoroughly review current data and discuss how to best sequence the various treatment modalities available at present, based on four distinct clinical presentations commonly seen in clinic. In addition, we review treatment options beyond checkpoint inhibitors and targeted therapy, which may be required by patients failing such effective treatments.

A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication.

Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying these lesions are discussed.

Continuous palliative sedation for patients with advanced cancer at a tertiary care cancer center.

BACKGROUND: Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely worldwide. The aim of our study was to evaluate the frequency, clinical indications and outcomes of PS in advanced cancer patients admitted to our tertiary comprehensive cancer center. METHODS: We retrospectively studied the use of PS in advanced cancer patients who died between March 1st, 2012 and December 31st, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms in the end of life. This study was approved by the Research Ethics Committee of our institution (project number 2481-15). RESULTS: During the study period, 552 cancer patients died at the institution and 374 met the inclusion criteria for this study. Main reason for exclusion was death in the Intensive Care Unit. Among all included patients, 54.2% (n = 203) received PS. Patients who received PS as compared to those not sedated were younger (67.8 vs. 76.4 years-old, p < 0.001) and more likely to have a diagnosis of lung cancer (23% vs. 14%, p = 0.028). The most common indications for sedation were dyspnea (55%) and delirium (19.7%) and the most common drugs used were midazolam (52.7%) or midazolam and a neuroleptic (39.4%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range - IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Patient survival (length of hospital stay from admission to death) of those who had PS was more than the double of those who did not (33.6 days vs 16 days, p < 0.001). The palliative care team was involved in the care of 12% (n = 25) of sedated patients. CONCLUSIONS: PS is a relatively common practice in the end-of-life of cancer patients at our hospital and it is not associated with shortening of hospital stay. Involvement of a dedicated palliative care team is strongly recommended if this procedure is being considered. Further research is needed to identify factors that may affect the frequency and outcomes associated with PS.

Ovarian yolk sac tumor coexisting with epithelial ovarian cancer: An aggressive rare entity.

Yolk sac tumor (YST) is the second most common subtype of ovarian germ cell tumors. It usually occurs in the second and third decades of life and is rare in postmenopausal women. In postmenopausal women, YST is commonly an aggressive tumor and can present as a pure germ cell component or as a mixed component with other germ cell or epithelial components. The recognition of this histological subtype is important not only for differential diagnosis but also for determining prognosis and treatment decisions. In this case report, we describe a 61-year-old woman with YST coexisting with epithelial carcinoma focusing on the efficacy of systemic therapies.

Does Time-to-Chemotherapy Impact the Outcomes of Resected Ovarian Cancer? Meta-analysis of Randomized and Observational Data.

OBJECTIVES: This study is a meta-analysis of prior publications evaluating the impact of time-to-chemotherapy (TTC) on disease recurrence and survival 3 years after the original surgery. METHODS: We performed a meta-analysis of studies published in PubMed (1950-2016) as of April 2016. Inclusion criteria were as follows: randomized controlled trials and prospective or retrospective cohorts that included patients with ovarian cancer who had undergone surgery with curative intent and use of adjuvant chemotherapy. We compared rates of disease recurrence and death according to the TTC ("early" vs "delayed") using a random-effects model and performed a metaregression to evaluate the impact of covariates on these outcomes. RESULTS: Of 239 abstracts in the original search, 12 were considered eligible. The cutoffs used for TTC were between 20 and 40 days. All studies used a platinum-based chemotherapy, and the rates of patients with suboptimal resection varied from 33% to 70%. A longer TTC was not associated with higher rates of disease recurrence (odds ratio, 0.89; 95% confidence interval, 0.63-1.24) or death at 3 years (odds ratio, 1.06; 95% confidence interval, 0.9-1.24). There was no evidence of significant publication bias (Egger test P = 0.472), but data were heterogeneous (I = 64.3%). Metaregression showed that the percentage of patients with suboptimal surgery and values used as cutoff to define "delayed" chemotherapy combined were a significant source of bias (residual I = 0%). CONCLUSIONS: In our analysis, TTC after surgery for ovarian cancer with curative intent was not associated with higher risk of disease recurrence or death. However, this association was influenced by the rate of optimal debulking and definition of "late" initiation of chemotherapy, so we must be careful when applying these data to patients with complete resection.

Hipersensibilidade a inalantes em adultos jovens que responderam o questionário do International Study of Asthma and Allergies in Childhood / Hypersensitivity to inhalants in young adults who answered to the International Study of Asthma and Allergies in Childhood questionnaire

Objetivo: A prevalência de doenças alérgicas, como asma, rinite e eczema, aumentou significativamente, tendo etiologia multifatorial como a exposição à alérgenos. Este estudo teve como objetivo determinar a prevalência de sensibilização à aeroalérgenos através de testes cutâneos em adultos jovens da Faculdade de Medicina do ABC, que responderam ao questionário padrão ISAAC (International Study of Asthma and Allergies in Childhood) em 2006 e 2007. Métodos: Estudo transversal realizado em 600 jovens que responderam ao questionário ISAAC. Desses, 100 foram randomizados para realizar testes cutâneos de hipersensibilidade imediata para os alérgenos: D. pteronyssinus e D. farinae, Blomia tropicalis, Blatella, epitélio de cão e gato. Os resultados foram correlacionados com as respostas dos questionários. Resultados: Nos questionários, 28 (28%) alunos apresentaram-se assintomáticos, 14 (14%) com asma ativa, 63 (63%) com rinite ativa e 12 (12%) com eczema. Entre os submetidos aos testes cutâneos, 37 (74,0%) apresentavam sintomas de rinite (p < 0,05), 9 (64,3%) de asma e 6 (50,0%) de eczema. Observou-se que 50 (50%) alunos apresentaram reações positivas para pelo menos um alérgeno, dos quais 39 (78%) apresentavam sintomas alérgicos e 11 (22,0%) eram assintomáticos (p = 0,18 e OR = 1,82). Entre os que mostraram positividade para mais de um alérgeno, 11 (73,3%) tinha asma, 13 (92,9%) tinham rinite e 7 (58,3%) eczema. (p < 0,05). Conclusões: Observou-se relação direta entre a prevalência de doenças alérgicas e positividade aos testes cutâneos. Rinite foi a doença mais frequente, seguida pela asma e eczema, nos quais os ácaros apresentaram maior prevalência, principalmente o D. farinae.

Objective: The prevalence of allergy diseases, such as asthma, rhinitis and eczema, increased significantly having the multifactorial etiology as the allergens exposure. The study objective was to appoint the prevalence of sensitization to the aeroallergens through the skin allergy test (prick test) in young adults from the Faculdade de Medicina do ABC, who filled the ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire in 2006 and 2007. Methods: Cross-sectional study of 600 young adults who answered the ISAAC questionnaire. From those, 100 were randomly picked to do the skin allergy test for immediate hypersensitivity to the allergens: D. pteronyssinus, D. farinae, Blomia tropicalis, Blatella, dog and cat epithelial. The results and the questionnaires answers were correlated. Results: In the questionnaires, 28 (28%) students presented themselves as asymptomatic, 14 (14%) with active asthma, 63 (63%) with active rhinitis and 12 (12%) with eczema. In the allergy skin tests, 37 (74.0%) had rhinitis symptoms (p < 0.05), 9 (64.3%) had asthma and 6 (50.0%) had eczema. It was proven that 50 (50%) students who had been tested positive for at least one allergen, from them 39 (78%) had allergic symptoms and 11 (22.0%) was asymptomatic (p = 0.18 and OR = 1.82). From those who has more than one allergen, 11 (73.3%) students had asthma, 13 (92.9%) had rhinitis and 7 (58.3%) had eczema (p < 0.05).Conclusions: It was noted a direct relationship to the prevalence of allergy diseases and a positivity in the skin allergy tests. The rhinitis was the main diseases founded followed by the asthma and eczema, which the mites had higher prevalence, specially the D. farinae.

Gabapentin for the prevention of chemotherapy- induced nausea and vomiting: a pilot study.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy. METHODS: Eighty chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy, were enrolled in this randomised, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day 1 and oral dexamethasone 4 mg twice a day on days 2 and 3. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: 5 and 4 days before chemotherapy once daily, 3 and 2 days before chemotherapy twice daily, 1 day before to 5 days after chemotherapy thrice daily. The primary endpoint was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24-120 h after chemotherapy). RESULTS: The proportion of patients achieving complete response improved from 40% to 62.5%, (p = 0.04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89.3 × 60.7%, p = 0.01). Adverse events did not significantly differ between study arms. CONCLUSIONS: Gabapentin is a low-cost strategy to improve complete control of CINV, specially delayed CINV control.

A relação da circunferência abdominal com outros componentes da síndrome metabólica em pacientes atendidos na feira de saúde da FMABC em 2008 / Relationship of abdominal circumference with other metabolic syndrome components in patients seen during the FMABC health fair in 2008

JUSTIFICATIVA E OBJETIVOS: Síndrome metabólica,atualmente considerada epidemia mundial, caracteriza-se pela associação de dislipidemia, diabetes mellitus/intolerância à glicose, hipertensão arterial e obesidade. Interligando estas alterações metabólicas está a resistência à insulina. Sua presença leva ao aumento do risco de doenças cardiovasculares. O objetivo deste estudo foi demonstrara existência de uma síndrome, ao invés de doenças isoladas, relacionando circunferência abdominal, glicemia e pressão arterial (PA). MÉTODO: Foram atendidos 473 pacientes na Feira de Saúde em 2008 da FMABC pela Liga de Controle do Diabetes. Variáveis mensuradas: glicemia, peso, altura, índicede massa corpórea (IMC), circunferência abdominal (CA) e pressão arterial. Dados coletados: hábitos, uso de medicamentos, antecedentes pessoais e familiares. Foram excluídos pacientes < 18 ou > 79 anos, em uso de anti-hipertensivos e antidiabéticos. RESULTADOS: Foram analisados 148 pacientes, sendo 92 mulheres, idade média de 40,37 ± 14,1 anos. A média de glicemia foi 100,3 ± 18,9 mg/dL, de CA foi 88,1 ± 13,4 cm e a de IMC 26,8 ± 5,4 kg/m2. Dos homens que estavam de jejum, 9% tinham CA aumentada (> 104 cm), sendo 50% intolerante à glicose (glicemia > 100 mg/dL), com p = 0,03. Já no sexo feminino 48,9% não estava de jejum, sendo 55% destas com CA > 88 cm. Entre os pacientes masculinos com CA alterada, 62,5% tinham PA > 130 x 85 mmHg, com p = 0,04. Já no sexo feminino, 23,9% com CA > 88 cm apresentaram níveis de PA elevados. Não houve significância estatística entre CA, hiperglicemiae PA entre as mulheres. CONCLUSÃO: O presente estudo mostrou que a circunferência abdominal aumentada se relaciona com intolerância à glicose e hipertensão, principalmente entre os homens. Isso corrobora com a literatura que busca demonstrar a existência de uma síndrome como fator de risco para fenômenos ateroscleróticos.

[Professional or household performance of patients with breast cancer undergoing chemotherapy]. / Desempenho profissional ou doméstico das pacientes em quimioterapia para câncer de mama.

OBJECTIVES: Evaluate patients with breast cancer undergoing chemotherapy with respect to their epidemiologic and clinical variables as well as performance at work or at home. METHODS: this was a cross-sectional study including 52 women interviewed during breast cancer chemotherapy, stratified in two groups: those who continued to work and do household tasks, and did not continue to work or do household tasks. Patients were from two public hospitals in the State of São Paulo, one in Santo Andre and the other in São Bernardo do Campo. The WPAI - GH (Work Productivity and Activity Impairment) questionnaire was used to evaluate work and household performance of professionals or housewives, respectively. RESULTS: Mean age of the patients was 55.7 (SD=13.8), most were Caucasian (88.5%), married (55.8%), employed (65.3%) and the majority had to stop working because of treatment (51.0%), at more advanced stage (p<0.05), fatigue and nausea (p<0.05). Mean WPAI - GH was 67.04 (|SD = 5.62) for patients who stopped working and 49.17 (SD = 6.89) for those who continued to work (Mann-Whitney U test: p = 0.04). CONCLUSION: Chemotherapy leads to a decrease in performance of a sizable fraction of women with breast cancer undergoing chemotherapy. A more advanced stage of neoplasia was positively associated with withdrawal from these activities probably due to side effects such as fatigue and nausea.

Desempenho profissional ou doméstico das pacientes em quimioterapia para câncer de mama / Professional or household performance of patients with breast cancer undergoing chemotherapy

OBJETIVOS: Analisar os aspectos epidemiológicos, clínicos, desempenho profissional e doméstico nas pacientes com câncer de mama em tratamento quimioterápico. MÉTODOS: O estudo foi transversal, com 52 mulheres entrevistadas, divididas em dois grupos: afastadas e não afastadas das atividades profissionais e domésticas, durante o tratamento com quimioterapia para câncer de mama. As pacientes foram provenientes de dois hospitais, um situado no município de Santo André e o outro no município de São Bernardo do Campo. Ambos são hospitais públicos de referência, que atendem a população de Santo André, São Bernardo do Campo, São Caetano do Sul, Diadema e Mauá, que são municípios vizinhos, pertencentes ao Estado de São Paulo, próximos da capital. Utilizou-se o questionário WPAI-GH (Work Productitity and Actitity Impairment) para avaliar a atividade profissional e/ou doméstica das pacientes. RESULTADOS: As pacientes tinham idade média de 55,7 anos (dp=13,8), a maior parte de etnia branca (88,5 por cento), casada (55,8 por cento), assalariada (65,3 por cento) e a maioria se afastou das atividades (51,0 por cento), com estadiamento da doença mais avançado (p<0,05), fadiga e náuseas (p<0,05). A média do WPAI - GH foi 67,04 (dp = 5,62) para as pacientes afastadas, e 49,17 (dp = 6,89) para as não afastadas do trabalho (teste U de Mann-Whitney: p = 0,04). CONCLUSÃO: A quimioterapia acarreta diminuição da capacidade produtiva em parte significativa das mulheres com câncer de mama. O estadiamento mais avançado da neoplasia associou-se positivamente com o afastamento das atividades diárias das pacientes, provavelmente decorrente dos efeitos colaterais provocados, como fadiga e náuseas.

OBJECTIVES: Evaluate patients with breast cancer undergoing chemotherapy with respect to their epidemiologic and clinical variables as well as performance at work or at home. METHODS: this was a cross-sectional study including 52 women interviewed during breast cancer chemotherapy, stratified in two groups: those who continued to work and do household tasks, and did not continue to work or do household tasks. Patients were from two public hospitals in the State of São Paulo, one in Santo Andre and the other in São Bernardo do Campo. The WPAI - GH (Work Productivity and Activity Impairment) questionnaire was used to evaluate work and household performance of professionals or housewives, respectively. RESULTS: Mean age of the patients was 55.7 (SD=13.8), most were Caucasian (88.5 percent), married (55.8 percent), employed (65.3 percent) and the majority had to stop working because of treatment (51.0 percent), at more advanced stage (p<0.05), fatigue and nausea (p<0.05). Mean WPAI - GH was 67.04 (SD = 5.62) for patients who stopped working and 49.17 (SD = 6.89) for those who continued to work (Mann-Whitney U test: p = 0.04). CONCLUSION: Chemotherapy leads to a decrease in performance of a sizable fraction of women with breast cancer undergoing chemotherapy. A more advanced stage of neoplasia was positively associated with withdrawal from these activities probably due to side effects such as fatigue and nausea.

Shoulder function following partial spinal accessory nerve transfer for brachial plexus birth injury.

Over a 5-year-period, 26 infants underwent a partial transfer of the spinal accessory nerve into the suprascapular nerve using a nerve graft, as part of the repair of a brachial plexus birth injury. At a minimum follow-up of 2.5 years, all children had shoulder function of Grade 4 or better using a modified Gilbert Scale. Average lateral rotation was measured at 53 degrees.