Predictors of cancer in patients with acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) can occur as a manifestation of an underlying cancer and be of paraneoplastic aetiology. A previously unknown cancer is sometimes diagnosed after the acute PE diagnosis. The identification of a group of patients with elevated probability of having an occult cancer underlying PE was never performed. We aimed to determine predictors of occult cancer in acute PE. Our hypothesis was that the D-dimer levels would be a predictor of cancer. PATIENTS AND METHODS: We retrospectively analysed a cohort of patients hospitalized with acute PE. EXCLUSION CRITERIA: <18 years, venous embolism only of veins other than pulmonary territory or when the embolism was considered chronic, and no image confirmation of acute PE. Patients were grouped according to the timing of cancer diagnosis: 1) known concomitant active cancer, 2) cancer diagnosed during acute PE admission or in the following 2 years and, 3) no known cancer during the 2-year follow-up since PE diagnosis. Predictors of concomitant cancer were determined using a logistic regression analysis. Multivariate models were built. RESULTS: We studied 562 patients; median age was 72 years and 219 (39.0 %) were men. In 223 (39.7 %) of the patients the PE was of central arteries and 61.4 % presented with bilateral PE. PE was considered unprovoked at time of discharge in 47.7 %. Median (interquartile range) D-dimer level was 7.98 (3.30-14.99) µg/mL. A total of 126 (22.4 %) patients were in group 1, 47 in group 2 (cancer diagnosed after the diagnosis of acute PE and up to 2 years) and 389 patients were in group 3. Elevated D-dimer levels were independently associated with already known cancer. D-dimer were independent predictors of future cancer diagnosis: OR = 1.07 ((95 % CI: 1.01-1.14) per each 5 ng/mL increase; for patients with D-dimer >15.0 µg/mL the OR of future cancer was 2.10 (1.05-4.18). If only patients with unprovoked PE upon admission (n = 307) were to be considered results were similar considering D-dimer; anaemia also predicted unknown cancer [OR = 2.13 (1.08-4.16)]. CONCLUSIONS: Patients with D-dimer >15 µg/mL presented a >2-fold higher risk of being diagnosed with a cancer condition in the upcoming 2 years. D-dimer may help clinicians in identifying which patients are at higher risk of occult cancer.

Tumor-Infiltrating Lymphocytes in Localized Prostate Cancer: Do They Play an Important Role?

Background Localized prostate cancer is a heterogeneous entity, and new biomarkers are required for risk stratification. This study aimed to characterize tumor-infiltrating lymphocytes (TILs) in localized prostate cancer and assess their potential prognostic markers. Methodology Radical prostatectomy specimens were analyzed to determine infiltration levels of CD4+, CD8+, T cells, and B cells (characterized by CD20+ cells) in the tumor tissue using immunohistochemistry and the recommendations of the International TILs Working Group 2014. The clinical endpoint was biochemical recurrence (BCR), and the study sample was divided into two cohorts (cohort 1: without BCR; cohort 2: with BCR). Prognostic markers were assessed using Kaplan-Meier and univariate/multivariate Cox regression analysis using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results We included 96 patients in this study. BCR occurred in 51% of the patients. Normal TILs infiltration was found in most of the patients (41/31, 87%/63%). T CD4+ infiltration was statistically superior in cohort 2. This enrichment was associated with BCR (p < 0.05; log-rank test). After adjustment for routine clinical variables and Gleason grade groups (grade group ≤2 and grade group ≥3), it remained an independent prognostic variable of early BCR (p < 0.05; multivariate Cox regression). Conclusions This study showed that immune cell infiltration appears to be an important prognostic variable for early recurrence in localized prostate cancer.

Reviewing Treatment Options for Advanced Renal Cell Carcinoma: Is There Still a Place for Tyrosine Kinase Inhibitor (TKI) Monotherapy?

Renal cell carcinoma (RCC) comprises a highly heterogeneous group of kidney tumours built upon distinct genetic- and epigenetic-driven mechanisms and molecular pathways. Therefore, responsiveness to treatment is considerably variable across patients, adding an extra layer of complexity to the already challenging therapeutic decision process. The last decade brought an unprecedented shift in the medical approach to advanced or metastatic RCC; in fact, immunotherapy-based combinations have significantly transformed the therapeutic arsenal and clinical outcomes of these patients. These strategies were quickly adopted by international guidelines committees as the new standards of care. However, this enhanced efficacy comes at the expense of tolerability, with a predictable negative impact on patients' quality of life. Moreover, subgroup and post hoc analyses of the major clinical trials have shown that not all patients benefit equally from these innovative approaches. In this context, a group of experts on kidney cancer met and discussed the state of the art in the field, with a special emphasis on the appropriateness of using monotherapy with an anti-angiogenesis tyrosine kinase inhibitor (TKI) to treat specific subgroups of patients with RCC. This article reviews the main topics that were considered to be pertinent for that discussion and establishes the profile of patients for whom TKI monotherapy remains a sensible frontline option by avoiding overtreatment and an unnecessary exposure to treatment-related toxicity.

Immunotherapy in stage IV non-small cell lung cancer in a patient with Grave's disease: safety and biomarkers of response.

Patients with cancer and pre-existing autoimmune diseases have been excluded from immunotherapy clinical trials. So, studying these patients who received immunotherapy is critical to increasing evidence of the treatment's safety and efficacy in this population. Furthermore, a complete and durable response to immunotherapy in metastatic non-small cell lung cancer (NSCLC) is rare. Therefore, it is imperative to study patients with a complete response in order to identify potential predictors of response to immunotherapy. In this case report, we highlight a 62-year-old man with a smoking history and Graves' disease who achieved a complete response with immunotherapy for metastatic NSCLC, with a long-lasting response and no immune-related adverse events. Male gender, high programmed death-ligand 1 expression, current smokers, epidermal growth factor receptor and anaplastic lymphoma kinase wild types could be biomarkers of response to immune checkpoint inhibitors presented at baseline. Caution should be exercised when interpreting this finding because it represents our patient.

Principales emergencias oncológicas en el cáncer de pulmón: un análisis de un único centro / Main structural oncologic emergencies in lung cancer: a single center analysis

Introduction: Lung cancer is the leading cause of structural oncologic emergencies (OE). The clinical outcome of patients with OE is often poor and mortality is high. The aim of this study was to evaluate the incidence, clinical presentation and outcomes of patients with structural OE in patients with lung cancer. Method: Retrospective cohort study involving all lung cancer patients admitted with a structural OE (superior vena cava syndrome (SVCS) and metastatic spinal cord compression (MSCC)) between January 1, 2015 and November 30, 2019. Long-term outcome was evaluated at 90 days after de OE and during the follow-up time. A comparative analysis between SVCS group and MSCC was also made. Data analysis was performed using the SPSSv.25.0.0 with a significant level of α=5%. Results: Of the 610 patients with the diagnosis of lung cancer, and 35 (~6%) had an OE:16 a SVCS and 19 had a MSCC. OE was the first manifestation of cancer in more than 50% of patients (8 in SVCS group and in 12 in MSCC group).The mortality rate was 66% 90 days after OE and 97% at the end of follow up. Patients with MSCC had worse outcomes when compared to SVCS, with more mortality in the first 3 months and more morbidity. Conclusion: In this study, structural OE was the first manifestation of lung cancer in more than 50% of patients and its occurrence is associated with a worse prognosis. We need to be aware of this situation, especially in the emergency department, in order to minimize those consequences. Future studies are needed to determine the impact of early diagnosis, treatment patterns on OE outcomes and strategies for reducing structural OE related costs. (AU)

Long lasting complete response with immunotherapy in a metastatic bladder carcinoma: a case report.

At diagnosis, approximately 25% of urothelial carcinoma are invasive and only 15% of stage IV are alive at 5-years. We report a case of a 69-year-old woman with oligometastatic bladder cancer, treated with Atezolizumab in first-line, achieving a complete response after 4 cycles. Presently, the patient has an overall survival and progression free survival of 26 months with an improvement in her quality of life. Therefore, immunotherapy seems to be a promising treatment in advanced urothelial carcinoma. The previously performed radiotherapy, in association with a good performance status and oligometastatic disease, might have contributed to this admirable outcome.

The Influence of Gender in The Prognostic Impact of Diabetes mellitus in acute Pulmonary Embolism.

Diabetes mellitus (DM) predicts ominous outcomes in acute pulmonary embolism (PE). The influence of gender on the prognostic impact of DM in PE is unknown. We did a retrospective analysis of a cohort of patients hospitalized with PE between 2006 and 2013. The exclusion criteria were age <18, non-pulmonary veins thromboembolism, recurrent PE, chronic thromboembolic pulmonary hypertension, no radiologic confirmation of PE, and active neoplasia. The primary endpoint was all-cause mortality. The follow-up was from diagnosis until October 2017. We assessed the prognostic impact of DM using a multivariate Cox regression analysis. The analysis was stratified according to gender. The interaction between gender and DM in the outcome of patients with PE was tested. We studied 577 PE patients (median age 65 years, 36.9% men, 19.8% diabetic). The genders were similar regarding the prevalence of DM, the extension and location of PE, and the thrombolytic therapy or brain natriuretic peptide (BNP) value. Diabetics presented higher all-cause mortality (Hazard ratio (HR) = 2.33 (95% confidence Interval (CI) 1.513.61)) when compared with non-diabetics. However, when analysis was stratified according to gender, DM was independently associated with a worse prognosis only in women (HR = 2.31 (95% CI 1.453.65)), while in men the HR was 1.10 (95% CI 0.592.04). The interaction between gender and DM was significant (p = 0.04). Gender influences the prognostic impact of DM in acute PE. Diabetic women with PE have twice the long-term mortality risk, while DM is not mortality-associated in men.

Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification.

BACKGROUND: Seminoma accounts for 30-50% of testicular germ cell tumors (TGCT)-the most common solid malignancy in men aged 15-35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification's potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions. METHODS: All consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed. RESULTS: Seminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median follow-up time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b (P <  0.0001 and P = 0.023, respectively), known adverse biological features. CONCLUSIONS: In our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.

A 10-year review of primary major salivary gland cancers.

Primary salivary gland cancers comprise a heterogeneous group of histological entities and represent less than 5% of head and neck malignancies. Surgical resection is the main treatment, and adjuvant radiotherapy is performed in selected cases. Chemotherapy is an option in metastatic or recurrent disease, with poor evidence. We aimed to review a 10-year experience of a cancer centre on major salivary gland cancers, focusing on clinical, pathological, treatment and patients' outcomes data. A total of 93 patients were identified, median age at diagnosis was 64 years (IQR, 23), and 51.6% were male. The parotid gland was the site of origin in 76.3% of cases. The most frequent histological type was salivary duct carcinoma (21.5%). All patients were submitted to surgery and adjuvant radiotherapy was performed in 74.2%. From 26 patients diagnosed with metastatic disease, 9 were treated with systemic therapy. At 8 years, disease-free survival was 54.6% and overall survival was 48.4%. Male sex, salivary duct carcinoma, stage pT3-4, stage pN2-3, high histologic grade, lymphovascular invasion and perineural invasion were negative prognostic indicators for disease-free survival and overall survival. Extracapsular spread was a negative prognostic indicator for overall survival. In the multivariable analysis, histological type-salivary duct carcinoma-kept significant negative impact in disease-free survival and high histologic grade in overall survival. The most frequent histological type was salivary duct carcinoma, which is estimated to represent only 9% of salivary tumours. Patients with salivary duct carcinoma relapsed more than other histological types. High histologic grade was a negative prognostic indicator for overall survival.

Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies.

Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies. This paper will review the current evidence of immunotherapy in advanced gastric cancer.

Stauffer's syndrome: A comprehensive review and proposed updated diagnostic criteria.

BACKGROUND: Stauffer's syndrome corresponds to a set of clinical and analytical changes of paraneoplastic nature firstly recognized more than 50 years ago, in association to renal cell carcinoma. A definitive review including universal diagnostic criteria and updated knowledge since the original description is lacking. BASIC PROCEDURES: The authors conducted a comprehensive bibliographical review and propose updated diagnostic criteria to standardize diagnosis for clinical practice purposes and avoid misclassification. MAIN FINDINGS: Although having been described in association with renal cell carcinoma, the syndrome has been reported in correlation with other malignancies-either solid or hematological tumors. Additionally, a variant syndrome presenting with jaundice has also been characterized, but appears to have a similar clinical course to that of the classical Stauffer's syndrome. Although often described as rare, it may be more frequent than previously recognized. Stauffer's syndrome etiopathogenesis is still poorly understood, but immune mechanisms seem to play a role underscored by the malignancies to which the syndrome is associated, several of which having immunotherapy drugs approved for their treatment. PRINCIPAL CONCLUSIONS: A set of diagnostic criteria should be used to simplify, broaden and standardized diagnosis, under the entity characterized by reversible paraneoplastic intrahepatic cholestasis. Clinicians should be aware of the syndrome, namely consider further investigation if a plausible cause for unexplained intrahepatic cholestasis in an otherwise healthy patient is not found. Even though no universal approach is available, investigation should be considered regarding metastatic disease after resection of a primary tumor which has revealed persistence or recurrence of symptoms.

Individualized multimodal treatment strategy for metastatic rectal adenocarcinoma: Case report.

Metastatic rectal cancer requires a multidisciplinary and individualized approach. The authors describe a case report of a 48-year-old man with recurrence of rectal adenocarcinoma that underwent multimodal treatment, which included chemotherapy with biologic agents, cytoreduction surgery with hyperthermic intraperitoneal chemotherapy, and radiotherapy with improvement in progression-free survival and overall survival.

Polymyalgia rheumatica and pulmonary adenocarcinoma: A case report and literature review.

Polymyalgia rheumatica is an inflammatory rheumatologic condition that occurs frequently in the elderly. It has been, although infrequently, associated with malignancies, in a synchronous or closely time-related appearance. In such circumstances, polymyalgia rheumatica is considered to be a paraneoplastic syndrome and is often atypical in presentation with poor response to glucocorticoid treatment. We report the case of a 79-year-old woman in which the simultaneous diagnosis of polymyalgia rheumatica and lung adenocarcinoma was made. Rheumatologic symptoms responded partially to anti-inflammatory medication, with further response to lung cancer targeted chemotherapy.

In vivo dosimetry using Gafchromic films during pelvic intraoperative electron radiation therapy (IOERT).

OBJECTIVE: To characterize in vivo dose distributions during pelvic intraoperative electron radiation therapy (IOERT) for rectal cancer and to assess the alterations introduced by irregular irradiation surfaces in the presence of bevelled applicators. METHODS: In vivo measurements were performed with Gafchromic films during 32 IOERT procedures. 1 film per procedure was used for the first 20 procedures. The methodology was then optimized for the remaining 12 procedures by using a set of 3 films. Both the average dose and two-dimensional dose distributions for each film were determined. Phantom measurements were performed for comparison. RESULTS: For flat and concave surfaces, the doses measured in vivo agree with expected values. For concave surfaces with step-like irregularities, measured doses tend to be higher than expected doses. Results obtained with three films per procedure show a large variability along the irradiated surface, with important differences from expected profiles. These results are consistent with the presence of surface hotspots, such as those observed in phantoms in the presence of step-like irregularities, as well as fluid build-up. CONCLUSION: Clinical dose distributions in the IOERT of rectal cancer are often different from the references used for prescription. Further studies are necessary to assess the impact of these differences on treatment outcomes. In vivo measurements are important, but need to be accompanied by accurate imaging of positioning and irradiated surfaces. ADVANCES IN KNOWLEDGE: These results confirm that surface irregularities occur frequently in rectal cancer IOERT and have a measurable effect on the dose distribution.

Investigação de Salmonella spp., Listeria spp., Campylobacter spp. e Pseudomonas spp. no trato intestinal de avestruzes (Struthio camelus) criados no estado do Rio de Janeiro, Brasil / Investigation of Salmonella spp., Listeria spp., Campylobacter spp. and Pseudomonas spp. in ostriches (Struthio camelus) intestine from Rio de Janeiro State, Brazil

Na estrutiocultura, pesquisas relacionadas com a prevalência de micro-organismos patogênicos para esses animais e de importância em saúde pública ainda são escassas. O objetivo deste trabalho foi investigar a presença de Salmonella spp., Listeria spp., Campylobacter spp. e Pseudomonas spp. a partir de 60 amostras de suabes cloacais, provenientes de quatro criatórios de avestruzes e avaliar o perfil de susceptibilidade destes micro-organismos frente aos antimicrobianos. Os micro-organismos dos gêneros Salmonella, Listeria e Campylobacter não foram encontrados nas amostras analisadas. Pseudomonas aeruginosa foi isolado a partir de 17 amostras (28,3,%), provenientes de animais de diferentes faixas etárias, oriundos dos quatro criatórios investigados. Adicionalmente, Escherichia coli foi isolado de 57 amostras (95%), Klebsiella spp., de cinco amostras (8,33%), Proteus mirabilis, Proteus vulgaris e Enterobacter spp. de uma amostra (1,66%). Das 17 cepas de P. aeruginosa submetidas ao teste de susceptibilidade aos antimicrobianos, todas (100%) apresentaram sensibilidade à Amicacina e à Ciprofloxacina e todas (100%) foram resistentes ao Sulfametoxazol/Trimetoprim e à Tetraciclina. Foram encontrados cinco perfis diferentes de resistência aos antimicrobianos, indicando uma variação da resistência entre as cepas de Pseudomonas isoladas, inclusive em animais do mesmo criatório e mantidos no mesmo piquete.

There has been limited research on the prevalence of ostrich intestinal pathogens and on the role of these animals as foodborne pathogens source. This study was conducted to estimate the frequence of Salmonella spp., Listeria spp., Campylobacter spp. and Pseudomonas spp. from intestinal swabs of ostriches and to investigate the antibiotic resistance of the isolates. Sixty samples collected from four ostrich farms were examined. Salmonella, Listeria and Campylobacter were not isolated from the samples investigated and Pseudomonas aeruginosa was isolated from 17 (28.3%) samples. Additionally, Escherichia coli was isolated from 57 samples, (95%), Klebsiella spp. from five (8.33%), and Proteus mirabilis, Proteus vulgaris and Enterobacter spp. from one sample (1,66%). All Pseudomonas isolates were susceptible to Amicacin and Ciprofloxacin, and all of them (100%) were resistant to Trimethoprin/Sulfametox and to Tetracicline. Five antimicrobial resistance profiles were found, showing a resistance diversity among the Pseudomonas isolates, even in the same farm and raised at the same pen.

Celulite em frangos de corte abatidos sob inspeção sanitária: aspectos anatomopatológicos associados ao isolamento de Escherichia coli

Objetivou-se descrever lesões macroscópicas e microscópicas consideradas típicas da celulite e sua associação com apresença de E.coli. Para esta pesquisa utilizaram-se 20 frangos de corte. Foram colhidas amostras de pele de dez carcaçascom suspeita de celulite e dez sem alterações macroscópicas, constituindo o grupo controle. As amostras de pele das dezaves com suspeitas de celulite mostraram úlcera cutânea, sendo que quatro apresentaram espessamento de pele, alteraçõesna coloração tendendo ao amarelo-avermelhado e irregularidade na superfície cutânea. Ao corte observaram-se fluido gelatinosoe placas amarelas destacáveis e em alguns casos acometimento da musculatura adjacente. As lesões suspeitas de celuliteforam confirmadas histologicamente através de aspectos microscópicos específicos da lesão, que se caracterizou por placasfibrinosas ricas em restos celulares, envoltas por infiltrado inflamatório rico em heterófilos ou histiócitos e células gigantesmultinucleadas. Na análise bacteriológica foi isolada E.coli em 100% das lesões de celulite. Como a inspeção veterináriarealizada nos matadouros é essencialmente macroscópica, a análise histopatológica torna-se uma ferramenta importantepara a confirmação do diagnóstico, permitindo uma rápida diferenciação entre as demais lesões cutâneas. Além disso, aanálise bacteriológica permite afirmar que estirpes de E.coli estão freqüentement

Enterotoxigenicidade de Staphylococcus aureus, isolados de vacas com mastite / Enterotoxicity of Staphylococcus aureus isolated from mastitic cows

A prevalência da mastite subclínica foi de 48 por cento, através da reação leucocitária pela prova do "California Mastitis Test" (CMT) em 2.317 vacas em lactação de 86 produtores de uma bacia leiteira no Estado do Rio de Janeiro. Do total de 2,725 lactoculturas, provenientes de 692 vacas, 1.026 (37,65 por cento) apresentaram CMT positivos e 546 (53,22 por cento) foram exame bacteriológico positivo. O Staphylococcus aureus foi o agente mais encontrado, sendo isolado de 229 (41,94 por cento) amostras de leite em todos os rebanhos trabalhados. A possibilidade de contaminação de produtos de origem láctea, por S. aureus e sua enterotoxina induziu a pesquisa da mesma em algumas amostras desse agente. As cepas de S. aureus isoladas de tetas com forte reação leucocitária, evidenciada através do CMT, foram semeadas em caldo cérebro coração com glicerina em partes iguais e mantidas no "freezer" a menos de 16ºC. A termonuclease foi determinada pelo método de Lachica et al. (1971). A pesquisa de enterotoxina dos tipos A, B, C, D e E foi feita pela técnica utilizada por Robbins et al. (1974) no Instituto de Microbiologia da UFRJ. Em 93 cepas de S. aureus analisadas apenas uma produziu enterotoxina do biotipo A, considerada a de maior ocorrência nas intoxicações alimentares, sendo encontrada em 75 por cento dos surtos. Em oito cepas não foi detectada a presença de nucleina termoestável. Mesmo tendo sido baixo o número de cepas enterotoxigênicas, acredita-se que sejam necessários cuidados com o rebanho leiteiro, evitando-se misturar o leite de fêmeas infectadas aos de animais sadios. Tal procedimento constitui uma ameaça à saúde humana, uma vez que o S. aureus é evidenciado em índice elevado na maioria dos rebanhos.