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Background and Objectives: EUS-guided biliary drainage (EUS-BD) is a promising alternative to ERCP in malignant distal biliary obstruction (MDBO). Despite accumulating data, however, its application in clinical practice has been impeded by undefined barriers. This study aims to evaluate the practice of EUS-BD and its barriers. Methods: An online survey was generated using Google Forms. Six gastroenterology/endoscopy associations were contacted between July 2019 and November 2019. Survey questions measured participant characteristics, EUS-BD in different clinical scenarios, and potential barriers. The primary outcome was the uptake of EUS-BD as a first-line modality, without previous ERCP attempts, in patients with MDBO. Results: Overall, 115 respondents completed the survey (2.9% response rate). Respondents were from North America (39.2%), Asia (28.6%), Europe (20%), and other jurisdictions (12.2%). Regarding the uptake of EUS-BD as first-line treatment for MDBO, only 10.5% of respondents would consider EUS-BD as a first-line modality regularly. The main concerns were the lack of high-quality data, fear of adverse events, and limited access to EUS-BD dedicated devices. On multivariable analysis, lack of access to EUS-BD expertise was an independent predictor against the use of EUS-BD, odds ratio 0.16 (95% confidence interval, 0.04-0.65). In salvage situations following failed ERCP, most favored EUS-BD (40.9%) over percutaneous drainage (21.7%) in unresectable cancer. In borderline resectable or locally advanced disease, however, most favored the percutaneous approach due to fear of EUS-BD complicating future surgery. Conclusions: EUS-BD has not reached widespread clinical adoption. Identified barriers include lack of high-quality data, fear of adverse events, and lack of access to EUS-BD dedicated devices. Fear of complicating future surgery was also identified as a barrier in potentially resectable disease.
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Background and Aim: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the standard of care in advanced pancreatic cancer. Its role in resectable disease, however, is controversial. This meta-analysis aims to ascertain the clinical outcomes of patients with resectable pancreatic cancer undergoing preoperative EUS-FNA compared to those going directly to surgery. Methods: A literature search was performed from 1996 to April 2019 using MEDLINE, EMBASE, and ISI Web of Knowledge for studies comparing preoperative EUS-FNA to EUS without FNA in resectable pancreatic cancer for clinical outcomes. The primary outcome is overall survival (OS). Secondary outcomes include cancer-free survival, tumor recurrence and peritoneal carcinomatosis, and post-FNA-pancreatitis rate. Results: Six retrospective studies were included. Preoperative EUS-FNA had better OS than the non-FNA group (WMD, 4.40 months [0.02 to 8.78]). Cancer-free survival did not differ significantly between the two groups (WMD, 2.08 months [-2.22 to 6.38]). EUS with FNA was not associated with increased rates of tumor recurrence or peritoneal carcinomatosis. Conclusion: Preoperative EUS-FNA in resectable pancreatic cancer may be associated with significantly greater OS when compared to the non-FNA group, with no significant difference in the rates of tumor recurrence or peritoneal seeding. Important limitations of our meta-analysis include the lack of prospective controlled data, which are unlikely to emerge given feasible constraints.
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Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that Claudin-2 is functionally required for colorectal cancer liver metastasis and that Claudin-2 expression in primary colorectal cancers is associated with poor overall and liver metastasis-free survival. We have examined the role of Claudin-2, and other claudin family members, as potential prognostic biomarkers of the desmoplastic and replacement histopathological growth pattern associated with colorectal cancer liver metastases. Immunohistochemical analysis revealed higher Claudin-2 levels in replacement type metastases when compared to those with desmoplastic features. In contrast, Claudin-8 was highly expressed in desmoplastic colorectal cancer liver metastases. Similar observations were made following immunohistochemical staining of patient-derived xenografts (PDXs) that we have established, which faithfully retain the histopathology of desmoplastic or replacement type colorectal cancer liver metastases. We provide evidence that Claudin-2 status in patient-derived extracellular vesicles may serve as a relevant prognostic biomarker to predict whether colorectal cancer patients have developed replacement type liver metastases. Such a biomarker will be a valuable tool in designing optimal treatment strategies to better manage patients with colorectal cancer liver metastases.
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Biomarcadores Tumorais/fisiologia , Claudinas/fisiologia , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/patologia , Animais , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Adesão Celular/genética , Adesão Celular/fisiologia , Claudinas/antagonistas & inibidores , Claudinas/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Células HT29 , Hepatócitos/patologia , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos SCID , Domínios PDZ/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Colorectal cancer liver metastases (CRCLM) that present with a replacement histopathological growth pattern (HGP) are resistant to neoadjuvant anti-angiogenic therapy. Surrogate biomarkers are not available to preoperatively identify patients with these tumors. Here we identify differentially expressed genes between CRCLM with a replacement HGP and those with a desmoplastic HGP using RNA sequencing. We demonstrate that LOXL4 is transcriptionally upregulated in replacement HGP CRCLM compared with desmoplastic HGP CRCLM and the adjacent normal liver. Interestingly, lysyl oxidase-like 4 (LOXL4) protein was expressed by neutrophils present in the tumor microenvironment in replacement HGP CRCLM. We further demonstrate that LOXL4 expression is higher in circulating neutrophils of cancer patients compared with healthy control patients and its expression can be induced by stimulation with lipopolysaccharide and TNF-α. Our study is the first to show the expression of LOXL4 in neutrophils and reveals the potential for LOXL4-expressing neutrophils to support the replacement HGP phenotype and to serve as a surrogate biomarker for this subtype of CRCLM. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Inibidores da Angiogênese/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enzimologia , Neutrófilos/efeitos dos fármacos , Proteína-Lisina 6-Oxidase/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neutrófilos/enzimologia , Fenótipo , Proteína-Lisina 6-Oxidase/genética , Transdução de Sinais , Transcrição Gênica , Microambiente Tumoral , Regulação para CimaRESUMO
A 28-year-old man previously diagnosed and treated for testicular sex cord-stromal tumour (TSCST) presented with symptoms of fever, night sweats and fatigue. Following initial investigations for an infectious aetiology, imaging studies detected two large liver lesions. Histopathological assessment of the tumours revealed that they were metastases from the TSCST for which the patient had radical inguinal orchiectomy and retroperitoneal lymph node dissection 5 years prior. The curative-intent management of the bilobar liver metastases necessitated staged resection due to the chemoresistant and radioresistant properties of TSCST. The size of the lesions was such that procedures to induce rapid liver hypertrophy were required between surgeries. Both liver metastases were successfully removed following this approach. The patient remains recurrence-free 1 year after surgery and has maintained predisease levels of performance. Nevertheless, he continues to be followed for routine CT scans at regular intervals.
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Neoplasias Hepáticas/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Neoplasias Testiculares/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Metástase Neoplásica , Orquiectomia , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico por imagem , Tumores do Estroma Gonadal e dos Cordões Sexuais/secundário , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Tomografia Computadorizada por Raios XAssuntos
Acidentes de Trânsito , Falso Aneurisma/terapia , Angioplastia com Balão/instrumentação , Artéria Pulmonar/lesões , Stents , Lesões do Sistema Vascular/terapia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/fisiopatologia , Criança , Angiografia por Tomografia Computadorizada , Humanos , Masculino , Desenho de Prótese , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/fisiopatologiaRESUMO
The most effective natural prevention against breast cancer is an early first full-term pregnancy. Understanding how the protective effect is elicited will inform the development of new prevention strategies. To better understand the role of epigenetics in long-term protection, we investigated parity-induced DNA methylation in the mammary gland. FVB mice were bred or remained nulliparous and mammary glands harvested immediately after involution (early) or 6.5 months following involution (late), allowing identification of both transient and persistent changes. Targeted DNA methylation (109 Mb of Ensemble regulatory features) analysis was performed using the SureSelectXT Mouse Methyl-seq assay and massively parallel sequencing. Two hundred sixty-nine genes were hypermethylated and 128 hypomethylated persistently at both the early and late time points. Pathway analysis of the persistently differentially methylated genes revealed Igf1r to be central to one of the top identified signaling networks, and Igf1r itself was one of the most significantly hypermethylated genes. Hypermethylation of Igf1r in the parous mammary gland was associated with a reduction of Igf1r mRNA expression. These data suggest that the IGF pathway is regulated at multiple levels during pregnancy and that its modification might be critical in the protective role of pregnancy. This supports the approach of lowering IGF action for prevention of breast cancer, a concept that is currently being tested clinically.