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1.
Bone Marrow Transplant ; 58(12): 1384-1389, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37699993

RESUMO

Recently there has been a growing interest in evaluating body composition as a marker for prognosis in cancer patients. The association of body composition parameters and outcomes has not been deeply investigated in patients with autologous hematopoietic stem cell transplantation (HSCT) recipients with non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of 264 NHL patients who received autologous HSCT. PreHSCT abdominal CT scans at the levels of L3 were assessed for body composition measures. We evaluated sarcopenia, myosteatosis, high visceral adipose tissue (VAT) and high visceral adipose tissue density (VATD). Using multivariable Cox proportional regression, we analyzed the association of clinical and transplant-related characteristics with overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM). In a multivariate regression model, patients with higher VATD had worse OS (HR 1.78; 95% confidence intervals CI 1.08-2.95, p = 0.02) and worse NRM (HR 2.31 95% CI 1.08-4.95, p = 0.02) than with lower VATD. Patients with lower levels of VAT also had worse RFS (HR 1.49 95% CI 1.03-2.15, p = 0.03). Sarcopenia and myosteatosis were not associated with outcomes. High pre-transplant VATD was associated with lower OS and higher NRM, and low pre-transplant VAT was associated with worse RFS in patients with NHL undergoing autologous HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Sarcopenia , Humanos , Estudos Retrospectivos , Sarcopenia/etiologia , Recidiva Local de Neoplasia , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/patologia , Transplante Autólogo , Composição Corporal
2.
United European Gastroenterol J ; 10(10): 1167-1178, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36326993

RESUMO

Strictures in Crohn's disease (CD) are a hallmark of long-standing intestinal damage, brought about by inflammatory and non-inflammatory pathways. Understanding the complex pathophysiology related to inflammatory infiltrates, extracellular matrix deposition, as well as muscular hyperplasia is crucial to produce high-quality scoring indices for assessing CD strictures. In addition, cross-sectional imaging modalities are the primary tool for diagnosis and follow-up of strictures, especially with the initiation of anti-fibrotic therapy clinical trials. This in turn requires such modalities to both diagnose strictures with high accuracy, as well as be able to delineate the impact of each histomorphologic component on the individual stricture. We discuss the current knowledge on cross-sectional imaging modalities used for stricturing CD, with an emphasis on histomorphologic correlates, novel imaging parameters which may improve segregation between inflammatory, muscular, and fibrotic stricture components, as well as a future outlook on the role of artificial intelligence in this field of gastroenterology.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Constrição Patológica/patologia , Inteligência Artificial , Intestinos/patologia , Fibrose
3.
J Am Coll Radiol ; 18(9): 1324-1331, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34004175

RESUMO

OBJECTIVE: To assess current practice patterns with respect to protocols used for incidental pancreatic cyst follow-up, management guidelines, and template reporting. METHODS: The Society of Abdominal Radiology Disease Focused Panel on intraductal pancreatic neoplasms distributed an anonymous 14-question survey to its members in June 2018 that focused on current utilization of incidental pancreatic cyst guidelines, protocols, and template reporting. RESULTS: Among the 1,390 email invitations, 323 responded, and 94.7% (306 of 323) completed all questions. Respondents were mainly radiologists (93.8%, 303 of 323) from academic institutions (74.7%, 227 of 304) in North America (93.7%, 286 of 305). Of respondents, 42.5% (136 of 320) preferred 2017 ACR recommendations, 17.8% (57 of 320) homegrown systems, 15.0% (48 of 320) Fukuoka guidelines, and 7.8% (25 of 320) American Gastroenterological Association guidelines. The majority (68.7%, 222 of 323) agreed or strongly agreed that developing a single international consensus recommendation for management was important, and most radiologists preferred to include them in reports (231 of 322, 71.7%); yet only half included recommendations in >75% of reports (161 of 321). MR cholangiopancreatography was the modality of choice for follow-up of <2.5 cm cysts. Intravenous contrast was routinely used by 69.7% (212 of 304). Standardized reporting templates were rarely used in practice (12.8% 39 of 306). CONCLUSIONS: Nearly 7 of 10 radiologists desire a unified international consensus recommendation for management of incidental cystic pancreatic lesions; ACR 2017 recommendations are most commonly used, followed by homegrown systems and Fukuoka guidelines. The majority of radiologists routinely use MR cholangiopancreatography with intravenous contrast for follow-up of incidental cystic lesions, but template reporting is rarely used.


Assuntos
Cisto Pancreático , Neoplasias Pancreáticas , Radiologia , Humanos , Achados Incidentais , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/terapia , Radiografia Abdominal , Inquéritos e Questionários
4.
JAMA Oncol ; 7(3): 421-427, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33475684

RESUMO

Importance: Clinical outcomes after curative treatment of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. To assess the potential of early control of systemic disease with multiagent perioperative chemotherapy, we conducted a prospective trial. Objective: To determine 2-year overall survival (OS) using perioperative chemotherapy for resectable PDA. Design, Setting, and Participants: This was a randomized phase 2 trial of perioperative chemotherapy with a pick-the-winner design. It was conducted across the National Clinical Trials Network, including academic and community centers all across the US. Eligibility required patients with Zubrod Performance Score of 0 or 1, confirmed tissue diagnosis of PDA, and resectable disease per Intergroup criteria. Interventions: Perioperative (12 weeks preoperative, 12 weeks postoperative) chemotherapy with either fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX, arm 1) or gemcitabine/nab-paclitaxel (arm 2). Main Outcomes and Measures: The primary outcome was 2-year overall survival (OS), using a pick-the-winner design; for 100 eligible patients, accrual up to 150 patients was planned to account for cases deemed ineligible at central radiology review. Results: From 2015 to 2018, 147 patients were enrolled; 43 patients (29%) had ineligible disease, beyond resectability criteria, at central radiology review. There were 102 eligible and evaluable patients, 55 in arm 1 and 47 in arm 2, of whom the median (range) age was 66 (44-76) and 64 (46-76) years, respectively; 36 patients (65%) in arm 1 and 24 (51%) in arm 2 were men. In arm 1, 34 (62%) had Zubrod Performance Score of 0, while in arm 2, 31 (66%) did; and 44 (80%) in arm 1 and 39 (83%) in arm 2 had head tumors. Of 102 patients, 84% and 85% completed preoperative chemotherapy, 73% and 70% underwent resection, and 49% and 40% completed all treatment. Adverse events were expected hematologic toxic effects, fatigue, and gastrointestinal toxicities. Two-year OS was 47% (95% CI, 31%-61%) for arm 1 and 48% (95% CI, 31%-63%) for arm 2; median OS was 23.2 months (95% CI, 17.6-45.9 months) and 23.6 months (95% CI, 17.8-31.7 months). Neither arm's 2-year OS estimate was significantly higher than the a priori threshold of 40%. Median disease-free survival after resection was 10.9 months in arm 1 and 14.2 months in arm 2. Conclusions and Relevance: This phase 2 randomized clinical trial did not demonstrate an improved OS with perioperative chemotherapy, compared with historical data from adjuvant trials in resectable pancreatic cancer. Two-year OS was 47% with mFOLFIRINOX and 48% with gemcitabine/nab-paclitaxel for all eligible patients starting treatment for resectable PDA. The trial also demonstrated adequate safety and high resectability rates with perioperative chemotherapy, and challenges in quality control for resectability criteria. Trial Registration: ClinicalTrials.gov Identifier: NCT02562716.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos
5.
Abdom Radiol (NY) ; 46(4): 1586-1606, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33185741

RESUMO

There have been many publications detailing imaging features of malignant transformation of intraductal papillary mucinous neoplasms (IPMN), management and recommendations for imaging follow-up of diagnosed or presumed IPMN. However, there is no consensus on several practical aspects of imaging IPMN that could serve as a clinical guide for radiologists and enable future data mining for research. These aspects include how to measure IPMN, define reporting terminology, standardize reporting and unify guidelines for surveillance. The Society of Abdominal Radiology (SAR) created multiple Disease-Focused Panels (DFP) comprised multidisciplinary panel members who focus on a particular disease, with the goal to develop ways for radiologists to improve patient care, education, and research. DFP members met to identify the current controversies and limitations of imaging pancreatic IPMN. This paper aims to provide a practical review of the key imaging characteristics of IPMN for trainees and practicing radiologists, to guide uniformity of performance and interpretation of surveillance imaging studies, and to improve communication with clinicians by providing a lexicon and reporting template based on the experience of the SAR-DFP panel members.


Assuntos
Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Radiologia , Humanos , Pâncreas , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Radiografia Abdominal
6.
Ann Surg ; 272(3): 481-486, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32740235

RESUMO

OBJECTIVE: The optimal neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDA) and the impact on surgical outcomes remains unclear. METHODS: S1505 (NCT02562716) was a randomized phase II study of perioperative chemotherapy with mFOLFIRINOX (Arm 1) or gemcitabine/nab-paclitaxel (Arm 2). Measured parameters included resection rate, margin positivity, pathologic response, and toxicity. RESULTS: Between 2015 and 2018, 147 patients were randomized. Of these, 44 (30%) were deemed ineligible (43 by central review). Of the 103 eligible patients, 77 (76%) completed preoperative therapy and underwent surgery; reasons patients did not undergo surgery included toxicity related to preoperative therapy (n = 9), progression (n = 9), or other (n = 7). Of the 77, 73 (95%) underwent successful resection; 21 (29%) required vascular reconstruction, 62 (85%) had negative (R0) margins, and 24 (33%) had a complete or major pathologic response to therapy. The grade 3-5 postoperative complication rate was 16%. Of the 73 patients completing surgery, 57 (78%) started and 46 (63%) completed postoperative therapy. This study represents the first prospective trial evaluating modern systemic therapy delivered in a neoadjuvant/perioperative format for resectable PDA. CONCLUSIONS: We have demonstrated: (1) Based on the high percentage of enrolled, but ineligible patients, it is clear that adherence to strict definitions of resectable PDA is challenging; (2) Patients can tolerate modern systemic therapy and undergo successful surgical resection without prohibitive perioperative complications; (3) Completion of adjuvant therapy in the perioperative format is difficult; (4) Major pathologic response rate of 33% is encouraging.


Assuntos
Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Pancreatectomia , Neoplasias Pancreáticas/terapia , Assistência Perioperatória/métodos , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/diagnóstico , Terapia Combinada , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/diagnóstico , Estudos Prospectivos , Resultado do Tratamento , Gencitabina
7.
Radiographics ; 40(2): 354-375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31951512

RESUMO

Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society for Pediatric Radiology, the American Gastroenterological Association, and other international experts recently reported consensus recommendations for standardized nomenclature for the interpretation and reporting of CT enterography and MR enterography findings of small bowel Crohn disease. The consensus recommendations included CT enterography and MR enterography bowel wall findings that are associated with Crohn disease, findings that occur with penetrating Crohn disease, and changes that occur in the mesentery related to Crohn disease. Also included were recommended radiology report impression statements that summarize the findings of small bowel Crohn disease at CT enterography and MR enterography. This article, authored by the Society of Abdominal Radiology Crohn's Disease-Focused Panel, illustrates the imaging findings and recommended radiology report impression statements described in the consensus recommendations with examples of CT enterography and MR enterography images. Additional interpretation guidelines for reporting CT enterography and MR enterography examinations are also presented. The recommended standardized nomenclature can be used to generate radiology report dictations that will help guide medical and surgical management for patients with small bowel Crohn disease. Online supplemental material is available for this article. ©RSNA, 2020See discussion on this article by Heverhagen.


Assuntos
Doença de Crohn/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Terminologia como Assunto , Tomografia Computadorizada por Raios X , Humanos
8.
Abdom Radiol (NY) ; 45(4): 1011-1017, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31982931

RESUMO

PURPOSE: To survey Society of Abdominal Radiology Crohn's Disease (CD) Disease-Focused Panel (DFP) members to understand state-of-the-art CT/MR enterography (CTE/MRE) protocols and variability between institutions. METHODS: This study was determined by an institutional review board to be "exempt" research. The survey consisted of 70 questions about CTE/MRE patient preparation, administration of contrast materials, imaging techniques, and other protocol details. The survey was administered to DFP members using SurveyMonkey® (Surveymonkey.com). Descriptive statistical analyses were performed. RESULTS: Responses were received from 16 DFP institutions (3 non-USA, 2 pediatric); 15 (94%) were academic/university-based. 10 (63%) Institutions image most CD patients with MRE; 4 (25%) use CTE and MRE equally. Hypoperistaltic medication is given for MRE at 13 (81%) institutions versus only 2 (13%) institutions for CTE. Most institutions have a technologist or nurse monitor oral contrast material drinking (n = 12 for CTE, 75%; n = 11 for MRE, 69%). 2 (13%) institutions use only dual-energy capable scanners for CTE, while 9 (56%) use either a single-energy or dual-energy scanner based on availability. Axial CTE images are reconstructed at 2-3 mm thickness at 8 (50%) institutions, > 3 mm at 5 (31%), and < 2 mm at 3 (19%) institutions. 13 (81%) institutions perform MRE on either 1.5 or 3T scanners without preference. All institutions perform MRE multiphase postcontrast imaging (median = 4 phases), ranging from 20 to 600 s after contrast material injection. CONCLUSION: CTE and MRE protocol knowledge from DFP institutions can help radiology practices optimize/standardize protocols, potentially improving image quality and patient outcomes, permitting objective comparisons between examinations, and facilitating research.


Assuntos
Doença de Crohn/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Padrões de Prática Médica , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste , Feminino , Humanos , Masculino , Sociedades Médicas , Inquéritos e Questionários
9.
Inflamm Bowel Dis ; 25(3): 421-426, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30346528

RESUMO

Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called "creeping fat") was described as a characteristic feature of Crohn's disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat-mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.


Assuntos
Tecido Adiposo/fisiopatologia , Constrição Patológica/fisiopatologia , Doença de Crohn/patologia , Intestinos/fisiopatologia , Mesentério/fisiopatologia , Doenças Musculares/complicações , Doença de Crohn/etiologia , Humanos , Prognóstico
10.
HPB (Oxford) ; 20(1): 34-40, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28890311

RESUMO

BACKGROUND: Patients with altered anatomy due to Roux-en-Y gastric bypass (RYGB) present unique diagnostic and therapeutic challenges when they present with periampullary pathology. We describe a series of patients who underwent pancreatoduodenectomy (PD) after gastric surgery with Roux-en-Y reconstruction and review the literature to highlight technical considerations and outcomes. METHODS: Patients from two institutions were identified and data regarding preoperative workup, operative conduct, and pathologic and clinical outcomes were collected. RESULTS: Eleven patients were included in the institutional series. At the time of periampullary pathology, the median age was 64 years and time since RYGB was 10 years. Median operative time was 361 minutes, estimated blood loss was 500 mLs, and length of stay was 6 days. Remnant gastrectomy was performed in nine patients and reconstruction was performed using the biliopancreatic limb (BP) without revision of the jejuno-jejunostomy in ten patients. Pathology revealed pancreatic cancer (8), chronic pancreatitis (2), and duodenal cancer (1). Three patients experienced major complications and there were no 90-day mortalities. CONCLUSION: Pancreatic surgeons will see an increasing number of patients with Roux-en-Y anatomy who will require evaluation and resection for periampullary diseases. For PD after RYGB, we recommend remnant gastrectomy with reconstruction using the BP limb.


Assuntos
Gastrectomia , Derivação Gástrica , Obesidade/cirurgia , Pancreatopatias/cirurgia , Pancreaticoduodenectomia , Idoso , Anastomose em-Y de Roux , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Duração da Cirurgia , Pancreatopatias/complicações , Estudos Retrospectivos
11.
Abdom Radiol (NY) ; 43(2): 364-373, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29116342

RESUMO

In this article, we review the information that radiologists need to know regarding the endoscopic approach to the diagnosis and management of pancreatic cancer. This includes a review of the indications, techniques, and complications of endoscopic ultrasound. We also review information regarding endoscopic retrograde cholangiopancreatography, including the various biliary drainage techniques and the use of endoscopic palliation for patients with pancreatic cancer.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Endoscopia Gastrointestinal/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Diagnóstico Diferencial , Drenagem/métodos , Endossonografia , Humanos , Biópsia Guiada por Imagem , Cuidados Paliativos , Tomografia Computadorizada por Raios X
12.
Abdom Radiol (NY) ; 43(2): 273-284, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29038855

RESUMO

Pancreatic ductal adenocarcinoma is the most common primary malignancy of the pancreas. The classic imaging features are a hypovascular mass with proximal ductal dilatation. Different pancreatic pathologies can mimic the imaging appearance of carcinoma including other tumors involving the pancreas (pancreatic neuroendocrine tumors, lymphoma, metastasis, and rare tumors like pancreatic acinar cell carcinoma and solid pseudopapillary tumors), inflammatory processes (chronic pancreatitis and autoimmune pancreatitis), and anatomic variants (annular pancreas). Differentiation between these entities can sometimes be challenging due to overlap of imaging features. The purpose of this article is to describe the common entities that can mimic pancreatic cancer on imaging with illustrative examples and to suggest features that can help in differentiation of these entities.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Variação Anatômica , Doenças Autoimunes/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Pâncreas/anormalidades , Pâncreas/diagnóstico por imagem , Pancreatopatias/diagnóstico por imagem , Pancreatite/diagnóstico por imagem
13.
Plast Reconstr Surg ; 139(6): 1466-1473, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28538578

RESUMO

BACKGROUND: Candidates for multivisceral transplantation present with complex defects often beyond traditional reconstructive options. In this study, the authors describe a dissection technique for a total abdominal wall vascularized composite flap. In addition, the authors suggest a classification system for complex abdominal wall defects. METHODS: Forty fresh, cadaveric hemiabdomens were dissected, with care taken to preserve the iliofemoral, deep circumflex iliac, superficial circumflex iliac, deep inferior epigastric, and superficial inferior epigastric arteries and corresponding veins. Perfusion patterns of the flaps were then studied using computed tomographic angiography. RESULTS: The deep circumflex iliac, superficial circumflex iliac, deep inferior epigastric, and superficial inferior epigastric arteries were identified along a 5-cm cuff of the iliofemoral artery centered on the inguinal ligament. Perfusion with an intact deep circumflex iliac artery yielded improvement in lateral perfusion based on computed tomographic angiography. CONCLUSIONS: The authors propose an algorithm for abdominal wall reconstruction based on defect size and abdominal wall perfusion, and their technique for harvesting a total vascularized composite abdominal wall flap for allotransplantation. Total abdominal wall transplantation should be considered in the subset of patients already receiving visceral organ transplants who also have concomitant abdominal wall defects.


Assuntos
Parede Abdominal/anatomia & histologia , Parede Abdominal/irrigação sanguínea , Retalho Miocutâneo/transplante , Procedimentos de Cirurgia Plástica/métodos , Músculos Abdominais/irrigação sanguínea , Músculos Abdominais/transplante , Parede Abdominal/cirurgia , Adulto , Cadáver , Dissecação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retalho Miocutâneo/irrigação sanguínea , Medição de Risco
14.
Expert Rev Clin Immunol ; 13(5): 425-437, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28277826

RESUMO

INTRODUCTION: Allergy results from an aberrant Type 2 inflammatory response, triggered by a wide range of environmental antigens (allergens) that lead to various immune responses, culminating in the production of immunoglobulin E (IgE). Two key cytokines, interleukin (IL)-4 and IL-13, are critical to the induction and perpetuation of the Type 2 response, and have been implicated in multiple atopic diseases. Area covered: This review summarizes recent milestone developments that have elucidated components of the pathogenesis of atopic diseases such as atopic dermatitis (AD), asthma, and chronic sinusitis with nasal polyposis (CSwNP). Expert commentary: Several therapeutic agents that selectively target potentiators of the Type 2 pathway have shown efficacy in one or more of these atopic diseases, but few agents have proven to be broadly applicable across all three atopic diseases. Dupilumab, a human monoclonal antibody that simultaneously inhibits signaling of IL-4 and IL-13, has demonstrated significant clinical efficacy in AD, asthma, and CSwNP. The fact that these diseases often occur as comorbidities and respond to the same therapy suggests that there is a common underlying pathogenic pathway, and that IL-4 and IL-13 cytokines are central to regulating the pathogenesis of these atopic diseases.


Assuntos
Asma/imunologia , Dermatite Atópica/imunologia , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Pólipos Nasais/imunologia , Sinusite/imunologia , Células Th2/imunologia , Alérgenos/imunologia , Doença Crônica , Humanos , Terapia de Alvo Molecular , Transdução de Sinais
15.
Surg Clin North Am ; 96(6): 1235-1256, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27865275

RESUMO

Imaging studies are critical for the detection, characterization, initial staging, management, and monitoring of pancreatic cancer cases. Treatment of pancreatic cancer requires a multidisciplinary approach. Ideally, assessing resectablility with imaging and subsequent treatment decisions should be made at a high-volume center of excellence with a multidisciplinary team. This article reviews the major imaging modalities used to evaluate pancreatic neoplasms, with an emphasis on pancreatic imaging protocols. The imaging appearance of solid pancreatic neoplasms and the imaging criteria used to stage and determine resectability for pancreatic ductal adenocarcinoma are described. An approach to standardized radiologic reporting is also reviewed.


Assuntos
Diagnóstico por Imagem , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/diagnóstico , Humanos
16.
Radiology ; 280(2): 436-45, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27077382

RESUMO

Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all half-dose reconstructions than with full-dose FBP (mean proportion: 0.117 for half-dose FBP, 0.054 for half-dose SAFIRE 3, 0.054 for half-dose SAFIRE 4, and 0.017 for full-dose FBP; P < .001). Conclusion The diagnostic accuracy of half-dose CT enterography with FBP and SAFIRE is statistically noninferior to that of full-dose CT enterography for active inflammatory terminal ileal Crohn disease, despite an inferior subjective image quality. (©) RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Doença de Crohn/diagnóstico por imagem , Ileíte/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Doença de Crohn/complicações , Feminino , Trato Gastrointestinal/diagnóstico por imagem , Humanos , Ileíte/complicações , Íleo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
17.
JAMA ; 315(5): 469-79, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26836729

RESUMO

IMPORTANCE: Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. OBJECTIVE: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. INTERVENTIONS: Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. MAIN OUTCOMES AND MEASURES: Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. RESULTS: Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95% CI, -2.4 to -0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95% CI, -25.6 to -10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%). CONCLUSIONS AND RELEVANCE: Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01920893.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Interleucina-13/antagonistas & inibidores , Interleucina-4/antagonistas & inibidores , Sinusite/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Asma/tratamento farmacológico , Doença Crônica , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Furoato de Mometasona/administração & dosagem , Pólipos Nasais/tratamento farmacológico , Sprays Nasais , Qualidade de Vida , Sinusite/complicações
18.
Nat Rev Drug Discov ; 15(1): 35-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26471366

RESUMO

Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype. More recently, efficacy was extended into a broad population of people with asthma. This argues that the Type 2 inflammation is broadly relevant across the severe asthma population if the key upstream drivers are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has shown significant clinical activity in diseases that are often co-morbid with asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting the hypothesis that targeting a central 'driver pathway' could benefit multiple allergic diseases.


Assuntos
Inflamação/tratamento farmacológico , Inflamação/imunologia , Terapia de Alvo Molecular/métodos , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Anticorpos Monoclonais/uso terapêutico , Humanos , Interleucina-13/antagonistas & inibidores , Interleucina-13/imunologia , Interleucina-4/antagonistas & inibidores , Interleucina-4/imunologia , Interleucina-5/antagonistas & inibidores , Interleucina-5/imunologia , Modelos Imunológicos
19.
J Gastrointest Surg ; 19(6): 1007-14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25820486

RESUMO

INTRODUCTION: Laparoscopy is accepted as a standard surgical approach for Crohn's disease. However, the rate of conversion is high, ranging from 15 to 70 % depending on the population. There are also concerns that conversion results in worsened outcomes versus an initial open procedure. METHODS: This study evaluated preoperative radiographic findings to determine who is at increased risk of conversion and may therefore benefit from an initial open approach. A case-matched study included patients from 2004 to 2013 with preoperative CTE/MRE who underwent laparoscopic surgery converted to an open approach, and compared them to laparoscopically completed controls with similar age, same surgeon, and number of previous abdominal operations. Studies were reviewed by two blinded radiologists. Variables included abdominal AP diameter, amount of subcutaneous fat, peritoneal versus pelvic location of disease (greater or lesser hemipelvis or abdomen), intestinal location of disease (colon, TI, ileum, jejunum), and presence, length, and location of strictures, simple or complex fistula, phlegmon, or abscess. Conditional logistic regression evaluated relationships between radiographic variables and conversion. Twenty-seven patients meeting study criteria were compared with 81 controls. RESULTS: A negative association between conversion and disease in the left lesser pelvis was found (p = 0.019) and neared significance for left abdomen (p = 0.08). Positive correlations were found with pelvic fistulas (p = 0.003), complex fistulas (p = 0.017), and pelvic abscesses (p = 0.009) and neared significance for Society of Abdominal Radiology classification (p = 0.058). CONCLUSION: Preoperative imaging in patients with Crohn's disease can help in selecting the most suitable cases to approach laparoscopically and reduce conversion rates and should be evaluated in conjunction with other preoperative factors.


Assuntos
Conversão para Cirurgia Aberta/métodos , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/cirurgia , Laparoscopia/métodos , Radiografia Abdominal/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Período Pré-Operatório , Prognóstico , Fatores de Risco
20.
Eur Radiol ; 24(12): 3134-41, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25100335

RESUMO

OBJECTIVES: To assess the value of secretin during magnetic resonance cholangiopancreatography (MRCP) in demonstrating communication between cystic lesions and the pancreatic duct to help determine the diagnosis of side-branch intraductal papillary mucinous neoplasm (SB-IPMN). METHODS: This is an IRB-approved, HIPAA-compliant retrospective study of 29 SB-IPMN patients and 13 non-IPMN subjects (control) who underwent secretin-enhanced MRCP (s-MRCP). Two readers blinded to the final diagnosis reviewed three randomised image sets: (1) pre-secretin HASTE, (2) dynamic s-MRCP and (3) post-secretin HASTE. Logistic regression, generalised linear models and ROC analyses were used to compare pre- and post-secretin results. RESULTS: There was no significant difference in median scores for the pre-secretin [reader 1: 1; reader 2: 2 (range -2 to 2)] and post-secretin HASTE [reader 1: 1; reader 2: 1 (range -2 to 2)] in the SB-IPMN group (P = 0.14), while the scores were lower for s-MRCP [reader 1: 0.5 (range -2 to 2); reader 2: 0 (range -1 to 2); P = 0.016]. There was no significant difference in mean maximum diameter of SB-IPMN on pre- and post-secretin HASTE, and s-MRCP (P > 0.05). CONCLUSION: Secretin stimulation did not add to MRCP in characterising pancreatic cystic lesions as SB-IPMN. KEY POINTS: Magnetic resonance cholangiopancreatography (MRCP) is used to evaluate pancreatic cystic lesions. Intraductal papillary mucinous neoplasm (IPMN) is a type of pancreatic cystic neoplasm. Secretin administration does not facilitate the diagnosis of IPMN on MRCP.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Papilar/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Secretina , Adenocarcinoma Mucinoso/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Colangiopancreatografia por Ressonância Magnética/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Método Simples-Cego
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