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1.
Laryngorhinootologie ; 103(6): 450-451, 2024 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-38830357
2.
Zentralbl Chir ; 149(3): 224-225, 2024 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-38838696
4.
Laryngorhinootologie ; 103(2): 133-134, 2024 02.
Artículo en Alemán | MEDLINE | ID: mdl-38320567
5.
Radiology ; 310(1): e230453, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38259204

RESUMEN

Background Splenic biopsy is rarely performed because of the perceived risk of hemorrhagic complications. Purpose To evaluate the safety of large bore (≥18 gauge) image-guided splenic biopsy. Materials and Methods This retrospective study included consecutive adult patients who underwent US- or CT-guided splenic biopsy between March 2001 and March 2022 at eight academic institutions in the United States. Biopsies were performed with needles that were 18 gauge or larger, with a comparison group of biopsies with needles smaller than 18 gauge. The primary outcome was significant bleeding after the procedure, defined by the presence of bleeding at CT performed within 30 days or angiography and/or surgery performed to manage the bleeding. Categorical variables were compared using the χ2 test and medians were compared using the Mann-Whitney test. Results A total of 239 patients (median age, 63 years; IQR, 50-71 years; 116 of 239 [48.5%] female patients) underwent splenic biopsy with an 18-gauge or smaller needle and 139 patients (median age, 58 years [IQR, 49-69 years]; 66 of 139 [47.5%] female patients) underwent biopsy with a needle larger than 18 gauge. Bleeding was detected in 20 of 239 (8.4%) patients in the 18-gauge or smaller group and 11 of 139 (7.9%) in the larger than 18-gauge group. Bleeding was treated in five of 239 (2.1%) patients in the 18-gauge or smaller group and one of 139 (1%) in the larger than 18-gauge group. No deaths related to the biopsy procedure were recorded during the study period. Patients with bleeding after biopsy had smaller lesions compared with patients without bleeding (median, 2.1 cm [IQR, 1.6-5.4 cm] vs 3.5 cm [IQR, 2-6.8 cm], respectively; P = .03). Patients with a history of lymphoma or leukemia showed a lower incidence of bleeding than patients without this history (three of 90 [3%] vs 28 of 288 [9.7%], respectively; P = .05). Conclusion Bleeding after splenic biopsy with a needle 18 gauge or larger was similar to biopsy with a needle smaller than 18 gauge and seen in 8% of procedures overall, with 2% overall requiring treatment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grant in this issue.


Asunto(s)
Biopsia Guiada por Imagen , Agujas , Bazo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiografía , Biopsia Guiada por Imagen/efectos adversos , Agujas/efectos adversos , Agujas/estadística & datos numéricos , Estudios Retrospectivos , Bazo/diagnóstico por imagen , Bazo/patología , Anciano
6.
Radiol Case Rep ; 19(3): 1128-1135, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38259705

RESUMEN

Leiomyosarcomas of the inferior vena cava (IVC) are uncommon malignancies. There is limited research detailing optimal diagnostic and clinical management. Here, we present 2 unique cases of IVC leiomyosarcoma including one in which the mass was partially ruptured through the vessel at initial presentation. We detail radiologic findings, 2 different transvenous approaches for biopsy of these masses, and subsequent oncological management.

9.
AJR Am J Roentgenol ; 221(5): 611-619, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37377359

RESUMEN

BACKGROUND. Splenomegaly historically has been assessed on imaging by use of potentially inaccurate linear measurements. Prior work tested a deep learning artificial intelligence (AI) tool that automatically segments the spleen to determine splenic volume. OBJECTIVE. The purpose of this study is to apply the deep learning AI tool in a large screening population to establish volume-based splenomegaly thresholds. METHODS. This retrospective study included a primary (screening) sample of 8901 patients (4235 men, 4666 women; mean age, 56 ± 10 [SD] years) who underwent CT colonoscopy (n = 7736) or renal donor CT (n = 1165) from April 2004 to January 2017 and a secondary sample of 104 patients (62 men, 42 women; mean age, 56 ± 8 years) with end-stage liver disease who underwent contrast-enhanced CT performed as part of evaluation for potential liver transplant from January 2011 to May 2013. The automated deep learning AI tool was used for spleen segmentation, to determine splenic volumes. Two radiologists independently reviewed a subset of segmentations. Weight-based volume thresholds for splenomegaly were derived using regression analysis. Performance of linear measurements was assessed. Frequency of splenomegaly in the secondary sample was determined using weight-based volumetric thresholds. RESULTS. In the primary sample, both observers confirmed splenectomy in 20 patients with an automated splenic volume of 0 mL; confirmed incomplete splenic coverage in 28 patients with a tool output error; and confirmed adequate segmentation in 21 patients with low volume (< 50 mL), 49 patients with high volume (> 600 mL), and 200 additional randomly selected patients. In 8853 patients included in analysis of splenic volumes (i.e., excluding a value of 0 mL or error values), the mean automated splenic volume was 216 ± 100 [SD] mL. The weight-based volumetric threshold (expressed in milliliters) for splenomegaly was calculated as (3.01 × weight [expressed as kilograms]) + 127; for weight greater than 125 kg, the splenomegaly threshold was constant (503 mL). Sensitivity and specificity for volume-defined splenomegaly were 13% and 100%, respectively, at a true craniocaudal length of 13 cm, and 78% and 88% for a maximum 3D length of 13 cm. In the secondary sample, both observers identified segmentation failure in one patient. The mean automated splenic volume in the 103 remaining patients was 796 ± 457 mL; 84% (87/103) of patients met the weight-based volume-defined splenomegaly threshold. CONCLUSION. We derived a weight-based volumetric threshold for splenomegaly using an automated AI-based tool. CLINICAL IMPACT. The AI tool could facilitate large-scale opportunistic screening for splenomegaly.

10.
Gastroenterology ; 164(1): 117-133.e7, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36209796

RESUMEN

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.


Asunto(s)
Cistadenoma Seroso , Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Cistadenoma Seroso/diagnóstico , Estudios Prospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Quiste Pancreático/diagnóstico , Quiste Pancreático/genética , Quiste Pancreático/terapia , Secuenciación de Nucleótidos de Alto Rendimiento , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Genómica , Proteínas Quinasas Activadas por Mitógenos/genética
11.
Cancer Med ; 12(3): 2312-2324, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36016484

RESUMEN

BACKGROUND: Liver transplantation (LT), resection (LR), and ablation (LA) are three curative-intent treatment options for patients with early hepatocellular carcinoma (HCC). We aimed to develop a prognostic calculator to compare the long-term outcomes following each of these therapies. METHODS: A total of 976 patients with HCC within the Milan criteria who underwent LT, LR, and LA between 2009 and 2019 from four institutions were evaluated. Multistate competing risks prediction models for recurrence-free survival (RFS), recurrence within the Milan criteria (RWM), and HCC-specific survival (HSS) were derived to develop a prognostic calculator. RESULTS: During a median follow-up of 51 months, 420 (43%) patients developed recurrence. In the multivariate analysis, larger tumor size, multinodularity, older age, male, higher alpha-fetoprotein (AFP), higher albumin-bilirubin (ALBI) grade, and the presence of portal hypertension were significantly associated with higher recurrence and decreased survival rates. The RFS and HSS were both significantly higher among patients treated by LT than by LR or LA and significantly higher between patients treated by LR than by LA (all p < 0.001). For multinodular HCC ≤3 cm, although LT had better RFS and HSS than LR or LA, LA was noninferior to LR. An online prognostic calculator was then developed based on the preoperative clinical factors that were independently associated with outcomes to evaluate RFS, RWM, and HSS at different time intervals for all three treatment options. CONCLUSIONS: Although LT resulted in the best recurrence and survival outcomes, LR and LA also offered durable long-term alternatives. This prognostic calculator is a useful tool for clinicians to guide an informed and personalized discussion with patients based on their tumor biology and liver function.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Masculino , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Hepatectomía/métodos , Trasplante de Hígado/métodos , Pronóstico , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología
12.
Paediatr Child Health ; 27(2): 93-98, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35599680

RESUMEN

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Primary-care physicians (PCPs) play a key role in identifying patients requiring specialist referral. In this study, we aim to determine PCPs' practice patterns for paediatric NAFLD, as knowledge gaps have been reported for adult NAFLD. Methods: A survey was sent to 60 PCPs in the Eastern Ontario Network from July 2019 to January 2020. Results: Thirty-seven (62%) PCPs responded to the survey. Twenty-one incorrectly considered the prevalence of paediatric NAFLD to be ≤10%. The majority (35/36) cared for less than five paediatric NAFLD patients. Thirty-four (92%) were only 'slightly familiar' or 'not familiar at all' with paediatric NAFLD. Only one PCP routinely screens for NAFLD. Only one PCP was aware of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) clinical guidelines for paediatric NAFLD. Twenty-five (68%) correctly selected lifestyle modifications as a treatment option. Lack of confidence in the knowledge of NAFLD was the most common barrier for managing paediatric cases. Conclusion: The majority of PCPs are not screening for paediatric NAFLD and are not familiar with its clinical spectrum, citing a lack of knowledge regarding NAFLD as the greatest barrier. This may cause delays in diagnosis and a presentation with advanced fibrosis at the time of specialist referral. Dissemination and implementation of clinical guidelines have the potential to improve knowledge and screening rates for NAFLD in children at the primary-care level.

13.
Radiology ; 302(2): 336-342, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34698566

RESUMEN

Background Imaging assessment for hepatomegaly is not well defined and currently uses suboptimal, unidimensional measures. Liver volume provides a more direct measure for organ enlargement. Purpose To determine organ volume and to establish thresholds for hepatomegaly with use of a validated deep learning artificial intelligence tool that automatically segments the liver. Materials and Methods In this retrospective study, liver volumes were successfully derived with use of a deep learning tool for asymptomatic outpatient adults who underwent multidetector CT for colorectal cancer screening (unenhanced) or renal donor evaluation (contrast-enhanced) at a single medical center between April 2004 and December 2016. The performance of the craniocaudal and maximal three-dimensional (3D) linear measures was assessed. The manual liver volume results were compared with the automated results in a subset of renal donors in which the entire liver was included at both precontrast and postcontrast CT. Unenhanced liver volumes were standardized to a postcontrast equivalent, reflecting a correction of 3.6%. Linear regression analysis was performed to assess the major patient-specific determinant or determinants of liver volume among age, sex, height, weight, and body surface area. Results A total of 3065 patients (mean age ± standard deviation, 54 years ± 12; 1639 women) underwent multidetector CT for colorectal screening (n = 1960) or renal donor evaluation (n = 1105). The mean standardized automated liver volume ± standard deviation was 1533 mL ± 375 and demonstrated a normal distribution. Patient weight was the major determinant of liver volume and demonstrated a linear relationship. From this result, a linear weight-based upper limit of normal hepatomegaly threshold volume was derived: hepatomegaly (mL) = 14.0 × (weight [kg]) + 979. A craniocaudal threshold of 19 cm was 71% sensitive (49 of 69 patients) and 86% specific (887 of 1030 patients) for hepatomegaly, and a maximal 3D linear threshold of 24 cm was 78% sensitive (54 of 69) and 66% specific (678 of 1030). In the subset of 189 patients, the median difference in hepatic volume between the deep learning tool and the semiautomated or manual method was 2.3% (38 mL). Conclusion A simple weight-based threshold for hepatomegaly derived by using a fully automated CT-based liver volume segmentation based on deep learning provided an objective and more accurate assessment of liver size than linear measures. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sosna in this issue.


Asunto(s)
Aprendizaje Profundo , Hepatomegalia/diagnóstico por imagen , Tamaño de los Órganos , Tomografía Computarizada por Rayos X/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
J Orthop Trauma ; 35(Suppl 2): S26-S27, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34227599

RESUMEN

SUMMARY: This video discusses treatment of pediatric femur fractures using 90-90 traction, followed by delayed spica casting. This study details the treatment of a 2-year-old girl with a subtrochanteric femur fracture featuring a 4-cm acute shortening and severe malalignment. The patient was placed in 90-90 traction in the operative setting. When adequate callous was observed radiographically, the patient was treated with a spica cast in the hospital on day 16. She was noted to have obtained uneventful healing of the fracture with no functional deficits, as detailed during serial office visits.


Asunto(s)
Fracturas del Fémur , Tracción , Moldes Quirúrgicos , Niño , Preescolar , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fémur , Humanos , Resultado del Tratamiento
15.
Semin Arthritis Rheum ; 51(4): 819-830, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34157577

RESUMEN

OBJECTIVE: To review: 1) degree of conformity to the American College of Rheumatology neuropsychological battery (ACR-NB) among studies that used a NB, 2) review definitions of cognitive impairment (CI) from studies that used a NB, and 3) characterize measurement tools used to assess CI in systemic lupus erythematosus (SLE). METHODS: The literature search was conducted in Ovid Medline, Embase, and PsycINFO for articles on CI in adult SLE patients. We reviewed studies that used a NB and compared their tests to the ACR-NB to assess the degree of conformity. Definitions of CI from studies that used a NB were reviewed when sufficient information was available. We reviewed and categorized CI measurement tools into four broad categories: NB, screening, incomplete/mixed batteries, and computerized batteries. RESULTS: Of 8727 references, 118 were selected for detailed review and 97 were included in the final analysis. Of 43 studies that used a NB, none of the studies used the ACR-NB exactly as published. Many studies supplemented with other tests. Overall, there was inconsistent use of ACR-NB tests. Definitions for CI varied, with cut-offs ranging from 1 to 3 standard deviations below normative values on domains/tests varying in type and number. The most frequently used measurement tool for assessing CI in SLE was a NB. Use of screening tests and computerized batteries have also increased over the last decade. CONCLUSION: The assessment and definition of CI in SLE remains heterogeneous. A consensus meeting to address existing inconsistencies should be considered to harmonize the field of CI in SLE.


Asunto(s)
Disfunción Cognitiva , Lupus Eritematoso Sistémico , Reumatología , Adulto , Benchmarking , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Pruebas Neuropsicológicas
16.
CMAJ Open ; 9(2): E667-E672, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34145049

RESUMEN

BACKGROUND: Nocturnists (overnight hospitalists) are commonly implemented in US teaching hospitals to adhere to per-resident patient caps and improve care but are rare in Canada, where patient caps and duty hours are comparatively flexible. Our objective was to assess the impact of a newly implemented nocturnist program on perceived quality of care, code status documentation and patient outcomes. METHODS: Nocturnists were phased in between June 2018 and December 2019 at Toronto General Hospital, a large academic teaching hospital in Toronto, Ontario. We performed a quality-improvement study comparing rates of code status entry into the electronic health record at admission, in-hospital mortality, the 30-day readmission rate and hospital length of stay for patients with cancer admitted by nocturnists and by residents. Surveys were administered in June 2019 to general internal medicine faculty and residents to assess their perceptions of the impact of the nocturnist program. RESULTS: From July 2018 to June 2019, 30 nocturnists were on duty for 241/364 nights (66.5%), reducing the mean maximum overnight per-resident patient census from 40 (standard deviation [SD] 4) to 25 (SD 5) (p < 0.001). The rate of admission code status entry was 35.3% among patients admitted by residents (n = 133) and 54.9% among those admitted by nocturnists (n = 339) (p < 0.001). The mortality rate was 10.5% among patients admitted by residents and 5.6% among those admitted by nocturnists (p = 0.06), the 30-day readmission rate was 8.3% and 5.9%, respectively (p = 0.4), and the mean acute length of stay was 7.2 (SD 7.0) days and 6.4 (SD 7.8) days, respectively (p = 0.3). Surveys were completed by 15/24 faculty (response rate 62%), who perceived improvements in patient safety, efficiency and trainee education; however, only 30/102 residents (response rate 29.4%) completed the survey. INTERPRETATION: Although implementation of a nocturnist program did not affect patient outcomes, it reduced residents' overnight patient census, and improved faculty perceptions of quality of care and education, as well as documentation of code status. Our results support nocturnist implementation in Canadian teaching hospitals.


Asunto(s)
Atención Posterior , Médicos Hospitalarios , Hospitales de Enseñanza , Internado y Residencia , Neoplasias , Atención Posterior/métodos , Atención Posterior/organización & administración , Canadá/epidemiología , Registros Electrónicos de Salud , Médicos Hospitalarios/educación , Médicos Hospitalarios/organización & administración , Hospitales de Enseñanza/métodos , Hospitales de Enseñanza/organización & administración , Humanos , Internado y Residencia/métodos , Internado y Residencia/normas , Neoplasias/epidemiología , Neoplasias/patología , Neoplasias/terapia , Evaluación de Resultado en la Atención de Salud , Mejoramiento de la Calidad/organización & administración , Mejoramiento de la Calidad/tendencias , Calidad de la Atención de Salud/normas
18.
J Viral Hepat ; 28(5): 739-754, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33556225

RESUMEN

The long-term effects of direct-acting antiviral therapies (DAAs) for chronic hepatitis C (CHC) remain uncertain. The objective of this systematic review and meta-analysis was to assess the impact of DAAs on CHC progression and mortality. We searched Ovid MEDLINE, Ovid EMBASE and PubMed databases (January 2011 to March 2020) for studies that compared the efficacy of DAAs to a non-DAA control in patients with CHC. Main outcomes were the adjusted hazard ratios (HRs) for mortality, liver decompensation, HCC occurrence and recurrence. Pooled estimates of HRs were determined using random-effects meta-analyses with inverse variance weighting, with sensitivity analyses and meta-regression to explore the effects of clinical factors. We identified 39 articles for the primary analysis. Compared with unexposed individuals, patients treated with DAA had a reduced risk of death (HR; CI = 0.44; 0.38-0.52), decompensation (HR; CI = 0.54; 0.38- 0.76) and HCC occurrence (HR; CI = 0.72; 0.61- 0.86). The protective effect of DAA on HCC recurrence was less clear (HR; CI = 0.72; 0.44-1.16). Sustained virologic response (SVR) attainment was a significant predictor of reduced mortality (HR; CI = 0.33; 0.23-0.46), decompensation (HR; CI = 0.11; 0.05-0.24), HCC occurrence (HR; CI = 0.31; 0.27-0.37) and HCC recurrence (HR; CI = 0.32; 0.20-0.51). Meta-regression showed no evidence of effect modification by patient age, sex, presence of cirrhosis or length of follow-up. In conclusion, our findings show protective effects of DAA treatment and DAA-related SVR on CHC progression and mortality.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Morbilidad , Recurrencia Local de Neoplasia , Respuesta Virológica Sostenida
19.
Clin Cancer Res ; 27(5): 1278-1286, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33277370

RESUMEN

PURPOSE: Immunotherapy is currently ineffective for nearly all pancreatic ductal adenocarcinomas (PDAC), largely due to its tumor microenvironment (TME) that lacks antigen-experienced T effector cells (Teff). Vaccine-based immunotherapies are known to activate antigen-specific Teffs in the peripheral blood. To evaluate the effect of vaccine therapy on the PDAC TME, we designed a neoadjuvant and adjuvant clinical trial of an irradiated, GM-CSF-secreting, allogeneic PDAC vaccine (GVAX). PATIENTS AND METHODS: Eighty-seven eligible patients with resectable PDAC were randomly assigned (1:1:1) to receive GVAX alone or in combination with two forms of low-dose cyclophosphamide. Resected tumors following neoadjuvant immunotherapy were assessed for the formation of tertiary lymphoid aggregates (TLA) in response to treatment. The clinical endpoints are disease-free survival (DFS) and overall survival (OS). RESULTS: The neoadjuvant treatment with GVAX either alone or with two forms of low-dose cyclophosphamide is safe and feasible without adversely increasing the surgical complication rate. Patients in Arm A who received neoadjuvant and adjuvant GVAX alone had a trend toward longer median OS (35.0 months) than that (24.8 months) in the historical controls who received adjuvant GVAX alone. However, Arm C, who received low-dose oral cyclophosphamide in addition to GVAX, had a significantly shorter DFS than Arm A. When comparing patients with OS > 24 months to those with OS < 15 months, longer OS was found to be associated with higher density of intratumoral TLA. CONCLUSIONS: It is safe and feasible to use a neoadjuvant immunotherapy approach for PDACs to evaluate early biologic responses. In-depth analysis of TLAs is warranted in future neoadjuvant immunotherapy clinical trials.


Asunto(s)
Adyuvantes de Vacunas/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Carcinoma Ductal Pancreático/mortalidad , Ciclofosfamida/administración & dosificación , Linfocitos/patología , Terapia Neoadyuvante/mortalidad , Neoplasias Pancreáticas/mortalidad , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Inmunoterapia , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Pronóstico , Tasa de Supervivencia
20.
PLoS One ; 15(6): e0234012, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32544183

RESUMEN

Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.


Asunto(s)
Carcinoma Ductal de Mama/patología , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral , Antígeno CD24/metabolismo , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Microfluídica/métodos , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias de la Mama Triple Negativas/clasificación , Neoplasias de la Mama Triple Negativas/genética
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