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1.
J Cancer Res Clin Oncol ; 149(6): 2559-2574, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35773429

RESUMO

PURPOSE: For patients with advanced HCC, predictors of immunotherapy response are scarce, and the benefits of tyrosine kinase inhibitor (TKI) treatment after immunotherapy are unclear. We explored whether clinical features, such as target lesion response, immune-mediated toxicity, or subsequent TKI therapy predict immunotherapy response. METHODS: We retrospectively studied 77 patients with advanced HCC receiving immunotherapy. Patient characteristics and outcomes were assessed using various statistical methods, including the log-rank test and Kaplan-Meier methods. Cox proportional hazard modeling was used for multivariable survival analysis. RESULTS: For all patients, median overall survival (mOS) was 13 months (95% CI 8-19), and median progression-free survival (mPFS) was 6 months (95% CI 4-10). Patients with partial response (PR) and stable disease (SD) compared to progressive disease (PD) had prolonged mPFS (27 vs. 5 vs. 1 month(s), p < 0.0001) and mOS (not met vs. 11 vs. 3 months, p < 0.0001). Patients with vs. without immune-mediated toxicities trended towards longer mPFS (9 vs. 4 months p = 0.133) and mOS (17 vs. 9 months; p = 0.095). Patients who did vs. did not receive a tyrosine kinase inhibitor (TKI) after immunotherapy had a significantly improved mOS (19 vs. 5 months, p = 0.0024)). Based on multivariate modeling, the hazard ratio (HR) of overall survival (OS) of patients receiving TKI vs. no TKI was 0.412 (p = 0.0043). CONCLUSION: We show that disease control predicts prolonged mOS and mPFS. Furthermore, TKI therapy administered after immunotherapy predicts prolonged mOS in patients with advanced HCC.


Assuntos
Carcinoma Hepatocelular , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Imunoterapia/métodos
2.
Cancers (Basel) ; 14(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35626165

RESUMO

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as RAD51C, and the potential use of reliable surrogate markers of HRD.

3.
Liver Int ; 42(1): 224-232, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34687281

RESUMO

BACKGROUND & AIMS: Known risk factors for hepatocellular adenoma (HCA) bleeding are size >5 cm, growth rate, visible vascularity, exophytic lesions, ß-catenin and Sonic Hedgehog activated HCAs. Most studies are based on European cohorts. The objective of this study is to identify additional risk factors for HCA bleeding in a US cohort. METHODS: Retrospective chart review was performed on patients diagnosed with HCA on magnetic resonance imaging (n = 184) at an academic tertiary institution. Clinical, pathological, and imaging data were collected. Primary outcomes measured were HCA bleeding and malignancy. Statistical analysis was performed with SAS 9.4 using Chi-Square, Fisher's exact test, sample t test, non-parametric Wilcoxon test, and logistic regression. RESULTS: After excluding patients whose pathology showed focal nodular hyperplasia and non-adenoma lesions, follow-up data were available for 167 patients. 16% experienced microscopic or macroscopic bleeding and 1.2% had malignancy. HCA size predicted bleeding (P < .0001) and no patients with lesion size <1.8 cm bled. In unadjusted analysis, hepatic adenomatosis (≥10 lesions) trended towards 2.8-fold increased risk of bleeding. Of patients with a single lesion that bled, 77% bled from a lesion >5 cm. In patients with multiple HCAs that bled, 50% bled from lesions <5 cm. In patients with multiple adenomas, size (P = .001) independently predicted bleeding and hepatic steatosis trended towards increased risk of bleeding (P = .05). CONCLUSIONS: In a large US cohort, size predicted increased risk of HCA bleeding while hepatic adenomatosis trended towards increased risk of bleeding. In patients with multiple HCAs, size predicted bleeding and hepatic steatosis trended toward increased risk of bleeding.


Assuntos
Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenoma de Células Hepáticas/complicações , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Proteínas Hedgehog , Humanos , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
4.
JNMA J Nepal Med Assoc ; 59(235): 280-283, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-34506438

RESUMO

INTRODUCTION: Changes in the lifestyle, food habits, lack of nutritious diet, stress, physical inactivity increases the body mass index among adults. Excess weight gain is an important risk factor for non-communicable diseases such as heart disease, stroke, diabetes, and some cancers (endometrial, breast, colon). Thus, this study aims to find out body mass index of medical students of a medical college in Nepal. METHODS: This descriptive cross-sectional study was conducted in the department of physiology of a tertiary care center from August 2019 to February 2020 after taking ethical clearence from Institutional Review Committee (Reference number 192/19). Height and weight were recorded and body mass index was then being calculated. Data entry was done in Microsoft Excel and analyzed using Statistical Package for the Social Sciences version 22. RESULTS: Out of 266 medical students, 39 (15%) were overweight and 32 (12%) were underweight with mean body mass index 26.60±1.99kg/m2 and 17.13±1.19kg/m2 respectively. Mean body mass index of males was 21.76±3.06kg/m2 and that of females was 21.70±2.96 kg/m2. CONCLUSIONS: Comparing with a similar study done in Nepal previously, we found a higher prevalence of overweight in medical students whereas majority of medical students had normal weight. Factors affecting body mass index in medical students should be explored further.


Assuntos
Estudantes de Medicina , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Nepal/epidemiologia , Magreza
6.
AJR Am J Roentgenol ; 211(1): 14-24, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29792748

RESUMO

OBJECTIVE: The purpose of this article is to review the classic and uncommon imaging findings of portal vein thrombosis (PVT) (acute, chronic, congenital, and septic thrombus) as visualized on multiple modalities, with an emphasis on MRI findings. Additional aims are to understand the imaging of obliterative portal venopathy and its clinical significance, appreciate morphologic changes of the biliary system that may accompany PVT, and recognize changes in liver enhancement patterns seen with PVT related to the hepatic arterial buffer response. The review also addresses morphologic changes of the liver that may occur after PVT, including nodular regenerative hyperplasia, central hepatic hypertrophy, and peripheral fibrosis that may stimulate cirrhosis, as well as the importance of portal vein mapping and the diagnostic findings and clinical significance of tumor within the portal vein in the liver transplant population. CONCLUSION: PVT may be a complication of liver cirrhosis, but it may also occur as a primary vascular disorder without liver disease. PVT can result in portal hypertension and may present with variceal bleeding or hypersplenism. Radiologists should be familiar with the imaging of PVT in patients of various ages and in different clinical scenarios. PVT can influence hepatic perfusion, the shape of the bile ducts, and liver architecture. Bland PVT and tumor-related PVT have major implications for hepatic transplant.


Assuntos
Imageamento por Ressonância Magnética , Veia Porta/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico por imagem , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Veia Porta/patologia , Trombose Venosa/patologia
7.
Radiology ; 286(1): 29-48, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29166245

RESUMO

The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/normas , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/normas , Tomografia Computadorizada por Raios X/normas , Bases de Dados Factuais , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
8.
Eur Radiol ; 28(4): 1529-1539, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29079914

RESUMO

PURPOSE: To determine if rare primary malignancies of the liver may have consistent features on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This IRB-compliant retrospective study reviewed the records from the pathology departments of four university centres over an 11-year period from 2005-2016 to identify rare primary malignant tumours, which were cross-referenced with MRI records. MRI studies of these patients were reviewed to determine if these tumours exhibited consistent and distinctive features. RESULTS: Sixty patients were identified with rare primary liver tumours. The following distinctive features and frequency of occurrence were observed: mixed hepatocellular carcinoma-cholangiocarcinoma showed regions of wash-out in 7/19 of patients; 6/6 of fibrolamellar carcinomas demonstrated large heterogeneous lesions with large heterogeneous central scars; epithelioid haemangioendothelioma larger than 2 cm showed target-like enhancement in late-phase enhancement in 9/13; sarcomas excluding angiosarcoma had central necrosis in 3/9 and haemorrhage in 5/9; angiosarcomas showed centripedal progressive nodular enhancement in 3/6 and showed regions of haemorrhage in 3/6; and 7/7 of primary hepatic lymphomas showed encasement of vessels. CONCLUSION: Although helpful features for the differentiation of rare primary malignancies of the liver are identified, no MRI features appear to be specific and therefore histopathological confirmation is usually required for definitive diagnosis. KEY POINTS: • No MRI features appear to be specific for rare primary liver malignancies. • Haemorrhage is a helpful sign in diagnosis of primary hepatic sarcomas. • Angiosarcomas may show progressive nodular enhancement towards the centre mimicking haemangioma. • Vessel encasement is a helpful sign in diagnosis of primary hepatic lymphoma.


Assuntos
Colangiocarcinoma/diagnóstico por imagem , Hemangioendotelioma Epitelioide/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Linfoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sarcoma/diagnóstico por imagem , Centros Médicos Acadêmicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Diagnóstico Diferencial , Feminino , Hemangioendotelioma Epitelioide/patologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/patologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/patologia , Adulto Jovem
9.
Radiology ; 286(1): 173-185, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091751

RESUMO

Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and magnetic resonance (MR) imaging, and the potential effect of reader demographics on agreement with a preselected nonconsecutive image set. Materials and Methods Institutional review board approval was obtained, and patient consent was waived for this retrospective study. Ten image sets, comprising 38-40 unique studies (equal number of CT and MR imaging studies, uniformly distributed LI-RADS categories), were randomly allocated to readers. Images were acquired in unenhanced and standard contrast material-enhanced phases, with observation diameter and growth data provided. Readers completed a demographic survey, assigned LI-RADS version 2014 categories, and assessed major features. Intraclass correlation coefficient (ICC) assessed with mixed-model regression analyses was the metric for interreader reliability of assigning categories and major features. Results A total of 113 readers evaluated 380 image sets. ICC of final LI-RADS category assignment was 0.67 (95% confidence interval [CI]: 0.61, 0.71) for CT and 0.73 (95% CI: 0.68, 0.77) for MR imaging. ICC was 0.87 (95% CI: 0.84, 0.90) for arterial phase hyperenhancement, 0.85 (95% CI: 0.81, 0.88) for washout appearance, and 0.84 (95% CI: 0.80, 0.87) for capsule appearance. ICC was not significantly affected by liver expertise, LI-RADS familiarity, or years of postresidency practice (ICC range, 0.69-0.70; ICC difference, 0.003-0.01 [95% CI: -0.003 to -0.01, 0.004-0.02]. ICC was borderline higher for private practice readers than for academic readers (ICC difference, 0.009; 95% CI: 0.000, 0.021). Conclusion ICC is good for final LI-RADS categorization and high for major feature characterization, with minimal reader demographic effect. Of note, our results using selected image sets from nonconsecutive examinations are not necessarily comparable with those of prior studies that used consecutive examination series. © RSNA, 2017.


Assuntos
Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Radiologistas/estatística & dados numéricos , Radiologistas/normas , Bases de Dados Factuais , Humanos , Imageamento por Ressonância Magnética , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
AJR Am J Roentgenol ; 209(6): W350-W359, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29023152

RESUMO

OBJECTIVE: This article describes, illustrates, and correlates imaging and pathologic features of primary vascular mesenchymal neoplasms of the liver, which arise from the vascular endothelium and perivascular epithelioid cells. CONCLUSION: Familiarity with the spectrum of benign, malignant-potential and malignant vascular neoplasms, and nonneoplastic mimickers allows consideration in the differential diagnosis of enhancing hepatic masses. Understanding relevant pathologic features facilitates recognition of key imaging features, specifically dynamic contrast enhancement patterns on CT and MRI, which provide a useful classification system.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Meios de Contraste , Diagnóstico Diferencial , Humanos
11.
Cancer Chemother Pharmacol ; 80(5): 945-954, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28932966

RESUMO

PURPOSE: We report our institutional observations of ten patients with advanced hepatocellular carcinoma (HCC) (seven and three were Child-Pugh class A and B, respectively) who received compassionate regorafenib therapy between June 2016 and January 2017. These patients did not fit the rigid criteria of a clinical trial and represented the use of regorafenib in an everyday clinic situation. METHODS: Regorafenib (160 mg P.O. daily) was administered to patients on a 4-week cycle (3 weeks on, 1 week off) until disease progression (assessed using mRECIST criteria) or discontinuation secondary to toxicity (assessed using CTCAE criteria). Relevant clinical data were abstracted from patient medical records and reviewed retrospectively. RESULTS: The median duration of patient treatment was 6.6 weeks, and the median time to disease progression was 12.5 weeks. Most common treatment emergent adverse events were fatigue, diarrhea, and hand-foot skin reaction. Elevated AST and ALT were the most commonly observed laboratory-assessed adverse events, which reached grade 3 status in the Child-Pugh class B patients only. We observed intolerance to regorafenib treatment in one patient who had previously received a liver transplant. We also saw lithium toxicity in one patient receiving long-term lithium treatment, suggesting a potential and unexpected drug-drug interaction with regorafenib. CONCLUSIONS: Taken together, our observations indicate that regorafenib is beneficial in the treatment of patients with advanced HCC who progressed on or demonstrated intolerance to sorafenib therapy; however, careful selection and close monitoring of patients is necessary to maximize the benefit while minimizing the toxicities of regorafenib treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacologia , Piridinas/administração & dosagem , Piridinas/farmacologia
12.
Cancer Immunol Res ; 4(5): 419-30, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26968206

RESUMO

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.


Assuntos
Complexo CD3/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Prognóstico , Recidiva , Fatores de Risco , Subpopulações de Linfócitos T/imunologia
13.
Am J Surg ; 211(1): 70-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26122361

RESUMO

BACKGROUND: Although pancreaticoduodenectomy (PD) is feasible in patients greater than or equal to 80 years, little is known about the potential strain on resource utilization. METHODS: Outcomes and inpatient charges were compared across age cohorts (I: ≤70, II: 71 to 79, III: ≥80 years) in 99 patients who underwent PD (2005 to 2013) at our institution. The generalized linear modeling approach was used to estimate the impact of age. RESULTS: Perioperative complications were equivalent among cohorts. Increasing age was associated with intensive care unit use, increased length of stay (LOS), and the likelihood of discharge to a skilled facility. After controlling for covariates, hospital charges were significantly higher in Cohort III (P = .006) and Cohort II (P = .035) when compared with Cohort I. However, hospital charges between Cohorts II and III were equivalent (P = .374). Complications (P = .005) and LOS (P < .001) were associated with higher hospital charges. CONCLUSIONS: Increasing age was associated with increased intensive care unit, LOS, and discharge to skilled facilities. However, octogenarians had equivalent PD charges and outcome measures when compared with septuagenarians and future studies should validate these findings in larger national studies.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Preços Hospitalares/estatística & dados numéricos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/economia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/economia , District of Columbia , Feminino , Humanos , Unidades de Terapia Intensiva/economia , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/economia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Pancreáticas/economia , Complicações Pós-Operatórias/economia , Estudos Retrospectivos
14.
World J Hepatol ; 7(26): 2696-702, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26609347

RESUMO

Reactive lymphoid hyperplasia (RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision.

15.
Cancer Chemother Pharmacol ; 76(5): 1073-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26449224

RESUMO

PURPOSE: To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC). METHODS: This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1-7 and 150 mg/m(2) TMZ PO daily on days 1-5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03. RESULTS: We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months. CONCLUSION: The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS. GOV IDENTIFIER: NCT01205828.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Carcinoma Hepatocelular/genética , Metilação de DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Fadiga/induzido quimicamente , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Fenilureia/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Terapia de Salvação , Sorafenibe , Temozolomida , Falha de Tratamento
16.
Acad Radiol ; 21(11): 1455-64, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25300723

RESUMO

RATIONALE AND OBJECTIVES: Current clinical practice favors imaging rather than biopsy to diagnose hepatocellular carcinoma (HCC). There is a need to better understand tumor biology and aggressiveness of HCC. Our goal is to investigate magnetic resonance imaging (MRI) features of HCC that are associated with faster growth rates (GRs). MATERIALS AND METHODS: After approval from institutional review board, a retrospective evaluation was performed of pre-liver transplant patients. Fifty-two patients who developed a >2 cm HCC on serial imaging were included in the study group, with a total of 60 HCCs seen. Precursor foci were identified on serial MRIs before the specific diagnostic features of >2 cm HCC could be made, and GRs and MRI features, including signal on T1- and T2-weighted images (WI), the presence of intralesional steatosis on chemical shift imaging, and enhancement pattern were analyzed. GRs were correlated with imaging features. RESULTS: The average GR of precursor lesions to >2 cm HCC was determined to be 0.23 cm/mo (standard deviation [SD], 0.32), with a doubling time of 5.26 months (SD, 5.44). The presence of increased signal intensity (SI) on T2-WI was associated with significantly higher growth (P = .0002), whereas increased intensity on T1-WI at the initial study was associated with a significantly lower GR (P = .0162). Furthermore, lesions with hypervascular enhancement with washout pattern had significantly higher GR (P = .0164). There is no evidence of differences in GRs seen in lesions with steatosis. CONCLUSIONS: Small precursor lesions with increased SI on T2-WI and a washout pattern of enhancement are associated with faster GRs, which may suggest more aggressive tumor biology. These features may be helpful in patient management and surveillance for HCC.


Assuntos
Algoritmos , Carcinoma Hepatocelular/patologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga Tumoral
17.
AJR Am J Roentgenol ; 203(1): W48-69, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24951229

RESUMO

OBJECTIVE: The purpose of this article is to review the imaging features and Liver Imaging Reporting and Data System (LI-RADS) categorization of benign and likely benign entities, including typical cirrhotic nodules, distinctive nodular observations, and benign entities that may simulate hepatocellular carcinoma. CONCLUSION: LI-RADS is a system of standardized criteria for interpreting liver CT and MR images of patients at risk of hepatocellular carcinoma. Most of the observations in these patients are not malignant. With the development of fibrosis and cirrhosis, these benign entities may take on an altered appearance.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Interpretação de Imagem Assistida por Computador/normas , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Front Oncol ; 4: 102, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24847445

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibrotic reaction or desmoplasia and complex involvement of the surrounding tumor microenvironment. Pancreatic stellate cells are a key mediator of the pancreatic matrix and they promote progression and invasion of pancreatic cancer by increasing cell proliferation and offering protection against therapeutic interventions. Our study utilizes human tumor-derived pancreatic stellate cells (HTPSCs) isolated from fine needle aspirates of pancreatic cancer tissue from patients with locally advanced, unresectable pancreatic adenocarcinoma before and after treatment with full-dose gemcitabine plus concurrent hypo-fractionated stereotactic radiosurgery. We show that HTPSCs survive in vivo chemotherapy and radiotherapy treatment and display a more activated phenotype post-therapy. These data support the idea that stellate cells play an essential role in supporting and promoting pancreatic cancer and further research is needed to develop novel treatments targeting the pancreatic tumor microenvironment.

19.
Surgery ; 156(2): 379-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24680859

RESUMO

BACKGROUND: We compared outcomes and postpancreatectomy quality of life (QOL) in paired cohorts of patients undergoing conventional open pancreaticoduodenectomy (OPD) or laparoscopic-assisted pancreaticoduodenectomy (LAPD). METHODS: Comparative analysis of QOL was performed in a matched cohort of 53 patients after OPD or LAPD between 2010 and 2013. The Medical Outcomes Study Short Form-36 Health Survey and the Karnofsky score were used. RESULTS: Physical component score, mental component score, and Karnofsky scores were calculated at multiple time points for OPD (n = 25) and LAPD (n = 28). Operative times, complications, and readmission rates were equivalent. Time to starting adjuvant therapy trended toward clinical importance in LAPD (61 vs 110 days, P = .0878). Duration of stay was less in LAPD (7.10 vs 9.44 days, P = .02). LAPD had a superior QOL centered on functional status compared with OPD (physical component score 49.09 vs 38.4, P = .04; Karnofsky 92.22 vs 66.92%, P = .003). These statistical differences were not observed beyond 6 months. CONCLUSION: LAPD provided a more favorable QOL within the first 6 months and shorter length of stay compared with conventional OPD. LAPD may serve as an alternative operative therapy to potentially minimize delays in receipt of and enhance tolerability of adjuvant therapies.


Assuntos
Pancreaticoduodenectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Estudos de Coortes , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Avaliação de Estado de Karnofsky , Laparoscopia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
20.
Abdom Imaging ; 39(3): 562-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24531353

RESUMO

PURPOSE: Although magnetic resonance imaging is often able to distinguish between adenomyosis and fibroids, occasionally the imaging features of focal adenomyosis and fibroids overlap. Diffusion-weighted imaging (DWI) may provide useful information in differentiating pathologies. Therefore, the purpose of our study was to evaluate differences, if any, in the apparent diffusion coefficient (ADC) values of fibroids and adenomyosis. MATERIAL AND METHODS: Patients (n = 50) with uterine fibroids and adenomyosis (n = 43), who underwent pelvic MR imaging including DWI, were included in this IRB approved HIPPA compliant retrospective study. DWI was performed with b factors of 50, 400, and 800 s/mm using a 1.5 T scanner. ADC ROI measurements were placed over a fibroid, an area of adenomyosis, unaffected normal myometrium, skeletal muscle, and urine. Histogram analysis of ADC maps in 20 cases each of adenomyosis and fibroids was evaluated to assess the degree of tissue heterogeneity. RESULTS: The ADC values of adenomyosis and fibroids were compared using Student's t test. The mean and the standard deviation of the ADC values of the control group were as follows: fibroid 0.64 ± 0.29, adenomyosis 0.86 ± 0.30, myometrium 1.39 ± 0.36, and urine 3.01 ± 0.2 × 10(-3) mm(2)/s. There was a statistically significant difference among the ADC values of normal myometrium and fibroids (p < 0.0001), normal myometrium and adenomyosis (p < 0.0001), and fibroids and adenomyosis (p < 0.001). Histogram analysis demonstrates less heterogeneity of adenomyosis as compared to fibroids. CONCLUSION: The present study shows that ADC measurements have the potential to quantitatively differentiate between fibroids and adenomyosis.


Assuntos
Adenomiose/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Leiomioma/diagnóstico , Miométrio/patologia , Neoplasias Uterinas/diagnóstico , Útero/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Estudos Retrospectivos
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