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1.
Gastroenterology ; 161(4): 1229-1244.e9, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34147519

RESUMO

BACKGROUND & AIMS: The pathogenesis of immune checkpoint inhibitor (ICI)-colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ulcerative colitis, and to determine potential novel therapeutic targets. METHODS: We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing. RESULTS: We demonstrate CD8+ tissue resident memory T (TRM) cells are the dominant activated T cell subset in ICI-colitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. CD8+ TRM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8+ TRM cells express high levels of transcripts for checkpoint inhibitors and interferon-gamma in ICI-colitis. We demonstrate similar findings in both anti-CTLA-4/PD-1 combination therapy and in anti-PD-1 inhibitor-associated colitis. On the basis of our data, we successfully targeted this pathway in a patient with refractory ICI-colitis, using the JAK inhibitor tofacitinib. CONCLUSIONS: Interferon gamma-producing CD8+ TRM cells are a pathological hallmark of ICI-colitis and a novel target for therapy.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Colite/induzido quimicamente , Colo/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/efeitos adversos , Memória Imunológica/efeitos dos fármacos , Interferon gama/metabolismo , Células T de Memória/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/metabolismo , Estudos de Casos e Controles , Colite/tratamento farmacológico , Colite/imunologia , Colite/metabolismo , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colo/imunologia , Colo/metabolismo , Estudos Transversais , Perfilação da Expressão Gênica , Humanos , Estudos Longitudinais , Ativação Linfocitária/efeitos dos fármacos , Células T de Memória/imunologia , Células T de Memória/metabolismo , Fenótipo , Piperidinas/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , Pirimidinas/uso terapêutico , RNA-Seq , Análise de Célula Única , Transcriptoma
2.
Br J Cancer ; 124(10): 1661-1669, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33723392

RESUMO

BACKGROUND: Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. METHODS: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed. RESULTS: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9-33.4) versus not-reached (P = 2.8 × 10-6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment. CONCLUSIONS: Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.


Assuntos
Doenças Autoimunes/induzido quimicamente , Linfócitos T CD8-Positivos/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Autoimunidade/efeitos dos fármacos , Autoimunidade/genética , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversos , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Transcriptoma/efeitos dos fármacos , Transcriptoma/imunologia , Resultado do Tratamento , Reino Unido/epidemiologia
3.
Cancer ; 125(1): 99-108, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30332497

RESUMO

BACKGROUND: In the current study, the authors sought to determine the maximum tolerated dose (MTD) of the novel class 1 selective histone deacetylase inhibitor CXD101 in a dose escalation study in patients with advanced solid tumors or recurrent/refractory lymphoma. METHODS: The authors escalated the dose of CXD101 from 1 mg twice daily orally for 5 days in a 21-day cycle (3+3 design). RESULTS: A total of 39 patients were enrolled, 36 of whom received CXD101. Of the 30 patients in the escalation cohort, 29 were evaluable for determination of the dose-limiting toxicity (DLT). DLTs were noted at doses of 16 mg twice daily (1 of 6 patients), 20 mg twice daily (1 of 6 patients), and 24/25 mg twice daily (2 of 5 patients, both of whom developed neutropenic fever). The MTD was 20 mg twice daily, which achieved maximal plasma concentrations (±standard deviation) of 231±76 nM to 342±126 nM, which was within the biologically active range. Six patients received 20 mg twice daily in an expansion cohort. The most frequent adverse events were fatigue, nausea, and reversible cytopenia. Key grade 3 to 4 adverse events (according to Common Terminology Criteria for Adverse Events criteria [version 4.03]) included thrombocytopenia (11%), neutropenia (17%), and neutropenic fever (2%) across the 133 CXD101 cycles given. The toxicity profile was similar to that of licensing studies with other histone deacetylase inhibitors. In 22 evaluable patients receiving a dose of ≥16 mg twice daily (17 of whom had lymphoma and 5 of whom had solid tumors), 3 partial responses (2 in patients with classic Hodgkin lymphoma after allogenic stem cell transplantation and 1 in a patient with angioimmunoblastic T-cell lymphoma) and 1 complete response (in a patient with follicular lymphoma) were noted (overall response rate of 18%) in addition to 9 patients who achieved durable stable disease. Responses were noted predominantly among patients with lymphoma (tumor reduction noted in 63% of patients on standard computed tomography). CONCLUSIONS: The MTD in the current study was found to be 20 mg twice daily. Encouraging and durable activity was observed in patients with Hodgkin lymphoma, T-cell lymphoma, and follicular lymphoma.


Assuntos
Inibidores de Histona Desacetilases/administração & dosagem , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma de Células T Periférico/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Esquema de Medicação , Feminino , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Linfoma Cutâneo de Células T/metabolismo , Linfoma de Células T Periférico/metabolismo , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
Rheumatology (Oxford) ; 58(Suppl 7): vii7-vii16, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816085

RESUMO

Immunotherapy has an increasing role in the management of cancer, both in metastatic disease and as an adjuvant therapy. However, sensitization of the immune system with checkpoint inhibitors comes with a unique side effect profile. Full appreciation of this can take some time to emerge as some adverse events are rare, or can be subtle and potentially overlooked. Clinician awareness of these side effects can be particularly important in patients with pre-existing autoimmune conditions. Here we describe common symptoms and diagnostic strategies for organ-specific side effects of anti-CTLA-4 and anti-PD-1/PD-L1 immunotherapy agents.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Toxidermias/etiologia , Doenças do Sistema Endócrino/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Doenças do Sistema Nervoso/induzido quimicamente , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Doenças Reumáticas/induzido quimicamente
5.
J Immunother Cancer ; 12(4)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663935

RESUMO

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Miocardite , Miosite , SARS-CoV-2 , Idoso , Feminino , Humanos , Masculino , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Miocardite/induzido quimicamente , Miosite/induzido quimicamente , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Idoso de 80 Anos ou mais
6.
Cell Oncol (Dordr) ; 46(2): 391-407, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36539575

RESUMO

PURPOSE: Despite recent advances, approximately 50% of patient with metastatic melanoma eventually succumb to the disease. Patients with melanomas harboring a BRAF mutation (BRAFMut) have a worse prognosis than those with wildtype (BRAFWT) tumors. Unexpectedly, interim AVAST-M Phase III trial data reported benefit from adjuvant anti-VEGF bevacizumab only in the BRAFMut group. We sought to find mechanisms underpinning this sensitivity. METHODS: We investigated this finding in vitro and in vivo using melanoma cell lines and clones generated by BRAFV600E knock-in on a BRAFWT background. RESULTS: Compared with BRAFWT cells, isogenic BRAFV600E clones secreted more VEGF and exhibited accelerated growth rates as spheroids and xenografts, which were more vascular and proliferative. Recapitulating AVAST-M findings, bevacizumab affected only BRAFV600E xenografts, inducing significant tumor growth delay, reduced vascularity and increased necrosis. We identified 814 differentially expressed genes in isogenic BRAFV600E/BRAFWT clones. Of 61 genes concordantly deregulated in clinical melanomas ROR2 was one of the most upregulated by BRAFV600E. ROR2 was shown to be RAF-MEK regulated in BRAFV600E cells and its depletion suppressed VEGF secretion down to BRAFWT levels. The ROR2 ligand WNT5A was also overexpressed in BRAFMut melanomas, and in ROR2-overexpressing BRAFV600E cells MEK inhibition downregulated WNT5A and VEGF secretion. CONCLUSIONS: These data implicate WNT5A-ROR2 in VEGF secretion, vascularity, adverse outcomes and bevacizumab sensitivity of BRAFMut melanomas, suggesting that this axis has potential therapeutic relevance.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Proteína Wnt-5a , Humanos , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Linhagem Celular Tumoral , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Proteína Wnt-5a/genética , Proteína Wnt-5a/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Nat Med ; 28(12): 2592-2600, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36526722

RESUMO

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma.


Assuntos
Interleucina-7 , Melanoma , Humanos , Interleucina-7/genética , Interleucina-7/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Melanoma/genética , Linfócitos T CD8-Positivos , Variação Genética
8.
Clin Cancer Res ; 26(21): 5709-5719, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33097493

RESUMO

PURPOSE: Angiogenesis is thought to be critical for tumor metastasis. However, inhibiting angiogenesis using antibodies such as bevacizumab (Avastin), has had little impact on melanoma patient survival. We have demonstrated that both angiogenesis and metastasis are increased in older individuals, and therefore sought to investigate whether there was an age-related difference in response to bevacizumab, and if so, what the underlying mechanism could be. EXPERIMENTAL DESIGN: We analyzed data from the AVAST-M trial of 1,343 patients with melanoma treated with bevacizumab to determine whether there is an age-dependent response to bevacizumab. We also examined the age-dependent expression of VEGF and its cognate receptors in patients with melanoma, while using syngeneic melanoma animal models to target VEGF in young versus old mice. We also examined the age-related proangiogenic factor secreted frizzled-related protein 2 (sFRP2) and whether it could modulate response to anti-VEGF therapy. RESULTS: We show that older patients respond poorly to bevacizumab, whereas younger patients show improvement in both disease-free survival and overall survival. We find that targeting VEGF does not ablate angiogenesis in an aged mouse model, while sFRP2 promotes angiogenesis in vitro and in young mice. Targeting sFRP2 in aged mice successfully ablates angiogenesis, while the effects of targeting VEGF in young mice can be overcome by increasing sFRP2. CONCLUSIONS: VEGF is decreased during aging, thereby reducing response to bevacizumab. Despite the decrease in VEGF, angiogenesis is increased because of an increase in sFRP2 in the aged tumor microenvironment. These results stress the importance of considering age as a factor for designing targeted therapies.


Assuntos
Melanoma/genética , Proteínas de Membrana/genética , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Bevacizumab/administração & dosagem , Linhagem Celular Tumoral , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Microambiente Tumoral/efeitos dos fármacos
11.
Surg Neurol ; 67(2): 204-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17254894

RESUMO

BACKGROUND: Infundibula are frequently regarded as incidental anatomical variants that are of no pathogenetic significance. CASE DESCRIPTION: A 51-year-old man presented with a sudden onset of severe occipital headache. Computed tomographic scan revealed a predominantly perimesencephalic pattern of SAH with a slight bias toward the left side. Angiography demonstrated a left PCo-A IF as the sole abnormality. At craniotomy, the left PCo-A IF was found to represent the sole abnormality. The IF was markedly reddened posteriorly, contained a capping clot, and lay immediately adjacent to a mass of xanthochromatous tissue. The PCo-A was hypoplastic and lacked perforating vessels; therefore, the IF base was successfully clipped with a straight Sugita clip parallel to the left ICA. At discharge and at clinical follow-up, our patient was asymptomatic and lacked neurologic signs. CONCLUSIONS: Infundibula may rarely represent a direct source of rupture and SAH. Exploratory craniotomy is required to establish the diagnosis and to provide definitive treatment. To label a case of SAH as angiogram-negative may be unwise when an IF potentially colocalizes to the SAH source.


Assuntos
Círculo Arterial do Cérebro/anormalidades , Círculo Arterial do Cérebro/patologia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/patologia , Hemorragia Subaracnóidea/patologia , Angiografia Digital , Círculo Arterial do Cérebro/diagnóstico por imagem , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Ruptura Espontânea , Hemorragia Subaracnóidea/fisiopatologia , Instrumentos Cirúrgicos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares
13.
Br J Hosp Med (Lond) ; 76(7): 409-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26140560

RESUMO

The main role of early phase clinical trials in cancer is to determine the dose to take forward for future clinical study. However, study design is changing in order to account for the change in focus of drug development toward molecularly targeted agents.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase I como Assunto/ética , Ensaios Clínicos Fase I como Assunto/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Dose Máxima Tolerável
14.
Eur J Cancer ; 51(3): 359-66, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25542057

RESUMO

BACKGROUND: We sought to determine the maximal tolerated dose of the MEK inhibitor trametinib with weekly paclitaxel, with a view to exploring the combination's activity in melanoma lacking a BRAF V600 mutation. METHODS: In this phase 1 study we used a fixed dose of paclitaxel (80 mg/m2 intravenous (IV) on days 1, 8 and 15 of each 4 week cycle) and escalated the dose of trametinib (to a maximum 2mg orally (PO) daily), following a 3+3 design. Eligible patients had advanced melanoma and could have received up to two previous lines of treatment for metastatic disease. FINDINGS: 15 patients were enrolled, all but one of whose melanoma was wild type for BRAF at codon 600. The maximal monotherapy dose of trametinib proved tolerable with weekly paclitaxel. The most frequent adverse events observed were rash and fatigue. Six (40%) partial responses were reported, including four of eight patients with NRAS mutations. Median progression free survival was 5.5 months (95% confidence interval (CI) 1.8-7.8 months) and overall survival, 14.1 months (95% CI 4.6-not reached). INTERPRETATION: Trametinib can safely be given with weekly paclitaxel at the full monotherapy dose. In this small group promising progression free and overall survival were observed in patients with melanoma lacking a V600 BRAF mutation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Melanoma/tratamento farmacológico , Paclitaxel/administração & dosagem , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos
15.
Ann Nucl Med ; 28(2): 128-35, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24297388

RESUMO

BACKGROUND AND OBJECTIVE: Gastric cancer remains a leading cause of malignancy-related mortality. Many patients with locally advanced disease succumb despite peri-operative chemotherapy and the survival benefit of chemotherapy for advanced disease is modest, suggesting that current staging is imperfect. The role of fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging of gastric cancer remains to be determined. This study aimed to determine, and compare with computerized tomography (CT), the association between FDG-PET uptake in the primary tumour and regional lymph nodes, and overall survival in patients with all stage gastric cancer. METHODS: Patients with histologically confirmed gastric cancer (any stage) who, at diagnosis, had received a staging FDG-PET-CT at our institution between 2006 and 2011 were included. Records were retrospectively analysed. Patients with >50 % of tumour above the gastro-oesophageal junction or an active second malignancy were excluded. RESULTS: 97 patients were included in the analysis. Surgery with curative intent was performed in 68 patients. In univariate analysis, an association with overall survival was seen in patients who had FDG-PET-positive primary tumours (hazard ratio (HR) for death 3.33, 95 % confidence interval (95 % CI) 1.63-6.80, p = 0.001). FDG-PET lymph node positive (vs node negativity) was associated with inferior overall survival (HR 8.66, 95 % CI 4.59-16.37, p < 0.0001), and remained an independent predictor in the multivariate analysis. In contrast, positive lymphadenopathy identified on CT was not associated with overall survival (HR 1.34, 95 % CI 0.79-2.29, p = 0.82). CONCLUSION: FDG-PET-positive tumours are associated with an inferior overall survival. In contrast to CT, FDG-PET-positive lymphadenopathy is associated with a decreased overall survival.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Análise de Variância , Humanos , Estimativa de Kaplan-Meier , Linfonodos/diagnóstico por imagem , Análise Multivariada , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
16.
J Palliat Med ; 16(8): 938-40, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23734592

RESUMO

BACKGROUND AND OBJECTIVE: Ascites complicates many advanced malignancies, resulting in abdominal pain, discomfort, anorexia, nausea, and dyspnea. Percutaneous drainage relieves symptoms in the vast majority of patients. The aim of this study was to determine the course and outcomes in a consecutive series of patients with recurrent ascites managed with permanent peritoneal ports. METHODS: A prospective longitudinal descriptive study from 2006 to 2011, involving patients treated at the Sydney Cancer Center (New South Wales, Australia). RESULTS AND CONCLUSIONS: A total of 155 drainages were performed in 24 patients; 26% of drainages (n=40) in the patient's home and the remainder in the ambulatory care clinic. Grade 3 or higher adverse events occured in less than 25% of all draining procedures. An improvement in symptoms was demonstrated in almost half of all individual drainage procedures. Our findings suggest that peritoneal ports are efficacious, safe, and are associated with symptomatic relief in most patients.


Assuntos
Ascite/terapia , Neoplasias/complicações , Cuidados Paliativos/métodos , Paracentese/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/complicações , Ascite/etiologia , Institutos de Câncer , Cateteres de Demora/efeitos adversos , Cateteres de Demora/normas , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , New South Wales , Paracentese/efeitos adversos , Paracentese/instrumentação , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Adulto Jovem
17.
J Pain Symptom Manage ; 43(5): 967-72, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22285283

RESUMO

Malignant pheochromocytoma is a rare disorder. We describe the case of a 41-year-old female with disseminated metastatic pheochromocytoma who was admitted for ongoing palliative and supportive care within an inpatient palliative care unit. Predominant symptoms included severe gastrointestinal pseudo-obstruction and orthostatic hypotension Pseudo-obstruction management included percutaneous enterogastric and percutaneous enterojejunostomy tubes for gastric decompression and delivery of nutrition, respectively. Debilitating symptoms of orthostatic hypotension were mitigated with judicious fluid balance and appropriate use of adrenergic blocking agents. The potential for metoclopramide to worsen symptoms also was a significant component of management. The case presents rare features of this unusual disease and is unique for its setting within the confines of a palliative care unit.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Catecolaminas/metabolismo , Cuidados Paliativos , Feocromocitoma/metabolismo , Neoplasias das Glândulas Suprarrenais/terapia , Adulto , Feminino , Humanos , Feocromocitoma/terapia
18.
Cardiovasc Intervent Radiol ; 32(4): 772-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19214628

RESUMO

We report our initial experience using the Amplatzer Vascular Plug II (AVP2) in the treatment of a left common iliac aneurysm. Following investigation by computerized tomographic angiography and catheter angiography, a 79-year-old man was found to have a markedly tortuous iliac system, with a left common iliac artery aneurysm that measured 48 mm in maximal diameter. Due to the patient's age and comorbidities the surgical opinion was that conventional open repair was not suitable. However, due to the tortuous nature of the aneurysm and iliac vessels, standard endovascular repair, using either a bifurcated or an aorto-uni-iliac stent graft, was also not possible. A combined approach was used by embolizing the ipsilateral internal iliac artery using coils and excluding the aneurysm using two AVP2 occlusion devices, followed by femorofemoral crossover grafting. Total aneurysm occlusion was achieved using this method and this allowed the patient to have a much less invasive surgical procedure than with conventional open repair of common iliac aneurysms, thus avoiding potential comorbidity and mortality.


Assuntos
Implante de Prótese Vascular/métodos , Prótese Vascular , Embolização Terapêutica/instrumentação , Artéria Femoral/cirurgia , Aneurisma Ilíaco/cirurgia , Idoso , Angiografia , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X , Grau de Desobstrução Vascular
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