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2.
BMC Surg ; 19(1): 73, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266494

RESUMO

BACKGROUND: Diagnosis and management of acute abdomen secondary to systematic lupus erythematosus (SLE) has always been a clinical challenge. CASE PRESENTATION: A 21-year-old lady, with BMI 17.7, presented to our department with acute abdomen. Laparoscopy was carried out to exclude surgical emergency when conservative regimen failed. The patient revealed a history of purpuric changes and lupus test was positive for SLE. CONCLUSION: Based on our experience, early laparoscopy to alleviate acute abdomen has shown to improve the prognosis of the patient.


Assuntos
Abdome Agudo/diagnóstico , Abdome Agudo/cirurgia , Ascite/etiologia , Lúpus Eritematoso Sistêmico/complicações , Mesentério/irrigação sanguínea , Vasculite/cirurgia , Abdome Agudo/tratamento farmacológico , Abdome Agudo/etiologia , Administração Intravenosa , Administração Oral , Antirreumáticos/administração & dosagem , Ascite/diagnóstico por imagem , Ascite/tratamento farmacológico , Ascite/cirurgia , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Laparoscopia , Mesentério/diagnóstico por imagem , Metilprednisolona/administração & dosagem , Prognóstico , Vasculite/diagnóstico por imagem , Vasculite/tratamento farmacológico , Vasculite/etiologia , Adulto Jovem
3.
BMC Cancer ; 19(1): 652, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269916

RESUMO

BACKGROUND: There is no standard first-line chemotherapy for advanced gastric cancer with severe peritoneal metastasis. Although fluoropyrimidine is often used, its efficacy is limited, and it remains unclear whether combination therapy with platinum improves clinical outcomes. METHODS: This retrospective study involved patients at six Japanese academic hospitals between 2010 and 2016. Patients with advanced gastric cancer and severe peritoneal metastasis were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. We then compared the efficacy and safety of fluoropyrimidine monotherapy with those of fluoropyrimidine/platinum combination therapy. RESULTS: Compared with the combination therapy group (n = 64), the monotherapy group (n = 65) had worse general health (more patients with elderly age, performance status > 2, and having both massive ascites and inadequate oral intake). Both overall survival (9.0 vs 5.0 months, p < 0.01) and progression-free survival (4.3 vs 2.3 months, p < 0.01) were significantly longer in the combination group, and the significance remained after adjusting for prognostic variables (hazard ratios of 0.47 and 0.41, respectively; p < 0.01). Improvements in ascites and oral intake were also greater in the combination group. Although neutropenia (grade ≥ 3) occurred more frequently with combination therapy, both treatments in this study were tolerable. CONCLUSIONS: Combination therapy with fluoropyrimidine and platinum might be more effective than monotherapy with fluoropyrimidine and was tolerable for patients with advanced gastric cancer and severe peritoneal metastasis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ascite/tratamento farmacológico , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Masculino , Desnutrição/tratamento farmacológico , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Ácido Oxônico/administração & dosagem , Neoplasias Peritoneais/secundário , Intervalo Livre de Progressão , Piridinas/administração & dosagem , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Resultado do Tratamento , Suspensão de Tratamento , Adulto Jovem
5.
Toxicol In Vitro ; 60: 305-312, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31207347

RESUMO

The objective of study was to examine the role of MBZ on malignant ascites cells and the involvement of C-MYC. Comet assay was used to assess the genotoxic effects of MBZ in AGP01 cells and human lymphocytes; differential staining by ethidium bromide and acridine orange, caspase 3/7 and flow cytometry assay was done to access the mechanisms of apoptosis and cell cycle analysis of MBZ in AGP01 cells. C-MYC amplification, C-MYC mRNA and C-MYC protein expression were evaluated by FISH, RT-qPCR and Western blotting, respectively. In addition, cytotoxicity of MBZ was evaluated in AGP01 and AGP01 shRNA MYC by MTT. MBZ significantly increased the damage index and no produced in human lymphocytes. MBZ caused remarkable cell cycle arrest in G0/G1 and G2/M phases at 0.5µM and 1.0 µM, respectively and induced significantly apoptosis in higher concentrations. Additionally, MBZ (0.5 µM and 1.0 µM) increased caspase 3 and 7 activities. MBZ decreased signals, C-MYC mRNA and C-MYC protein expression in AGP01 cells. MBZ induced lower cell viability in AGP01 cells compared AGP01 shRNA MYC in the same concentration. Therefore, our results show the evidence of C-MYC gene as one of the pathways by which MBZ induces cell death in gastric cancer cells.


Assuntos
Ascite/tratamento farmacológico , Mebendazol/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Moduladores de Tubulina/farmacologia , Apoptose/efeitos dos fármacos , Ascite/genética , Ascite/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Humanos , Linfócitos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
6.
J Ethnopharmacol ; 241: 112034, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31226385

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine boasts a 440-year-long history of treating refractory ascites via combinations of herbal medicines, called formulae. Xiaozhang Tie (XT) is a proprietary herbal-compound-based formula that has been proven to be very effective in the treatment of cirrhosis-associated ascites in clinical practice, but the mechanism of action of XT remains unknown. AIM OF THE STUDY: In this study, we used a metabolomics-based systematic method to elucidate the mechanism of XT in the treatment of cirrhotic ascites. METHODS: Decompensated liver cirrhosis was induced in rats by intraperitoneal injection of Carbon tetrachloride (CCl4). Ultra performance liquid chromatography-mass spectrometry (UPLC-MS) combined with pattern recognition approaches were used to determine differentiating metabolites relevant to XT treatment. Biomarkers were further validated by a targeted quantitative method and by the results from serum and urine analyses. Pathway analysis and correlation network construction were used to reveal the therapeutic targets associated with XT treatment, and the potential mechanisms were verified by the results from biochemical, histopathological and immunohistochemical assays. RESULTS: XT synergistically mediated the abnormalities of amino acid metabolic pathways in cirrhotic rats. XT significantly elevated the arginine levels, reduced the serum nitric oxide (NO) levels and alleviated the gastrointestinal motility disorder of cirrhotic rats. This effect of XT has been confirmed by the inhibition of the activities of inducible NO synthase and neuronal NO synthase in the small intestine. CONCLUSIONS: These results reveal that XT promotes gastrointestinal motility by acting on multiple targets in multiple pathways, of which the L-arginine/NO pathway is most affected.


Assuntos
Arginina/metabolismo , Ascite/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática Experimental/tratamento farmacológico , Óxido Nítrico/metabolismo , Animais , Ascite/metabolismo , Ascite/fisiopatologia , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/fisiopatologia , Masculino , Metabolômica , Fitoterapia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
7.
Medicine (Baltimore) ; 98(19): e15477, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083181

RESUMO

RATIONALE: Recurrent massive hemorrhagic ascites secondary to endometriosis is extremely rare in the medical literature. PATIENT CONCERNS: We report the case of a 24-year-old nulliparous woman presenting with severe abdominal distention, massive ascites, moderate anemia, menstrual pain, and an elevated CA-125 level. DIAGNOSIS: We found a thickened peritoneum in the left lower abdomen by ultrasound during the follow-up period, and endometriosis was subsequently diagnosed by performing core needle biopsy (CNB). INTERVENTIONS AND OUTCOMES: The patient received medical treatment for endometriosis and had a good response to the treatment. LESSONS: This is the first case in which endometriosis ectopic to peritoneum was diagnosed by CNB. Endometriosis should be considered a differential diagnosis when recurrent massive hemorrhagic ascites occur. CNB should be valued as a method for diagnosing endometriosis.


Assuntos
Ascite/diagnóstico , Endometriose/diagnóstico , Hemorragia/diagnóstico , Ascite/complicações , Ascite/tratamento farmacológico , Ascite/patologia , Biópsia com Agulha de Grande Calibre , Tratamento Conservador , Diagnóstico Diferencial , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/patologia , Feminino , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Hemorragia/patologia , Humanos , Peritônio/diagnóstico por imagem , Peritônio/patologia , Recidiva , Adulto Jovem
8.
Can J Physiol Pharmacol ; 97(8): 691-698, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31071278

RESUMO

We assessed the effect of sorafenib-loaded polyamidoamine (PAMAM) dendrimer on liver fibrosis induced by bile duct ligation (BDL). Male Wistar rats were divided into 9 groups: intact, sham, DMSO + BDL, BDL, sorafenib (30 mg/kg), sorafenib (60 mg/kg), PAMAM + BDL, sorafenib (30 mg/kg) + PAMAM + BDL, sorafenib (60 mg/kg) + PAMAM + BDL. BDL was induced and then rats were treated daily with sorafenib and (or) PAMAM for 4 weeks. Improvement of liver was detected via assessment of ascites formation, collagen deposition, liver blood flow, vascular endothelial growth factor level, and blood cells count. Sorafenib-loaded PAMAM dendrimer in both 30 and 60 mg/kg doses reduced ascites formation, reduced collagen deposition, and improved drug-induced hematological side effects of sorafenib alone in comparison with sorafenib-alone treatment. Sorafenib-loaded PAMAM dendrimer increased liver blood flow compared with sorafenib-received groups. Sorafenib-loaded PAMAM dendrimer reduced BDL-induced liver injury compared with sorafenib-received groups. Moreover, sorafenib-loaded PAMAM dendrimer decreased vascular endothelial growth factor level in serum and liver tissue in comparison with sorafenib-received groups. Sorafenib-loaded PAMAM dendrimer profoundly improved the therapeutic effects of sorafenib in BDL rats.


Assuntos
Ductos Biliares/cirurgia , Dendrímeros/química , Portadores de Fármacos/química , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Sorafenibe/química , Sorafenibe/farmacologia , Animais , Ascite/tratamento farmacológico , Colágeno/metabolismo , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Ligadura/efeitos adversos , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Sorafenibe/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
J Pharm Biomed Anal ; 170: 254-263, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947126

RESUMO

Malignant ascites (MA) is one of the severe complications of gastrointestinal tumors, affecting the patients' survival time and quality of life. Euphorbia kansui is a commonly used toxic Chinese herbal medicine for malignant ascites. Our previous study showed that the biological and toxicological effects of kansui were closely related to the gastrointestinal tract. The ingenane-type and jastrophane-type diterpenoids are both toxic and active components of kansui. The contents of kansuiphorin C (KPC) and kansuinin A (KA) take highest accounts in each type of diterpene. Hence, in this study, the efficacy and toxicity of KPC and KA on normal rats and MA rats were firstly evaluated by serum liver enzymes (ALT and AST), oxidative damage indicators (GSH, SOD, MDA and LDH), inflammatory indexes (TNF-α, IFN-γ and IL-2) and the volume of ascites. Changes in the levels of these indices showed that although the toxicity of KPC on normal rats was stronger than KA, KPC exhibited better efficacy to the malignant ascites with no obvious side effects at the dose of 10 mg·kg-1. Then, accurate and reliable methods for the determination of KPC and KA in the rat feces by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) were established, detected by the multiple reaction monitoring mode. The chromatographic separation was conducted on an XBbridge C18 column (50 mm × 2.1 mm, 2.5 µm) using gradient elution composed of 0.1% formic acid in water and acetonitrile. The flow rate was 0.5 mL·min-1 and column temperature was 30 °C. The method was finally applied to the comparative study on normal and malignant ascites rats given KPC and KA, respectively. Interestingly, the results showed that KPC's accumulative fecal excretion rate (normal, 19.22%±5.36%; model, 15.96%±3.47%) were much higher than that of KA (normal, 2.928%±0.741%; model, 2.835%±0.873%) at the same dose within 48 h. This suggested KPC had higher in-vivo transformations in comparison with KA, providing guidance for the further preclinical research of KPC and KA as promising compounds treating MA.


Assuntos
Ascite/tratamento farmacológico , Diterpenos/química , Fezes/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Euphorbia/química , Masculino , Qualidade de Vida , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
10.
World J Gastroenterol ; 25(8): 888-908, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30833797

RESUMO

Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.


Assuntos
Ascite/tratamento farmacológico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Hemorragia Gastrointestinal/tratamento farmacológico , Encefalopatia Hepática/tratamento farmacológico , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Anticoagulantes/uso terapêutico , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Ascite/etiologia , Ascite/prevenção & controle , Doença Crônica/tratamento farmacológico , Modelos Animais de Doenças , Diuréticos/uso terapêutico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/prevenção & controle , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/prevenção & controle , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão Portal/etiologia , Hipertensão Portal/prevenção & controle , Cirrose Hepática/complicações , Inibidores da Bomba de Prótons/uso terapêutico , Prevenção Secundária/métodos , Resultado do Tratamento
11.
J Pharmacol Sci ; 139(4): 373-376, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30857764

RESUMO

To investigate the relationship between the exposure and efficacy of tolvaptan, we measured pharmacokinetics of total drug at 7 days after repeated doses of 3.75 mg/day tolvaptan in 16 patients with hepatic edema. Nine patients (56.3%) were responders, which were defined as those with body weight reduction of >1.5 kg/week. Serum albumin levels were significantly lower in responders than in non-responders (P = 0.031). However, the pharmacokinetics varied greatly among individuals and was not relevant to the clinical response.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacocinética , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Ascite/tratamento farmacológico , Ascite/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Tolvaptan/farmacocinética , Tolvaptan/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas dos Receptores de Hormônios Antidiuréticos/sangue , Ascite/complicações , Edema/complicações , Feminino , Humanos , Cirrose Hepática/complicações , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade , Albumina Sérica/metabolismo , Tolvaptan/sangue , Resultado do Tratamento
12.
Trials ; 20(1): 127, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760320

RESUMO

BACKGROUND: Ascites is one of the most common complications of cirrhosis. Umbilical therapy with traditional Chinese medicines has been increasingly prescribed to treat cirrhotic ascites. However, high-quality evidence from clinical trials supporting such application of traditional Chinese medicines remains limited. Therefore, we designed a clinical trial to evaluate the efficacy and safety of umbilical therapy with the Lishui Xiaogu cataplasm formulation applied to treat cirrhotic ascites. METHODS/DESIGN: This ongoing study is a double-blind, randomized, parallel, placebo-controlled trial. A total of 82 patients will be recruited and randomly assigned to either a treatment group or a placebo group, in a 1:1 ratio. The treatment group will receive umbilical therapy with the Lishui Xiaogu cataplasm plus red light irradiation along with conventional treatment; the placebo group will receive umbilical therapy with a placebo cataplasm plus red light irradiation along with conventional treatment. Interventions for both groups will be administered once daily for up to 10 days, with a 30-day follow-up after the last treatment. The primary efficacy measurement will be ascites depth. Secondary efficacy measurements will include abdominal perimeter, weight, urine volume, the symptomatic score of traditional Chinese medicine, and the Chronic Liver Disease Questionnaire. Adverse events will also be reported. DISCUSSION: This randomized trial will be the first rigorous study designed to evaluate the efficacy and safety of umbilical therapy with Lishui Xiaogu cataplasm applied for cirrhotic ascites. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16007686 . Registered on 1 January 2016.


Assuntos
Ascite/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Cirrose Hepática/complicações , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Umbigo
13.
Asia Pac J Clin Oncol ; 15(5): e126-e131, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30693655

RESUMO

PURPOSE: Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. METHODS: We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. RESULTS: Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. CONCLUSIONS: Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Ascite/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adenocarcinoma/patologia , Afatinib/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ascite/patologia , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Prognóstico
14.
Proc Natl Acad Sci U S A ; 116(6): 2210-2219, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30659155

RESUMO

In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated "solid stress," leading to better anticancer therapeutic effect. We report here four translatable findings: (i) losartan treatment enhances the efficacy of paclitaxel-a drug used for ovarian cancer treatment-via normalizing the tumor microenvironment, resulting in improved vessel perfusion and drug delivery; (ii) losartan depletes matrix via inducing antifibrotic miRNAs that should be tested as candidate biomarkers of response or resistance to chemotherapy; (iii) although losartan therapy alone does not reduce tumor burden, it reduces both the incidence and the amount of ascites formed; and (iv) our retrospective analysis revealed that patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer exhibited 30 mo longer overall survival compared with patients on other antihypertensives. Our findings provide the rationale and supporting data for a clinical trial on combined losartan and chemotherapy in ovarian cancer patients.


Assuntos
Antineoplásicos/farmacologia , Ascite/patologia , Losartan/farmacologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Células Estromais/patologia , Animais , Ascite/tratamento farmacológico , Colágeno/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Camundongos , MicroRNAs/genética , Modelos Teóricos , Estadiamento de Neoplasias , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Prognóstico , Estresse Fisiológico/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Dig Dis ; 37(3): 239-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625470

RESUMO

AIMS: Ascites is one of the major complications in advanced cirrhotic patients. Tolvaptan is a non-peptide orally available arginine vasopressin V2 receptor antagonist. We investigated and found that tolvaptan therapy improved the prognosis and predictive factor of cirrhotic patients with ascites. METHODS: Overall, 99 patients with newly diagnosed ascites with cirrhosis were enrolled. No patients had intrahepatic malignancy. The patients were divided into 2 groups based on tolvaptan therapy: 86 patients treated with tolvaptan (tolvaptan-group) and 13 patients treated without tolvaptan (non-tolvaptan-group). Tolvaptan-responder was defined as body weight loss of ≥1.5 kg/week after administering tolvaptan. RESULTS: Tolvaptan therapy was effective in 61.6% of cirrhotic patients. There was a significant difference in the overall survival (OS) between the tolvaptan-responder-group and the other groups (p < 0.001). Male (HR 5.05; p = 0.01), tolvaptan responder (HR 0.21; p = 0.02), and dosage of furosemide < 40 mg/day (HR 0.17; p = 0.01) were factors that were independently associated with the OS. The multivariate analysis revealed that C-reactive protein < 0.9 mg/dL (HR 0.07; p = 0.001), and furosemide dosage < 40 mg/day (HR 0.09; p = 0.003) were independently associated with the tolvaptan response. CONCLUSION: Therapeutic response to tolvaptan was associated with longer survival in cirrhosis patients complicated with ascites. These preliminary findings warrant validation and further exploration.


Assuntos
Ascite/complicações , Ascite/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Tolvaptan/uso terapêutico , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Feminino , Furosemida/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/patologia , Masculino , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento
16.
Ann Transplant ; 24: 1-8, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30598518

RESUMO

BACKGROUND Patients with massive ascites (MA) after liver transplantation (LT, defined here as daily ascitic drainage more than 1000 ml per day for more than 7 days after liver transplantation) are at increased risks of infection, hypoalbuminemia, graft loss, and even mortality. The aim of this retrospective cohort study was to investigate the effects of somatostatin on patients with MA after LT. MATERIAL AND METHODS Twenty-eight patients with liver cirrhosis or hepatocellular carcinoma who underwent LT complicated by MA postoperatively were included. Ten participants were receiving somatostatin therapy. The postoperative course and adverse drug effects were investigated. Daily postoperative ascitic drainage and urine output were also recorded and compared to those in the non-somatostatin group. RESULTS The somatostatin group had significantly less ascites drainage after LT compared to the non-somatostatin group (p=0.002). Urine output was significantly increased after somatostatin administration (p<0.001). No serious adverse effects influencing graft function or fatal complications occurred after somatostatin therapy. CONCLUSIONS Somatostatin treatment is beneficial for the management of MA after liver transplantation.


Assuntos
Ascite/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Somatostatina/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Idoso , Ascite/etiologia , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Resultado do Tratamento
17.
J Gastroenterol Hepatol ; 34(7): 1231-1235, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30370940

RESUMO

BACKGROUND AND AIM: The goals of the study were to identify an effective treatment for ascites and to examine the influence of tolvaptan on outcomes by investigating non-responders to tolvaptan and comparing outcomes of hepatic cirrhosis in patients treated with and without tolvaptan. METHODS: In Study 1, of 145 patients with hepatic cirrhosis who were treated with tolvaptan between September 2013 and March 2018, 45 who did not achieve weight loss of ≥1.5 kg within one week were investigated. In Study 2, 83 patients who received tolvaptan for ascites between September 2013 and March 2017 were compared with 131 patients who were treated for ascites without use of tolvaptan between January 2006 and January 2012. RESULTS: In Study 1, the 45 patients were divided into three groups based on changes in dosing of diuretics. Renal function was retained in the dose reduction group compared with that in the other groups, and the rate of discharge with remission and the outcomes were also favorable in patients with dose reduction. In Study 2, survival was significantly more favorable in patients treated with tolvaptan. CONCLUSIONS: Dose reduction of diuretics may be effective for patients with reduced renal function for whom tolvaptan is ineffective or the effect is insufficient and may also improve outcomes of patients with hepatic cirrhosis by preventing a decline in renal function caused by an increased dose of diuretics.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Ascite/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Tolvaptan/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Ascite/diagnóstico , Ascite/etiologia , Ascite/fisiopatologia , Diuréticos/administração & dosagem , Interações de Medicamentos , Resistência a Medicamentos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Tolvaptan/efeitos adversos , Resultado do Tratamento
18.
Clin Drug Investig ; 39(1): 45-54, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30284699

RESUMO

BACKGROUND AND OBJECTIVE: Tolvaptan, an oral vasopressin V2 receptor antagonist, has been widely used for the treatment of patients with cirrhosis and ascites. However, its efficacy in patients with renal dysfunction remains unknown. The objective of this study was to investigate the efficacy and safety of tolvaptan in patients with decompensated cirrhosis and severe chronic kidney disease (s-CKD). METHODS: We studied 43 patients with liver cirrhosis who received tolvaptan (7.5 mg/day) for refractory ascites. s-CKD was defined as an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Response to tolvaptan was defined as weight loss ≥ 1.5 kg in 7 days of treatment. RESULTS: Eighteen patients (42%) had s-CKD (s-CKD group), while the other 25 patients (58%) did not have s-CKD (n-CKD group). Rates of response to tolvaptan were similar: 68% in the n-CKD group and 56% in the s-CKD group. Urine volumes increased significantly from baseline to day 7 in both groups. Incidences of adverse events were also similar (P = 0.93). Mean eGFR did not decline even in the s-CKD group (27.3 ± 2.2 mL/min/1.73 m2 at baseline vs. 26.6 ± 2.3 mL/min/1.73 m2 on day 7; P = 0.9). The cumulative survival rate did not differ significantly between the n-CKD and s-CKD groups. In the s-CKD group, responders obtained a better prognosis than non-responders. CONCLUSIONS: Tolvaptan significantly increased urine volumes similarly in patients with s-CKD and n-CKD without affecting renal function. As responders achieved a better prognosis, tolvaptan could be a good option to treat ascites in patients with cirrhosis and s-CKD.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Ascite/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Tolvaptan/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos
19.
Hematol Oncol Stem Cell Ther ; 12(1): 54-59, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28390215

RESUMO

Waldenström's macroglobulinemia is a rare hematology malignancy which often presents with "B symptoms," anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström's macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström's macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ascite , Antígeno Ca-125/metabolismo , Neoplasias Peritoneais , Macroglobulinemia de Waldenstrom , Ascite/diagnóstico , Ascite/tratamento farmacológico , Ascite/metabolismo , Ascite/patologia , Cloridrato de Bendamustina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Rituximab/administração & dosagem , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/metabolismo , Macroglobulinemia de Waldenstrom/patologia
20.
Zhonghua Gan Zang Bing Za Zhi ; 27(12): 929-932, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31941255

RESUMO

Ascites is the most common clinical symptom in the decompensated stage of patients with liver cirrhosis, and its co-existence in complex conditions, such as refractory ascites, hyponatremia, hepatorenal syndrome and other complications may harm seriously. Splanchnic vasodilation is the key pathological link of cirrhotic ascites-related complications and the treatment of this link can help to eliminate the symptoms of ascites and prevent the further deterioration of decompensated cirrhosis. This paper summaries the pharmacological basis, clinical evidence and application characteristics of a vasocative drugs-terlipressin in the treatment of cirrhotic ascites-related complications, and further analyzes the problems existing in the current research, then proposes a prospect.


Assuntos
Ascite/tratamento farmacológico , Síndrome Hepatorrenal/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Terlipressina/uso terapêutico , Vasoconstritores/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Ascite/etiologia , Síndrome Hepatorrenal/complicações , Humanos , Cirrose Hepática/complicações , Resultado do Tratamento
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