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1.
Artigo em Inglês | MEDLINE | ID: mdl-32565861

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy and safety of Qidong Yixin (QY) oral liquid in the treatment of viral myocarditis (VMC). METHODS: We searched seven databases for randomized clinical trials on QY for treating VMC. The retrieval period was from database establishment to December 31, 2019. Cochrane risk of bias tool in the Cochrane Handbook was used to assess the methodological quality. Review Manager (RevMan) 5.3 was used to analyze the results. RESULTS: We included 19 studies comprising 2,608 patients, albeit with low methodological quality. Our meta-analysis revealed that combination therapy with QY and western medicine was more effective than western medicine alone (QY vs other Chinese patent medicines: RR = 1.37, 95% Cl: 1.23∼1.52, P < 0.00001; QY + coenzyme Q10 + routine treatment vs coenzyme Q10 + routine treatment: RR = 1.20, 95% Cl: 1.14∼1.27, P < 0.00001; QY + trimetazidine + acyclovir vs trimetazidine + acyclovir: RR = 1.59, 95% Cl: 1.38∼1.83, P < 0.00001; QY + routine treatment vs routine treatment: RR = 1.09, 95% Cl: 1.03∼1.15, P < 0.003). A study on posttreatment myocardial enzyme levels revealed that QY with western medicine downregulated creatine kinase isoenzyme (CK-MB) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment group: MD = -11.28, 95% CI: -13.33∼-9.22, P < 0.00001; QY + routine treatment vs routine treatment: MD = -4.96, 95% CI: -5.56∼-4.32, P < 0.00001), creatine kinase (CK) (MD = -32.10, 95% CI: -35.63∼-28.57, P < 0.00001), and lactate dehydrogenase (LDH) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment: MD = -48.76 95% CI: -58.18∼-39.33, P < 0.00001; QY + routine treatment vs routine treatment: MD = -23.52, 95% CI: -30.10-16.94, P < 0.00001) rather than western medicine alone, with no evidence of aspartate aminotransferase (AST) downregulation on treatment with QY with western medicine (MD = 2.88, 95% CI: -0.95∼6.71, P < 0.00001) in patients. Two studies reported adverse events, indicating that QY is relatively safe. CONCLUSION: Although QY may have potential advantages in treating VMC, they remain unclear owing to the poor methodological quality of most studies. Larger, multicenter, high-quality randomized controlled trials are required to verify the effectiveness of QY.

2.
J Diabetes Res ; 2020: 3695689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377518

RESUMO

BACKGROUND: Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic ß-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. METHODS: MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. RESULTS: Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. CONCLUSION: BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , terc-Butil Hidroperóxido/farmacologia , Animais , Caspase 3/metabolismo , Linhagem Celular , Proteína Forkhead Box O1/metabolismo , Glutationa Peroxidase/metabolismo , Células Secretoras de Insulina/metabolismo , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
3.
J Clin Invest ; 127(9): 3527-3542, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28758902

RESUMO

The most frequent chromosomal structural loss in hepatocellular carcinoma (HCC) is of the short arm of chromosome 8 (8p). Genes on the remaining homologous chromosome, however, are not recurrently mutated, and the identity of key 8p tumor-suppressor genes (TSG) is unknown. In this work, analysis of minimal commonly deleted 8p segments to identify candidate TSG implicated GATA4, a master transcription factor driver of hepatocyte epithelial lineage fate. In a murine model, liver-conditional deletion of 1 Gata4 allele to model the haploinsufficiency seen in HCC produced enlarged livers with a gene expression profile of persistent precursor proliferation and failed hepatocyte epithelial differentiation. HCC mimicked this gene expression profile, even in cases that were morphologically classified as well differentiated. HCC with intact chromosome 8p also featured GATA4 loss of function via GATA4 germline mutations that abrogated GATA4 interactions with a coactivator, MED12, or by inactivating mutations directly in GATA4 coactivators, including ARID1A. GATA4 reintroduction into GATA4-haploinsufficient HCC cells or ARID1A reintroduction into ARID1A-mutant/GATA4-intact HCC cells activated hundreds of hepatocyte genes and quenched the proliferative precursor program. Thus, disruption of GATA4-mediated transactivation in HCC suppresses hepatocyte epithelial differentiation to sustain replicative precursor phenotype.


Assuntos
Carcinoma Hepatocelular/metabolismo , Fator de Transcrição GATA4/metabolismo , Hepatócitos/metabolismo , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Hepatocelular/genética , Diferenciação Celular , Linhagem Celular Tumoral , Linhagem da Célula , Proliferação de Células , Células Epiteliais/citologia , Feminino , Fator de Transcrição GATA4/genética , Deleção de Genes , Mutação em Linhagem Germinativa , Haploinsuficiência , Células Hep G2 , Hepatócitos/citologia , Humanos , Inflamação , Cariotipagem , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Knockout , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único
4.
J Biol Chem ; 292(12): 4789-4800, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28179425

RESUMO

Endoglycoceramidases (EGCases) specifically hydrolyze the glycosidic linkage between the oligosaccharide and the ceramide moieties of various glycosphingolipids, and they have received substantial attention in the emerging field of glycosphingolipidology. However, the mechanism regulating the strict substrate specificity of these GH5 glycosidases has not been identified. In this study, we report a novel EGCase I from Rhodococcus equi 103S (103S_EGCase I) with remarkably broad substrate specificity. Based on phylogenetic analyses, the enzyme may represent a new subfamily of GH5 glycosidases. The X-ray crystal structures of 103S_EGCase I alone and in complex with its substrates monosialodihexosylganglioside (GM3) and monosialotetrahexosylganglioside (GM1) enabled us to identify several structural features that may account for its broad specificity. Compared with EGCase II from Rhodococcus sp. M-777 (M777_EGCase II), which possesses strict substrate specificity, 103S_EGCase I possesses a longer α7-helix and a shorter loop 4, which forms a larger substrate-binding pocket that could accommodate more extended oligosaccharides. In addition, loop 2 and loop 8 of the enzyme adopt a more open conformation, which also enlarges the oligosaccharide-binding cavity. Based on this knowledge, a rationally designed experiment was performed to examine the substrate specificity of EGCase II. The truncation of loop 4 in M777_EGCase II increased its activity toward GM1 (163%). Remarkably, the S63G mutant of M777_EGCase II showed a broader substrate spectra and significantly increased activity toward bulky substrates (up to >1370-fold for fucosyl-GM1). Collectively, the results presented here reveal the exquisite substrate recognition mechanism of EGCases and provide an opportunity for further engineering of these enzymes.


Assuntos
Glicosídeo Hidrolases/metabolismo , Rhodococcus equi/enzimologia , Sequência de Aminoácidos , Clonagem Molecular , Cristalografia por Raios X , Gangliosídeo G(M1)/metabolismo , Gangliosídeo G(M3)/metabolismo , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/genética , Modelos Moleculares , Filogenia , Conformação Proteica , Engenharia de Proteínas , Rhodococcus equi/química , Rhodococcus equi/genética , Rhodococcus equi/metabolismo , Alinhamento de Sequência , Especificidade por Substrato
6.
Ann Acad Med Singap ; 40(6): 269-75, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21779615

RESUMO

INTRODUCTION: This study aims to determine if the quantitative method of region-of-interest (ROI) analysis of lesion attenuation on CT may be a useful adjunct to the conventional approach of diagnosis by visual assessment in assessing tracer wash-out in hepatocellular carcinomas. MATERIALS AND METHODS: From a surgical database of 289 patients from 2 institutions, all patients with complete surgical, pathological and preoperative multiphasic CT scans available for review were selected. For each phase of scanning, HU readings of lesion obtained (Lesion(arterial), Lesion(PV) and Lesion(equilibrium)) were analysed using receiver operating curves (ROC) to determine the optimal method and cut-off value for quantitative assessment of tumour wash-out (Lesion(arterial - equilibrium), Lesion(PV - equilibrium) or Lesion(peak - equilibrium)). RESULTS: Ninety-four patients with one lesion each met the inclusion criteria. The area under the curve (AUC) values for Lesion(arterial - equilibrium) (0.941) was higher than the AUC for Lesion(pv - equilibrium) (0.484) and for Lesion(peak - equilibrium) (0.667). Based on ROC analysis, a cut-off of 10HU value for Lesion(arterial - equilibrium) would yield sensitivity and specificity of 91.5% and 80.9%, respectively. ROI analysis detected 9/21 (42.9%) of lesions missed by visual analysis. Combined ROI and visual analysis yields a sensitivity of 82/94 (87.2%) compared to 73/94 (77.7%) for visual analysis alone. CONCLUSION: Using a cut-off of 10 HU attenuation difference between the arterial and equilibrium phases is a simple and objective method that can be included as an adjunct to visual assessment to improve sensitivity for determining lesion wash-out on CT.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Tomografia Computadorizada por Raios X/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalos de Confiança , Bases de Dados Factuais , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
7.
ANZ J Surg ; 81(1-2): 79-85, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21299804

RESUMO

BACKGROUND: Presently, several systems for the prognostication of pancreatic endocrine neoplasms (PENs) exist and the most appropriate classification system has not been clearly defined. This study aims to validate the performance of the 2004 World Health Organization (WHO), European Neuroendocrine Tumor Society (ENETS), Memorial Sloan-Kettering Cancer Center (MSKCC), American Joint Committee for Cancer (AJCC) TNM staging and Bilimoria criteria in a cohort of patients with PENs who underwent surgery at a single institution. METHODS: This study is a retrospective review of 61 consecutive patients who underwent surgical treatment for PEN. Actuarial disease-specific survival (DSS) of all 61 patients and recurrence-free survival (RFS) of 53 patients who had curative resection were analysed. RESULTS: On univariate analyses, tumour size ≥50 mm, non-curative resection, lymph node involvement, presence of distant metastases, presence of necrosis, mitotic count ≥2/10 hpf and poor differentiation were associated with decreased DSS. Tumour size ≥50 mm, lymph node involvement, lymphovascular invasion, presence of necrosis and mitotic count ≥2/10 hpf were associated with decreased actuarial RFS. All five staging systems were useful in stratifying the 61 patients according to actuarial DSS. However, the MSKCC grading and ENETS grading systems were not statistically significant in stratifying DSS in the 61 patients. In the 53 patients who underwent curative resection, the WHO, ENETS, MSKCC, AJCC staging and the MSKCC grading systems were successful in stratifying the patients according to actuarial RFS. However, the Bilimoria scoring and ENETS grading systems were not useful in prognosticating these 53 patients. CONCLUSION: All five classification systems were useful for the prognostication of surgically treated PENs in our patient cohort.


Assuntos
Estadiamento de Neoplasias/métodos , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Singapura , Análise de Sobrevida
8.
Int J Surg ; 9(2): 145-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21029795

RESUMO

OBJECTIVES: Whilst there are theoretical benefits from pre-operatively draining the biliary tree prior to pancreatoduodenectomy (PD), the current literature does not support this intervention. The aim of this study was to explore the relationship between pre-operative stenting, bactibilia and outcome in a large United Kingdom tertiary referral practice. METHODS: Patients undergoing PD were identified from a prospectively maintained database. The presence or absence of a stent prior to PD, and the results of bile cultures taken at PD were related to the subsequent post-operative course and the development of complications. RESULTS: 280 patients underwent PD for periampullary malignancies, all of whom presented with jaundice. 118 patients were stented prior to referral (98 ERCP, 20 PTC). Bile cultures were positive more frequently in the stent group (83% vs. 55%; p = 0.000002) and bactibilia was more common after ERCP than PTC (83% vs. 56%; p = 0.006). The overall prevalence of complications was 54% in the stented and 41% in the non-stented group (p = 0.03) with statistical significance achieved for pancreatic leak (p = 0.013) and haemorrhagic complications (p = 0.03). Comparing stent with no stent, there as no difference in the 30-day mortalities (8.5% vs. 6.8%; p = 0.6) or the 1-year mortality rates (35% vs. 28%; p = 0.21). Mortality rates in the infection versus no infection groups were comparable at 30 days (8.5% vs. 5.5%; p = 0.21), and at 1 year (30.7% vs. 26.4%; p = 0.25). CONCLUSIONS: Pre-operative stent insertion prior to PD is associated with increased morbidity but not mortality and this is greatest for stents placed at ERCP.


Assuntos
Pancreaticoduodenectomia , Complicações Pós-Operatórias/epidemiologia , Cuidados Pré-Operatórios/instrumentação , Stents/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bile/microbiologia , Colangiografia , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Stents/microbiologia
9.
Int J Cancer ; 126(10): 2353-61, 2010 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19816939

RESUMO

Cholangiocarcinoma (CC) and hepatocellularcarcinoma (HCC) are two main forms of liver malignancies, which exhibit differences in drug response and prognosis. Immunohistotochemical staining for cytokeratin markers has been used to some success in the differential diagnosis of CC from HCC. However, there remains a need for additional markers for increased sensitivity and specificity of diagnosis. In this study, we have identified a p38 MAP kinase, p38delta (also known as MAPK13 or SAPK4) as a protein that is upregulated in CC relative to HCC and to normal biliary tract tissues. We performed microarray gene expression profiling on 17 cases of CC, 12 cases of adjacent normal liver tissue, and three case of normal bile duct tissue. p38delta was upregulated in 16 out of 17 cases of CC relative to normal tissue. We subsequently performed immunohistochemical staining of p38delta in 54 cases of CC and 54 cases of HCC. p38delta staining distinguished CC from HCC with a sensitivity of 92.6% and a specificity of 90.7%. To explore the possible functional significance of p38delta expression in CC, we examined the effects of overexpression and knockdown of p38delta expression in human CC cell lines. Our results indicate that p38delta is important for motility and invasion of CC cells, suggesting that p38delta may play an important role in CC metastasis. In summary, p38delta may serve as a novel diagnostic marker for CC and may also serve as a new target for molecular based therapy of this disease.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/diagnóstico , Proteína Quinase 13 Ativada por Mitógeno/metabolismo , Antígenos de Neoplasias/metabolismo , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Western Blotting , Movimento Celular , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Colágeno , Diagnóstico Diferencial , Combinação de Medicamentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Imunoprecipitação , Laminina , Proteína Quinase 13 Ativada por Mitógeno/genética , Proteína Quinase 13 Ativada por Mitógeno/imunologia , Invasividade Neoplásica , Valor Preditivo dos Testes , Proteoglicanas , Sensibilidade e Especificidade , Regulação para Cima
10.
Hepatol Int ; 3(4): 587-92, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19763713

RESUMO

A 71-year-old man presented to our hospital with 3-week history of fever in the background of loss of both weight and appetite over the past 3 months. He was found to have a large 10-cm mass in the right lobe of the liver on a triple-phase computed tomographic scan. The tumor showed a distinct fatty component, with areas of arterial enhancement and venous washout suggestive of hepatocellular carcinoma (HCC), another component showing progressive and late enhancement suggestive of cholangiocarcinoma (CC), and a third component showing persistent hypoenhancement relative to the liver parenchyma. He underwent surgical resection. This was histopathologically a biphasic tumor composed of areas showing hepatocytic differentiation, in contiguity with areas showing infiltrative glands set within fibrous stroma in keeping with combined hepatocellular and cholangiocarcinoma (cHCC-CC). A third component of pleomorphic spindle and epithelioid appearance in keeping with sarcomatous transformation was also found intimately related to the CC component. The patient developed extensive thoracic and abdominal metastases 2 months after surgery and died shortly after.

11.
J Gastrointest Surg ; 13(6): 1071-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19291334

RESUMO

INTRODUCTION: Presently, the need for and choice of preoperative localization tests for insulinomas remain controversial. We report the results from a single institution experience whereby the management policy adopted was that of accurate preoperative localization before surgical exploration. MATERIALS AND METHODS: From 1990 to 2008, 17 patients with a clinical and biochemical diagnosis of an insulinoma who underwent surgery were retrospectively reviewed. The diagnosis of all insulinomas were confirmed pathologically. RESULTS: All tumors were localized preoperatively and an average of 2.2 preoperative localization studies including 1.4 noninvasive studies and 0.8 invasive studies were utilized per patient. Invasive localization modalities were more sensitive (92%) than noninvasive modalities in localizing insulinomas (71%). Intra-arterial calcium stimulation with hepatic venous sampling was the most sensitive invasive modality (100%), whereas magnetic resonance imaging was the most sensitive noninvasive modality (63%). Fifteen of 17 tumors (88%) were localized intraoperatively via inspection/palpation and/or intraoperative ultrasonography. Both insulinomas which were not localized intraoperatively were localized correctly to the distal pancreas via preoperative transhepatic portal venous sampling. None of the patients required a blind resection or surgical reexploration for failed localization. All 17 patients underwent complete surgical resection which included eight enucleations and nine distal pancreatectomies with a cure rate of 94% (16/17) at a median follow-up of 35 (range, 1-217) months. The postoperative morbidity and long-term outcome of enucleation was similar to distal pancreatectomy despite a higher rate of microscopic margin involvement. CONCLUSION: Accurate preoperative localization of insulinomas is useful as it eliminates the need for blind distal pancreatectomy and avoids reoperation. Complete surgical resection is the treatment of choice, and whenever possible, a pancreas-sparing approach such as enucleation should be adopted.


Assuntos
Insulinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Insulinoma/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Resultado do Tratamento
12.
Arch Surg ; 143(10): 956-65, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18936374

RESUMO

OBJECTIVE: To critically analyze a large single-institution experience with distal pancreatectomy (DP), with particular attention to the risk factors, outcome, and management of the postoperative pancreatic fistula (PF). DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 232 consecutive patients with pancreatic or extrapancreatic disease necessitating DP over 21 years. INTERVENTIONS: Twenty-one patients underwent spleen-preserving DP, 117 underwent DP with splenectomy, and 94 underwent DP with multiorgan resection. MAIN OUTCOME MEASURES: The perioperative and postoperative data of patients who underwent DP were analyzed. This included factors associated with postoperative morbidity with particular attention to the PF (defined by the International Study Group of Pancreatic Fistula) and changing trends in operative and perioperative data during the study period. RESULTS: The overall operative morbidity and mortality were 47% (107 patients) and 3% (7 patients), respectively. During the study period, the rates of resection increased from 3 cases to 23 per year, and increasingly these were performed for smaller and incidental lesions. The morbidity rate remained unchanged, but there was a decline in postoperative stay and the need for care in the intensive care unit. Pancreatic fistulas occurred in 72 patients (31%); 41 (18%) were grade A, 13 (6%) grade B, and 18 (8%) grade C. Increased weight, higher American Society of Anesthesiologists score, blood loss greater than 1 L, increased operation time, decreased albumin level, and sutured closure of the stump without main duct ligation were associated with a postoperative PF on univariate analysis. A DP with splenectomy was associated with a higher incidence of grade B or C PF and non-PF-related complications. Ninety-two percent of PFs were successfully managed nonoperatively. Clinical outcomes correlated well with PF grading, as evidenced by the progressive increase in outcome measures such as postoperative stay, readmissions, reoperations, radiologic interventions, and non-PF-related complications from grade A to C PFs. CONCLUSIONS: Pancreatic fistula is the most common complication after DP and its incidence varies depending on the definition applied. Several risk factors for developing a PF were identified. Splenic preservation after DP is safe. The grade of a PF correlates well with clinical outcomes, and most PFs may be managed nonoperatively.


Assuntos
Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Pancreatopatias/mortalidade , Pancreatopatias/cirurgia , Fístula Pancreática/terapia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Causas de Morte , Estudos de Avaliação como Assunto , Feminino , Humanos , Incidência , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparotomia/efeitos adversos , Laparotomia/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreatopatias/patologia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Singapura , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
13.
Dig Surg ; 25(1): 32-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18292659

RESUMO

OBJECTIVES: To determine the outcome of patients undergoing distal pancreatectomy for pancreatic adenocarcinoma. METHODS: A retrospective review of 39 patients undergoing distal pancreatectomy for adenocarcinoma. RESULTS: Thirty patients underwent surgery for ductal adenocarcinoma, 5 for malignant intraductal papillary mucinous neoplasm and 4 for mucinous cystadenocarcinoma. Malignant cystic neoplasms were significantly less likely to demonstrate perineural invasion, more likely to be well-differentiated, of lower T stage and of lower AJCC staging compared to ductal adenocarcinoma. These had a longer median disease-specific survival (42 (3-144) vs. 15 (14-16) months, p = 0.002). Eight patients underwent extended resections. These were associated with longer operating times compared to standard resections but there was no difference in surgical morbidity or mortality, blood transfusions, length of hospitalization or long-term survival. Univariate analysis demonstrated that R2 resection, size >30 mm, lymph node involvement, need for perioperative blood transfusion, serum albumin <40 g/l and platelet count <200/microl were predictors of survival for ductal adenocarcinoma. CONCLUSIONS: Malignant cystic neoplasms have less aggressive behavior and more favorable outcome compared to ductal adenocarcinoma. R2 resection, larger tumor size, lymph node involvement, perioperative transfusion, decreased serum albumin and low platelet count are factors associated with decreased survival in patients with ductal adenocarcinoma undergoing distal pancreatectomy.


Assuntos
Adenocarcinoma/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento
14.
J Am Coll Surg ; 206(1): 17-27, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18155564

RESUMO

BACKGROUND: This study aims to determine the use of preoperative clinical, biochemical, and cross-sectional imaging features for predicting malignancy in cystic lesions of the pancreas (CLP). STUDY DESIGN: Two hundred twenty patients who underwent operations for CLP or suspected CLP were reviewed. Patients were divided into two groups, patients undergoing operations for pseudocysts and patients undergoing operations for suspected cystic neoplasms. The predictive effect of various preoperative factors on the malignant potential of CLP was evaluated. RESULTS: Forty-four patients with a preoperative diagnosis of pseudocysts underwent operations for complications of pseudocyst. Forty-two were confirmed pathologically to have pseudocysts, but two were found, unexpectedly, to harbor malignant lesions. One hundred seventy-six patients underwent operations for suspected pancreatic cystic neoplasms. There were 70 benign, 51 potentially malignant, and 55 malignant CLP. On multivariate analysis, three factors, ie, elevated serum carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9; cyst size > 3 cm; and presence of one or more of three morphologic features, such as solid component; peripheral calcification; and main duct dilation on cross-sectional imaging were independent predictors of malignancy. Presence of two or three of these factors had a positive predictive value of 88% in predicting a premalignant or malignant CLP. CONCLUSIONS: Most pancreatic pseudocysts can be accurately diagnosed preoperatively. In patients with suspected pancreatic cystic neoplasms, elevated serum CEA or carbohydrate antigen 19-9, cyst size > 3 cm, and presence of suspicious morphologic features on imaging are predictors of potentially malignant or malignant CLP. Patients with a high likelihood of a potentially malignant or malignant lesion based on these three factors should undergo operation without additional investigations.


Assuntos
Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Imageamento por Ressonância Magnética/métodos , Pancreatectomia/métodos , Cisto Pancreático/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cisto Pancreático/sangue , Cisto Pancreático/cirurgia , Pseudocisto Pancreático/sangue , Pseudocisto Pancreático/diagnóstico , Pseudocisto Pancreático/cirurgia , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Singapura
15.
Am J Surg ; 193(6): 749-55, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17512290

RESUMO

BACKGROUND: Currently, the management strategy of pancreatic cyst (PC) remains controversial because of the inability to diagnose this type of cyst accurately and the limited knowledge of its natural history. Previously, many clinicians have advocated an aggressive resectional policy. This approach is no longer appropriate, and the number of PCs detected incidentally has increased. This study reviews the present literature and attempts to provide a management algorithm of pancreatic cysts based on currently available evidence. METHODS: A Medline search was conducted to identify studies investigating PC, with particular emphasis placed on studies addressing its diagnosis and management. Additional articles were obtained from the reference lists of key articles and recent reviews. COMMENTS: Based on current evidence, the optimal management of PC remains an art and should be individualized based on the risk-benefit ratio of surgery, which is influenced by multiple factors, such as the patient's potential life expectancy, surgical risk; and malignant potential of the cyst. Our proposed management algorithm is based on an individual's predicted risk-benefit ratio of surgery. Prospective evaluation of the algorithm is needed to determine its integrity.


Assuntos
Algoritmos , Pancreatectomia/métodos , Cisto Pancreático/diagnóstico , Cisto Pancreático/cirurgia , Biópsia por Agulha Fina , Diagnóstico Diferencial , Progressão da Doença , Endossonografia , Humanos , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X
16.
J Gastrointest Surg ; 11(5): 612-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17468919

RESUMO

Liver resection is commonly performed for solitary hepatocellular carcinoma (HCC) in well-compensated cirrhotic and noncirrhotic patients. Data concerning exacerbation of chronic hepatitis B (ECHB) post-liver resection are scant. To determine the incidence, risk factors, and clinical outcomes of ECHB in patients who underwent hepatic resection for HCC. The methods consisted of a retrospective review of consecutive patients with chronic hepatitis B virus (HBV) infection who had undergone liver resection for HCC from January 2002 to December 2004. Seventy-seven patients underwent 82 liver resections; the mean age was 58.0 +/- 12.1 years; 87% male; 20% hepatitis B e-antigen positive. Incidence of all causes of postoperative hepatitis was 25.6% (n = 21), and ECHB was 8.5% (n = 7). Both groups had their peak alanine aminotransferases, 231.0 IU/L (74-1,400) and 312 IU/L (147-1,400), respectively, observed at day 84 postresection. Three patients died as a result of ECHB within 4 months postsurgery. One- and 2-year survival rates were poorest for the ECHB group at 42.9 and 21.4%, compared with those with postoperative hepatitis due to other causes at 60.3 and 45.2% and those without postoperative hepatitis at 87.7 and 73.5% (p < 0.001). Liver resection for HCC in patients with chronic HBV infection carries a risk for ECHB, and affected patients have poorer clinical outcomes. There is a need for close monitoring of these patients preoperatively and in the early postoperative period.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Hepatite B Crônica/fisiopatologia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Causas de Morte , Feminino , Seguimentos , Hepatite/etiologia , Antígenos E da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
17.
J Surg Oncol ; 95(8): 640-4, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17477365

RESUMO

INTRODUCTION: The aim of this study is to report an update of the surgical experience at a single institution with these unusual tumors. METHODS: Sixteen consecutive patients who underwent surgery for a pathologically confirmed solid pseudopapillary neoplasm (SPPN) were retrospectively reviewed. RESULTS: Fifteen of the patients were female and the median age at diagnosis was 30 years (range, 14-53 years). Abdominal and back pain were the most common presenting symptoms. The tumors appeared on cross-sectional imaging as solid and cystic (n = 14) or cystic (n = 2) masses. The median tumor size was 9.5 cm (range, 5.0-24.0 cm). All 16 patients had curative resections including 3 pancreaticoduodenectomies and 13 distal pancreatectomies. Three patients required extended resections including pancreaticoduodenectomy with portal vein resection, distal pancreatectomy with tranverse colectomy, and distal pancreactomy with omentectomy. Two of the resections were R1 whereas 14 were R0. All patients were alive and disease-free at a median follow-up of 43 months (range, 3-186 months). CONCLUSION: SPPNs should be considered in young women presenting with a large solid-cystic pancreatic mass. Aggressive en bloc resection should always be attempted including resection of concomitant metastases as patients demonstrate excellent long-term survival even in the presence of distant spread.


Assuntos
Carcinoma Papilar/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pseudocisto Pancreático/cirurgia , Pancreaticoduodenectomia , Adolescente , Adulto , Carcinoma Papilar/patologia , Colectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omento/cirurgia , Neoplasias Pancreáticas/patologia , Pseudocisto Pancreático/patologia , Veia Porta/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
18.
Dig Surg ; 23(5-6): 319-24, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17170527

RESUMO

BACKGROUND/AIM: A cholangiocarcinoma, the second most common primary hepatic malignancy, can present with diagnostic dilemmas. The aim of this study is to assess the role of CA 19-9 in patients with a cholangiocarcinoma without primary sclerosing cholangitis. METHODS: The prospectively collected information on patients with biopsy-proven cholangiocarcinomas who had the CA 19-9 level measured was obtained (n = 68) from our computer database and medical records. These patients were compared with patients who had benign liver tumours (n = 25) and benign bile duct strictures (n = 13) who also had their CA 19-9 concentration measured. RESULTS: Sensitivity and specificity of CA 19-9 in the diagnosis of a cholangiocarcinoma were 77.9 and 76.3%, respectively, when using a cut-off value of 35 kU/l, while sensitivity and specificity were 67.5 and 86.8%, respectively, when the cut-off value was raised to 100 kU/l. The specificity was found to be higher in patients with peripheral cholangiocarcinomas (96%) using a CA 19-9 cut-off value >100 kU/l. A CA 19-9 value >600 kU/l was associated with non-resectable tumours (p = 0.05). CONCLUSIONS: This study demonstrates that CA 19-9 is a useful adjunct in the diagnosis of cholangiocarcinomas without primary sclerosing cholangitis, especially in the diagnosis of peripheral cholangiocarcinomas. However, it does not provide a reliable guide for the pathological staging of these tumours.


Assuntos
Neoplasias dos Ductos Biliares/sangue , Ductos Biliares Intra-Hepáticos , Antígeno CA-19-9/sangue , Colangiocarcinoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia , Colangite Esclerosante , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
19.
World J Surg ; 30(12): 2236-45, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17103100

RESUMO

INTRODUCTION: Despite formal definitions of mucinous cystic neoplasms (MCNs) and intraductal papillary neoplasms (IPMNs) by the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP), several controversies with regard to MCNs remain. The aim of this review was to determine the clinicopathological features of MCNs defined by ovarian-type stroma (OS) as proposed by the WHO and AFIP and to compare them with MCNs defined by less stringent criteria. METHODS: A MEDLINE search was conducted to identify English-language articles on pancreatic MCNs from 1996 to 2005. Twenty-five studies were identified. The studies were divided into 2 groups: group A included 10 studies with 344 patients whereby the presence of OS was a criteria for the diagnosis of MCNs, and group B, included 15 studies comprising 761 patients whereby the presence of OS was not mandatory for the diagnosis of MCNs. RESULTS: Patients in group A (MCNs as defined by OS) were almost always female (99.7%), with a mean age of 47 (range, 18-95) years. MCNs were located predominantly in the body or tail of the pancreas (94.6%) and had a mean size of 8.7 cm (range, 0.6-35 cm); 76% were symptomatic, 6.8% demonstrated ductal communication, and 27% were malignant. At a mean follow-up of 57.5 (range, 1-264) months and 43 (range, 2-257) months after surgery, 97.9% of benign and 61.9% of malignant neoplasms were disease free, respectively. Patients in group B were older and had a higher proportion of males. Neoplasms were more evenly distributed in the pancreas, were smaller, communicated more frequently with the pancreatic duct, and were composed of a higher proportion of malignant tumors compared with group A. Their clinicopathological features were intermediate between those of group A and patients with IPMN. CONCLUSION: Pancreatic MCNs with OS have unique and distinct clinicopathological features. MCNs should be defined by the presence of OS, as it is the most reliable way of distinguishing MCNs from IPMN. Adoption of "looser" criteria will result in misclassification of some IPMNs as MCNs.


Assuntos
Cistadenocarcinoma Mucinoso/classificação , Cistadenocarcinoma Mucinoso/patologia , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Pancreatology ; 6(6): 520-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17124434

RESUMO

BACKGROUND/AIMS: The occurrence of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary neoplasm (IPMN) of the pancreas has rarely been reported. We describe our experience with 3 patients with this association and review the existing literature. METHODS: From 1990 to 2005, 65 patients who underwent surgery for a PEN or IPMN were retrospectively reviewed. Forty-three patients had a PEN, 19 had an IPMN and 3 had both an IPMN and PEN. The 3 patients with concomitant IPMN and PEN are the focus of the current study and their clinicopathological features are reported together with 7 patients previously reported in the literature. RESULTS: There were 10 patients with a median age of 62 years (range 40-73). The male:female ratio was equal. Seven of 10 patients were symptomatic and the most common symptoms were abdominal pain (n = 5), jaundice (n = 2) and loss of weight (n = 2). The median size of the endocrine neoplasms was 14 mm (range 2-30) and they occurred in the head (n = 3), body (n = 2) and tail (n = 5). Seven of the PENs were classified as benign, 2 were potentially malignant, and 1 was frankly malignant with lymph node involvement. None of the endocrine neoplasms were functioning. The IPMNs were found in the tail (n = 4), head (n = 3), head and body (n = 1), body (n = 1) and the entire pancreas (n = 1). Five of these neoplasms were benign, 2 were borderline and 3 were malignant (1 carcinoma in situ). CONCLUSION: The occurrence of concomitant IPMN and PEN is more frequent than would be expected. However, it is difficult in the present analysis to determine if this association is more than just fortuitous.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Segunda Neoplasia Primária/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/cirurgia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/metabolismo , Carcinoma Papilar/cirurgia , Cromograninas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirurgia , Sinaptofisina/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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