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1.
World J Clin Cases ; 12(12): 2099-2108, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38680271

RESUMO

BACKGROUND: The clinical incidence of spinal infection is gradually increasing, and its onset is insidious, easily leading to missed diagnosis and misdiagnosis, which may lead to serious complications such as nervous system dysfunction, spinal instability and/or deformity, and cause a huge burden on society and families. Early identification of the causative agent and precision medicine will greatly reduce the suffering of patients. At present, the main pathogenic bacteria that cause spinal infection are Staphylococcus aureus, Streptococcus, Pneumococcus, Escherichia coli, and Klebsiella. There are no reports of spinal infection caused by Pseudomonas fluorescens. CASE SUMMARY: We report a 32-year-old female patient with spinal infection. She presented with flank pain, initially thought to be bone metastases or bone tuberculosis, and had a family background of tumors. Her clinical features and changes in imaging and laboratory tests led to the suspicion of thoracic spine infection. Histopathology of the lesion showed inflammation, tissue culture of the lesion was negative several times, and the possible pathogen - Pseudomonas fluorescens was found after gene sequencing of the lesion. The patient recovered completely after a full course of antibiotic treatment. CONCLUSION: This report increases the range of pathogens involved in spinal infections, highlights the unique advantages of gene sequencing technology in difficult-to-diagnose diseases, and validates conservative treatment with a full course of antibiotics for spinal infections without complications.

2.
Genet Mol Biol ; 45(3): e20210419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36098487

RESUMO

Vascular hypo-responsiveness to vasopressors in patients with obstructive jaundice (OJ) is a common anesthetic event, which leads to perioperative complications and increased mortality. The cause of this clinical issue remains unclear. In this study, we estimated the actin cytoskeleton and arterial protein level in the artery of OJ patients by proteomic analysis. Ten patients with OJ due to bile duct diseases or pancreatic head carcinoma were enrolled, while another ten non-jaundice patients with chronic cholecystitis or liver hemangioma as the control group. Vascular reactivity to noradrenaline was measured before anesthesia on the day of surgery. Artery samples in adjacent tissues of removed tumor were collected and evaluated by 2-dimensional electrophoresis. Proteins with differential expression were detected by MALDI-TOF mass spectrometry with immunoblot confirmation. The results confirmed the phenomenon of vascular hypo-reactivity in OJ patients as suppressed aortic response to noradrenaline were existed in these patients. We also found that actin cytoskeleton and several actin-binding proteins were up- or down-regulated in the artery of OJ patients. These proteins changed in OJ patents might be the basic mechanism of vascular hypo-reactivity, further studies to uncover the role of these proteins in OJ is critical for clinical treatment of these patients.

3.
Front Pharmacol ; 13: 939912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147313

RESUMO

Background: Hepatocellular carcinoma (HCC) is a lethal disease with high relapse and dismal survival rates. Alternative splicing (AS) plays a crucial role in tumor progression. Herein, we aim to integratedly analyze the relapse-associated AS events and construct a signature predicting tumor relapse in stage I-III HCC. Methods: AS events of stage I-III HCC with tumor relapse or long-term relapse-free survival were profiled to identify the relapse-associated AS events. A splicing network was set up to analyze the correlation between the relapse-associated AS events and splicing factors. Cox regression analysis and receiver operating characteristic curve were performed to develop and validate the relapse-predictive AS signature. Single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm were used to assess the immune infiltration status of the HCC microenvironment between different risk subgroups. Unsupervised cluster analysis was conducted to assess the relationship between molecular subtypes and local immune status and clinicopathological features. Results: In total, 2441 ASs derived from 1634 mRNA were identified as relapse-associated AS events. By analyzing the proteins involved in the relapse-associated AS events, 1573 proteins with 11590 interactions were included in the protein-protein interaction (PPI) network. In total, 16 splicing factors and 61 relapse-associated AS events with 85 interactions were involved in the splicing network. The relevant genes involved in the PPI network and splicing network were also analyzed by Gene Ontology enrichment analysis. Finally, we established a robust 16-gene AS signature for predicting tumor relapse in stage I-III HCC with considerable AUC values in all of the training cohort, testing cohort, and entire cohort. The ssGSEA and ESTIMATE analyses showed that the AS signature was significantly associated with the immune status of the HCC microenvironment. Moreover, four molecular subgroups with distinguishing tumor relapse modes and local immune status were also revealed. Conclusion: Our study built a novel 16-gene AS signature that robustly predicts tumor relapse and indicates immune activity in stage I-III HCC, which may facilitate the deep mining of the mechanisms associated with tumor relapse and tumor immunity and the development of novel individualized treatment targets for HCC.

4.
World J Gastroenterol ; 27(36): 6079-6092, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34629821

RESUMO

BACKGROUND: Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally. Cisplatin (DDP) is one of the most common and effective chemotherapies for patients with gastric cancer, but DDP resistance remains a severe clinical challenge. AIM: To explore the function of M2 polarized macrophages-derived exosomal microRNA (miR)-588 in the modulation of DDP resistance of gastric cancer cells. METHODS: M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis. The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers. The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells. The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay, apoptosis analysis, colony formation assay, Western blot analysis, qPCR analysis, and luciferase reporter assay in SGC7901 and SGC7901/DDP cells, and by tumorigenicity analysis in nude mice. RESULTS: M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin (IL)-13 and IL-4. Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance. M2 polarized macrophages-derived exosomes could transfer in gastric cancer cells to enhance DDP resistance. Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells. miR-588 promoted DDP-resistant gastric cancer cell growth in vivo. miR-588 was able to target cylindromatosis (CYLD) in gastric cancer cells. The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP. CONCLUSION: In conclusion, we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD. miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Macrófagos , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
5.
Curr Med Sci ; 41(4): 788-802, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403105

RESUMO

OBJECTIVE: Antipsychotics, in particular olanzapine, are first-line medications for schizophrenia. The prefrontal cortex (PFC) is an important region for antipsychotics' therapeutic effects. The PFC inflammatory and immune pathways are associated with schizophrenia pathogenesis. However, the effect of antipsychotics on the inflammatory and immune pathways in the PFC remains unclear. We aimed to examined the time-dependent effect of olanzapine on inflammatory and immune markers in the PFC of rats. Since the inflammatory and immune pathways are related to endoplasmic reticulum (ER) stress, we further investigated whether or not olanzapine-induced inflammation and immune responses were related to ER stress. METHODS: Expression of pro-inflammatory markers including IkappaB kinase ß (IKKß), nuclear factor kappa B (NFκB), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and IL-1ß, and immune-related proteins including inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2) and cluster of differentiation 14 (CD14) were examined by Western blotting. RESULTS: Olanzapine treatments for 1, 8 and 36 days significantly activated the inflammatory IKKß/NFκB signaling, and increased the expression of TNF-α, IL-6, IL-1ß and immune-related proteins such as iNOS, TLR4 and CD14. Olanzapine treatment for 1 day, 8 and 36 days also induced ER stress in the PFC. Co-treatment with an ER stress inhibitor, 4-phenylbutyrate, inhibited olanzapine-induced inflammation and the immune response in the PFC. CONCLUSION: These results suggested olanzapine exposure could be a factor that induces central inflammation and immunological abnormities in schizophrenia subjects. Olanzapine induces PFC inflammation and immune response, possibly via activating ER stress signaling.


Assuntos
Estresse do Retículo Endoplasmático/genética , Inflamação/metabolismo , Olanzapina/farmacologia , Córtex Pré-Frontal/metabolismo , Esquizofrenia/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Quinase I-kappa B/genética , Imunidade/efeitos dos fármacos , Imunidade/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Óxido Nítrico Sintase Tipo II/genética , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Ratos , Esquizofrenia/complicações , Esquizofrenia/genética , Esquizofrenia/patologia , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/genética
6.
World J Surg Oncol ; 18(1): 239, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891147

RESUMO

PURPOSES: This study was designed to evaluate the effect of preoperative jaundice on long-term prognosis of gallbladder carcinoma (GBC) after radical resection (R0). METHODS: A total of 267 GBC patients who underwent R0 resection from January 2004 to December 2014 were enrolled, including 54 patients with preoperative jaundice and 213 patients without jaundice. The clinicopathological parameters between the two groups were compared, and the correlation between preoperative jaundice and the long-term prognosis was furtherly analyzed. RESULTS: Unilateral and multivariate analyses of 267 GBC patients showed that the depth of tumor invasion (pT stage), lymphatic metastasis, and hepatic invasion were independent prognostic factors. The univariate and multivariate analysis of 54 GBC patients with preoperative jaundice showed that only pT stage was an independent factor for prognosis. Furthermore, the intraoperative blood transfusion and pT stage were significant different between long-term survival (survive for more than 3 years) and those who died within 3 years (P < 0.05). CONCLUSION: Preoperative jaundice was not the independent factor resulting in the poor long-term prognosis of gallbladder carcinoma after R0 resection. The pT stage was the only long-term prognostic factor in all GBC patients regardless of preoperative jaundice.


Assuntos
Neoplasias da Vesícula Biliar , Icterícia , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Icterícia/etiologia , Icterícia/patologia , Fígado/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
7.
Hepatobiliary Pancreat Dis Int ; 19(2): 138-146, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32139295

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) are commonly used to treat intrahepatic recurrent liver cancers. However, there is no information regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma (ICC) after resection. METHODS: A total of 275 patients with localized recurrent ICC who received either TACE (n = 183) or PMCT (n = 92) were studied. A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT. Prognostic factors for TACE and PMCT were identified respectively. Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values. RESULTS: Both TACE and PMCT provided curativeness in partial patients (5-year overall survival: 21.4% and 6.1%, respectively), but TACE provided better survival benefit in both overall patients (hazard ratio [HR] = 0.71; 95% confidence interval [CI]: 0.50-0.97; P = 0.034) and propensity score matching analysis (HR = 0.69; 95% CI: 0.47-0.98; P = 0.041). Independent prognostic factors for TACE were tumor size >5 cm, poor differentiation, and major resection, whereas poor differentiation, hepatitis B virus infection, cholelithiasis, and lymph node metastasis were identified for PMCT. Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70, respectively. CONCLUSIONS: TACE provided better survival benefits compared to PMCT. However, there was a disparity in prognostic factors, suggesting evaluation of the two nomograms may be supportive in modality selection. Further prospective validation studies are required for the results to be applied in clinical medicine.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Quimioembolização Terapêutica , Colangiocarcinoma/terapia , Micro-Ondas/uso terapêutico , Recidiva Local de Neoplasia/terapia , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Coagulação Sanguínea , Colangiocarcinoma/secundário , Colangiocarcinoma/cirurgia , Colelitíase/complicações , Cães , Feminino , Hepatite Infecciosa Canina/complicações , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
8.
Cell Res ; 29(1): 8-22, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30361550

RESUMO

The study of pathophysiological mechanisms in human liver disease has been constrained by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. We and others have previously shown that mouse mature hepatocytes can be converted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD + -dependent deacetylase SIRT1 signaling. These HepLPCs could be expanded significantly during in vitro passage. The expanded cells can readily be converted back into metabolically functional hepatocytes in vitro and upon transplantation in vivo. Under three-dimensional culture conditions, differentiated cells generated from HepLPCs regained the ability to support infection or reactivation of hepatitis B virus (HBV). Our work demonstrates the utility of the conversion between hepatocyte and liver progenitor-like cells for studying HBV biology and antiviral therapies. These findings will facilitate the study of liver diseases and regenerative medicine.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B/patologia , Hepatócitos , Fígado/patologia , Células-Tronco , Animais , Diferenciação Celular , Células Cultivadas , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Camundongos , Sirtuína 1/metabolismo , Células-Tronco/citologia , Células-Tronco/patologia
9.
J Gastroenterol Hepatol ; 34(6): 1049-1057, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30515890

RESUMO

BACKGROUND AND AIM: Mucosal traction as a "second hand" in endoscopic submucosal dissection (ESD) is very helpful for ESD operators. The efficacy of using a snare combined with endoclips to assist in ESD (SC-ESD) was evaluated whether it could achieve peroral external traction (PET) and peroral internal traction (PIT) and real-time adjustment of mucosal traction position. This study aimed to preliminarily evaluate its feasibility. METHODS: A snare was fixed using endoclips to the incised mucosal flap that was intended for dissection. Subsequently, the snare was adjusted to achieve mucosal traction. This study included 54 gastroesophageal neoplasias in 54 consecutive patients who underwent SC-ESD. The operative and clinical data were retrospectively collected. RESULTS: Peroral external tractions were performed for 22 esophageal neoplasias, and PETs and PITs were performed for 32 gastric neoplasias. The median (interquartile range) sizes of lesions were 4.3 (2.5) and 4.2 (2.1) cm, operation times were 73.4 (43.8) and 60.0 (45.2) min, and submucosal dissection times were 27.0 (32.0) and 31.0 (34.5) min in the esophagus and stomach, respectively. Mucosal traction position could be effectively adjusted by fixing the snare to the incised mucosal flap intended for dissection during SC-ESD. All lesions in the esophagus and stomach were completely resected, with R0 resection rates of 100%. Besides postoperative bleeding in a patient with gastric neoplasia, no intraoperative and postoperative perforations occurred. CONCLUSIONS: SC-ESD seems to be feasible for resecting gastroesophageal neoplasia, and two types of mucosal tractions (PET and PIT) could be effectively achieved during SC-ESD. Further prospective comparative study with a large sample is warranted.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/cirurgia , Mucosa Gástrica/cirurgia , Neoplasias Gástricas/cirurgia , Tração/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ressecção Endoscópica de Mucosa/instrumentação , Mucosa Esofágica/patologia , Estudos de Viabilidade , Feminino , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Tração/instrumentação , Resultado do Tratamento
10.
Gastroenterology ; 152(5): 1187-1202, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28065789

RESUMO

BACKGROUND & AIMS: Choline kinase α (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor-adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor-adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor-adjacent tissues) were also analyzed. CHKA gene copy number was quantified and findings were validated by quantitative reverse transcription polymerase chain reaction analysis. CHKA messenger RNA and protein levels were determined by polymerase chain reaction, immunohistochemical, and immunoblot analyses. CHKA was examined in 2 hepatocyte cell lines and 7 HCC-derived cell lines, and knocked down with small interfering RNAs in 3 HCC cell lines. Cells were analyzed in proliferation, wound healing, migration, and invasion assays. Cells were injected into tail veins of mice and tumor growth and metastasis were quantified. Immunoprecipitation and immunofluorescence assays were conducted to determine interactions between CHKA and the epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin complex 2. RESULTS: Levels of CHKA messenger RNA were frequently increased in HCC tissues compared with nontumor tissues; increased expression was associated with amplification at the CHKA loci. Tumors that expressed high levels of CHKA had more aggressive phenotypes, and patients with these tumors had shorter survival times after surgery compared to patients whose tumors expressed low levels of CHKA. HCC cell lines that stably overexpressed CHKA had higher levels of migration and invasion than control HCC cells, and formed larger xenograft tumors with more metastases in mice compared to HCC cells that did not overexpress CHKA. CHKA was required for physical interaction between EGFR and mechanistic target of rapamycin complex 2. This complex was required for HCC cells to form metastatic xenograft tumors in mice and to become resistant to EGFR inhibitors. CONCLUSIONS: We found levels of CHKA to be increased in human HCCs compared to nontumor tissues, and increased expression to be associated with tumor aggressiveness and reduced survival times of patients. Overexpression of CHKA in HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and ability to form metastatic tumors in mice by promoting interaction of EGFR with mechanistic target of rapamycin complex 2.


Assuntos
Carcinoma Hepatocelular/metabolismo , Colina Quinase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/metabolismo , Neoplasias Hepáticas/metabolismo , Complexos Multiproteicos/metabolismo , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Colina Quinase/metabolismo , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/farmacologia , Gefitinibe , Células Hep G2 , Humanos , Immunoblotting , Imuno-Histoquímica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Invasividade Neoplásica/genética , Transplante de Neoplasias , Quinazolinas/farmacologia , Cicatrização/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncotarget ; 8(5): 7710-7721, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28032598

RESUMO

Signal transducer and activator of transcription 3 (STAT3) promotes tumor progression in many types of cancer. In this study, we analyzed the prognostic value of this marker in human intrahepatic cholangiocarcinoma (ICC). Using real-time PCR, western blot and immunohistochemistry assays, we found that STAT3 is overexpressed in ICC patients. STAT3 expression correlated with several clinicopathological features, including tumor size, pathological satellite, vascular invasion, undifferentiated-type histology, lymph node metastasis and TNM stage in two independent cohorts of ICC patients. Patients with high STAT3 levels had a poor prognosis in terms of overall survival (OS) and disease-free survival (DFS). Multivariate survival analysis indicated that STAT3 is an independent prognostic factor for OS and DFS. Furthermore, we observed that STAT3 overexpression promotes the invasion, metastasis and proliferation of ICC cells in vitro and in vivo, and also promotes STAT3 phosphorylation. These findings suggest that STAT3 expression correlated negatively with surgical outcome and inhibition of STAT3 expression may constitute a novel target for the treatment of ICC patients.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Movimento Celular , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirurgia , Hepatectomia , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Distribuição de Qui-Quadrado , Colangiocarcinoma/genética , Colangiocarcinoma/secundário , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatectomia/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Fosforilação , Modelos de Riscos Proporcionais , Fatores de Risco , Fator de Transcrição STAT3/genética , Transdução de Sinais , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Regulação para Cima
12.
BMC Cancer ; 14: 652, 2014 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-25187159

RESUMO

BACKGROUND: Preoperative jaundice is frequent in gallbladder cancer (GBC) and indicates advanced disease. Resection is rarely recommended to treat advanced GBC. An aggressive surgical approach for advanced GBC remains lacking because of the association of this disease with serious postoperative complications and poor prognosis. This study aims to re-assess the prognostic value of jaundice for the morbidity, mortality, and survival of GBC patients who underwent surgical resection with curative intent. METHODS: GBC patients who underwent surgical resection with curative intent at a single institution between January 2003 and December 2012 were identified from a prospectively maintained database. RESULTS: A total of 192 patients underwent surgical resection with curative intent, of whom 47 had preoperative jaundice and 145 had none. Compared with the non-jaundiced patients, the jaundiced patients had significantly longer operative time (p < 0.001) and more intra-operative bleeding (p = 0.001), frequent combined resections of adjacent organs (23.4% vs. 2.8%, p = 0.001), and postoperative complications (12.4% vs. 34%, p = 0.001). Multivariate analysis showed that preoperative jaundice was the only independent predictor of postoperative complications. The jaundiced patients had lower survival rates than the non-jaundiced patients (p < 0.001). However, lymph node metastasis and gallbladder neck tumors were the only significant risk factors of poor prognosis. Non-curative resection was the only independent predictor of poor prognosis among the jaundiced patients. The survival rates of the jaundiced patients with preoperative biliary drainage (PBD) were similar to those of the jaundiced patients without PBD (p = 0.968). No significant differences in the rate of postoperative intra-abdominal abscesses were found between the jaundiced patients with and without PBD (n = 4, 21.1% vs. n = 5, 17.9%, p = 0.787). CONCLUSIONS: Preoperative jaundice indicates poor prognosis and high postoperative morbidity but is not a surgical contraindication. Gallbladder neck tumors significantly increase the surgical difficulty and reduce the opportunities for radical resection. Gallbladder neck tumors can independently predict poor outcome. PBD correlates with neither a low rate of postoperative intra-abdominal abscesses nor a high survival rate.


Assuntos
Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Icterícia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Drenagem , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Icterícia/complicações , Icterícia/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Taxa de Sobrevida
13.
PLoS One ; 9(4): e92010, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24727803

RESUMO

BACKGROUND: Mucin-producing bile duct tumors (MPBTs) are unusual, and we present our experience with nine surgically proven cases. METHODS: Between November 2002 and November 2012, 9 patients with surgically proven MPBTs (including history of relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical, imaging, and surgical findings were reviewed. RESULTS: The most common symptom is intermittent jaundice, which occurs in seven patients. The diagnostic specificity was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy, accompanied caudate lobectomy in one case and concomitant Roux-en-Y choledochojejunostomy in four cases. Postoperative course was uneventful. One patient, who had intra-abdominal recurrence 59 months after surgery, was received reoperation without recurrence at the last follow-up. The remaining eight patients were alive without disease recurrence. CONCLUSION: Based on our follow up of 9 cases that were surgically treated for MPBTs, we conclude that ipsilateral hemihepatectomy is a safe surgical procedure with an observed recurrence risk of 11.1% and all long-term survival.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia/métodos , Mucinas/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/cirurgia , Idoso , Feminino , Hepatectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Chin Med J (Engl) ; 126(24): 4633-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24342302

RESUMO

BACKGROUND: Reflux cholangitis has been the most common complication after Roux-en-Y choledochojejunostomy. In this study we intended to evaluate the perioperative and long-term efficacy of a new anastomosis method for choledochojejunostomy. METHODS: Clinical data of 143 eligible patients who underwent choledochojejunostomy in the Eastern Hepatobiliary Surgery Hospital affiliated to the Second Military Medical University, China between January 2007 and December 2010 were retrospectively analyzed. Among the patients, 38 consecutive cases underwent this new anastomosis method for choledochojejunostomy (improved group, IG) and 105 underwent standard Roux-en-Y choledochojejunostomy (control group, CG). Changes in the incidence of cholangitis, the time of beginning to eat liquid meals, post-operative delayed gastric emptying and liver function between the two groups were compared. RESULTS: There was no statistical difference in the levels of alanine transaminase, alkaline phosphomonoesterase and gamma-glutamy transferase between the two groups. The time of beginning to eat liquid meals was significantly shorter in IG than CG (P < 0.05). The incidence of delayed gastric emptying was lower in IG than CG, with statistical tendency between the two groups (P = 0.052). Among nine patients with different degrees of acute cholangitis in the two groups, one patient (2.6%) in IG and eight (7.6%) in CG suffered from acute cholangitis within six months of follow-up after discharge, but with no statistical difference between the two groups (P > 0.05). Of the nine patients with acute cholangitis, none in IG and four in CG were hospitalized for further treatment (P > 0.05). CONCLUSIONS: Patients in IG had satisfactory perioperative and long-term prognosis with shorter time of beginning to eat liquid meals and lower incidence of delayed gastric emptying. This new procedure of choledochojejunostomy by the way behind antrue pyloricum was easy and safe to perform with no mortality and low complication rates.


Assuntos
Anastomose Cirúrgica/métodos , Colangite/cirurgia , Coledocostomia/métodos , Adulto , Anastomose em-Y de Roux/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
16.
Mar Drugs ; 10(7): 1445-1458, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22851918

RESUMO

Seven new formamido-diterpenes, cavernenes A-D (1-4), kalihinenes E and F (5-6), and kalihipyran C (7), together with five known compounds (8-12), were isolated from the South China Sea sponge Acanthella cavernosa. Structures were established using IR, HRESIMS, 1D and 2D NMR, and single X-ray diffraction techniques. The isolated compounds were assessed for their cytotoxicity against a small panel of human cancer cell lines (HCT-116, A549, HeLa, QGY-7701, and MDA-MB-231) with IC(50) values in the range of 6-18 µM. In addition, compound 9 showed weak antifungal activity against Trichophyton rubrum and Microsporum gypseum with MIC values of 8 and 32 µg/mL, respectively, compound 10 displayed weak antifungal activity against fungi Candida albicans, Cryptococcus neoformans, T. rubrum, and M. gypseum with MIC values of 8, 8, 4, and 8 µg/mL, respectively.


Assuntos
Diterpenos/isolamento & purificação , Poríferos/química , Animais , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética
17.
Hepatogastroenterology ; 59(120): 2432-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22497947

RESUMO

BACKGROUND/AIMS: To summarize the experience of diagnosis and surgical treatment of mucin-producing bile duct tumors (MPBTs). METHODOLOGY: A retrospective analysis was undertaken to determine the radiography characteristics and results of surgical treatment of MPBTs over the past 9 years. Only eight patients underwent such treatment. The detailed data of diagnosis, treatment and prognosis were carefully studied. RESULTS: Intermittent jaundice was the most frequently clinical manifestation of MPBTs, with unique characteristics on magnetic resonance cholangiopancreatography (MPCP) when compared with gallbladder carcino-ma, hilar cholangiocarcinoma and distal bile duct can-cer. All the 8 patients with MPBTs received appropriate surgical procedure and were cured. CONCLUSIONS: Appropriate diagnosis and curative hepatectomy for MPBTs made it possible to achieve long-term survival.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Biomarcadores Tumorais/análise , Mucinas/análise , Idoso , Neoplasias dos Ductos Biliares/química , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Extra-Hepáticos/química , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/química , Ductos Biliares Intra-Hepáticos/patologia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/mortalidade , Colangiopancreatografia por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Valor Preditivo dos Testes , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
18.
PLoS One ; 7(12): e51513, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23300551

RESUMO

BACKGROUND: This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with gallbladder cancer (GBC) treated by surgical resection with curative intent. METHODS: Between January 2003 and January 2011, 76 patients with GBC underwent surgical resection with curative intent at our department. We then conducted a retrospective analysis of clinicopathologic data. Fourteen clinicopathological variables were selected for univariate and multivariate analysis to evaluate their influence on the outcome. RESULTS: The actuarial 1-, 3-, and 5-year survival rates in the 76 resected cases were 56.6%, 32.7%, and 23.8%, respectively. The univariate analysis revealed that curative resection (P<0.001), lymph node metastasis (P<0.001), AJCC stage (P = 0.030), tumor location (P = 0.008), histologic differentiation (P = 0.028), intraoperative blood loss (P = 0.011), and preoperative jaundice (P = 0.012) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection and tumor location on gallbladder neck were significant risk factors for poor outcome. Among jaundiced patients, we discovered that gallbladder carcinoma with tumor thrombus in common bile duct (CBD) was very rare but with relatively special clinical manifestation and characteristic radiography manifestation. The prognosis of gallbladder carcinoma with tumor thrombus in CBD after surgical procedure was apparently better than gallbladder carcinoma with invasion of hilar tissues. CONCLUSIONS: Curative surgical resection remains the only effective approach to the treatment of GBC. This series confirm that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (when R0 resection is achievable). Gallbladder carcinoma with tumor thrombus in CBD has special clinical characteristics, which need to be awared by radiologists and clinicians.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias da Vesícula Biliar/mortalidade , Trombose/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Feminino , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Morbidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Hepatobiliary Pancreat Dis Int ; 5(2): 278-82, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16698591

RESUMO

BACKGROUND: Carcinoma of the hepatic duct confluence is the most common site of bile duct malignancies. Although hilar cholangiocarcinoma has been characterized as a slow-growing and late metastasizing tumor, post-therapeutic prognosis has remained poor. The study was undertaken to analyze factors influencing the surgical curative effect of hilar cholangiocarcinoma. METHODS: A retrospective clinical analysis was made of 198 patients with hilar cholangiocarcinoma who had been surgically treated at our hospital from 1997 to 2002. Jaundice (94.5%, 187 patients), pruritus (56.6%, 112) and abdominal pain (33.8%, 67) were the main symptoms. According to the Bismuth-Corlette classification, there were 14 type I patients, 19 type II patients, 12 type IIIa patients, 15 type IIIb patients, 112 type IV patients, and 26 unclassified patients. 144 patients received laparotomy, and 120 tumor resection including radical resection (59 patients) and palliative resection (61). Fifty-four patients were treated by endoscopic surgery and 16 patients by postoperative adjuvant radiation. RESULTS: Occupation, preoperative level of total serum bilirubin, operative procedure and postoperative adjuvant radiation affected postoperative survival of the patients. The postoperative survivals of endoscopic nose-biliary drainage (ENBD) group, endoscopic retrograde biliary drainage (ERBD) or endoscopic metal biliary endoprosthesis (EMBE) group, biliary exploration and drainage group, palliative resection group and radical resection group differed (chi2=87.0489, P<0.01). CONCLUSION: Early diagnosis and radical resection are important to improve the prognosis of hilar cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colangiocarcinoma/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Biópsia por Agulha , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Resultado do Tratamento
20.
Liver Int ; 25(5): 962-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16162153

RESUMO

BACKGROUND/AIM: Expression alteration of Glypican-3 (GPC3) is associated with several malignancies and has been identified as an overexpressed gene in hepatocellular carcinoma (HCC). In this study GPC3 expression in intrahepatic chanlangiocarcinoma (ICC), gallbladder cancer and HCC was quantitatively detected. METHODS: Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression level of GPC3. RESULTS: GPC3 expression was elevated more than two-fold in HCC compared with adjacent tissue in 90 of 100 HCC cases. The average expression level of GPC3 was significantly higher in HCC than that in adjacent liver tissues (P<0.0001). Only in four of 21 ICC cases GPC3 expression was upregulated more than two-fold in tumor tissues. GPC3 expression was downregulated in gallbladder cancer in 12 of 13 cases and the average expression level was significantly lower than that in normal gallbladder tissues (P<0.05). CONCLUSION: The different expression patterns of GPC3 in HCC and ICC suggested that it might play a different role in theses tumors and could serve as a biomarker for differential diagnosis of HCC and ICC.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico , Colangiocarcinoma/diagnóstico , Diagnóstico Diferencial , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/metabolismo , Regulação Neoplásica da Expressão Gênica , Glipicanas , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade
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