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1.
Indian J Pathol Microbiol ; 62(3): 384-390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31361225

RESUMO

Background: Gallbladder cancer (GBC) is the most frequent biliary tract cancer, with high morbidity and poor prognosis, and shows early metastasis and invasiveness. No reliable biomarkers are available for detection of GBC progression. Aim: To investigate the immunohistochemical expression of Oct-4 and CD133 in malignant and nonneoplastic lesions of gallbladder and to analyze the clinical significance of the expressions related to clinicopathological parameters. Settings and Design: This is a prospective case control study, conducted in medical college background. Materials and Methods: A total of 103 cases of gallbladder were grouped into malignant lesions (n = 48) and nonneoplastic lesions (simple epithelial hyperplasia; n = 35 and chronic cholecystitis; n = 20). All tissue samples were evaluated for expression of Oct-4 and CD133 using immunohistochemistry in an effort to elucidate the correlation between their expressions with clinicopathological parameters. Statistical Analysis: The final score was calculated by multiplying the intensity to the percentage of positive cells. The scores ≥2 were considered as positive. Results: Significant positive correlation of higher expression levels of Oct-4 and CD133 were observed in malignant as compared to nonneoplastic lesions of gallbladder (P < 0.0001). High expression of Oct-4 and CD133 were significantly associated with tumor grading (Oct-4, P = 0.04; CD133, P = 0.02), staging (Oct-4, P = 0.03; CD133, P = 0.02), and liver metastasis (Oct-4, P = 0.01; CD133, P = 0.007). Significantly reduced survival was observed with high expression of Oct-4 (P = 0.002). No significant correction was observed between CD 133 and survival. Conclusion: This study revealed that high expression level of Oct-4 may provide a new insight for the prognosis of the disease in terms of clinical staging and grade.


Assuntos
Antígeno AC133/genética , Neoplasias da Vesícula Biliar/diagnóstico , Vesícula Biliar/patologia , Células-Tronco Neoplásicas/citologia , Fator 3 de Transcrição de Octâmero/genética , Adenocarcinoma/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Neoplasias da Vesícula Biliar/fisiopatologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Prospectivos , Adulto Jovem
2.
Pol Przegl Chir ; 91(2): 16-19, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31032806

RESUMO

Gallbladder carcinoma (GBC) is a rare pathology. We reviewed our hospital database for prognosticating the patients with post-cholecystectomy abdominal wall nodule. On reviewing the database we could find 7 patients who were diagnosed with GBC after simple cholecystectomy. Three of those patients were diagnosed after evaluation of a scar site nodule. Two patients were females and one patient was male. The mean age of the patients was 55 years. Two patients underwent laparoscopic cholecystectomy and one patient underwent open cholecystectomy. The average time of detection of malignancy was 10.6 months. The gallbladder was not subjected to histopathological examination in all three patients. The patients had the unresectable disease on restaging workup. Two patients had adenocarcinoma while one patient had a neuroendocrine tumor. abdominal wall nodule is a rare marker of occult gallbladder carcinoma. Subjecting every gallbladder specimen to histopathology should help in improving the survival in these patients.


Assuntos
Parede Abdominal/fisiopatologia , Carcinoma/etiologia , Carcinoma/cirurgia , Colecistectomia/efeitos adversos , Cicatriz/fisiopatologia , Neoplasias da Vesícula Biliar/etiologia , Neoplasias da Vesícula Biliar/cirurgia , Adulto , Idoso , Carcinoma/fisiopatologia , Feminino , Neoplasias da Vesícula Biliar/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia , Resultado do Tratamento
3.
BMC Surg ; 19(1): 23, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777042

RESUMO

BACKGROUND: Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. METHODS: We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy. RESULTS: Univariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35). CONCLUSIONS: Cases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.


Assuntos
Embolização Terapêutica , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/cirurgia , Regeneração Hepática/fisiologia , Fígado , Veia Porta/fisiopatologia , Idoso , Embolização Terapêutica/métodos , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/fisiopatologia , Neoplasias da Vesícula Biliar/cirurgia , Hemodinâmica , Hepatectomia , Humanos , Hipertrofia/diagnóstico por imagem , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/fisiopatologia , Circulação Hepática/fisiologia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia
5.
Cell Death Dis ; 9(3): 410, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540696

RESUMO

Gallbladder carcinoma (GBC), the most common malignant tumour of the bile duct, is highly aggressive and has a poor prognosis. MicroRNA-30a-5p (miR-30a-5p) is an important tumour suppressor that participates in many aspects of carcinogenesis and cancer development. However, the role of miR-30a-5p in GBC development remains to be determined, as do the mechanisms underlying its effects in GBC. Using samples collected from 42 subjects with gallbladder carcinoma (GBC), we showed decreased miR-30a-5p expression in the primary lesions vs. non-tumour adjacent tissues (NATs). Decreased miR-30a-5p was associated with shorter disease-free survival (DFS) and overall survival (OS). Inhibiting miR-30a-5p expression in 2 representative GBC cell lines (GBC-SD and NOZ) increased cell proliferation, migration, invasiveness, as well as ß-catenin nuclear translocation, vice versa. In nude mice, NOZ cells transfected with miR-30a-5p mimics grew slower (vs. miR-NC) upon subcutaneous inoculation, and had lower rate of hepatic metastasis upon spleen inoculation. Dual luciferase assay confirmed that E2F transcription factor 7 (E2F7) was a direct target of miR-30a-5p and antagonized the effects induced by miR-30a-5p downregulation in GBC cells. MiR-30a-5p attenuates the EMT and metastasis in GBC cells by targeting E2F7, suggesting miR-30a-5p is a tumour suppressor that may serve as a novel potential prognostic biomarker or molecular therapeutic target for GBC.


Assuntos
Fator de Transcrição E2F7/genética , Neoplasias da Vesícula Biliar/genética , MicroRNAs/metabolismo , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fator de Transcrição E2F7/metabolismo , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica
6.
Appl Immunohistochem Mol Morphol ; 25(5): 346-350, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26990743

RESUMO

Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, is a poor prognostic marker for cancers of organs such as the stomach, ovary, and breast as well as a useful diagnostic marker for pancreatobiliary adenocarcinoma. However, its expression pattern and prognostic significance have not been studied in gallbladder adenocarcinoma. We constructed a tissue microarray from samples from 82 consecutive patients with gallbladder adenocarcinoma treated by cholecystectomy at the Kangbuk Samsung Hospital from 2000 to 2011. CK17 expression was examined by immunohistochemistry and correlated with clinicopathologic prognostic factors. CK17 stained the cytoplasm of tumor cells and immunohistochemical interpretation was possible in 77 cases. Among these, 41 (53.2%) were considered positive using a 5% cutoff determined by a receiver operating characteristic curve (area under the curve=0.656, P=0.021). CK17 expression was associated with poor tumor differentiation (P<0.001), high pT stage (P<0.001), presence of distant metastasis (P=0.036), and low disease-specific survival rate (P<0.001). These results indicate that CK17 can be used as a marker for poor prognosis for gallbladder adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/normas , Neoplasias da Vesícula Biliar/diagnóstico , Regulação Neoplásica da Expressão Gênica , Queratina-17/genética , Adenocarcinoma/genética , Adenocarcinoma/fisiopatologia , Feminino , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/fisiopatologia , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Queratina-17/metabolismo , Masculino , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos
7.
An. sist. sanit. Navar ; 38(2): 333-337, mayo-ago. 2015. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-140737

RESUMO

El angiosarcoma de vesícula es una patología poco frecuente pero con una alta morbi-mortalidad del que sólo hay 10 referencias en la literatura internacional. Presentamos un caso tratado en nuestro centro y realizamos una revisión de los casos publicados desde 1956. Paciente varón de 81 años con dolor abdominal, astenia y disnea. Analíticamente anemia y leucocitosis. En la exploración destacaba un abdomen distendido, doloroso en hipocondrio derecho, con defensa. Se solicitó ecografía abdominal y un TC con diagnóstico de colecistitis aguda y se ingresó para tratamiento antibiótico. El paciente no evolucionó favorablemente y se intervino de urgencia hallando un hemoperitoneo y una vesícula de aspecto tumoral que no se pudo extirpar en su totalidad. Falleció a los 20 días de la intervención. El informe de anatomía patológica fue compatible con angiosarcoma epiteloide de vesícula biliar. El angiosarcoma de vesícula es una neoplasia de mal pronóstico, cuya presentación clínica puede confundirse con la colecistitis aguda. Conseguir mejorar el pronóstico de esta enfermedad pasa por realizar un diagnóstico y tratamiento quirúrgico precoces (AU)


Angiosarcoma of the gallbladder is an infrequent pathology but has a high morbidity and mortality. There are only 10 references in the international literature. We present a case treated in our center and we review the cases published since 1956. An 81 year-old male patient with abdominal pain, asthenia and dyspnea. Analytically anemia and leukocytosis. Exploration found a distended abdomen, right hypochondrium pain, with defense. Abdominal echography and a CT were requested with a diagnosis of acute cholecystitis and he was admitted for antibiotic treatment. The patient did not evolve favorably and was subjected to emergency surgery, which found a haemoperitoneum and a gallbladder with a tumoral appearance that could not be totally extirpated. He died 20 days after the operation. The report from pathological anatomy was compatible with epithelioid angiosarcoma of the biliary gallbladder. Gallbladder angiosarcoma is a neoplasia with a bad prognosis, whose clinical presentation can be mistaken for acute cholecystitis. Improving the prognosis of this disease involves carrying out early diagnosis and surgical treatment (AU)


Assuntos
Idoso de 80 Anos ou mais , Humanos , Masculino , Sarcoma/complicações , Sarcoma/cirurgia , Sarcoma , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Vesícula Biliar , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar , Indicadores de Morbimortalidade , Dor Abdominal/etiologia , Dor Abdominal , Tomografia Computadorizada de Emissão , Neoplasias da Vesícula Biliar/fisiopatologia , Neoplasias da Vesícula Biliar/cirurgia , Colecistite/complicações , Colecistite
9.
Pol Przegl Chir ; 86(5): 218-22, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24988239

RESUMO

UNLABELLED: Polyps of the gall-bladder has long been a serious diagnostic problem. Their detection in routine ultrasound is not yet satisfactory and often does not allow you to select the proper method of operating the gall-bladder. The aim of the study was to assess the accuracy of ultrasound diagnosis of polypoid lesions of the gall-bladder through its verification by histopathology in patients treated with cholecystectomy. MATERIAL AND METHODS: In the years 2010-2013, 1196 patients underwent surgery due to diseases of the gall-bladder at the Department of General and Transplant Surgery, Medical University in Lódz. The study evaluated the sensitivity of ultrasound in detecting polyps of the gallbladder and histopathological findings of the formulations investigated. RESULTS: Preoperative ultrasound examination (USG) revealed a polypoid lesion in 64 patients; only in 29 of them (44.6%) this diagnosis was confirmed by histopathological examination. In the other cases, cholecystolithiasis or inflammatory lesions were found. The most common histopathological findings included cholesterol polyps, adenomatous polyps, and inflammatory polyps. Malignant lesions (gall-bladder cancer) were found in five patients preoperatively diagnosed with a polypoid lesion, i.e 7.8% of patients preoperatively diagnosed with a polyp and 0.4% of all patients who received surgical treatment. Patients qualified for surgery due to polyps diagnosed by means of ultrasound examination constitued 5.4% of all patients who underwent cholecystectomy. On histopathological examination, the presence of polyps was confirmed in 2.4% patients treated with excision of the gall-bladder. CONCLUSIONS: Detection of gall-bladder polyp on ultrasound examination is an indication for cholecystectomy, in particular when the polyp diameter exceeds 10 mm. In each case of a polyp, cholecystolithiasis should also be taken into account and the presence (or absence) of indications for cholecystectomy should be discussed with the patient.


Assuntos
Neoplasias da Vesícula Biliar/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Pólipos/diagnóstico por imagem , Bexiga Urinária/anatomia & histologia , Bexiga Urinária/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/fisiopatologia , Ondas de Choque de Alta Energia , Humanos , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polônia , Pólipos/fisiopatologia , Sensibilidade e Especificidade , Ultrassonografia , Adulto Jovem
10.
Pain Pract ; 14(2): E63-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23944980

RESUMO

INTRODUCTION: Percutaneous anterior abdominal ultrasound guidance for performing celiac plexus neurolysis is a relatively new but more economical, less time-consuming, more comfortable bedside technique for interventional pain management. Paucity of studies evaluating the efficacy of single-site vs. double-site injections at celiac trunk for ultrasound-guided celiac plexus neurolysis (USCPN) prompted us to conduct a prospective, randomized, single-blind clinical trial to compare USCPN using bilateral paramedian (double needle) technique with unilateral paramedian (single needle) technique. METHODS: Sixty patients aged 18 years or older with unresectable upper abdominal cancers were randomized into two groups to receive USCPN. A 20-mL mixture of 50% ethanol with 0.25% bupivacaine was injected either unilaterally (20 mL×1 site) or bilaterally (10 mL×2 sites) depending on the randomization group. Subjects were assessed for the pain relief using Numerical rating scale (NRS) to assess their pain relief. RESULTS: Baseline parameters being comparable (P > 0.05), the site of drug injections (single or double needle) had no bearing on the onset of pain relief and patient satisfaction scores (P > 0.05). Pain relief during follow-up visits was comparable between the two groups (P > 0.05). The discomfort score correlated well with the pain relief scoring without any significant difference between the two groups except in the last visit (at 3 month). Incidences of the complications were comparable in the two groups (P > 0.05). CONCLUSION: Ultrasound-guided celiac plexus neurolysis using unilateral paramedian (single needle) needle-insertion technique is comparable with bilateral paramedian (double needle) needle-insertion technique with regard to pain relief and side effects.


Assuntos
Dor Abdominal/tratamento farmacológico , Bloqueio Nervoso Autônomo/métodos , Plexo Celíaco/diagnóstico por imagem , Neoplasias da Vesícula Biliar/fisiopatologia , Manejo da Dor/métodos , Neoplasias Pancreáticas/fisiopatologia , Sistemas Automatizados de Assistência Junto ao Leito , Dor Abdominal/etiologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Anestésicos Locais/uso terapêutico , Bloqueio Nervoso Autônomo/efeitos adversos , Bupivacaína/administração & dosagem , Bupivacaína/efeitos adversos , Bupivacaína/uso terapêutico , Plexo Celíaco/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas , Medição da Dor , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia
11.
Zhonghua Wai Ke Za Zhi ; 51(12): 1067-70, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24499713

RESUMO

OBJECTIVE: To study the relationship between the change of coagulation and the clinicopathologic characteristics in patients with gallbladder cancer. METHODS: The 64 gallbladder cancer patients (GBC group) and 60 cholecystitis patients (control group) had been reviewed from January 2007 to June 2013. The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), and thrombin time (TT) had been measured and compared between patients of GBC group and control group. The relationship of coagulation function and prognosis were analyzed. RESULTS: Compared with control group, APTT in GBC group ((29.0 ± 4.2) s) was significantly shortened (t = -4.265, P = 0.000) and PT ((11.5 ± 1.4) s), TT ((15.3 ± 3.5) s), Fib ((4.1 ± 0.9) g/L) were significantly increased in GBC group (t = 2.521, 4.147 and 4.365, all P < 0.05). The level of Fib was higher in patients with medium or poor-differentiated tumor cells (F = 4.069, P = 0.022), lymph metastasis (t = 2.640, P = 0.010) and advanced staging (II-IV) (t = 3.003, P < 0.01) than those of well-differentiated, non-lymph metastasis and early staging (0-I). The ratio of gallbladder cancer with hyperfibrinogenemia (32/64) was significantly higher than control group (11/60, χ(2) = 13.709, P < 0.01). In GBC group, compared with normal Fib patients, hyperfibrinogenemia patients showed significantly difference in clinicopathologic characteristics (χ(2) = 5.851-10.573, P < 0.05). The average survival period of hyperfibrinogenemia patients and normal Fib patients were 8.63 months and 16.73 months. The 1-, 3-year survival rate of patients with hyperfibrinogenemia were significantly lower than those with normal Fib (64.7%, 14.9% vs. 74.9%, 21.1%, P < 0.05). CONCLUSION: Preoperative plasma level of Fib might be a new promising biomarker in patients with gallbladder cancer for evaluating disease progression and prognosis.


Assuntos
Coagulação Sanguínea , Neoplasias da Vesícula Biliar/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Tempo de Protrombina
12.
Dig Liver Dis ; 45(1): 70-4, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22999058

RESUMO

BACKGROUND: Biliary tract cancer presents a poor prognosis. AIMS: The objective of this study is to find clinical-laboratory parameters like prognostic factors to select patients who can benefit from surgery and post-operative treatments. METHODS: Between 2005 and 2010, 41 patients underwent radical surgery at our Institution. A novel score was retrospectively calculated assigning a grade to the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0 and SCORE 1. RESULTS: Patients with cholangiocarcinoma or Klatskin tumours or asymptomatic at diagnosis presented a significantly better overall survival (OS) than patients with different primary sites or who presented pain, jaundice or cholangitis. At univariate analysis, high levels of aspartate aminotransferase, alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and after surgery had a negative correlation with OS. A worse OS was observed in patients with a higher score (median OS in the "score 0" group=30.79 months vs. median OS in the "score 1"=17.98 months). CONCLUSION: Our results suggest that pre and post-surgery clinical-laboratory parameters and the novel score, could be useful, especially for intrahepatic tumours, in predicting the outcome in patients undergoing surgery and in selecting patients to receive adjuvant therapy.


Assuntos
Neoplasias do Sistema Biliar/fisiopatologia , Neoplasias do Sistema Biliar/cirurgia , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Aspartato Aminotransferases/sangue , Neoplasias do Sistema Biliar/diagnóstico , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/fisiopatologia , Colangiocarcinoma/cirurgia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/fisiopatologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Hiperbilirrubinemia , Tumor de Klatskin/diagnóstico , Tumor de Klatskin/fisiopatologia , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
13.
Clin Cancer Res ; 18(12): 3270-80, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22553346

RESUMO

PURPOSE: Although recent studies have suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) is important in the progression of various malignancies, its role in gallbladder carcinoma (GBC) remains unknown. We investigated CXCL12 expression in GBC and its biologic and prognostic role in GBC tumorigenesis. EXPERIMENTAL DESIGN: We examined CXCL12 expression in tumor specimens from 72 patients with GBC by immunohistochemistry and analyzed the correlation between CXCL12 expression and clinicopathologic factors or survival. The functional significance of CXCL12 expression was investigated by CXCL12 treatment and suppression of CXCR4, a major receptor of CXCL12, as well as by CXCL12 overexpression in in vitro and in vivo studies. RESULTS: CXCL12 was differentially expressed in GBC tissues. CXCL12 expression was significantly associated with a high histologic grade (P = 0.042) and nodal metastasis (P = 0.015). Multivariate analyses showed that CXCL12 expression (HR, 8.675; P = 0.014) was an independent risk factor for patient survival. CXCL12 significantly increased anchorage-dependent and -independent growth, migration, invasion, adhesiveness, and survival of GBC cells in vitro, and these effects were dependent on CXCR4. Consistent with these results, overexpression of CXCL12 significantly promoted GBC tumorigenicity in a xenograft model. CONCLUSIONS: Our results indicate that GBC cells express both CXCL12 and its receptor CXCR4, and CXCL12 may have a role in GBC progression through an autocrine mechanism. In addition, CXCL12 is a novel independent poor prognostic factor in patients with GBCs. Thus, targeting CXCL12 and CXCR4 may provide a novel therapeutic strategy for GBC treatment.


Assuntos
Quimiocina CXCL12/metabolismo , Progressão da Doença , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/fisiopatologia , Receptores CXCR4/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Transformação Celular Neoplásica , Quimiocina CXCL12/genética , Feminino , Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Interferência de RNA , RNA Interferente Pequeno , Receptores CXCR4/genética , Transplante Heterólogo
14.
Indian J Pathol Microbiol ; 55(1): 75-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22499306

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is a lethal malignancy presenting at an advanced stage. The pathogenesis is not well categorized, and surgery is the only treatment available at the early stage of the disease. There have been few reports on role of growth factor receptors in GBC. C-erbB2 is one such receptor whose over-expression is being explored in GBC as one of the factors involved in carcinogenesis and possible target for therapy. MATERIALS AND METHODS: One hundred and four consecutive cases of GBC were retrospectively studied with regard to clinical features, histological type, grade and stage of tumor. Immunohistochemistry for C-erbB2 was done and expression was correlated with different clinic-pathological parameters and survival. RESULTS: C-erbB2 overexpression was seen in 9.4% cases with complete staining and both complete and incomplete staining (2+ and 3+) was seen in 13.4% cases. Eighty percent of the C-erbB2 over-expressed cases were well differentiated and in stage II to stage IV disease. Dysplasia adjacent to carcinoma did not show any expression. No correlation was found with tumor grade, stage, gall stones, and patient survival. Xanthogranulomatous inflammation was inversely correlated with C-erbB2 over-expression. Median survival was 30 months in C-erbB2 over-expressed cases, and 12 months in C-erbB2 negative cases. CONCLUSION: We found complete membranous staining of C-erbB2 in 9.4% of GBC which was frequent in well differentiated and stage II to stage IV tumors. C-erbB2 tumors had longer median survival than C-erbB2 negative tumors. C-erbB2 is not involved early in the carcinogenetic process as none of the dysplasia showed expression. C-erbB2 over-expression may be considered as target for therapy in advanced stage of GBC.


Assuntos
Neoplasias da Vesícula Biliar/patologia , Perfilação da Expressão Gênica , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias da Vesícula Biliar/fisiopatologia , Histocitoquímica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Índice de Gravidade de Doença , Análise de Sobrevida
15.
World J Gastroenterol ; 17(35): 4023-30, 2011 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-22046092

RESUMO

AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). CONCLUSION: Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.


Assuntos
Colangiocarcinoma/fisiopatologia , Neoplasias da Vesícula Biliar/fisiopatologia , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Progressão da Doença , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
16.
Am J Med Sci ; 342(5): 388-94, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22033073

RESUMO

Cell junction regulatory proteins such as claudin-1, occludin, E-cadherin and snail play an important role in modulation of human cancer development. This study assessed the association of the expression of these proteins in lesions of gallbladder with clinicopathologic data. Tissue sections from adenocarcinoma, peritumoral tissues, adenomatous polyp and chronic cholecystitis were immunohistochemically analyzed for expression of claudin-1, occludin, E-cadherin and snail proteins. Expression of claudin-1, occludin and E-cadherin was significantly lower in adenocarcinoma than in peritumoral tissues, adenomatous polyp or chronic cholecystitis. Expression of snail was significantly higher in adenocarcinoma than in peritumoral tissues, adenomatous polyp or chronic cholecystitis. Furthermore, expression of claudin-1, occludin and E-cadherin was significantly higher in well-differentiated adenocarcinoma, defined by a maximal tumor size < 2 cm with neither lymph node metastasis nor invasion to the regional tissues, than those in poorly differentiated adenocarcinoma with a maximal tumor size ≥ 2 cm, lymph node metastasis and such invasion. Expression of snail was in reverse association. Patients with expression of claudin-1, occludin-1 and E-cadherin survived longer than the patients without these proteins, but patients with snail expression died earlier than those who did not. Cox multivariate regression analysis showed the characteristics of poorly differentiated adenocarcinoma (tumor size ≥ 2 cm, lymph node metastasis and tumor invasion to the regional tissues) were poor-prognostic factors negatively correlated with postoperative survival. Expression of claudin-1, occludin-1 and E-cadherin were favorable-prognostic factors. Snail expression, which was a poor-prognostic factor, was negatively correlated with postoperative survival.


Assuntos
Caderinas/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Proteínas de Membrana/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Claudina-1 , Feminino , Vesícula Biliar/fisiopatologia , Neoplasias da Vesícula Biliar/fisiopatologia , Humanos , Junções Intercelulares/química , Junções Intercelulares/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ocludina , Fatores de Transcrição da Família Snail
17.
J Exp Clin Cancer Res ; 30: 46, 2011 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-21529356

RESUMO

BACKGROUND: Vasculogenic mimicry (VM), as a new blood supply for tumor growth and hematogenous metastases, has been recently described in highly aggressive human melanoma cells, etc. We previously reported VM in human gallbladder carcinomas and its clinical significance. In this study, we further studied histomorphology and hemodynamic of VM in gallbladder carcinomas in vivo and in vitro. METHODS: The invasive potential of human gallbladder carcinoma cell lines GBC-SD and SGC-996 were identified by Transwell membrane. The vasculogenic-like network structures and the signal intensities i.e. hemodynamic in gallbladder carcinomas stimulated via the three-dimensional matrix of GBC-SD or SGC-996 cells in vitro, the nude mouse xenografts of GBC-SD or SGC-996 cells in vivo were observed by immunohistochemistry (H&E staining and CD31-PAS double staining), electron microscopy and micro-MRA with HAS-Gd-DTPA, respectively. RESULTS: Highly aggressive GBC-SD or poorly aggressive SGC-996 cells preconditioned by highly aggressive GBC-SD cells could form patterned networks containing hollow matrix channels. 85.7% (6/7) of GBC-SD nude mouse xenografts existed the evidence of VM, 5.7% (17/300) channels contained red blood cells among these tumor cell-lined vasculatures. GBC-SD xenografts showed multiple high-intensity spots similar with the intensity observed at tumor marginal, a result consistent with pathological VM. CONCLUSIONS: VM existed in gallbladder carcinomas by both three-dimensional matrix of highly aggressive GBC-SD or poorly aggressive SGC-996 cells preconditioned by highly aggressive GBC-SD cells in vitro and GBC-SD nude mouse xenografts in vivo.


Assuntos
Carcinoma/patologia , Neoplasias da Vesícula Biliar/patologia , Hemodinâmica , Neovascularização Patológica/patologia , Animais , Carcinoma/fisiopatologia , Linhagem Celular Tumoral , Feminino , Neoplasias da Vesícula Biliar/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/fisiopatologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Dig Endosc ; 23(2): 140-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21429019

RESUMO

BACKGROUND: Celiac plexus neurolysis (CPN) is an established treatment for upper abdominal cancer pain. Recently, endoscopic ultrasound-guided CPN (EUS-CPN) was introduced and has enabled the performance of CPN under real-time imaging guidance, thereby making this technique much safer and easier. However, this procedure is not always efficacious, and a limited number of patients benefit from it. It should not be recommended for patients suspected of having unfavorable outcomes. We determined the predictive factors for response to EUS-CPN in order to enable rational selection of the therapeutic strategy. PATIENTS AND METHODS: Forty-seven consecutive patients who underwent EUS-CPN at our institutions were eligible for this study. Absolute ethanol containing a contrast medium was injected just above the origin of the celiac trunk from the aorta under real-time EUS guidance, and abdominal computed tomography was performed immediately after the procedure to evaluate the distribution of the injected ethanol. The efficacy in pain relief was evaluated based on the pain score at day 7 after EUS-CPN. RESULTS: Pain relief was obtained in 32 patients (68.1%). Multivariate analysis using a multiple logistic regression model revealed that direct invasion of the celiac plexus and distribution of ethanol only on the left side of the celiac artery were significant factors for a negative response to EUS-CPN (odds ratio = 4.82 and 8.67, P = 0.0387 and 0.0224, respectively). CONCLUSION: EUS-CPN seems to be less effective in patients with direct invasion of the celiac plexus. Ethanol should be injected on both sides of the celiac axis to obtain greater pain relief.


Assuntos
Dor Abdominal/cirurgia , Bloqueio Nervoso Autônomo/métodos , Neoplasias dos Ductos Biliares/fisiopatologia , Plexo Celíaco/cirurgia , Endossonografia/instrumentação , Neoplasias da Vesícula Biliar/fisiopatologia , Medição da Dor , Dor Intratável/cirurgia , Neoplasias Pancreáticas/fisiopatologia , Cirurgia Assistida por Computador/métodos , Ultrassonografia Doppler em Cores/instrumentação , Ultrassonografia de Intervenção/instrumentação , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Plexo Celíaco/diagnóstico por imagem , Etanol/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
19.
Cancer Biomark ; 8(3): 113-21, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-22012766

RESUMO

In this study, we investigated the expressions of Msi-1 and ALDH1 in gallbladder adenocarcinoma (n=100), peritumoral tissues (n=46), adenomatous polyp (n=15), and chronic cholecystitis (n=35) using immunohistochemical method. The percentage of cases with positive Msi-1 and ALDH1 expression were significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues, adenomatous polyp and chronic cholecystitis (ps < 0.01). The expression of Msi-1 and ALDH1 was significantly associated with differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinoma. The expression of Msi-1 and ALDH1 was found to be highly consistent in gallbladder adenocarcinoma (p < 0.01). Univariate Kaplan-Meier analysis showed a negative correlation between Msi-1 (p=0.042) or ALDH1 (p< 0.001) expression with overall survival. The average survival time of patients with both low or no Msi-1 expression and ALDH1 expression was significantly longer than patients with the other three subtypes (p< 0.001). Multivariate Cox regression analysis showed that positive expression of Msi-1 or ALDH1 (p=0.016, p=0.006, respectively) was an independent bad-prognostic predictor in gallbladder adenocarcinoma. Our study suggested that Msi-1 and/or ALDH1 expression might be closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.


Assuntos
Adenocarcinoma/fisiopatologia , Biomarcadores Tumorais/análise , Neoplasias da Vesícula Biliar/fisiopatologia , Isoenzimas/análise , Proteínas do Tecido Nervoso/análise , Proteínas de Ligação a RNA/análise , Retinal Desidrogenase/análise , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Pólipos Adenomatosos/metabolismo , Adulto , Idoso , Aldeído Desidrogenase 1 , Colecistite/metabolismo , Progressão da Doença , Feminino , Vesícula Biliar/química , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/química , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Isoenzimas/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Prognóstico , Proteínas de Ligação a RNA/genética , Retinal Desidrogenase/genética
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(12): 2495-6, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20034911

RESUMO

OBJECTIVE: To compare the effect of laparoscopic cholecystectomy (LC) and open cholecystectomy (OC) on liver function and immune function. METHODS: Forty-two patients with normal liver function underwent LC (n=21) or OC (n=21) according to the patients' preference. One day before and 7 days after the operations, the liver functions (ALT, AST, TBIL, ALB) and immune functions (CD3, CD4, CD8, NK cell percentage, IgA, IgM, IgG and C3, C4) of the patients were measured. RESULTS: No statistical differences were found in the liver functions or immune functions between the two groups after the operation. CONCLUSION: LC and OC show no significant difference in the effects on the liver function and immune function.


Assuntos
Colecistectomia Laparoscópica , Colecistectomia , Colelitíase/cirurgia , Imunidade , Fígado/fisiopatologia , Adulto , Formação de Anticorpos/imunologia , Colelitíase/imunologia , Colelitíase/fisiopatologia , Feminino , Neoplasias da Vesícula Biliar/imunologia , Neoplasias da Vesícula Biliar/fisiopatologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Células Matadoras Naturais/imunologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pólipos/imunologia , Pólipos/fisiopatologia , Pólipos/cirurgia
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