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1.
Ann Surg ; 261(2): 361-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24509187

RESUMEN

OBJECTIVE: To characterize clinical and radiological features associated with biliary cystic tumors (BCTs) of the liver, and to define recurrence-free and overall survival. BACKGROUND: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare tumors that arise in the liver. METHODS: Between 1984 and 2013, 248 patients who underwent surgical resection of BCA or BCAC were identified. Clinical and outcome data were analyzed. RESULTS: Median total bilirubin, CA19-9, and carcinoembryonic antigen (CEA) levels were 0.6 mg/dL, 15.0 U/mL, and 2.7 ng/mL, respectively. Preoperative imaging included computed tomography only (62.5%), magnetic resonance imaging only (6.9%), or CT + MRI (18.5%). Features on cross-sectional imaging included multiloculation (56.9%), mural nodularity (16.5%), and biliary ductal dilatation (17.7%). The presence of these factors did not reliably predict BCAC versus BCA (sensitivity, 81%; specificity, 21%). Median biliary cyst size was 10.0 cm (interquartile range, 7-13 cm). Operative interventions included unroofing/partial excision of the lesion (14.1%), less than hemihepatectomy (48.8%), or hemi-/extended hepatectomy (36.3%). On pathology most lesions were BCA (89.1%), whereas 27 (10.9%) were BCAC. At last follow-up, there were 46 (18.3%) recurrences; 2 patients who initially had BCA recurred with BCAC. Median overall survival was 18.1 years; 1-year, 3-year, and 5-year survival was 95.0%, 86.8%, and 84.2%, respectively. Long-term outcomes were associated with BCAC versus BCA, as well as the presence of spindle cell/ovarian stroma (both P < 0.05). CONCLUSIONS: Among patients undergoing surgery for BCT, associated malignancy was uncommon (10%) and no preoperative findings reliably predicted underlying BCAC. After excision of BCA, long-term outcomes were good; however, patients with BCAC had a worse long-term prognosis.


Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/cirugía , Cistadenocarcinoma/cirugía , Cistoadenoma/cirugía , Hepatectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/mortalidad , Cistadenocarcinoma/diagnóstico , Cistadenocarcinoma/mortalidad , Cistoadenoma/diagnóstico , Cistoadenoma/mortalidad , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto Joven
2.
BMC Gastroenterol ; 15: 67, 2015 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-26058559

RESUMEN

BACKGROUND: Intrahepatic biliary mucinous cystic neoplasms are rare hepatic tumors and account for less than 5% of intrahepatic cystic lesions. Accurate preoperative diagnosis is difficult and the outcome differs among various treatment modalities.The aim of this study is to investigate the clinico-radiological characteristics of intrahepatic biliary mucinous cystic neoplasms and to establish eligible diagnostic and treatment suggestions. METHODS: Nineteen patients with intrahepatic biliary cystadenomas and two patients with biliary cystadenocarcinomas were retrospectively reviewed. Their clinico-radiological variables and survival outcome were analyzed. RESULTS: Of the 19 patients with biliary cystadenoma, 16 (84.2 %) were female. 11 (57.9 %) patients had symptoms before operation with the most common presenting symptom being abdominal pain. Among the patients with available data, serum and cystic fluid CA 19-9 levels were invariably elevated and the CA 19-9 level in the cystic fluid was significantly higher than that in the serum. Loculations (84.2 %) and septations (63.2 %) were the most common radiologic findings. For treatment, 11 (57.9 %) patients received radical resection by either enucleation or hepatic resection, while the remaining 8 (42.1 %) patients underwent only fenestration of liver cysts. Radical resection provided a significantly better clinical outcome than fenestration in terms of tumor recurrence (p = 0.018). The only two male patients with biliary cystadenocarcinoma received radical hepatic resection and achieved a disease-free survival of 16.5 months and 33 months, respectively. CONCLUSION: Intrahepatic biliary mucinous cystic neoplasms are rare and preoperative diagnosis is difficult. Internal septations and loculations on radiologic examinations should raise some suspicion of this diagnosis. Complete tumor excision is the standard treatment that may provide patients with better long term results after the operation.


Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Conductos Biliares Intrahepáticos , Cistadenocarcinoma/diagnóstico , Cistoadenoma/diagnóstico , Hepatectomía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/cirugía , Cistadenocarcinoma/diagnóstico por imagen , Cistadenocarcinoma/mortalidad , Cistadenocarcinoma/cirugía , Cistoadenoma/diagnóstico por imagen , Cistoadenoma/mortalidad , Cistoadenoma/cirugía , Femenino , Estudios de Seguimiento , Hepatectomía/métodos , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Radiografía , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
3.
Histopathology ; 59(6): 1163-72, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22175896

RESUMEN

AIMS: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. METHODS AND RESULTS: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n = 5) and clinical samples of ovarian borderline tumours (n = 21) and invasive cancers (n = 108) when compared with ovarian epithelial cell lines (n = 3) and benign cystadenomas (n = 10) (P < 0.05). High Dock180 cytoplasmic expression in ovarian cancer (n = 108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P < 0.05), as well as poor overall and disease-free survival (P = 0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P < 0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. CONCLUSIONS: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target.


Asunto(s)
Carcinoma/enzimología , Cistoadenoma/enzimología , Neoplasias Ováricas/enzimología , Proteínas de Unión al GTP rac/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Western Blotting , Carcinoma/mortalidad , Carcinoma/patología , Movimiento Celular/genética , Cistoadenoma/mortalidad , Cistoadenoma/patología , Femenino , Humanos , Inmunohistoquímica , Microscopía Confocal , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Fenotipo , Pronóstico , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Regulación hacia Arriba , Adulto Joven , Proteínas de Unión al GTP rac/análisis
4.
Liver Int ; 31(9): 1337-44, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21745301

RESUMEN

BACKGROUND: Hepatobiliary cystadenomas and cystadenocarcinomas are rare and often misdiagnosed. AIMS: We report our experience with 33 cases over 20 years to discuss an algorithm for these diseases. METHODS: Patients presenting with a diagnosis of hepatobiliary cystadenomas and cystadenocarcinomas were retrospectively reviewed from January 1991 to October 2010. Clinical data were collected by examining hospital records and by follow-up questionnaire interviews. RESULTS: Thirty-three patients had pathologically diagnosed hepatobiliary cystadenomas (19/33, 17 females and two males) or cystadenocarcinomas (14/33, five females and nine males). Symptoms of cystadenomas at hospitalization were abdominal bloating or pain (9/19). Nine patients had an elevated level of carbohydrate antigen (CA) 19-9. The surgical procedures, i.e. cyst enucleation, segmentectomy, sectionectomy and hemihepatectomy, were performed with satisfactory outcomes. Symptoms of cystadenocarcinomas included abdominal bloating or pain (8/14) and fever (3/14). Seven patients had elevated CA19-9. The imaging characteristics of cystadenocarcinomas were similar to those of cystadenomas. The clinical outcomes for cystadenocarcinomas were mostly poor after either surgical or conservative treatment. CONCLUSIONS: Clinical symptoms are unreliable for these diagnoses and their differential diagnosis. Imaging evaluations and CA19-9 are of value for the recognition of cystadenoma and cystadenocarcinoma, but not for their differential diagnosis. Any recurrence of liver cyst after surgery or other treatments should lead one to suspect one of these diseases. Invasive examination and percutaneous fine-needle aspiration cytology are not recommended. Complete excision or careful enucleation should be the first treatment choice for a better prognosis.


Asunto(s)
Neoplasias del Sistema Biliar , Cistadenocarcinoma , Cistoadenoma , Neoplasias Hepáticas , Dolor Abdominal/etiología , Adulto , Anciano , Neoplasias del Sistema Biliar/complicaciones , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/cirugía , Procedimientos Quirúrgicos del Sistema Biliar , Antígeno CA-19-9/sangre , China , Cistadenocarcinoma/complicaciones , Cistadenocarcinoma/diagnóstico , Cistadenocarcinoma/mortalidad , Cistadenocarcinoma/patología , Cistadenocarcinoma/cirugía , Cistoadenoma/complicaciones , Cistoadenoma/diagnóstico , Cistoadenoma/mortalidad , Cistoadenoma/patología , Cistoadenoma/cirugía , Femenino , Fiebre/etiología , Hepatectomía , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Regulación hacia Arriba
5.
Int J Gynecol Cancer ; 21(7): 1248-55, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21841490

RESUMEN

OBJECTIVE: Although human chemokinelike factor (CKLF)-like MAL and related proteins for vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been proved to play an important role in carcinogenesis and apoptosis in several types of human tumors, the expression of CMTM5 in ovarian cancer remains unclear. We aimed to investigate the association between CMTM5 expression and the survival of patients with epithelial ovarian cancer. METHODS: Normal surface ovarian epithelium tissues, ovarian cystadenoma tissues, ovarian cancer tissues, and 5 ovarian cancer cell lines were collected. The CMTM5 expressions were determined by reverse transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. The survival information was analyzed by the Kaplan-Meier method. RESULTS: The CMTM5 expression was down-regulated in ovarian cancers. The expression of CMTM5 was absent in 30% (24 of 80) of ovarian cancers compared with 4.55% (1 of 22) of normal surface ovarian epithelium tissues and ovarian cystadenomas by immunohistochemistry. The results from the reverse transcription polymerase chain reaction were consistent with those from Western blotting. Furthermore, we found that although CMTM5 expression has no significant correlation with the age of the patients (P = 0.342), clinical stages (P = 0.155), pathologic types (P = 0.0605), or status of metastasis (P = 0.554), it was associated with the 3 groups of different differentiation levels (P = 0.0026) and an increase of CMTM5 loss of expression ratio in patients with preoperative CA125 level more than 500 mIU/mL compared to those with less than 500 mIU/mL (48.57% vs 16.67%, P = 0.0130). Statistical analysis by the Kaplan-Meier method showed that CMTM5 expression had no significant impact on the prognosis of patients with ovarian cancer (P = 0.24). CONCLUSIONS: The reduced expression of CMTM5 correlates significantly with poorly differentiated ovarian cancer and high preoperative CA125 level. CMTM5 may contribute to the pathogenesis of human epithelial ovarian cancer.


Asunto(s)
Quimiocinas/metabolismo , Cistadenocarcinoma/metabolismo , Cistoadenoma/metabolismo , Neoplasias Ováricas/metabolismo , Ovario/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Línea Celular Tumoral , China/epidemiología , Cistadenocarcinoma/mortalidad , Cistadenocarcinoma/patología , Cistoadenoma/mortalidad , Cistoadenoma/patología , Regulación hacia Abajo , Femenino , Humanos , Proteínas con Dominio MARVEL , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Ovario/patología , Pronóstico
6.
J Gastroenterol Hepatol ; 24(7): 1211-7, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19476563

RESUMEN

AIMS: The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN). METHODS: During a 17-year period, 99 successive IPMN patients (52 men, 47 women; mean age, 64 years) were included and divided into two groups for further comparison: one group had branch duct IPMN, whereas the other had mixed IPMN. RESULTS: Patients from the mixed IPMN group (n = 52) displayed a greater rate of symptoms (83% vs 55%, P = 0.004), pancreatic resection (67% vs 38%, P = 0.007), malignancy (35% vs 13%, P = 0.017) and death (15% vs 4%, P = 0.09) than those from the branch duct IPMN group. A 38-month follow up of non-operated, symptom-free patients confirmed that more than 85% of branch duct IPMN patients were asymptomatic without evidence of malignancy. Borderline lesions and carcinoma are found in up to 50% of symptomatic resected branch duct IPMN cases. CONCLUSION: Patients with the mixed form of IPMN as well as with symptomatic branch duct IPMN should require pancreatic resection because of symptoms and the risk for malignancy. In silent branch duct IPMN without radiological signs of malignancy, a non-operative watch-and-wait strategy can be discussed.


Asunto(s)
Adenocarcinoma Mucinoso/cirugía , Carcinoma Ductal Pancreático/cirugía , Carcinoma Papilar/cirugía , Cistoadenoma/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Cistoadenoma/mortalidad , Cistoadenoma/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Selección de Paciente , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento
7.
Mol Oncol ; 12(11): 1935-1948, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30107086

RESUMEN

Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in tumor development and progression. The current study focuses on the influence of exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA profiles were determined in exosomes from plasma of 106 EOC patients, eight ovarian cystadenoma patients, and 29 healthy women by TaqMan real-time PCR-based miRNA array cards containing 48 different miRNAs. In cell culture experiments, the impact of miR-200b and miR-320 was determined on proliferation and apoptosis of ovarian cancer cell lines. We report that miR-21 (P = 0.0001), miR-100 (P = 0.034), miR-200b (P = 0.008), and miR-320 (P = 0.034) are significantly enriched, whereas miR-16 (P = 0.009), miR-93 (P = 0.014), miR-126 (P = 0.012), and miR-223 (P = 0.029) are underrepresented in exosomes from plasma of EOC patients as compared to those of healthy women. The levels of exosomal miR-23a (P = 0.009, 0.008) and miR-92a (P = 009, 0.034) were lower in ovarian cystadenoma patients than in EOC patients and healthy women, respectively. The exosomal levels of miR-200b correlated with the tumor marker CA125 (P = 0.002) and patient overall survival (P = 0.019). MiR-200b influenced cell proliferation (P = 0.0001) and apoptosis (P < 0.008). Our findings reveal specific exosomal miRNA patterns in EOC and ovarian cystadenoma patients, which are indicative of a role of these miRNAs in the pathogenesis of EOC.


Asunto(s)
Carcinoma Epitelial de Ovario , MicroARN Circulante/sangre , Cistoadenoma , Exosomas/metabolismo , Neoplasias Ováricas , ARN Neoplásico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario/sangre , Carcinoma Epitelial de Ovario/mortalidad , Cistoadenoma/sangre , Cistoadenoma/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/sangre , Neoplasias Ováricas/mortalidad , Tasa de Supervivencia
8.
Am J Surg ; 211(1): 102-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26307421

RESUMEN

BACKGROUND: This study compared the morbidity and mortality following hepatectomy for benign liver tumors and hepatic metastases. METHODS: This retrospective cohort study compared patients who underwent hepatectomy for benign liver tumors and metastases reported to National Surgical Quality Improvement Program between 2005 and 2011. RESULTS: A total of 5,542 patients underwent hepatectomy: 1,164 (21%) for benign and 4,378 (79%) for metastatic diseases. Patients with benign tumors were younger, predominantly female, and were less likely to have preoperative comorbidities (all P < .037). Rates of major complications including infections, embolism, renal failure, stroke, coma, cardiac arrest, reoperation, and ventilator dependence were similar between the 2 groups (all P ≥ .05). Thirty-day mortality was .9% among patients with benign tumors and 1.4% among patients with metastases (P = .128). After adjusting for significant effects of age and major complications (both P ≤ .007), benign vs malignant diagnosis and extent of hepatectomy was not associated with 30-day survival (both P ≥ .083). CONCLUSIONS: Despite patients with benign disease being younger and healthier, risks of major complications are similar after hepatectomy for benign and metastatic disease. Hepatectomy should be offered selectively for patients with benign liver tumors.


Asunto(s)
Adenoma/cirugía , Hemangioma/cirugía , Hepatectomía/mortalidad , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Adenoma/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cistoadenoma/mortalidad , Cistoadenoma/cirugía , Femenino , Hemangioma/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
9.
Clin Cancer Res ; 3(9): 1473-7, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9815833

RESUMEN

Expression of the p16 gene product in human primary pancreatic carcinoma (PC) was investigated in paraffin-embedded tissue using a monoclonal antibody against p16 protein, clone G175-405, by means of immunohistochemistry, and the correlation of results with various clinicopathological parameters was evaluated. All six cases of normal pancreas and all but 1 of 20 cases of chronic pancreatitis expressed p16 protein, whereas 37.5% (3 of 8) of cystadenomas and 41. 9% (26 of 62) of PCs lost p16 expression. There was a significant difference between chronic pancreatitis and PC for frequency of the loss of p16 expression (P < 0.01). Moreover, loss of p16 expression in pancreatic malignancy was significantly associated with histological grade (G1 versus G2 and G3, P < 0.01) but not with sex, age, clinical stage, tumor location, or resectability. The survival period was shorter and metastasis is more likely in those cases that did not show p16 expression than those that did.


Asunto(s)
Genes p16 , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Animales , Anticuerpos Monoclonales/inmunología , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/patología , Enfermedad Crónica , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/inmunología , Cistadenocarcinoma/genética , Cistadenocarcinoma/metabolismo , Cistadenocarcinoma/mortalidad , Cistadenocarcinoma/patología , Cistoadenoma/genética , Cistoadenoma/metabolismo , Cistoadenoma/mortalidad , Cistoadenoma/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Tablas de Vida , Masculino , Ratones , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/inmunología , Páncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pancreatitis/metabolismo , Pronóstico , Análisis de Supervivencia
10.
Hum Pathol ; 46(10): 1471-9, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26232863

RESUMEN

Ovarian cancer is the most lethal gynecologic malignancy worldwide, and the survival rates have remained low in spite of medical advancements. More research is dedicated to the identification of novel biomarkers for this deadly disease. The association between ARMc8 and ovarian cancer remained unraveled. In this study, immunohistochemical staining was used to examine ARMc8 expression in 247 cases of ovarian cancer, 19 cases of borderline ovarian tumors, 41 cases of benign ovarian tumors, and 9 cases of normal ovarian tissues. It was shown that ARMc8 was predominantly located in the cytoplasm of tumor cells, and its expression was up-regulated in the ovarian cancer (61.9%) and the borderline ovarian tumor tissues (57.9%), in comparison with the benign ovarian tumors (12.2%; P < .05) and the normal ovarian tissues (11.1%; P < .05). In ovarian cancer, ARMc8 expression was closely related to International Federation of Gynecology and Obstetrics stages (P = .002), histology grade (P < .001), lymph node metastasis (P = .008), and poor prognosis (P < .001). Univariate and multivariate Cox analyses revealed that ARMc8 expression was an independent prognostic factor for ovarian cancer (P = .039 and P = .005). In addition, ARMc8 could promote the invasion and migration of ovarian cancer cells. Overexpressing ARMc8 enhanced the invasion and metastasis capacity of ARMc8-low Cavo-3 cells (P < .001), whereas interfering ARMc8 significantly reduced cell invasion and metastasis in ARMc8-high SK-OV-3 cells (P < .001). Furthermore, ARMc8 could up-regulate matrix metalloproteinase-7 and snail and down-regulate α-catenin, p120ctn, and E-cadherin. Collectively, ARMc8 may enhance the invasion and metastasis of ovarian cancer cells and likely to become a potential therapeutic target for ovarian cancer.


Asunto(s)
Proteínas del Dominio Armadillo/biosíntesis , Biomarcadores de Tumor/análisis , Cistadenocarcinoma/patología , Cistoadenoma/patología , Neoplasias Ováricas/patología , Adulto , Proteínas del Dominio Armadillo/análisis , Western Blotting , Células Cultivadas , Cistadenocarcinoma/mortalidad , Cistoadenoma/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección
11.
Virchows Arch ; 466(6): 665-74, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25796395

RESUMEN

In contrast to pancreatic ductal adenocarcinomas (PDAs), intraductal papillary mucinous neoplasms (IPMNs) frequently harbour GNAS mutations. To characterise GNAS-mutated pancreatic carcinomas, we examined mutations of GNAS and KRAS in 290 pancreatic adenocarcinomas and 77 pancreatic intraepithelial neoplasias (PanINs). In 64 % (39/61) of IPMNs and 37 % (11/30) of IPMN-associated adenocarcinomas, a GNAS mutation was found. GNAS mutations were frequent (78 %, 7/9) in mucinous carcinomas, with or without associated IPMN. In contrast, GNAS mutations were rarely observed in PDAs (1 %, 1/88) and PanINs (3 %, 2/77), and not at all in mucinous cystic neoplasms (MCNs) (0/10), neuroendocrine neoplasms (0/52), acinar cell neoplasms (0/16), serous cystadenomas (0/10), and solid-pseudopapillary neoplasms (0/14). We found GNAS mutations in 55/91 IPMNs with or without associated invasive carcinoma, solely in intestinal-type (78 %, 21/27) and gastric-type (62 %, 34/55) IPMNs. Of the IPMN-associated adenocarcinomas, mucinous-subtype tumours harboured GNAS mutations more frequently (83 %, 5/6) than tubular-subtype tumours (25 %, 6/24) (p = 0.02). We separately analysed GNAS in the adenocarcinoma and the IPMN component in the IPMN-associated adenocarcinomas. In all mucinous-subtype tumours, the two components exhibited identical genotypes. In contrast, the two components in 8 of 24 tubular-subtype tumours exhibited different genotypes, indicating intratumour heterogeneity. In conclusion, mucinous carcinomas with or without associated IPMN as well as IPMNs frequently harbour a GNAS mutation, reinforcing the notion that these constitute a spectrum of pancreatic tumours. Clinically and pathologically, these tumours are associated, but GNAS mutation sheds further light on this spectrum.


Asunto(s)
Adenocarcinoma Mucinoso/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Papilar/genética , Cistoadenoma/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mutación , Neoplasias Pancreáticas/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Cromograninas , Cistoadenoma/mortalidad , Cistoadenoma/patología , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Microdisección , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
12.
Am J Surg Pathol ; 18(11): 1078-91, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7943529

RESUMEN

Fifty-two hepatobiliary cystadenomas and 18 hepatobiliary cystadenocarcinomas were drawn from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital and studied in an attempt to correlate light microscopic features of the tumors with immunohistochemical and follow-up data. The cystadenoma patients ranged in age from 2 to 87 years at the time of initial diagnosis (mean, 45 years). All the cystadenomas were multilocular with benign cuboidal to columnar epithelium, and 44 (85%) had densely cellular spindle cell ("ovarian-like") stromata; 96% were female. Fifty-one cystadenomas were macrocystic lesions, typically lined by mucinous epithelium; one of the benign lesions was a serous cystadenoma (microcystic adenoma) reminiscent of the more commonly encountered pancreatic lesion of the same name. The cystadenocarcinoma patients ranged in age from 24 to 90 years at the time of first diagnosis (mean, 59 years); eight patients (44%) were male. All but one of the lesions were multilocular with malignant in situ (one case) or invasive tubulopapillary (15 cases), solid (one case), or adenosquamous (one case) epithelial components. Areas of preexisting benign cystadenoma were found in six (33%), an observation suggesting that benign lesions may evolve into malignant ones in some patients. Most cystadenomas and cystadenocarcinomas arose in the liver, a few in the extrahepatic biliary system (including the gallbladder). On follow-up, the cystadenoma patients in general were successfully treated by surgical excision of the lesions in toto; patients treated by subtotal resection often had persistent symptomatic disease. Four cystadenocarcinoma patients died of their tumors; another two patients were alive with persistent disease at last follow-up. In both the benign and the malignant lesions, most tumor cells were positive on immunohistochemical staining with antibodies to cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen; scattered chromogranin-positive cells also appeared in a few tumors of both types. Immunohistochemistry did not yield a diagnostic immunoprofile to distinguish cystadenoma from cystadenocarcinoma or from other epithelial lesions arising within the abdominal cavity. At least two types of cystadenocarcinoma exist, one developing exclusively in female patients, usually accompanied by an "ovarian-like" stroma, which follows an indolent course; and the other, lacking the distinctive cellular stroma, seen in males, follows a more aggressive course and is more likely to result in the patient's death from tumor. It remains an open question whether the cystadenocarcinomas lacking a mesenchymal stroma, which arise in women, will follow the same aggressive course as similar lesions arising in men.


Asunto(s)
Neoplasias del Sistema Biliar/patología , Cistadenocarcinoma/patología , Cistoadenoma/patología , Neoplasias Hepáticas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/mortalidad , Niño , Preescolar , Cistadenocarcinoma/mortalidad , Cistoadenoma/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia
13.
Am J Clin Pathol ; 69(3): 289-98, 1978 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-637043

RESUMEN

Thirty-four cases of microcystic adenoma of the pancreas were studied. These benign tumors have traditionally been classified as cystadenomas, but have not been clearly distinguished from those cystic neoplasms of the pancreas that have a significant malignant potential. Microcystic adenomas are benign, usually large (mean diameter 10.8 cm), and are composed of many tiny cysts lined by small cuboidal cells containing glycogen but little or no mucin. The tumor may be found incidentally at autopsy or, more commonly, may manifest as an abdominal mass with some associated local pain or discomfort. There is no sex predilection. The patients are usually elderly, both mean and median ages being 68. A microcystic pattern is apparent both grossly and microscopically. Electron microscopy confirms the presence of intracytoplasmic glycogen and the epithelial character of the cells. Follow-up data (mean 6.4 years), available in all cases, indicate that when these tumors occur in the head of the pancreas, fatalities may result either from complications of radical surgery or from gastrointestinal or biliary obstruction. When the tumors occur in the body or tail of the pancreas, biopsy alone may be sufficient.


Asunto(s)
Cistoadenoma/patología , Adulto , Anciano , Cistoadenoma/complicaciones , Cistoadenoma/diagnóstico , Cistoadenoma/mortalidad , Gránulos Citoplasmáticos/ultraestructura , Epitelio/ultraestructura , Femenino , Estudios de Seguimiento , Glucógeno , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/patología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidad
14.
Obstet Gynecol ; 51(4): 483-9, 1978 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-662232

RESUMEN

Reports of 78 cases of mucinous cystadenocarcinoma of the ovary were collected from the Emil Novak Ovarian Tumor Registry and the files of the Gynecologic Pathology Laboratory of the Johns Hopkins Hospital between the years 1942 and 1966. Two-year and 5-year followups were available for 91 and 83% of the cases, respectively. The prognosis was related to the most aggressive area of the tumor as the histologic grade was based on the maximum number of mitoses per high-powered field. In view of the clinical and histopathologic differences between these lesions and the serous and endometrioid varieties, it is suggested that each tumor be considered on its own merits in order to offer an accurate prognosis.


Asunto(s)
Cistoadenoma/patología , Neoplasias Ováricas/patología , Adulto , Cistoadenoma/diagnóstico , Cistoadenoma/mortalidad , Cistoadenoma/cirugía , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/cirugía , Paridad , Pronóstico
15.
Arch Surg ; 122(4): 443-6, 1987 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3566528

RESUMEN

From 1963 to 1983, 26 patients with cystic neoplasms of the pancreas were treated at the Lahey Clinic, Burlington, Mass. Cystadenoma (15 patients) was more common than cystadenocarcinoma (11 patients). Preoperative symptoms, such as abdominal pain, were present for as long as 18 years before diagnosis. The mean size of cysts was 7 cm. Distal pancreatectomy, the most common operation, was performed in ten patients. Eight of the 11 patients with cystadenocarcinoma had metastatic disease at the time of surgical exploration. There was one postoperative death (3.8%). Patients with cystadenocarcinoma had an adjusted median survival time after operation of 6.0 months. The long prodrome in many of the cancer patients suggests that benign cystadenomas, particularly of the mucinous type, may undergo malignant degeneration. Benign cystadenoma seems unlikely to recur after adequate resection. Whenever possible, complete excision of cystadenoma and cystadenocarcinoma is the procedure of choice.


Asunto(s)
Cistadenocarcinoma/cirugía , Cistoadenoma/cirugía , Neoplasias Pancreáticas/cirugía , Análisis Actuarial , Adulto , Anciano , Cistadenocarcinoma/mortalidad , Cistoadenoma/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pancreatectomía , Neoplasias Pancreáticas/mortalidad
16.
Int J Mol Med ; 9(3): 287-92, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11836635

RESUMEN

c-Ets1 controls the expression of some genes involved in extracellular matrix remodeling. To elucidate the involvement of c-Ets1 in epithelial ovarian carcinogenesis, we investigated the role of the proto-oncogene c-ets1 in the regulation of physiological processes such as cell proliferation, differentiation, and tumor invasion. Using fluorescent immunohistochemistry, we analyzed serial frozen sections for c-Ets1 protein expression in 26 patients with ovarian epithelial carcinoma, 10 patients with benign cystadenoma of the ovary, and 10 premenopausal patients with normal ovaries. We analyzed the relationship between the percentage of c-Ets1 stained cells in a patient and characteristics of the patient including histological classification, clinical stage, histological grade, and clinical outcome. c-Ets1 was not detected in any cases of benign ovarian cystadenoma. Most of the c-Ets1 proteins were found in the cytoplasm and some in the nucleus of epithelial ovarian cancer tissues. Moreover, c-Ets1 was strongly expressed in the head portion of papillary cancer tissues that had invaded the stroma. c-Ets1 expression was significantly associated with clinical stage (p<0.01), histological grade (p<0.01), and clinical outcome (p<0.01). Survival data were available for all patients and univariate Cox regression analysis showed that c-Ets1 expression was significantly associated with a poor prognosis (p<0.05). Our results demonstrate that c-Ets1 expression in epithelial ovarian cancer correlates to the malignant potential of the tumor.


Asunto(s)
Biomarcadores de Tumor , Carcinoma/diagnóstico , Cistoadenoma/diagnóstico , Neoplasias Ováricas/diagnóstico , Proteínas Proto-Oncogénicas/análisis , Factores de Transcripción/análisis , Carcinoma/metabolismo , Carcinoma/mortalidad , Cistoadenoma/metabolismo , Cistoadenoma/mortalidad , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Ovario/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Proto-Oncogenes Mas , Proteína Proto-Oncogénica c-ets-1 , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-ets , Análisis de Supervivencia , Factores de Transcripción/biosíntesis
17.
Anticancer Res ; 19(4A): 2509-11, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10470184

RESUMEN

Soluble interleukin-2 receptors (sIL-2R) are measurable in the sera of patients with ovarian cancer and several other benign and malignant diseases. However, the function of these sIL-2R is still unclear. Since high levels of sIL-2R are thought to be an indicator of an activated immune system we investigated the correlation of sIL-2R concentration and prognosis of ovarian cancer patients. sIL-2R measurement was performed on the preoperative sera of 130 patients with benign, and 119 patients with malignant ovarian tumors. The IMMULITE sIL-2R assay by DPC Biermann, Bad Nauheim, Germany was used. In ovarian cancer patients sIL-2R concentrations were significantly higher than in those with benign tumors. By defining the 95th percentile of the sIL-2R concentration distribution in patients with benign diseases as the cut-off (1200 U/ml) 35% of the ovarian cancer patients had elevated concentrations. Concentrations of sIL-2R increased with FIGO stage. FIGO-III patients with highly elevated sIL-2R concentrations tended to have better prognosis than those with sIL-2R levels within normal range in contrast to FIGO IV patients. Since sIL-2R concentrations indicate an immunological activation in ovarian cancer patients our data give hints of the possible role of sIL-2R in the assessment of the risk of recurrence in ovarian cancer patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Ováricas/diagnóstico , Receptores de Interleucina-2/sangre , Adenofibroma/diagnóstico , Adenofibroma/mortalidad , Adenofibroma/patología , Adenofibroma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cistoadenoma/diagnóstico , Cistoadenoma/mortalidad , Cistoadenoma/patología , Cistoadenoma/cirugía , Quiste Dermoide/diagnóstico , Quiste Dermoide/mortalidad , Quiste Dermoide/patología , Quiste Dermoide/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Quistes Ováricos/diagnóstico , Quistes Ováricos/mortalidad , Quistes Ováricos/patología , Quistes Ováricos/cirugía , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Análisis de Supervivencia , Factores de Tiempo
18.
Hepatogastroenterology ; 36(6): 424-30, 1989 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2613166

RESUMEN

During the period 1963 to 1988, we treated 45 patients with cystic neoplasms of the pancreas. The patients were divided into group 1, which included 26 patients treated between 1963 and 1983, and group 2, which included 19 patients treated between 1984 and 1988. The rate of resection for cystadenoma was 67% for group 1 (n = 15) and 100% for group 2 (n = 11). The operative mortality rate was 0% for both groups. Pathologically, 17 patients (69%) had serous cystadenoma and nine (31%) mucinous adenoma. Except for 5 of the 15 patients from group 1 who died of other causes, all patients are healthy. The resection rate for cystadenocarcinoma was 36% for group 1 (n = 11) and 100% for group 2 (n = 8). In 2 patients from group 1 and 1 patient from group 2, the tumors had been diagnosed previously as benign by operative biopsy of the cyst wall. There was no operative mortality in either group. Cystic neoplasm was suspected from the results of ultrasonography and computed tomography in 70% of the patients in group 2. In 2 patients (25%), the preoperative diagnosis of pseudocyst associated with chronic pancreatitis was made. Adenocarcinoma was diagnosed in 3 patients by needle biopsy and cytologic examination of pancreatic juice. Eighty-two percent (9 patients) of group 1 died of recurrent carcinoma; 2 patients were alive without disease at 5 and 8 years. Thirty-eight percent (3 patients) of patients in group 2 died of recurrent carcinoma, two patients died of other causes, and 3 patients are still alive.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Cistadenocarcinoma/cirugía , Cistoadenoma/cirugía , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Cistadenocarcinoma/mortalidad , Cistoadenoma/mortalidad , Femenino , Humanos , Japón/epidemiología , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/mortalidad
19.
Int J Gynaecol Obstet ; 24(1): 27-34, 1986 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-2874066

RESUMEN

The prognostic significance of periodic acid-Schiff (PAS) stain in 112 serous: 43 benign, 25 borderline and 44 malignant cystadenomas: and in 106 mucinous: 60 benign, 32 borderline and 14 malignant cystadenomas of the ovary were investigated. The amount of positively stained mucin was estimated morphometrically. The outcome of most patients with benign or borderline lesion was good. One patient with benign mucinous cystadenoma died, however, of pseudomyxoma peritonei and another patient with borderline mucinous cystadenoma died of peritoneal carcinosis. Other patients were alive and free of the disease after a follow-up of 1-14 years, or had died of causes unrelated to the ovarian disease. Abundant PAS positive mucin predicted a longer survival both in serous and in mucinous malignant tumors. The 5-year survivals for the serous cystadenocarcinomas with and without PAS positive mucin were 21% and 13%, respectively (not statistically significant). For mucinous cystadenocarcinomas with mucin value over and below the median, the 5-year survival rates were 57% and 14%, respectively (P less than 0.10). High PAS positivity in both serous and mucinous cystadenocarcinomas clearly indicated better prognosis, although statistical significance was not achieved. Thus, further studies are needed for final evaluation of the prognostic significance of the PAS stain in these ovarian tumors.


Asunto(s)
Cistadenocarcinoma/patología , Cistoadenoma/patología , Neoplasias Ováricas/patología , Cistadenocarcinoma/mortalidad , Cistoadenoma/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Reacción del Ácido Peryódico de Schiff , Pronóstico
20.
Chirurg ; 75(6): 615-21, 2004 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-15103421

RESUMEN

Cystic tumors comprise only 1% of all pancreatic tumors, although there is an increasing number of publications about them. These tumors divide into other tumor entities, some of them benign and some of them borderline or malignant. Therefore, the kind of therapy is presently under discussion. Between 1986 and 2003, we treated 97 patients with cystic tumors of the pancreas, evaluated the data retrospectively, and followed the patients up. Sixty-seven percent were treated by radical resection and 32% by organ-preserving resection. With 41%, postoperative "new" diabetes mellitus was significantly more frequent after radical resection than after organ-preserving resection at 24% ( P<0.01). Long-term survival was worst after mucinous cystadenocarcinoma (59% after 36 months), and 90% of all other patients lived longer than 36 months. We conclude that organ-preserving resection should be considered in all serous cystic tumors and solid pseudopapillary tumor of the pancreas. All mucinous cystic tumors are of malignant or borderline nature and should be treated as such by radical resection.


Asunto(s)
Carcinoma Ductal Pancreático/cirugía , Carcinoma Papilar/cirugía , Cistadenocarcinoma/cirugía , Cistoadenoma/cirugía , Linfangioma/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Cistadenocarcinoma/mortalidad , Cistadenocarcinoma/patología , Cistoadenoma/mortalidad , Cistoadenoma/patología , Femenino , Estudios de Seguimiento , Humanos , Linfangioma/mortalidad , Linfangioma/patología , Masculino , Persona de Mediana Edad , Páncreas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
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