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1.
Br J Surg ; 107(11): 1429-1439, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32492186

RESUMEN

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).


ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.


Asunto(s)
Adenocarcinoma/cirugía , Gastrectomía/métodos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Ganglio Linfático Centinela/cirugía , Neoplasias Gástricas/cirugía , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Ganglio Linfático Centinela/patología , Neoplasias Gástricas/patología , Resultado del Tratamiento
2.
Br J Surg ; 99(3): 397-403, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22101572

RESUMEN

BACKGROUND: Positive peritoneal washing cytology is a poor prognostic factor in patients with gastric cancer. The right therapeutic approach for this condition has not been well documented. METHODS: Patients who underwent surgery for gastric cancer with suspected serosal invasion and peritoneal washing cytology at the Korean National Cancer Centre between May 2001 and December 2009 were included in this retrospective study. Clinicopathological factors and overall survival were analysed with respect to the cytological results and presence of peritoneal metastases. Prognostic factors were analysed in patients with positive cytology but without overt peritoneal metastases. RESULTS: A total of 1072 patients were included in the analysis, of whom 900 had negative cytology (C0 group) and 172 had positive cytology (C1 group). No peritoneal metastases (P0) were found in 830 patients (92·2 per cent) in the C0 group. Peritoneal metastases (P1) were found in 76 patients (44·2 per cent) in the C1 group. Median overall survival times in the P0 C1, P1 C0 and P1 C1 subgroups were 20·0, 14·0 and 10·0 months respectively. Multivariable analysis of the P0 C1 subgroup revealed that clinical N0-2 category and gastric resection were significantly associated with better prognosis (median survival 24·0 versus 13·0 months for N0-2 versus N3, and 21·0 versus 4·0 months for resected versus non-resected). CONCLUSION: Positive washing cytology in patients with gastric cancer is a negative prognostic factor for patients with, as well as those without, overt peritoneal metastases. Resection is an option in patients with clinical stage N0-2 disease without peritoneal metastases but with a positive washing cytology finding.


Asunto(s)
Líquido Ascítico/patología , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patología , Anciano , Femenino , Gastrectomía/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Siembra Neoplásica , Lavado Peritoneal/métodos , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Análisis de Supervivencia
3.
Endoscopy ; 43(6): 465-71, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21425043

RESUMEN

BACKGROUND AND AIMS: Therapeutic guidelines have not yet been established for low-grade gastric adenomas/dysplasias (LGD), which have a low risk of progression to high-grade adenomas/dysplasias (HGD) or to invasive carcinomas. This study aimed to evaluate risk factors for HGD/carcinoma that indicate a need for resection in biopsy-proven LGD lesions. PATIENTS AND METHODS: In total, 236 LGD lesions from 208 consecutive patients treated with endoscopic resection (ER) were retrospectively studied between 2004 and 2008. The Vienna classification was used for histological diagnosis. A generalized estimating equation (GEE) logistic regression model was used for multivariate analysis. RESULTS: Among the 236 LGD lesions, the final pathology diagnosed 9 (3.8 %) as invasive carcinoma (category 5), 71 (30.1 %) as HGD (category 4), 148 (62.7 %) as LGD (category 3), and 8 (3.4 %) as negative/indefinite for dysplasia (category 1/2). Lesions ≥ 1 cm were classified as HGD/carcinoma in 39.4 % of patients (65/165). Multivariate analysis indicated that size of ≥ 1 cm (OR 1.93 [95 % CI, 1.06 - 3.52]), depressed morphology (OR 3.81 [95 % CI, 1.22 - 11.9]), and erythema (OR 2.49 [95 % CI, 1.31 - 4.72]) were significantly associated with HGD/carcinoma. The OR increased to 47.6 (95 % CI, 4.27 - 530.65) when the risk factors were all positive. The sensitivity and negative predictive value for ≥ 1 risk factors were 93.8 % and 90.9 %, respectively. As the number of risk factors of a lesion increased, the specificity and positive predictive value also increased. CONCLUSIONS: Endoscopic resection can be recommended if a low-grade dysplastic lesion has at least one of the following risk factors: depressed morphology, surface erythema, or a size of 1 cm or greater. For lesions that have none of the three risk factors, follow-up endoscopy is recommended.


Asunto(s)
Adenoma/patología , Carcinoma/patología , Mucosa Gástrica/patología , Lesiones Precancerosas/patología , Neoplasias Gástricas/patología , Adenoma/clasificación , Adenoma/cirugía , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma/cirugía , Femenino , Mucosa Gástrica/cirugía , Gastroscopía , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Neoplasias Gástricas/cirugía
4.
Br J Surg ; 97(5): 732-6, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20235088

RESUMEN

BACKGROUND: Early gastric cancer with signet ring cell histology has been reported as a favourable histological type. The aim of this study was to identify risk factors associated with lymph node metastasis in patients with this type of early gastric cancer. METHODS: A cross-sectional study of patients with early gastric cancer with differentiated and signet ring cell histology undergoing surgery was conducted. Risk factors were evaluated using multiple logistic regression analysis with odds ratios and 95 per cent confidence intervals. RESULTS: In 1362 patients undergoing gastrectomy for early gastric cancer, the rate of lymph node metastasis was similar for tumours with signet ring cell and differentiated histological findings (10.7 versus 9.0 per cent respectively; P = 0.307). Logistic regression analysis showed that depth of tumour invasion was predictive of lymph node metastasis in patients with signet ring cell histology (P < 0.001). Tumour size was not associated with lymph node metastasis in either univariable or multivariable analysis. Lesions smaller than 2 cm were not uncommon in patients with signet ring cell gastric tumours and lymph node metastases (six of 48; 13 per cent). CONCLUSION: Patients with early gastric cancer with signet ring cell-type histology are probably best treated by gastrectomy with lymph node dissection.


Asunto(s)
Carcinoma de Células en Anillo de Sello/secundario , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células en Anillo de Sello/cirugía , Estudios Transversales , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Factores de Riesgo , Neoplasias Gástricas/cirugía
5.
Dig Surg ; 26(6): 465-70, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20068318

RESUMEN

BACKGROUND/AIMS: Lymph node metastasis is the most important point to consider when deciding on the modality of resection in patients with early gastric cancer. This study was conducted to evaluate the learning curve for identification of sentinel lymph nodes in patients with gastric cancer. METHODS: The investigators included the results from 2 prospective series of sentinel lymph node mapping. Cumulative sum (CUSUM) analysis was performed to assess the learning curves for identification of sentinel lymph nodes at CUSUM target success rates of 95%. RESULTS: One surgeon performed 135 sentinel lymph node mappings for 2 prospective series. The success rate exceeded 90%. The learning period for gastric cancer sentinel node mapping was calculated to be 26 cases for achieving a 95% success rate. Multiple logistic regression analysis for successful detection of sentinel nodes showed that surgical experience of sentinel lymph node mapping was an independent factor for successful detection of sentinel nodes. CONCLUSIONS: This study suggests that the learning period for identification of sentinel lymph nodes in gastric cancer would be 26 cases. In clinical trials for gastric cancer with sentinel lymph node mapping, the learning curve should be considered to minimize bias due to surgical factors.


Asunto(s)
Competencia Clínica , Rol del Médico , Biopsia del Ganglio Linfático Centinela , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adulto , Anciano , Detección Precoz del Cáncer , Educación Médica Continua , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Regresión , Proyectos de Investigación
6.
Eur J Surg Oncol ; 43(8): 1542-1549, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28511775

RESUMEN

BACKGROUND: Prognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC) remains elusive so far due to disparities in cohort size and baseline characteristics in previous studies. A propensity score matching (PSM) analysis as well as multivariable model was performed for unbiased evaluation of the outcome in AFPGC. METHODS: Among 3034 gastric cancer patients who underwent curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea between 2002 and 2007, we identified 97 patients being positive for AFP either by elevation of serum-AFP levels >10 µg/L or by immunohistochemical staining. Due to marked disparities in baseline characteristics and cohort size, propensity-score-matching was performed which matched 87 AFPP-GC patients to the same number of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were compared using χ2-test. Survival curves were compared using the Kaplan-Meier-method and multivariable regression analysis was performed to evaluate the effect of AFP-positivity while adjusting the effects of confounding variables. RESULTS: AFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts. After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location, grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren histologic type and stage distribution. In multivariable regression analysis of the PSM-groups, only AFP-positivity and pathologic stage were predictive for overall survival (HR 2.98, CI 95% {1.7-5.1}, p < 0.0001). Five-year-survival rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014). Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003). CONCLUSION: AFP can be considered as an independent negative predictor of overall and recurrence-free survival in patients with gastric cancer.


Asunto(s)
Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirugía , alfa-Fetoproteínas/metabolismo , Biomarcadores de Tumor/sangre , Femenino , Gastrectomía , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Estudios Prospectivos , Neoplasias Gástricas/patología , Tasa de Supervivencia , Resultado del Tratamiento
7.
Histol Histopathol ; 20(1): 59-66, 2005 01.
Artículo en Inglés | MEDLINE | ID: mdl-15578423

RESUMEN

Gallbladder carcinomas are rare but highly lethal neoplasms. We examined the expression of five cell-cycle-related molecules (p53, RB, cyclin D1, p27, Ki-67), and MSH2, in 46 carcinomas, 14 adenomas, 15 low-grade dysplasias, 9 intestinal metaplasias and 20 normal gallbladder epithelia. The expression of these molecules was altered in gallbladder carcinomas and adenomas. In gallbladder carcinomas we observed increased expression of p53, cyclin D1, Ki-67, and MSH2 together with decreased expression of RB and p27 protein. Aberrant expression of cyclin D1 and reduced expression of RB were noted in adenomas, and expression of cyclin D1 was elevated in low-grade dysplasias. However, there was no change in the levels of these cell-cycle molecules in metaplasia. Expression of p53, p27, Ki-67, and MSH2 was correlated with clinical stage (P<0.05) and there was also a correlation between the expression of Ki-67 and MSH-2 and patient age (P<0.05). These results suggest that altered expression of cell-cycle molecules p53, cyclin D1, RB, p27, and of MSH-2 is involved in the progression of gallbladder carcinomas.


Asunto(s)
Carcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Neoplasias de la Vesícula Biliar/metabolismo , Anciano , Carcinoma/genética , Carcinoma/fisiopatología , Proteínas de Ciclo Celular/biosíntesis , Ciclina D1/biosíntesis , Ciclina D1/genética , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Femenino , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/fisiopatología , Humanos , Inmunohistoquímica , Antígeno Ki-67/biosíntesis , Antígeno Ki-67/genética , Masculino , Proteína 2 Homóloga a MutS , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Antígeno Nuclear de Célula en Proliferación/genética , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/genética , Proteína de Retinoblastoma/biosíntesis , Proteína de Retinoblastoma/genética , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética
8.
Virchows Arch ; 433(2): 113-7, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9737788

RESUMEN

ILK (beta1-integrin-linked protein kinase) is a recently identified 59-kDa serine/threonine protein kinase that interacts with the cytoplasmic domain of the beta1-integrin containing four ankyrin-like repeats. We have developed a polyclonal antibody against ILK and explored the ILK immunoreactivity in normal human cells and tissues. ILK was mainly expressed in cardiac muscle and skeletal muscles. Surprisingly, ILK expression was observed in Ewing's sarcoma (ES; 100%), primitive neuroectodermal tumour (PNET; 100%), medulloblastoma (100%), and neuroblastoma (33.3%), whereas other small round cell sarcomas were not stained by the anti-ILK antibody. These results suggest that ILK could be a novel marker for tumours with primitive neural differentiation. Our findings support the notion that ES is a tumour that is closely related to PNET and that both originate from the neuroectoderm. ILK may be a sensitive and specific immunohistochemical marker and useful for the positive identification of ES and PNET in formalin-fixed, paraffin-embedded tissue sections.


Asunto(s)
Biomarcadores de Tumor/análisis , Inmunohistoquímica , Tumores Neuroectodérmicos Primitivos/enzimología , Proteínas Serina-Treonina Quinasas/análisis , Sarcoma de Ewing/enzimología , Adolescente , Adulto , Animales , Western Blotting , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Tumores Neuroectodérmicos Primitivos/diagnóstico , Especificidad de Órganos , Sarcoma de Ewing/diagnóstico , Sensibilidad y Especificidad
9.
Virchows Arch ; 434(5): 443-9, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10389628

RESUMEN

In a significant proportion of cases, anencephaly is associated with thymic enlargement, suggesting a possibility that anencephalic fetuses have a functional disturbance in thymocyte differentiation and development. In this report, we demonstrated that CD99 expression was consistently reduced in cortical thymocytes of all anencephalic fetuses. In addition, the CD99-dependent aggregation of immature cortical thymocytes was almost completely impaired and apoptosis of thymocytes was markedly reduced in several cases. These results are in agreement with previous findings that CD99 regulates the aggregation and apoptosis of various types of cells. These data strongly suggest that functional disturbance of thymocytes and thymic hyperplasia are related to the reduced expression of CD99 molecule in anencephalic fetuses.


Asunto(s)
Anencefalia/patología , Antígenos CD/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Feto/patología , Linfocitos T/patología , Timo/patología , Antígeno 12E7 , Anencefalia/metabolismo , Antígenos CD/inmunología , Apoptosis , Moléculas de Adhesión Celular/inmunología , Agregación Celular , Regulación hacia Abajo , Edad Gestacional , Humanos , Inmunohistoquímica , Linfocitos T/metabolismo , Timo/metabolismo , Hiperplasia del Timo/metabolismo , Hiperplasia del Timo/patología
10.
Mol Cells ; 9(6): 657-61, 1999 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-10672934

RESUMEN

Anaplastic myeloma is a rare but distinct, biologically aggressive variant of myeloma which usually results from dedifferentiation or anaplastic transformation of the myeloma cells. The molecular mechanisms that determine the biologic behavior of anaplastic myeloma and effective treatment modalities have not been well known due to lack of in vitro models. In the present study, we have developed an anaplastically transformed mutant from a human myeloma-derived cell line. In the process of long-term culture of the myeloma-derived IM-9 cell line in low serum and nutrient conditions, an adherent mutant line was developed and named IM-9/AD. This mutant cell line displayed several characteristics resembling anaplastic myeloma such as: 1, large cells with large vesicular nucleus and prominent nucleolus, multinuclearity and high mitotic figures; 2, loss of leukocyte-associated antigens; and 3, higher tumorigenecity in scid mice than its parental cell line. This newly developed mutant cell line may serve as a readily available in vitro model to investigate the biology of anaplastic myeloma.


Asunto(s)
Transformación Celular Neoplásica/genética , Animales , Antígenos CD/inmunología , Adhesión Celular/genética , Trasplante de Células , Humanos , Cadenas Pesadas de Inmunoglobulina/análisis , Ratones , Ratones SCID , Mieloma Múltiple , Fenotipo , Células Tumorales Cultivadas
11.
Mol Cells ; 9(6): 662-7, 1999 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-10672935

RESUMEN

Cell-cell adhesion is essential for the appropriate immune response, differentiation, and migration of lymphocytes. This important physiological event is reflected in vitro by homotypic cell aggregation. We have previously reported that a 120 kDa cell surface glycoprotein, JL1, is a unique protein specifically expressed by immature double positive (DP) human thymocytes which are in the process of positive and negative selections through the interaction between thymocyte and antigen-presenting cells (APCs). The function of the JL1 molecule, however, is yet to be identified. We show here that anti-JL1 monoclonal antibody (mAb) induced the homotypic aggregation of human thymocytes in a temperature- and Mg2+-dependent manner. It required an intact cytoskeleton and the interaction between leucocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) since it was blocked by cytochalasin B and D, and mAb against LFA-1 and ICAM-1 which are known to be involved in the aggregation of thymocytes. Translocation of phosphatidylserine (PtdSer) through the cell membrane was not detected, implying that the molecular mechanism of JL-1-induced homotypic aggregation is different from that of CD99-induced homotypic aggregation. In summary, JL1 is a cell surface molecule that induces homotypic adhesion mediated by the LFA-1 and ICAM-1 interaction and cytoskeletal reorganization. These findings suggest that JL1 may be an important regulator of thymocyte development and thymocyte-APC interaction.


Asunto(s)
Antígenos de Diferenciación de Linfocitos T/metabolismo , Agregación Celular/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/farmacología , Antígeno-1 Asociado a Función de Linfocito/farmacología , Linfocitos T/metabolismo , Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Adhesión Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Leucemia , Fosfatidilserinas/metabolismo , Transducción de Señal/efectos de los fármacos , Temperatura , Células Tumorales Cultivadas
12.
AJNR Am J Neuroradiol ; 16(9): 1903-8, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8693993

RESUMEN

PURPOSE: To compare the MR signal intensity patterns and enhancement pattern of intracranial tuberculomas with their histopathologic features. METHODS: MR images of six patients with surgically proved intracranial tuberculoma were reviewed retrospectively and were compared with histologic findings of the resected specimen. Detailed histologic examination was performed to look for the extent and characteristics of caseation necrosis, fibrosis, and inflammatory cellular infiltrates at each area of different signal intensities and at the enhancing areas on MR. Signal intensities for T1- and T2-weighted images were compared with normal gray matter. RESULTS: On T1-weighted images, the granulomas showed a slightly hyperintense rim surrounded by a complete or partial rim of slight hypointensity and central isointensity or mixed isointensity and hyperintensity in five patients and homogeneous isointensity in one patient. Histologically, the zone of central isointensity or mixed intensity corresponded to caseation necrosis plus adjacent cellular infiltrates. The hyperintense and hypointense rims corresponded to the layers of collagenous fiber and the layers of the inflammatory cellular infiltrates, respectively. On T2-weighted images, the entire portion of the granuloma showed slightly heterogeneous isointensity or hypointensity with small markedly hypointense foci in five patients, and a hyperintense center surrounded by a hypointense rim in one patient. Histologic layers were not discriminated on T2-weighted images. On postcontrast T1-weighted images, there were single or multiple conglomerate ring enhancements within a tuberculoma in all six patients, corresponding to the layers of both collagenous and inflammatory cells. CONCLUSION: Combination of the described signal intensity patterns and conglomerate ringlike enhancing appearance of the lesion is characteristic of tuberculoma, and may play an important role in differentiating intracranial tuberculomas from other ring-enhancing brain lesions.


Asunto(s)
Encéfalo/patología , Imagen por Resonancia Magnética , Tuberculoma Intracraneal/diagnóstico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculoma Intracraneal/patología
13.
Oncogene ; 33(41): 4941-51, 2014 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-24681952

RESUMEN

The translation of high-throughput gene expression data into biologically meaningful information remains a bottleneck. We developed a novel computational algorithm, PATHOME, for detecting differentially expressed biological pathways. This algorithm employs straightforward statistical tests to evaluate the significance of differential expression patterns along subpathways. Applying it to gene expression data sets of gastric cancer (GC), we compared its performance with those of other leading programs. Based on a literature-driven reference set, PATHOME showed greater consistency in identifying known cancer-related pathways. For the WNT pathway uniquely identified by PATHOME, we validated its involvement in gastric carcinogenesis through experimental perturbation of both cell lines and animal models. We identified HNF4α-WNT5A regulation in the cross-talk between the AMPK metabolic pathway and the WNT signaling pathway, and further identified WNT5A as a potential therapeutic target for GC. We have demonstrated PATHOME to be a powerful tool, with improved sensitivity for identifying disease-related dysregulated pathways.


Asunto(s)
Algoritmos , Transducción de Señal , Neoplasias Gástricas/genética , Transcriptoma , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Neoplasias Experimentales , Reproducibilidad de los Resultados , Neoplasias Gástricas/patología , Vía de Señalización Wnt
14.
Aliment Pharmacol Ther ; 39(8): 854-63, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24612291

RESUMEN

BACKGROUND: Metformin use has been associated with a decreased incidence and mortality of various cancers. AIM: To evaluate the association between metformin use and gastric cancer. METHODS: We randomly selected 100 000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39 989 patients (aged 30-97 years) who were regularly treated with anti-diabetic drugs and followed-up from 2004 to 2010. In total, 26 690 patients had used metformin out of 32 978 diabetics who had not regularly used insulin (insulin non-users), and 5855 patients had used metformin out of 7011 regular insulin users. RESULTS: Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P = 0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P = 0.059). Duration of metformin use was associated with the reduction in gastric cancer risk (AHR, 0.88; 95% CI 0.81-0.96, P = 0.003), especially in patients who used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37-0.87; P = 0.009). CONCLUSION: Metformin use >3 years in type 2 diabetics who do not use insulin is associated with a significantly reduced gastric cancer risk.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Neoplasias Gástricas/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/administración & dosificación , Incidencia , Insulina/uso terapéutico , Masculino , Metformina/administración & dosificación , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Neoplasias Gástricas/epidemiología , Factores de Tiempo
16.
Eur J Surg Oncol ; 39(12): 1407-14, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24119717

RESUMEN

AIMS: According to the recent Japanese Gastric Cancer Association's gastric cancer treatment guidelines, bursectomy is recommended for tumors penetrating the serosa of the posterior gastric wall. However, there is still little data to show whether bursectomy improves patient survival. The aim of this study is to evaluate the efficacy of bursectomy for subserosa or serosa-positive gastric cancer in terms of overall survival. METHOD: From April 2001 to December 2006, 470 patients underwent curative resection for macroscopically subserosa or serosa-positive gastric cancer. These patients were grouped according to whether bursectomy was performed or not (bursectomy+/bursectomy-). Clinicopathological characteristics and incidence of complications were compared between the groups. The overall survival rates were analyzed using a Cox proportional hazards model. RESULTS: There was no significant difference in morbidity and mortality between the bursectomy+ and bursectomy- groups. In the multivariable analysis for overall survival, bursectomy was not a significant independent factor (p = 0.978). In the subgroup analysis for clinical and pathological stage III and IV, and tumors penetrating the serosa of the posterior gastric wall, bursectomy did not have significant effect on overall survival as well (p = 0.582, 0.453, and 0.532, respectively). In the propensity score-matched patients, bursectomy still showed no significant effect on overall survival (p = 0.804). CONCLUSIONS: Bursectomy is unlikely to improve overall survival in patients with macroscopically subserosa or serosa-positive gastric cancer.


Asunto(s)
Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia , Cavidad Peritoneal/cirugía , Membrana Serosa/patología , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Gastrectomía , Hospitales de Alto Volumen , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Tempo Operativo , Estudios Retrospectivos , Tasa de Supervivencia
17.
Transplant Proc ; 45(2): 597-604, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23498796

RESUMEN

BACKGROUND: It has been reported that an HY antigen-mismatched islet transplantation can induce peripheral tolerance. However, the factors that initiate the peripheral tolerance are not clear. This study was designed to examine which genes were most important for the induction of peripheral tolerance. METHODS: Islets from female Balb/c and male C57BL/6 mice were transplanted underneath the left perirenal capsule of female C57BL/6 recipient mice rendered diabetic by intraperitoneal injection of streptozotocin. Before rejection or tolerance phenotypes arose, we harvested islet grafts for cDNA microarray analysis. RESULTS: Minor antigen-mismatched islets transplanted into recipient mice showed no rejection or tolerance phenotypes until 12 days posttransplantation. When we confirmed, decreased functional islet grafts and increased inflammatory cell infiltration. Gene expression profiles revealed differences in expression among groups. Major histocompatibility complex-mismatched islets induced upregulation of 209 genes and downregulation of 10 genes compared with the HY antigen-mismatched islet (2-fold; P < .05). Of these, 3 genes exhibited significant changes in expression levels in Balb/c donor islet grafts compared with C57BL/6 donor islet grafts: Gad1, Gdf10, and Scg2 (P < .01). CONCLUSIONS: The present study suggested that 3 genes showed a significant relationship to protection against graft rejection. The identification of these genes may help to understand signaling pathways, involved in the communication between transplanted islet grafts and recipients in vivo.


Asunto(s)
Diabetes Mellitus Experimental/cirugía , Perfilación de la Expresión Génica , Rechazo de Injerto/genética , Supervivencia de Injerto/genética , Histocompatibilidad/genética , Trasplante de Islotes Pancreáticos/inmunología , Tolerancia al Trasplante/genética , Animales , Glucemia/metabolismo , Carboxiliasas/genética , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/inmunología , Femenino , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Factor 10 de Diferenciación de Crecimiento/genética , Antígeno H-Y/inmunología , Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Secretogranina II/genética , Factores de Tiempo , Técnicas de Cultivo de Tejidos
18.
Aliment Pharmacol Ther ; 38(10): 1292-302, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24134499

RESUMEN

BACKGROUND: Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. AIM: To validate the OLGA and OLGIM staging systems in a region with high risk of GC. METHODS: This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. RESULTS: More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. CONCLUSION: As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer.


Asunto(s)
Gastritis/patología , Neoplasias Intestinales/patología , Metaplasia/patología , Neoplasias Gástricas/patología , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Gastritis/clasificación , Humanos , Modelos Logísticos , Masculino , Metaplasia/clasificación , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo
19.
Aliment Pharmacol Ther ; 38(5): 477-89, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23822578

RESUMEN

BACKGROUND: Helicobacter pylori eradication is recommended for early gastric cancer (GC) patients after resection. AIM: To evaluate whether H. pylori eradication improves glandular atrophy and intestinal metaplasia (IM) in GC patients undergoing subtotal gastrectomy. METHODS: This randomised, double-blind trial was performed in tertiary care setting. Distal GC patients with H. pylori infection were randomised to receive proton pump inhibitor-based triple therapy or placebo. The histology was evaluated using the updated Sydney system before and at 36 months after surgery. The endpoints were the comparison of atrophy and IM score changes between the allocated groups and according to final H. pylori status. RESULTS: Overall, 190 patients were randomised to the treatment and placebo groups. For lesser curvature of the corpus, mean atrophy and IM scores did not differ between the treatment and placebo groups. However, the H. pylori-eradicated patients had significantly lower mean scores than the H. pylori-persistent patients regarding atrophy (0.55 ± 0.95 vs. 1.05 ± 1.10 respectively; P = 0.0046) and IM (0.66 ± 0.99 vs. 1.05 ± 1.16 respectively; P = 0.0284). The percentage change from baseline was more marked in the H. pylori-negative than in the H. pylori-positive groups (-58.6% vs. -11.0% for atrophy and -60.5% vs. -35.6% for IM respectively). For greater curvature, mean atrophy score was lower in the H. pylori-negative group than in the H. pylori-positive group (0.14 ± 0.50 vs. 0.41 ± 0.75 respectively; P = 0.0281). The percentage change was -36.4% vs. 86.3%. CONCLUSION: Helicobacter pylori eradication in GC patients is beneficial, as reflected by lower scores of atrophy and IM at 36 months after subtotal gastrectomy. (ClinicalTrials.gov number, NCT01002443).


Asunto(s)
Adenocarcinoma/cirugía , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Intestinos/patología , Inhibidores de la Bomba de Protones/uso terapéutico , Neoplasias Gástricas/cirugía , Estómago/patología , Adenocarcinoma/microbiología , Adenocarcinoma/patología , Adulto , Atrofia , Método Doble Ciego , Femenino , Gastrectomía , Mucosa Gástrica/efectos de los fármacos , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Complicaciones Posoperatorias , Lesiones Precancerosas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Factores de Tiempo , Resultado del Tratamiento
20.
Eur J Surg Oncol ; 38(1): 57-63, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21945625

RESUMEN

AIMS: The authors aimed to compare the surgical performance and the short-term clinical outcomes of robotic assisted laparoscopic distal gastrectomy (RADG) with laparoscopy-assisted distal gastrectomy (LADG) in distal gastric cancer patients. METHOD: From April 2009 to August 2010, 62 patients underwent LADG and 30 patients underwent RADG for preoperative stage I distal gastric cancer by one surgeon at the National Cancer Center, Korea. Surgical performance was measured using lymph node (LN) dissection time and number of retrieved LNs, which were viewed as surrogates of technical ease and oncologic quality. RESULTS: In clinicopathologic characteristics, mean age, depth of invasion and stage were significantly different between the LADG and RADG group. Mean dissection time at each LN station was greater in the RADG group, but no significant intergroup difference was found for numbers of retrieved LNs. Furthermore, proximal resection margins were smaller, and hospital costs were higher in the RADG group. In terms of the RADG learning curve, mean LN dissection time was smaller in the late RADG group (n = 15) than in the early RADG group (n = 15) for 4sb/4d, 5, 7-12a stations, but numbers of retrieved LNs per station were similar. CONCLUSION: With the exception of operating time and cost, the numbers of retrieved LNs and the short-term clinical outcomes of RADG were found to be comparable to those of LADG, despite the surgeon's familiarity with LADG and lack of RADG experience. Further studies are needed to evaluate objectively ergonomic comfort and to quantify the patient benefits conferred by robotic surgery.


Asunto(s)
Gastrectomía/instrumentación , Gastrectomía/métodos , Laparoscopía , Robótica , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento
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