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1.
Surg Today ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969868

RESUMEN

Treatment of early breast cancer using breast-conserving surgery (BCS) commonly leads to local control and acceptable cosmetic results. We report a useful technique to achieve symmetry of the breast shape and nipple-areola, with excellent results. A Japanese patient with early breast cancer located in the inner central area of the breast was enrolled in this study. Intraductal spread of breast cancer to the nipple was suspected; however, no invasion was observed outside the nipple wall. We preserved the cylindrical surface, but resected the inner tissue with the top surface of the nipple. After coring the nipple, the remnant cylindrical surface was cut into a spiral shape. Nipple reconstruction using the spiral-peeling technique during oncoplastic breast-conserving surgery (OPBCS) may be useful for patients who desire nipple preservation.

2.
Surg Today ; 52(3): 514-518, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34398273

RESUMEN

The treatment of early breast cancer using oncoplastic breast surgery (OBS) has been gradually increasing in popularity and is recognized for its efficacy in local control and excellent cosmetic results. We herein report a useful technique for obtaining symmetry of the breast shape for an early breast lesion located in an outer area, close to the nipple-areola, in a Japanese patient with ptotic, fatty breasts. We designed two equilateral triangles: one just upon the resected area and the other on the axilla. They were located on a straight line, with one top pointed to the cranial side and one to the caudal side. A crescent area around the areola was de-epithelialized in the 12 o'clock and 6 o'clock directions. Columnar-shaped breast tissue and an equilateral triangular skin flap and fatty tissue were removed together. To fill the defect, a skin-glandular flap was slid horizontally after suturing the inframammary line. Although an incision scar was formed on the breast and lateral chest wall in a Z-shape, this new technique was able to achieve not only cancer control but also excellent cosmetic results.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/métodos , Mastectomía , Mastectomía Segmentaria/métodos , Pezones/cirugía
3.
J Hum Genet ; 66(5): 519-534, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33177704

RESUMEN

Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expression levels of two miRNAs derived from pre-miR-99a (miR-99a-5p and miR-99a-3p) were suppressed in cancerous tissues. The aim of this study was to identify oncogenic genes controlled by pre-miR-99a that are closely involved in the molecular pathogenesis of BrCa. A total of 113 genes were identified as targets of pre-miR-99a regulation (19 genes modulated by miR-99a-5p, and 95 genes regulated by miR-99a-3p) in BrCa cells. Notably, FAM64A was targeted by both of the miRNAs. Among these targets, high expression of 16 genes (C5orf22, YOD1, SLBP, F11R, C12orf49, SRPK1, ZNF250, ZNF695, CDK1, DNMT3B, TRIM25, MCM4, CDKN3, PRPS, FAM64A, and DESI2) significantly predicted reduced survival of BrCa patients based upon The Cancer Genome Atlas (TCGA) database. In this study, we focused on FAM64A and investigated the relationship between FAM64A expression and molecular pathogenesis of BrCa subtypes. The upregulation of FAM64A was confirmed in BrCa clinical specimens. Importantly, the expression of FAM64A significantly differed between patients with Luminal-A and Luminal-B subtypes. Our data strongly suggest that the aberrant expression of FAM64A is involved in the malignant transformation of BrCa. Our miRNA-based approaches (identification of tumor-suppressive miRNAs and their controlled targets) will provide novel information regarding the molecular pathogenesis of BrCa.


Asunto(s)
Neoplasias de la Mama/genética , Estrógenos , Regulación Neoplásica de la Expresión Génica/genética , Genes Supresores de Tumor , Péptidos y Proteínas de Señalización Intracelular/genética , MicroARNs/genética , Proteínas de Neoplasias/genética , Neoplasias Hormono-Dependientes/genética , Proteínas Nucleares/genética , Oncogenes , Progesterona , ARN Neoplásico/genética , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Genes erbB-2 , Humanos , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Péptidos y Proteínas de Señalización Intracelular/fisiología , Estimación de Kaplan-Meier , MicroARNs/fisiología , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/fisiología , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/mortalidad , Neoplasias Hormono-Dependientes/patología , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/fisiología , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Pronóstico , Supervivencia sin Progresión , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Interferencia de ARN , ARN Neoplásico/fisiología , ARN Interferente Pequeño/genética , Resultado del Tratamiento
4.
Surg Today ; 51(7): 1241-1245, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33033958

RESUMEN

The treatment of early breast cancer using breast conservation therapy (BCT) commonly ensures local control and acceptable cosmetic results. We herein report a useful technique for obtaining symmetry of the breast shape and a level inframammary line and nipple-areola that achieved excellent results. Four Japanese patients with early breast cancer located on the upper inner area of the breast were enrolled into this study. De-epithelialized skin close to the resected area and skin from the epigastric area with subdermal fatty tissue were moved to repair the defect. Oncoplastic breast surgery (OBS) combining partial mastectomy with the V-rotation mammoplasty technique was useful for patients with breast cancer on the upper inner area of minimal ptotic breasts.


Asunto(s)
Neoplasias de la Mama/cirugía , Mama/cirugía , Mamoplastia/métodos , Mastectomía Segmentaria/métodos , Tratamientos Conservadores del Órgano/métodos , Adulto , Anciano , Mama/patología , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento
5.
Cancer Sci ; 111(12): 4359-4370, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32976661

RESUMEN

Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44+ cancer cells metastasized to the liver than those at the primary site. Knockdown of S100A10 in breast cancer cells suppressed and overexpression of S100A10 in breast cancer PDX cells enhanced their invasion abilities and 3D organoid formation capacities in vitro. Mechanistically, S100A10 regulated the matrix metalloproteinase activity and the expression levels of stem cell-related genes. Finally, constitutive knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers.


Asunto(s)
Anexina A2/metabolismo , Neoplasias de la Mama/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas S100/metabolismo , Regulación hacia Arriba , Animales , Anexina A2/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Receptores de Hialuranos/metabolismo , Lentivirus/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Metaloproteinasas de la Matriz/metabolismo , Ratones , Invasividad Neoplásica , Metástasis de la Neoplasia , Células Madre Neoplásicas/patología , Organoides , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas S100/genética
6.
Surg Today ; 50(12): 1707-1711, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32524271

RESUMEN

The treatment of early breast cancer using breast conservation therapy (BCT) commonly ensures local control and acceptable cosmetic results. We herein report a useful technique to obtain symmetry of the breast shape and a level inframammary line and nipple-areola, which achieved excellent results. Six Japanese patients with early breast cancer located on the upper area of the breast were enrolled into this study. A triangle-shaped area of skin was removed together with cancerous and healthy-surrounding breast tissue. Two crescents were designed and de-epithelialized in the directions of 9 o'clock and 3 o'clock. The width of the crescent was decided to be the same as a half or the length of the base of a triangle to be removed. After partial mastectomy, the inner and outer glandular flaps were horizontally sutured. The operations were simple to perform and were not associated with any postoperative complications. Oncoplastic breast surgery combining partial mastectomy with triangular skin resection and re-centralization of the nipple-areola was useful for patients with breast cancer on the upper quadrant area of non-ptotic breasts.


Asunto(s)
Neoplasias de la Mama/cirugía , Procedimientos Quirúrgicos Dermatologicos/métodos , Mastectomía Segmentaria/métodos , Pezones/cirugía , Procedimientos de Cirugía Plástica/métodos , Cirugía Plástica/métodos , Neoplasias de la Mama/patología , Femenino , Humanos , Márgenes de Escisión , Biopsia del Ganglio Linfático Centinela , Técnicas de Sutura , Resultado del Tratamiento
7.
Ann Surg Oncol ; 26(2): 644-651, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30523468

RESUMEN

BACKGROUND: A metabolic shift to glycolysis is reportedly involved in radioresistance. We examined whether pretreatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect enhanced glucose uptake, was able to predict the therapeutic response to chemoradiotherapy (CRT) in patients with pancreatic cancer (PC). METHODS: Of 125 PC patients (75 unresectable and 50 borderline resectable), 37 and 26 underwent induction chemotherapy before CRT and surgical resection after CRT, respectively. FDG-PET was performed at three different institutions. RESULTS: Of the 88 patients who underwent upfront CRT, 31 (35%), 34 (39%), and 23 (26%) showed a partial response (PR), stable disease, and progressive disease, respectively. The tumor PR rate was an independent factor associated with longer overall survival (OS) on multivariate analysis. We evaluated the optimal cut-off of maximum standardized uptake values (SUVmax) at initial diagnosis to detect the tumor PR rate at the three institutions separately. The SUVmax was independently associated with tumor response rate on multivariate analysis. In the low SUVmax group, induction chemotherapy had no significant impact on OS. In contrast, induction chemotherapy was significantly associated with longer OS in the high SUVmax group. CONCLUSIONS: FDG-PET SUVmax was significantly associated with the therapeutic response to CRT in PC patients. Moreover, induction chemotherapy may improve the prognosis of patients with a high SUVmax tumor.


Asunto(s)
Quimioradioterapia/métodos , Fluorodesoxiglucosa F18/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Anciano , Femenino , Estudios de Seguimiento , Glucólisis , Humanos , Masculino , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/metabolismo , Pronóstico , Tasa de Supervivencia , Carga Tumoral
8.
Cancer Sci ; 109(3): 814-820, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29345842

RESUMEN

Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis. This study assessed the clinical significance of PD-L1 mRNA expression in blood specimens obtained from patients with gastric cancer. Peripheral blood specimens were collected before treatment from 124 patients with gastric cancer. The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death-ligand 1 mRNA expression was significantly higher in patients with advanced gastric cancer than in patients with early gastric cancer (P = .002). Moreover, PD-L1 expression correlated significantly with depth of tumor invasion, distant metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients with high PD-L1 expression showed significantly poorer prognosis than those with low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1 expression as an independent prognostic factor. Expression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer.


Asunto(s)
Antígeno B7-H1/genética , Neoplasias Gástricas/genética , Regulación hacia Arriba , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/sangre , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Biopsia Líquida , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/sangre
9.
Cancer Sci ; 109(6): 2013-2026, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29660218

RESUMEN

We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre-miR-148a (miR-148a-5p: the passenger strand and miR-148a-3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR-148a-5p and miR-148a-3p significantly inhibited cancer cell migration and invasion, indicating that both strands of pre-miR-148a had tumor-suppressive roles in PDAC cells. In silico database and genome-wide gene expression analyses identified a total of 15 genes that were putative targets regulated by these miRNAs. High expression of miR-148a-5p targets (PHLDA2, LPCAT2 and AP1S3) and miR-148a-3p targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement of the passenger strand of pre-miR-148a (miR-148-5p) is a new concept in cancer research. Novel approaches that identify tumor-suppressive miRNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.


Asunto(s)
Carcinoma Ductal Pancreático/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias Pancreáticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Interferencia de ARN
10.
Biochim Biophys Acta Mol Basis Dis ; 1864(4 Pt A): 1060-1071, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29309924

RESUMEN

Metastatic breast cancer is a leading cause of cancer-related deaths in women worldwide. Patients with triple negative breast cancer (TNBCs), a highly aggressive tumor subtype, have a particularly poor prognosis. Multiple reports demonstrate that altered content of the multicopy mitochondrial genome (mtDNA) in primary breast tumors correlates with poor prognosis. We earlier reported that mtDNA copy number reduction in breast cancer cell lines induces an epithelial-mesenchymal transition associated with metastasis. However, it is unknown whether the breast tumor subtypes (TNBC, Luminal and HER2+) differ in the nature and amount of mitochondrial defects and if mitochondrial defects can be used as a marker to identify tumors at risk for metastasis. By analyzing human primary tumors, cell lines and the TCGA dataset, we demonstrate a high degree of variability in mitochondrial defects among the tumor subtypes and TNBCs, in particular, exhibit higher frequency of mitochondrial defects, including reduced mtDNA content, mtDNA sequence imbalance (mtRNR1:ND4), impaired mitochondrial respiration and metabolic switch to glycolysis which is associated with tumorigenicity. We identified that genes involved in maintenance of mitochondrial structural and functional integrity are differentially expressed in TNBCs compared to non-TNBC tumors. Furthermore, we identified a subset of TNBC tumors that contain lower expression of epithelial splicing regulatory protein (ESRP)-1, typical of metastasizing cells. The overall impact of our findings reported here is that mitochondrial heterogeneity among TNBCs can be used to identify TNBC patients at risk of metastasis and the altered metabolism and metabolic genes can be targeted to improve chemotherapeutic response.


Asunto(s)
ADN Mitocondrial , Mitocondrias , Proteínas Mitocondriales , Proteínas de Neoplasias , Proteínas de Unión al ARN , Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Femenino , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología
11.
J Hum Genet ; 63(12): 1197-1210, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30228364

RESUMEN

Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed the most dramatic downregulation. We then examined the antitumor roles of miR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays. AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer cell aggressiveness. We further analyzed downstream RNA networks regulated by AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.


Asunto(s)
Movimiento Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs/biosíntesis , ARN Neoplásico/biosíntesis , Neoplasias de la Mama Triple Negativas/metabolismo , Línea Celular Tumoral , Femenino , Estudio de Asociación del Genoma Completo , Humanos , MicroARNs/genética , Invasividad Neoplásica , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , ARN Neoplásico/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología
12.
Ann Surg Oncol ; 25(5): 1432-1439, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29404819

RESUMEN

BACKGROUND: This study aimed to examine the prognostic relevance of glucose transporter type 1 (GLUT-1), which is a key regulator of the glucose metabolism. In particular, the study aimed to examine the association between GLUT-1 expression and the therapeutic effect of chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with PDAC were enrolled in the study. Patients with distant metastases and those who received only chemotherapy as treatment were excluded from the study. Specimens for immunohistochemical evaluations were obtained through surgical resection and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the primary tumor before any treatment. RESULTS: This study included 197 patients. Of these 197 patients, 100 underwent upfront surgery, and 97 received neoadjuvant CRT (NACRT), which was performed mainly for patients with locally advanced tumors. Of the 97 patients who received NACRT, 21 later underwent surgical resection. For the patients who underwent upfront surgery, low GLUT-1 expression was an independent factor for a better prognosis. For the patients who underwent NACRT, low GLUT-1 expression was significantly associated with greater tumor size reduction, a higher resection rate, and a better prognosis. Additionally, GLUT-1 expression was significantly increased after NACRT treatment. CONCLUSIONS: Among the patients with PDAC, those with low GLUT-1 expression in the primary tumor had a better prognosis those with high GLUT-1 expression. Moreover, the patients with low GLUT-1 expression displayed a better therapeutic response to NACRT.


Asunto(s)
Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Transportador de Glucosa de Tipo 1/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Anciano , Carcinoma Ductal Pancreático/patología , Quimioradioterapia Adyuvante , Supervivencia sin Enfermedad , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Femenino , Humanos , Masculino , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas/patología , Tasa de Supervivencia
13.
Ann Surg Oncol ; 25(2): 449-455, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29188501

RESUMEN

BACKGROUND: While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not. METHODS: Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis. RESULTS: The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor. CONCLUSION: Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Quimioradioterapia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Terapia Neoadyuvante , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
14.
Langenbecks Arch Surg ; 403(1): 45-51, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28875312

RESUMEN

PURPOSE: Extrahepatic bile duct (EHBD) resection is performed as part of radical cholecystectomy for gallbladder (GB) cancer. However, the indication for EHBD resection is still controversial. The aim of the present study was to evaluate the prognostic value of this procedure. METHODS: Patients who underwent surgical resection for GB cancer with curative intent were enrolled. We divided GB cancer into two categories based on the tumor location: proximal-type and distal-type tumors. The former refers to tumors involving the neck or cystic duct, while the latter comprises tumors located between the body and fundus. RESULTS: This study included 80 patients, 40 each with proximal- and distal-type tumors. Proximal tumor location, lymph node metastasis, and a serum carcinoembryonic antigen level > 5.0 ng/mL were independent predictors of poor prognosis. The 5-year survival rates of patients with proximal-type and distal-type tumors were 33.3 and 73.5%, respectively. Patients with proximal-type tumors showed significantly lower rates of R0 resection, more frequently had ≥ 3 metastatic lymph nodes, and exhibited a higher rate of perineural invasion. EHBD resection improved prognoses only in patients with proximal-type tumors but not in those with distal-type tumors. In the former group, EHBD resection significantly reduced the rate of local or regional lymph node recurrence. CONCLUSIONS: Extended cholecystectomy with EHBD resection should be performed for patients with GB cancer involving the neck and cystic duct to reduce local and regional lymph node recurrence and achieve better prognosis.


Asunto(s)
Conductos Biliares Extrahepáticos/cirugía , Colecistectomía , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Hepatectomía , Selección de Paciente , Anciano , Anciano de 80 o más Años , Conductos Biliares Extrahepáticos/patología , Femenino , Neoplasias de la Vesícula Biliar/mortalidad , Humanos , Masculino , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
15.
Cancer Sci ; 108(2): 193-199, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27889946

RESUMEN

Patients with advanced esophageal squamous cell carcinoma (ESCC) is received chemoradiotherapy or chemotherapy for clinical management. However, it is difficult to predict tumor response and prognosis using blood markers before starting treatments. The purpose of this study was to investigate the pre-treatment plasma fibrinogen and neutrophil-lymphocyte ratio (NLR) in patients with advanced ESCC treated with chemoradiotherapy or chemotherapy, and to assess the clinical utility of a combined score using these blood markers, named as the F-NLR (fibrinogen and NLR) score, as a predictor of tumor response and prognosis. A total of 98 advanced ESCC patients, treated with chemoradiotherapy or chemotherapy, were classified into three groups: F-NLR score of 2, having both hyperfibrinogenemia (>400 mg/dL) and high NLR (>3.0), score of 1, one of these hematological abnormalities, and score of 0, having neither hyperfibrinogenemia nor high NLR. Fibrinogen and NLR were significantly higher in the progressive disease (PD) group than the non-PD group (P = 0.0419, and P = 0.0001, respectively). A significantly higher F-NLR score was found in the PD group than the non-PD group (P = 0.0140). Overall survival was significantly lower in patients with an F-NLR score of 2 than in those with an F-NLR score of 0 or 1 (P < 0.0001). Multivariate analysis showed that the F-NLR score was one of the independent prognostic factors (P = 0.0081). Our study demonstrates that the F-NLR score is promising as a predictive marker for therapeutic effects and prognosis in patients with advanced ESCC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Esofágicas/sangre , Fibrinógeno/análisis , Linfocitos , Neutrófilos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Proteína C-Reactiva/análisis , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Albúmina Sérica/análisis
16.
Gastric Cancer ; 20(5): 802-810, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28247164

RESUMEN

BACKGROUND: The E-cadherin, N-cadherin, and Snail genes are epithelial-mesenchymal transition (EMT)-inducible genes. Previous studies demonstrated that the expression of EMT markers in the primary tumor sites of gastric cancer correlates with tumor progression and prognosis. However, the clinical significance of the expression of these EMT markers in metastatic lymph nodes remains unclear. In the present study, we investigated the expression of these EMT markers in the primary tumor sites and metastatic lymph nodes. METHODS: Immunohistochemistry was used to investigate the expression of E-cadherin, N-cadherin, and Snail in 89 primary tumors and 511 metastatic lymph nodes obtained from patients with gastric cancer. RESULTS: The weak expression of E-cadherin in tumors and lymph nodes increased with more lymph node metastasis and in more undifferentiated tumors. The strong expression of N-cadherin in lymph nodes correlated with more lymph nodes metastasis, an advanced stage, and poor prognosis. The weak expression of Snail in tumors correlated with lymphatic invasion. The strong expression of Snail in lymph nodes correlated with more lymph node metastasis and an advanced stage. The strong expression of Snail in tumors and its weak expression in lymph nodes correlated with more lymph node metastasis, an advanced stage, and poor prognosis. CONCLUSIONS: The expression of N-cadherin in metastatic lymph nodes is useful for predicting the prognosis of patients with gastric cancer. The Snail switch-namely, the positive-to-negative conversion of the Snail status-between primary tumors and lymph node metastasis may be important for confirming EMT and mesenchymal-epithelial transition.


Asunto(s)
Cadherinas/genética , Factores de Transcripción de la Familia Snail/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD , Biomarcadores de Tumor/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología
17.
World J Surg ; 41(6): 1506-1512, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28168320

RESUMEN

BACKGROUND: Intraoperative identification of the difficult-to-spot parathyroid gland is critical during surgery for thyroid and parathyroid disease. Recently, intrinsic fluorescence of the parathyroid gland was identified, and a new method was developed for intraoperative detection of the parathyroid with an original fluorescent detection apparatus. Here, we describe a method for intraoperative detection of the parathyroid using a ready-made photodynamic eye (PDE) system without any fluorescent dye or contrast agents. METHODS: Seventeen patients who underwent surgical treatment for thyroid or parathyroid disease at Kagoshima University Hospital were enrolled in this study. Intrinsic fluorescence of various tissues was detected with the PDE system. Intraoperative in vivo and ex vivo intrinsic fluorescence of the parathyroid, thyroid, lymph nodes and fat tissues was measured and analyzed. RESULTS: The parathyroid gland had a significantly higher fluorescence intensity than the other tissues, including the thyroid glands, lymph nodes and fat tissues, and we could identify them during surgery using the fluorescence-guided method. Our method could be applicable for two intraoperative clinical procedures: ex vivo tissue identification of parathyroid tissue and in vivo identification of the location of the parathyroid gland, including ectopic glands. CONCLUSION: The PDE system may be an easy and highly feasible method to identify the parathyroid gland during surgery.


Asunto(s)
Enfermedades de las Paratiroides/cirugía , Glándulas Paratiroides/cirugía , Enfermedades de la Tiroides/cirugía , Adulto , Anciano , Femenino , Fluorescencia , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de las Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/diagnóstico por imagen , Enfermedades de la Tiroides/diagnóstico por imagen
18.
Langenbecks Arch Surg ; 402(1): 87-93, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27491729

RESUMEN

PURPOSE: The purpose of this retrospective study was to evaluate the relationship between the surgical margin status of the bile duct and the prognosis and recurrence of extrahepatic bile duct (EHBD) cancer. METHODS: The clinical data of 100 patients who underwent surgery for EHBD cancer between February 2002 and September 2014 were analyzed. The ductal margin status was classified into the following three categories: negative (D-N), positive with carcinoma in situ (D-CIS), and positive with invasive carcinoma (D-INV). RESULTS: The number of patients with D-N, D-CIS, and D-INV was 69, 16, and 15, respectively. Local recurrence rates of patients with D-CIS (56.3 %) and D-INV (66.7 %) were significantly higher compared to those of patients with D-N (10.1 %; P < 0.001). D-CIS was a significant predictor of shorter recurrence-free survival (RFS). Lymph node metastasis (P = 0.037) and D-INV (P = 0.008) were independent predictors of shorter disease-specific survival (DSS). The prognostic relevance of the ductal margin status was high, particularly in patients without lymph node metastasis. CONCLUSION: The surgical margin status of the bile duct was significantly associated with RFS, DSS, and the recurrence site.


Asunto(s)
Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Extrahepáticos , Carcinoma/patología , Carcinoma/cirugía , Márgenes de Escisión , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Carcinoma/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
19.
Oncology ; 90(4): 186-92, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26981856

RESUMEN

OBJECTIVE: We assessed the clinical applicability of the F-NLR score, which is based on fibrinogen (F) and the neutrophil-lymphocyte ratio (NLR), and the Glasgow Prognostic Score (GPS) to predict the therapeutic effects of chemotherapy or chemoradiotherapy on advanced gastric cancer and the prognoses of patients. METHODS: Sixty-eight patients with advanced gastric cancer treated with first-line chemotherapy or chemoradiotherapy were classified into two groups based on tumor response. Furthermore, we categorized patients according to cutoff F-NLR scores of 2 [hyperfibrinogenemia (>400 mg/dl) and high NLR (>3.0)], 1 [one of these hematological abnormalities], and 0 [neither hyperfibrinogenemia nor high NLR]. RESULTS: A total of 27 patients had progressive disease (PD) and 41 did not. The F-NLR scores were significantly higher in the PD than in the non-PD group (p = 0.003). Survival was significantly shorter for patients with high F-NLR scores and GPS (p = 0.0071 and p = 0.0065, respectively). Multivariate analysis selected the F-NLR score as an independent prognostic factor (p = 0.017). CONCLUSION: A novel grading system based on F-NLR scores, as well as the GPS, appears to have value as a clinical predictor of the therapeutic response of advanced gastric cancer to chemotherapy or chemoradiotherapy and the prognoses of patients.


Asunto(s)
Fibrinógeno/metabolismo , Linfocitos/citología , Neutrófilos/citología , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Cisplatino/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/radioterapia , Resultado del Tratamiento
20.
Int J Clin Oncol ; 21(5): 934-939, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26894390

RESUMEN

BACKGROUND: An association between inflammation and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the influence of preoperative biliary drainage-related inflammation in patients with biliary tract cancer. METHODS: The clinical data of 97 patients who underwent surgery for extrahepatic bile duct cancer between February 2002 and September 2014 were analyzed, and the prognostic significance of tube-obstructive cholangitis after preoperative biliary drainage and pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) was evaluated. RESULTS: Eighty-four (86.6 %) of the 97 patients underwent ERCP and preoperative biliary drainage. Tube-obstructive cholangitis occurred in 25 cases and post-ERCP pancreatitis in 8 cases. Collectively, 30 patients experienced preoperative biliary drainage-related inflammation consisting of tube-obstructive cholangitis and/or post-ERCP pancreatitis. Drainage-related inflammation was significant risk factor of postoperative complications (P = 0.006), and significant poor predictors of shorter progression-free survival (P = 0.003) and overall survival (OS; P = 0.006) after surgery. In multivariate analysis, drainage-related inflammation was an independent predictor of shorter OS (hazard ratio, 1.924; P = 0.037) after surgery. CONCLUSION: Preoperative biliary drainage-related inflammation was an independent prognostic factor for shorter OS in biliary tract cancer patients.


Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Extrahepáticos , Colangitis/complicaciones , Pancreatitis/complicaciones , Complicaciones Posoperatorias/etiología , Anciano , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangitis/etiología , Supervivencia sin Enfermedad , Drenaje/efectos adversos , Femenino , Humanos , Masculino , Pancreatitis/etiología , Cuidados Preoperatorios/efectos adversos , Pronóstico , Factores de Riesgo , Tasa de Supervivencia
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