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Masaru Morita,
Hajime Otsu,
Hiroyuki Kawano,
Yuta Kasagi,
Yasue Kimura,
Hiroshi Saeki,
Koji Ando,
Satoshi Ida,
Eiji Oki, Eriko Tokunaga,
Tetsuo Ikeda,
Tetsuya Kusumoto,
Yoshihiko Maehara
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ABSTRACT: PURPOSE: The purpose of this study was to clarify the gender differences in the prognosis, as well as mortality and morbidity, of patients who have undergone esophagectomy for esophageal cancer. METHODS: The clinical results of esophagectomy were compared between 975 male and 156 female patients with esophageal cancer. RESULTS: The male to female ratios of cervical and thoracic esophageal cancer were 1.87 and 7.38, respectively (P < 0.01). The incidence of preoperative comorbidities was 32.4 and 17.4 %, respectively, and the rates of both tobacco and alcohol abuse were significantly lower in the females than in the males. The mortality rate was lower in the females (3.8 %) than in the males (5.7 %), although the differences were not significant. The overall survival was significantly better in the female than in the male patients (P = 0.039). The 5- and 10-year overall survival rates were 32.6 and 20.5 % in the males and 39.5 and 32.5 % in the females, respectively. A multivariate analysis revealed gender to be an independent prognostic factor. However, no significant differences were recognized in disease-specific survival. CONCLUSIONS: These results suggest that the prognosis of females with esophageal cancer is better than that of males after esophagectomy, most likely due to multiple clinical factors, such as a more favorable lifestyle and general status.
Surgery Today 04/2013; · 1.22 Impact Factor
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Masaru Morita,
Hajime Otsu,
Hiroyuki Kawano,
Ryuichi Kumashiro,
Kenji Taketani,
Yasue Kimura,
Hiroshi Saeki,
Koji Ando,
Satoshi Ida,
Eiji Oki, Eriko Tokunaga,
Tetsuo Ikeda,
Tetsuya Kusumoto,
Yoshihiko Maehara
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ABSTRACT: Aim: To justify esophagectomy for elderly patients.
A total of 1,002 patients with thoracic esophageal cancer who underwent esophagectomy were divided into three groups: I (≤74 years old, n=898); II (75-79 years, n=81); and III (≥80 years, n=23). Historical changes were compared between the first surgical period (1964-1989) and the second period (1990-2011).
The morbidity rates were 40%, 41% and 26% in the respective groups. Pulmonary complications decreased historically in groups II and III (36% to 15% and 43% to 0%, respectively). The mortality was higher in the older groups (4.8%, 8.6% and 13.0%, respectively); however, there was a marked historical decrease in groups II (18.2% to 5.1%) and III (28.6% to 6.3%). The 5-year survival improved from 5% to 35% in group II and from 0% to 17% in group III.
The outcomes of esophagectomy for elderly patients have markedly improved, with acceptable mortality even in octogenarians.
Anticancer research 04/2013; 33(4):1641-7. · 1.73 Impact Factor
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Fusanori Yotsumoto, Eriko Tokunaga,
Eiji Oki,
Yoshihiko Maehara,
Hiromi Yamada,
Kyoko Nakajima,
Sung Ouk Nam,
Kohei Miyata,
Midori Koyanagi,
Keiko Doi,
Senji Shirasawa,
Masahide Kuroki,
Shingo Miyamoto
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ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is one of several pro-angiogenic factors, and represents a possible therapeutic target for patients with triple-negative breast cancer (TNBC). However, the role of HB-EGF in promoting tumor aggressiveness in TNBC remains unclear. In order to investigate specific genes and pathways involved in TNBC tumorigenesis, we profiled gene expression changes in two TNBC cell lines under two-dimensional culture (2DC) and three-dimensional culture (3DC) and in a tumor xenograft model. We identified simultaneous upregulation of HB-EGF, vascular endothelial growth factor A (VEGFA) and angiopoietin-like 4 (ANGPTL4) in 3DC and tumor xenografts, compared with 2DC. We show that HB-EGF regulates the expression of VEGFA or ANGPTL4 via transcriptional regulation of hypoxia inducible factor-1 alpha and nuclear factor kappa B. Furthermore, suppression of VEGFA or ANGPTL4 expression enhanced HB-EGF expression, highlighting a unique regulatory loop underlying this angiogenesis network. Targeted knockdown of HB-EGF significantly suppressed tumor formation in a TNBC xenograft model, compared with individual knockdown of either VEGFA or ANGPTL4, by reducing the expression of both VEGFA and ANGPTL4. In patients with TNBC, VEGFA or ANGPTL4 expression was also significantly correlated with HB-EGF expression. Low concentrations of exogenously added HB-EGF strongly activated the proliferation of endothelial cells, tube formation and vascular permeability in blood vessels, in a similar fashion to high doses of VEGFA and ANGPTL4. Taken together, these results suggest that HB-EGF plays a pivotal role in the acquisition of tumor aggressiveness in TNBC by orchestrating a molecular hierarchy regulating tumor angiogenesis.
Molecular Cancer Research 02/2013; · 4.29 Impact Factor
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ABSTRACT: PURPOSE: Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, is a highly heterogeneous disease. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin, one of the most major factors associated with EMT was investigated in TNBC. MATERIALS AND METHODS: Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14 %) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: The mRNA expression of vimentin was significantly upregulated in the basal-type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p = 0.0042) in TNBC compared with the other subtypes. Vimentin expression was associated with a younger age (p = 0.016), high nuclear grade (p = 0.023) and high Ki67 expression (p < 0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p = 0.0058) and overall survival (OS) (p = 0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p = 0.043). Vimentin expression was also associated with a significantly shorter RFS (p = 0.021) and OS (p = 0.017) in patients with basal-like breast cancer (BLBC). CONCLUSIONS: The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.
Journal of Cancer Research and Clinical Oncology 01/2013; · 2.56 Impact Factor
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ABSTRACT: Breast magnetic resonance imagings (MRIs) including diffusion-weighted MRI (DWI) of 110 breast cancers (26 with pathologically proven axillary node metastasis and 84 without metastasis) were retrospectively studied. Axillary nodes were detected as high-signal-intensity areas on DWI in 71 cancers (24 with metastasis and 47 without) and not detected in 39 cancers (2 with metastasis and 37 without). The ADC of metastatic nodes was significantly greater than that of the benign ones (1.08±0.18×10(-3) mm(2)/s vs. 0.92±0.22×10(-3) mm(2)/s, P=.004). When detectability of axillary nodes on DWI and ADC over 1.05×10(-3) mm(2)/s was applied as a threshold, 53.8% sensitivity, 86.9% specificity, and 79.1% accuracy were provided.
Clinical imaging 01/2013; 37(1):56-61. · 0.73 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 09/2012; 70 Suppl 7:438-42.
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ABSTRACT: BACKGROUND: Metadherin (MTDH) plays functional roles in the tumorigenesis and tumor progression of various cancers. This study investigated the associations between MTDH and the clinicopathological features in primary breast carcinomas to clarify the role of MTDH in the phenotypes and prognosis of breast cancer. METHODS: A total of 195 primary invasive breast cancer samples were evaluated. The MTDH DNA copy number and MTDH mRNA expression were analyzed by quantitative genomic polymerase chain reaction (PCR) and quantitative reverse transcriptase PCR. MTDH protein expression was analyzed by immunohistochemistry. RESULTS: A positive correlation was found between the expression of MTDH protein and mRNA expression and the MTDH DNA copy number. MTDH overexpression was significantly associated with a high nuclear grade, negative estrogen receptor (ER) and progesterone receptor (PR) expression, high Ki67 index, poor disease-free survival (P = 0.0001), poor distant metastasis-free survival (P = 0.009), and poor overall survival (P = 0.0101). MTDH overexpression showed a particularly negative impact on the prognosis in node-negative patients. A multivariate analysis showed MTDH overexpression to be independently associated with a poor disease-free survival rate [HR 3.45, 95 % confidence interval (CI) 1.69-6.84, P = 0.0010] and a poor distant metastasis-free survival rate (HR 2.39, 95 % CI 1.08-5.01, P = 0.0319). CONCLUSION: MTDH overexpression contributes to an aggressive phenotype, thus leading to a poor prognosis for primary invasive breast cancer.
Breast Cancer 08/2012; · 1.36 Impact Factor
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ABSTRACT: Fanconi anemia protein, FANCJ, directly interacts with MLH1, a key protein involved in DNA mismatch repair. Deficient mismatch repair, or microsatellite instability, is a potent marker for the ineffectiveness of 5-fluorouracil (5-FU) in colorectal cancer (CRC). We investigated the significance of FANCJ expression in CRC, focusing on the effects of 5-FU-based adjuvant chemotherapy.
Clinicopathologic features and immunohistochemical expression of FANCJ and MLH1 were studied in 219 patients with CRC. We also analyzed 5-FU sensitivity in CRC cell lines with varying levels of FANCJ expression.
FANCJ expression was elevated in tumor tissues compared with normal epithelial tissue. High expression of FANCJ was significantly associated with 5-FU resistance measured by the SDI test (P < 0.05) and poor recurrence-free survival (RFS) (P < 0.05). Among patients with stage II/III tumors who received 5-FU, patients with tumors exhibiting high FANCJ expression had significantly worse RFS than did patients with tumors exhibiting low FANCJ expression (P < 0.01). Among patients who did not receive adjuvant chemotherapy, FANCJ expression was not correlated with RFS (P = 0.76). High FANCJ expression was correlated with 5-FU resistance in tumors with normal MLH1 expression (P < 0.05) but not in tumors not expressing MLH1 (P = 0.9). In vitro, FANCJ overexpression was correlated with 5-FU resistance in MLH1-proficient HCT116 3-6 cells but not in MLH1-deficient HCT116 cells.
FANCJ could be a useful biomarker to predict the response to 5-FU and prognosis of CRC, particularly in tumors with normal MLH1 expression.
Annals of Surgical Oncology 04/2012; 19(11):3627-35. · 4.17 Impact Factor
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ABSTRACT: BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common.
LOH at BRCA1 and BRCA2 loci were investigated in 202 Japanese invasive breast cancer patients. The relationships between LOH at these gene loci and clinicopathologic characteristics were analyzed.
Among 166 informative cases for both BRCA1 and BRCA2 loci, 69 (41.6%) and 52 (31.3%) tumors revealed LOH at BRCA1 and BRCA2 loci, respectively. LOH at BRCA1 LOH or BRCA2 locus was associated with higher nuclear grade (P < 0.0001, P = 0.0187). LOH at BRCA1 locus was associated with estrogen receptor and progesterone receptor negativity (P = 0.001 and P = 0.015) and significantly shorter disease-free survival (P < 0.0001), distant metastasis-free survival (P < 0.0001), and overall survival (P < 0.0001). In contrast, LOH at BRCA2 locus had no associations with estrogen receptor or progesterone receptor status and prognosis. LOH at BRCA1 locus was independently associated with poor prognosis in terms of disease-free survival (hazard ratio 3.08, 95% confidence interval [CI] 1.58-6.18, P = 0.0009), distant metastasis-free survival (hazard ratio 5.18, 95% CI 2.35-12.19, P < 0.0001), and overall survival (hazard ratio 4.97, 95% CI 1.84-15.1, P = 0.0013).
LOH at BRCA1 locus could be an independent prognostic biomarker useful in identifying a subgroup of patients with poor prognosis.
Annals of Surgical Oncology 12/2011; 19(5):1499-507. · 4.17 Impact Factor
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ABSTRACT: Assessing indications for adjuvant chemotherapy (CT) in patients with hormone receptor (HR)-positive/human epidermal receptor 2 (HER2)-negative breast cancer remains a challenge for oncologists. In this study, we evaluated whether forkhead-box protein A1 (FOXA1) expression was a prognostic and predictive marker for HR-positive breast cancer.
FOXA1 expression was analyzed immunohistochemically in 239 primary breast cancers. Associations between FOXA1 expression and clinicopathological characteristics and prognosis were evaluated.
FOXA1 expression was positively correlated with estrogen receptor (ER) (P<0.0001) and progesterone receptor (PR) expression (P=0.0011), and inversely correlated with nuclear grade (P=0.0048) and Ki67 index (P=0.0112). High FOXA1 was associated with longer recurrence-free survival (RFS) in all cases (P<0.0001) and in ER-positive cases (P<0.0001), but not in ER-negative cases. In addition, FOXA1 expression was associated with good prognosis, regardless of the Ki67 index, in HR-positive cases. FOXA1 was an independent prognostic factor on multivariate analysis in all cases and in ER-positive cases. Among HR-positive/HER2-negative cases with high FOXA1 expression, there was no difference in RFS between those given hormone therapy (HT) alone and those given CT plus HT.
In HR-positive breast cancer, FOXA1 expression was significantly associated with good prognosis. FOXA1 expression may be a useful marker for HR-positive/HER2-negative breast cancer to identify patients with good prognosis who may not require CT.
Annals of Surgical Oncology 10/2011; 19(4):1145-52. · 4.17 Impact Factor
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Hidetake Yabuuchi,
Yoshio Matsuo,
Shunya Sunami,
Takeshi Kamitani,
Satoshi Kawanami,
Taro Setoguchi,
Shuji Sakai,
Masamitsu Hatakenaka,
Makoto Kubo, Eriko Tokunaga,
Hidetaka Yamamoto,
Hiroshi Honda
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ABSTRACT: To compare the detectability of non-palpable breast cancer in asymptomatic women by using mammography (MMG), dynamic contrast-enhanced MR imaging (DCE-MRI) and unenhanced MR imaging with combined diffusion-weighted and T2-weighted images (DWI+T2WI).
Forty-two lesions in 42 patients with non-palpable breast cancer in asymptomatic women were enrolled. For the reading test, we prepared a control including 13 normal and 8 benign cases. Each imaging set included biplane MMG, DCE-MRI and DWI+T2WI. Five readers were asked to rate the images on a scale of 0 to 100 for the likelihood of the presence of cancer and the BI-RADS category. Confidence level results were used to construct receiver operating characteristic analysis. Sensitivity and specificity were calculated for each technique.
DWI+T2WI showed higher observer performances (area under the curve, AUC, 0.73) and sensitivity (50%) for the detection of non-palpable breast cancer than MMG alone (AUC 0.64; sensitivity 40%) but lower than those of DCE-MRI (AUC 0.93; sensitivity 86%). A combination of MMG and DWI+T2WI exhibited higher sensitivity (69%) compared with that of MMG alone (40%).
DWI+T2WI could be useful in screening breast cancer for patients who cannot receive contrast medium and could be used as a new screening technique for breast cancer.
European Radiology 01/2011; 21(1):11-7. · 3.22 Impact Factor
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ABSTRACT: Basal-like and HER2-overexpressing breast carcinomas are histologically undifferentiated, high-grade tumors with a high proliferation rate and associated with a poor outcome. Most basal-like tumors lack the expression of ER, PR, and HER2 (triple-negative; TN). Loss of heterozygosity (LOH) is thought to reflect random chromosomal instability, and recent studies have shown that DNA-copy number alterations or LOH occur with a high frequency in basal-like and HER2-amplified tumors.
The levels and patterns of LOH were analyzed by the microsatellite alteration analysis using fluorescence-labeled primers and an automated DNA sequencer at 5 randomly selected loci in 246 Japanese primary breast cancers. Associations between the level of LOH and breast cancer subtypes and tumor aggressiveness were investigated.
The incidence and frequency of LOH was significantly higher in HER2 (56.3, 26.7%) and TN groups (44.4, 27.1%) than in luminal A (ER-positive and/or PR-positive and HER2-negative) groups (32.0, 12.2%). The incidence and frequency of LOH increased as nuclear grade was elevated. There were significantly more grade 3 tumors in the HER2 (80.0%) and TN (68.2%) subgroups (p < 0.0001). Even in HER2 and TN cases, the incidence and frequency of LOH was significantly higher in nuclear grade 3 cases than in grade 1 or 2 cases. Relapse-free survival of patients with LOH was significantly shorter than for those without LOH. In addition, the survival time was shorter as the frequency of LOH elevated. The incidence of LOH was an independent prognostic factor for relapse-free survival by multivariate analysis.
High incidence and frequency of LOH, which indicate increased genetic instability, were found to be associated with the aggressive features of high-grade HER2 and TN breast cancers.
Breast Cancer 11/2010; 19(2):161-9. · 1.36 Impact Factor
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ABSTRACT: The aim of this study was to report on the early experiences using a real-time 3-dimensional (3D) virtual reality navigation system with open MRI for breast-conserving surgery.
We developed a real-time 3D virtual reality navigation system with open MRI, and evaluated the mismatch between the navigation system and real distance using a 3D phantom. Two patients with nonpalpable MRI-detected breast tumors underwent breast-conserving surgery under the guidance of the navigation system. An initial MRI for the breast tumor using skin-affixed markers was performed immediately before excision. A percutaneous intramammary dye marker was applied to delineate an excision line, and the computer software "3D Slicer" generated a real-time 3D virtual reality model of the tumor and the puncture needle in the breast. Excision of the tumor was performed in the usual manner along the excision line indicated with the dye. The resected specimens were carefully examined histopathologically.
The mean mismatch between the navigation system and real distance was 2.01 +/- 0.32 mm when evaluated with the 3D phantom. Under guidance by the navigation system, a percutaneous intramammary dye marker was applied without any difficulty. Fiducial registration errors were 3.00 mm for patient no. 1, and 4.07 mm for patient no. 2. Histopathological examinations of the resected specimens of the 2 patients showed noninvasive ductal carcinoma in situ. The surgical margins were free of carcinoma cells.
Real-time 3D virtual reality navigation system with open MRI is feasible for safe and accurate excision of nonpalpable MRI-detected breast tumors. Long-term outcomes of this technique should be evaluated further.
Journal of the American College of Surgeons 06/2010; 210(6):927-33. · 4.55 Impact Factor
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ABSTRACT: A number of therapeutic strategies targeting epidermal growth factor receptor (EGFR) have not always led to success in the present state of breast cancer therapy. Notably, there is currently no way to treat trastuzumab-resistant and triple-negative breast cancer (TNBC). Here, we found that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGFR ligands, was predominantly expressed in breast cancer and that treatment with crossreacting material 197 (CRM197), a specific inhibitor of HB-EGF, blocked ERK as well as AKT activation via complexes of EGFR and unknown growth factor receptors in TNBC or through complexes of EGFR and human epidermal growth factor receptor-2 in trastuzumab-resistant breast cancer, caused significant cell apoptosis and inhibited tumor growth. Accordingly, we can provide a novel concept that a certain EGFR ligand is recognized as a rational target against breast cancer. In addition, it is plausible that CRM197 could be an effective anticancer agent for molecularly targeted therapies.
International Journal of Cancer 05/2010; 127(11):2707-17. · 5.44 Impact Factor
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Jeong-Hun Kang,
Yoji Asami, Masaharu Murata,
Hirotaro Kitazaki,
Noriaki Sadanaga, Eriko Tokunaga,
Satoko Shiotani,
Satoko Okada,
Yoshihiko Maehara,
Takuro Niidome,
Makoto Hashizume,
Takeshi Mori,
Yoshiki Katayama
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ABSTRACT: A novel gold nanoparticle (GNP)-based colorimetric assay was developed for cancer diagnosis. This system is based on the noncrosslinking aggregation mechanism with a cationic protein kinase C (PKC) alpha-specific peptide substrate, which is used as a coagulant of citrate-coated GNP with anionic surface charges. The phosphorylation of peptide substrates by PKCalpha suppressed GNP aggregation, resulting in a red color, but in the case of non-phosphorylation, the color of the GNP solution changed from red to blue, indicating particle aggregation. Moreover, a correlation between the color change of the GNP dispersions and the level of activated PKCalpha was identified from experiments using cancer cell lines, or xenografted mouse cancer and normal mouse tissues. When our system was applied to human breast cancers and normal human breast tissues, cancer tissue lysates became red in color, indicating GNP dispersion, while all lysates from normal tissue turned the GNP solution blue. MALDI-TOF MS analysis and Western blotting experiment confirmed that these different results between cancer and normal tissues reflected the difference in PKCalpha activity. This study is the first report on the application of the GNP-based colorimetric assay to the diagnosis of cancer.
Biosensors & bioelectronics 12/2009; 25(8):1869-74. · 5.43 Impact Factor
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ABSTRACT: The link between BRCA1 dysfunction and basal-like breast cancer or triple-negative breast cancer (TNBC) has been suggested; however, the associations of other factors involved in the Fanconi anemia (FA)/BRCA pathway with the pathogenesis of basal-like breast cancer remain unidentified. FANCF protein is a component of the FA core complex. The methylation of CpG islands in the FANCF gene plays an important role in occurrence of ovarian cancer and also is an important regulator of cisplatin sensitivity of ovarian cancer. The purpose of this study is to investigate the frequency of FANCF methylation, and to discuss its involvement in the pathogenesis of TNBC and its potency as a predictor of cisplatin sensitivity for breast cancer.
The methylation of the FANCF gene promoter was investigated, using methylation-specific PCR, in genomic DNA of 99 invasive breast carcinoma specimens obtained from Japanese patients.
FANCF methylation was recognized in only 4 of 99 cases (4.0%). No significant correlation was found between FANCF methylation and the expression of ER, PR, HER2, and TNBC.
FANCF methylation is a rare event in Japanese primary invasive breast cancer. This suggests it is not involved in the pathogenesis of TNBC, and it could not be used as a predictor of cisplatin sensitivity in breast cancer.
Breast Cancer 10/2009; 18(2):120-3. · 1.36 Impact Factor
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Hidetake Yabuuchi,
Yoshio Matsuo,
Takeshi Kamitani,
Taro Setoguchi,
Takashi Okafuji,
Hiroyasu Soeda,
Shuji Sakai,
Masamitsu Hatakenaka,
Makoto Kubo, Eriko Tokunaga,
Hidetaka Yamamoto,
Hiroshi Honda
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ABSTRACT: To evaluate the diagnostic accuracy of a combination of dynamic contrast-enhanced MR imaging (DCE-MRI) and diffusion-weighted MR imaging (DWI) in characterization of lesions showing non-mass-like enhancement on breast MR imaging and to find the strongest discriminators between carcinoma and benignancy.
We analyzed consecutive MR images in 45 lesions showing non-mass like enhancement in 41 patients. We analyzed lesion size, distribution, internal enhancement, kinetic curve pattern, and apparent diffusion coefficient (ADC) values. We applied univariate and multivariate analyses to find the strongest indicators for malignancy. In a validation study, 22 non-mass-like enhancement lesions in 21 patients were examined. We calculated diagnostic accuracy when we presume category 4b, 4c, and 5 lesions as malignant or high to moderate suspicion for malignancy, and category 4a and 3 as low suspicion for malignancy or benign.
Segmental distribution (P=0.018), clumped internal enhancement (P=0.005), and ADC less than 1.3 x 10(-3) mm(2)/s (P=0.047) were the strongest MR indicators of malignancy. In a validation study, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87% (13/15), 86% (6/7), 93% (13/14), 75% (6/8) and 86% (19/22), respectively.
The combination of DCE-MRI and DWI showed high diagnostic accuracy in characterization of non-mass-like enhancement lesions on breast MR images.
European journal of radiology 09/2009; 75(1):e126-32. · 2.65 Impact Factor
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ABSTRACT: The factors associated with the clinical results of preoperative chemoradiotherapy (CRT) for esophageal cancer and its effect on postoperative complications are still unclear.
The 686 patients with esophageal cancer were classified into 376 who received preoperative CRT (group I) and 310 who received surgery alone (group II).
A multivariate analysis for group I patients revealed pathologically complete response to be a favorable prognostic factor. Preoperative use of cisplatin was significantly associated with pathological effect and patients' prognosis. Both pulmonary complications and anastomotic leakage more frequently developed in group I (16.0 and 27.9%) than in group II (10.0%, p<0.05 and 16.5%, p<0.01, respectively). A multivariate analysis revealed preoperative CRT to be an independent factor of postoperative complications.
Although preoperative CRT for esophageal cancer may be associated with postoperative complications, a pathologically complete response, which is associated with a cisplatin-based regimen, is critical for improving patient prognosis.
Anticancer research 07/2009; 29(7):2555-62. · 1.73 Impact Factor
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ABSTRACT: To examine the methylation status of the promoter region of the checkpoint with forkhead-associated and ring finger (CHFR) and microsatellite mutator status in 59 primary gastric cancers.
We investigated the promoter methylation of CHFR in 59 cases of gastric cancer using methylation-specific PCR. Five microsatellite loci were analyzed using high-intensity microsatellite analysis reported previously, and p53 gene mutations were investigated by direct sequencing.
Twenty cases (33.9%) showed promoter methylation and no relation was observed with the clinicopathological factors. We found that the promoter methylation of CHFR was frequently accompanied with microsatellite instability (MIN). Seven of 20 (35.0%) cases showed MIN in hypermethylation of the CHFR tumor, while three of 39 (7.7%) cases showed MIN in the non-methylated CHFR tumor (P < 0.01). However, we failed to find any relationship between CHFR methylation and p53 mutation status.
The coordinated loss of both the mitotic check point function and mismatch repair system suggests the potential to overcome the cell cycle check point, which may lead to an accumulation of mutations. However, the p53 mutation was not related to hypermethylation of the CHFR promoter and MIN, which indicates that an abnormality in p53 occurs as an independent process from the mismatch repair deficiency in carcinogenesis.
World Journal of Gastroenterology 05/2009; 15(20):2520-5. · 2.47 Impact Factor
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Hiroyuki Kitao,
Yoshihiko Fujinaka,
Nobuhide Kubo,
Tomonori Nakanoko,
Keiji Yoshinaga, Eriko Tokunaga,
Hiroshi Saeki,
Kazuya Endo,
Masaru Morita,
Yoshihiro Kakeji,
Yoshihiko Maehara
Fukuoka igaku zasshi = Hukuoka acta medica 07/2008; 99(6):115-22.
