High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer

Aneuploidy is a result of the abnormal expression of spindle assembly checkpoint (SAC) proteins and resulting abnormal spindle function during mitosis. High expression of cell division cycle 20 homolog (CDC20) and mitotic arrest defective protein 2 (MAD2), key components of the SAC, has been reported in various carcinomas. However, the clinicopathological significance of CDC20 and MAD2 expressions in urothelial carcinoma of the human bladder (UCB) is unknown. We therefore studied the expression of CDC20 and MAD2 in UCB specimens by immunohistochemistry. High expression of CDC20 and MAD2 was observed in 59.0 % (200/339) and 51.0 % (173/339) of UCB cases, respectively. Most high-grade tumor cells exhibited diffuse nuclear and/or cytoplasmic staining for CDC20 and MAD2, whereas most low-grade tumor cells and normal urothelial cells were not stained. CDC20 overexpression was associated with advanced age (p?=?0.010), high grade (p?<?0.001), advanced stage (p?<?0.001), non-papillary growth pattern (p?<?0.001), and distant metastasis (p?=?0.042). Similarly, high MAD2 expression correlated with high grade (p?<?0.001), advanced stage (p?<?0.001), and non-papillary growth pattern (p?<?0.001). In univariate survival analyses, high CDC20 expression correlated with shorter recurrence-free survival (RFS) (p?=?0.032) and poorer overall survival (OS) (p?=?0.007) in patients with UCB, whereas high MAD2 expression was associated with poorer OS (p?=?0.008). In multivariate analyses, high CDC20 expression correlated with shorter RFS of patients with Ta stage UCB (hazard ratio, 1.91; p?=?0.01). In conclusion, increased expression of CDC20 and MAD2 is related to poor prognosis of UCB.     

Factors affecting metastases to non-sentinel lymph nodes in breast cancer

AIMS: Because sentinel lymph node (SLN) biopsy for breast cancer has become well established, one of the challenges now is to determine which patients require a completion axillary dissection following a positive SLN biopsy. METHODS: A prospective database of patients who underwent SLN biopsy for invasive breast cancer from July 1999 to November 2002 (n = 180) was analysed. Fifty four patients (30%) had one or more positive SLN, and all underwent a completion axillary dissection. This subgroup was further analysed to delineate which factors predicted non-SLN metastasis. RESULTS: Twenty six of the 54 patients with a positive SLN had additional metastases in non-SLNs. Significant variables that predicted non-SLN metastasis included extranodal extension (odds ratio (OR), 17.399; 95% confidence interval (CI), 1.69 to 178.96) and macrometastasis within the SLN (OR, 6.985; 95% CI, 1.291 to 37.785). CONCLUSIONS: In patients with invasive breast cancer and a positive SLN, extranodal extension or macrometastasis within the SLN were both independent predictors of non-SLN involvement.     

乳腺癌非前哨淋巴结转移的预测

目的 :预测非前哨淋巴结 (non SLN)转移 ,以筛选出转移局限于前哨淋巴结 (SLN)的乳腺癌患者。方法 :采用99mTc SC作为示踪剂 ,对 95例乳腺癌患者行前哨淋巴结活检 ,对乳腺癌非前哨淋巴结转移进行单因素和多因素分析。结果 :95例患者中成功发现 91例患者有SLN (95 8% ) ,其中 85例患者SLN能准确反映腋窝淋巴结的病理状况 (93 4% )。临床肿块大小(P =0 0 2 8)、肿瘤分级 (P =0 0 40 )和原发灶cyclinD1蛋白 (P =0 0 17)的表达与non SLN转移显著相关。而Logistic多因素分析证实 ,临床肿块大小、肿瘤分级为独立的预测非前哨淋巴结转移的因子。结论 :可根据临床病理学特征 ,筛选出乳腺癌转移只局限于前哨淋巴结的患者 ,也存在免除腋窝淋巴结清扫的可能性     

Leishmania donovani-specific 25- and 28-kDa urinary proteins activate macrophage effector functions, lymphocyte proliferation and Th1 cytokines production

Growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. Notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. In this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation. A total four proteins of molecular mass 25, 28, 54 and 60 kDa were identified in human urine samples. The 25 and 28 kDa proteins significantly induced NADPH oxidase (p?<?0.001), superoxide dismutase (p?<?0.001) and inducible nitric oxide synthase (p?<?0.001) activities in stimulated RAW264.7 macrophages. The release of nitric oxide, tumor necrosis factor-alpha and interleukin (IL)-12 was also significantly (p?<?0.001) higher in 25 and 28 kDa activated macrophages as compared with cells activated with other two proteins. These two proteins also induced significant (p?<?0.001) proliferation and release of IFN-γ and IL-12 in human peripheral blood mononuclear cells.     

Dipyridamole prevents triple-negative breast-cancer progression

Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated β-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkBα (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways.     

Aberrations of MET are associated with copy number gain of EGFR and loss of PTEN and predict poor outcome in patients with salivary gland cancer

Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n?=?42), high polysomy (n?=?27), amplification (n?=?2) and deletion (n?=?18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p?=?0.003), male gender (p?=?0.01), increased tumour size (p?=?0.002), lymph node metastases (p?<?0.001), high-grade malignancy (p?<?0.001) and unfavourable overall survival (p?<?0.001). Both copy number gain (p?<?0.001) and deletion (p?=?0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n?=?48) concurrently presented aberration of genomic MET (p?<?0.001). MET gene status significantly correlated with protein status (p?=?0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.     

乳腺癌前哨淋巴结不同转移状态下局部淋巴结成熟树突状细胞的研究

目的：研究乳腺癌前哨淋巴结不同转移状态 下前哨淋巴结与非前哨淋巴结成熟树突状细胞密度的改变。方法:回顾 性分析79例符合研究标准的女性乳腺癌患者。根据前哨淋巴结的转移状况分为3组：A组（2 8例），所有淋巴结转移阴性；B组（25例），仅微小肿瘤出现于前哨淋巴结，包括B1组（16 例），仅游离肿瘤细胞出现于前哨淋巴结；B2组（9例），仅微转移出现于前哨淋巴结；C组 （26例），转移出现于前哨淋巴结，非前哨淋巴结有或无转移。所有前哨淋巴结及非前哨淋 巴结蜡块切片均行与DC-LAMP抗体免疫反应的免疫组织学检查以确认成熟树突状细胞。蔡司 图像分析系统定量分析每个淋巴结DC-LAMP阳性细胞的相对密度（DC-LAMP阳性细胞面积/淋 巴结面积）。Wicoxon检验和Mann-Whitney检验分别用于DC-LAMP阳性细胞的相对密度的组内 和组间比较。结果:DC-LAMP阳性细胞密度的组内比较显示A组和B组前哨 淋巴结DC-LAMP阳性细胞平均密度较非前哨淋巴结高（P<0.05，P<0.01）；C组前哨淋 巴结DC-LAMP阳性细胞平均密度与非前哨淋巴结比较无明显差异（P>0.05）。组间比较 显示各组前哨淋巴结DC-LAMP阳性细胞平均密度无显著差异；而B组(尤其B2组)非前哨淋巴结 DC-LAMP阳性细胞密度较A组和C组显著升高（P<0.05，P<0.01）。结论： 前哨淋巴结和非前哨淋巴结DC-LAMP阳性细胞平均密度在淋巴结肿瘤转移形成过程发生改变,揭示前哨淋巴结在肿瘤与引流淋巴结间相互作用中起重要作用。     

Immunomodulatory effect of Kalpaamruthaa on 7,12-dimethyl benz(a)anthracene-induced mammary carcinoma studied in rats

Kapaamruthaa is a modified Siddha preparation prepared in our laboratory. It has been proven to have therapeutic effect against arthritis and liver cancer. The present study was carried out to bring about the protective effect of Kalpaamruthaa on experimental mammary carcinoma in rats with special reference to cytokines, carcinoembryonic antigen (CEA), carbohydrate antigen 15–3 (CA 15–3), immunoglobulin levels, and glycoprotein components. Breast cancer was induced in rats by administering 7,12-dimethylbenz(a)anthracene (DMBA) orally (25 mg/rat) as a single dose. After 90 days of induction, Semecarpus anacardium Linn. (200 mg/kg body weight) and Kalpaamruthaa (KA) (300 mg/kg body weight) were administered for 14 days, by gastric intubation. In mammary carcinoma-bearing rats, the levels of interleukin-6, interleukin-8, and tumor necrosis factor-α were significantly increased (p?<?0.001) in serum when compared to control rats. The levels of CEA and CA 15–3 were found to be significantly increased (p?<?0.001) in mammary carcinoma-bearing rats. The levels of IgG and IgM were significantly decreased (p?<?0.001) whereas IgA levels were significantly increased (p?<?0.001) in mammary carcinoma-bearing rats. The levels of glycoprotein components namely hexose, hexosamine, and sialic acid were significantly (p?<?0.001) increased in the spleen and thymus of the mammary carcinoma-bearing (group II) rats when compared to control rats. Treatment with KA significantly altered the levels of cytokines, CEA, CA 15–3, immunoglobulins, and glycoprotein components to near normal levels when compared to breast cancer-induced rats. The present study suggests the therapeutic effect of KA in DMBA-induced mammary carcinoma in rats.     

Overexpression of carbonic anhydrase IX (CAIX) in vulvar cancer is associated with tumor progression and development of locoregional lymph node metastases

Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. The protein is specifically overexpressed in a wide variety of malignant tumors. This study was designed to assess the role of CAIX in primary vulvar cancer. One hundred forty-two well-characterized primary vulvar carcinomas were analyzed on a tissue microarray (TMA). Three tissue cores were sampled from each tumor. CAIX expression was determined by immunohistochemistry, using a four-step scoring system. To determine CAIX expression in benign vulvar tissue, we constructed a TMA with 120 samples of normal mucosa and non-neoplastic diseases. CAIX expression was found in 77/135 (57%) of all assessable vulvar cancer specimens and 48 (35.5%) exhibited a moderate or strong expression. CAIX expression in vulvar carcinomas was significantly stronger compared to non-neoplastic vulvar tissue (p?<?0.001). High levels of CAIX expression were related to pT stage (p?<?0.01), tumor size (p?<?0.01), depth of invasion (p?<?0.05), as well as inguinal lymph node metastases (p?<?0.05). There was also a trend towards shorter recurrence-free patient survival in CAIX-positive compared to CAIX-negative vulvar cancers. CAIX staining results in different tissue cores from the same tumor were homogeneous, raising the possibility of a hypoxia-independent expression. In conclusion, CAIX is overexpressed in the majority of vulvar carcinomas with relationships to advanced tumor stages and development of lymph node metastases. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced vulvar cancer.     

Differential expression of HER2 and downstream proteins in prediction of advanced tumor phenotypes and overall survival of patients with Epstein-Barr virus-positive vs. negative gastric cancers

This study evaluated the associations of HER2 protein, HER2 gene amplification, and positivity for p-AKT, p-ERK, and p-PLCγ proteins with clinicopathological status and overall survival (OS) of patients who had Epstein-Barr virus-associated gastric cancer (EBVaGC; n = 58) or EBV-negative GC (EBVnGC; n = 329). Tissue samples were subjected to immunohistochemistry and fluorescence in situ hybridization (FISH). Results showed that EBVaGC less expressed HER2 and amplified HER2 gene. p-AKT (p = 0.035) and p-ERK (p = 0.001) were inhibited in EBVaGC than in EBVnGC, while p-PLCγ (p = 0.034) was upregulated. Among EBVaGC patients, p-ERK positivity was associated with Lauren classification (p = 0.023), and p-PLCγ positivity was inversely associated with TNM stage (p = 0.041) and lymph node metastasis (p = 0.041). In contrast, among EBVnGC patients, HER2 expression was associated with distant metastasis (p = 0.043) and p-AKT positivity was associated with intestinal subtype (p < 0.004), lymph node metastasis (p = 0.031), distant metastasis (p < 0.001), and elder age (>60y, p < 0.004). Overall analysis showed that EBVaGC patients presented better OS than EBVnGC patients (p = 0.044). Among EBVaGC patients, p-AKT positivity (p = 0.008) was associated with worse OS; as well as, HER2 high expression (p < 0.001), p-AKT positivity (p = 0.010), and p-PLCγ (p < 0.001) were associated with worse OS in EBVnGC patients. Multivariate analysis showed that distant metastasis (95% CI: 1.559 to 4.028, p < 0.001), HER2 high expression (95% CI: 1.058 to 2.454, p = 0.026), and p-PLCγ positivity (95% CI: 1.056 to 2.435, p = 0.027) were independent prognostic predictors of OS in EBVnGC patients. Our results indicated that p-AKT positive patients presented worse OS than p-AKT negative ones in EBVaGC, as well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC patients.     

Cancer stem cell characteristics, ALDH1 expression in the invasive front of nasopharyngeal carcinoma

The invasive tumor front underlies the biological aggressiveness and epithelial–mesenchymal transition (EMT) in various human malignances. However, the molecular and biological characteristics of invasive tumor front in NPC have rarely been described. Additionally, the features of cancer stem cells (CSCs) in the invasive front of tumors and its correlation with EMT also remain elusive. Our study was to investigate the expression of CSCs marker aldehyde dehydrogenase 1 (ALDH1) in the invasive front of nasopharyngeal carcinoma (NPC) and its clinical significance. Immunohistochemistry was mainly used to detect ALDH1 expression in the invasive front of NPC. The relationship between ALDH1 expression and EMT-associated markers was also examined. ALDH1 expression in the invasive front correlated strongly with lymphatic invasion (p?<?0.001), T classification (p?=?0.001), M classification (p?<?0.001), clinical stage (p?<?0.001), and local recurrence (p?=?0.008). ALDH1 overexpression in the invasive front contributed to worse survival of NPC, particularly in patients with early stage (T1-T2 or N0-N1) (p?<?0.001 and p?=?0.002, respectively), though it was not an independent prognostic factor (p?=?0.196). Furthermore, in the invasive front of NPC, ALDH1 expression correlated significantly with EMT-related biomarkers E-cadherin (p?=?0.026), Vimentin (p?<?0.001), Periostin (p?<?0.001), and Snail (p?<?0.001), but not with β-catenin (p?=?0.143). Our findings demonstrate first that ALDH1 expression in the invasive front links closely with EMT characteristics and tumor aggressiveness, which might provide a useful prognostic marker for NPC patients.     

Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer

Heat shock protein 70 (HSP70) is a molecular chaperone which plays an important role in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. This study was conducted in gastric carcinoma (GC) to assess correlations of HSP70 expression with clinicopathological parameters and overall survival (OS). Tissue microarray blocks were constructed from 172 GCs and immunohistochemically stained for HSP70. Low HSP70 expression was found in 122 GCs (71 %), whereas 50 (29 %) had high expression. HSP70 expression was higher in tumours in the cardia (p?=?0.008), with non-signet ring cell histology (p?<?0.001), of intestinal type (p?=?0.045) and of higher pathological T stage (p?=?0.026). When considering the cohort as a whole, HSP70 expression did not correlate with OS (p?=?0.092). In intestinal type carcinomas, however, high HSP70 expression significantly correlated with worse OS (p?=?0.034). These results suggest that HSP70 expression might be an unfavourable prognostic factor in patients with GC, especially of intestinal type.     

Impact of disease free status on prognosis in metastatic non-small round cell soft tissue sarcomas

The aim of this study is to examine the impact of disease free (DF) status on the prognosis in patients with metastatic non-small round cell soft tissue sarcoma (STS). We retrospectively reviewed 51 metastatic STS patients who were treated in Nagoya University Hospital from 2005 to 2015. The relation between various clinical factors and overall survival (OS) was analyzed. The log rank test and Cox’s proportional hazards test were used to evaluate the differences between groups. p-values of <0.05 were considered to indicate significance. The median follow-up period after first metastasis was 23.5 (1.6–97.1) months. There were 30 males and 21 females with a median age of 62 (15–88) years at first metastasis. The histologic subtypes were 17 undifferentiated pleomorphic sarcoma, 10 liposarcoma, 8 malignant peripheral nerve sheath tumor, and 16 others. Thirty patients had more than 2 metastases, and 15 patients had primary or local recurrent tumors. The metastatic sites were 31 lung only, 8 bone only, and 12 others. Twenty-two patients achieved DF status after surgeries and in one case proton radiotherapy for bone metastasis. DF status was marginally or significantly associated with good prognosis in patients with both pulmonary (p = 0.055) and extrapulmonary metastasis (p = 0.029). On multivariate analysis, DF status (p = 0.010) was an independent good prognostic factors for OS. In metastatic non-small round cell STS, it is an important treatment concept to achieve DF status whenever possible. This concept can apply both to pulmonary and extrapulmonary metastasis.     

Comparing Clinicopathologic and Radiographic Findings Between TT-UMP,Classical, and Non-Encapsulated Follicular Variants of Papillary Thyroid Carcinomas

Thyroid tumors of uncertain malignant potential (TT-UMP) comprise an accepted subgroup of follicular-patterned thyroid tumors for which benignancy or malignancy cannot be precisely assessed. We aimed to evaluate the demographic characteristics, ultrasound (US) findings, and cytological results of patients with TT-UMP and compare these findings to a classical variant of papillary thyroid carcinoma (CV-PTC) and non-encapsulated follicular variant of PTC (NEFV-PTC) patients; we also evaluated the immunohistochemical characteristics of patients with TT-UMP. Twenty-four patients with TT-UMP, 672 with CV-PTC, and 132 with NEFV-PTC were included in the study. Mean longitudinal nodule size and median nodule volume were higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p?<?0.001 and p?<?0.001 for CV-PTC; p?<?0.001 and p?=?0.008 for NEFV-PTC). The presence of halo and peripheral vascularization was observed more frequently in the TT-UMP group than in the CV-PTC group (p?=?0.002 and p?=?0.024). Benign and follicular neoplasm/suspicious for follicular neoplasm cytological results were higher in the TT-UMP group than in the CV-PTC group (p?=?0.030 and p?=?0.001). US findings were similar between TT-UMP and NEFV-PTC groups (all, p?>?0.05). However, none of the patients with TT-UMP were called malignant; 105 patients (31.2 %) of CV-PTC and 11 patients (9.5 %) of NEFV-PTC (infiltrative FV) were classified as malignant cytologically. Tumor size was higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p?<?0.001 and p?=?0.006). In the TT-UMP group, positive expression of HBME-1, CK-19, and Gal-3 was found in 50, 33.3, and 25 % of patients, respectively. This study demonstrated that none of the TT-UMP patients were evaluated as malignant in preoperative cytology. However, patients with TT-UMP had higher nodule and tumor sizes than CV-PTC and NEFV-PTC patients; US features were similar between NEFV-PTC and TT-UMP patients.     

Intraoperative cytologic evaluation of sentinel lymph nodes in patients with breast carcinoma by scrape preparation

Intraoperative evaluation of sentinel lymph nodes (SLNs) in patients with breast carcinoma allows surgeons to complete axillary lymph node dissection in one procedure if any SLN shows metastasis. The accuracy of intraoperative pathological diagnosis is critical for decision-making. The purpose of this study was to evaluate our rapid intraoperative cytologic diagnosis of SLN through comparing with the final surgical pathologic diagnosis of the corresponding lymph nodes. A total of 454 SLNs from 159 consecutive female patients with a preoperative diagnosis of breast carcinoma over 3-year period were included in this study. After gross examination of each bisected lymph node, a scrape preparation was prepared for each submitted lymph node and was stained by the rapid Papanicolaou method. The intraoperative cytologic diagnosis was compared with the final surgical pathologic diagnoses. The overall sensitivity of intraoperative cytology was 52.5% with specificity of 100%. There were 17 false-negative cases. Of them, six nodes had isolated tumor cells, seven nodes had micrometastasis (0.2-2 mm), and four nodes had macrometastasis (>2 mm). There were no interpretive errors identified. The size of metastasis and tumor grade appeared to be significant factors in detecting metastasis by cytology. In addition, subsequent non-SLN involvement was 9% in patients with micrometastasis versus 50% in patients with macrometastasis (P < 0.05). Our study shows that the intraoperative cytologic evaluation of SLNs in breast carcinoma is a reasonably accurate method. The majority of false-negative cases were due to micrometastasis and isolated tumor cells.     

Prognosis of hepatocellular carcinoma patients with extrahepatic metastasis and the controllability of intrahepatic lesions

Although advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is recommended to be treated by a systemic chemotherapeutic agent without local treatment targeting the liver, studies reported that causes of death in these patients were mostly from progression of intrahepatic lesions. Thus, this study investigated prognosis and factors predicting survival in these patients so as to evaluate the role of local treatments against intrahepatic lesions when the patients already had extrahepatic metastasis. This retrospective study evaluated medical records of 277 patients with HCC and extrahepatic metastasis. The median survival was 5.9 months, and 257 patients died during the follow up. Factors affecting survival of HCC patients with extrahepatic metastasis were poor response to treatment of hepatic lesions (HR 2.207; 95 % CI; p < 0.001), applying local treatment specifically targeting intrahepatic lesions (HR 0.591; 95 % CI 0.436–0.803; p = 0.001), intrahepatic tumor size larger than 3 cm (HR 2.065; 95 % CI 1.444–2.954; p < 0.001), and ECOG performance status 2 or higher (HR 1.543; 95 % CI 1.057–2.253; p = 0.025). The patients with either complete or partial response to the therapy had 1- and 2-year survival rate of 48.8 and 12.1 % whereas patient with either stable or progressive disease had 1-year survival rate of 11.4 %. These results suggest that even in the HCC patients with extrahepatic metastasis, effective local treatment may still be beneficial for the survival especially in patients with acceptable performance status.     

Inflammatory Cytokines Imbalance in the Very Early Phase of Acute Coronary Syndrome: Correlations with Angiographic Findings and In-Hospital Events

The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-??, and interferon (IFN)-??. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-??, and IFN-??) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p?<?0.001; TNF-?? and IFN-??, p?<?0.05) and more often incurred early complications (IL-2, p?<?0.05; IFN-??, p?<?0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r?=?0.47; lactate dehydrogenase, r?=?0.54; troponin I, r?=?0.58; p?<?0.05). TNF-?? levels were associated with a worse prognosis at follow-up (Log rank, p?<?0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.     

Risk factor analysis for bone marrow histiocytic hyperplasia with hemophagocytosis: an autopsy study

The excessive release of inflammatory cytokines occasionally induces life-threatening hemophagocytosis referred to as hemophagocytic syndrome (HPS). A similar condition, histiocytic hyperplasia with hemophagocytosis (HHH), is often seen in bone marrow collected during autopsy. Unlike HPS, the pathogenesis of HHH remains unclear. Therefore, we performed a clinicopathological analysis of HHH from 70 autopsy cases at the University of Fukui Hospital. HHH was detected in 29 of 70 autopsies (41.4 %) and was significantly complicated with hematological diseases (p?<?0.05) and sepsis (p?<?0.05). The percentage of macrophages in bone marrow (BM) nucleated cells was significantly increased in HHH (p?<?0.001). Data from medical records indicated no significant changes, except for the minimum values of white blood cell counts (p?<?0.05) and platelet counts (p?<?0.05) in HHH patients as compared with non-HHH patients. Concentrations of inflammatory mediators including IL-1β, IL-6, and IL-8 were significantly increased in HHH patients. Multivariate risk factor analysis identified hematological diseases (odds ratio (OR), 11.71), ≥15 % BM macrophages (OR, 9.42), sepsis (OR, 7.77), and high serum IL-6 levels (OR, 1.00) as independent risk factors for HHH. HHH with hypocellular BM, the most aggressive form of HHH, was recognized in 8 of 29 HHH patients and was associated with ≥25 % BM macrophages (p?<?0.001), leukocytopenia (p?<?0.05), and high IL-8 levels (p?<?0.05). None of the HHH patients fulfilled the diagnostic criteria of HPS. These findings suggest that HHH is a different entity from HPS and that it preferentially develops under conditions of excessive inflammation and its associated risks, such as hematological diseases and sepsis.     

Mother-child bonding at 1 year; associations with symptoms of postnatal depression and bonding in the first few weeks

Some mothers experience neutral or negative feelings toward their new infant. This study examined the association between symptoms of postnatal depression and mother–infant bonding and the persistence of these feelings over the first year. Bonding was assessed using the Mother–Infant Bonding Scale (MIBQ), at four times postnatal, “early weeks” (1–4 weeks), 9 weeks, 16 weeks and 1 year, in 50 depressed, Edinburgh Postnatal Depression scale (EPDS) ≥13 at 4 weeks post natal, and 29 non-depressed mothers. A significant association between the EPDS score at 4 weeks and bonding score at 1–4 weeks, 9 weeks, and at 1 year postnatal, χ ²(1)?=?9.85, p?<?0.01, 5.44, p?<?0.05 and 5.21, p?<?0.05, respectively, was found, with a trend at 16 weeks. There was a strong association between bonding in the early weeks and all later time points χ ²(1)?=?17.26, p?<?0.001, 7.89, p?<?0.01 and 13.69, p?<?0.001, respectively. Regression showed early bonding rather than early depression was the major predictor of bonding at 1 year. Women who are depressed postnatally can fail to bond well with their baby and this can persist for a year. Early identification and intervention for poor bonding is indicated.