Predictive Factor For Poor Prognosis Research Articles

Prognostic factors for elderly patients with primary malignant bone and soft tissue tumors.

The number of patients with primary malignant bone and soft tissue tumors in Japan is increasing in line with the increasing size of the elderly population. The aim of the present study was to determine the prognostic factors of primary malignant bone or soft tissue tumors in elderly patients. Clinical data was obtained from 90 patients, aged ≥65 years, with primary malignant bone or soft tissue tumors (bone, 20 cases; and soft tissue, 70 cases), treated at the Osaka City University Hospital between 1993 and 2013. Clinical information prior to treatment and tumor type, location, size, depth, grade and American Society of Anesthesiologists-Physical Status (ASA-PS) score were evaluated in order to identify prognostic factors using the Cox proportional hazards regression model. In addition, 5-year survival rates were evaluated using the Kaplan-Meier method. The average follow-up period was 44.8 months and the 5-year overall survival rate was 77.5%. In the multivariate analysis, ASA-PS score and high-grade sarcoma were found to be associated with a poorer overall survival. No significant differences were observed between the patient group aged 65-74 years and that aged ≥75 years. In general, aging is associated with physically reduced function and an increased prevalence of comorbidities. It was therefore expected that increasing age may be a predictive factor for poor prognosis. However, the results of the present study suggested that ASA-PS score and tumor grade were significant factors associated with poor prognosis, whereas increasing age was not. Therefore, the treatment of elderly patients with primary bone and soft tissue tumors should not be based on age.

Quantitative proteomic analysis shows differentially expressed HSPB1 in glioblastoma as a discriminating short from long survival factor and NOVA1 as a differentiation factor between low-grade astrocytoma and oligodendroglioma.

BackgroundGliomas account for more than 60 % of all primary central nervous system neoplasms. Low-grade gliomas display a tendency to progress to more malignant phenotypes and the most frequent and malignant gliomas are glioblastomas (GBM). Another type of glioma, oligodendroglioma originates from oligodendrocytes and glial precursor cells and represents 2–5 % of gliomas. The discrimination between these two types of glioma is actually controversial, thus, a molecular distinction is necessary for better diagnosis.MethodsiTRAQ-based quantitative proteomic analysis was performed on non-neoplastic brain tissue, on astrocytoma grade II, glioblastoma with short and long survival and oligodendrogliomas.ResultsWe found that expression of nucleophosmin (NPM1), glucose regulated protein 78 kDa (GRP78), nucleolin (NCL) and heat shock protein 90 kDa (HSP90B1) were increased, Raf kinase inhibitor protein (RKIP/PEBP1) was decreased in glioblastoma and they were associated with a network related to tumor progression. Expression level of heat shock protein 27 (HSPB1/HSP27) discriminated glioblastoma presenting short (6 ± 4 months, n = 4) and long survival (43 ± 15 months, n = 4) (p = 0.00045). Expression level of RNA binding protein nova 1 (NOVA1) differentiated low-grade oligodendroglioma and astrocytoma grade II (p = 0.0082). Validation were done by Western blot, qRT-PCR and immunohistochemistry in a larger casuistry.ConclusionTaken together, our quantitative proteomic analysis detected the molecular triad, NPM1, GRP78 and RKIP participating together with NCL and HSP27/HSPB1 in a network related to tumor progression. Additionally, two new important targets were uncovered: NOVA1 useful for diagnostic refinement differentiating astrocytoma from oligodendroglioma, and HSPB1/HSP27, as a predictive factor of poor prognosis for GBM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1473-9) contains supplementary material, which is available to authorized users.

A 10-year analysis of the oral squamous cell carcinoma profile in patients from public health centers in Uruguay.

The aim of this study was to evaluate the demographic, clinical, and therapeutic characteristics and predictive factors of poor prognosis in patients with primary oral squamous cell carcinoma (OSCC) in Uruguay. Medical records of patients with the diagnosis of primary OSCC treated between 2000 and 2010 in Uruguayan public hospitals were selected. Data on demographic characteristics, risk factors, clinical features, treatment, and outcome were collected. Associations of independent variables with outcomes were assessed using Pearson chi-squared and Fisher's tests. Of 200 patients with OSCC, 79.4% were men (3.8:1 male:female ratio), with a mean age of 60.75 ± 11.26 years. Tobacco and alcohol consumption were reported by 85.3% and 63.5% of patients, respectively. The most commonly affected location was the tongue (42.5%), with lesions exhibiting ulcerous aspects in 87.9% of cases and pain at the time of diagnosis in 70.4% of cases. One hundred sixty-one (82.1%) patients had advanced-stage (III/IV) OSCC. Surgery was the most common treatment option, and the overall 5-year survival rate was 58.5%. Univariate analysis showed that the predictors of poor prognosis were clinical aspect, size, regional metastasis, clinical stage, and treatment. In Uruguay, OSCC is diagnosed late, which is associated with a low survival rate. Educational and preventive measures and investment to improve early diagnosis should be undertaken.

Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway.

Rab31 belongs to the Ras superfamily of small GTP-binding proteins, which has been found to regulate the vesicle transport from the Golgi apparatus to early and late endosomes. The investigation here detected the expression of Rab31 in 96 patients with hepatocellular carcinoma (HCC) and tried to identify its significance on outcome of HCCs after liver resection. By immunohistochemistry staining, it was found that Rab31 expression in HCC tissues was remarkably higher than that in adjacent liver tissues. Aberrant Rab31 overexpression in HCC tissues was identified to be associated with worse prognosis after liver resection. Univariate analysis showed that advanced tumor-nodes-metastasis (TNM) staging of HCC, intrahepatic metastases, portal vein invasion, and higher Rab31 were the predictive factors of poor prognosis. Multivariate analysis demonstrated that intrahepatic metastases and higher Rab31 were the independent prognostic factors. Furthermore, forced expression of Rab31 in Huh7 cells was found to promote cell growth via upregulation of Bcl-2/BAX ratio induced by PI3K/AKT. Correspondingly, silencing Rab31 induced cell apoptosis and in turn suppressed the growth capacity of MHCC97 cells in vitro. Taken together, this study provides the evidence of Rab31 overexpression in HCC, and Rab31 is potentially used as a novel biomarker of poor prognosis in patients with HCC. PI3K/AKT/Bcl-2/BAX axis was involved in Rab31-promoting HCC progression.

Elevated level of serum carbohydrate antigen 19.9 as predictor of mortality in patients with advanced medullary thyroid cancer.

Medullary thyroid cancer (MTC) is capable of secreting several proteins, such as calcitonin (Ct), carcinoembryonic antigen (CEA), chromogranin and others. Recently, we observed an aggressive MTC with high levels of serum carbohydrate antigen 19.9 (Ca 19.9) and a rapid evolution to death. The aim of this study was to evaluate whether high levels of serum Ca 19.9 could be a prognostic factor of death in patients with advanced MTC. We measured Ca 19.9, CEA and Ct in 100 advanced structural recurrent/persistent MTC patients and in 100 cured or biochemically affected MTC patients. Clinical and pathological data were also collected. Sixteen percent of the patients with advanced MTC had high levels of Ca 19.9. The group with abnormal Ca 19.9 levels had significantly higher levels of CEA and Ct compared with the group with normal values of Ca 19.9 (P<0.0001 for both Ct and CEA). At variance, all 100 patients in the MTC control group showed normal levels of Ca 19.9. Moreover, among the advanced cases, the Ca 19.9-positive group showed a higher mortality rate than the group with normal levels. A logistic regression analysis demonstrated that an elevated level of Ca 19.9 is a predictor of mortality (OR=3.78, P=0.04), independent from Ct doubling time. These results demonstrated that an elevated value of serum Ca 19.9 appears to be a predictive factor of poor prognosis in advanced MTC patients and identifies those cases with a higher risk of mortality in the short term.

Evaluation of the quality of life of patients with high grade subarachnoid hemorrhage following aneurysmal rupture

Introduction: Patients presenting with high grade (HG) subarachnoid hemorrhage (SAH) from aneurysmal rupture may have persisting neurologic deficits which may lead to questioning the decision of treating aggressively. The objective of this study aims at analyzing outcome and long-term quality of life (QOL) of patients with HG SAH treated surgically. Methods: Retrospective study of patients with Hunt Hess (HH) grade IV or V SAH treated surgically at our institution. Long-term outcome was evaluated based on the modified Rankin Scale (mRS) at 3 years. Survivors were evaluated for QOL using various scales. Results: 63 patients (mean age of 52 year-old) were included. Intraparenchymal hemorrhage (IPH) was found in 85% of cases. 19 patients died. Predictive factors of poor prognosis and mortality were initial cerebral ischemia (p=0.003) and IPH (p=0.007). Favourable outcome (mRS 0-3) was found in 41% of patients. QOL questionnaires revealed that 80 % of responders showed more than 50% recovery. Mild or absent depression was observed in 78% of patients. Conclusion: In this surgical series, performed in an endovascular era, nearly all patients presented with SAH-associated IPH at admission. Despite the presence of such negative prognostic factor and the poor condition at admission, a high rate of favourable outcome and QOL was observed, therefore justifying aggressive surgical treatment.

The impact of matrix metalloproteinase 2 on prognosis and clinicopathology of breast cancer patients: a systematic meta-analysis.

BackgroundsMatrix metalloproteinase 2 (MMP-2) plays a crucial role in the progression of breast cancer (BC). The prognostic role of MMP-2 expression in BC patients has been widely reported, but the results were inconsistent. Thus, a meta-analysis was conducted to gain a better insight into the impact of MMP-2 expression on survival and clinicopathological features of BC patients.MethodsIdentical search strategies were used to search relevant literatures in electronic databases update to August 1, 2014. Individual hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were extracted and pooled to evaluate the strength of the association between positive MMP-2 expression and survival results and clinicopathological features of BC patients. Begg’s tests, Egger’s tests and funnel plots were used to evaluate publication bias. Heterogeneity and sensitivity analysis were also assessed. All the work was completed using STATA.ResultsPooled HRs and 95% CIs suggested that MMP-2 expression had an unfavorable impact on both OS (HR: 1.53, 95% CI: 1.29–1.82) and DFS/RFS/DDFS (HR: 1.41, 95% CI: 1.07–1.86) in BC patients. Furthermore, MMP-2 expression was significantly associated with lymph node metastasis (positive vs negative: OR 1.91, 95% CI 1.17–3.12).ConclusionIn conclusion, positive MMP-2 expression might be a significant predictive factor for poor prognosis in patients with BC.

Distribution of human papillomavirus genotypes in early-stadge cervical adenocarcinoma and its clinical significance

To explore the distribution of high-risk HPV-genotypes in early-stage cervical adenocarcinoma and understand the clinical significance of HPV genotyping. From June 2000 to May 2010, a total of 101 paraffin surgical specimens of cervical adenocarcinoma were genotyped by nested polymerase chain reaction (nested PCR). The associations of HPV18 with clinicopathological parameters and survival were further analyzed. DNA extraction was successfully performed for 96 samples. The HPV-positive rate of early-stage cervical adenocarcinoma was 95.8% (92/96). Two common HPV types were HPV16 (59.4%) and HPV18 (60.4%). The prevalence rates of single, double and multiple HPV infections were 22.9%, 32.3% and 40.6% respectively. The positive rates of lymph node metastasis and vascular involvement with HPV18 infection were 27.6% and 22.4% versus 7.9% and 7.9% for those without HPV18 infection.Univariate analysis showed that positive surgical margin, uterine corpus invasion, lymph node metastasis and HPV18 infection were the predictive factors for poor prognosis of patients with cervical adenocarcinoma. Multivariate analysis revealed that lymph node metastasis was an independent prognostic factor for both disease-free and overall survivals. And uterine corpus invasion was an independent prognostic factor of overall survival for early-stage cervical adenocarcinoma patients. HPV16 and HPV18 are major types responsible for early-stage cervical adenocarcinoma.Infection with HPV18 is prone to lymph node metastasis and vascular involvement.However, there is no correlation with disease-free survival or overall survival.

Long noncoding RNA HOTAIR as an independent prognostic marker in cancer: a meta-analysis.

Background HOTAIR, a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in many types of cancers. This meta-analysis summarizes its potential role as a biomarker in malignancy.MethodsA quantitative meta-analysis was performed through a systematic search in Pubmed, Medline and Web of Science for eligible papers on the prognostic impact of HOTAIR in cancer from inception to Feb. 28, 2014. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect.ResultsNineteen studies were included in the study, with a total of 2033 patients. A significant association was observed between high HOTAIR expression and poor overall survival (OS) in patients with cancer (pooled HR 2.22, 95% CI: 1.68–2.93). Place of residence (Asian or Western countries), type of cancer (digestive or non-digestive disease), sample size (more or less than 100), and paper quality (score more or less than 85%) did not alter the significant predictive value of HOTAIR in OS from various kinds of cancer but preoperative status did. By combining HRs from Cox multivariate analyses, we found that HOTAIR expression was an independent prognostic factor for cancer patients (pooled HR 2.26, 95% CI: 1.62–3.15). Subgroup analysis showed that HOTAIR abundance was an independent prognostic factor for cancer metastasis (HR 3.90, 95% CI: 2.25–6.74). For esophageal carcinoma, high HOTAIR expression was significantly associated with TNM stage (III/IV vs. I/II: OR 6.90, 95% CI: 2.81–16.9) without heterogeneity. In gastric cancer, HOTAIR expression was found to be significantly associated with lymph node metastases (present vs. absent: OR 4.47, 95% CI: 1.88–10.63) and vessel invasion (positive vs. negative: OR 2.88, 95% CI: 1.38–6.04) without obvious heterogeneity.Conclusions HOTAIR abundance may serve as a novel predictive factor for poor prognosis in different types of cancers in both Asian and Western countries.

The prognostic role of matrix metalloproteinase 2 in gastric cancer: a systematic review with meta-analysis

The prognostic role of matrix metalloproteinase 2 (MMP-2) in gastric cancer remains controversial. We systematically reviewed the evidence for assessment of MMP-2 expression in gastric cancer to elucidate this issue. Pubmed, Embase and Web of Science were searched to identify eligible studies to evaluate the association of MMP-2 expression and overall survival and clinicopathological features of gastric cancer. MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients (HR 1.92, 95 % CI 1.48-2.48). Subgroup analysis indicated that MMP-2 overexpression had an unfavorable impact on OS in Asian countries (HR 2.23, 95 % CI 1.57-3.17) and European countries (HR 1.43, 95 % CI 1.13-1.80). Furthermore, MMP-2 overexpression was significantly associated with TNM stage (TIII/TIV vs TI/TII: OR 2.17, 95 % CI 1.64-2.87), the depth of invasion (T3/T4 vs T1/T2: OR 2.59, 95 % CI 1.63-4.12), lymph node metastasis (positive vs negative: OR 2.21, 95 % CI 1.69-2.88), and distant metastasis (positive vs negative: OR 4.44, 95 % CI 1.24-15.94). This meta-analysis indicated that MMP-2 overexpression might be a predictive factor for poor prognosis for gastric cancer.

Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: a meta-analysis.

To evaluate the effect of β-catenin immunohistochemical expression on the prognosis of gastric cancer (GC). We searched Pubmed and Embase to identify eligible studies. The search ended on November 10, 2013, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. We included studies reporting sufficient information to estimate the HR and 95%CI, and information to estimate the OR in the analysis of clinicopathological features. The qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs and ORs and their variance were calculated and pooled using Review Manager Version 5.2. A total of 24 studies were identified and comprised 3404 cases. β-catenin expression was significantly correlated with poor overall survival (OS) in GC patients (HR = 1.85, 95%CI: 1.39-2.46), but showed a significant degree of heterogeneity (I (2) = 71%, P < 0.0001). Subgroup analysis indicated that an abnormal pattern of β-catenin expression had an unfavorable effect on OS (HR = 1.79, 95%CI: 1.39-2.32). However, accumulation in the nucleus or loss of membrane did not influence the survival of GC patients independently. Moreover, the combined OR of β-catenin indicated that β-catenin expression was associated with Lauren classification (OR = 1.98, 95%CI: 1.19-3.29), lymph node metastasis (OR = 2.00, 95%CI: 1.44-2.77), distant metastasis (OR = 2.69, 95%CI: 1.35-5.38) and grade of differentiation (OR = 2.68, 95%CI: 1.66-4.34). β-catenin expression did not correlate with TNM stage (OR = 1.34 95%CI: 0.96-1.86), the depth of invasion (OR = 1.48, 95%CI: 0.94-2.33) or vascular invasion (OR = 1.11, 95%CI: 0.70-1.76). Abnormal β-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC.

Evaluation of accuracy for detection and extent of occult myocardial scars using delayed-enhancement CT in patients with asymptomatic diabetes: results from the ACCREDIT study

Background Occult myocardial scar is known to be a predictive factor of poor prognosis in the diabetes patients. The purposes of this study are to evaluate through an exploratory substudy the accuracy of delayed-enhancement CT (DE-CT) for detecting occult myocardial scars (OMS) and to evaluate the transmurality of OMS using DE-CT compared with delayed enhancement MRI (DE-MRI) in asymptomatic patients with type 2 diabetes.

Expressions of CD147, MMP-2 and MMP-9 in Laryngeal Carcinoma and its Correlation with Poor Prognosis

The objectives of this study are to investigate the expressions of matrix metalloproteinase inducing factor (CD147), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) in laryngeal tumor tissues and its significant correlation with tumor infiltration, metastasis and prognosis. Laryngeal tumor tissue from 48 laryngeal cancer patients with complete clinical information was collected. The laryngitis tissue from 15 patients were collected as control group. Immunohistochemical analysis for CD147, MMP-2 and MMP-9 was performed for all the tissue. The results showed the expression rates of CD147, MMP-2 and MMP-9 in laryngeal carcinoma were 87.5 %, 75.0 % and 79.2 % respectively, significantly higher than those (26.7 %, 6.7 %, and 33.3 % respectively) in the control group are (P < 0.01). High expression of CD147, MMP-2 and MMP-9 related to the clinical stages and lymphatic metastasis of laryngeal carcinoma. Univariate survival analysis showed that the 5-year survival of laryngeal carcinoma patients with low expression of CD147, MMP-2 and MMP-9was 83.3 %, 83.3 % and 90 % respectively, while the patients with high expression had 5-year survival at 25 %, 7.7 % and 18.2 % respectively (P < 0.05). Multiple regression analysis showed that high expression of MMP-9 was independently associated with poor prognosis (P < 0.05). High expression of CD147, MMP-2 and MMP-9 were related with laryngeal carcinoma invasion and metastasis. High expressions of CD147, MMP-2 and MMP-9 were all predictive factors of poor prognosis of laryngeal carcinoma.

Noninvasive and mainstream end-tidal carbon dioxide monitoring via nasal cannula is a unique and useful technique for diagnosing pulmonary hypertension in patients with heart failure

Purpose: End-tidal carbon dioxide (ETCO2) monitoring is commonly used for intubated patients receiving mechanical ventilation in the fields of anesthesiology and critical care medicine. Noninvasive and mainstream ETCO2 monitoring has been long-awaited so as to expand its use to other clinical settings. The partial pressure of ETCO2 (PETCO2) depends on the pulmonary ventilation-perfusion (V/Q) relationship and cell metabolism, and in normal subjects, PETCO2 values of around 40 mmHg reflect normal alveolar PCO2. Heart failure (HF) is one of the suitable pathological conditions to apply ETCO2 monitoring and recently low PETCO2 has been reported to be a predictor of prognosis in patients with HF. In this study, we aimed to clarify the association between hemodynamic parameters and PETCO2 in patients with HF. Methods: Twenty-four consecutive patients who received both right heart catheterization (RHC) and ETCO2 monitoring were enrolled for analysis. We measured pulmonary capillary wedge pressure (PCWP), pulmonary arterial pressure (PAP), and right atrial pressure. Cardiac output was calculated using two approaches, thermodilution and the Fick method. The cardiac index, pulmonary vascular resistance index (PVRI) and trans-pulmonary gradient (TPG) were also calculated. Mixed venous oxygen saturation (SvO2) was obtained by analyzing pulmonary arterial blood gas. PETCO2 was simultaneously obtained during RHC using a newly developed mainstream ETCO2 monitoring technique that obtains noninvasive measurements via nasal cannula. Results: Study participants included 12 patients with dilated cardiomyopathy, 3 with hypertrophic cardiomyopathy, 7 with heart transplant, 1 with peripartum cardiomyopathy, and 1 with ischemic cardiomyopathy. In all cases, cardiomyopathy was complicated by New York Heart Association (NYHA) functional class II to IV HF, and heart transplant patients had NYHA functional class I to II symptoms. No patients had any lung disease complications. The average PETCO2 of all patients was 28±6 mmHg, and PETCO2 showed significant negative correlations with mean PAP, PCWP, PVRI and TPG respectively (r=0.78, p<0.0001; r=0.70, p<0.0001; r=0.75, p<0.0001; r=0.64, p=0.0006). Further, receiver operating characteristic analysis suggested that PETCO2 <27 mmHg was an appropriate cut-off value for diagnosing the presence of pulmonary hypertension (PH). Conclusions: This study demonstrates that PETCO2 measurement may be a simple and promising technique for determining the presence and severity of PH, a well-known predictive factor for poor prognosis in patients with HF.

The Prognostic Value of p16 Hypermethylation in Cancer: A Meta-Analysis

BackgroundThe prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue.MethodsWe searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of p16 hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model.ResultsThe analysis indicated that p16 hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36–2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27–2.55). Moreover, the significant correlation was present between p16 hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19–3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35–2.39) and CRC (HR 1.96, 1.16–3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21–3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73).Conclusions p16 hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.

THU0255 Marked increase in serum KL-6 and SP-D levels during 1st 4 weeks after tratment predicts poor prognosis in patients with active interstitial pneumonia associated with polymyositis/dermatomyositis

BackgroundInterstitial pneumonia (IP) is a serious complication associated with polymyositis (PM) and dermatomyositis (DM). Predictive factors for poor prognosis have not been fully identified. KL-6 and surfactant protein D (SP-D)...

Tu1061 Impact of Multiple Tumors or Portal Hypertension on the Results of Second Hepatectomy for Recurrent Hepatocellular Carcinoma: A Single Center Experience

Background & Aims: Roayaie et al. reported a 5-year overall survival (OS) rate of 67% after second hepatectomy for recurrent hepatocellular carcinoma (HCC) in highly selected patients with a single nodule, preserved liver function, and noportal hypertension (PHT). The aim of this study was whether second liver resection can offer survival benefit for patients with multiple HCCs and/or PHT. Methods: We retrospectively studied 101 patients who had undergone second liver resection for recurrent HCC and stratified them into 3 groups according to the number of tumors and the presence of PHT, defined as a platelet count , 100,000/μL and/or the presence of esophageal varices: group A, patients with solitary tumor and no-PHT (n = 45); group B, those with either multiple tumor or PHT (n = 48); and Group C, those with both multiple tumor and PHT (n = 8). Overall survival (OS) and recurrence rate (RR) curves were constructed by the Kaplan-Meier method, and multivariate regression analysis was performed using the Cox proportional hazard model. Results: There was no 30-day mortality. The morbidity rate was comparable among the groups. The 5year OS rates and the 2-year recurrent rates were 67% and 60% in group A, 62%and 55% in group B, and 38% and 88% in group C, respectively, showing no significant differences among the three groups. In a multivariate analysis, neither multiple tumors nor presence of PHT was a predictive factor for poor prognosis. Conclusions: We can extend the indication of second hepatectomy for recurrent HCC, at least, to the patients with either multiple HCCs or PHT.

EGFR and TTF-1 Gene Amplification in Surgically Resected Lung Adenocarcinomas: Clinicopathologic Significance and Effect on Response to EGFR-Tyrosine Kinase Inhibitors in Recurred Cases

Gene amplifications are implicated in cancer development and progression. In this study we investigated the clinicopathologic characteristics associated with EGFR or TTF-1 amplification in lung adenocarcinomas and its prognostic significance. We analyzed 118 cases of surgically resected primary lung adenocarcinomas. Amplification of the EGFR or TTF-1 gene was evaluated by fluorescence in situ hybridization and correlated with patients' clinicopathologic features, including disease-free survival (DFS) and overall survival (OS), in all patients and a subset that were TTF-1 positive or had EGFR mutation. Progression-free survival (PFS) also was analyzed among patients with EGFR mutation who had recurred cancer that was treated with EGFR tyrosine kinase inhibitors. EGFR or TTF-1 gene amplification was an independent poor prognostic factor for DFS in all patients (p=0.001), in patients with TTF-1 positivity (p=0.010), and in patients with EGFR mutation (p<0.001) and for OS in patients with TTF-1 positivity (p=0.021) and patients with EGFR mutation (p<0.001). Patients with TTF-1 amplification had a shorter PFS following EGFR TKI treatment (p=0.040). EGFR or TTF-1 gene amplification was a predictive factor for poor prognosis in terms of DFS and OS, especially in patients with TTF-1 positivity or EGFR mutation. Our results also suggested that TTF-1 amplification might be a predictive marker of poor response to EGFR-TKI therapy in patients with recurrent tumor after surgical resection.

TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos)

Since the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07), diagnostic criteria and severity assessment criteria for acute cholangitis have been presented and extensively used as the primary standard all over the world. However, it has been found that there are crucial limitations in these criteria. The diagnostic criteria of TG07 do not have enough sensitivity and specificity, and its severity assessment criteria are unsuitable for clinical use. A working team for the revision of TG07 was organized in June, 2010, and these criteria have been updated through clinical implementation and its assessment by means of multi-center analysis. The diagnostic criteria of acute cholangitis have been revised as criteria to establish the diagnosis where cholestasis and inflammation demonstrated by clinical signs or blood test in addition to biliary manifestations demonstrated by imaging are present. The diagnostic criteria of the updated Tokyo Guidelines (TG13) have high sensitivity (87.6 %) and high specificity (77.7 %). TG13 has better diagnostic capacity than TG07. Severity assessment is classified as follows: Grade III: associated with organ failure; Grade II: early biliary drainage should be conducted; Grade1: others. As for the severity assessment criteria of TG07, separating Grade II and Grade I at the time of diagnosis was impossible, so they were unsuitable for clinical practice. Therefore, the severity assessment criteria of TG13 have been revised so as not to lose the timing of biliary drainage or treatment for etiology. Based on evidence, five predictive factors for poor prognosis in acute cholangitis--hyperbilirubinemia, high fever, leukocytosis, elderly patient and hypoalbuminemia--have been extracted. Grade II can be diagnosed if two of these five factors are present. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

Expressions of CCR7 and CXCR4 Are Associated with Differentiation in Gastrointestinal Cancer

Purpose: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer invasion and metastasis. This study was aimed to investigate CCR7 and CXCR4 expressions and evaluate the association between their expressions and the clinicopathological features in gastrointestinal cancer. Method: 27 paired tissue samples from patients who had curative surgery for gastrointestinal cancer were obtained. Quantitative real-time PCR, immunochemistry assay and western blot analysis were carried out to investigate the expressions of CCR7, CXCR4 expressions in gastrointestinal cancer. Results: The cancer tissues expressed significant higher level of CCR7 (P = 0.000) and CXCR4 (P = 0.000) protein than the adjacent normal mucosa. Expressions of CCR7 (P = 0.002) and CXCR4 (P = 0.003) protein in cancer tissues exhibited significant correlation with differentiation in gastrointestinal cancer. Conclusion: Expressions of CCR7 and CXCR4 protein were associated with differentiation in gastrointestinal cancer. CCR7 and CXCR4 may be predictive factors for poor prognosis in patients with gastrointestinal cancer.