Adolescent and Young Adult Cancer Survivors' Experiences of the Healthcare System: A Qualitative Study

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Microvascular ultrastructural changes precede cognitive impairment in the murine APPswe/PS1dE9 model of Alzheimer’s disease

Abstract

Cerebral and systemic organ microvascular pathologies coexist with human Alzheimer's disease (AD) neuropathology. In this study, we hypothesised that both cerebral and systemic microvascular pathologies exist in 4- to 5-month-old male APPswe/PS1dE9 (APP/PS1) transgenic mice prior to the onset of cognitive impairment. To assess this we examined recognition memory in both wild-type and APP/PS1 mice using the object recognition task (ORT; n = 11 per group) and counted thioflavin-S-positive plaques in brain (n = 6 per group). Vascular casts of brain, liver, spleen and kidneys were examined using scanning electron microscopy (n = 6 per group), and the urinary albumin-to-creatinine ratio (uACR; n = 5 per group) was measured as an index of glomerular permeability. Murine recognition memory was intact, as demonstrated by a significant preference for the novel object in the ORT paradigm. Brain sections of wild-type mice were devoid of thioflavin-S positivity, whereas age-matched APP/PS1 mice had an average of 0.88 ± 0.22 thioflavin-S-positive plaques in the cortex, 0.42 ± 0.17 plaques in the dentate gyrus and 0.30 ± 0.07 plaques in the cornus ammonis 1 region. The profiles of casted cerebral capillaries of wild-type mice were smooth and regular in contrast to those of APP/PS1 mice which demonstrate characteristic (0.5–4.6 μm) 'tags'. APP/PS1 mice also had a significantly reduced hepatic vessel number (p = 0.0002) and an increase in the number of splenic microvascular pillars (p = 0.0231), in the absence of changes in either splenic microvascular density (p = 0.3746) or glomerular ultrastructure. The highly significant reduction in uACR in APP/PS1 mice compared to wild-type (p = 0.0079) is consistent with glomerular microvascular dysfunction. These findings highlight early microvascular pathologies in 4- to 5-month-old APP/PS1 transgenic mice and may indicate an amenable target for pharmacological intervention in AD.

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Charting the Future of Cancer Health Disparities Research: A Position Statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute

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Concurrent administration of anti-HER2 therapy and radiotherapy: Review of the literature

Background: Over the past few years, anti-HER2 targeted therapies have proven to be a key treatment in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers, as well as gastrointestinal tract tumors and head and neck tumors. Anti-HER2 therapies administered alone or in combination with chemotherapy have been extensively studied, but only limited robust data are available concerning the safety and efficacy of anti-HER2 molecules in combination with radiotherapy. Methods: We searched on Medline, Embase and Cochrane databases the articles providing data on the concomitant association between the antiHER2 therapies used in clinical practice (trastuzumab, pertuzumab, lapatinib and T-DM1) with radiotherapy.

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Dose de-escalation to the elective lymph nodes in head and neck cancer. Reply to Amdur et al.

We would like to thank Amdur et al. for the comments raised on our series of papers on dose de-escalation to the elective neck in head and neck cancer [1–3]. We strongly agree that the bar should be set high for studies on this matter and that investigators need to be encouraged to further clarify the role of dose de-escalation to the elective neck in head and neck cancer. However, we want to point out that we never concluded that outcome was substantially better in the 40Gy group since our paper had a non-inferiority setting.

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The Androgen Receptor Supports Tumor Progression After the Loss of Ovarian Function in a Preclinical Model of Obesity and Breast Cancer

Abstract

The androgen receptor (AR) has context-dependent roles in breast cancer growth and progression. Overall, high tumor AR levels predict a favorable patient outcome, but several studies have established a tumor promotional role for AR, particularly in supporting the growth of estrogen receptor positive (ER-positive) breast cancers after endocrine therapy. Our previous studies have demonstrated that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat model of postmenopausal breast cancer. Here, we investigated a potential role for AR in obesity-associated post-OVX mammary tumor progression following ovarian estrogen loss. In this model, we found that obese but not lean rats had nuclear localized AR in tumors that progressed 3 weeks after OVX, compared to those that regressed. AR nuclear localization is consistent with activation of AR-dependent transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear localization and expression were maintained in tumors that had progressed, but AR expression was nearly lost in tumors that were regressing. The anti-androgen enzalutamide effectively blocked tumor progression in obese rats by promoting tumor necrosis and also prevented the formation of new tumors after OVX. Neither circulating nor mammary adipose tissue levels of the AR ligand testosterone were elevated in obese compared to lean rats; however, IL-6, which we previously reported to be higher in plasma from obese versus lean rats, sensitized breast cancer cells to low levels of testosterone. Our study demonstrates that, in the context of obesity, AR plays a role in driving ER-positive mammary tumor progression in an environment of low estrogen availability, and that circulating factors unique to the obese host, including IL-6, may influence how cancer cells respond to steroid hormones.

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Non-canonical WNT/PCP signalling in cancer: Fzd6 takes centre stage

Non-canonical WNT/PCP signalling in cancer: Fzd6 takes centre stage

Oncogenesis 6, e364 (July 2017). doi:10.1038/oncsis.2017.69

Authors: G Corda & A Sala

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Overexpression of zinc finger protein 687 enhances tumorigenic capability and promotes recurrence of hepatocellular carcinoma

Overexpression of zinc finger protein 687 enhances tumorigenic capability and promotes recurrence of hepatocellular carcinoma

Oncogenesis 6, e363 (July 2017). doi:10.1038/oncsis.2017.63

Authors: T Zhang, Y Huang, W Liu, W Meng, H Zhao, Q Yang, S-J Gu, C-C Xiao, C-C Jia, B Zhang, Y Zou, H-P Li & B-S Fu

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Cytogenetic Profile and Gene Mutations of Childhood Acute Lymphoblastic Leukemia

Background: Childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. Aims: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results. Materials and methods: Patients—We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis—Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations—Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835) using polymerase chain reaction methods. Result: Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22), t(12;21), and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7%) and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22), MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group (P = .031).The event-free survival was also found to be worse (P = .040). Conclusions: Our data are in accordance with those published previously, confirming the overall frequency of cytogenetic abnormalities and their prognostic relevance.

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Issue Information

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Ezrin-Radixin-Moesin Binding Phosphoprotein 50 (EBP50) Suppresses the Metastasis of Breast Cancer and HeLa Cells by Inhibiting Matrix Metalloproteinase-2 Activity

Background: Expression of ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) is correlated with human breast and cervical cancer development, but its effects on the metastasis of breast and cervical cancer and the underlying mechanism are not fully understood. Materials and Methods: In this study, EBP50 was overexpressed in MDA-MB-231 breast cancer and HeLa cervical cancer cells; moreover, EBP50 was knocked-down in MCF-7 breast cancer cells and HeLa cells. Metastasis-related ability and matrix metalloproteinase-2 (MMP-2) activity of these cells were investigated. Results: Cell adhesion, wound-healing and invasion were significantly suppressed in EBP50-overexpressing cells. Contrarily, EBP50-knockdown promoted cell adhesion, wound healing and invasion. EBP50 overexpression inhibited MMP-2 activity, and the knockdown of EBP50 promoted the activity of MMP-2, suggesting that EBP50 inhibited cell metastasis via suppression of MMP-2 activity. Conclusion: Our work reveals the anti-metastatic effect and a new mechanism of EBP50 action in breast and cervical cancer cells.

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miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells

Background: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). Materials and Methods: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence. Transwell assay was conducted to determine the migration rates of cells. Subcutaneous xenograft models were used to examine the effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays were used to interrogate MAPK and RTK pathway activation. Results: miR-141 directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and miR-141-knockdown cells and found that inhibition of miR-141 significantly increased the expression of ZEB2. In vitro study revealed that miR-141 overexpression inhibited the expression of Ki-67. Furthermore, overexpression of miR-141 led to a significant reduction in the proliferation of SW480 cells via induction of cell-cycle arrest at the G₁ stage. In contrast, inhibition of miR-141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle progression. Moreover, overexpression of miR-141 significantly inhibited SW480 cell migration in vitro. In addition, overexpression of miR-141 significantly reduced tumor size and weight, and inhibited the growth of SW480 cell-derived tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET) following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and mTOR, etc., in SW480 cells was not affected by miR-141. Conclusion: Our results suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC cells.

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Phase II Study of the Efficacy and Safety of High-dose Pemetrexed in Combination with Cisplatin Versus Temozolomide for the Treatment of Non-small Cell Lung Cancer with Brain Metastases

The aim of this study was to explore the efficacy and safety of high-dose pemetrexed with cisplatin versus combination with temozolomide in patients with brain metastases (BM) of lung adenocarcinoma. After standard whole-brain radiotherapy (WBRT, 30 Gy/10 fractions), patients with BM of non-small cell lung cancer (NSCLC) were given high-dose pemetrexed (900 mg/m²) on day 1 of each cycle (3 weeks), and cisplatin was administered on days 1-3 in the cisplatin-treated group. The temozolomide-treated group was treated as follows: 75 mg/m² temozolomide orally with concurrent WBRT followed by 150 mg/m² temozolomide on days 1-5 with high-dose pemetrexed (900 mg/m²) on day 1 of each cycle (3 weeks). Six cycles later, high-dose pemetrexed (900 mg/m²) monotherapy or the best available supportive therapy was administered to both groups. An evaluation was carried out every 2-3 cycles. The primary end-points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Secondary end-points included safety and tolerability. Thirty-two patients in the pemetrexed plus cisplatin (PC) group and 28 patients in the pemetrexed plus temozolomide (PT) group were enrolled from November 2013 to October 2015. The ORR was 68.8% and 75%, in the PC and PT groups, respectively, and there was no statistically significant difference between the two groups (p=0.711). The median PFS rates of the PC and PT groups were 13.6 months and 16.9 months, respectively, and the median OS rates of the PC and PT groups were 18.9 months and 19.3 months, respectively. There were no differences in PFS and OS between the two groups. There were no grade 4 or higher side-effects in either group, but grade 3 side-effects such as leucopenia (2/32, 6.3%), nausea/vomiting (2/32, 6.3%), alopecia (1/32, 3.1%), rash (3/32, 9.4%) and renal insufficiency (1/32, 3.1%) were observed in the PC group, whereas the PT-group-only showed the following grade 3 side-effects: leucopenia (1/28, 3.6%) and nausea/vomiting (2/28, 7.1%). The data showed that the PT group achieved the same efficacy in PFS and OS as the PC group but with fewer toxicities. Therefore, high-dose pemetrexed plus temozolomide may be a better regimen for treating NSCLC with BM due to its better safety.

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Effect of Interventional Therapy on the Expression of Survivin mRNA in Cervical Cancer

Aim: To examine the expression of survivin mRNA in cervical squamous cancer at different time points during interventional therapy in order to find the optimal time point for continual treatment. Patients and Methods: Fifty patients with stage IB2-IIB cervical squamous cancer receiving transarterial infusion chemotherapy and chemoembolization were included in the present study. The expression of survivin mRNA in cancer samples before and after interventional therapy (on days 7, 14 and 21) were examined by reverse transcription-polymerase chain reaction. Results: The expression of survivin mRNA in cancer samples before the interventional therapy was significantly higher than that of any time point after the interventional therapy (p<0.05). After treatment, the expression of survivin mRNA decreased until day 14. Conclusion: The expression of survivin mRNA was inhibited by the interventional therapy. It seems that day 14 after interventional treatment is the right time point for continuation of treatment.

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Study of Preoperative Antiviral Treatment of Patients with HCC Negative for HBV-DNA

Aim: To study preoperative HBV-DNA negative HBV-related hepatocellular carcinoma (HCC) which was reactivated after surgery and could influence liver function and HCC recurrence. Patients and Methods: Patients were divided into two groups according to preoperative antiviral therapy status. The control group comprised of 102 preoperative HBV-DNA-negative patients who had not undergone antiviral therapy before surgery. In the treatment group, all HBV-DNA-negative patients (n=63) received entecavir 3-5 days before surgery and for 12 months after surgery. Patients were followed-up regularly, during the preoperative period, and at 1, 3, 6, 12, 18, 24, 30 and 36 months postoperatively. The data for the two groups were analyzed including the level of HBV-DNA and HBV-DNA activation; liver function; 1-, 2- and 3-year survival rate; cumulative survival time; and tumor recurrence. Results: Liver function in the treatment group was better than that of the control group12 months after surgery. Compared to the control group, total bilirubin in the treatment group was significantly better at 6 and 12 months after surgery (p<0.05 and p<0.001, respectively). Serum albumin, alanine aminotransferase and prothrombin time in the treatment group was significantly better than that of controls 12 months after surgery (p<0.001). In the treatment group, two cases (3.17%) had HBV-DNA activation while there were 13 cases (12.75%) with HBV-DNA activation in the control group (p<0.05). There were 51 cases with tumor recurrence in the control group, that was statistically significantly higher than recurrent cases in the treatment group (p<0.05). Postoperative 1-, 2- and 3-year cumulative overall survival rates were 94.12%, 81.37% and 52.94%, respectively, for the control group and 93.65%, 77.78% and 71.43%, respectively, for the treatment group (p=0.006). There was no statistically significant difference in disease-free survival between the two groups (p=0.231). Conclusion: Antiviral treatment of HBV-related HCC with negative HBV-DNA is beneficial to liver function, coagulation function, disease control, prevention of tumor recurrence, improvement of patient quality of life, reduces the death rate and prolongs survival duration.

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Independent Correlation Between Ki67 Index and Circulating Tumor Cells in the Diagnosis of Colorectal Cancer

Background: The Ki67 index is a biomarker of proliferation, while the circulating tumor cell (CTC) count acts as a metastasis-related biomarker. In this study, we analyzed the potential value of CTC count and Ki67 index in diagnosis of colorectal cancer (CRC). Materials and Methods: A total of 105 patients with CRC undergoing surgery were included in the study. Isolation and identification of CTCs were performed by negative enrichment and immuno-fluorescence in situ hybridization, respectively. Expression of Ki67 was assessed by immunohistochemistry. Results: Patients with CTC count ≥2 were defined as CTC-positive. Ki67 index ≥50% was regarded as highly proliferative. Overall, 71 cases were CTC-positive, while 82 cases displayed a high Ki67 index. CTC count and Ki67 index had no correlation with tumor size, tumor site, age, gender and TNM stages of the patients. CTC count was correlated with tumor size (p=0.018) and Ki67 index with level of differentiation (p<0.001). However, there was no relationship between CTC count and Ki67 index (p=0.198). Conclusion: Our results suggest that CTCs can act as a potent metastasis-related biomarker for the diagnosis of CRC, independently of the Ki67 index.

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Efficacy and Safety of Nab-Paclitaxel as Second-line Chemotherapy for Locally Advanced and Metastatic Non-small Cell Lung Cancer

Aim: To investigate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for locally advanced or metastatic non-small cell lung cancer (NSCLC) as second-line chemotherapy. Patients and Methods: We retrospectively reviewed the treatment of 34 patients with advanced NSCLC whose first-line treatment had failed. These patients received nab-paclitaxel 260 mg/m² on day 1 and day 8 of a 21-day cycle from July 2014 to February 2016. One cycle of treatment lasted 3 weeks and all patients completed more than two cycles. All patients were assessed for adverse events related to treatment. Results: No patient achieved complete response (CR); 12 patients reached partial response (PR), 12 patients achieved stable disease (SD) and 10 patients progressive disease (PD). The overall response rate (ORR) was 35.3% and the disease control rate (DCR) 70.6 %. There was no significant difference in either ORR or DCR within the subgroups. The median progression-free survival (PFS) was 5.7 months (95% confidence interval (CI)=3.8-7.6) and the median overall survival (OS) was 9 months (95% CI=8.3-9.7). There was no statistical difference in OS (p=0.066), but subgroup analysis showed that patients with squamous carcinoma benefited more in PFS (the median PFS of squamous carcinoma vs. adenocarcinoma was 7.3 months vs. 5 months, p=0.001). Major adverse events included myelosuppression, gastrointestinal response, baldness, myalgia and neurotoxicity. Hypersensitivity reactions were not reported. Conclusion: Nab-paclitaxel is an effective chemotherapy for locally advanced and metastatic NSCLC as treatment and has a superior application prospect for squamous NSCLC. Toxicity is generally mild and manageable.

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Clinical Characteristics and Prognosis of Elderly Small Cell Lung Cancer Patients Complicated with Hyponatremia: A Retrospective Analysis

Aim: This study was designed to evaluate the clinical characteristics and prognosis of elderly small cell lung cancer (SCLC) patients complicated with hyponatremia, thus providing increased attention for appropriate intervention and improving outcomes in symptomatic subjects. Patients and Methods: The clinical data of 320 patients with SCLC in the Yuhuangding Hospital from March 1st, 2006, to March 1st, 2012, were studied retrospectively. The prognosis and possible association with hyponatremia was investigated. Results: The incidence rate of hyponatremia in SCLC was 46.56% (149/320). The mean survival time was 1.10±0.42 years in patients with normal values and 0.83±0.35 years in patients with subnormal serum sodium. In the hyponatremia group, the mean survival time of corrected hyponatremia patients was 0.91±0.42 years, which was significantly longer than uncorrected hyponatremia patients whose mean survival time was 0.68±0.26 years (t=2.75, p<0.05) after symptomatic treatment. The mean survival time of the normal group and the hyponatremia group in elderly patients had a tendency to decrease when compared to another group of patients younger than 60 years old. Hyponatremia at 1- and 3-year follow-up was associated with worse survival rates (p<0.05). Conclusion: The severity of hyponatremia has unfavorable prognostic impacts. Elderly SCLC patients with hyponatremia are difficult to cure and associated with significantly shorter survival, especially in the uncorrected group. It is important that the cause of the hyponatremia is diagnosed at an early stage and precise medical treatment is provided.

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Gastric Cancer Mortality Trends in China (2006-2013) Reveal Increasing Mortality in Young Subjects

Background/Aim: Although the advent of Helicobacter pylori eradication and global societal changes are widely assumed to impact on gastric cancer (GC)-related mortality, there is remarkable little quantitative and qualitative insight into the nature of its effects. Here, we exploited a nationwide reporting system to investigate the epidemiological features of GC-related mortality in China between 2006 and 2013. Patients and Methods: GC mortality data between 2006 and 2013 were obtained from the National Disease Surveillance System published by the China Center for Disease Control and Prevention (CDC). Results: GC mortality increased by 8.2% (from 18.87/100,000 to 20.41/100,000), while GC mortality standardized by the age scale of the population in 2010 decreased by 17.8% (from 21.87/100,000 to 17.98/100,000). Standardized GC mortality in males (25.66/100,000 to 33.89/100,000) was higher compared to females (10.72/100,000 to 14.79/100,000), while standardized GC mortality in rural areas (19.17/100,000 to 26.46/100,000) was higher than in urban areas (15.48/100,000 to 20.04/100,000). Both crude and standardized rates in the 0- to 29-year-old group increased by 22.3% and 16.2%, respectively; while these rates declined in the 30- to 59-year-old group and over 60-year-old group. The proportion of GC deaths that accounts for all cancer deaths declined from 15.99% (2006) to 13.6% (2013); however, the proportion in the 0- to 29-year-old group revealed an increasing trend from 2006 (3.20%) to 2013 (3.87%). Conclusion: Our results reveal a remarkable increase in GC-related mortality in subjects under the age of 30 calling for further measures to prevent the increase in the incidence of GC in young patients.

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Effects of Different Palliative Jaundice Reducing Methods on Immunologic Functions in Patients with Advanced Malignant Obstructive Jaundice

Background/Aim: This study aimed to investigate the effects of three treatment methods on the immunological function of patients with advanced malignant obstructive jaundice (MOJ). Patients and Methods: Patients with advanced MOJ were randomly divided into three groups according to biliary drainage methods. Detection of levels of multi-indices were investigated in different time periods. Results: After drainage, the levels of complement 3 (C3) and complement 4 (C4) were increased. Forteen days post-operation, the levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) in the group undergoing palliative surgery decreased significantly compared to those in both percutaneous transhepatic cholangio drainage (PTCD) and endoscopic retrograde biliary drainage (ERBD) groups. The level of serum endotoxin in the group undergoing palliative surgery decreased gradually. Conclusion: Palliative surgery for reducing jaundice is superior to PTCD and ERBD in improving immune function of patients with MOJ.

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Preoperative High Neutrophil-to-Lymphocyte Ratio Is Associated with High-grade Bladder Cancer

Aim: To evaluate the correlation between the neutrophil–to–lymphocyte ratio (NLR) and histopathological characteristics of bladder cancer. Materials and Methods: A retrospective analysis was performed on a cohort of patients (n=302) who were diagnosed with bladder cancer and underwent transurethral resection of bladder tumor or cystectomy between 2009 and 2016. The pathological outcomes were compared between patients with low NLR and those with high NLR with a cut-off value of 2.5, and a logistic regression analysis was performed to find potential predictors of pathological tumor outcomes. Results: Patients with high-grade disease had significantly higher NLRs compared to those with low-grade disease (median NLR=4.42 vs. 3.42, p<0.001). Univariate analysis suggested that age, neutrophil count and NLR, as a continuous or binary variable, were significantly associated with high-grade disease. Multivariate analysis suggested that age and NLR, as a continuous variable, were predictors of pathologically high-grade disease. Conclusion: Preoperative NLR was found to be associated with pathological tumor grading, but was not associated with pathological tumor staging in patients with bladder cancer.

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Predictors of Malignancy for Female Patients with Suspicious Nipple Discharge: A Retrospective Study

Background: Suspicious nipple discharge (ND) in females requires further treatment, including biopsy or selective duct excision. It is important to identify predictors of malignancy in female patients with suspicious ND. Materials and Methods: This retrospective study included patients with suspicious ND who underwent surgical treatment at our center between January 2007 and December 2014. Clinicopathological features were compared between patients with and without malignancy. We used a Chi-square test and a logistic regression model as the univariate and multivariate analysis for identification of predictors of malignancy. Results: A total of 334 patients were eligible and included. The median age of the study population was 45 (range=19-81) years; 18.0% (60/334) of the entire study population had breast cancer. The univariate analysis suggested that older age (p=0.002) and presence of suspicious lumps (p<0.001) were significantly associated with malignancy. In contrast, presence of bloody discharge was not significantly associated with malignancy (p=0.324). The multivariate analysis confirmed that older age (p=0.023) and presence of suspicious lumps (p<0.001) were independent predictors of malignancy. For patients without suspicious lumps, we did not observe any association between the presence of bloody discharge and malignancy. For patients with suspicious lumps, tumor size was significantly associated with malignancy (p<0.001). Conclusion: Our study suggests that older age and the presence of suspicious lumps are predictors of the presence of malignancy in females with suspicious ND.

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Clinical Study on Using 125I Seeds Articles Combined with Biliary Stent Implantation in the Treatment of Malignant Obstructive Jaundice

Aim: To study the feasibility and curative effect of ¹²⁵I seeds articles combined with biliary stent implantation in the treatment of malignant obstructive jaundice. Patients and Methods: Fifty patients with malignant obstructive jaundice were included. Twenty-four were treated by biliary stent implantation combined with intraluminal brachytherapy by ¹²⁵I seeds articles as the experimental group, while the remaining 26 were treated by biliary stent implantation only as the control group. The goal of this study was to evaluate total bilirubin, direct bilirubin and tumor markers (cancer antigen (CA)-199, CA-242 and carcinoembryonic antigen (CEA)), as well as biliary stent patency status and survival time before and after surgery. Results: Jaundice improved greatly in both groups. The decreases of CA-199 and CA-242 had statistical significance (p=0.003 and p=0.004) in the experimental group. The ratio of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (p=0.048). The biliary stent patency time in the experimental group was 1~15.5 (mean=9.84) months. The biliary stent patency time in the control group was 0.8~9 (mean=5.57) months, which was statistically significant (p=0.018). The median survival time was 10.2 months in the experimental group, while 5.4 months in control group (p<0.05). Conclusion: ¹²⁵I seeds articles combined with biliary stent implantation significantly prolongs biliary stent patency time and survival time for patients with malignant obstructive jaundice possibly by inhibiting the proliferation of vascular endothelial cells and the growth of tumor.

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Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced Esophageal Carcinoma

Background/Aim: Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. Patients and Methods: One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. Results: There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. Conclusion: The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia.

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MR-guided Percutaneous Biopsy of Focal Hepatic Dome Lesions with Free-hand Combined with MR Fluoroscopy Using 1.0-T Open High-field Scanner

Aim: To prospectively estimate the safety, feasibility and accuracy of 1.0T open-magnetic resonance (MR)-guided percutaneous biopsy in free-hand of focal lesions located in the hepatic dome. Materials and Methods: All percutaneous MR-guided biopsies of the lesions were performed at the Shandong Medical Imaging Research Institute. Thirty-six patients with focal liver lesions located in the hepatic dome measuring 6-36 mm in the maximum diameter were included in this study. Lesions were divided into two groups on the basis of maximum nodule diameters: ≤1.5 cm (n=14) and >1.5 cm (n=22). Surgical pathology of nodules or clinical and imaging follow-up for at least 12 months were used to establish final diagnosis. Diagnostic accuracy, specificity, sensitivity, average procedure time and complications were recorded and analyzed. Results: All obtained samples were sufficient for diagnosis. Accuracy, sensitivity and specificity of MRI-guided percutaneous liver lesions biopsy in diagnosing malignant tumors were 97.2%, 96.7% and 100%, respectively. Accuracy, sensitivity and specificity were 92.9%, 90.9% and 100% for the lesions that were 1.5 cm or smaller in diameter and 100%, 100% and 100% for lesions larger than 1.5 cm in diameter, respectively. There was no significant difference between the two groups (p>0.05). The average procedure time for each pass of the needle from skin entry to the target lesion was 1.1 min and the total procedural time was 28.5 min. Biopsy-induced complications included peri-hepatic hemorrhage in 8.3% (3/36) of cases. No serious complications occurred. Conclusion: 1.0T open-MR-guided free-hand percutaneous biopsy is a safe, feasible and highly accurate diagnostic method for pathological diagnosis of focal liver lesions located in the hepatic dome.

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Exploration of the Radiotherapeutic Clinical Target Volume Delineation for Gastric Cancer from Lymph Node Metastases

Aim: To clarify the clinical target volume of regional lymph nodes (CTVn) delineation of gastric adenocarcinoma. Materials and Methods: The pattern of lymph node metastases (LNM) of a total of 1,473 patients with gastric cancer (GC) who had undergone gastrectomy and lymphadenectomy with more than 15 lymph nodes retrieved was retrospectively examined. Results: A univariate analysis showed that T stage (p<0.001), macroscopic type (p=0.001), tumor differentiation (p<0.001), maximum diameter of tumor (p<0.001) as well as cancer embolus (p<0.001) were closely associated with the rate of LNM. While by multivariate analysis, gender [odds ratio (OR=0.687, p<0.05], maximum diameter (OR=1.734, p<0.001), tumor differentiation (OR=1.584, p<0.001), T stage (OR=2.066, p<0.001) and cancer embolus (OR=4.912, p<0.001) were strongly associated with the rate of LNM. Conclusion: In conclusion, for male patients with GC with large, deeply invasive, poorly differentiated, diffusely infiltration and positive cancer embolus, the radiation fields should be enlarged appropriately.

http://ift.tt/2tUNTaw

Comparison of Efficiency of Video Endoscopy and Open Inguinal Lymph Node Dissection

Aims: To compare the efficiency and complications of video endoscopy, inguinal lymphadenectomy and open inguinal lymph node dissection. Patients and Methods: Nineteen video endoscopy inguinal lymphadenectomies were performed on 16 patients from September 2014 to December 2015, and 21 open inguinal lymph node dissections were performed on 18 patients from September 2013 to September 2014. Surgical time, operative blood loss, incidence of complications, length of stay, lymph node harvest and suture removal time were compared between the two groups. Results: Operative time (135.5±45.52 vs. 169.8±55.19 min), lymph node harvest (10.78±5.22 vs. 12.60±5.53), and hospital stay (10.43±2.53 vs. 12.50±4.98 days) did not statistically differ between the two groups (p>0.05). However, operative blood loss (22.50±14.24 vs. 68.44±42.19 ml), drainage tube removal time (7.23±1.79 vs. 11.44±2.69 days), incidence of complications (21.05% vs. 61.9%), and suture removal time (7.52±1.24 vs. 12.81±2.04 min) were significantly reduced in the video endoscopy surgery group compared with the open surgery group (p<0.05). Conclusion: Compared with open surgery, video endoscopy surgery achieved the same efficiency, and had the advantage of reduction of complications, suture removal time and in-surgery blood loss.

http://ift.tt/2tEVezP

The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective Analysis

Background/Aim: The American Joint Committee on Cancer (AJCC) released its 8th edition of tumor staging which is to be implemented in early 2018. The present study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging System in HER2-enriched breast cancer, on a retrospective cohort. Patients and Methods: This study was a retrospective single-center study of HER2-enriched breast cancer cases diagnosed from January 2008 to December 2014. Clinicopathological features and follow up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore prognostic factors for disease outcome. We restaged patients based on the 8th edition of the AJCC cancer staging system and analyzed prognostic value of the Anatomic Stage Group and the Prognostic Stage Group. Results: The study enrolled 170 HER2-enriched subtype breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5-year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%) changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged case. The Anatomic Stage Groups had a significant prognostic impact on DFS (²=16.752, p<0.001) and OS (²=25.038, p<0.001). The Prognostic Staging Groups had a significant prognostic impact on DFS (²=6.577, p=0.037) and OS (²=21.762, p<0.001). In the multivariate analysis, both stage groups were independent predictors of OS. Conclusion: Both Anatomic and Prognostic Stage Groups in the 8th edition of the AJCC breast cancer staging system had prognostic value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a breakthrough on the basis of anatomic staging system.

http://ift.tt/2tUpqlq

Cyclosporin A Reversed Chemoresistance of a Patient with Pure Red Cell Aplasia Secondary to Thymoma

Case Report: This case study reports on a patient who relapsed with thymoma (mixed type) nine years after tumor resection. After four courses of rescue chemotherapy (docetaxel and cisplatinum), the patient was further diagnosed with pure red cell aplasia. It was noticed that cyclosporin A (CsA), which was administered to treat aplasia, could reverse chemoresistance. Its mechanism is not completely clear, but the hypothesis of CsA inhibiting P-glycoprotein mediated drug efflux is the most acceptable.

http://ift.tt/2tE8mVO

Explored Risk Factors for Lymph Node Metastasis with Siewert II/III Adenocarcinoma of the Gastroesophageal Junction

Aim: To explore the risk factors and prognosis for lymphatic metastasis (LNM) in patients with Siewert II/III adenocarcinoma of the gastroesophageal junction (AEG). Patients and Methods: This study retrospectively reviewed 49 patients with Siewert II/III AEG. Clinical characteristics and pathological features were analyzed by the Chi-square the and binary logistic regression. Survival data were analyzed using the Kaplan–Meier method. Results: LNM frequency was found in lymph nodes No.1, No.2, No.3, No.7, No.11 and No.110. The results revealed that depth of infiltration, neoplasms by histological type and lymphatic embolus were independent risk factors for LNM. The 1- and 3-year survival of patients without LNM were both 100%, while patients with LNM had 70% and 60% survival, respectively. Although the differences were not statistically significant, survival rate with negative lymph nodes was higher than in patients with LNM. Conclusion: Total gastrectomy combined with D2 No.110 lymphadenectomy might improve the prognosis for LNM patients.

http://ift.tt/2tU86xh

Amplification of EGFR and cyclin D1 genes associated with human papillomavirus infection in oral squamous cell carcinoma

Abstract

Human papillomavirus (HPV) infection is associated with several genetic alterations including oncogene amplification, leading to increased aggression of tumors. Recently, a relationship between HPV infection and oncogene amplification has been reported, but this finding remains controversial. This study therefore investigated relationships between HPV infection and amplification of genes in the epidermal growth factor receptor (EGFR) signaling cascade in oral squamous cell carcinoma (OSCC). Extracted DNA from 142 formalin-fixed paraffin-embedded (FFPE) OSCC tissues was performed to investigate the copy number of EGFR, KRAS, c-myc and cyclin D1 genes using real-time polymerase chain reaction (RT-PCR) and compared with calibrators. A tissue microarray of OSCC tissues was used for detection of c-Myc expression and HPV infection by immunohistochemistry and HPV E6/E7 RNA in situ hybridization, respectively. HPV infection was also investigated using PCR and RT-PCR. Of the 142 OSCC samples, 81 (57%) were HPV-infected cases. The most frequently amplified gene was c-myc (55.6%), followed by cyclin D1 (26.1%), EGFR (23.9%) and KRAS (19.7%). Amplification of c-myc was significantly associated with levels of its protein product. EGFR amplification was also significantly associated with amplification of genes in the signaling cascade: KRAS (50.0%), c-myc (34.2%) and cyclin D1 (46.0%). Interestingly, HPV infection was significantly associated with amplification of both EGFR (76.5%) and cyclin D1 (73.0%). Only cyclin D1 amplification was significantly associated with severity of OSCC histopathology. HPV infection may play an important synergistic role in amplification of genes in the EGFR signaling cascade, leading to increased aggression in oral malignancies.

http://ift.tt/2gXmq6U

Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma

Abstract

Background

Germline mutations in genes encoding subunits of succinate dehydrogenase (SDH) are associated with the development of pheochromocytoma (PC) and/or paraganglioma (PGL). As assembly factors have been identified as playing a role in maturation of individual SDH subunits and assembly of the functioning SDH complex, we hypothesized that SDHAF3 variants may be associated with PC/PGL and functionality of SDH.

Methods

DNA was extracted from the blood of 37 individuals (from 23 families) with germline SDH mutations and 18 PC/PGL (15 sporadic, 3 familial) and screened for mutations using a custom gene panel, containing SDHAF3 (SDH assembly factor 3) as well as eight known PC/PGL susceptibility genes. Molecular and functional consequences of an identified sequence variant of SDHAF3 were assessed in yeast and mammalian cells (HEK293).

Results

Using massively parallel sequencing, we identified a variant in SDHAF3, c.157 T > C (p.Phe53Leu), associated with increased prevalence in familial and sporadic PC/PGL (6.6%) when compared to normal populations (1.2% [1000 Genomes], p = 0.003; 2.1% [Exome Aggregation Consortium], p = 0.0063). In silico prediction tools suggest this variant is probably damaging to protein function, hence we assessed molecular and functional consequences of the resulting amino acid change (p.Phe53Leu) in yeast and human cells. We showed that introduction of SDHAF3 p.Phe53Leu into Sdh7 (ortholog of SDHAF3 in humans) null yeast resulted in impaired function, as observed by its failure to restore SDH activity when expressed in Sdh7 null yeast relative to WT SDHAF3. As SDHAF3 is involved in maturation of SDHB, we tested the functional impact of SDHAF3 c.157 T > C and various clinically relevant SDHB mutations on this interaction. Our in vitro studies in human cells show that SDHAF3 interacts with SDHB (residues 46 and 242), with impaired interaction observed in the presence of the SDHAF3 c.157 T > C variant.

Conclusions

Our studies reveal novel insights into the biogenesis of SDH, uncovering a vital interaction between SDHAF3 and SDHB. We have shown that SDHAF3 interacts directly with SDHB (residue 242 being key to this interaction), and that a variant in SDHAF3 (c.157 T > C [p.Phe53Leu]) may be more prevalent in individuals with PC/PGL, and is hypomorphic via impaired interaction with SDHB.

http://ift.tt/2utD1lL

Prevention of HPV-Related Oral Cancer by Dentists: Assessing the Opinion of Dutch Dental Students

Abstract

The aim of this study is to assess dental students' opinions of the dentists' role in primary prevention of human papillomavirus (HPV)-related oral cancer using a cross-sectional web-based survey. A questionnaire, containing questions about knowledge of HPV and oral cancer, confidence in head and neck examination and role of the dentist in preventing HPV-related oral cancer, was sent to all students of the Academic Centre of Dentistry Amsterdam (n = 912). One hundred and twenty-six (n = 126) students completed the questionnaire. Significantly, more master students (75%) than bachelor students (54.3%) were aware that HPV is a causative factor for oral cancer. Master students had more knowledge of HPV than bachelor students, but knowledge about HPV vaccination was irrespective of the study phase. The majority of dental students agreed that it is important to discuss HPV vaccination with patients. Eighty-nine percent of the students think that more education about symptoms of oral cancer will increase screening for oral cancer. Development of a protocol for screening in dental practices was considered even more important. According to dental students, dentists should discuss HPV as a risk factor for oral cancer with patients. Future dentists are willing to be involved in both primary and secondary prevention of HPV-related oral cancer. Therefore, screening for oral cancer and education about HPV vaccination should be integral elements of the dental curriculum.

http://ift.tt/2vTf6vJ

Application of the new 8th TNM staging system for non-small cell lung cancer: treated with curative concurrent chemoradiotherapy

The eighth tumor, node, metastasis (TNM) staging system (8-TNM) for non-small cell lung cancer (NSCLC) was newly released in 2015. This system had limitation because most patients included in the analysis were...

http://ift.tt/2uQtBU3

A potent indolylquinoline alleviates growth of human lung cancer cell tumorspheres

Abstract

To fight cancer at its roots by targeting cancer stem cells is a promising approach for therapy. Previously, an indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), was reported effectively inhibiting the growth of lung cancer cells through impairment of cellular mitochondria functions. To address more on drug efficiency, the study further exploited if EMMQ can impede the propagation of tumorspheres stemmed from non-small cell lung cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal models, administration of the drug attenuated the spheroid tumorigenicity. The activated apoptosis alleviated growth of xenograft tumors in immune-deficient mice as established by the enriched tumorspheres. More evidence suggested that the reduced stemness of the spheroid tumors is attributed to apoptotic death. The findings supported that EMMQ is an eligible approach to eradicate the minor but tumorigenic lung cancer tumorspheres.

http://ift.tt/2ut0qnq

Role of long non-coding RNAs in glucose metabolism in cancer

Abstract

Long-noncoding RNAs (lncRNAs) are a group of transcripts that are longer than 200 nucleotides and do not code for proteins. However, this class of RNAs plays pivotal regulatory roles. The mechanism of their action is highly complex. Mounting evidence shows that lncRNAs can regulate cancer onset and progression in a variety of ways. They can not only regulate cancer cell proliferation, differentiation, invasion and metastasis, but can also regulate glucose metabolism in cancer cells through different ways, such as by directly regulating the glycolytic enzymes and glucose transporters (GLUTs), or indirectly modulating the signaling pathways. In this review, we summarized the role of lncRNAs in regulating glucose metabolism in cancer, which will help understand better the pathogenesis of malignant tumors. The understanding of the role of lncRNAs in glucose metabolism may help provide new therapeutic targets and novel diagnostic and prognosis markers for human cancer.

http://ift.tt/2utFXPa

Metformin suppresses cancer initiation and progression in genetic mouse models of pancreatic cancer

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide with an overall five-year survival rate less than 7%. Accumulating evidence has revealed the cancer preventive and therapeutic effects of metformin, one of the most widely prescribed medications for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully elucidated. Herein, we aimed to further study the preventive and therapeutic effects of metformin in genetically engineered mouse models of pancreatic cancer.

Methods

LSL-Kras^G12D/+; Pdx1-Cre (KC) mouse model was established to investigate the effect of metformin in pancreatic tumorigenesis suppression; LSL-Kras^G12D/+; Trp53^fl/+; Pdx1-Cre (KPC) mouse model was used to evaluate the therapeutic efficiency of metformin in PDAC. Chronic pancreatitis was induced in KC mice by peritoneal injection of cerulein.

Results

Following metformin treatment, pancreatic acinar-to-ductal metaplasia (ADM) and mouse pancreatic intraepithelial neoplasia (mPanIN) were decreased in KC mice. Chronic pancreatitis induced a stroma-rich and duct-like structure and increased the formation of ADM and mPanIN lesions, in line with an increased cytokeratin 19 (CK19)-stained area. Metformin treatment diminished chronic pancreatitis-mediated ADM and mPanIN formation. In addition, it alleviated the percent area of Masson's trichrome staining, and decreased the number of Ki67-positive cells. In KPC mice, metformin inhibited tumor growth and the incidence of abdominal invasion. More importantly, it prolonged the overall survival.

Conclusions

Metformin inhibited pancreatic cancer initiation, suppressed chronic pancreatitis-induced tumorigenesis, and showed promising therapeutic effect in PDAC.

http://ift.tt/2uPVQSS

Assessing Cancer Health Literacy among Spanish-Speaking Latinos

Abstract

Health literacy is a dynamic construct that changes with specific health conditions; thus, new disease-specific health literacy tools are needed. Since cancer is the leading cause of death among Latinos, the largest and fastest-growing minority population in the nation, there is a need to develop tools to assess cancer health literacy (CHL) among the Spanish-speaking population. The Cancer Health Literacy Test, Spanish version (CHLT-30-DKspa) was applied to identify Spanish-speaking individuals with low CHL and ascertain which items in the tool best discriminate between CHL level groups. Cross-sectional field test of the CHLT-30-DKspa among Spanish-speaking Latinos. Latent class analysis (LCA) identified participants with varying CHL levels. Probability of correct answers, odds ratios, and standardized errors were used to identify the items that allow the classification of individuals among the latent classes. LCA resulted in a three-latent-class model predicting 39.4% of participants to be in the HIGH class, 43.3% in the MEDIUM class, and 17.3% in the LOW class. Eleven items (the CHLT-11-DKspa) meet the criteria to clearly separate participants with HIGH and LOW classes of CHL. Although the best model fit was a three-class solution, results showed a clear separation of individuals from HIGH versus LOW levels of CHL, but separation of those in the MEDIUM level was not as clear. The CHLT-11-DKspa is a shorter measure that may be relatively easy to use in a clinical encounter to identify Spanish-speaking patients with the poorest levels of CHL who may require additional support to understand medical instructions and care plans.

http://ift.tt/2gWY3Gm

A new key player in VEGF-dependent angiogenesis in human hepatocellular carcinoma: dimethylarginine dimethylaminohydrolase 1

Abstract

Background

Anti-angiogenic therapies, targeting VEGF, are a promising treatment for hepatocellular carcinoma (HCC). To enhance this potential therapy, identification of novel targets in this pathway is of major interest. Nitric oxide (NO) plays a crucial role in VEGF-dependent angiogenesis. NO production depends on arginine as substrate and asymmetric dimethylarginine (ADMA) as inhibitor. Dimethylarginine dimethylaminohydrolase 1 (DDAH-1) catabolizes ADMA and therefore regulates NO and VEGF expression. This study unravels additional mechanisms to improve VEGF targeting therapies.

Methods

The expression of DDAH-1 was examined in HCC specimen and non-tumorous background liver of 20 patients undergoing liver resection. Subsequently, arginine/ADMA balance, NO production, and VEGF expression were analyzed. The influence of hypoxia on DDAH-1 and angiogenesis promoting factors was evaluated in HepG2 cells and primary human hepatocytes.

Results

DDAH-1 expression was significantly induced in primary HCC tumors compared to non-tumorous background liver. This was associated with an increased arginine/ADMA ratio, higher NO formation, and higher VEGF expression in human HCC compared to non-tumorous liver. Hypoxia induced DDAH-1, iNOS, and VEGF expression in a time-dependent manner in HepG2 cells.

Conclusions

Our results indicate that DDAH-1 expression is increased in human HCC, which is associated with an increase in the arginine/ADMA ratio and enhanced NO formation. Hypoxia may be an initiating factor for the increase in DDAH-1 expression. DDAH-1 expression is associated with promotion of angiogenesis stimulating factor VEGF. Together, our findings for the first time identified DDAH-1 as a key player in the regulation of angiogenesis in human HCC, and by understanding this mechanism, future therapeutic strategies targeting VEGF can be improved.

http://ift.tt/2vBzty5

Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer families

Abstract

Background

BRCA1 and BRCA2 mutations explain approximately one-fifth of the inherited susceptibility in high-risk Finnish hereditary breast and ovarian cancer (HBOC) families. EMSY is located in the breast cancer-associated chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that has been implicated in DNA damage repair and genomic instability. We analysed the role of germline EMSY variation in breast/ovarian cancer predisposition. The present study describes the first EMSY screening in patients with high familial risk for this disease.

Methods

Index individuals from 71 high-risk, BRCA1/2-negative HBOC families were screened for germline EMSY sequence alterations in protein coding regions and exon-intron boundaries using Sanger sequencing and TaqMan assays. The identified variants were further screened in 36 Finnish HBOC patients and 904 controls. Moreover, one novel intronic deletion was screened in a cohort of 404 breast cancer patients unselected for family history. Haplotype block structure and the association of haplotypes with breast/ovarian cancer were analysed using Haploview. The functionality of the identified variants was predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or-Not-Pipeline 2.

Results

Altogether, 12 germline EMSY variants were observed. Two alterations were located in the coding region, five alterations were intronic, and five alterations were located in the 3'untranslated region (UTR). Variant frequencies did not significantly differ between cases and controls. The novel variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer patients, and the carrier showed a bilateral form of the disease. The deletion was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer patients unselected for family history. No haplotype was identified to increase the risk of breast/ovarian cancer. Functional analyses suggested that variants, particularly in the 3'UTR, were located within regulatory elements. The novel deletion was predicted to affect splicing regulatory elements.

Conclusions

These results suggest that the identified EMSY variants are likely neutral at the population level. However, these variants may contribute to breast/ovarian cancer risk in single families. Additional analyses are warranted for rare novel intronic deletions and the 3'UTR variants predicted to have functional roles.

http://ift.tt/2tUmKEx

Assessing Cancer Health Literacy among Spanish-Speaking Latinos

Abstract

Health literacy is a dynamic construct that changes with specific health conditions; thus, new disease-specific health literacy tools are needed. Since cancer is the leading cause of death among Latinos, the largest and fastest-growing minority population in the nation, there is a need to develop tools to assess cancer health literacy (CHL) among the Spanish-speaking population. The Cancer Health Literacy Test, Spanish version (CHLT-30-DKspa) was applied to identify Spanish-speaking individuals with low CHL and ascertain which items in the tool best discriminate between CHL level groups. Cross-sectional field test of the CHLT-30-DKspa among Spanish-speaking Latinos. Latent class analysis (LCA) identified participants with varying CHL levels. Probability of correct answers, odds ratios, and standardized errors were used to identify the items that allow the classification of individuals among the latent classes. LCA resulted in a three-latent-class model predicting 39.4% of participants to be in the HIGH class, 43.3% in the MEDIUM class, and 17.3% in the LOW class. Eleven items (the CHLT-11-DKspa) meet the criteria to clearly separate participants with HIGH and LOW classes of CHL. Although the best model fit was a three-class solution, results showed a clear separation of individuals from HIGH versus LOW levels of CHL, but separation of those in the MEDIUM level was not as clear. The CHLT-11-DKspa is a shorter measure that may be relatively easy to use in a clinical encounter to identify Spanish-speaking patients with the poorest levels of CHL who may require additional support to understand medical instructions and care plans.

http://ift.tt/2gWY3Gm

Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma

Abstract

Background

The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.

Methods

Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs.

Results

On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis.

Conclusion

TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.

http://ift.tt/2tubUpt

Microglial depletion and activation: A [ 11 C]PBR28 PET study in nonhuman primates

Abstract

Background

The 18-kDa translocator protein (TSPO) is an important target for assessing neuroimmune function in brain with positron-emission tomography (PET) imaging. The goal of this work was to assess two [¹¹C]PBR28 imaging paradigms for measuring dynamic microglia changes in Macaca mulatta.

Methods

Dynamic [¹¹C]PBR28 PET imaging data with arterial blood sampling were acquired to quantify TSPO levels as [¹¹C]PBR28 V _T. Scans were acquired at three timepoints: baseline, immediately post-drug, and prolonged post-drug.

Results

In one animal, a colony-stimulating factor 1 receptor kinase inhibitor, previously shown to deplete brain microglia, reduced [¹¹C]PBR28 V _T in brain by 46 ± 3% from baseline, which recovered after 12 days to 7 ± 5% from baseline. In a different animal, acute lipopolysaccharide administration, shown to activate brain microglia, increased [¹¹C]PBR28 V _T in brain by 39 ± 9% from baseline, which recovered after 14 days to −11 ± 3% from baseline.

Conclusions

These studies provide preliminary evidence of complementary paradigms to assess microglia dynamics via in vivo TSPO imaging.

http://ift.tt/2tDBVXF

Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with hyperbaric oxygen therapy

Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy.

http://ift.tt/2uQK36e

Case of a strangulated right paraduodenal fossa hernia in a malrotated gut

We report an unusual case of a strangulated internal hernia resulting from a right paraduodenal fossa hernia (PDH) in the context of bowel malrotation. There are few documented cases of PDHs associated with a concomitant gut malrotation. Emergency laparotomy was performed based on clinical and radiological. Intraoperatively, the proximal jejunum was seen to enter a hernia sac formed by an aberrant duodenojejunal flexure located to the right of the aorta. This was presumed to be a strangulated internal hernia of the paraduodenal recess in a malrotated gut. The hernia neck was widened and the sac obliterated to allow reduction of the contents. On reduction and warming, the insulted small bowel appeared viable and returned to the abdominal cavity without resection.

http://ift.tt/2usDrZz

Silent tracheobronchial chondritis in a patient with a delayed diagnosis of relapsing polychondritis

Relapsing polychondritis is a very rare autoimmune disease characterised by a relapsing inflammation of hyaline, elastic and fibrous cartilaginous tissues. The incidence is estimated to be between 3.5 and 4.5 per million people per year. Clinical signs and symptoms can be very subtle, and if left undiagnosed for a prolonged period, airway involvement can cause fibrosis of the tracheobronchial wall, leading to a fixed tracheobronchial stenosis. Eventually, this can progress to life-threatening tracheobronchomalacia due to irreversible damage and loss of tissue integrity. We report an elderly man who presented with recurrent bilateral ear inflammation and intermittent polyarthritis who was diagnosed with relapsing polychondritis with asymptomatic involvement of his large airways.

http://ift.tt/2uRaiJP

Loculated empyema due to tuberculosis in a child

A 9-year-old girl from black ethnic origin presented with a history of fever, cough, loss of weight and right-sided chest wall pain for 2 weeks. Chest X-ray demonstrated an effusion, which was shown to be loculated on chest CT scan. She was not responding to medical treatment and at thoracotomy loculated pus was drained. Mycobacterium tuberculosis (TB) was cultured from the pus. TB is a rare cause of loculated empyema with an overlapping clinical and radiological picture with pyogenic infections.

http://ift.tt/2usB8WC

Unusual genitourinary tract activity

A 23-year-old woman presented to the emergency department after manually inserting foreign bodies into the urinary bladder through her urethra. A plain abdominal film of the kidneys, ureters and bladder confirmed three radio-opaque densities in the urinary bladder. She was taken to the operating room where cystourethroscopy was performed. At cystoscopy 2 'corn-on-the-cob' skewers and 1 battery were identified but were too large to be retrieved safely with a grasper through the protective sheath. The objects were grasped with a 'sponge-holding forceps' (placed alongside the cystoscope) and extracted one at a time. A psychiatric consultation was sought and the patient was diagnosed and treated for borderline personality disorder. Unusual genitourinary activity (UGUA) has been described for several centuries and is characterised by the deposition of foreign objects in the genitalia.¹ The most common incentive for UGUA is sexual stimulation, but psychiatric disorders and intoxication are also associated.² Management involves retrieval of foreign bodies and evaluation of psychosocial factors.

http://ift.tt/2uQR0Eu

Posterior meningeal artery DMSO injection resulting in reproducible asystole prior to Onyx therapy of a dural arteriovenous fistula: a previously undescribed variant of the trigeminocardiac reflex or a new phenomenon?

We describe a case of reproducible asystole during endovascular treatment of a posterior fossa dural arteriovenous fistula. Catheterisation of the posterior meningeal artery, a branch of the vertebral artery in this patient, followed by dimethyl sulfoxide injection prior to Onyx administration resulted in two episodes of asystole.

To the best of our knowledge, this is the first reported case of asystole occurring during endovascular intervention in the posterior meningeal artery. This may represent a previously undescribed variant of the trigemino-cardiac reflex (TGCR) caused by chemical stimulation of small areas of trigeminally innervated posterior fossa dura. Alternatively, this may represent a newly identified phenomenon with chemical stimulation of regions of posterior fossa dura innervated by branches of the vagus nerve leading to increased parasympathetic activity and resultant asystole.

In either case, it is important to recognise the potential for such episodes in this vascular territory to allow case planning and management.

http://ift.tt/2usGWzn

Dengue fever presenting as cauda equina syndrome

Description

Dengue is an arboviral disease transmitted by Aedes sp. mosquitoes. A wide spectrum of illness is observed, ranging from dengue fever to dengue shock syndrome. The common neurological complications noted are encephalitis and encephalopathy. Haemorrhagic complications due to thrombocytopenia can result in various neurological sequelae.1 We report a case of dengue fever with spontaneous spinal hematoma presenting as cauda equina syndrome.

A 47-year-old man presented with moderate grade fever and arthralgia for 5 days. On day 6 of illness, he got admitted with complaints of lower backache, urinary retention, bilateral lower limb weakness and numbness below ankle. This was followed by reduced perianal sensations. On clinical examination, the patient was found to have MRC grade 4/5 power in extensor hallucis longus and ankle plantar flexors. The ankle reflexes were absent bilaterally with other deep tendon reflexes being normal. Babinski reflex was negative. The patient had...

http://ift.tt/2uQXcMX

Efficacy of new low-dose oral anticoagulants in recalcitrant livedoid vasculopathy

Livedoid vasculopathy (LV) is a thrombotic skin disease characterised by recurrent painful ulcerations and irreversible scar formation on the lower legs, which is caused by occlusion of the cutaneous microcirculation. Edoxaban is one of new oral anticoagulants. It directly inhibits factor Xa in the coagulation pathway and prevents thrombus formation. A 17-year-old Japanese male presented with a 1-year history of recalcitrant cutaneous ulcers and livedo racemosa on his lower extremities. Initially, the ulcers were treated with antiplatelets therapies; however, he experienced recurrence of ulcerations during summer time. A histological examination revealed dermal vessel thrombosis consistent with occlusive vasculopathy. These findings were diagnostic for LV. The patient was treated with oral low-dose edoxaban (15 mg/day). The skin ulcers were epithelised and livedo racemosa disappeared within 8 weeks. We herein report the successful treatment of recalcitrant LV with low-dose edoxaban in a patient with no identifiable coagulopathy.

http://ift.tt/2usOn9P

Oncogenic long noncoding RNA landscape in breast cancer

Abstract

Background

Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified.

Methods

Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation. To elucidate the mechanisms of the regulation of these lncRNAs, genomic alterations from the TCGA, Broad, Sanger and BCCRC data, as well as epigenetic modifications from GEO data, were then applied and examined to meet this objective. Finally, cell proliferation assays, flow cytometry analyses and TUNEL assays were applied to validate the oncogenic roles of these lncRNAs in vitro.

Results

A cluster of oncogenic lncRNAs that was upregulated in breast cancer tissue and was associated with worse survival outcomes was identified. These oncogenic lncRNAs are involved in regulating immune system activation and the TGF-beta and Jak-STAT signalling pathways. Moreover, TINCR, LINC00511, and PPP1R26-AS1 were identified as subtype-specific lncRNAs associated with HER-2, triple-negative and luminal B subtypes of breast cancer, respectively. The up-regulation of these oncogenic lncRNAs is mainly caused by gene amplification in the genome in breast cancer and other solid tumours. Finally, the knockdown of TINCR, DSCAM-AS1 or HOTAIR inhibited breast cancer cell proliferation, increased apoptosis and inhibited cell cycle progression in vitro.

Conclusions

These findings enhance the landscape of known oncogenic lncRNAs in breast cancer and provide insights into their roles. This understanding may potentially aid in the comprehensive management of breast cancer.

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Paediatric chest wall trauma causing delayed presentation of ventricular arrhythmia

This report describes a paediatric patient presenting with haemodynamically stable non-sustained ventricular tachycardia 1 day after minor blunt chest trauma. Initial laboratory studies, chest X-ray and echocardiography were normal; however, cardiac MRI revealed precordial haematoma, myocardial contusion and small pericardial effusion. Throughout her hospital course, she remained asymptomatic aside from frequent couplets and triplets of premature ventricular contractions. Ectopy was controlled with oral verapamil. This case highlights how significant cardiac injury may be missed with standard diagnostic algorithms.

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An unusual presentation of a benign pancreatic lesion containing amyloid

We present a unique case of a benign pancreatic lesion which was positive for amyloid in a 55-year-old female patient without systemic amyloidosis. Further testing revealed islet-type amyloid polypeptide (or amylin), a protein found in various diseases such as diabetes, insulinoma and pancreatic adenocarcinoma—none of which was seen in our patient.

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Lipoma of superior vena cava: a rare occurrence

Most benign primary cardiac tumours are myxomas; non-myxomatous tumours are less common but comprise a wide variety. Cardiac lipoma is a rare non-myxomatous variety. A 70-year-old Caucasian woman with right breast cancer status postpartial mastectomy underwent surveillance MRI of the breast and was found to have a possible right atrial (RA) mass. She also reported frequent headaches and palpitations. She underwent a transoesophageal echocardiogram which showed a 2.6x1.6x1.6 cm echogenic mass at the superior vena cava (SVC) and RA junction. She was anticoagulated for a possible thrombus without resolution. Surgical excision was undertaken in view of ongoing symptoms and partial occlusion of the SVC. Intraoperatively, a 2–3 cm smoothly textured lobulated mass was found and histopathology showed adipose tissue consistent with lipoma. The postoperative course was uneventful, and the patient was discharged in stable condition.

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Benign paroxysmal positional vertigo (BPPV) diagnosis and treatment in an elite professional football (soccer) player

A 33-year-old male professional football player suffered from acute-onset dizziness following a lower limb soft tissue treatment in prone lying. Symptoms included spinning vertigo lasting for 30's, headache, visual vertigo and disorientation. Clinical examination of balance and vestibular systems confirmed a left posterior canalithiasis benign paroxysmal positional vertigo (BPPV) and excluded other central and peripheral causes of dizziness. Two cycles of a left Epley manoeuvre were performed. An Epley manoeuvre abolished the BPPV and negated the need for medication. The player was able to return to play without dizziness within 24 hours completely symptom free. BPPV can be successfully identified and treated in elite football players and they can see a return to training and games within 24 hours. There are no epidemiology studies for this group of elite athletes either male or female despite increased occupational risk factors.

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Q fever prosthetic joint infection

Coxiella burnetii is the causative pathogen of the zoonotic infection Q fever. Most patients with Q fever experience a non-specific febrile illness, hepatitis or pneumonia. Q fever has recently been described as a cause of prosthetic joint septic arthritis, but remains very uncommonly reported. We present a case of Q fever prosthetic joint septic arthritis that has responded to a combination of two-stage surgical exchange and prolonged medical treatment with doxycycline and hydroxychloroquine.

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Soft tissue laceration caused by lower extremity intraosseous access insertion in an obese patient

Description

Intravenous access placement in the obese could be challenging due to unreliable anatomical landmarks and impact overall care. Intraosseous (IO) access remains a quick and reliable alternative to emergent intravenous access.1 2 The adult IO demonstrates an excellent safety profile with serious complications, such as compartment syndrome, osteomyelitis and skin abscesses, occurring in less than 1% of insertions.3

An 85-year-old woman presented with septic shock due to lobar pneumonia. Physical examination revealed a dehydrated, hypotensive, morbidly obese woman with anasarca and lower extremity lymphoedema. After several failed peripheral intravenous access attempts, IO access was achieved using the Arrow® EZ-IO® system, 2 cm distal and slightly medial to the tibial tuberosity in the right lower extremity during first attempt by an experienced emergencist without difficulties. The IO needle length was 45 mm and its gauge 15 Ga. EZ-IO® stabiliser dressing was not used during placement. IO...

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Importance of temporal changes in myocardial strain in Takotsubo cardiomyopathy

Strain imaging is a sensitive marker of myocardial dysfunction and may be underused in Takotsubo cardiomyopathy (TC). We present a case of biventricular TC in which early improvement in left ventricular longitudinal strain predated subsequent improvement in ejection fraction. Early temporal patterns of strain of the left and right ventricles have not previously been described in TC. Our case illustrates how strain can be a sensitive marker for myocardial dysfunction and recovery in TC. Increased use of strain in TC may have further implications on prognosis and management.

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Apical ballooning (takotsubo) syndrome with concurrent ST-segment elevation myocardial infarction

We present the case of a 61-year-old woman admitted with chest pain and an ECG demonstrating ST-segment elevation in the lateral leads. Emergency coronary angiography demonstrated an occluded obtuse marginal branch. Percutaneous intervention was unsuccessful as the lesion could not be crossed with a wire. Left ventriculography and transthoracic echocardiography demonstrated hypokinesis of the entire apex but preserved contractility of the basal segments, consistent with a diagnosis of apical ballooning syndrome (ABS). Cardiac MRI demonstrated myocardial oedema in all mid to apical segments, with a left ventricular ejection fraction (LVEF) of 38%. Repeat study at 5 months demonstrated an infarct in the distribution of the occluded artery with late gadolinium enhancement, consistent with a diagnosis of a lateral wall myocardial infarction and an improvement in the LVEF to 51%. The case illustrates the novel observation that ABS and acute myocardial infarction may rarely occur simultaneously.

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Atypical presentation of Parsonage-Turner syndrome confounded by surgical rotator cuff injury

Parsonage-Turner syndrome (PTS) is a rare neuropathy that commonly presents as unexpected severe shoulder and arm pain that eventually subsides while weakness or paralysis ensues. During exceptions to this classic presentation, confirming PTS can be challenging. Alternative causes of upper extremity pain may confound the diagnostic algorithm. Moreover, objective findings from necessary diagnostic tests depend on when those tests are performed. We present an atypical onset of PTS, whereby the initial presentation of severe neuropathic pain was preceded by mild shoulder pain that should decrease one's clinical suspicion for PTS. This milder pain coincided with the presence of a rotator cuff injury, whereby surgical intervention preceded impending paralysis and hindered postoperative rehabilitation. Physicians should be aware of the possibility of atypical presentations of PTS in hopes of avoiding either untimely surgery or delays in diagnosis.

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Primary bilateral adrenal nodular disease with Cushing's syndrome: varying aetiology

Primary adrenal disorders contribute 20%â"30% of patients with endogenous Cushing's syndrome. Most of the primary adrenal diseases are unilateral and include adenoma and adrenocortical carcinoma, whereas bilateral adrenal lesions are uncommon and include primary pigmented nodular adrenocortical disease, primary bilateral macronodular adrenocortical hyperplasia, isolated micronodular adrenocortical disease, bilateral adenomas or carcinomas, and rarely pituitary adrenocorticotropic hormone-dependent adrenal nodular disease. Cyclic adenosine monophosphate-dependent protein kinase A signalling is the major activator of cortisol secretion in primary adrenal nodular disorders. We report two cases of bilateral adrenal nodular disease with endogenous Cushing's syndrome, including one each of primary pigmented nodular adrenocortical disease and primary bilateral macronodular adrenocortical hyperplasia.

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A rare case of fatal meningoencephalitis with septic thromboembolism due to otitis media: a forensic case and review of literature

Description

Meningitis is an inflammatory syndrome involving the meninges, and it manifests with headache and stiff neck. On the contrary, encephalitis refers to the inflammation of the brain parenchyma. The causative pathogens can be manifold though, except for immunocompromised patients; in literature, there are no cases of meningoencephalitis caused by bacteria usually present in the bowel.

We report the case of a 40-year-old man. Following an earache, the man went to the hospital. In anamnesis, the man reported a chronic otitis media for many years, and clinicians, noting auricular bleeding, advised local antibiotic treatment. The next day, he had fever, treated with paracetamol. After 3 days, following the worsening of the clinical condition, the man returned to the hospital where physicians detected temporal and spatial disorientation, neck stiffness and fever of 39.5°C. Despite medical therapy, the man died after a few hours. An autopsy was performed. It showed an abscess...

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Awakening with amantadine from a persistent vegetative state after subarachnoid haemorrhage

We report the case of a 36-year-old woman with a subarachnoid haemorrhage (SAH) caused by a rupture of a right-sided middle cerebral artery aneurysm and subsequent malignant infarction of the right hemisphere leading to a persistent vegetative state and severe spastic tetraparesis with recurrent myocloni. Nine months after disease onset, the patient was transferred to our department for diagnostic and therapeutic re-evaluation. The poor clinical condition could not be explained by the brain lesion caused by the SAH or infarction. Moreover, glucose metabolism was normal in brain regions not affected by SAH and infarction as shown by positron emission tomography with ¹⁸F-fluorodeoxyglucose. We terminated baclofen and reduced antiepileptics known to impair vigilance and cognitive functions. However, only after starting amantadine treatment we observed a stunning awakening of the patient fully orientated within days. Our findings warrant trials to investigate amantadine in the treatment of unresponsive wakefulness syndromes due to acute central nervous system diseases.

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An unusual case of interstitial lung disease in a patient with cardiopulmonary syndrome as the initial presentation of Erdheim-Chester disease

Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600 cases reported in the literature. ECD has been recently reclassified as a histiocytic dendritic cell neoplasm. The clinical spectrum ranges from asymptomatic tissue accumulation of histiocytes to invasive tissue infiltration, which can cause fulminant multisystem failure. It typically presents with bone pain and constitutional symptoms. Extraosseous manifestations are not uncommon. ECD-associated interstitial lung disease has been described in 20%-35% of patients. Diagnosis is primarily by tissue biopsy and immunohistochemistry showing xanthogranulomas composed of foamy histiocytes that stain positive for CD68, CD14 and CD163 and negative for CD1á and langerin. We report a case of ECD in a young man with cardiopulmonary involvement who presented with haemoptysis and dyspnoea.

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Klippel-Trenaunay syndrome: diagnosis in a neonate

Description

A male newborn was evaluated due to a port-wine stain. Mother, 40 years old, father and brother were healthy. Gestation was uneventful. Amniocentesis revealed a normal male karyotype. A caesarean delivery was performed at 38 weeks. First physical examination showed a port-wine stain affecting the abdomen, back and left limb (figure 1) and hypertrophy of the affected limb. A biopsy was performed and histological findings revealed capillary malformations. Therefore, a Klippel-Trenaunay syndrome was diagnosed. Abdominal and lower limb doppler ultrasound and brain MRI excluded other vascular abnormalities. He was followed by a multidisciplinary team. At 9 months, there was a slight difference in the length of legs and the circumference of thighs (figure 2).

Figure 1

A port-stain affecting the abdomen and left limb at first physical examination of the neonate.

Figure 2

Appearance of the...

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Reconstruction of urethra using appendix in a patient with cloacal malformation

We report a case of 21-year-old young woman with congenital cloacal malformation. She was operated at the age of 1.5 years separating the rectum from common opening as a two-stage repair. She was incontinent in the earlier part of her life but she became continent to some extent later in early adulthood. She presented with urinary stress incontinence following delivery of dead fetus of 6 months. She underwent multiple investigations revealing common opening of bladder neck and vagina. A multidisciplinary evaluation was done and she underwent closure of common channel and neourethra reconstruction using pedicled appendix. Patient was continent and voiding by herself on discharge.

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Trans-scaphoid perilunate fracture dislocation: 'notjust a scaphoid fracture

Description

Perilunate dislocations are uncommon high-energy injuries which are missed in approximately 25% of cases on initial presentation.1 We present the X-rays of a 25-year-old man who fell from a height of approximately 2 metres onto an extended wrist. Plain radiographs (figure 1) show classical signs of a trans-scaphoid perilunate fracture dislocation. Pre-reduction, he had median nerve symptoms which settled with reduction and elevation. Reduction was performed in the emergency department with analgesia/sedation.

Figure 1

Posteroanterior and lateral pre-reduction radiographs of the wrist.

The sequence of events in this injury is well described: (1) the force begins radially and passes through the scaphoid causing it to fracture; (2) the force is transmitted ulnarly through the lunocapitate interval, and the lunate projects through the space of Poirier (between the intercarpal ligaments volar to the bones); (3) the distal portion...

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Patient-reported outcome measures (PROMs): enhancing decision making and follow-up

A case presentation of patient undergoing elective total knee replacement. Patient-reported outcome measures prospectively collected electronically pre and postoperatively allowed real-time review, aiding follow-up and reducing the need for clinical, face-to-face follow-up.

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Angioscopic observation of an atherosclerotic coronary aneurysm without yellow plaque

Description

A-58-year-old man with diabetes mellitus was admitted to our hospital with angina following physical effort. Coronary CT angiography (CCTA) revealed a saccular coronary aneurysm at the left main trunk bifurcation and a significant stenosis at the middle portion of the calcified left anterior descending artery (LAD) (figure 1). Invasive coronary angiography showed a large coronary aneurysm (12.3x11.0 mm) arising from the ostial LAD and stenoses in the middle of the LAD and in the middle of the left circumflex artery (figure 2). Intravascular ultrasound showed a severely calcified LAD, as shown on CCTA; however, it failed to reveal the entire picture with regard to the aneurysm because of the limited echo depth. Non-obstructive angioscopy (NOA)1 was performed to investigate the intimal injury of the aneurysm and demonstrated a rough, salmon-pink coloured surface without the presence of thrombus or atheromatous yellow plaque

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Silicone implant incompatibility syndrome (SIIS) in a 57-year-old woman with unilateral silicone breast implant

Since the 1960s, silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery. Tissue exposed to silicone can react with multiple adverse advents. Autoimmune/inflammatory syndrome induced by adjuvants due to silicone exposure from ruptured silicone implants can lead to different interstitial lung manifestations predominantly with granuloma evolvement, leading to the so-called silicone implant incompatibility syndrome (SIIS). This case describes a 57-year-old woman with multiple lung infiltrations and a left-sided breast implant. The implant had been replaced twice, once due to implant rupture 36 years ago. The nodular infiltrates could not be related to infection, malignancy, interstitial lung disease, vasculitis or connective tissue disorder, and it was concluded that the nodular infiltrations were of inflammatory origin due to an autoimmune response secondary to the silicone implants (SIIS). After explantation, the patient's symptoms subsided and her physical condition has remarkably improved.

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Non-canonical WNT/PCP signalling in cancer: Fzd6 takes centre stage

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Overexpression of zinc finger protein 687 enhances tumorigenic capability and promotes recurrence of hepatocellular carcinoma

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History and conceptual developments in vascular biology and angiogenesis research: a personal view

Abstract

Vascular biology is an important scientific domain that has gradually penetrated many medical and scientific fields. Scientists are most often focused on present problems in their daily scientific work and lack awareness regarding the evolution of their domain throughout history and of how philosophical issues are related to their research field. In this article, I provide a personal view with an attempt to conceptualize vascular development research that articulates lessons taken from history, philosophy, biology and medicine. I discuss selected aspects related to the history and the philosophy of sciences that can be extracted from the study of vascular development and how conceptual progress in this research field has been made. I will analyze paradigm shifts, cross-fertilization of different fields, technological advances and its impact on angiogenesis and discuss issues related to evolutionary biology, proximity of different molecular systems and scientific methodologies. Finally, I discuss briefly my views where the field is heading in the future.

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MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells

Abstract

Background

Human mesenchymal stem cells (MSCs) have been shown to be involved in the formation and modulation of tumor stroma and in interacting with tumor cells, partly through their secretome. Exosomes are nano-sized intraluminal multi-vesicular bodies secreted by most types of cells and have been found to mediate intercellular communication through the transfer of genetic information via coding and non-coding RNAs to recipient cells. Since exosomes are considered as protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior, particularly angiogenesis.

Methods

Exosomes derived from MSCs were isolated and characterized by scanning electron microscopy analyses, dynamic light scattering measurements, and Western blotting. Fold changes in miR-100 expression levels were calculated in exosomes and their corresponding donor cells by qRT-PCR. The effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and Western blotting of the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. The quantification of secreted VEGF protein was determined by enzyme-linked immunosorbent assay. The putative paracrine effects of MSC-derived exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays including endothelial cell proliferation, migration and tube formation assays.

Results

We found that MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of vascular endothelial growth factor (VEGF) through modulating the mTOR/HIF-1α signaling axis in breast cancer-derived cells. We also found that miR-100 is enriched in MSC-derived exosomes and that its transfer to breast cancer-derived cells is associated with the down-regulation of VEGF in a time-dependent manner. The putative role of exosomal miR-100 transfer in regulating VEGF expression was substantiated by the ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived exosomes on the expression of VEGF in breast cancer-derived cells. In addition, we found that down-regulation of VEGF mediated by MSC-derived exosomes can affect the vascular behavior of endothelial cells in vitro.

Conclusions

Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.

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Ruptured Retinal Arterial Macroaneurysm Secondary to Toxoplasmic Kyrieleis Arteriolitis: A Case Report

Purpose: The aim of this report was to describe multimodal ocular imaging findings in a patient who presented with a ruptured retinal arterial macroaneurysm (RAM) associated with toxoplasmic Kyrieleis arteriolitis. Methods: We report the case of a 64-year-old man with a history of systemic hypertension and dense amblyopia of the left eye who presented with decreased vision and new floaters in the left eye. Color fundus photography, spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography were used as diagnostic imaging tools. Results: No signs of hypertensive retinopathy were noted in the right eye. Multiple chorioretinal scars characteristic of previous toxoplasmosis were revealed in the left eye, with one covering most of the macula. Periarterial plaques or Kyrieleis arteriolitis were observed in retinal arteries surrounding the toxoplasmic retinal scars. Multiple RAMs were observed in these vessels, one of which was acutely ruptured. A perivenular plaque associated with a chronic branch retinal vein occlusion (BRVO) was noted along the same arcade at the arteriovenous crossing. Conclusion: RAM formation and BRVO can present as possible long-term complications of toxoplasmic Kyrieleis arteriolitis. This is the first reported case demonstrating an association between toxoplasmic Kyrieleis arteriolitis and RAM formation.
Case Rep Ophthalmol 2017;8:390–395

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Concurrent chemoradiotherapy with weekly nedaplatin versus radiotherapy alone in elderly patients with non-small-cell lung cancer

Abstract

Purpose

We conduct this study to compare the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) concurrent weekly nedaplatin (NDP) versus IMRT alone in the stage III/IV non-surgical elderly patients with non-small-cell lung cancer (NSCLC).

Methods

117 patients were enrolled into our study. The patients were assigned into two different groups: radiotherapy (RT) group and chemoradiotherapy (CRT) group. Patients in RT group were treated with IMRT at a single daily dose of 2 Gy for 5 days per week, totally 52–66 Gy. The CRT group, IMRT concurrent weekly NDP at a dose of 25 mg/m².

Results

In CRT group, the median survival was 11.0 months (95% confidence interval [CI], 8.894–13.106 months) and in RT group, it was 7.0 months (95% CI 5.771–8.229 months). The 1-year, 2-year, 3-year, survival rates in the combined treatment arm were higher than the radiation therapy arm (46.8 vs 25.9%, 25.1 vs 11.8%, 14.7 vs 8.0%; p < 0.001). The Cox's multiple regression analysis showed that CRT had significantly better overall survival than RT (HR 0.523; 95.0% CI 0.338–0.807; p = 0.003). The objective response rate provided that 73.3% treated with CRT compared with 51.1% (p = 0.018) received RT alone. Of the hematologic toxicities, leukocytes (35.0 vs 0%; p < 0.001), neutrophils (33.3 vs 0%; p < 0.001) were significantly more common in the CRT group than the RT group.

Conclusions

We first discovered that NDP concurrent IMRT for treating stage III/IV non-surgical elderly patients with NSCLC was good curative effect of better objective response rate and well-tolerated. However, within the low number of patients, only stage IV gained a survival benefit.

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Concurrent chemoradiotherapy with weekly nedaplatin versus radiotherapy alone in elderly patients with non-small-cell lung cancer

Abstract

Purpose

We conduct this study to compare the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) concurrent weekly nedaplatin (NDP) versus IMRT alone in the stage III/IV non-surgical elderly patients with non-small-cell lung cancer (NSCLC).

Methods

117 patients were enrolled into our study. The patients were assigned into two different groups: radiotherapy (RT) group and chemoradiotherapy (CRT) group. Patients in RT group were treated with IMRT at a single daily dose of 2 Gy for 5 days per week, totally 52–66 Gy. The CRT group, IMRT concurrent weekly NDP at a dose of 25 mg/m².

Results

In CRT group, the median survival was 11.0 months (95% confidence interval [CI], 8.894–13.106 months) and in RT group, it was 7.0 months (95% CI 5.771–8.229 months). The 1-year, 2-year, 3-year, survival rates in the combined treatment arm were higher than the radiation therapy arm (46.8 vs 25.9%, 25.1 vs 11.8%, 14.7 vs 8.0%; p < 0.001). The Cox's multiple regression analysis showed that CRT had significantly better overall survival than RT (HR 0.523; 95.0% CI 0.338–0.807; p = 0.003). The objective response rate provided that 73.3% treated with CRT compared with 51.1% (p = 0.018) received RT alone. Of the hematologic toxicities, leukocytes (35.0 vs 0%; p < 0.001), neutrophils (33.3 vs 0%; p < 0.001) were significantly more common in the CRT group than the RT group.

Conclusions

We first discovered that NDP concurrent IMRT for treating stage III/IV non-surgical elderly patients with NSCLC was good curative effect of better objective response rate and well-tolerated. However, within the low number of patients, only stage IV gained a survival benefit.

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Late onset asymptomatic pancreatic neuroendocrine tumor – A case report on the phenotypic expansion for MEN1

Abstract

Background

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome associated with several endocrine as well as non-endocrine tumors and is caused by mutations in the MEN1 gene. Primary hyperparathyroidism affects the majority of MEN1 individuals by age 50 years. Additionally, MEN1 mutations trigger familial isolated hyperparathyroidism. We describe a seemingly unaffected 76-year-old female who presented to our Genetics Clinic with a family history of primary hyperparathyroidism and the identification of a pathogenic MEN1 variant.

Case Presentation

The patient was a 76 year-old woman who appeared to be unaffected. She had a family history of a known MEN1 pathogenic variant. Molecular testing for the known MEN1 mutation c.1A > G, as well as, biochemical testing, MRI of the brain and abdomen were all performed using standard methods. Molecular testing revealed our patient possessed the MEN1 pathogenic variant previously identified in her two offspring. Physical exam revealed red facial papules with onset in her seventies, involving her cheeks, nose and upper lip. Formerly, she was diagnosed with rosacea by a dermatologist and noted no improvement with treatment. Clinically, these lesions appeared to be facial angiofibromas. Brain MRI was normal. However, an MRI of her abdomen revealed a 1.5 cm lesion at the tail of the pancreas with normal adrenal glands. Glucagon was mildly elevated and pancreatic polypeptide was nearly seven times the upper limit of the normal range. The patient underwent spleen sparing distal pancreatectomy and subsequent pathology was consistent with a well-differentiated pancreatic neuroendocrine tumor (pNET).

Conclusions

Age-related penetrance and variable expressivity are well documented in families with MEN1. It is thought that nearly all individuals with MEN1 manifest disease by age 40. We present a case of late-onset MEN1 in the absence of the most common feature, primary hyperparathyroidism, but with the presence of a pNET and cutaneous findings. This family expands the phenotype associated with the c.1A > G pathogenic variant and highlights the importance of providing comprehensive assessment of MEN1 mutation carriers in families that at first blush may appear to have isolated hyperparathyroidism.

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