CT-based radiomics to distinguish progressive from stable neuroendocrine liver metastases treated with somatostatin analogues: an explorative study.

BACKGROUND: Accurate response evaluation in patients with neuroendocrine liver metastases (NELM) remains a challenge. Radiomics has shown promising results regarding response assessment. PURPOSE: To differentiate progressive (PD) from stable disease (SD) with radiomics in patients with NELM undergoing somatostatin analogue (SSA) treatment. MATERIAL AND METHODS: A total of 46 patients with histologically confirmed gastroenteropancreatic neuroendocrine tumors (GEP-NET) with ≥1 NELM and ≥2 computed tomography (CT) scans were included. Response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST1.1). Hepatic target lesions were manually delineated and analyzed with radiomics. Radiomics features were extracted from each NELM on both arterial-phase (AP) and portal-venous-phase (PVP) CT. Multiple instance learning with regularized logistic regression via LASSO penalization (with threefold cross-validation) was used to classify response. Three models were computed: (i) AP model; (ii) PVP model; and (iii) AP + PVP model for a lesion-based and patient-based outcome. Next, clinical features were added to each model. RESULTS: In total, 19 (40%) patients had PD. Median follow-up was 13 months (range 1-50 months). Radiomics models could not accurately classify response (area under the curve 0.44-0.60). Adding clinical variables to the radiomics models did not significantly improve the performance of any model. CONCLUSION: Radiomics features were not able to accurately classify response of NELM on surveillance CT scans during SSA treatment.

Predicting local tumour progression after ablation for colorectal liver metastases: CT-based radiomics of the ablation zone.

PURPOSE: To assess whether CT-based radiomics of the ablation zone (AZ) can predict local tumour progression (LTP) after thermal ablation for colorectal liver metastases (CRLM). MATERIALS AND METHODS: Eighty-two patients with 127 CRLM were included. Radiomics features (with different filters) were extracted from the AZ and a 10 mm periablational rim (PAR)on portal-venous-phase CT up to 8 weeks after ablation. Multivariable stepwise Cox regression analyses were used to predict LTP based on clinical and radiomics features. Performance (concordance [c]-statistics) of the different models was compared and performance in an 'independent' dataset was approximated with bootstrapped leave-one-out-cross-validation (LOOCV). RESULTS: Thirty-three lesions (26 %) developed LTP. Median follow-up was 21 months (range 6-115). The combined model, a combination of clinical and radiomics features, included chemotherapy (HR 0.50, p = 0.024), cT-stage (HR 10.13, p = 0.016), lesion size (HR 1.11, p = <0.001), AZ_Skewness (HR 1.58, p = 0.016), AZ_Uniformity (HR 0.45, p = 0.002), PAR_Mean (HR 0.52, p = 0.008), PAR_Skewness (HR 1.67, p = 0.019) and PAR_Uniformity (HR 3.35, p < 0.001) as relevant predictors for LTP. The predictive performance of the combined model (after LOOCV) yielded a c-statistic of 0.78 (95 %CI 0.65-0.87), compared to the clinical or radiomics models only (c-statistic 0.74 (95 %CI 0.58-0.84) and 0.65 (95 %CI 0.52-0.83), respectively). CONCLUSION: Combining radiomics features with clinical features yielded a better performing prediction of LTP than radiomics only. CT-based radiomics of the AZ and PAR may have potential to aid in the prediction of LTP during follow-up in patients with CRLM.

The effect of the ginger on the apoptosis of hippochampal cells according to the expression of BAX and Cyclin D1 genes and histological characteristics of brain in streptozotocin male diabetic rats.

Diabetes is the most common endocrine disorder in humans with multiple complications including nervous system damages. The aim of the present study was to determine the effect of ginger extract on apoptosis of the neurons of hippocampus, via evaluation of BAX and Cyclin D1 and also histological analysis, in male diabetic rats. In this experimental study, 60 Wistar rats (220 ± 30gr) were conducted in 5 groups as follow: diabetic group treated with saline (group 1), normal group treated with saline (group 2), diabetic group treated with ginger (group 3), diabetic group treated with ginger-insulin (group 4), diabetic group treated with insulin (group 5). STZ (60 mg/kg) was intraperitoneally used to induce the diabetes. Expression levels of BAX and Cyclin D1 were examined using Real-Time PCR technique and the normality of neurons was evaluated using H&E staining method. The results showed that blood glucose level significantly decreased in group 4 when compared to group 1. In molecular analysis, there was no significant difference between groups regarding the expression of BAX gens, while, the expression of Cyclin D1 were significantly decreased in group 4 compared with group 1. Histological analysis revealed that pathological symptoms were lower in group 4 than the other diabetic groups. The results of present study showed that the ginger in addition to lowering blood sugar level, changes the expression of Cyclin D1 gene and histological characteristics in a positive manner. This means that the ginger may protects neurons of the hippocampus from apoptosis in diabetic patients.

Different ideas associated renal malformation and laminin α5 expression caused by maternal nicotine exposures.

The number of smokers is increasing specially in pregnant mothers and millions of children with health problems are born from the smoker mothers. Nicotine as a toxic substance crosses from placenta and accumulates in the developing organs of fetus. In this study, the effects of maternal nicotine exposure on expression levels of kidney laminin α5 in newborn mice were examined. Timed pregnant mice were injected subcutaneously with nicotine at a dose of 2 mg/kg/day from day 7 of gestation to the last day of the pregnancy (Group 1) and from day 7 until the two weeks of postnatal (Group 2). Sham control groups were injected with saline. After the last injection, all the newborn mice were anesthetized; their kidneys were removed and prepared for analysis of mRNA and protein expression of laminin α5 using Real-Time PCR and immunohistochemical techniques, respectively. Our results showed that mRNA levels of kidney laminin α5 in newborn mice were increased in group 1 when compared to sham control group and also group 2. Immunohistochemical analysis demonstrated that the protein levels of laminin α5 in the glomerulus have significantly increased in group 1 when compared to group 2. In the proximal convoluted tubules, the parameter had a high significant increase in group 1 in comparison to control and also group 2. According to the results, it seems that maternal nicotine exposure may induce abnormal laminin α5 expression which may cause defects in kidney function during life time.

DNA Methylation and microRNA patterns are in association with the expression of BRCA1 in ovarian cancer.

Ovarian cancer is the sixth most prevalent cancer in women and is considered the most lethal gynecological malignancy. It can be inherited as a familial disease but also has a strong spontaneous occurrence. Although the disease is associated with genome instability brought on by genetics and environmental factors there is evidence that mutations in the gene encoding for the breast cancer type 1 susceptibility protein (BRCA1) or its down-regulation are involved in its development. Down-regulation of BRCA1 expression by hypermethylation of its promoter may account for some cases of ovarian cancer but this does not explain the cause of the majority of the disease. This review explores the role of BRCA1 promoter hypermethylation and micro-RNAs (miRNA) involved in the regulation of BRCA1 and their role in ovarian cancer development as well as some of the exciting discoveries which could lead to targeting miRNA with a view to restoring BRCA1 expression in diseased tissues.

Immunomodulatory efficacy of ethanol extract of propolis on tumor-bearing mice with disseminated candidiasis.

OBJECTIVE: This study was aimed at investigating the effect of propolis on immunosurveillance by measuring the levels of serum interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in tumor-bearing mice with disseminated candidiasis. METHODS: The ethanol extract of propolis was selected for this study. Balb/C female mice were infected with Candida albicans (C. albicans) and inoculated with spontaneous mouse mammary tumor (SMMT). The serum levels of tissue inhibitor of metalloproteinase-1(TIMP-1) were assessed by enzyme- linked immunosorbent assay (ELISA). Mice were treated daily with propolis solution (100mg/kg, 0.1 mL, orally) for 3 days before IV challenge with C. albicans and SC challenge with SMMT and continued for 10 days. The rates of survival and tumor growth of understudy mice were investigated as well. The levels of TNF-α, IFN-γ, IL-4, IL-10 and IL-17 cytokines in culture supernatants were determined by ELISA. RESULTS: The mean tumor size was significantly increased in tumor-bearing mice infected with C. albicans (16.98 ± 0.49 mm(2)) as compared to other mice groups (P<0.05). The results showed a significant decline of IL-4 and IL-10 levels after propolis administration to tumor-bearing mice infected with C. albicans (53.41 pg/mL, 156.81 pg/mL and 63.45 pg/mL) (P < 0.05). The increment of TNF-α (433.85 pg/mL) and IFN-γ (120.43 pg/mL) levels were also observed. CONCLUSION: Data revealed that propolis has remarkable immunomodulatory effect, which provides a scientific validation for the popular use of this natural substance, and further investigation will help to understand propolis usefulness during immunosuppressive conditions.

[Preventive crisis management in general outpatient palliative care - prospectively cross-sectional study of General Practitioners in Eastern Bavaria]. / Vorbeugendes Krisenmanagement in der allgemeinen ambulanten Palliativversorgung. Prospektive Querschnittstudie bei Hausärzten in Ostbayern.

BACKGROUND: General out-patient palliative care (GOPC) must be integrated into the care of patients with life-limiting diseases. Aim of the study was to evaluate experiences of general practitioners concerning advance directives and palliative emergency sheets. METHODS: A self-provided survey was mailed to all general practitioners in Regensburg (cross-sectional study). Main outcome measures included responses regarding a palliative emergency sheet (PES) and a palliative emergency plan (PEP). The investigation period was four months. The analysis was performed using defined criteria (e. g. professional experience concerning palliative care patients, patients treated in nursing homes, patients with dementia). RESULTS: Sixty-nine questionnaires from 259 were analysed (response rate 27 %). 86 % of respondents named practical experience in the care of palliative patients, 46 % named theoretical knowledge in this field. 41 % and 40 % consider creating an advance directive for their practical work as important/very important (p = 0.004 concerning the treatment of more than five palliative care patients per three months). 52 % and 49 % regard a PES or a PEP to be relevant (PES median: 6.5, SD ± 2.7; PEP median: 6.5 SD ± 2.9; inter-group analysis p < 0.05). 94 % of respondents name the general practitioner to be suitable for creating an advance directive. CONCLUSION: In Germany, GOPC in end-of-life care is very important. This study shows that advance directives were declared as an important instrument for patients? autonomy. The sense of PES and PEP to ensure patients? autonomy, especially for acute emergency medical palliative care, must be better recognized. However, the increase in acceptance in the GOPC for such instruments must be disclosed. Further studies to investigate this problem are necessary.

Teratogenic effects of HESA-A, a natural anticancer product from Iran, in mice.

HESA-A is a natural product containing herbal and marine animal substances, which has been patented in Iran. It has shown antioxidant, cytotoxic and anticancer effects. The aim of this study was to evaluate the teratogenic effects of HESA-A in mice. HESA-A (50, 100, 200, 400 and 800 mg/kg) was administered orally to pregnant mice on days 6 to 14 of gestation. Mouse reproductive developmental toxicity study was performed according to the ICH guideline. Embryos from the treated dam were sectioned and studied for external morphological abnormalities and skeletal malformations. HESA-A at two doses (400 and 800 mg/kg) slowed weight gain of pregnant mice. These two doses of HESA-A led to reduction in uterus weight (17% and 20% for the 400 and 800 mg/kg doses, respectively), increase in post-implantation resorption (150% and 200%, respectively), reduction in fetus weight (22% and 32%, respectively) and crown-lump length (15% and 19%, respectively). HESA-A at 400 and 800 mg/kg doses caused mild external and skeletal malformation significantly higher than the normal saline group. However, higher doses caused embryo malformations such as short limbs, spinal abnormalities, dermal cysts, microphtalmia and cleft palate. According to this study, only higher doses of HESA-A, which are 20 to 40 times higher than the usual therapeutic doses based on body surface conversion, may cause embryonic toxicity. This provides a reasonable safety margin for the use of HESA-A in pregnancy. Mechanisms of these abnormalities are not clear and need to be determined.

[Cancer pain therapy in palliative care patients: knowledge of prehospital emergency physicians in training. Prospective questionnaire-based investigation]. / Kenntnisse angehender Notfallmediziner über die Tumorschmerztherapie bei Palliativpatienten. Prospektive fragebogenbasierte Untersuchung.

BACKGROUND: Cancer diseases are often associated with acute and chronic pain. Therefore, cancer pain is a symptom frequently reported by palliative care patients with cancer diseases. Prehospital emergency physicians may be confronted with exacerbation of pain in cancer patients. The aim of this study was to evaluate the knowledge of prehospital emergency physicians in training concerning cancer pain therapy. METHODS: A total of 471 prehospital emergency physicians received a questionnaire (period of time: 2007-2009). The questionnaire was prepared for the study ("mixed methods design"). Twenty-four questions concerning cancer pain therapy (response options: scaling, open) were designed. The evaluation was done descriptively according to professional experience, field name and experience in treating patients with cancer as well. RESULTS: A total of 469 participants completed the questionnaire (response rate 99%). On average, 10.8 (SD +5.7, range 2-24) questions were answered correctly. Resident physicians answered statistically significantly more questions correctly than consultants (p=0.02). Only physicians working in internal medicine achieved statistically significantly better results than other disciplines (e.g., surgery; p=0.01). Physicians with professional experience of less than 5 years answered statistically significantly more questions correctly (p=0.004). CONCLUSIONS: The results of this study verify that emergency physicians in training have insufficient knowledge of pain therapy and end-of-life decisions. The data of this investigation suggest that more attention should be paid to education on pain therapy and end-of-life care in medical curricula. Prehospital emergency physicians may thus be better prepared to provide quality care for palliative patients.

Sirenomelia (mermaid syndrome): an infant from parents who used a special form of snuff.

We report the first case of a fetus with sirenomelia or mermaid syndrome, whose Afghanian parents were heavy user of a special form of snuff. The case was diagnosed as a mermaid syndrome but some of the features were common to both symmelia dipus and symmelia apus, for example, the single lower extremity had the normal femur, tibia and fibula, but the single foot was rotated medially. The digestive tube ended to a massive closed saclike structure and the anus was absence. The external genital organs were rudiment and the normal testes were undescended. Aorta was divided to branches, such that the external iliac arteries were very small in comparison to the internal iliac arteries. Inferior Vena cava was placed on to the left side of the aorta and unlike the majority of reported mermaid syndrome, the bladder was present. So, the researchers believe that the present case is a rare variant of the mermaid syndrome.