Comment on: Keratosis Pilaris and Its Subtypes: Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options

https://ift.tt/2DUXPcM

Study on the influence of surface potential on the nitrate adsorption capacity of metal modified biochar

Abstract

Carbon materials, as effective adsorbents to numerous aqueous cationic contaminants, have been hardly applied to remove anions in wastewater. In this work, different modifying agents were used to modify corncob biochars (CC) and the surface potentials of these modified biochars were determined. Based on the findings, modification principle was determined to reveal the relationship between surface potentials of the biochars and their nitrate adsorption capacities. The surface potential was dominated by the metal cations and multivalent cations led to even positive zeta potential. The formation of metal oxide not only led to the augment in surface area but also increase the surface charge. FeCl₃-modified biochar (Fe-CC) with the highest positive surface charge was utilized to remove anions (nitrate) from aqueous solutions. Characterization results confirm that Fe₂O₃ structure were successfully formed on biochar surface. This led to the formation of iron nitrate hydrate (Fe(NO₃)₃·9H₂O), which enabled higher nitrate adsorption performance than that of pristine biochar. Batch experiments showed that nitrate adsorption on the Fe-CC was stable and almost independent of experimental pH and temperature. Based on the Langmuir model results, the maximum nitrate adsorption capacity of Fe-CC was 32.33 mg/g. Coexisting anions had negative influence on the adsorption performance. Findings of this work suggest that the modified biochar can be used in wastewater treatment to remove anions such as nitrate.

Graphic abstract

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Correction to: Analysis of swale factors implicated in pollutant removal efficiency using a swale database

The original publication of this paper contains an error. Correct presentation of Equation 1 is presented in this paper.

https://ift.tt/2ADPxml

Correction to: Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: influence of the disease severity and therapy on the ovarian reserve

The original version of this article unfortunately contained a mistake in given and family names of all the authors.

https://ift.tt/2RrzO0G

Correction to: Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: influence of the disease severity and therapy on the ovarian reserve

The original version of this article unfortunately contained a mistake in given and family names of all the authors.

https://ift.tt/2RrzO0G

Split-mouth evaluation of connective tissue graft with or without enamel matrix derivative for the treatment of isolated gingival recession defects in dogs

Abstract

Objectives

The potential additive effect of an enamel matrix derivative (EMD) to a subepithelial connective tissue graft (CTG) for recession coverage is still controversially discussed. Therefore, the aim of this study was to histologically evaluate the healing of gingival recessions treated with coronally advanced flap (CAF) and CTG with or without EMD in dogs.

Materials and methods

Gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 7 dogs. After 8 weeks of plaque accumulation and subsequent 2 weeks of chemical plaque control, the 14 chronic defects were randomized to receive either CAF with CTG (CAF/CTG) or CAF with CTG and EMD (CAF/CTG/EMD). The animals were sacrificed 10 weeks after reconstructive surgery for histologic evaluation.

Results

Treatment with CAF/CTG/EMD demonstrated statistically significantly better results in terms of probing pocket depth reduction (P < 0.05) and clinical attachment level gain (P < 0.001). The length of the epithelium was statistically significantly shorter in the CAF/CTG/EMD group than in the CAF/CTG group (1.00 ± 0.75 mm vs. 2.38 ± 1.48 mm, respectively, P < 0.01). Cementum formation was statistically significantly greater in the CAF/CTG/EMD group than following treatment with the CAF/CTG group (3.20 ± 0.89 mm vs. 1.88 ± 1.58 mm, respectively, P < 0.01). The CAF/CTG/EMD group showed statistically significantly greater complete periodontal regeneration (i.e., new cementum, new periodontal ligament, and new bone) than treatment with CAF/CTG (0.54 ± 0.73 mm vs. 0.07 ± 0.27 mm, respectively, P < 0.05).

Conclusion

Within their limits, the present findings indicate that the additional use of EMD in conjunction with CAF + CTG favors periodontal regeneration in gingival recession defects.

Clinical relevance

The present findings support the use of EMD combined with CTG and CAF for promoting periodontal regeneration in isolated gingival recession defects.

https://ift.tt/2E9eZV5

LC3A, LC3B and Beclin-1 Expression in Gastric Cancer

Background: The current study examined the key proteins involved in autophagosome formation and their prognostic role in gastric cancer. Materials and Methods: Paraffin-embedded tissues from 121 consecutive patients treated with surgery for gastric cancer were analyzed immunohistochemically for the expression of autophagic proteins microtubule-associated proteins 1A/1B light chain 3A and 3B (LC3A, LC3B) and beclin-1 (encoded by BECN1 gene). Assessment of proliferative index using E3 ubiquitin-protein ligase (MIB1) and correlations with histopathological parameters and overall survival were performed. Results: Strong cytoplasmic expression was noted for all studied proteins, although to a varying proportion, the median percentage being 30% for LC3A, and 40% for LC3B and beclin-1. The median score of LC3A⁺ stone-like structures (SLS) was 0.2 (range 0-1) and the median proliferative index was 30% (range=0-95%). A significant association between LC3A, LC3B and beclin-1 expression was confirmed (p<0.01). SLS score was higher in tumors of the gastro-esophageal junction (p=0.009), and beclin-1 was overexpressed in intestinal-type tumors (p=0.001). High SLS score (p=0.008) was significantly related to poor prognosis, and this finding persisted in multivariate analysis (hazard ratio(HR)=2.01, p=0.003). Conclusion: Intense autophagic activity, as assessed by LC3A immunostaining and SLS quantification, is a strong prognostic marker in gastric cancer and can be useful for clinical application.

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Efficacy of Enteral Access in Patients with Esophageal Squamous Cell Carcinoma Under Neoadjuvant Therapy

Background: Enteral feeding tubes used to manage the nutritional status of esophageal cancer were evaluated regarding their effectiveness in patients receiving neoadjuvant therapy. Patients and Methods: A retrospective study evaluating patients with esophageal squamous cell carcinoma undergoing neoadjuvant therapy between 2001 and 2014 was conducted at a medical center. Hospital patients' records for enteral access (EA) insertion and treatment outcomes were statistically analyzed. Results: Patients with EA at initial diagnosis had lower body mass index than the group without EA (p=0.012). Chemotherapy-related adverse events with grade 3-4 mucositis were significantly less frequent in the EA group (p=0.008), and grade 3-4 anemia was significantly more frequent (p=0.012). The 4-year mortality rate was 63.0% in the EA group and 67.7% in the group without EA (p_{non-inferiority}=0.035), which met the non-inferiority criterion with a non-inferiority margin of 10%. Conclusion: Patients with esophageal squamous cell carcinoma with malnutrition status undergoing neoadjuvant therapy with EA showed an improved outcome at maintaining nutritional status, reduced severity of mucositis and improved survival rate.

https://ift.tt/2rd7LH3

Application of Artificial Intelligence-based Technology in Cancer Management: A Commentary on the Deployment of Artificial Neural Networks

Artificial intelligence was recognised many years ago as a potential and powerful tool to predict disease outcome in many clinical situations. The conventional approaches using statistical methods have provided much information, but are subject to limitations imposed by the complexity of medical data. The structures of the important variants of the machine learning system artificial neural networks (ANN) are discussed and emphasis is given to the powerful analytical support that could be provided by ANN for the prediction of cancer progression and prognosis. The predictive ability of the cellular markers, DNA ploidy and cell-cycle profiles, and molecular markers, such as tumour promoter and suppressor gene, and growth factor and steroid hormone receptors in breast cancer management were also analysed. ANN systems have been successfully deployed to evaluate microRNA profiles of tumours which saliently sway cancer progression and prognosis of the disease, thus counteracting the negative implications of their numerical abundance. Finally, in this setting, the prospective technical improvements in artificial neural networks, as hybrid systems in combination with fuzzy logic and artificial immune networks were also addressed.

https://ift.tt/2FLXU4W

Prognostic Significance of Survivin Expression and Combined Analysis with Cancer Stem Cell and Epithelial-Mesenchymal Transition-related Markers in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy

Aim: To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT). Patients and Methods: Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial–mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated. Results: The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003). Conclusion: Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.

https://ift.tt/2reV3aQ

Does Transdermal Testosterone Increase the Risk of Developing Breast Cancer? A Systematic Review

Background/Aim: Hypoactive sexual desire disorder (HSDD) is hypothesised to manifest in postmenopausal women at onset of menopause due to decreased oestrogen levels. Transdermal testosterone is a potential treatment option. This systematic review explores the relationship between the incidence of breast cancer and transdermal testosterone use. Materials and Methods: Searches were conducted on the PubMed and Ovid databases. In Ovid, the advanced search function was used: 'transdermal testosterone not male'. In PubMed, the following search terms were used: 'transdermal, testosterone, menopausal, women, breast cancer, women'. Abstracts that fitted our initial criteria were further investigated. Results: A total of 25 publications from PubMed and 192 publications from Ovid were initially assessed. Three randomised control trials were judged to have sufficiently met our inclusion criteria. However, these trials were too heterogeneous for a meta-analysis. A systematic review was deemed the most appropriate analysis of the data available. Conclusion: The publications examined in this systematic review suggest that the use of transdermal testosterone to treat HSDD in postmenopausal women does not increase breast cancer incidence. However, further research in the form of adequately powered randomised controlled trials with breast cancer incidence being the primary end point is required in order to confirm this.

https://ift.tt/2G31oQX

Chemotherapy in Patients with Hereditary Angioedema

Background: Hereditary angioedema (HAE) is an autosomal dominant hereditary disorder characterized by episodic swelling of many body regions (especially throat and abdomen), potentially triggered by medication. No data are available for HAE in patients with cancer assigned to standard chemotherapy. The aim of our study was to identify circulating mediators potentially predictive of acute HAE attacks during chemotherapy. Patient and Methods: Repeated blood testing (approximately every week) for complement system members (C3, C4, CH50, C1 inhibitor, C1-inhibitor functional C1Q), D-dimers and for routine haematochemistry were performed in a 42-year-old male affected by type 2 HAE during standard adjuvant oxaliplatin/fluorouracil-based chemotherapy administered for stage III radically resected rectal cancer. Pre-medication with 1,000 U Berinert inhibitor C1 was administered every week throughout treatment. Mann–Whitney U-test was used to determine statistical differences in measures between the first 30 days of therapy and beyond day 30 of therapy. Results: Pre-chemotherapy values of tested variables (day 0) were: C3: 101 mg/dl, C4: 5.71 mg/dl, CH50: 74%, C1 inhibitor: 43.4 mg/dl, C1-inhibitor functional: 18%, C1Q: 150 mg/dl, and D-dimers: 113 g/ml. A significant change in circulating values was observed for C3, D-dimers and C1-inhibitor functional. Four HAE attacks were observed, they started from the forth cycle of treatment and all were manageable. Changes in C3, D-dimers and C1-inhibitor functional preceded the attacks. Conclusion: The stress induced by chemotherapy such a standard oxaliplatin/fluorouracil increases the risk of attacks in patients with HAE. However, circulating biomarkers such as D-dimers, C3 and C1-inhibitor functional may serve as early predictors of acute HAE crisis.

https://ift.tt/2rd7y6J

Potent Antitumor T-Cell Memory Is Generated by Curative Viral Oncolytic Immunotherapy But Not Curative Chemotherapy

Background: Late developing breast cancer metastases are common and lethal despite treatment with adjuvant chemotherapy at the time of primary tumor excision. Stimulation of an antitumor immune response is an alternative strategy for preventing this devastating development. Materials and Methods: A mouse model of the human epidermal growth factor receptor 2 (HER2/neu)-positive mammary cancer was used to compare the antitumor memory T-cell response following tumor cure by viral oncolytic immunotherapy, chemotherapy, surgical excision, or surgical excision plus virus infection. Memory T-cell response was assessed by functional in vivo assays. Results: Antitumor T-cell memory was generated most powerfully by curative viral oncolytic immunotherapy and poorly by curative chemotherapy. Cure by surgical excision generated an immune antitumor response which was increased by neo-adjuvant virus infection. CD4 memory T-cells were most potent. Conclusion: Virus infection of tumor generates an antitumor memory immune response and chemotherapy suppresses this response. Clinical trials testing adjuvant immune stimulation instead of chemotherapy may be worth exploring because memory antitumor T-cells have the unique potential to find and eliminate small nests of metastatic cancer cells in sanctuary sites and prevent emergence of tumors from dormant cancer cells.

https://ift.tt/2FNSpCQ

Prognostic Significance of 14-3-3{varepsilon}, Aldo-keto Reductase Family 1 B10 and Metallothionein-1 in Hepatocellular Carcinoma

Background/Aim: Expression of 14-3-3 is associated with prognostic outcomes of hepatocellular carcinoma (HCC) patients. Metallothionein-1 (MT-1) proteins and aldo-keto-reductase family 1 B10 (AKR1B10) are considered potential tumor regulators of HCC. The aim of this study, was to examine the prognostic value of 14-3-3, MT-1 and AKR1B10 expression in HCC. Materials and Methods: The expression levels of 14-3-3, MT-1 and AKR1B10 in HCC cell lines and paraffin-embedded tissues were examined by western blotting and immunohistochemical analysis. Results: 14-3-3 positivity was significantly associated with decreased MT-1 expression in HCC. Patients with decreased MT-1 expression had worse survival rates and a higher risk of metastasis than 14-3-3-positive HCC patients with unchanged MT-1 expression. Distinct expression patterns of 14-3-3/MT-1/AKR1B10 were significantly associated with the metastatic incidence and survival rates of HCC patients. Patients with negative 14-3-3 staining in primary tumors had better prognostic outcomes. In contrast, patients with positive 14-3-3 staining, decreased MT-1 expression and no increase in AKR1B10 expression in primary tumors had the worst overall and disease-free survival rates and the highest metastatic risk. Conclusion: 14-3-3, AKR1B10, and MT-1 act as potential prognostic biomarkers of HCC.

https://ift.tt/2rmQ6wJ

Cytolytic Activity (CYT) Score Is a Prognostic Biomarker Reflecting Host Immune Status in Hepatocellular Carcinoma (HCC)

Background/Aim: The cytolytic activity (CYT) score is a new index of cancer immunity calculated from the mRNA expression levels of GZMA and PRF1. We assessed the clinical significance of the CYT score in HCC. Materials and Methods: The calculated CYT scores of peripheral blood cells (GSE24759), cell lines (CCLE) and HCC tissues (TCGA, GSE14520 and Kyushu cohorts) were assessed. Then, immunohistochemical analysis (IHC) of GZMA and PRF1 was performed. Results: The CYT scores of HCC tissues were lower than those of non-cancerous tissues. The 5-year recurrence-free survival of patients with low CYT scores was significantly shorter than that of patients with high CYT scores. Multivariate analysis indicated that the CYT score was an independent prognostic factor for RFS in TCGA and GSE14520 cohorts. Conclusion: CYT score could be a useful prognostic biomarker in HCC, possibly through reflecting the host immune status.

https://ift.tt/2FLXOu6

A Phase II Study of Tri-weekly Low-dose Nab-paclitaxel Chemotherapy for Patients with Advanced Gastric Cancer

Background/Aim: Nanoparticle albumin-bound (nab)-paclitaxel has demonstrated antitumor activity against advanced gastric cancer. However, gastric cancer patients can be difficult to treat with the recommended dose because of the high incidence of adverse toxicities. The aim of this study was to evaluate the safety and effectiveness of low-dose nab-paclitaxel in a multicenter, single-arm, phase II study. Patients and Methods: Treatment included low doses of 180 mg/m² nab-paclitaxel administered on day 1 of each 21-day cycle. The primary endpoint was defined as the overall response rate (ORR). The secondary endpoints included progression-free survival (PFS), safety, and overall survival (OS). A total of 34 patients were enrolled in the full-analysis set. Results: The ORR was 5.9%. The median PFS and OS were 2.4 months and 9.2 months, respectively. The most common grade 3/4 toxicities were anemia (8.8%), neutropenia (5.9%), appetite loss (5.9%) and peripheral sensory neuropathy (5.9%). No treatment-related deaths occurred. Conclusion: The tri-weekly low dose of nab-paclitaxel therapy is effective towards advanced gastric cancer patients with good tolerability and an acceptable margin of safety.

https://ift.tt/2rmQ1sV

Evaluation of the Usefulness of FDG-PET/CT for Nodal Staging of Breast Cancer

Background/Aim: Positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorodeoxyglucose (18F-FDG) has recently been used to investigate lymph node (LN) metastases and several predictive features in patients with breast cancer (BC). The aim of this study was to assess the value of this non-invasive imaging procedure for axillary staging. Patients and Methods: Fifty patients with early primary unilateral, locally advanced, or recurrent invasive operable BC were enrolled. All patients underwent preoperative 18F-FDG PET/CT, and the results were compared with the histopathology of dissected axillary LNs and their biological and immunohistochemical characteristics. The diagnostic performance of 18F-FDG PET/CT in detecting LN metastases from primary or recurrent BC was analyzed. The mean values of the initial PET/CT parameters, including the primary tumour (SUV T) and ipsilateral axillary LNs (SUV LN), were compared with the clinicopathological features of patients to determine their usefulness for predicting clinical interactions. Results: The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT for axillary LN staging were 87%, 90%, 88%, 93%, and 82%, respectively. Bivariate analyses showed strong interactions of nuclear grade (p=0.05), progesterone receptor expression (p=0.001), Ki-67 index (0.027), and local relapse with the SUV T. A high SUV LN value was significantly correlated with a higher nuclear grade score (p=0.05), oestrogen receptor negativity (p=0.001), progesterone receptor negativity (p=0.014), a high Ki-67 index (>20%; p=0.048), LN metastasis (p<0.001), a basal tumour (p=0.04), and locoregional recurrence (p<0.001). Conclusion: PET/CT is a reproducible, non-invasive imaging modality that is useful for evaluating a primary BC mass and its relationship with metastatic axillary LNs, thereby predicting tumour behaviour and guiding clinical practice.

https://ift.tt/2G31mZl

Targeted Therapies for Pancreatic Cancer and Hurdles Ahead

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a median survival of 6 months after diagnosis. Intrinsic resistance to chemotherapeutics and lack of effective targeted therapies are the major factors contributing to dismal prognosis. Several important genetic alterations (i.e., mutations, deletions) have been identified to be involved in the initiation and progression of pancreatic cancer, including KRAS and inactivation of tumor suppressors, such as TP53, SMAD4 and CDKN2A. Unique tumor microenvironment with excessive stroma due to desmoplastic reaction is one of the major characteristics of PDAC, promoting tumor growth and leading to treatment failures. In addition, tumor stroma represents an important biological barrier for drug delivery and successful treatment of PDAC. Small interfering RNA (siRNA) has recently emerged as a potential and targeted therapeutic approach which is now evaluated in clinical trials. However, siRNA-based therapeutics face important challenges, including rapid serum degradation, poor tumor cell uptake and cellular uptake, leading to off-target effects. Therefore, there is a great need for the development of safe and effective nanoparticles for better tumor-specific delivery of anti-cancer therapeutics. In this article, the main challenges in the treatment of pancreatic cancer and recent advancements on nano delivery systems of chemotherapeutics and gene-targeted agents, used both in preclinical and clinical trials are reviewed.

https://ift.tt/2rd1r27

Effect of Combined Epigenetic Treatments and Ectopic NIS Expression on Undifferentiated Thyroid Cancer Cells

Background: Poorly differentiated (PDTC) and anaplastic thyroid (ATC) cancer cells are characterized by the acquisition of epigenetic abnormalities, leading to the silencing of both the sodium iodide co-transporter and the Coxsackie adenovirus receptor. As aberrant histone acetylation and DNA methylation represent epigenetic mechanisms involved in neoplastic transformation, our study investigated the anticancer properties of epigenetic modifiers in thyroid carcinoma. Materials and Methods: The cytotoxicity and gene expression modulation of histone deacetylase and DNA methyltransferase inhibitors were evaluated in both PDTC and ATC. Results: Epigenetic treatments were cytotoxic to tumor thyrocytes and restored sodium iodide co-transporter and Coxsackie adenovirus receptor, expression as well as radioiodine uptake, in PDTC but not in ATC. However, ectopic expression sodium iodide co-transporter re-activated radioiodine incorporation in ATC. Conclusion: The ability of epigenetic treatments to interfere with tumor proliferation and induce Coxsackie adenovirus receptor expression, coupled with the ability of ectopic sodium iodide co-transporter to restore radioiodine uptake, raise the possibility that these therapeutic approaches may provide clinical benefit to patients with thyroid carcinoma refractory to radioiodine treatment.

https://ift.tt/2FQlkGu

Outcomes of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Severe Cirrhosis and Ineligibility for Transplant

Background/Aim: Our study reviewed the results of patients with hepatocellular carcinoma and Child–Pugh score 8-11 cirrhosis treated with stereotactic body radiotherapy when liver transplant was not an option. Patients and Methods: A retrospective review was performed on 15 patients with Child–Pugh class B and C cirrhosis treated with stereotactic body radiotherapy. The median total dose was 35 Gy in 4-5 fractions. None were listed for a liver transplant due to either being outside of the Milan criteria or to medical contraindications. Results: The overall survival was 26.7% at 6 months, with a mean survival of 152 days. The mean survival with and without ascites was 3.3 months and 8.3 months, respectively. Conclusion: For hepatocellular carcinoma with cirrhosis of Child–Pugh score 8 or more, prognosis after liver stereotactic body radiotherapy was suboptimal. While irradiation achieved local tumor control, progressive cirrhosis was a common cause of death. Patients without ascites at the time of radiotherapy had the best prognosis.

https://ift.tt/2rcAk7n

Embryonal Origin of Metanephric Adenoma and its Differential Diagnosis

Background/Aim: The association of Wilms' tumor (WT), papillary renal cell tumor (PRCT) and mucinous tubular and spindle cell carcinoma (MTSCC) with embryonal rests has already been documented, but the cellular origin of metanephric adenoma (MA) is not yet known. The aim of this study was to understand their developmental evolution and find diagnostic markers. Materials and Methods: CD57, KRT7, AMACR, SCEL, WT1 and CDH17 expression was analysed by immunohistochemistry in the four types of tumors and the associated pre-neoplastic lesions. Results: Immunohistochemistry was able to differentiate WT, MA, MTSCC and PRCT. A phenotypic correlation between MA and perilobar nephrogenic rest associated with WT was identified. Conclusion: Perilobar nephrogenic rest and MA arise from differentiation arrested cells of the proximal domain of the S-shape body. We propose that WT1, MA, MTSCC and PRCT derive from different forms of maturation arrested embryonal rests.

https://ift.tt/2FRJ2C3

Prognostic Factors and a Survival Score in Patients Irradiated for Metastatic Epidural Spinal Cord Compression from Urothelial Carcinoma Cancer of the Bladder

Background/Aim: Prognoses of patients with metastatic epidural spinal cord compression (MESCC) from urothelial carcinoma of the bladder are generally poor. This study aimed to identify prognostic factors that can facilitate personalized care of these patients. Patients and Methods: In 46 patients, 10 factors were evaluated for overall response (OR), post-radiotherapy (RT) ambulatory status, local control of MESCC and overall survival (OS). Independent predictors of OS were incorporated in a scoring system. Results: Being ambulatory post-RT was associated with pre-RT ambulatory status (p<0.001) and better performance score (p<0.001). No factor was significantly associated with OR and local control. On multivariate analyses, lack of visceral metastases (p=0.002), being ambulatory pre-RT (p=0.001) and performance score 1-2 (p=0.004) were associated with improved OS. Based on these factors, there were three distinct prognostic groups with 0, 1-2 and 3 points and median OS times of 2, 4 and 11.5 months, respectively. Conclusion: Prognostic factors were identified and a new survival score was created that will help physicians aiming to personalize treatment for patients with MESCC from urothelial carcinoma of the bladder.

https://ift.tt/2rfjWmt

Cell Harvesting Methods Affect Cellular Integrity of Adherent Cells During Apoptosis Detection

Background/Aim: Annexin V and propidium iodide (PI) dual staining is commonly applied in bioscience as a method to detect apoptosis. However, excessive handling of adherent cells may interfere with the integrity of plasma membrane and hence impede the accuracy of this method. Here, we exploited PI uptake as an indicator of cell integrity and investigated how cell harvesting methods and solutions involved in common apoptosis detection techniques affected measurement results. Materials and Methods: Different cell harvesting techniques, staining with PI and flow cytometry were performed. Results: Non-fixed scrapped cells revealed significantly higher fractions of PI-positive staining compared to non-fixed trypsinized cells. In the case of harvesting cells by scrapping, samples stained in binding buffer (68.30±3.55%) showed consistently higher PI-positive staining than samples stained in PBS (36.37±5.90%) in a significant manner (p=0.015). Conclusion: Enzymatic harvesting using 0.25% trypsin instead of mechanical harvesting by rubber scraper caused less damage of cell integrity. Furthermore, the binding buffer used in the apoptosis detection protocol aggravated the existing plasma membrane damage caused by the rubber scraper.

https://ift.tt/2G0nMtQ

No Renal Toxicity After Repeated Treatment with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Unresectable Peritoneal Metastasis

Background/Aim: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal metastasis (PM). The aim of this study was to report renal toxicity for patients who received at least 3 repeated PIPAC procedures. Patients and Methods: All patients who underwent at least 3 PIPAC cycles of cisplatin (7.5 mg/m²) and doxorubicin (1.5 mg/m²) for unresectable PM from December 2015 to September 2017, were analysed regarding postoperative renal toxicity. Results: Among 103 patients registered in a prospective single center database, 43 patients underwent at least 3 PIPAC cycles representing a total of 175 PIPAC. Median age was 59.8 years, 24 (55.8%) patients were female and median BMI was 22.2 kg/m². Most common origins of PM were gastric 22 (51.1%) and ovarian 11 (25.6%) cancer. Median peritoneal cancer index (PCI) was 17 (range=5-39). For 39 (90.1%) patients, systemic chemotherapy was performed in addition to PIPAC. Forty-three (100%), 17 (39.5%), 14 (32.5%), 8 (18.6%), 3 (7%), 2 (4.7%) and 2 (4.7%) patients underwent three, four, five, six, seven, eight and nine PIPAC procedures, respectively. Repeated PIPAC did not induce significant acute nor cumulative renal toxicity in any patients. Conclusion: Repeated PIPAC did not induce clinically relevant renal toxicity. This study confirms the previous published results in a larger group of patients.

https://ift.tt/2reUXQw

Expression of CK7 and CDKN2 in Cervical Intraepithelial Neoplasia and Correlation with Clinical Outcome

Aim: To evaluate cyclin-dependent kinase inhibitor 2A (CDKN2A) and cytokeratin 7 (CK7) expression in cervical intraepithelial neoplasia (CIN) formalin-fixed samples. Materials and Methods: Staining with antibody clones G175-405 for CDKN2A and OV-TL 12/30 for CK7 were evaluated and the detection of protein expressions were compared in 147 patients with CIN. Results: Clinical follow-up of patients with CIN1 and CIN2 showed that most patients had a favorable outcome. Single CDKN2A or CK7 expression and their combined expression had a greater sensitivity and negative predictive value in CIN1, corresponding to the non-development of the disease. The positive predictive value of CDKN2A was greater than that of CK7. Combined expression of CDKN2A and CK7 showed that the sensitivity, specificity, positive predictive values, and negative predictive values had their maximum index in the CIN1 group. Analysis of combined expression of CDKN2A and CK7 showed that 85.7% of patients presented unfavorable clinical outcomes, with positive expression for both markers identified in CIN2. Conclusion: Combined expression of CK7 and CDKN2A was associated with a better diagnosis of CIN, and negative expression in CIN1/2 groups had a greater negative predictive value for patient clinical outcome.

https://ift.tt/2FPHWqt

Outcomes After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients with Oligo-metastatic Breast Cancer

Background/Aim: Patients with oligo-metastatic breast cancer are a unique patient subgroup with more favourable outlook than most patients with metastatic disease. Prognostic factors in these patients with metastatic spinal cord compression (MSCC) were evaluated. Patients and Methods: In 159 patients irradiated for MSCC from oligo-metastatic breast cancer, seven characteristics were retrospectively analyzed including age, interval between breast cancer diagnosis and irradiation of MSCC, time developing motor deficits, ambulatory status, involved vertebrae, performance score (ECOG-PS) and radiotherapy regimen. Results: Improvement of motor function was significantly associated with time developing motor deficits (p=0.017), post-radiotherapy ambulatory status with pre-radiotherapy ambulation (p=0.012) and ECOG-PS 1-2 (p=0.029). Radiation doses of 39-40 Gy (equivalent doses) resulted in 1- and 2-year local control of 100% and 95%. On multivariate analyses, higher doses were associated with local control (p=0.011). Pre-radiotherapy ambulatory status (p=0.001) and ECOG-PS 1-2 (p=0.002) were associated with survival. Conclusion: Significant prognostic factors were identified for patients with MSCC from oligo-metastatic breast cancer. Higher radiation doses improved local control.

https://ift.tt/2re1Otf

Challenges in diffusion MRI tractography – Lessons learned from international benchmark competitions

Publication date: Available online 29 November 2018

Source: Magnetic Resonance Imaging

Author(s): Kurt G. Schilling, Alessandro Daducci, Klaus Maier-Hein, Cyril Poupon, Jean-Christophe Houde, Vishwesh Nath, Adam W. Anderson, Bennett A. Landman, Maxime Descoteaux

Abstract

Diffusion MRI (dMRI) fiber tractography has become a pillar of the neuroimaging community due to its ability to noninvasively map the structural connectivity of the brain. Despite widespread use in clinical and research domains, these methods suffer from several potential drawbacks or limitations. Thus, validating the accuracy and reproducibility of techniques is critical for sound scientific conclusions and effective clinical outcomes. Towards this end, a number of international benchmark competitions, or "challenges", has been organized by the diffusion MRI community in order to investigate the reliability of the tractography process by providing a platform to compare algorithms and results in a fair manner, and evaluate common and emerging algorithms in an effort to advance the state of the field. In this paper, we summarize the lessons from a decade of challenges in tractography, and give perspective on the past, present, and future "challenges" that the field of diffusion tractography faces.

https://ift.tt/2SjNuuQ

Sex, Microbes, and Polycystic Ovary Syndrome

Publication date: Available online 29 November 2018

Source: Trends in Endocrinology & Metabolism

Author(s): Varykina G. Thackray

Recent studies have shown that sex and sex steroids influence the composition of the gut microbiome. These studies also indicate that steroid regulation of the gut microbiome may play a role in pathological situations of hormonal excess, such as PCOS. Indeed, studies demonstrated that PCOS is associated with decreased alpha diversity and changes in specific Bacteroidetes and Firmicutes, previously associated with metabolic dysregulation. These studies suggest that androgens may regulate the gut microbiome in females and that hyperandrogenism may be linked with a gut 'dysbiosis' in PCOS. Future mechanistic studies will be required to elucidate how sex steroids regulate the composition and function of the gut microbial community and what the consequences of this regulation are for the host.

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