G2 G3 Research Articles

Radiomics for Tumor Characterization in Breast Cancer Patients: A Feasibility Study Comparing Contrast-Enhanced Mammography and Magnetic Resonance Imaging.

The aim of our intra-individual comparison study was to investigate and compare the potential of radiomics analysis of contrast-enhanced mammography (CEM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast for the non-invasive assessment of tumor invasiveness, hormone receptor status, and tumor grade in patients with primary breast cancer. This retrospective study included 48 female patients with 49 biopsy-proven breast cancers who underwent pretreatment breast CEM and MRI. Radiomics analysis was performed by using MaZda software. Radiomics parameters were correlated with tumor histology (invasive vs. non-invasive), hormonal status (HR+ vs. HR−), and grading (low grade G1 + G2 vs. high grade G3). CEM radiomics analysis yielded classification accuracies of up to 92% for invasive vs. non-invasive breast cancers, 95.6% for HR+ vs. HR− breast cancers, and 77.8% for G1 + G2 vs. G3 invasive cancers. MRI radiomics analysis yielded classification accuracies of up to 90% for invasive vs. non-invasive breast cancers, 82.6% for HR+ vs. HR− breast cancers, and 77.8% for G1+G2 vs. G3 cancers. Preliminary results indicate a potential of both radiomics analysis of DCE-MRI and CEM for non-invasive assessment of tumor-invasiveness, hormone receptor status, and tumor grade. CEM may serve as an alternative to MRI if MRI is not available or contraindicated.

Phase I results from a phase 1/2 multi-center study of nab-sirolimus combined with mFOLFOX6+bevacizumab (FB) as first-line (1L) therapy in patients (pts) with metastatic colorectal cancer (mCRC) with or without PTEN loss.

e16050 Background: The PI3K/mTOR pathway overactivation and loss of PTEN occur in 20-40% of mCRC pts. A recent phase 1/2 study in mCRC pts showed evidence that everolimus added to 1L SOC treatment improved outcomes, in particular in pts with PTEN loss (Gilcrease, 2019). This prospective, single-arm phase 1/2 study aims to identify the optimal dose and schedule of nab-sirolimus (ABI-009), an mTOR inhibitor, plus FB and evaluate the safety and preliminary efficacy of this regimen. Methods: Eligible pts have no prior therapy, ≥18 years old, ECOG performance status of 0-2. PTEN loss (by IHC) is evaluated for all pts. nab-Sirolimus IV starting dose and schedule was 30mg/m2 weekly for 3 weeks followed by a week of rest (on D1, 8, and 15 in a 28-day cycle, qw3/4) plus standard doses of FB on D1 and D15. Dose escalation to 45 and 60mg/m2 or de-escalation to 20 and 10mg/m2 followed the 3+3 design. Dose limiting toxicity (DLT) was assessed in cycle 1. Results: As of Jan 31, 2020, 24 pts were treated in the phase 1 study and 18 were evaluable for response. No DLTs were observed in the first 3 pts treated with nab-sirolimus at 30mg/m2 qw3/4; however, all 3 pts missed D8 doses (due to G2 thrombocytopenia and G3 neutropenia) and the cohort expanded to additional 3 pts for further observation. 5/6 pts missed D8 doses and a new dose cohort enrolled pts at 20mg/m2 qw3/4. No DLTs were observed and the cohort was expanded to 10 pts. A safety review of the first 18 pts observed that 9/18 pts missed doses on D8 and a new cohort was added to enroll pts at 20 mg/m2 q2w (D1 and D15, as for FB). This cohort enrolled 8 pts with no DLTs and represents the recommended-phase-2-dose (RP2D) and continues enrollment in phase 2. For all pts, 15/24 (63%) pts had G3-4 treatment-related adverse events (TRAEs); most common were neutropenia (6/24, 25%) and thrombocytopenia (4/24, 17%). At the RP2D 3/8 (38%) pts had G3-4 TRAEs (thrombocytopenia, weight loss, and hypertension, 1 pt each). Among 18 evaluable pts, best response was: 7/18 (39%) partial response, 10/18 (56%) stable disease, and 16/18 (89%) had tumor shrinkage. PTEN was assessed in 14 pts: 4/14 (29%) had PTEN loss, 2/4 (50%) PTEN loss pts responded, while 3/10 (30%) pts that were PTEN+ (WT) had a response. Conclusions: The RP2D of nab-sirolimus is 20mg/m2 q2w in combination with standard mFOLFOX+bevacizumab. The phase 2 portion of the study is ongoing. Clinical trial information: NCT03439462 .

A phase I study to evaluate the T-cell engager AMV564 alone and in combination with pembrolizumab in subjects with advanced solid tumors.

3101 Background: Overcoming the immune-suppressive tumor environment induced by myeloid-derived suppressor cells (MDSC) is a major challenge in immune therapy. CD33 signaling in immature myeloid cells promotes expansion of MDSC and production of immune-suppressive factors. AMV564 is a bivalent, bispecific T-cell engager that binds CD3 and CD33. Preferential binding of AMV564 to areas of high CD33 density enables selective targeting of MDSC. Ex vivo data (Cheng 2017; Blood;130:51) and an ongoing clinical trial in acute myeloid leukemia (NCT03144245) demonstrate the ability of AMV564 to deplete MDSC while sparing monocytes and neutrophils. Methods: In this 3+3 dose escalation study, patients with advanced solid tumors receive AMV564 once daily via subcutaneous (SC) injection for 2 out of 3 wks per cycle, alone or in combination with pembrolizumab (200 mg every 3 wks). Key objectives are to evaluate AMV564 safety, identify a maximum tolerated or recommended phase 2 dose, and evaluate PK, immunophenotype of myeloid and T cell compartments, and preliminary efficacy. Results: Eleven patients have been enrolled: 8 monotherapy (3 at 15 mcg/d, 5 at 50 mcg/d) and 3 combination (5 mcg/d). Tumor types include ovarian (n = 2), small bowel, gastroesophageal junction, endometrial, rectal, penile, urothelial, squamous cell carcinoma (skin), appendiceal, and non-small cell lung. AMV564 was associated with grade (G) 1-2 injection site reactions and G1-2 fevers, which were manageable with acetaminophen and diphenhydramine, as well as G2 weight gain and G3 anemia. No dose-liming toxicity has been observed in any cohort. Three monotherapy patients (15 mcg/d) were evaluable for efficacy with ≥1 on-treatment scan; 2 had SD and 1 PD per RECIST 1.1 criteria. T cell activation, as shown by redistribution from the periphery (margination), was apparent in the first week of dosing for most patients. Compensatory myelopoiesis led to initial expansion of MDSC which were then depleted by AMV564. Increased cytotoxic T cell activation and T-helper (Th) 1 response was evidenced by increased T-bet positive CD4 and CD8 cells and controlled or decreased regulatory T cells. In some patients, effector memory CD8 cell populations (Tem and Temra) were expanded. Conclusions: AMV564 is safe and tolerable when administered SC at doses of 15 mcg/d alone and 5 mcg/d in combination with pembrolizumab. AMV564 depleted MDSC populations and altered T cell profiles consistent with activation of cytotoxic T cells and a Th1 response. Clinical trial information: NCT04128423 .

Investigation of Nonwoven Geotextiles for Full Contact Flexible Mould Used in Preparation of MICP-treated Geomaterial

This study is concerned with needle-punched, nonwoven geotextile materials that have been used to develop full contact flexible moulds (FCFM) to treat soil specimens through microbial calcite precipitation (MICP) process by immersing method. MICP was induced through bacteria-urea reactions. The objective of this study was to figure out how different geotextiles influence the preparation of MICP-treated specimens. Five types of geotextiles were selected to prepare FCFM used for MICP treatment in this study. There is one singeing geotextile with the sintered side during these five geotextiles. Unconfined compression tests, four-point bending tests, and direct shear tests were conducted on MICP-treated specimens prepared by different geotextiles. The experimental results indicated that the mechanical properties of MICP-treated soil specimen prepared in FCFM made by G2 geotextile and G3 geotextile were similar. The unconfined compressive strength of the MICP-treated specimen reached 1.12 MPa (G2) and 0.90 MPa (G3), and MICP-treated specimens prepared by singeing geotextile had better performance than original geotextiles.

Chemopreventive effect of olive oil in experimentally induced hamster buccal pouch epithelial dysplasia (Randomized control trial)

The progression of tumor depends on the level of Bcl-2 which protects the cells from undergoing apoptosis, and its level should be more than the level of the death inducer. So, our Aim: To investigate chemopreventive effect of olive oil in epithelial alteration which induced in hamster buccal pouch. Methods: Epithelial dysplasia will occur by the application of DMBA on alternative days for 8 weeks on hamster buccal pouch. Hematoxylin and Eosin (H&E) and Streptavidin-biotin immunoperoxidase staining techniques were used to detect the expression of Bcl-2 in three groups (G1 negative control or normal group, G2 DMBA group and G3 olive oil chemoprevention group). Evaluation of the immunostaining was done by using computer image analyzer system. Results: H & E stained histological section in G1 with normal mucosa of HBP intact, and continuous epithelium of thin keratinized stratified squamous epithelium while in G2 there were incidence of severe epithelial dysplasia with hyperkeratosis & G3 reduced dysplasia incidence and severity as compared to G2. Bcl-2 immunohistochemical expression in G1 in basal & suprabasal layers while in G2 & G3 located in all epithelial layers with statistically highly significant difference (P G1, G3) and (G3>G1). Conclusion: Olive oil plays an important role in reduction and prevention of transformation of normal oral epithelium into epithelial dysplasia. The liquid form of olive oil may be considered as a new line of chemoprevention in oral dysplasia and the Bcl-2 expression evidenced this reduction of abnormality in epithelial dysplasia.

Comparison of Effect of Various non-pharmacologic Methods on Pain in Infants during Vaccination

Objective: To compare the effect of various non pharmacologic methods on pain in infants during vaccination as assessed by Neonatal Infant Pain Scale (NIPS). Design: Prospective randomized controlled trial. Sample: 120 infants for pentavalent vaccination (30 in each group G1, G2 G3 and G4).Methods: The enrolled infants were randomized into three intervention groups (Breast feeding G1, buzzy device group G2, Helfer technique group G3 and control group G4). During vaccination procedure was videographed and pain score assessed by independent blinded observer. Result: The mean pain score of four groups (G1, G2, G3 & G4) were 3.77, 3.80, 4.50 and 4.83. Breast feeding effectively reduces pain score than mechanical stimulation by buzzy device. Comparison of pain score of different group by F value is not significant at 0.05 level of significance. How to cite this article:Bhattacharya R, Batra B. Comparison of Effect of Various non-pharmacologic Methods on Pain in Infants during Vaccination. Int J Preven Curat Comm Med 2019; 5(4): 7-11. DOI: https://doi.org/10.24321/2454.325X.201922

Non-Targeted Metabolomic Analysis Reveals Serum Phospholipid Alterations in Patients with Early Stages of Diabetic Foot Ulcer.

Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.

Influence of seasonal climatic factors on the dynamics of birds interactions with oaks consortia

The article is devoted to the bird communities in individual oak consortia (Quercus robur L.) of the linden-ash oak forests. This work material was collected during different seasons of the 2004–2010 years in a linden-ash oak grove on the test plot No. 209 of the ecological profile of the NSC «Bel'gard Prisamar`e International Biospheric stationary», Novomoskovsk district, Dnepropetrovsk region. The individual consortia of 281 examples of three age conditions oak trees (virgins – virg, young generative – gl, mature and old generative individuals – g2–g3) has been investigated. The daily time budget decreases by 2–2,5 times in autumn for all oak ages that have been studied. But the number of consort birds is reduced by 2 times only for virgin and old generative oaks. The young generative oak is attractive enough for birds in autumn. The ratio of the trophic and topical share interactions for all trees ages does not change significantly in autumn. Birds don’t interact with the virgin oak in winter practically. This age oak can’t propose enough food or places for birds’ protection from predators. Oaks in age g1–g3, on the contrary, are in demand by the birds. There 7 birds species on g1 oaks and 13 species on g2–g3 oaks were recorded in winter. The birds’ daily time buds for the one oak example are low in winter, and by the 90 times reduce compared with the summer. The bird time budget basis in winter are the trophic interactions. The birds’ activity on oak sharply increases in spring and exceeds 1,5–2 times the summer parameters on virgin and mature generative oak (g2–g3). Birds on oak spend most of their time on topical interactions during this season because of the oak important role in the birds reproduction. On the other hand, the young generative oak (g1) is not in demand by the birds in spring because of insufficient crown density and the oaks of this age location at the edge. The number of bird species on oak in spring is less than in summer due to the late onset of leaf blooming on the oak. A significant part of the birds’ activity in the spring moves to the lower tier of the forest because of the earlier vegetation beginning. As a result of the research, it was revealed that the consorting groups of common oak throughout the year retain the main features of their organization. The virgin oak is characterized by a stochastic nature of the birds interaction with the consortium core and almost hasn’t obligate consort birds. Young generative oak is actively forming a trophic relations system with consorts due to intensive linear growth. At this age, first of all, general indicators are formed – time and mass budgets. The consortium of mature and old generative oak has a significantly larger number of bird species consorts and their interactions diversity with the tree. This can help to increase the stability of consorting groups. In most cases in the oak consortium the trophic component of the consortium form earlier then the topical. The specific location of the virgin and young generative oak at the lit positions in the lime-ash oak forests influences the oak consortia formation in a considerable scale. The number of types of interactions between the consort and the autotroph is the most effective indicator, which shows a high level of the consortium development. The stability of consortial relations between birds and English oak grows throughout the year from virgin oak to mature and old generative. The virgin oak unstable consorting groups have fluctuations of the species number during the year up to 100 % (the number of consort species in summer was chosen as the initial value). The consortia species composition fluctuations reach 81,82 % for young generative oak, and 59,26 % – for mature and old generative oak. The mature and old generative oak consortia attract seasonal bird species that replace each other throughout the year more actively. This ensures the stability of year-round control of phytophage populations.

Modeling and simulation of trajectory smoothing and feedrate scheduling for vibration-damping CNC machining

The mathematical models of tool path smoothing and feedrate scheduling in Computer Numerical Control (CNC) system are critical for high-precision manufacture. Inthe existing studies, G2/G3 (curvature-continuous/-smooth) trajectory smoothing, and jerk-limited/-continuous feedrate scheduling schemes have been developed. Nonetheless, there are exist some requirements that cannot be satisfied simultaneously, including confined chord error, G01 points interpolated, analytical curvature extremum, real-time performance, kinematic time-optimality, and the smoothness of tool-path and feedrate profile. Recently the scholars found the potentials of the tool path with high-order geometric continuity and the feedrate with high-order kinematic constraints, respectively in increasing the smoothness of tool path and reducing the impact caused by axis actuators during the process. Aiming to reduce the vibration and guarantee high machining efficiency, this work proposes G4 (curvature-variation-smooth) interpolative trajectory model with confined chord error and analytical curvature extrema for trajectory smoothing, and employs jerk-smooth (jerk-differentiable) feedrate mode to perform time-optimal feedrate scheduling. Finally, a real-time tool path processing strategy under various geometric and kinematic constraints is developed. The simulation shows approximation error, curvature extrema, and feedrate fluctuation are reduced compared with G2 transition and G3 interpolation schemes. The experimental results demonstrate advantages of the proposed method in vibration damping, surface quality, compared with the previous works.

Influence of seasonal climatic factors on the dynamics of birds interactions with maples consortia

The article is devoted to the bird communities in individual maple consortia (Acer campestre). This work material has been collected during different seasons of 2004‒2010 years in the linden-ash oak grove on the test plot No. 209 of NSC «Bel'gard Prisamar`e International Biospheric stationary» ecological profile, Novomoskovsk district, Dnepropetrovsk region. The individual consortia of 214 examples of three age conditions maple trees (virgins – virg, young generative – gl, mature and old generative individuals– g2–g3) has been investigated. Some bird species daily time budget (DTB) per autotroph exampl on average has been the basic parameter for the birds’ participation in the consortia functioning assessment. The maple consortia communities have been revealed in the result of investigation to be the basic for the oak birds. Non-forest birds species almost have not appeared in them, which differs them from the consortia of the oak forests edificators, for instance, oak. Field maple attracts birds in the cold seasons because of its participation in the forest stand formation and of its ontogenesis course. Field maple seeds remain on the tree during the autumn and winter and support the birds vital activity in this period, unlike oak. The total birds’ activity in the trees decreases significantly in the fall. But such situation is observed in autumn only on virg maple. Maples g1, g2–g3, on the contrary, attract birds in autumn more than in summer. There are more DTB birds on these maples in autumn than in summer, because of the late leaf falling and numerous fruits availability. Birds eat actively phytophages on maple fruits. The autumn community of wild maple birds aged g2–g3 is the most active on DTB index. On the other hand, the species composition on generative maples decreases two to three times in comparison with summer. In winter the birds DTB activity on maple decreases by 15–20 times, because of the wintering birds migration to the settlements. Very few birds remain in the oak forest in winter. But the birds wintering in the oak forest species composition is quite diverse, which affects the birds’ species composition of the maple consortiums in winter. It is more diverse than in the fall. Mistletoe infects maple quite often and its fruits also attract birds to the maple consort in winter. As a result, the birds DTB index on old generative maples is higher than on oak this time of year. The birds’ species composition in g2–g3 maple consortiums is represented by 14 species in winter. This figure is 2.5 times more than in autumn. The virgin maple consortium has a high birds DTB index in spring. The main reasons are – this tree vegetation early start and the dense thickets formation of this tree young growth. As a result, the virgin maple has a diverse trophic base for birds in the spring. This consortium is comparable with the consortium of g1maple in the birds’ species composition and exceeds it in the DTB index. The time budget of birds’ trophic interactions is 75% of the total DTB in the maple consort at the age of virg. The time budget of the bird topical interactions is 80% of the total DTB in the g1 maple consortium. The birds almost do not hunt on this age maples, but show a variety of behavioral activity. The birds’ community in the g2–g3 age maple consort is very diverse in spring and yield in to that only in old generative oak. The time budget of the birds’ topical interactions is 75% of the total DTB in the g2–g3 maple consortium. Thus, birds use g2–g3 maple in spring mainly for singing, resting, cleaning feathers, mating games, etc., rather than feeding.

Long Peritoneal Dialysis Dwells With Icodextrin: Kinetics of Transperitoneal Fluid and Polyglucose Transport.

Background and objective: During peritoneal dialysis (PD), the period of effective net peritoneal ultrafiltration during long dwells can be extended by using the colloidal osmotic agent icodextrin but there are few detailed studies on ultrafiltration with icodextrin solution exceeding 12 h. We analyzed kinetics of peritoneal ultrafiltration in relation to icodextrin and its metabolites for 16-h dwells with icodextrin.Design, setting, participants, and measurements: In 20 clinically stable patients (mean age 54 years; 8 women; mean preceding time on PD 26 months), intraperitoneal dialysate volume (VD) was estimated from dilution of 125I-human serum albumin during 16-h dwell studies with icodextrin 7.5% solution. Sodium was measured in dialysate and plasma. In 11 patients, fractional absorption of icodextrin from dialysate, dialysate, and plasma amylase and high and low (Mw <2 kDa) Mw icodextrin fractions were analyzed.Results: Average VD increased linearly with no difference between transport types. At 16 h, the cumulative net ultrafiltration was 729 ± 337 ml (range −18 to 1,360 ml) and negative in only one patient. Average transcapillary ultrafiltration rate was 1.40 ± 0.36 ml/min, and peritoneal fluid absorption rate was 0.68 ± 0.38 ml/min. During 16 h, 41% of the initial mass of icodextrin was absorbed. Plasma sodium decreased from 138.7 ± 2.4 to 136.5 ± 3.0 mmol/L (p < 0.05). Dialysate glucose G2–G7 oligomers increased due to increase of G2–G4 metabolites while G6–G7 metabolites and higher Mw icodextrin fractions decreased. In plasma maltose and maltotriose (G2–G3 metabolites) increased while higher Mw icodextrin oligomers were almost undetectable. Dialysate amylase increased while plasma amylase decreased.Conclusions: Icodextrin resulted in linear increase of VD with sustained net UF lasting 16 h and with no significant difference between peritoneal transport types. In plasma, sodium and amylase declined, G2–G3 increased whereas larger icodextrin fractions were not detectable. In dialysate, icodextrin mass declined due to decrease of high Mw icodextrin fractions while low Mw metabolites, especially G2–G3, increased. The ability of icodextrin to provide sustained UF during very long dwells – which is usually not possible with glucose-based solutions – is especially important in anuric patients and in patients with fast peritoneal transport.

Endoscopic management of 345 small rectal neuroendocrine tumours: A national study from the French group of endocrine tumours (GTE)

Small rectal neuroendocrine tumours are good candidates for endoscopic resection provided that complete pathological resection (R0) is obtained and their risk of metastatic progression is low. We conducted a large multicentre nationwide study to evaluate the outcomes of the management of non-metastatic rectal neuroendocrine tumours ≤2 cm diagnosed endoscopically. The medical records, the endoscopic and pathological findings of patients with non-metastatic rectal neuroendocrine tumours ≤2 cm managed from January 2000-June 2018 in 16 French hospitals, were retrospectively analysed. The primary objective was to describe the proportion of R0 endoscopic resections. A total of 329 patients with 345 rectal neuroendocrine tumours were included, 330 (96%) tumours were managed by local treatments: 287 by endoscopy only and 43 by endoscopy followed by transanal endoscopic microsurgery. The final endoscopic R0 rate was 134/345 (39%), which improved from the first endoscopy (54/225, 24%), to the second (60/100, 60%) and the third endoscopy (20/26, 77%). R0 was associated with endoscopic technique (90% for advanced techniques, 40% for mucosectomy and 17% for polypectomy), but not with tumour or patient characteristics. Twenty patients had metastatic disease, which was associated with tumour size ≥10 mm (odds ratio: 9.1, 95% confidence interval (3.5-23.5)), tumour grade G2-G3 (odds ratio: 4.2, (1.5-11.7)), the presence of muscular (odds ratio: ∞, (11.9-∞)) and lymphovascular invasion (odds ratio: 57.2, (5.6-578.9)). The resection of small rectal neuroendocrine tumours often requires multiple procedures. Training of endoscopists is necessary in order to better recognise these tumours and to perform the appropriate resection technique.

Epigenetic effects of in utero bisphenol A administration: Diabetogenic and atherogenic changes in mice offspring.

Objective(s):Bisphenol A (BPA) that is a monomer of plastic products may possibly interfere with epigenetics and be involved in onset and progression of several diseases. This study was aimed to detect the epigenetic effects of in utero BPA exposure in mice offspring.Materials and Methods:All experiments were performed according to the national guidelines for laboratory animals and after ethical approval. Thirty adult BALB/c female mice were divided into 3 equal groups, G1 (controls), G2 (ethanol 0.10 ml/100ml of PBS so that final concentration would be 0.01%) vehicle control and G3 (BPA 10 mg/kg). Chemicals were given twice a week throughout the pregnancy. Once delivered at term, female offspring were observed for body weight, behavior and movements. Blood glucose, serum insulin, cholesterol and high-density lipoprotein cholesterol (HDLc) were measured at 5 and 15 months postnatal. Animals were sacrificed at 15 months and pancreas, kidney, adipose tissue and uterine tissue were taken and stained with either Hematoxylin and eosin (H & E) or immunostaining and examined under light microscope.Results:Offspring of group G3 revealed abnormal changes of body weight, behavior and movements. Blood glucose, serum insulin, cholesterol and HDLc were high in group G3 offspring compared to controls. H & E staining showed changes in the parenchyma of pancreas, kidneys and uterus, which were confirmed by staining with anti- islet-1, kidney-specific (Ksp) cadherin, and anti- MLH antibody.Conclusion: In utero exposure of BPA exerts diabetogenic and atherogenic effects with less parenchymal tissue in endocrine pancreas, kidney and uterus.

Outcomes and prognosticators of stage 4 renal cell carcinoma with pathological T4 primary lesion using a large, Canadian, multi-institutional database.

The primary objective of this study was to evaluate outcomes and prognosticators in patients who underwent radical nephrectomy (RN) or cytoreductive nephrectomy (CN), depending on the clinical stage of disease preoperatively, with a pathological T4 (pT4) renal cell carcinoma (RCC) outcome. There is little data on the outcome of this specific subset of patients. From 2009-2016, we identified patients in the Canadian Kidney Cancer information system (CKCis) who underwent RN or CN and were found to have pT4 RCC. Clinical, operative, and pathological variables were analyzed with univariable and multivariable Cox proportional hazard models to identify factors associated with overall survival (OS). Survival curves were created using Kaplan-Meier methods and compared using the log-rank test. A total of 82 patients were included in the study cohort. Median patient age was 62 years (interquartile range [IQR] 55, 70). Fifty (61%) patients had clear-cell histology and 14 (17%) had sarcomatoid characteristics. Median followup was 12 months (IQR 3, 24). At last followup, eight (10%) patients are alive with no evidence of disease, 27 (33%) are alive with disease, four (5%) were lost to followup, 36 (44%) died of disease, and seven (8%) died of other causes. Tumor histological subtype (clear-cell vs. non-clear-cell) (p=0.0032), larger tumor size (cm) (p=0.012), and Fuhrman grade (G4 vs. G2-G3) (p=0.045) were significantly associated with mortality in a multivariable Cox regression model. For patients with pT4 RCC after RN or CN, survival is poor. Sarcomatoid features, non-clear-cell histology, and presence of systemic symptoms were associated with worse OS.

Preliminary study on the relationship between the contrast-enhanced ultrasonography of liver metastasis and the differentiation degree of neuroendocrine tumors

Objective To retrospectively analyze contrast-enhanced ultrasound (CEUS) manifestations of neuroendocrine tumors (NETs) liver metastases, and explore the relationship between CEUS parameters and differentiation of NETs. Methods From January 2014 to June 2018, 36 patients who had been performed CEUS due to liver metastasis of NETs with pathological diagnosis and immunohistochemical staining results were enrolled in this study. The CEUS findings of NETs liver metastases were summarized. According to the Ki-67 index, CgA results, and the stage G, the patients were divided into Ki-67>20% group and Ki-67≤20% group, CgA negative group and CgA positive group, and group G1+ G2 and group G3, respectively. The CEUS parameters of NETs liver metastases between the above groups were compared. Results In 36 lesions, during the arterial phase of CEUS, 66.7% (24/36) showed hyperenhancement, 16.7% (6/36) isoenhancement, 13.9% (5/36) rim-like enhancement, and 5.6% (2/36) hypoenhancement; During the portal phase, 13.9% (5/36) showed hyper or iso enhancement, 86.1% (31/36) showed hypoenhancement. The average washout time was (67.5±56.1)s, of which 5 (13.9%) lesions were washed out after 120 s. The mean starting washout time was statistically different between the CgA negative group and the positive group [(91.6±81.5)s vs (60.1±38.7)s, P=0.001]. There was no statistically significant difference in all observations between the group of Ki-67≤20% and >20%, group G1+ G2 and group G3(P>0.05). Conclusions CEUS of NETs liver metastasis has certain characteristics, among which hyperenhancement is its main enhancement mode, and some lesions have a longer wash out time. The relationship with the degree of differentiation needs further investigation. Key words: Ultrasonography; Contrast-enhanced ultrasound; Neuroendocrine neoplasms; Differentiation degree

Expression of anti-apoptothic protein survinin and its gene BIRC5 in primary breast carcinoma as a prognostic factor for the disease

Objective:to study the expression of anti-apoptotic protein survivin and its gene BIRC5 in primary breast carcinoma as a potential predictive and prognostic marker.Materials and methods.Using immunohistochemical methods and real-time polymerase chain reaction 67 samples (biopsy) of the primary breast carcinoma were studied for the presence of expression of survivin protein and its gene BIRC5.Results.Expression of survivin was determined in 47 (70.15 %) mammary carcinoma samples. Expression of survivin was most often determined in medium and high grade ductal carcinoma (G2–G3), and was associated with lymphovenous stromal invasion in most cases. Expression of survivin protein correlated with the expression of HER2/neu. In 59.6 % of cases survivin was expressed in tumors with a low Ki-67 index. Most often, survivin was expressed in luminal A and luminal B molecular-biological tumor subtypes. Real-time polymerase chain reaction determined the expression of BIRC5 gene in all 67 carcinoma samples. The level of normalized expression of BIRC5 gene significantly moderately correlated with the expression of its product – survivin protein (r = 0.704, p &lt;0.01) and slightly correlated with the expression of oncoprotein HER2/neu (r = –0.285, p &lt;0.05). The median follow-up was 40 months. Overall survival of patients without survivin expression in primary tumor was 100 %, overall survival of patients with survivin expression was 77.16 % (range 74.6–80.1 %) (p = 0.041), relapse-free survival was 100 % and 71.9 % (range 70.1–74.2 %) respectively (p = 0.037). The ratio of progression risks in the survivin expression group was 10.6 (95 % confidence interval 0.85–132.2) (p = 0.041).Conclusion.Expression of the protein survivin and its gene BIRC5 is an independent adverse prognostic factor and can be used as a predictive and prognostic marker.

Abstract PD5-01: KEYNOTE-173: Phase 1b multicohort study of pembrolizumab (Pembro) in combination with chemotherapy as neoadjuvant treatment for triple-negative breast cancer (TNBC)

Abstract Background: TNBC has poor outcome and limited therapeutic options. Pembro monotherapy demonstrated antitumor activity and acceptable safety in metastatic TNBC. KEYNOTE-173 (NCT02622074) is a 6-cohort, phase 1b study of different doses and schedules of platinum and taxanes in combination with pembro as neoadjuvant treatment in patients (pts) with locally advanced TNBC. Methods: Eligible pts were women aged ≥18 y with newly diagnosed, locally advanced, previously untreated TNBC. In all cohorts, patients received single pembro 200 mg administration on day 1 of cycle 1.Cycles 2-5 included pembro 200 mg with either nab-paclitaxel 125 mg/m2 QW (cohort A), nab- paclitaxel 100 mg/m2 QW plus carboplatin AUC6 Q3W(cohort B), nab-paclitaxel 125 mg/m2 QW plus carboplatin AUC5 Q3W (cohort C), nab- paclitaxel 125 mg/m2 QW plus carboplatin AUC2 QW (cohort D),paclitaxel 80 mg/m2 QW plus carboplatin AUC5 Q3W (cohort E) and paclitaxel 80 mg/m2 QW plus carboplatin AUC2 QW (cohort F) followed by doxorubicin 60 mg/m2 Q3W and cyclophosphamide 600mg/m2 Q3W with pembro 200 mg Q3W in all cohorts (Cycles 6-9) prior to surgery. Breast MRI was performed at screening and after cycles 5 and 9. Dose-limiting toxicities (DLTs) were assessed during cycles 1-3 and 6-7. Dose levels were deemed toxic if ≥3 of the first 6 pts or ≥4 of 10 pts had DLT. Primary end points were safety and recommended phase 2 dose (RP2D). Key efficacy end points were pCR (ypT0/Tis ypN0, or ypT0 ypN0), objective response rate (ORR) based on RECIST v1.1 as assessed by investigator, event-free survival (EFS), and overall survival (OS). Results: 60 pts were enrolled by 5-31-18 (10/cohort): median age, 48.5 y (range 26-71); most had ductal histology (83.3%), T2/T3 (88.3%) and nodal involvement (66.7%). 22 pts had DLTs (2, A; 4, B/F; 6, C/D); most common was febrile neutropenia (9 pts: 1, A; 2, B/C; 4, D). The most common G≥3 TRAEs were neutropenia (73%), febrile neutropenia (22%), anemia (20%) and thrombocytopenia (8%). 18 pts had immune-related AEs; most common were G2 hypothyroidism (4 pts), G1 hyperthyroidism (3 pts), G3 colitis (2 pts), and G3 rash (2 pts). 11 pts discontinued pembro due to TRAEs (1, A/B/E; 4, D/F). The overall pCR rate (ypT0/Tis ypN0) was 60% (90% CI 30-85). ORR was 100% (74-100) in B/C, 90% (61-100) in D/F, 80% (49-96) in A and 70% (39-91) in E. At a median follow-up of 19.6 mo, EFS rate at 12 mo was 100% in B/C/E/F, 90% (58-98) in D, and 80% (49-93) in A. EFS rate at 12 mo was 100% and 88% for pts who did and did not achieve pCR (71-95). Conclusion: Pembro+chemo as TNBC neoadjuvant therapy results in promising antitumor activity with manageable toxicity. Results support the ongoing KEYNOTE-522 trial. Citation Format: Schmid P, Park YH, Muñoz-Couselo E, Kim S-B, Sohn J, Im S-A, Holgado E, Foukakis T, Kuemmel S, Dent R, Yin L, Ding Y, Tryfonidis K, Cortés J. KEYNOTE-173: Phase 1b multicohort study of pembrolizumab (Pembro) in combination with chemotherapy as neoadjuvant treatment for triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD5-01.

Mould-based surface high-dose-rate brachytherapy for eyelid carcinoma.

PurposeTo evaluate toxicity and clinical outcomes in patients with eyelid tumour treated with contact high-dose-rate brachytherapy (HDR-BT).Material and methodsBetween April 2010 and August 2017, 10 consecutive patients with tumour of the eyelid underwent contact HDR-BT and custom-made surface mould. Every applicator was manually built using conventional thermoplastic material and standard plastic catheters. The median dose prescribed was 42 Gy (range, 30-48) with a median dose per fraction of 3.5 Gy (range, 2-4.5). The dose was delivered in a median of 12 fractions (range, 10-17) over a median of 16 days. In all cases, an ocular shield was placed to reduce the dose to the eye. Acute and late toxicity was evaluated according to RTOG toxicity criteria.ResultsWe analyzed data of 9 of 10 patients (one patient was excluded because he did not give consent for investigation). The median age was 68 years (range, 31-88). According to the TNM-UICC staging system, 4, 1 and 4 patients were stage IA, IB and IC, respectively. Basal cell and sebaceous gland carcinomas were reported in 5 and 2 patients, respectively; other histological types were non-Hodgkin lymphoma and plasmacytoma. After a median follow-up of 51 months (range, 16-90), there was no evidence of local or distant recurrence. The treatment was very well tolerated. Most commonly acute reactions consisted of low grade (G1-G2) conjunctivitis and skin erythema. Only one patient required a temporary interruption of the treatment due to acute G2 conjunctivitis and G3 lid erythema. Only one G2 late toxicity was reported (corneal ulceration), without resulting in functional impairment or blindness.ConclusionsOur results suggest that contact HDR-BT with a customized applicator is safe, effective and offers very good local control and can be considered for the treatment of eyelid tumours.

Prognostic value of the albumin-to-alkaline phosphatase ratio on urologic outcomes in patients with non-metastatic renal cell carcinoma following curative nephrectomy.

Background: Few studies focused on the relationship between the albumin-to-alkaline phosphatase ratio (AAPR) and the urologic outcomes in patients with non-metastatic renal cell carcinoma (RCC) following curative surgery. The aim of this study was to evaluate the prognostic value of preoperative AAPR in non-metastatic RCC patients.Methods: The prognostic value of AAPR was evaluated in a primary cohort with 419 non-metastatic RCC patients following curative radical or partial nephrectomy and then further validated in an independent cohort consisting of 204 patients. A nomogram was developed based on the independent predictors, and its predictive value was assessed.Results: Kaplan-Meier survival analysis demonstrated that patients with low AAPR levels were significantly associated with worse overall survival (OS) and cancer-specific survival (CSS) compared with patients with high AAPR levels both in two cohorts. Univariate and multivariate analyses revealed that low AAPR was an independent risk factor for OS (HR = 2.745; 95%CI, 1.266-5.953; P = 0.011) and CSS (HR = 3.042; 95%CI, 1.278-7.243; P = 0.012). Moreover, subgroup analysis (Fuhrman grade G1+G2 and Fuhrman grade G3+G4; T1+T2 stage and T3+T4 stage) revealed that low AAPR was also related to worse urological outcomes. Although no significant differences between patients with low AAPR and patients with high AAPR can be observed with regard to CSS under Fuhrman grade G1+G2 (P=0.058) and T1+T2 stage (P=0.318), there was a worse CSS trend in low AAPR patients. The established nomograms for OS and CSS were well calibrated and had moderate discriminative ability (concordance index: 0.821 and 0.839, respectively)Conclusions: Preoperative AAPR might be an independent prognostic factor in patients with non-metastatic RCC. The ratio should be applied in RCC patients for risk stratification and clinical decision-making.

Quality of sesame seeds produced under soil salinity levels1

ABSTRACT Sesame is considered an alternative crop for small and medium farmers in the Brazilian Northeast region. However, under the conditions of the northeastern semi-arid region, the scarcity of good quality water for irrigation may lead to a reduction in the quality of the final product. This study aimed to evaluate the physiological quality of sesame seeds produced under levels of soil salinity. The experiment was carried out in a completely randomized design, in a 5 × 5 factorial scheme, with three replicates, corresponding to sesame cultivars (BRS Seda, BRS G2, BRS G3, BRS G4 and BRS Anahi) and soil salinity levels with the following values for electrical conductivity: 0.6 dS m-1, 1.2 dS m-1, 1.8 dS m-1, 2.4 dS m-1 and 3.0 dS m-1. The physiological quality was characterized based on tests of germination, first germination count, germination speed index, radicle length, seed electrical conductivity, emergence, emergence speed index and seedling dry matter. BRS Seda, BRS G2 and BRS G3, cultivated under salinity levels, present seeds with a better physiological quality, demonstrating a higher tolerance to salt stress conditions. The BRS Seda and BRS G2 cultivars tolerate salinity levels of up to 2.4 dS m-1, while BRS G3 tolerates levels of up to 1.8 dS m-1. BRS G4 and BRS Anahi have the physiological quality of their seeds compromised by the increase in the soil salinity, during their production.