Diagnostic power of VEGF,MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

PurposeVascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.Materials/methodsThe study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.ResultsTissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II–75%, III–85%, IV–70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: ‘vascular endothelial growth factor + CA15-3′. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.ConclusionsThe combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.     

Synchronous occurrence of HPV-associated cervical squamous cell carcinoma (FIGO IIA) in prolapsed uterus and adenocarcinoma of the anal canal cT1N0M0: Case report

Rationale:Guidelines of rare synchronous tumours treatment are often unavailable due to lack of wide prospective studies. Additionally, their management is not just a simple sum of coexisting tumours management and has to regard many circumstances like symptoms, age, comorbidities, advancement.Patient concerns:Herein, we report a case of an 81-year-old woman who presented with bleeding from the prolapsed uterus.Diagnoses:Based on physical examination, that is, speculum examination, bimanual, and per rectum, followed by rectoscopy and histopathology, the diagnosis of cervical squamous cell carcinoma FIGO IIA2 in prolapsed uterus with anal canal adenocarcinoma cT1N0M0 was made.Interventions:Dominating complaint of bleeding from prolapsed cervix was managed with radical vaginal hysterectomy in conjunction with wide colpectomy preceded by laparoscopic pelvic and paraaortic lymphadenectomy. Due to the lack of consent for removal of the anus, only radiotherapy was applied instead.Outcomes:The patient underwent magnetic resonance image follow-up. No recurrence was found at 18 months.Lessons:Imaging is useful method of synchronous cancers diagnostics. These cancers may vary in aetiology and stage. Cervical cancer may be co-existing with another anogenital cancer. Therapy of synchronous cancers should be individualized taking into account patient''s consent, age, physical condition, and comorbidities.     

Transformation of Selected Fusarium Toxins and Their Masked Forms during Malting of Various Cultivars of Wheat

This study investigated the impact of malting of six wheat cultivars inoculated with Fusarium culmorum on the dynamics of content changes of selected Fusarium toxins. The grains of all the tested cultivars showed a high content of deoxynivalenol (DON), zearalenone (ZEN), and their derivatives, whereas nivalenol (NIV) and its glucoside were found only in the Legenda cultivar. Our experiments confirmed that the malting process of wheat grain enables the secondary growth of Fusarium, and mycotoxin biosynthesis. The levels of toxins in malt were few-fold higher than those in grain; an especially high increase was noted in the case of ZEN and its sulfate as the optimal temperature and pH conditions for the biosynthesis of these toxins by the pathogen are similar to those used in the grain malting process. This is the first paper reporting that during the malting process, biosynthesis of ZEN sulfate occurs, instead of glycosylation, which is a typical modification of mycotoxins by plant detoxication enzymes.     

DNA methylation profile in patients with indolent systemic mastocytosis

BackgroundMastocytosis is a clinically heterogeneous, usually acquired disease of the mast cells with a survival time that depends on the onset of the disease and ranges from skin‐limited to systemic disease, including indolent and more aggressive variants. The crucial element in pathogenesis is the presence of oncogenic KIT somatic mutation D816V. Further epigenetic alterations are responsible for regulating the expression of genes. It is essential to identify indicators of disease progression, and the specific clinical picture to establish an appropriate therapeutic strategy.ObjectiveThe aim of this study was to analyze the relation of mastocytosis symptoms and epigenetic changes, and to identify epigenetic predictors of the disease.MethodsGlobal DNA methylation profile analysis was performed in peripheral blood collected from 73 patients with indolent systemic mastocytosis (ISM) and 43 healthy adult volunteers. Levels of 5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) were determined using an ELISA‐based method, while the methylation of the Alu and LINE‐1 repeats were assayed with the quantitative methylation‐specific PCR technique. A questionnaire interview was conducted among the study participants to collect data on possible epigenetic modifiers. Additionally, the methylation profile was compared between three human mast cell lines: ROSA KIT D816V, ROSA KIT WT, and HMC‐1.1 KIT V560G, in order to assess the association between KIT mutations and methylation profile.ResultsA significantly lower level of DNA hydroxymethylation (5‐hmC) in the blood was found in patients with ISM as compared to the controls (0.022% vs. 0.042%, p = 0.0001). Differences in the markers of global DNA methylation (5‐mC, Alu, LINE‐1) were not statistically significant, although they did indicate generally higher DNA methylation in patients with mastocytosis. The 5‐hmC level was significantly associated with allergy (p = 0.011) in patients with ISM, showing a higher level of 5‐hmC in patients with allergy as compared to patients without allergy. The in vitro study revealed significant differences between the studied cell lines at the level of 5‐mC, Alu, and LINE‐1.ConclusionsThis study confirms that epigenetic changes are involved in mastocytosis, and suggests that allergy may be an important epigenetic modifier of the disease. A possible association between KIT mutations and methylation status observed in human mast cell lines requires further investigation in human studies.Clinical ImplicationsEpigenetic alterations are involved in mastocytosis pathology. The possible role of allergy as an important epigenetic modifier suggests the more impaired function of mast cells in ISM patients without allergy.Capsule summaryDecreased DNA demethylation in the blood DNA of patients with ISM confirms that epigenetic alterations are involved in mastocytosis pathology. We observed a possible role of allergy as an important epigenetic modifier. There is a possible association between KIT mutations and the methylation status observed in human mast cell lines.     

Current epidemiology and practice patterns in prevention and treatment of PD-related infections in Poland

Background

Peritoneal dialysis (PD) related infections are associated with technique failure and mortality. The aim of this multicentre study was to examine epidemiology, treatment and outcomes of PD-related infections in Poland as well as practice patterns for prevention of these complications in the context of current ISPD recommendations.

Methods

A survey on PD practices in relation to infectious complications was conducted in 11 large Polish PD centres. Epidemiology of peritonitis and exit-site infections (ESI) was examined in all patients treated in these units over a 2 year period.

Results

The study included data on 559 PD patients with 62.4% on CAPD. Practice patterns for prevention of infectious complications are presented. The rate of peritonitis was 0.29 episodes per year at risk, with Gram positive microorganisms responsible for more than 50% of infections and 85.8% effectively treated. Diagnosis and treatment followed ISPD guidelines however most units did not provide an anti-fungal prophylaxis. Although neither of the centres reported routine topical mupirocin on catheter exit-site, the rate of ESI was low (0.1 episodes per year at risk), with Staphylococcus aureus as most common pathogen and full recovery in 78.3% of cases.

Conclusion

The study shows rewarding outcomes in prevention and treatment of PD-associated infections, mainly due to a thorough compliance with the current ISPD guidelines, although some deviations from the recommendations in terms of practice patterns have been observed. More studies are needed in large numbers of patients to differentiate the importance of specific recommendations and further support the guidelines.

     

Dialysate copeptin and peritoneal transport in incident peritoneal dialysis patients

International Urology and Nephrology - Systemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD)....     

Thyroid Function after Postoperative Radiation Therapy in Patients with Breast Cancer

Objective: The aim of this study was to assess thyroid function in breast cancer patients exposed to therapeutic external beam radiation. The focus was on possible progressive changes and any relationships between the incidence of primary hypothyroidism, the time required to become hypothyroid, and factors such as chemotherapy, hormonotherapy and immunotherapy. Materials and Methods: Seventy females undergoing 3D conformal and IMRT radiation therapy for breast cancers were enrolled in a non-randomized prospective study. The patients was divided into two groups: those after mastectomy or breast conserving surgery (BCS) were irradiated to a scar of the chest wall/breast and the ipsilateral supraclavicular and the axillary areas (supraclavicular radiotherapy group - SC-RT group – 32 patients) and the control group receiving adjuvant chest wall/breast RT only (BCT group - 38 patients).The total doses were 50.0 to 70 Gy in 5 to 7 weeks. The median follow-up term was 24 months (range, 1–40 months). Thyroid function was evaluated by measuring thyroid stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) levels. The minimum, maximum and mean thyroid gland doses for 20 Gy (V20) were calculated for all patients. Results: Statistically significant results were obtained for the SC-RT group. Two yearsa fter the end of RT the chance of an event was increased in 6% of the population (p=0.009) in the SC-RT group. In the BCT group no significance was noted. No statistically significant differences were found for V20, chemio-, immunotherapy and hormonotherapy or Ki67 values (p=0.12). No significant results were obtained for development of hypothyroidism and clinical factors (age, thyroid volume, treatment modalities). Conclusion: Radiotherapy is associated with a higher incidence of thyroid toxicity in breast cancer patients. Routine thyroid function monitoring should be recommended in such cases.     

Influence of W Addition on Microstructure and Resistance to Brittle Cracking of TiB2 Coatings Deposited by DCMS

The aim of this work was to determine the influence of the tungsten addition to TiB₂ coatings on their microstructure and brittle cracking resistance. Four coatings of different compositions (0, 7, 15, and 20 at.% of W) were deposited by magnetron sputtering from TiB₂ and W targets. The coatings were investigated by the following methods: X-ray diffraction (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). All coatings had a homogeneous columnar structure with decreasing column width as the tungsten content increased. XRD and XPS analysis showed the presence of TiB₂ and nonstoichiometric TiBx phases with an excess or deficiency of boron depending on composition. The crystalline size decreased from 27 nm to 10 nm with increasing W content. The brittle cracking resistance improved with increasing content of TiBx phase with deficiency of B and decreasing crystalline size.     

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with -13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (P<0.0028) and in patients with at least one mild mutation (P < 0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable.