Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy

PURPOSETo report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution.METHODSSeventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3–3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4–7 Gy given once or twice a week).RESULTSMedian follow-up was 76 months (7–204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9–54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation.CONCLUSIONSHDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.     

Synthesis and biological evaluation of N‐acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors

Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un‐sulfated forms and promotes the growth of various hormone‐dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid‐sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N‐acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4‐(2‐perfluoroundecanoylaminoethyl)‐phenyl sulfamate, 5r , demonstrated the greatest inhibitory effect, with an IC₅₀ value of 2.18 μm (IC₅₀ value of 2.13 μm for coumarin‐7‐O‐sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.     

Balloon Dilatation for Removal of an Irretrievable Permanent Hemodialysis Catheter: The Safest Approach

Long‐term hemodialysis catheter dwell time in the central vein predisposes to fibrin sheath development, which subsequently causes catheter malfunction or occlusion. In very rare cases, the catheter can be overgrown with fibrin and rigidly connected with the vein or heart structures. This makes its removal almost impossible and dangerous because of the possibility of serious complications, namely vein and heart wall perforation, bleeding, or catheter abruption in deep tissues. We describe two cases in which standard retrieval of long‐term catheters was not possible. Balloon dilatation of catheter lumens was successfully used to increase the catheter diameter with simultaneous tearing of the fibrin sheath surrounding it. This allowed the catheter to be set free safely. Based on this experience, we present recent literature and our point of view.     

Complex relationship of obesity and obesity paradox in heart failure – higher risk of developing heart failure and better outcomes in established heart failure

Heart failure (HF) and obesity are major public health problems. Studies have shown that obesity may increase the risk of developing new HF but after patients have developed HF, obesity may be associated with improved outcomes. This paradoxical association of obesity with HF remains poorly understood. It is believed that the obesity paradox may in part be due to the inherent limitations of body mass index (BMI) as a measure of obesity. BMI may not appropriately measure important components of body mass like body fat, fat distribution, lean body mass, and body fluid content and may not be ideal for examining the relationship of body composition with health outcomes. Differentiating between body fat and lean body mass may explain some of the paradoxical association between higher BMI and better prognosis in patients with HF. Paradoxical outcomes in HF may also be due to phenotypes of obesity. Future studies need to develop and test metrics that may better measure body composition and may serve as a better tool for the estimation of the true association of obesity and outcomes in HF and determine whether the association may vary by obesity phenotypes.

• KEY MESSAGES

• Obesity predisposes to heart failure in all age groups. But obesity in heart failure is an area of controversy, because of obesity paradox, the apparent protective effect of overweight and mild obesity on mortality after development of heart failure.

• Traditional markers of obesity do not measure different components of body weight like muscle mass, fat, water, and skeletal weight. Body Mass Index in heart failure subjects does not measure accurately body fat or fluid retention. So new markers of obesity like visceral adiposity index, body composition analysis, sarcopenic status assessment may be helpful in the assessment of heart failure outcomes.

• Different phenotypes of obesity may be responsible for the different morbidity, mortality as well as therapeutic outcomes in heart failure.

     

Evaluation of selected parameters of the antioxidative system in patients with type 2 diabetes in different periods of metabolic compensation

Introduction: The aim of the study was to evaluate some selected parameters of the antioxidative system in patients with type 2 diabetes. Materials and Methods: Eighty-one type 2 diabetes patients took part in the study (39 patients with metabolically balanced and 42 with metabolically unbalanced diabetes). The control group consisted of 30 healthy people. The total antioxidant capacity of plasma was measured fluorometrically using phycoerythrin. To calculate the low-molecular-weight antioxidant concentration in the plasma samples, the duration of Trolox activity as a function of its concentration in the sample was measured. The activity of antioxidative enzymes in red blood cells was determined using the Misra and Fridovich method and Beers and Sizer method. Results: The total plasma antioxidant capacity and the low-molecular-weight antioxidant concentration in the group of patients with metabolically compensated type 2 diabetes were statistically significantly higher than in the group of patients with metabolically uncontrolled diabetes. The activity of antioxidative enzymes was found to be higher in the group of type 2 diabetes patients at the stage of metabolic balance. Conclusions: The obtained results confirm the thesis of glucose toxicity and intensification of oxidative stress in patients with diabetes.     

Quantitative analysis of estrogen receptor heterogeneity in breast cancer

Immunohistochemical analyses (IHC) of biomarkers are extensively used for tumor characterization and as prognostic and predictive measures. The current standard of single slide analysis assumes that one 5 microM section is representative of the entire tumor. We used our automated image analysis technology (AQUA) using a modified IHC technique with fluorophores to compare estrogen receptor (ER) expression in multiple blocks/slides from cases of primary breast cancer with the objective of quantifying tumor heterogeneity within sections and between blocks. To normalize our ER scores and allow slide-to-slide comparisons, 0.6 microm histospots of representative breast cancer cases with known ER scores were assembled into a 'gold standard array' (GSA) and placed adjacently to each whole section. Overall, there was excellent correlation between AQUA scores and the pathologist's scores and reproducibility of GSA scores (mean linear regression R value 0.8903). Twenty-nine slides from 11 surgical cases were then analyzed totaling over 2000 AQUA images. Using standard binary assignments of AQUA (>10) and pathologist's (>10%) scores as being positive, there was fair concordancy between AQUA and pathologist scores (73%) and between slides from different blocks from the same cases (75%). However using continuous AQUA scores, agreement between AQUA and pathologist was far lower and between slides from different blocks from the same cases only 19%. Within individual slides there was also significant heterogeneity in a scattered pattern, most notably for slides with the highest AQUA scores. In sum, using a quantitative measure of ER expression, significant block-to-block heterogeneity was found in 81% of cases. These results most likely reflect both laboratory-based variability due to lack of standardization of immunohistochemistry and true biological heterogeneity. It is also likely to be dependent on the biomarker analyzed and suggests further studies should be carried out to determine how these findings may affect clinical decision-making processes.     

A representative of arylcyanomethylenequinone oximes effectively inhibits growth and formation of hyphae in Candida albicans and influences the activity of protein kinases in vitro

In this study, we applied various assays to reveal new activities of phenylcyanomethylenequinone oxime-4-(hydroxyimino) cyclohexa-2,5-dien-1-ylidene](phenyl)ethanenitrile (4-AN) for potential anti-microbial applications. These assays demonstrated (a) the antimicrobial effect on bacterial and fungal cultures, (b) the effect on the in vitro activity of the kinase CK2, (c) toxicity towards human erythrocytes, the Caco-2 cancer cell line, and embryonic development of Zebrafish. We demonstrated the activity of 4-AN against selected bacteria and Candida spp. The MIC ranging from 4?µg/ml to 125?µg/ml proved effective in inhibition of formation of hyphae and cell aggregation in Candida, which was demonstrated at the cytological level. Noteworthy, 4-AN was found to inhibit the CK2 kinase with moderate potency. Moreover, at low concentrations, it did not exert any evident toxic effects on human erythrocytes, Caco-2 cells, or Zebrafish embryos. 4-AN can be a potential candidate as a novel drug against Candida infections.