Infection rate and complications after 621 transperineal MRI-TRUS fusion biopsies in local anesthesia without standard antibiotic prophylaxis.

PURPOSE: The aim of this study was to assess the post biopsy infection rate, feasibility and prostate cancer (PCa) detection rate (CDR) by performing transperineal MRI-TRUS fusion biopsy of the prostate (TPBx) under local anesthesia (LA) without antibiotic prophylaxis (AP). METHODS: We prospectively screened 766 men with suspicious lesions on mpMRI, an elevated PSA level or a suspect digital examination undergoing MRI-TRUS-TPBx in LA, from May 2019 to July 2020. Patients with the need for antibiotic prophylaxis or without a PI-RADS target lesion were excluded from final analyses. We reported CDR, perioperative pain (0-10) and postoperative complications. PCa with an ISUP grade ≥ 2 was classified as clinically significant PCa (csPCa). RESULTS: We included 621 patients with a median age of 68 years (IQR 62-74), a PSA of 6.43 ng/mL (IQR 4.72-9.91) and a prostate volume of 45 cc (IQR 32-64). In median, 4 targeted (TB) (IQR 3-4) and 6 (IQR 5-7) systematic biopsies (SB) detected in combination overall 416 (67%) PCa and 324 (52%) csPCa. Overall CDR of TB for PI-RADS 3, 4 and 5 was 26%, 65% and 84%, respectively. Patients reported a median perioperative pain level of 2 (IQR 1-3). Four patients (0.6%) developed a post biopsy infection, one experienced urosepsis. CONCLUSION: Our results demonstrate that transperineal MRI-TRUS fusion-guided prostate biopsy under LA without AP is feasible, safe and well tolerated.

Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Spectroscopic detection and quantification of heme and heme degradation products.

Heme and heme degradation products play critical roles in numerous biological phenomena which until now have only been partially understood. One reason for this is the very low concentrations at which free heme, its complexes and the partly unstable degradation products occur in living cells. Therefore, powerful and specific detection methods are needed. In this contribution, the potential of nondestructive Raman spectroscopy for the detection, quantification and discrimination of heme and heme degradation products is investigated. Resonance Raman spectroscopy using different excitation wavelengths (413, 476, 532, and 752 nm) is employed to estimate the limit of detection for hemin, myoglobin, biliverdin, and bilirubin. Concentrations in the low micromolar range (down to 3 µmol/L) could be reliably detected when utilizing the resonance enhancement effect. Furthermore, a systematic study on the surface-enhanced Raman spectroscopy (SERS) detection of hemin in the presence of other cellular components, such as the highly similar cytochrome c, DNA, and the important antioxidant glutathione, is presented. A microfluidic device was used to reproducibly create a segmented flow of aqueous droplets and oil compartments. Those aqueous droplets acted as model chambers where the analytes have to compete for the colloid. With the help of statistical analysis, it was possible to detect and differentiate the pure substances as well as the binary mixtures and gain insights into their interaction.

Cytotoxic T lymphocyte recognition of the influenza hemagglutinin gene product expressed by DNA-mediated gene transfer.

We have used the technique of DNA-mediated gene transfer to examine cytotoxic T lymphocyte (CTL) recognition of the product of the cloned A/JAPAN/305/57 hemagglutinin (HA) gene in murine (L929) cells. Using both heterogeneous and homogeneous (clonal) populations of type A influenza-specific CTL, we have demonstrated that the HA molecule can serve as a target antigen for both the subtype-specific and the cross-reactive subpopulations of influenza-specific CTL. Our results also raise the possibility that other virus-specified polypeptides may serve as target molecules for cross-reactive CTL.

Expression of a murine polyclonal T cell receptor marker correlates with the use of specific members of the V beta 8 gene segment subfamily.

A series of murine T lymphocyte clones were examined for reactivity with the KJ16-133 and F23.1 mAbs. Clones that were KJ16-133+,F23.1+ and KJ16-133-,F23.1+ were identified, but no KJ16-133+,F23.1- clones were observed. Within our panel of clones, therefore, the KJ16-133 antibody identifies a subset of F23.1+ cells. All F23.1+ clones examined express members of the V beta 8 subfamily of beta chain variable region genes; clones expressing V beta 8.1 or V beta 8.2 reacted with both KJ16-133 and F23.1, while clones expressing V beta 8.3 reacted only with F23.1. Thus, the differential reactivity of the KJ16-133 and F23.1 antibodies with cloned T cells correlates with the V beta gene expression of each clone. Reactivity with these antibodies should therefore be of utility for predicting the V beta gene expression in some T cell clones.

In vitro activity of anidulafungin and other agents against esophageal candidiasis-associated isolates from a phase 3 clinical trial.

The efficacy of anidulafungin, an echinocandin antifungal agent with potent anti-Candida activity, in treating esophageal candidiasis was tested in a double-blind study versus oral fluconazole. Isolates were identified and tested for susceptibility. Candida albicans represented >90% of baseline isolates. The MIC(90) of anidulafungin for all strains was 0.06 mg/liter.

Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign prostatic hyperplasia: 4-year data from the CombAT study.

OBJECTIVE: To investigate the effect of combination therapy with dutasteride plus tamsulosin compared with each monotherapy on patient-reported health outcomes over 4 years in men with moderate-to-severe lower urinary tract symptoms (LUTS) because of benign prostatic hyperplasia (BPH). METHODS: CombAT was a 4-year international, double-blind, randomised, parallel-group trial in men (n = 4844) with moderate-to-severe symptoms of BPH and at increased risk of disease progression [age > or = 50 years, International Prostate Symptom Score (IPSS) > or = 12, prostate volume > or = 30 cc, serum prostate-specific antigen > or = 1.5 ng/ml to < or = 10 ng/ml and maximum urinary flow rate 5-15 ml/s with minimum voided volume > or = 125 ml]. Subjects were randomised to receive 0.5 mg dutasteride, 0.4 mg tamsulosin or the combination once daily for 4 years. The primary endpoint at 4 years was the time to event and proportion of subjects with acute urinary retention or undergoing BPH-related prostate surgery. Secondary endpoints included the health-outcomes measures, BPH Impact Index (BII), IPSS question 8 (IPSS Q8) and the Patient Perception of Study Medication (PPSM) questionnaire. RESULTS: At 4 years, combination therapy resulted in significantly superior improvements from baseline in BII and IPSS Q8 than either monotherapy; these benefits were observed from 3 months onwards compared with dutasteride and from 9 months (BII) or 12 months (IPSS Q8) onwards compared with tamsulosin. Also at 4 years, the PPSM questionnaire showed that a significantly higher proportion of patients was satisfied with, and would request treatment with, combination therapy compared with either monotherapy. CONCLUSIONS: Combination therapy (dutasteride plus tamsulosin) provides significantly superior improvements in patient-reported quality of life and treatment satisfaction than either monotherapy at 4 years in men with moderate-to-severe BPH symptoms.

New species of Entolomataceae from Cameroon.

Six species of Entoloma (Entolomataceae, Agaricales, Basidiomycota) are described from recent Cameroonian collections: E. bisterigmatum, E. brunneoloaurantiacum, E. djaense, E. intricatum, E. versiforme, and E. parvistellatum.These species occur in tropical rainforests dominated by ectomycorrhizal trees in the genera Gilbertiodendron and Uapaca. Data on macromorphology, micromorphology, DNA sequences, habitat and comparisons with similar taxa are provided for each. This is the first contemporary taxonomic work on the Entolomataceae from Cameroon.

Proteins controlling the nuclear uptake of NF-kappa B, Rel and dorsal.

The two DNA-binding subunits of the transcription factor NF-kappa B, the products of the rel oncogene family and the product of the developmental control gene dorsal of Drosophila are homologous within a 300 amino acid region. This sequence represents a novel DNA-binding and dimerization domain. The access of the NF-kappa B/Rel/dorsal (NRD) transcription factor family to the cell nucleus is regulated. There is now evidence that functionally and structurally related accessory proteins of NF-kappa B, Rel and dorsal control the nuclear entry as well as DNA-binding activity of the transcription factors. This review summarizes current knowledge about the nuclear-uptake regulatory proteins (NURPs) I kappa B-alpha, I kappa B-beta/pp40 and cactus.

Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa.

The Epstein-Barr virus (EBV) transactivator protein, termed Epstein-Barr virus nuclear antigen 2 (EBNA2), plays a critical role in the regulation of latent viral transcription and in the immortalization of EBV-infected B cells. Unlike most transcription factors, EBNA2 does not bind directly to its cis-responsive DNA element but requires a cellular factor, termed C-promoter binding factor 1 (CBF1). Here, CBF1 was purified and was found to directly interact with EBNA2. CBF1 is identical to a protein thought to be involved in immunoglobulin gene rearrangement, RBPJ kappa. Contrary to previous reports, CBF1-RBPJ kappa did not bind to the recombination signal sequences but instead bound to sites in the EBV C-promoter and in the CD23 promoter.

Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.

The sequence reported in our 22 March 1991 report "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NFkappaB" [Science 251, 1490 (1991)], contained some errors. Resequencing under strong denaturing conditions revealed three insertions at nucleotide positions 1194, 1212, and 1220, which changed the AA sequence from RSAR-PRLGP to QISQASALAP (residues 372 to 380), thus accounting for some of the divergence in this region. A corrected sequence has been sent to GenBank.

Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.

A DNA probe that spanned a domain conserved among the proto-oncogene c-rel, the Drosophila morphogen dorsal, and the p50 DNA binding subunit of NF-kappa B was generated from Jurkat T cell complementary DNA with the polymerase chain reaction (PCR) and degenerate oligonucleotides. This probe was used to identify a rel-related complementary DNA that hybridized to a 2.6-kilobase messenger RNA present in human T and B lymphocytes. In vitro transcription and translation of the complementary DNA resulted in the synthesis of a protein with an apparent molecular size of 65 kilodaltons (kD). The translated protein showed weak DNA binding with a specificity for the kappa B binding motif. This protein-DNA complex comigrated with the complex obtained with the purified human p65 NF-kappa B subunit and binding was inhibited by I kappa B-alpha and -beta proteins. In addition, the 65-kD protein associated with the p50 subunit of NF-kappa B and the kappa B probe to form a complex with the same electrophoretic mobility as the NF-kappa B-DNA complex. Therefore the rel-related 65-kD protein may represent the p65 subunit of the active NF-kappa B transcription factor complex.

New species of Amanita subgen. Lepidella from Guyana.

New species of Amanita subgen. Lepidella are described from Guyana. Amanita cyanochlorinosma sp. nov., Amanita fulvoalba sp. nov., and Amanita guyanensis sp. nov. represent the latest additions to the growing body of newly described ectomycorrhizal fungi native to Dicymbe-dominated tropical rainforests. Macro- and micromorphological characters, habitat, and DNA sequence data for the ITS, nrLSU, rpb2, and ef1-α are provided for each taxon, and ß-tubulin for most. Distinctive morphological features warrant the recognition of the three new species and a molecular phylogenetic analysis of taxa across Amanita subgen. Lepidella corroborates their infrageneric placements.

Assessment of a HER2 scoring system for gastric cancer: results from a validation study.

AIMS: Human epidermal growth factor receptor 2 (HER2) overexpression/amplification is implicated in the development of various solid tumour types. Validated methods and scoring systems for evaluating HER2 status exist in breast cancer, but not in gastric cancer. The aim was to establish a HER2 scoring system for gastric cancer to identify suitable patients for enrollment in a trial of trastuzumab (Herceptin) in advanced metastatic gastric cancer. METHODS AND RESULTS: Formalin-fixed paraffin-embedded gastric cancer samples were tested for HER2 status using the fluorescence in situ hybridization (FISH) pharmDxt kit (Dako Denmark A/S). Immunohistochemistry (IHC) was performed using the HercepTest (Dako). Concordance between FISH and IHC was 93.5% in 168 evaluable samples. Eleven samples were scored as FISH+ but IHC- or equivocal. CONCLUSIONS: IHC/FISH discrepancies were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumour heterogeneity in gastric cancer compared with breast cancer. With modifications to the IHC scoring system, the HercepTest is considered valid for the identification of HER2+ gastric tumours for this clinical trial. Correlation of HER2 scores with clinical outcomes will be needed to determine which patients might benefit from trastuzumab therapy.

Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2.

The Notch/Lin-12/Glp-1 receptor family participates in cell-cell signaling events that influence cell fate decisions. Although several Notch homologs and receptor ligands have been identified, the nuclear events involved in this pathway remain incompletely understood. A truncated form of Notch, consisting only of the intracellular domain (NotchIC), localizes to the nucleus and functions as an activated receptor. Using both an in vitro binding assay and a cotransfection assay based on the two-hybrid principle, we show that mammalian NotchIC interacts with the transcriptional repressor CBF1, which is the human homolog of Drosophila Suppressor of Hairless. Cotransfection assays using segments of mouse NotchIC and CBF1 demonstrated that the N-terminal 114-amino-acid region of mouse NotchIC contains the CBF1 interactive domain and that the cdc10/ankyrin repeats are not essential for this interaction. This result was confirmed in immunoprecipation assays in which the N-terminal 114-amino-acid segment of NotchIC, but not the ankyrin repeat region, coprecipitated with CBF1. Mouse NotchIC itself is targeted to the transcriptional repression domain (aa179 to 361) of CBF1. Furthermore, transfection assays in which mouse NotchIC was targeted through Gal4-CBF1 or through endogenous cellular CBF1 indicated that NotchIC transactivates gene expression via CBF1 tethering to DNA. Transactivation by NotchIC occurs partially through abolition of CBF1-mediated repession. This same mechanism is used by Epstein-Barr virus EBNA2. Thus, mimicry of Notch signal transduction is involved in Epstein-Barr virus-driven immortalization.

[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Identification of Shell Colour Pigments in Marine Snails Clanculus pharaonius and C. margaritarius (Trochoidea; Gastropoda).

Colour and pattern are key traits with important roles in camouflage, warning and attraction. Ideally, in order to begin to understand the evolution and ecology of colour in nature, it is important to identify and, where possible, fully characterise pigments using biochemical methods. The phylum Mollusca includes some of the most beautiful exemplars of biological pigmentation, with the vivid colours of sea shells particularly prized by collectors and scientists alike. Biochemical studies of molluscan shell colour were fairly common in the last century, but few of these studies have been confirmed using modern methods and very few shell pigments have been fully characterised. Here, we use modern chemical and multi-modal spectroscopic techniques to identify two porphyrin pigments and eumelanin in the shell of marine snails Clanculus pharaonius and C margaritarius. The same porphyrins were also identified in coloured foot tissue of both species. We use high performance liquid chromatography (HPLC) to show definitively that these porphyrins are uroporphyrin I and uroporphyrin III. Evidence from confocal microscopy analyses shows that the distribution of porphyrin pigments corresponds to the striking pink-red of C. pharaonius shells, as well as pink-red dots and lines on the early whorls of C. margaritarius and yellow-brown colour of later whorls. Additional HPLC results suggest that eumelanin is likely responsible for black spots. We refer to the two differently coloured porphyrin pigments as trochopuniceus (pink-red) and trochoxouthos (yellow-brown) in order to distinguish between them. Trochopuniceus and trochoxouthos were not found in the shell of a third species of the same superfamily, Calliostoma zizyphinum, despite its superficially similar colouration, suggesting that this species has different shell pigments. These findings have important implications for the study of colour and pattern in molluscs specifically, but in other taxa more generally, since this study shows that homology of visible colour cannot be assumed without identification of pigments.

[Focal therapy for small renal masses : Observation, ablation or surgery]. / Fokale Therapie von kleinen Nierentumoren : Beobachtung, Ablation oder Operation.

BACKGROUND: The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION: During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS: Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.