Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

A review of Hyphodiscaceae.

In a recently published classification scheme for Leotiomycetes, the new family Hyphodiscaceae was erected; unfortunately, this study was rife with phylogenetic misinterpretations and hampered by a poor understanding of this group of fungi. This manifested in the form of an undiagnostic familial description, an erroneous familial circumscription, and the redescription of the type species of an included genus as a new species in a different genus. The present work corrects these errors by incorporating new molecular data from this group into phylogenetic analyses and examining the morphological features of the included taxa. An emended description of Hyphodiscaceae is provided, notes and descriptions of the included genera are supplied, and keys to genera and species in Hyphodiscaceae are supplied. Microscypha cajaniensis is combined in Hyphodiscus, and Scolecolachnum nigricans is a taxonomic synonym of Fuscolachnum pteridis. Future work in this family should focus on increasing phylogenetic sampling outside of Eurasia and better characterising described species to help resolve outstanding issues. Citation: Quijada L, Baral HO, Johnston PR, Pärtel K, Mitchell JK, Hosoya T, Madrid H, Kosonen T, Helleman S, Rubio E, Stöckli E, Huhtinen S, Pfister DH (2022). A review of Hyphodiscaceae. Studies in Mycology 103: 59-85. doi: 10.3114/sim.2022.103.03.

Resurrecting the genus Geomorium: Systematic study of fungi in the genera Underwoodia and Gymnohydnotrya (Pezizales) with the description of three new South American species.

Molecular phylogenetic analyses have addressed the systematic position of several major Northern Hemisphere lineages of Pezizales but the taxa of the Southern Hemisphere remain understudied. This study focuses on the molecular systematics and taxonomy of Southern Hemisphere species currently treated in the genera Underwoodia and Gymnohydnotrya. Species in these genera have been identified as the monophyletic /gymnohydnotrya lineage, but no further research has been conducted to determine the evolutionary origin of this lineage or its relationship with other Pezizales lineages. Here, we present a phylogenetic study of fungal species previously described in Underwoodia and Gymnohydnotrya, with sampling of all but one described species. We revise the taxonomy of this lineage and describe three new species from the Patagonian region of South America. Our results show that none of these Southern Hemisphere species are closely related to Underwoodia columnaris, the type species of the genus Underwoodia. Accordingly, we recognize the genus Geomorium described by Spegazzini in 1922 for G. fuegianum. We propose the new family, Geomoriaceae fam. nov., to accommodate this phylogenetically and morphologically unique Southern Hemisphere lineage. Molecular dating estimated that Geomoriaceae started to diverge from its sister clade Tuberaceae c. 112 MYA, with a crown age for the family in the late Cretaceous (c. 67 MYA). This scenario fits well with a Gondwanan origin of the family before the split of Australia and South America from Antarctica during the Paleocene-Eocene boundary (c. 50 MYA).

Surgical management of complex residual masses following systemic chemotherapy for metastatic testicular germ cell tumours.

Background: Post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) represents the treatment of choice in patients with residual masses following chemotherapy for metastatic germ cell tumours. Involvement of major retroperitoneal vessels or thoracic/lumbar spine is rare and challenging but needs complete resection for curative intent. We report on our experience in the management of such complex cases. Patients and methods: A total of 185 patients underwent PC-RPLND and we identified 25 (13.5%) patients who needed complex adjunctive vascular (n = 16, 8.6%), skeletal (n = 5, 2.7%) and pancreaticoduodenal (n = 4, 2.2%) surgeries. We performed a retrospective analysis of treatment-associated complications according to the Clavien-Dindo classification. Progression-free, cancer-specific and overall survival was calculated. Results: All patients were of intermediate/poor prognosis according to IGCCCG. Median tumour diameter at time of surgery was 18.6 (9.0-35) cm. Sixteen (8.6%) underwent vascular surgery including aortic resection and replacement, complete or partial resection of the inferior vena cava with thrombectomy, and resection and replacement of the iliac vessels. In five patients, 1-2 metastatic lumbar vertebral bodies were resected, stabilized and replaced. Four patients underwent en-bloc resection of a suprahilar mass with pancreas and duodenum. Pathohistology revealed vital cancer in five patients; teratoma and malignant somatic transformation was identified in 12 and 6 patients, respectively. Complications occurred more often in the group of complex RPLND (41.7 versus 7.2%, P = 0.02) with the majority representing grade I-IIa. After a median follow-up of 28.5 months, four patients developed recurrent disease and one patient died of the disease. Conclusions: Few patients with advanced GCT need complex vascular, skeletal or intestinal surgery in an interdisciplinary setting with good functional and oncological outcome. Due to the complexity, treatment should be performed at specialized centres.

A phase II study of temsirolimus added to low-dose weekly carboplatin and paclitaxel for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Background: Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy. Patients and methods: In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC. The primary end point was objective response rate after two cycles of treatment. Secondary end points include the safety and tolerability profile and overall survival. Correlative studies with exome mutational analysis were performed in pre-treatment biopsy samples from 21 patients. Results: Fifteen (41.7%) patients had an objective response, which were all partial responses, and 19 (52.3%) patients had stable disease as best response. The two patients who were designated as 'non-responders' were removed from study prior to two cycles of treatment, but are included in the efficacy and safety analyses. The median duration on study was 5.3 months and the median progression-free survival and overall survival were 5.9 months (95% confidence interval, 4.8-7.1) and 12.8 months (95% confidence interval, 9.8-15.8), respectively. The most common grade 3 and 4 adverse events were hematologic toxicities. Three (3.8%) patients developed neutropenic fever on study. Three of four patients with PIK3CA mutations experienced tumor regressions, and responses were also seen in patients with other genetic alterations in the PI3K/mTOR pathway. Conclusion: The combination of temsirolimus with low-dose weekly carboplatin and paclitaxel appears to have meaningful clinical efficacy in the treatment of R/M HNSCC. This regimen has a relatively high response rate compared to other treatments evaluated in R/M HNSCC, and potential associations with genetic alterations in the PI3K/mTOR pathway should be further explored.

A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma.

BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. PATIENTS AND METHODS: This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site. Progressive or symptomatic disease was required. Patients were treated with axitinib 5 mg oral twice daily; dose escalation was allowed. The primary end point was best overall response (BOR). An exploratory analysis correlating biomarkers to drug benefit was conducted, including next-generation sequencing (NGS) in 11 patients. RESULTS: Thirty-three patients were registered and evaluable for response. Fifteen patients had the axitinib dose increased. Tumor shrinkage was achieved in 22 (66.7%); 3 (9.1%) had confirmed partial responses. Twenty-five (75.8%) patients had stable disease, 10 of whom had disease stability for >6 months. The median progression-free survival (PFS) was 5.7 months (range 0.92-21.8 months). Grade 3 axitinib-related toxicities included hypertension, oral pain and fatigue. A trend toward superior PFS was noted with the MYB/NFIB rearrangement, although this was not statistically significant. NGS revealed three tumors with 4q12 amplification, producing increased copies of axitinib-targeted genes PDGFR/KDR/KIT. Two 4q12 amplified patients achieved stable disease for >6 months, including one with significant tumor reduction and the longest PFS on study (21.8 months). CONCLUSIONS: Although the primary end point was not met, axitinib exhibited clinical activity with tumor shrinkage achieved in the majority of patients with progressive disease before trial enrollment. Analysis of MYB biomarkers and genomic profiling suggests the hypothesis that 4q12 amplified ACCs are a disease subset that benefit from TKI therapy.

Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. PATIENTS AND METHODS: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m(2)), given with standard weekly cetuximab (450 mg/m(2) loading dose followed by 250 mg/m(2) weekly) and concurrent IMRT (total dose, 70 Gy). RESULTS: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m(2)) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m(2)), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). CONCLUSION: The recommended phase II dose for nab-paclitaxel is 60 mg/m(2) weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone. CLINICALTRIALSGOV ID: NCT00736619.

Anaplastic thyroid carcinoma: a 25-year single-institution experience.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive solid tumors accounting for 1-5 % of primary thyroid malignancies. In this retrospective review, we aim to evaluate the prognostic factors, treatment approaches, and outcomes of patients with ATC treated at a single institution. MATERIALS AND METHODS: We retrospectively identified 95 patients with ATC from an institutional database between 1985 and 2010. A total of 83 patients with sufficient records were included in this study. Patient, tumor, and treatment characteristics were recorded. Disease-specific survival (DSS) was determined by the Kaplan-Meier method, and factors predictive of outcome were determined by univariate and multivariate analysis. RESULTS: Of the 83 patients, 41 were male and 42 were female. The median age at presentation was 60 years (range 28-89 years) with a median survival of 8 months. The 1- and 2-year DSS were 33 and 23 %, respectively. On univariate analysis, age less than 60 years, clinically N0 neck, absence of clinical extrathyroidal extension (cETE), gross total resection, and multimodality treatment were statistically significant predictors of improved survival. On multivariate analysis, absence of cETE, multimodality therapy, and gross total resection were predictors of improved outcome. CONCLUSIONS: In patients with locoregional limited disease, multimodality treatment with gross total surgical resection and postoperative radiotherapy with or without chemotherapy offers the best local control and DSS.

[Importance of pathology for therapy planning of testicular germ cell tumors]. / Bedeutung der Pathologie für die Therapieplanung testikulärer Keimzelltumoren.

Testicular tumors can be divided into germ cell tumors and sex cord stromal tumors. Malignant testicular germ cell tumors (TGCT) represent about 90-95 % of all testicular tumors and are the most common solid neoplasms in young men aged 20-40 years with an increasing incidence in industrialized countries. Treatment of TGCT is performed by an individual and risk-adapted approach taking primary tumor histology, histopathlogical and molecular prognostic risk factors, tumor stage and for metastasized tumors the response to systemic chemotherapy into consideration. Knowledge of the specific histopathology of the primary tumor and the prognostic factors is of utmost importance for the treating urologist and oncologist in order to avoid undertreatment or overtreatment. Established risk factors which have been validated in retrospective and prospective studies for clinical stage I non-seminomatous TGCT are the presence of vascular invasion and the percentage of embryonal carcinoma. In clinical stage I seminomas tumor size (> 4 cm) and presence of rete testis infiltration have been identified as risk factors in retrospective but not in prospective studies. Quantitative histopathology of the primary tumor is also important for the management of small residual masses following chemotherapy: if the masses are ≤ 1 cm, postchemotherapy retroperitoneal lymph node dissection is only indicated if the primary tumor contains ≥ 50 % teratoma. Quantitative pathohistology of the resected residual masses is of importance for the decision-making process of a consolidating chemotherapy which is only of benefit if the amount of vital cancer tissue is > 10 %. Resection of residual hepatic and thoracic masses is indispensable. For gonadal stromal tumors knowledge of atypical nuclear forms, increased rate of mitosis and increased growth fractions are important for therapy planning.

High diversity and widespread occurrence of mitotic spore mats in ectomycorrhizal Pezizales.

Fungal mitospores may function as dispersal units and/ or spermatia and thus play a role in distribution and/or mating of species that produce them. Mitospore production in ectomycorrhizal (EcM) Pezizales is rarely reported, but here we document mitospore production by a high diversity of EcM Pezizales on three continents, in both hemispheres. We sequenced the internal transcribed spacer (ITS) and partial large subunit (LSU) nuclear rDNA from 292 spore mats (visible mitospore clumps) collected in Argentina, Chile, China, Mexico and the USA between 2009 and 2012. We collated spore mat ITS sequences with 105 fruit body and 47 EcM root sequences to generate operational taxonomic units (OTUs). Phylogenetic inferences were made through analyses of both molecular data sets. A total of 48 OTUs from spore mats represented six independent EcM Pezizales lineages and included truffles and cup fungi. Three clades of seven OTUs have no known meiospore stage. Mitospores failed to germinate on sterile media, or form ectomycorrhizas on Quercus, Pinus and Populus seedlings, consistent with a hypothesized role of spermatia. The broad geographic range, high frequency and phylogenetic diversity of spore mats produced by EcM Pezizales suggests that a mitospore stage is important for many species in this group in terms of mating, reproduction and/or dispersal.

Metastatic castration-resistant prostate cancer: integrating new learnings to optimise treatment outcomes.

The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy significantly. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and the biological aggressiveness of the disease. Furthermore, treatment associated side effects differ between the various drugs. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of the current article to: (1) summarize the data of established treatment options in mCRPC; (2) highlight new developments of medical treatment; (3) provide clinically useful algorithms for the daily routine and to (4) point out future developments of medical treatment.

Minimally invasive treatment for localized prostate cancer.

The vast majority of men newly diagnosed with prostate cancer have clinically localized disease. Besides active surveillance in low risk cancers and open radical prostatectomy as the traditional gold standard more and more patients demand a effective tumor control through a minimally invasive approach. After the introduction of laparoscopy for the treatment of prostate cancer especially the robot-assisted radical prostatectomy gained in importance. In recent years the accuracy for cancer localisation within the prostate was considerably improved, which enables the increasing use of focal therapy techniques. In addition to the robot-assisted and conventional laparoscopic radical prostatectomy the current and future importance of cryotherapy, HIFU and vascular targeted photodynamic therapy for localized prostate cancer will be analyzed in the following review article.

Two new species of Phaeohelotium (Leotiomycetes: Helotiaceae) from Chile and their putative ectomycorrhizal status.

Species of the genus Phaeohelotium (Leotiomycetes: Helotiaceae) are cup fungi that grow on decaying wood, leaves, litter, and directly on soil. Northern Hemisphere species are primarily found on litter and wood, whereas in the Southern Hemisphere the genus includes a mix of saprotrophs as well as taxa that grow on soil in association with ectomycorrhizal trees. The diversity of this genus has not been fully explored in southern South America. Here we describe two species from Chile, Phaeohelotium maiusaurantium sp. nov. and Ph. pallidum sp. nov., found on soil in Patagonian Nothofagaceae-dominated forests. We present macro- and micromorphological descriptions, illustrations, and molecular phylogenetic analyses. The two new species are placed in Phaeohelotium with high support in our 15-locus phylogeny as well as phylogenetic reconstructions based on the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA gene. Our ITS phylogeny places both Ph. maiusaurantium and Ph. pallidum in a well-supported subclade that includes ectomycorrhizal root tip samples from Australasia. Similar species can be separated from these new taxa based on morphological characteristics, biogeography, substrate, and sequence data. In addition, two unnamed species from Chilean Nothofagaceae forests (Phaeohelotium sp. 1 and Phaeohelotium sp. 2) are documented from scant collections and sequence data and await description until more material becomes available. Citation: Grupe II AC, Smith ME, Weier A, Healy R, Caiafa MV, Pfister DH, Haelewaters D, Quandt CA (2022). Two new species of Phaeohelotium (Leotiomycetes: Helotiaceae) from Chile and their putative ectomycorrhizal status. Fungal Systematics and Evolution 10: 231-249. doi: 10.3114/fuse.2022.10.10.

[Validation of the Bonn test for knowledge in palliative care (BPW)]. / Validierung des Bonner Palliativwissenstests (BPW).

BACKGROUND: Palliative care in nursing homes has become an increasing focal point of healthcare in Germany and the evaluation of the specific quality of palliative care in this setting is under discussion. The assessment of quantitative data has the advantage of allowing pre-post comparisons of different interventions and implementation procedures and can therefore be used for evaluation of effectiveness. However, no assessment tool in German is available yet. Recent research on the assessment of healthcare professionals' knowledge indicated that knowing about technical and psychosocial aspects of palliative care is an easily measurable index for the quality of care. In consequence this index will be used as the core of the test instrument. The specific self-efficacy related to palliative care should be additionally included. METHOD: An analysis of the two most common tests of palliative care knowledge by three experts revealed that these instruments were only partly useful in Germany because of differences in the healthcare systems. The experts also criticised that the tests included only a few items concerning psychosocial care and that these items often showed ceiling effects. In addition, the instruments were not suitable for use in nursing homes. For specific self-efficacy only one test is available in Dutch. The items of these three instruments were face validated by 5 experts and new items were generated where needed. The content validity was verified again by five experts with the think-aloud method. Items were validated in 23 calliative care trainers whose expert knowledge served as an external criterion. Items that scored low in this group were eliminated. A second sample of 36 assistant nurses working in nursing homes who took part in a workshop for palliative care was used to assess change sensitivity before and after training. RESULTS: A total of 23 items for the knowledge test and 15 items for specific self-efficacy were selected. The level of difficulty was suitable because an expert group could answer the questions while for assistant nurses the items were sufficiently difficult to show a difference between groups. Items were very sensitive to change after a training course. CONCLUSION: The BPW is the first standardized test instrument for palliative care in the German language. In comparison to the other tests it includes items from the psychosocial domain without demonstrating a ceiling effect for these items. Content and criterion validity were good. Additional tests with larger samples and with other groups of nurses working in other settings would be needed to improve the data on reliability and to extend the validation to other settings.

[COVID-19 in urology : Influence of the pandemic on telemedicine, education and surgery]. / COVID-19 im urologischen Alltag : Einfluss der Pandemie auf Telemedizin, Ausbildung und Operationen in der Urologie.

The COVID-19 (coronavirus disease 2019) pandemic has caused a worldwide economic and clinical disaster. During times with the highest infection rates, clinical practice for all specialties including urology shifted to the emergency setting. Proper patient selection needs to be done to avoid infection; however, there is a fine line between postponing surgery and negatively affecting the outcome of the disease to be treated. The rapid integration of telemedicine has helped to keep up outpatient medical care, interdisciplinary communication and education. Nevertheless, surgical education of urological residents initially fell behind. The real impact of the COVID-19 pandemic on urology will probably first be seen after the awaited vaccine and control of COVID-19.

[Influence of the working model on the education of young urologists : Education through the ages]. / Auswirkung eines Arbeitszeitmodells auf den Facharzt für Urologie : Eine Ausbildung im Wandel der Zeit.

BACKGROUND: There is a trend of increasing discontent of urologic residents with educational programs. One point being mentioned is lack of time during residency for education and self-training. We analyzed the available time for education in our department depending on the used working model through the last 25 years. MATERIALS AND METHODS: We calculated the absolute availability of residents during their residency for working models in 1996, 2000, 2007 and 2017. As a basis we used the working model of 1996 as no compensatory time-off for being on call was used. All days on which a delayed start is planned and no schedule in daily routine is possible had been excluded from education time. The numbers implemented in the regulation on further education in the corresponding years had been used to calculate the expenditure of time on the basis of median length of the different intervention. In addition, the patient numbers on the ward and our outpatient clinic had been documented over time. RESULTS: With increasing patient numbers in the in- and outpatient clinic there is a continuous decreasing time available for education. The absolute available time in our department is calculated to be 3.1 years compared to 5 years in 1996. With the first day of training a resident has to complete 66.9 min of self-contained diagnostics or interventions per day in addition to clinical routine and administration to meet the requested numbers of the regulation on further education. CONCLUSIONS: The limited time being available for the educational program is improved by the current regulation of education. To teach the complex segments of urology there is an urgent need for a well-structured curriculum, which should be used nationwide.

Wanted on Agave americana! Hymenobolus agaves, an overlooked introduced pathogen in the western palearctic region.

Hymenobolus agaves has been reported only in Europe and Africa on the American plant Agave americana (Asparagaceae). This fungus has never been found in the native range of its host, in arid ecosystems of northern and central Mexico and Texas, USA. It has been suggested to be a pathogen that can kill its host. The fungus grows on succulent leaf bases of the plant. The morphology - black apothecia with a hymenium that disintegrates when asci mature and dark ornamented ascospores - make this species very distinctive, but it has been collected and reported only a few times since its first description. Its systematic position has been unclear, and it has been treated as incertae sedis, that is of uncertain placement, in Leotiomycetes. With recent collections and additional data on the ecology of H. agaves, we use integrative taxonomy (DNA sequences, morphology, ecology) to show its relationships is with Cenangiaceae.

[Targeted molecular therapy and immunotherapy for prostate cancer]. / Molekulare zielgerichtete Therapie und Immuntherapie des Prostatakarzinoms.

For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes. The progress in translational research in recent years has led to innovations in the therapeutic environment. With the decoding of the homologous repair deficiency (HRD) machinery and its ability to be influenced by PARP inhibitors, targeted therapies moved into the therapeutic focus for selected patients. The first positive phase III study for PARP inhibitors is already available. In addition, immunotherapy for the treatment of prostate cancer, which is now widely used in oncology, is also making progress; both checkpoint inhibitors and bispecific antibodies have shown clinically useful activities. Cellular therapies such as CAR T cells, which are directed against prostate-specific membrane antigen (PSMA), are still at an early stage of development. In this review, the authors provide a summary of the basic principles and clinical development of these new therapies.

Geodina (Pezizomycetes: Wynneaceae) has a single widespread species in tropical America.

Geodina salmonicolor is shown to be a synonym of G. guanacastensis, the type and only species of the genus. Comparisons of ITS rDNA sequences of a paratype and two recent collections of G. guanacastensis with published ITS sequences of G. salmonicolor, from the Dominican Republic, show that these are nearly identical. When G. salmonicolor was erected no sequences of the type species were available. Morphological comparisons supports the conspecificity. Details regarding the description of G. salmonicolor are pointed out. A four-gene phylogeny places Geodina and Wynnea as a supported sister group to the rest of the Sarcoscyphaceae. Species in these genera share morphological traits of cyanophobic spore markings, dark angular outer excipular cells that give rise to hairs and the origin of several apothecia from a common basal stalk. Their occurrence on soil rather than on wood or plant material distinguish them from other Sarcoscyphaceae. Based on morphology, phylogenic relationships and trophic interactions we erect a new family, Wynneaceae, for Geodina and Wynnea.