Testicular tumours from a clinical point of view: What urologists and oncologists need to know from the pathologist about testicular cancer [Hodentumoren aus klinischer Sicht: Was Urolog:Innen und Onkolog:Innen von Patholog: Innen \ufcber Hodentumoren wissen m\ufcssen]

\ua9 2022, The Author(s). Background: Testicular germ cell tumours (GCTs) are the most frequent solid malignancy in younger males aged 15–40. The differentiation between seminomas and non-seminomas impacts prognosis, clinical management and follow-up procedures. With stage- and risk-adapted multimodal treatment approaches, GCTs have an exceptionally good prognosis. Therefore, avoiding overtreatment to reduce treatment-related long-term side effects is of utmost importance. Clinical and histopathological risk factors aid in treatment decision-making. Objectives: Discussion of (histo-)pathological characteristics that directly influence treatment decision-making by urologists and oncologists. Materials and methods: Non-systematic literature review to describe histopathological features for interdisciplinary treatment planning. Results: Key histopathological characteristics for clinicians are: (i) identification of a GCT, if necessary by 12p aberration analysis, (ii) description of the different subtypes, and (iii) risk factors, including lymphovascular invasion and/or rete testis infiltration and size of the primary tumour. Molecular pathological analyses, that is, genomic sequencing, is not part of routine diagnostics due to the lack of prognostic/predictive markers and effective targeted treatment approaches. Discussion: Detailed histopathology reporting, ideally with a synoptic template, is the basis for planning and conducting guideline-endorsed, risk-adapted, multi-disciplinary management of GCTs. Along with radiographic imaging and assessment of the serum tumour markers AFP and β‑HCG (especially in non-seminomas), histopathology is crucial to maintain success and reduce the burden of GCT treatment

Oncological Follow-up Strategies for Testicular Germ Cell Tumours: A Narrative Review

\ua9 2022 The Authors. Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients

Practice Patterns Among Penile Cancer Surgeons Performing Dynamic Sentinel Lymph Node Biopsy and Radical Inguinal Lymph Node Dissection in Men with Penile Cancer: A eUROGEN Survey.

Dynamic sentinel lymph node biopsy (DSNB) and radical inguinal lymph node dissection (ILND) are important in the management of penile cancer patients, but high-level evidence for preoperative, perioperative, and postoperative management remains scarce. According to an online survey of 35 surgeons from ten European countries, 57% perform >10 ILND procedures per year and 86% offer DSNB. Furthermore, management differs substantially for dye injection site, use of lymphoscintigraphy, preferred incision sites, techniques for lymphatic control, duration of empiric antibiotic therapy, perioperative thromboprophylaxis, time points for drain removal, and definition of the ILND dissection floor. Consensus was observed for the use of perioperative antibiotics (although not duration and type) and the borders for ILND template definitions. We conclude that there is significant variation in patient management among eUROGEN penile cancer surgeons. This heterogeneity may confound multicentre studies; therefore, a consensus to standardise inguinal node management in penile cancer across European penile cancer centres is warranted. PATIENT SUMMARY: Our survey reveals that preferences and surgical techniques for inguinal lymph node sampling and removal varies significantly between European penile cancer surgeons. Consensus is needed to standardise the management approach for penile cancer

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy

\ua9 2022 The Authors. Purpose: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. Methods and Materials: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. Results: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients’ symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. Conclusions: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy

Accuracy of ultrasound vs computed tomography scan for upper urinary tract malignancies and development of a risk-based diagnostic algorithm for haematuria in a UK tertiary centre

Purpose There is no consensus across guidelines on a diagnostic algorithm for upper urinary tract (UUT) evaluation following presentation with haematuria. Our aim is to compare the diagnostic accuracy of ultrasound (USS) compared to CT-scan for UUT malignancies and also determine the considerations important for a risk-based diagnostic protocol for haematuria. Methods We reviewed our ‘haematuria clinic’ database to identify patients who had both USS and CT-scan for UUT evaluation between September 2015 and August 2017, and calculated the diagnostic accuracy of these imaging modalities for histologically confirmed UUT cancers. Furthermore, we identified risk factors in our diagnostic algorithm for haematuria and conducted regression analysis to determine their ability to predict UUT malignancies. Results Overall, 575 patient records were studied. Age range was 21–92 years, M:F was 1.4:1, majority (81.2%) had visible haematuria, and 12 (2.1%) UUT cancers were diagnosed [renal cell carcinoma—1.4%; upper tract urothelial cancer—0.7%]. USS and CT-scan had diagnostic accuracy for UUT cancers of 95.8 and 99.1%, respectively (p < 0.001). Haematuria type was a significant consideration only on univariate analysis, while multivariate binary logistic regression showed that male gender, smoking, occupational exposure, and positive urologic history were the main risk factors associated with UUT malignancies. Conclusion USS and CT-scan have comparably high diagnostic accuracy for detecting UUT malignancies. USS may, therefore, be considered as the first-line UUT imaging modality when utilized in a risk-based diagnostic algorithm. Larger, multicentred studies are needed to validate our findings and influence guideline development

Inherent Structural Disorder and Dimerisation of Murine Norovirus NS1-2 Protein

Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. The first open reading frame of the norovirus RNA genome encodes for a polyprotein that is cleaved by the viral protease into six non-structural proteins. The first non-structural protein, NS1-2, lacks any significant sequence similarity to other viral or cellular proteins and limited information is available about the function and biophysical characteristics of this protein. Bioinformatic analyses identified an inherently disordered region (residues 1–142) in the highly divergent N-terminal region of the norovirus NS1-2 protein. Expression and purification of the NS1-2 protein of Murine norovirus confirmed these predictions by identifying several features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-2 protein also identified the presence of an NS1-2 dimer in Escherichia coli and transfected HEK293T cells. Inherent disorder provides significant advantages including structural flexibility and the ability to bind to numerous targets allowing a single protein to have multiple functions. These advantages combined with the potential functional advantages of multimerisation suggest a multi-functional role for the NS1-2 protein

Arabidopsis cell expansion is controlled by a photothermal switch

In Arabidopsis, the seedling hypocotyl has emerged as an exemplar model system to study light and temperature control of cell expansion. Light sensitivity of this organ is epitomized in the fluence rate response where suppression of hypocotyl elongation increases incrementally with light intensity. This finely calibrated response is controlled by the photoreceptor, phytochrome B, through the deactivation and proteolytic destruction of phytochrome-interacting factors (PIFs). Here we show that this classical light response is strictly temperature dependent: a shift in temperature induces a dramatic reversal of response from inhibition to promotion of hypocotyl elongation by light. Applying an integrated experimental and mathematical modelling approach, we show how light and temperature coaction in the circuitry drives a molecular switch in PIF activity and control of cell expansion. This work provides a paradigm to understand the importance of signal convergence in evoking different or non-intuitive alterations in molecular signalling

NUCLEAR FACTOR Y, Subunit C (NF-YC) Transcription Factors Are Positive Regulators of Photomorphogenesis in Arabidopsis thaliana

We thank Dr. Ben Smith (University of Oklahoma) for assistance with FLIM-FRET measurements and Dr. Min Ni (University of Minnesota) for critical reading of the manuscript. The cop1-4 mutant allele and cop1-4 co-9 cross were kindly provided by George Coupland (Max Planck Institute).Author Summary Light perception is critically important for the fitness of plants in both natural and agricultural settings. Plants not only use light for photosynthesis, but also as a cue for proper development. As a seedling emerges from soil it must determine the light environment and adopt an appropriate growth habit. When blue and red wavelengths are the dominant sources of light, plants will undergo photomorphogenesis. Photomorphogenesis describes a number of developmental responses initiated by light in a seedling, and includes shortened stems and establishing the ability to photosynthesize. The genes regulating photomorphogenesis have been studied extensively, but a complete picture remains elusive. Here we describe the finding that NUCLEAR FACTOR-Y (NF-Y) genes are positive regulators of photomorphogenesis—i.e., in plants where NF-Y genes are mutated, they display some characteristics of dark grown plants, even though they are in the light. Our data suggests that the roles of NF-Y genes in light perception do not fit in easily with those of other described pathways. Thus, studying these genes promises to help develop a more complete picture of how light drives plant development.Yeshttp://www.plosgenetics.org/static/editorial#pee