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Since the introduction of cisplatin-based combination chemotherapy, patients with metastatic germ cell tumours achieve very high cure rates of >80%. Nevertheless, about 30% of patients relapse despite guideline-endorsed first-line treatment. Of these, again about 50% of patients can still achieve cure with platinum-based salvage chemotherapy and eventually post-chemotherapy residual mass resection.Salvage chemotherapy generally involves platinum-based combination chemotherapy, either as conventional dose cisplatin-based combinations again or as high-dose chemotherapy with subsequent autologous stem cell transplantation.To date, high level evidence from randomised trials supporting the use of salvage high-dose chemotherapy for all patients relapsing after first-line treatment remains lacking, but a large international retrospective registry study had shown a 15% overall survival benefit for patients undergoing salvage high-dose chemotherapy.In this article, we summarise the available literature on the different salvage treatment approaches and discuss these in the light of current treatment guideline recommendations for the management of testicular cancer., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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., (© 2022. The Author(s).)

In the tradition of Harvey and according to Otto Frank the heart muscle structure is arranged in a strictly tangential fashion hence all contractile forces act in the direction of ventricular ejection. In contrast, morphology confirms that the heart consists of a 3-dimensional network of muscle fibers with up to two fifths of the chains of aggregated myocytes deviating from a tangential alignment at variable angles. Accordingly, the myocardial systolic forces contain, in addition to a constrictive also a (albeit smaller) radially acting component. Using needle force probes we have correspondingly measured an unloading type of force in a tangential direction and an auxotonic type in dilatative transversal direction of the ventricular walls to show that the myocardial body contracts actively in a 3-dimensional pattern. This antagonism supports the autoregulation of heart muscle function according to Frank and Starling, preserving ventricular shape, enhances late systolic fast dilation and attenuates systolic constriction of the ventricle wall. Auxotonic dilating forces are particularly sensitive to inotropic medication. Low dose beta-blocker is able to attenuate the antagonistic activity. All myocardial components act against four components of afterload, the hemodynamic, the myostructural, the stromatogenic and the hydraulic component. This complex interplay critically complicates clinical diagnostics. Clinical implications are far-reaching (see Part II, https://doi.org/10.1007/s00059-018-4735-x).

Extramammary Paget's disease (EPD) is a rare, slowly growing, cutaneous adenocarcinoma with an incidence of 0.1-2.4 per 1,000,000 inhabitants. Histologically, EPD is characterized by the presence of epidermal Paget's cells, similarly to mammary Paget's disease. The EPD is typically divided into primary EPD (type I) and secondary EPD (type II associated with colorectal carcinoma and type III associated with urogenital carcinoma). From a clinical point of view, EPD is unspecific commonly mimicking chronic inflammatory skin disorders. This unspecific clinical picture can impede and delay the diagnosis of EPD. The treatment of choice for local EPD is the micrographically controlled excision. The extent of the infiltration of adnexal structures should be histologically determined prior to topical therapies, such as imiquimod and superficial ablative therapy. The complete excision of the tumor can be challenging due to ill-defined borders. In the metastatic stage the EPD has a poor prognosis. Controlled clinical trials for systemic treatment are still lacking.

Bipolar depression is linked with substantial burden and a high suicide risk, making a rapid and highly efficacious treatment mandatory. However, similar to mania, aspects of long-term treatment should already be considered at treatment initiation. With comparable efficacy, drugs with a beneficial safety and tolerability profile should be preferred. Additional psychotherapy can also noticeably improve both short- and long-term outcome of bipolar depression. Electroconvulsive therapy (ECT) still has its place in severe, treatment-resistant bipolar depression. Whereas ECT is a domain of specialised centres, correct diagnosis and both pharmacological and psychotherapeutic treatment initiation are essential tasks of primary care practitioners and secondary care psychiatrists.