The development of the upper limb begins during the fourth week of in utero life, when a limb bud consisting of undifferentiated mesenchymal cells encased in ectoderm develops. By 9 weeks, the bud has developed into an arm and hand with identifiable digits, and by 12 weeks, the digits have differentiated. Growth and differentiation are under the control of signal regions at the tip of the developing limb, with complicated interactions and feedback systems (Figure 16.1). Induction of mesenchymal cells in the ‘progress zone’ at the tip of the developing limb occurs under the influence of specific zones. The apical ectodermal ridge (AER) is the director of growth in the proximo-distal axis (excision of the AER results in a limb stump only, and transplantation may result in a duplicate limb).

This chapter aims to cover the commonest benign and malignant bone tumours in paediatric orthopaedics practice (and exams). Table 20.1 summarizes bone tumours and their cells of origin, and Table 20.2 summarizes bone tumour-like conditions. The selected tumours in this chapter are those that are most frequently addressed in the FRCS exams. The current evidence is discussed, and the identifiable radiological and histological features are illustrated. To this aim, we have also included the soft tissue tumour rhabdomyosarcoma.

The elbow is a combination hinge and pivot trocho-ginglymoid joint, formed by the ulno-humeral, radio-humeral, and proximal radioulnar articulations. The joint capsule is thickened medially and laterally to form the collateral ligaments, which are the major stabilizers of the elbow joint. Details of these ligaments are shown and described in Figure 15.1.

The androgen receptor (AR) is part of a superfamily of nuclear receptors. The AR has a diverse set of downstream effects on male phenotype and sexual function, muscle mass and strength, bone density, hematopoiesis, cognition, and metabolism. Testosterone replacement therapy (TRT) to treat male hypogonadism utilizes exogenously administered testosterone to activate the AR. However, TRT is known to have potential risks, including erythrocytosis, dyslipidemia, prostatic hypertrophy, hepatotoxicity, impaired fertility, aromatization of testosterone to estrogen, and testicular atrophy. Selective androgen receptor modulators, also known as SARMs, are compounds that have shown tissue-selective activation of the AR. These compounds potentially offer the ability to treat hypogonadal conditions where activating the AR in the bone, muscle, or brain is desired while sparing undesired effects in tissues such as the prostate, liver, or bone marrow. Currently, there is a dearth of data in human subjects regarding the treatment of male hypogonadism with SARMs. However, from animal models and preliminary studies of SARMs in humans, there appears to be a possible role for SARMs in the hypogonadal man, and their efficacy and safety warrant further study.

Knowledge of the anatomy and physiology of the hypothalamic-pituitary-gonadal axis is paramount for the understanding and management of hypogonadism in men. Although the definition of hypogonadism may seem elusive, there is a framework to assist with the diagnosis once a history, physical examination, and appropriate lab testing are obtained. There are a number of treatment options to consider with their associated risks and benefits.

Male factor infertility contributes to roughly 50% of the causes of infertility among couples. Advancements in the diagnostic field of reproduction allowed for the recognition of various etiologies for male factor infertility. Various pretesticular, testicular, and posttesticular etiologies have been identified and are believed to arise from genetic causes in 15–30% of cases. While a number of laboratory tests are available, the indication of genetic testing relies primarily on the findings in the history, physical examination, and semen analysis. Men with suspicion of nonobstructive azoospermia and those with idiopathic severe oligozoospermia are investigated with karyotype and Y-chromosome microdeletion assays. Analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is reserved for patients with obstructive azoospermia secondary to a unilateral or bilateral complete absence of the vas deference. In addition to the more commonly adopted tests, the genetic evaluation may have a role in patients with congenital hypogonadotropic hypogonadism and androgen insensitivity syndrome. Genetic testing of male infertility is a rapidly evolving field in andrology. Epigenetics, next-generation DNA sequencing, and microarray-based technologies represent some of the promising development in the area and may further expand the clinical utilization of genetic evaluation.

Human spermatogonial stem cells (hSSCs), the only type of germline stem cells in adult men, are responsible to ensure lifetime-long sperm production in men after sex maturation. As the starting point of spermatogenesis, this cell type delicately balances its self-renewal and differentiation, which is essential for spermatogenesis to proceed continuously. A deep and systematic understanding of hSSCs is critical for treating testis-related pathology such as male infertility and testicular germ cell tumor. In this chapter, we provide a systematic review of our previous and current understanding of hSSCs, as well as the advancement of ex vivo systems to culture human germline. Ultimately, the successful establishment of an hSSC-based human germline culture system will not only greatly benefit the study of human germ cell biology by serving as a useful platform, but also provide potential therapeutic options to treat male infertility and preserve fertility for childhood cancer patients.

In this chapter, we will review how men’s health has evolved into a distinct subspecialty of medicine and changed over the past two decades. There exists a large disparity between men and women when it comes to health. However, as the drivers for men seeking health care are changing, the urologist is in a unique position to help quarterback men’s health initiatives. Men’s health advocacy and the creation of men’s health centers are on the rise. Areas of advancement in the field include prostate cancer diagnosis and treatment, erectile dysfunction therapies, surgical treatment for chronic testicular pain, and new approaches to male factor infertility. The burgeoning field of men’s health has seen many advancements in the past two decades and will continue to make significant gains in the years to come.

This chapter reviews the current limitations of CASA in routine clinical andrology and describes a path by which it could become a robust analytical technology that can be employed in accredited expert clinical andrology laboratories. Particular focus is on the need for premarketing validation by manufacturers for CASA-based semen analysis applications, as well as the impact that software differences have on the absolute values reported for sperm kinematics. Without close comparability between CASA systems it will continue to be extremely difficult to establish either decision limits or reference ranges that can be applied clinically for either diagnostic or prognostic purposes.

Sexual health and, specifically, erectile function play an important role in the lives of many men. Lifestyle modification, considered first-line therapy for many disease processes, is often overlooked and underdiscussed, particularly with the advent of pharmacologic and surgical interventions to restore erectile function. Even though these medical and surgical interventions are highly successful, discussion of lifestyle modification for prevention of erectile dysfunction, as solo therapy, or as adjunct to other therapies, still plays a role in the armamentarium of the healthcare provider. The aim of our chapter is to review the literature assessing impact of lifestyle modification on erectile function.

Varicoceles are the most common correctable cause of male factor infertility. Varicocele repair, therefore, has an important role in the treatment of infertility. Performing varicocelectomy prior to assisted reproductive technology has the potential to improve male fertility and increase pregnancy and live birth rates. It can also be a cost-effective treatment method in infertile men with clinical varicoceles.

We have previously reported in several publications the existence of a nuclease that is present in the luminal fluid of the epididymis and in higher concentrations in the lumina fluid of the vas deferens in the mouse. This luminal nuclease has the ability to digest the sperm DNA into loop-sized fragments but is restricted to digesting DNA that is not bound by protamines. In this chapter, we describe new data that show that the luminal nuclease is active in SDS for up to 30 min, complicating the analysis of sperm DNA damage that must be extracted by SDS for electrophoretic analysis on gels. High concentrations of EDTA can protect the DNA from the luminal nuclease if added before SDS is applied. This new data provides an update on our toroid loop model for sperm chromatin structure. We discuss the implications of this updated model for the study of sperm chromatin structure and for clinical assays for sperm DNA damage.

Given the wide spectrum in practice standards and patterns, array of covered versus out-of-pocket conditions, and role of adjunct streams of revenue, the business landscape of men’s health is diverse. Fundamental to the fiscal success of many providers is the efficacy of direct to consumer marketing in the setting of inelastic demand for solutions to aging, erectile dysfunction (ED), and Peyronie’s disease; this has created enormous markets surrounding supplemental testosterone, online platforms for ED treatment, and out-of-pocket products such as platelet-rich plasma, stem-cell therapy, and shock wave treatments. The contemporary story of men’s health has been defined by the gender health gap; uncovering the link between coronary artery disease (CAD) and ED unveiled a touchpoint for establishing holistic men’s health. University and large hospital systems have the infrastructure to support comprehensive Men’s Health Centers and have therefore maximized the downstream revenue associated with prescriptions, long-term screening, and future hospitalizations.