The first half of this review examines the boundary between endocrinology and embryonic development, with the aim of highlighting the way hormones and signaling systems regulate the complex morphological changes to enable the intra-abdominal fetal testes to reach the scrotum. The genitoinguinal ligament, or gubernaculum, first enlarges to hold the testis near the groin, and then it develops limb-bud-like properties and migrates across the pubic region to reach the scrotum. Recent advances show key roles for insulin-like hormone 3 in the first step, with androgen and the genitofemoral nerve involved in the second step. The mammary line may also be involved in initiating the migration. The key events in early postnatal germ cell development are then reviewed because there is mounting evidence for this to be crucial in preventing infertility and malignancy later in life. We review the recent advances in what is known about the etiology of cryptorchidism and summarize the syndromes where a specific molecular cause has been found. Finally, we cover the recent literature on timing of surgery, the issues around acquired cryptorchidism, and the limited role of hormone therapy. We conclude with some observations about the differences between animal models and baby boys with cryptorchidism.

Testicular descent is a complex developmental process involving anatomical and hormonal regulation. The gubernaculum undergoes a "swelling reaction" during the transabdominal phase and is mainly under the control of Insulin-Like Peptide 3 (INSL-3) and Mullerian Inhibitory Substance/Anti-Mullerian Hormone (MIS/AMH). The second phase of testicular descent is regulated by androgens and calcitonin gene-related peptide (CGRP) release from the sensory nucleus of the genitofemoral nerve (GFN). In rodents, the active proliferation of the gubernacular tip and cremaster muscle, its rhythmic contraction, as well as the chemotactic gradient provided by the CGRP result in eventual migration of the testis into the scrotum. This review illustrates the structural aspects and hormonal control of cremaster muscle development to better understand the mechanism of testicular descent in normal rodents and humans, compared to diseased rodent models. The analysis showed the cremaster muscle is formed from mesenchymal differentiation of the gubernacular tip and is not a direct passive extension of internal oblique muscle. Cremaster muscle matures slower than other body muscles, and the persistence of immature myogenic proteins seen in cardiac muscle allows rhythmic contraction to guide the testis into the scrotum. Finally, remodelling of the cremaster muscle enables gubernacular eversion. Further understanding of the molecular regulators governing the structural and hormonal changes in the cremaster muscle may lead to new advances in the treatment of undescended testes.

No abstract

Malignant pleural mesothelioma (MPM) remains a deadly disease with limited therapeutic options beyond platinum/pemetrexed chemotherapy. Immune checkpoint inhibitors have demonstrated modest benefit in the second to later-line settings. An MPM patient from our institute developed myocarditis and myositis after 2 cycles of second-line nivolumab. Despite immunosuppression with corticosteroids and mycophenolate mofetil, there was ongoing rise in troponin levels which remained elevated for months.The patient developed an impressive but brief response following cessation of nivolumab. Myocarditis and myositis are rare complications of immune checkpoint inhibitors. Clinicians should be aware of these possible complications as myocarditis can result in mortality.