Primers in 2017

Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and comprises two major subtypes — oesophageal squamous cell carcinoma and oesophageal adenocarcinoma — which are epidemiologically and biologically distinct. In this Primer, Cunningham and colleagues describe the epidemiology, pathophysiology and management of oesophageal cancer.

Multiple myeloma — a malignancy of terminally differentiated plasma cells — is the second most common haematological malignancy. This Primer by Kumar et al. highlights the mechanisms and epidemiology of multiple myeloma, and describes how updates to the diagnostic criteria have impacted patient management.

Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23. Clinically, TIO is associated with hypophosphataemia and skeletal abnormalities. This Primer focuses on the epidemiological, pathophysiological, diagnostic and clinical aspects of TIO.

Urinary incontinence symptoms in women are prevalent and substantially affect health-related quality of life. These issues are compounded by the limited attention that urinary incontinence receives at the policy or research-funding levels. Despite these challenges, the field has witnessed considerable innovations in practice over the past decade, which are summarized in this Primer.

Vitamin B₁₂ (also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. In this Primer, Green et al. describe the causes, consequences and management of vitamin B₁₂ deficiency.

Periodontal diseases are characterized by inflammation and loss of the tissues supporting the teeth, which could lead to eating and speaking problems. Although some risk factors are non-modifiable (for example, genetic susceptibility), others, such as smoking, can be effectively managed.

Obesity is considered to be an epidemic of the 21st century; >2 billion individuals are considered to be overweight or obese globally. In this Primer, Martinez and colleagues discuss obesity and its association with pathophysiological abnormalities that increase health risk, such as features of the metabolic syndrome.

Granulopoiesis arrest in the bone marrow at the promyelocyte level is the hallmark of severe congenital neutropenias. Patients have an increased risk of infections and leukaemic progression; granulocyte colony-stimulating factor therapy can restore neutrophil counts in most cases.

In recent years, the molecular characterization of gastric adenocarcinoma — the most common stomach cancer — has identified numerous targets for potential exploitation into therapy. However, advances are still lagging compared with other cancers of similar incidence. In this Primer, Ajani et al. describe these advances and the work still needed to be done.

The formation of dental caries involves the interaction between the tooth, the microbial biofilm at the tooth surface and dietary sugars. This Primer by Pitts et al. aims to provide a global overview of caries, focusing on current, patient-centred, tooth-preserving preventive care.

Anaemia, thrombosis and smooth muscle dystonias are manifestations of paroxysmal nocturnal haemoglobinuria, a rare but potentially life-threatening haematological disorder. Inhibition of complement activation is the treatment of choice; stem cell transplantation is recommended for patients who also develop severe bone marrow failure.

Pemphigus is an autoimmune disorder characterized by blisters in the oral mucosa and epidermis. Acantholysis (loss of cell adhesion, which results in blisters) is caused by the presence of autoantibodies that target desmosomal proteins, in particular, desmoglein 1 and desmoglein 3.

Anxiety disorders are characterized by prolonged fear or anxiety, the avoidance of perceived threats and, in some cases, panic attacks. Here, Craske et al. discuss the mechanisms, diagnosis and management of anxiety disorders, and provide an overview of the quality-of-life issues faced by patients.

Spinal cord injury (SCI) can be divided into traumatic and non-traumatic aetiologies. This Primer focuses on traumatic SCI, which is caused by an external physical impact to the spinal cord and can lead to permanent, severe neurological deficits.

Urothelial bladder cancer is one of the most common, and most deadly, malignant diseases worldwide. This Primer summarizes the current epidemiological and outcome data of patients with this disease, as well as describing how new molecular subtyping strategies might improve patient care in the future.

Haemolytic anaemia, thrombocytopenia and microthrombi are hallmarks of thrombotic thrombocytopenic purpura (TTP), a rare microangiopathy that can cause severe ischaemic organ damage. The majority of cases have an autoimmune aetiology and, therefore, can be managed with immunosuppressive drugs, in addition to plasma therapy.

Type 1 diabetes mellitus is an autoimmune disease that is characterized by insulin deficiency due to pancreatic β-cell loss and results in hyperglycaemia. This Primer by Lernmark and colleagues describes this chronic disorder, which requires lifelong insulin administration and affects >500,000 children worldwide.

Parkinson disease is a common neurodegenerative disorder that is characterized by neuronal loss in the substantia nigra, which causes striatal dopamine deficiency. In this Primer, Poewe et al. discuss the epidemiology, pathophysiology, diagnosis and management of Parkinson disease.

Alopecia areata is an autoimmune disorder characterized by transient hair loss. Severity can range from distinct patches to total hair loss. In this Primer, the authors describe the underlying pathophysiology of this complex polygenic disease, as well as the epidemiology, diagnosis and management.

Renal cell carcinoma (RCC) is a neoplasm of the renal epithelium and accounts for >90% of kidney cancers. Cancer genomic studies have identified numerous molecular events that lead to RCC and marked intra-tumour heterogeneity, which have prognostic and therapeutic relevance. In this Primer, the authors describe these advances, as well as highlight the considerable advances in the systemic treatment of metastatic RCC.