A Century of Advances in Neuroendocrine Tumor Biology and Treatment

 

Foreword

On September 17, 1907, a paper entitled “Carcinoid Tumors of the Small Intestine” was presented by the German pathologist Siegfried Oberndorfer of Munich to the German Pathological Society in Dresden. The work was novel in that it proposed the existence of a new neoplastic entity – Karzinoide – that was different and possibly more benign and slow-growing than bowel cancer. Although initially not widely considered, the acceptance of Oberndorfer’s work created the basis of our modern understanding of neuroendocrine tumors and, in turn, led to the development of agents to suppress the secretion of their bioactive products and to identify their location and extent.

One hundred years later, Ipsen Pharma memorialized the anniversary of Oberndorfer’s extraordinary contribution by inviting 300 leading international physicians and scientists to celebrate his discovery. The discussions reflected the current status of neuroendocrine tumor disease and cutting-edge developments in the understanding of amine and peptide secretion and suppression, as well as progress in the clinical management of the ubiquitous entity of carcinoid disease.

The meeting was chaired by Irvin Modlin (USA) and Kjell Oberg (Sweden), and the speakers included numerous eminent figures in the field of gastroenterology and gastrointestinal surgery. Among them was the Nobel Prize winner Sir James Black, whose seminal work produced the first agents to effectively suppress cell secretion and block receptor activation (beta adrenergic and histamine-2 receptor antagonists – H2RAs). A similar concept led to the award of the Nobel Prize to Guillemin and Schally for the identification of somatostatin and the development of the somatostatin receptor class of agonists so effective in the treatment of neuroendocrine tumor disease. Their efficacy and unparalleled anti-secretory activity has revolutionized the management of neuroendocrine tumor disease.

In the century since Oberndorfer’s discovery, the knowledge of the physiology and pathophysiology of neuroendocrine cells and tumors has increased dramatically. Medical therapy has become widely accepted as a life-long adjunct to all other interventions due to its safety and high efficacy. The advances in symptom suppression have been especially augmented by the identification of improvement in quality of life and the avoidance of potentially lethal complication of carcinoid crisis.

As recently as three decades ago, carcinoid was considered to be an exotic, rare and almost unmanageable condition caused by diverse lesions that were ill-understood, difficult to diagnose and for whom no rational therapeutic strategy existed. However, in the past few years, a growing body of evidence has demonstrated the molecular and genomic basis, defined the mechanistic elements of secretion and proliferation and provided evidence that neuroendocrine cells can be identified, regulated and even ablated. The identification of an increasingly larger population of patients exhibiting the disease yet diagnosed very late, has proved frustrating and highlighted the need for a sensitive and specific surveillance test. A further important observation has been that neuroendocrine disease is symptomatically represented by a constellation of mundane symptoms that are often ignored, indicating the need for increased patient and physician education. For therapy to be regarded as effective and successful, it is necessary to provide control not only of the symptoms and quality of life but also the growth and spread of the neoplasm. In this respect much progress is still required.

This book serves to provide a broad state-of-the-art overview of the substantial developments in the field of neuroendocrine tumors in the century since Oberndorfer’s seminal description of carcinoid tumors. It presents a compendium of clinical and scientific information that summarizes the advances in neuroendocrine tumor biology, pathology and clinical practice in the last century. Both we and the distinguished physicians present acknowledge and celebrate the life and times of Oberndorfer, whose great accomplishment led to the elucidation of neuroendocrine tumor disease.

 

 

Irvin M Modlin MD, PhD and Kjell Oberg MD, PhD

 

 

 

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