Helge L. Waldum

By Helge Waldum and Patricia Mjønes

The dominating type of kidney cancer is the clear cell renal cell cancer (ccRCC), hitherto been thought to develop from proximal tubule cells. However, the ability of tubule cells to proliferate is at best controversial. ccRCCs show many peculiarities like erythrocytosis due to erythropoietin overproduction and a combination of early metastases and sometimes apparent dormancy and late recurrence, features in common with neuroendocrine tumours (NETs). We have shown that most ccRCCs express erythropoietin and the neuroendocrine marker neuron-specific enolase, and other neuroendocrine markers in a percentage of the cancers. Missense mutation in von Hippel–Lindau (VHL) factor is rather specific for ccRCC found in familial and sporadic forms. The function of VHL factor is together with other proteins to destroy hypoxia-inducible factors (HIFs), central in adaptation to hypoxia. Lack of functioning VHL factor results in continuous overstimulation of the erythropoietin-producing cell to release erythropoietin and parallelly to proliferate, and in long-term mutations and malignant transformation. Thus, ccRCC occurs about 30 years later in sporadic cases compared with familial von Hippel–Lindau syndrome, reflecting the time necessary for two versus one genetic change. Embryologically, there are many arguments favouring neural crest origin of the erythropoietin-producing cell.

Part of the book: Renal Cell Carcinoma

By Helge L. Waldum

The discovery that Helicobacter pylori was the dominating cause of gastritis is among the most important findings in the last century. It gave rise to the understanding and treatment of serious and common diseases, such as peptic ulcer disease and gastric cancer. The gastric hormone gastrin is involved in the pathogenesis of both duodenal ulcer and gastric cancer, whereas reduction in the defense mechanism (mucus and bicarbonate) by the inflammation itself predisposes to gastric ulcer. The search for carcinogenic H. pylori factors has been unsuccessful and based upon the fact that H. pylori predispose to gastric cancer only after having induced oxyntic atrophy is an important argument in favor of a central role of gastrin increase secondary to reduced acidity. The only cell with an undisputed gastrin receptor is the enterochromaffin-like cell where gastrin has a trophic effect leading to hyperplasia, neuroendocrine tumor (NET), and long-term carcinoma of diffuse type. H. pylori may be eradicated by a combination of antibiotics with a potent inhibitor of acid secretion. H. pylori is dependent on acid surrounding to thrive, and therefore anacidity due to complete oxyntic atrophy or profound inhibition of acid secretion by drugs will promote its disappearance.

Part of the book: Helicobacter pylori Infection