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Genetic Disorders of the Exocrine Pancreas
  1. D Fine

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This multiauthor work, derived from a symposium held in April 2001, summarises our current knowledge of the genetics of exocrine pancreatic disease. As is usual with such publications, the individual chapters have been written as free standing presentations which results in a degree of repetition. The editors have grouped the chapters into sections; a “consensus conference” dealing with ethical issues and with guidelines for prevention, screening, and treatment is followed by sections on hereditary pancreatitis (HP), pancreatic cancer, and cystic fibrosis. Finally, there is a conference report and a monograph celebrating the work of Henry Lynch of the eponymous cancer syndromes.

The first section will be of the most practical interest to general gastroenterologists. Gastrointestinal physicians and surgeons should already be aware of the ethics of screening from more common conditions such as colon cancer. A brief overview of these issues is followed by clear advice on whom to test, appropriate pre-test information, post-test information, and acting on the results. The algorithm looks forbidding but is straightforward and logical. Both service and research testing are covered. Screening for cancer in HP is a more difficult issue. The advice that patients over 40 years should have annual screening at a specialist centre however may build a knowledge base for future patients but will not necessarily help our current population.

The HP section suffers from its symposium origins. In the six years since David Whitcombe and his colleagues identified a mutation of the PRSS1 (cationic trypsinogen) gene in a kindred with HP, a new understanding of the relationship between the three entities of acute and chronic pancreatitis and pancreatic cancer has developed. It is a pity that the format of this book has not allowed this to be made explicit. It starts well with a two page overview neatly logging the known PRSS1 and SPINK mutations. Unfortunately, the chapters dealing with the mechanisms by which these mutations might translate into clinical disease, which logically should follow, are instead towards the end of the section (although an earlier chapter on gene mutations in children does cover some of this ground). The general reader might well find the intervening chapters on national experiences superfluous. The review of inborn errors of metabolism is useful but surely belongs at the end of the section rather than in the middle.

The pancreatic cancer section is better organised and provides a comprehensive review of the contribution of genes to disease. In contrast with HP, there are no defined single gene mutations identified for pancreatic cancer. Families with two or more affected members have been reported: whether this simply represents random clustering is discussed. The risk of pancreatic cancer in accepted cancer syndromes such as FAMM, Lynch syndrome II, BRCA2 mutation, and Peutz-Jehgers syndrome is also considered. The chapters on surveillance and molecular diagnosis will be of particular interest as they offer the first glimpse of hope for early detection and treatment. Non-pancreatologists may not be aware that premalignant ductal lesions termed PanINs have now been described and classified. Ways in which this discovery and molecular markers such as K-ras mutations may be exploited in screening strategies are reviewed, as are the practical difficulties of assessing the pancreas even with the benefit of EUS and CT. Ultimately however, all strategies being considered or tried will lead to a prophylactic pancreatectomy: the practicalities of the timing and extent of pancreatectomy are covered in the final chapter.

The final section covering cystic fibrosis and the Shwachman-Diamond syndrome is limited in its scope and appears to reflect one centre’s interests and research.

Currently, pancreatic disease is either self limiting or incurable. Effective treatments for pancreatitis and pancreatic cancer will come from molecular and genetic research of the type described here. The presentation of this book is not perfect but the information it contains should be available to anyone dealing with pancreatic disease. Ask your library to buy it.