Elsevier

The Lancet Oncology

Volume 8, Issue 11, November 2007, Pages 1007-1017
The Lancet Oncology

Review
Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients

https://doi.org/10.1016/S1470-2045(07)70341-8Get rights and content

Summary

Gastrointestinal symptoms after pelvic radiotherapy, which affect quality of life, are substantially more common than generally recognised and are frequently poorly managed. These symptoms develop because radiation can induce change in one or more specific physiological functions in widely separated parts of the gastrointestinal tract that lie in the path of the radiotherapy beam. Radiation-induced changes are not confined by normal anatomical boundaries. Furthermore, pre-existing subclinical disease might be destabilised because of minor gastrointestinal changes induced by radiotherapy. New diseases might manifest after radiotherapy and be confused with symptoms induced by radiotherapy. Different functional deficits might cause the same symptoms. Many patients have more than one cause for their symptoms, which sometimes need very different treatments. Simple diagnostic tests that are used in other contexts, if applied appropriately to patients with new gastrointestinal symptoms after radiotherapy, can identify the underlying causes of new-onset symptoms. Starting treatment without knowing the cause of the symptom is commonly ineffective because prediction of the combination of treatments needed is difficult. Evidence suggests that many patients have unusual but highly treatable malfunctions of gastrointestinal physiology, which if correctly diagnosed may enable a patient with difficult symptoms to be helped.

Introduction

Researchers have investigated the effects of radiotherapy on some of the complex neurological, hormonal, muscular, immune, and enzyme functions of the human gastrointestinal tract, although definitive studies are few. Almost all information about the cellular and molecular response of the gastrointestinal tract to radiotherapy is derived from animal experiments. However, the relevance of animal studies is unclear because different animals respond to identical irradiation differently and because the doses delivered might not be comparable to those given to humans.

The available data suggest a sequelae of events where oedema progresses to an inflammatory, mainly mucosal, reaction that later extends to the submucosa. These events stimulate regenerative processes, which either induce mucosal repair or develop into severe inflammation with ulceration, finally producing fibrosis. These changes are mediated by a cytokine cascade, which might persist for decades.

Most patients starting pelvic radiotherapy will have normal gastrointestinal function apart from local tumour effects. During radiotherapy, normal tissues that surround the tumour will be exposed to some radiation (figure 1). The rectum and sigmoid are in close physical proximity to the tumour being treated and are at particular risk. The caecum is fairly fixed and may receive a sizeable dose. The transverse colon and small bowel frequently loop down into the pelvis and are at risk, so too is the proximal small bowel and pancreas when para-aortic nodes are irradiated.

Injury to the gastrointestinal tract depends on the type of radiotherapy given, the dose delivered to tissues, the way it is delivered, and how radiation energy dissipates through tissues. Specific doses that lead to an unacceptable risk of macroscopic pathological change in different parts of the gastrointestinal tract are well established. However, neither the doses of radiotherapy that will lead to permanent changes in gastrointestinal physiology, nor which patients are excessively sensitive to radiotherapy because of abnormal DNA-repair genes, are known. Furthermore, smoking; previous abdominal surgery; concomitant chemotherapy; and disorders such as diabetes, hypertension, pelvic inflammatory disease, HIV, connective-tissue disorders, and inflammatory bowel disease may increase the risk of acute and chronic problems after pelvic radiotherapy. There are no adequate data for the degree of risk posed by any of these factors.

The hypothesis underlying this review is that symptoms arise after pelvic radiotherapy because of changes to normal gastrointestinal physiology that are induced by radiotherapy. Although at present pathological changes caused by radiotherapy cannot be reversed, there is no reason why symptoms cannot be treated through identification and correction of physiological deficits that are induced by pathological changes. Here, I will discuss the changes induced in gastrointestinal physiology after pelvic radiotherapy, what symptoms these cause, and possible treatments for these acquired disorders of physiology. I aim to challenge clinicians to adopt a more-positive approach to the management of gastrointestinal symptoms that start after pelvic radiotherapy.

Section snippets

Acute and chronic symptoms

Acute changes in gastrointestinal physiology can occur in any part of the gastrointestinal tract that is exposed to radiotherapy. Some changes may lead to clinical symptoms; others remain subclinical.1 Symptoms tend to start during the second week of treatment (when histological change is probably at a maximum) and peak by the fourth to fifth week (when histological changes are stable or improving).2

Chronic radiation-induced toxic effects are substantially more common than generally recognised.

Loose stool or diarrhoea

Although psychological factors may contribute to episodes of loose stool after pelvic radiotherapy, specific physiological problems can commonly be defined, including small-bowel bacterial overgrowth, bile-salt malabsorption, carbohydrate malabsorption, changes in transit, development of strictures, neoplasia, or new-onset primary inflammatory bowel disease.

Conclusion

In the past few decades, oncology research has focused on improving patient response and survival, and therefore adequate attention has not been paid to the long-term effects of treatment. To expect oncologists to have the expertise to manage all side-effects of cancer treatment is unreasonable, but they can enhance patient quality of life by identifying long-term problems that arise as a result of treatment—especially now that cancer treatment is increasingly effective and that many patients

Search strategy and selection criteria

A search of the original published work from 1996 to 2007 was done by use of MEDLINE and EMBASE databases. Search terms included: “lactose intolerance”, “disaccharide malabsorption”, “diarrhoea”, “steatorrhoea”, “bile salt malabsorption”, “bacterial overgrowth”, “faecal incontinence”, “pancreatic insufficiency”, “gastrointestinal bleeding”, “argon”, “formalin”, “radiation proctitis OR proctopathy”, “radiation colitis OR colopathy”, “radiation enteritis OR enteropathy”, “prostate”,

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