Article Text
Abstract
Background A recent randomised trial suggested that an algorithmic approach to investigating and managing gastrointestinal symptoms of pelvic radiation disease (PRD) is beneficial and that specially trained nurses can manage patients as effectively as a gastroenterologist.
Aims The aim of the development and peer review of the guide was to make the algorithm used in the trial accessible to all levels of clinician.
Methods Experts who manage patients with PRD were asked to review the guide, rating each section for agreement with the recommended measures and suggesting amendments if necessary. Specific comments were discussed and incorporated as appropriate, and this process was repeated for a second round of review.
Results 34 gastroenterologists, 10 nurses, 9 dietitians, 7 surgeons and 5 clinical oncologists participated in round one. Consensus (defined prospectively as 60% or more panellists selecting ‘strongly agree’ or ‘agree’) was reached for 27 of the original 28 sections in the guide, with a median of 75% of panellists agreeing with each section. 86% of panellists agreed that the guide was acceptable for publication or acceptable with minor revisions. 55 of the original 65 panellists participated in round two. 89% agreed it was acceptable for publication after the first revision. Further minor amendments were made in response to round two.
Conclusions Development of the guide in response to feedback included
▸ improvement of occasional algorithmic steps
▸ a more user-friendly layout
▸ clearer timeframes for referral to other teams
▸ expansion of reference list
▸ addition of procedures to the appendix.
- RADIATION ENTERITIS
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Introduction
This guide is designed mainly to aid clinical nurse specialists looking after patients with pelvic radiation disease (PRD) working in conjunction with a gastroenterologist. However, it might also help general practitioners and generalists in investigating and treating the gastrointestinal symptoms of patients following pelvic radiotherapy.
This guide defines best practice although not every investigation modality or treatment will be available in every trust.
Those using the guide, especially if non-medically qualified, should identify a senior gastroenterologist or other appropriately qualified and experienced professionals whom they can approach easily for advice if they are practising in an unsupervised clinic.
Practitioners should not use this guide outside the scope of their competency and must identify from whom they will seek advice about abnormal test results, which they do not fully understand before they start using the guide.
Where it is stated that ‘this is an emergency’, the user of this guide must discuss the issue with a suitably qualified person for immediate action.
Managing patients with PRD requires a different approach to those with other forms of bowel pathology. The guide also identifies test findings that may indicate that the underlying situation is potentially serious and that advice needs to be sought urgently.
Specific therapies are usually not listed by name but as a ‘class’ of potential drugs as different clinicians may have local constraints or preferences as to the medications available.
Important principles to consider when using the algorithms are
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Patients may have up to 22 gastrointestinal (GI) symptoms after pelvic radiotherapy simultaneously.
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Each symptom may have more than one cause.
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Symptoms must be investigated systematically, otherwise causes may be missed.
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Arranging all investigations at the first consultation reduces follow-up and allows directed treatment at all causes for symptoms at the earliest opportunity.
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Patients who have had radiotherapy need a different approach to patients who have GI symptoms for other reasons.
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Specialist centres only very rarely reach a new diagnosis of ‘irritable bowel syndrome’ in this patient group.
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Endoscopic or surgical intervention in tissues exposed to radiotherapy carries increased risk of serious complications.
This guide has three parts:
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Introduction, guide to blood tests, how to use the algorithm and taking a history.
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An algorithm detailing the individual investigation and treatment of each of the 22 symptoms identified as particularly relevant to this patient group.
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A brief description of the diagnosis, treatment and management techniques of common conditions found in patients with PRD.
Guideline for blood tests used within the guide⇓⇓⇓
How to use the algorithm
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Identify the symptoms by systematic history taking.
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Examine the patient appropriately.
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Use the algorithm to plan investigations for troublesome/severe symptoms.
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Most patients have more than one symptom and so investigations need to be requested for each symptom.
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Usually all investigations are ordered at the same time and the patient reviewed with all the results.
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When investigations should be ordered sequentially, the algorithm indicates this by stating first line, second line, etc.
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Treatment options are generally offered sequentially but clinical judgement should be used.
Taking an appropriate history
Patients cannot be helped without an accurate history being taken.
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Taking a history of GI symptoms is a skill that must be learnt.
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Tools such as a Bristol Stool Chart can often clarify exactly what patients mean.
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Specialist units find that symptom questionnaires completed by the patient before the consultation often help clarify which issues are really troubling the patient.
Taking a history needs to elicit:
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What was bowel function like before the cancer emerged?
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How have the symptoms changed over time?
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Are key features indicative of reversible underlying pathology present, for example,
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Steatorrhoea?
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Nocturnal waking to defecate?
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Rapid progressive worsening of symptoms?
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Rapid weight loss?
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Has the patient noticed any masses?
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Patients and clinicians alike often miss the presence of intermittent steatorrhoea—ask:
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Is there an oily film in the lavatory water?
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Is the stool ever pale/putty-like/foul smelling/difficult to flush/floating?
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A very clear definition of what a patient means when they use specific terms—for example, ‘diarrhoea’/‘loose stool’—what type on the Bristol Stool Chart?; ‘frequency’—true bowel opening or tenesmus and incomplete evacuation?
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Is there a consistent impact of a specific component of diet on their symptoms, especially
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Fibre: how much are they eating—too much/too little?
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Fat: does this promote type 6–7 stool/steatorrhoea?
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Lactose-containing foods?
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Gluten-containing foods?
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Alcohol intake?
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Is there an association between the start of specific medication or increase in its dose and their symptoms—for example, metformin, proton pump inhibitor, β-blockers?
GI symptoms
Bleeding (rectal): bright red ± clots⇓
Bleeding (rectal): dark bleeding⇓
Bloating/abdominal cramps⇓
Borborygmi
(A rumbling/gurgling noise produced by the movement of fluid or gas through the intestine)⇓
Constipation/difficulty evacuating rectum⇓
Diarrhoea (stool type 6–7 Bristol Stool Chart)
Also use this section if patient has ‘frequency of defecation’, ‘nocturnal defecation’ or ‘urgency of defecation’⇓
Flatulence (oral—burping)⇓
Flatulence (rectal)⇓
Loss of sensation
(Unable to discriminate between need to defecate and pass urine)⇓
Mucus discharge⇓
Nausea and vomiting⇓
Pain (abdominal)⇓
Pain (back—new onset)⇓
Pain (anal/perianal/rectal): typical proctalgia fugax
(A sudden, severe pain in the anorectal region lasting less than 20 min, resolving spontaneously)⇓
Pain (anal/perianal/rectal): related to defecation⇓
Pruritus (perianal)⇓
Tenesmus
(a feeling of constantly needing to pass stools, despite an empty rectum) ⇓
Weight loss (unexplained)⇓
Acknowledgments
We sincerely thank the following experts who participated in the Delphi process and read and provided detailed feedback on this algorithm: Dr Ang Yeng, Mr Anthony Antoniou, Mrs Sharon Becker, Mr Neil Borley, Dr Stuart Cairns, Miss Helen Chave, Professor Susan Clark, Dr Susan Cleator, Dr Sue Cullen, Dr Tina Diggory, Dr NC Direkze, Ms Mhairi Donald, Dr Clare Donnellan, Dr Roland Ede, Dr Birgitte-Elise Grinde Emken, Ms Andreia Fernandes, Mr Nader Francis, Dr Lorenzo Fuccio, Dr Simon Gabe, Mrs Claire Gill, Mrs Loraine Gillespie, Dr Stephen Gore, Dr John Green, Dr Caroline Henson, Ms Linda Hill, Dr Barbara Hoeroldt, Ms Lynn Holmes, Mr Terry Irwin, Mr John (Ian) Jenkins, Mrs Penny Kaye, Dr Mark Kelly, Dr Simon Lal, Dr Susan Lalondrelle, Dr Jimmy K Limdi, Ms Michelle McTaggart, Dr Tracie Miles, Dr Michael Mitchell, Ms Kassandra Montanheiro, Dr A Frank Muller, Dr Andrew Murdock, Dr Penny Neild, Dr John O'Malley, Dr Parth Paskaran, Professor David Rampton, Dr Jeremy Shearman, Dr Norma Sidek, Ms Ramani Sitamvaram, Dr John Staffurth, Dr Alexandra Stewart, Dr Sreedhar Subramanian, Dr Claire Taylor, Dr Kathy Teahon, Dr Jeff Turner, Mrs Julie Walker, Dr Sean Weaver, Ms Sarah Wemyss, Dr Mark Wilkinson, Miss Natalie Wilkinson, Mrs Tracy Wood, Dr Jeremy Woodward. We would like to thank Dr Claire Dearden, Dr Mohid Khan and Dr Daniel Morganstein for additional helpful input into this document. We are very grateful to Barbara E. Benton for help with maintaining the integrity of early drafts of this guide.
Appendix:
Common conditions in this group
Bile acid malabsorption (BAM)
Exocrine pancreatic insufficiency (EPI)
Carbohydrate malabsorption—for example, lactose or other disaccharide intolerance
Pelvic floor dysfunction
Small intestinal bacterial overgrowth (SIBO)
Bile acid malabsorption
Definition
BAM is a defect in the enterohepatic circulation of bile acids. Two types of BAM exist: ileal dysfunction whereby the ability to absorb bile acids in the terminal ileum is impaired and secondly, hepatic overproduction that overwhelms terminal ileal absorption capacity.1 Bile is secreted by the liver in direct response to the amount of ingested dietary fat.
Common causes:
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High dose chemotherapy
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Ileal disease/resection
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Upper GI resectional surgery including cholecystectomy
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Pancreatic disease
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Pelvic radiotherapy
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Idiopathic
Diagnosis:
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SeHCAT scan
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C4 blood test
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Trial of bile acid sequestrant
Severity scores of BAM
7 day SeHCAT retention BAM status⇓
Treatment options include
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dietary fat reduction
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antidiarrhoeal medication
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bile acid sequestrant
Options 1 and 2 may be useful in mild BAM. Generally bile acid sequestrants are required for moderate BAM. For severe BAM developing after radiotherapy, most patients need a bile acid sequestrant and advice about long-term reduction in dietary fat intake.2
Drugs that may be helpful include aluminium hydroxide, budesonide, colesevelam, colestipol and colestyramine.
Patients with steatorrhoea usually require colesevelam.
If dietary intervention is required, advice to reduce dietary fat intake to 20% of total calories can be useful but requires dietetic expertise, patient education and supportive literature.
Many patients with moderate/severe BAM will be deficient in trace elements and fat-soluble vitamins. These should be checked periodically and supplemented as appropriate.
Exocrine pancreatic insufficiency
Definition
EPI is the inadequate production and secretion of pancreatic enzymes and may occur after pelvic radiotherapy with para-aortic lymph node irradiation.3 ,4
Diagnosis:
Non-liquid stool sample for faecal elastase measurement (<200 μg FE1 per 1 g stool)—N.B. Falsely low readings may be present in patients with small bowel bacterial overgrowth.
Clinical response to pancreatic replacement.
Treatment:
Pancreatic enzyme replacement therapy: requires equivalent of 150 000 international units Creon (Abbott Healthcare Products Limited, Southampton, UK) per day.
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Optimal 30–50 000 units with each meal, 10–30 000 units with drinks and snacks, depending on size of snack.
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Consider long-term multivitamin and trace element supplementation.
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Occasionally dietary advice is also required to optimise bowel function.
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Occasionally addition of proton pump inhibitor is required to reduce loss of replacement enzymes by gastric acid.
Long-term management:
Ongoing treatment with pancreatic enzyme replacement medication.
Carbohydrate malabsorption—for example, lactose or other disaccharide intolerances
Definition
Intolerance occurs from the inability to digest carbohydrates. Lactose, a component of milk and some other dairy products, is the intolerance most frequently recognised. It is due to lack of the enzyme lactase in the small intestine. Primary hypolactasia affects 70% of the world's population. Lactose or other disaccharide or monosaccharide malabsorption (eg, fructose) may occur de novo during cancer therapies (such as 5-FU chemotherapy or radiotherapy) due to damage to brush border enzymes and in some patients persists long term.5 ,6
Diagnosis of carbohydrate intolerance:
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Trial of exclusion of products containing that specific carbohydrate in diet for 1 week. Patient to keep a record of symptoms before and during the exclusion.
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Specific carbohydrate breath test. Duodenal biopsies and assessment for the specific disaccharide or monosaccharide activity.
Treatment:
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Long-term exclusion of products containing the carbohydrate in diet.
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Dietitian assessment to ensure diet remains balanced. With lactose intolerance special attention should be paid to calcium intake. Other bone health risk factors should also be considered and vitamin and mineral supplementation started as appropriate.5
Pelvic floor dysfunction
Definition
Symptoms of pelvic floor dysfunction include urinary incontinence, bladder storage problems, altered bladder sensation, voiding and post micturition problems, anorectal symptoms, pelvic pain, sexual difficulties and pelvic organ prolapse (in females). Anorectal symptoms can include faecal incontinence, flatal incontinence, faecal urgency, straining to defecate, tenesmus, diminished rectal sensation, constipation, rectal prolapse, rectal bleeding and mucus discharge.7
Diagnosis:
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rectal examination (sphincter tone and squeeze)
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endo-anal ultrasound
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anorectal physiology investigations:
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anal resting pressure
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sphincter muscle squeeze
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15 s squeeze
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rectal sensitivity to rectal distension
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Treatment:
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pelvic floor exercises (page 18)
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toileting posture exercises (page 18)
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biofeedback (page 18)
A contributing factor is often constipation and a non-fermentable stool bulking agent such as Normacol can be helpful to restore rectal volume and is less likely to cause flatulence than other fibre supplements.
Small intestinal bacterial overgrowth
Definition
SIBO is the presence of excessive bacteria in the small intestine. Small bowel bacterial overgrowth occurs in 25% of patients during the acute phase of radiotherapy and is a cause of diarrhoea in up to 15% of patients after radiotherapy.5 ,8 ,9
Diagnosis10:
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There is no gold standard for diagnosing SIBO.
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Glucose hydrogen/methane breath testing ± duodenal (D2) aspirate via upper GI endoscopy.
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RBC folate and total serum bile acid levels may be elevated and vitamin B12 levels and faecal elastase may be low.
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10–15% patients with negative tests still have SIBO.11
Suggested antibiotic treatment options if no growth on culture to direct treatment
7–10 days treatment with
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Ciprofloxacin 500 mg bd
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Doxycycline 200 mg day 1, 100 mg days 2–7/10
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Clarithromycin 500 mg bd
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Metronidazole 400 mg tds
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Rifaximin 550 mg bd
Symptoms can recur any time after antibiotics are stopped because the underlying cause of bacterial overgrowth cannot always be addressed. If symptoms return, repeat treatment with antibiotics for a few days every month or continually at the lowest effective dose may be helpful in managing symptoms long term. Some clinicians recommend rotating antibiotics, but this may not be effective if the organisms involved are not sensitive to the antibiotics used.
Treatment decisions should be individualised and consider the risks of long-term antibiotic therapy such as Clostridium difficile infection, cumulative irreversible neuropathy with metronidazole, Achilles tendon rupture with ciprofloxacin, intolerance, side effects, bacterial resistance and costs.8–11
Appendix:
Management techniques
Written information is often helpful to supplement the management of specific diagnoses. If information sheets are not available locally, information sheets on the following can be obtained from Dr Andreyev's office at The Royal Marsden (+44 (0)20 7811 8216):
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advice for those with constipation or who often need to strain
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having a SeHCAT scan
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having a glucose hydrogen/methane breath test
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pancreatic insufficiency.
Specific leaflets are also available on the following treatments:
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lactose free diet
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managing fibre in your diet
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taking antidiarrhoeal medication
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taking colesevelam
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taking loperamide
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taking Normacol
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treatment of radiation-induced gastrointestinal bleeding.
Dietary fibre manipulation
The mean UK average consumption of non-starch polysaccharides for healthy adults (aged 19–64 years) is 14.9 g/day for men and 12.8 g/day for women.12 The current dietary recommended daily intake for fibre—18 g non-starch polysaccharides per day—is based on the effect that total dietary fibre has on stool weight. The rationale for this is that daily stool output of <100 g/day is associated with a non-starch polysaccharides intake of below 12 g/day and with an increased risk of bowel disease. In healthy populations, increasing non-starch polysaccharides intake from 13 to 18 g/day is associated with a 25% increase in stool weight. Some patients after pelvic radiotherapy cannot tolerate as much fibre as this.
Reduction in soluble dietary fibre intake can be helpful when patients complain of any of the following symptoms: bloating, constipation, bowel obstruction, diarrhoea, rectal flatulence, mucus discharge and abdominal pain and may require help from a dietitian.12–14
Biofeedback
Biofeedback is widely regarded as a useful, non-invasive treatment in constipation, evacuatory disorders and faecal incontinence. Biofeedback is a behavioural approach to which there are no side effects and offers a non-surgical approach for patients with bowel dysfunction. It includes toileting exercises and pelvic floor exercises.15 ,16
Biofeedback services are available locally around the UK.
Pelvic floor exercises
The pelvic floor muscles include the levator ani, the coccygeus and associated connective tissue and, if weakened, can cause several symptoms associated with pelvic floor dysfunction (page 17). Exercises can strengthen the pelvic muscles so that they give support and are better coordinated. Pelvic floor exercises can improve problems with urinary incontinence, faecal incontinence or leakage and sexual function.17 ,18
Technique:
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Sit, stand or lie with your knees slightly apart. Tighten and pull up your bottom muscles as tightly as you can. Hold for at least 5 s and then relax for at least 10 s. Repeat at least five times. This will work on the strength of your muscles.
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Next, pull the muscles up to about half of their maximum squeeze. See how long you can hold this for. Then relax for at least 10 s. Repeat at least five times. This will work on the endurance or staying power of your muscles and will improve their coordination.
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Pull up the muscles as quickly and tightly as you can and then relax and then pull up again, and see how many times you can do this before you get tired. Try for at least five quick pull-ups.
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Repeat exercises 1, 2 and 3 at least 10 times every day.
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As the muscles get stronger, you will find that you can hold for longer than 5 s, and that you can do more pull-ups each time without the muscle getting tired.
Patient information:
Toilet posture exercises
Adopting the correct position on the lavatory can improve constipation and ease evacuation difficulties together with pelvic floor exercises.19⇓
Technique
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Sitting on the toilet, lean forward with the forearms resting on your thighs and raise your feet 8–10 inches off the floor.
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Relax and lower the shoulders. Breathe slowly, regularly and gently—do not hold your breath as this will encourage straining. Try and stay as relaxed as possible
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Try and brace your abdominal muscles. This is best done by putting your hands on your waist. Expand your waist and feel your hands being pushed out sideways. Concentrate on relaxing your anus to allow the stool to pass. Only push down from above once your anus is relaxed.
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Relax very slightly for 1 s maintaining pressure but without the push.
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Then brace outwards and push down again.
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Repeat steps 1–5.
Advise the patient to be careful to relax and use the correct technique, not to spend endless time in the toilet and not to strain—try again the next day. Excessive straining uses the wrong muscles and does not help the evacuating process.
Treating bleeding telangiectasia
Radiation-induced bleeding typically starts 6–12 months after radiotherapy, is at its worse 4 years after the end of radiotherapy and has disappeared by 8–10 years.
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Investigate with flexible endoscopy to determine the cause of the bleeding.
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Optimise bowel function and stool consistency.
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If bleeding is not staining clothes, causing anaemia or interfering with daily activities, reassure and do nothing.
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If bleeding affects quality of life, stop anticoagulants if possible and consider sucralfate enemas ± metronidazole 400 mg tds for 4 weeks.
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Discuss definitive treatment to ablate the telangiectasia:
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Hyperbaric oxygen therapy: Advantages: supported by RCT evidence, may improve other symptoms, for example, urinary; disadvantages: time consuming (8 weeks of daily treatment), expensive and patients may need to travel long distances to their nearest unit.
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Any thermal therapy (eg, APC): Advantages: easily available and simple; disadvantages: significant risk of non-healing ulceration/perforation as the tissue is ischaemic and unproven efficacy in heavy bleeding. Absolutely contraindicated in patients treated with brachytherapy. If used, the bowel must be fully prepared (as for colonoscopy).
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Formalin therapy: Advantages: simple to perform; disadvantages: long-term outcomes poorly known, small risks of serum sickness, severe proctitis or chemical burn to the skin if there is spillage.
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Using intrarectal formalin for radiation induced telangiectasia
Formalin chemically cauterises by hydrolysing protein and superficially coagulating the tissue. In general, the procedure seems to be effective, safe, well tolerated by the patient, inexpensive and technically simple. The use of intrarectal formalin for radiation-induced bleeding is contraindicated if the rectal mucosa is ulcerated.8 ,20–23
Preparation:
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Prepare the bowel as for colonoscopy with full bowel preparation.
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Use a gastroscope not a colonoscope.
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30–35 mL of 5% formalin is usually sufficient to cover the telangiectasia.
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Initial instillation of saline can help assess how much formalin will be required.
Technique:
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Patient position: prone.
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Instil the formalin through a catheter passed through the gastroscope channel into the rectum.
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Apply with wet cloths and continued pressure to the perianal area to prevent leakage of formalin during the procedure (by endoscopy nurse).
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Keep the gastroscope in place during the procedure.
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Leave the formalin in the rectum for 3 min exactly.
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Then remove the formalin with copious washes of water.
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Continue the perianal pressure/pads until all of the rectal formalin removed.
Considerations after treatment:
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Advise patients they may not notice any improvement in bleeding for 1–2 weeks.
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Consider the use sucralfate enemas for 2–3 weeks twice daily to help healing.
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Consider retreating if necessary 6–8 weeks later and repeat if necessary a third time after a further 6–8 weeks.
How to refer for hyperbaric oxygen therapy
Hyperbaric oxygen for radiation-induced damage requires a funding application to the Specialised Commissioning Group. The local hyperbaric oxygen unit and the referring clinician need to fill in the application jointly.8
Hyperbaric units that provide medically supervised hyperbaric oxygen therapy with the correct pressures believed to be useful for treating radiation injury are only found at the following centres:
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DDRC Hyperbaric Medical Centre, Tamar Science Park, Plymouth
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James Paget Hospital, Great Yarmouth
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Midlands Diving Chamber, Hospital of St Cross, Rugby
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Spire Hospital, Cardiff
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Spire Hull and East Riding Hospital, Hull
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Spire Murrayfield Hospital, Wirral
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St John and Elizabeth Hospital, North London
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St Richards Hospital, Chichester
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Whipps Cross Hospital, East London
There is no evidence at all that non-medically supervised hyperbaric oxygen therapy as provided by MS treatment centres is of any benefit for treating radiation-induced toxicity.
Sucralfate enemas
Sucralfate forms a mechanical protective layer over radiation-induced telangiectasia and improves healing.
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Use 2 g (10 mL) sucralfate suspension (1 g in 5 mL) made up to 50 mL using warm tap water in a bladder syringe.
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Attach a soft, lubricated Foley catheter to the syringe.
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The patient should insert the catheter gently into their rectum and instil the enema twice a day until the bleeding has stopped.
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The enema should be held in the rectum as long as possible.
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The patient should roll over at least once to coat the entire rectum but spend the majority of the time lying prone so the solution treats the anterior rectal wall.
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Long-term once-daily enemas may help prevent the bleeding recurring.
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If bleeding starts again, go back to using sucralfate enemas twice a day.
Perianal skin care
Radiotherapy skin reactions may present as skin irritation, erythema and ulceration and atrophy of the skin within the radiotherapy field that may be worsened by enzymes present in faecal fluid when incontinent or leaking.
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Keep skin dry
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Keep skin free of faeces
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Prevent the development of perianal dermatitis by:
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Use ‘simple’ soap or ‘Dove Sensitive’ soap that will not affect the pH of the skin (normally 5.5). Regular soap has a pH of nine and can disrupt the skin pH, which inhibits the growth of bacteria and thus increases dermatitis.
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1. Treating the underlying cause:
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Use a skin barrier: cream or film.
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Please note whether the patient has any allergies to any of the constituents.
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If the skin is damaged, Cavilon No Sting Barrier Film (3M, Loughborough, UK) or Epaderm (Molnlycke Health Care Group, Dunstable, UK) can be very useful.
-
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Consider the use of antifungal creams or corticosteroids (for a short period only).
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Consider referral for specialist dermatology assessment and advice.
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Patient information:
http://www.stmarkshospital.org.uk/patientinformation-leaflets
Using prokinetics
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Erythromycin: largely ineffective after 4–8 weeks through tachyphylaxis. Recommended dose 250 mg bd as a syrup 30 min before food.
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Domperidone: no tachyphylaxis for 8 weeks, may occur after longer use. Recommended dose 10 mg qds 30 min before food as a syrup orally or 30 mg qds as a rectal suppository. Increased risk of cardiac arrhythmia.
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Metoclopramide: risk of tardive dyskinesia with use >3 months.
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Naloxone by subcutaneous infusion.
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Paroxetine that stimulates SI motility only.
How to perform a duodenal aspirate
Treatment:
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Flush 100 mL of sterile saline into the duodenum via the endoscope channel.
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Follow this by 20 mL of air to ensure no saline remains in the endoscope channel.
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Turn down the suction.
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Leave the fluid to equilibrate with the duodenal contents for 10–20 s.
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Aspirate 20 mL of fluid into a sterile trap.
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Send the duodenal aspirate sample directly to microbiology.
References
Footnotes
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Contributors All authors contributed to the study design. Algorithm development was performed by HJNA, ACM, CN and JOL. Guarantor of the article: HJNA.
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Funding This study was undertaken at The Royal Marsden NHS Foundation Trust that received a proportion of its funding from the NHS Executive. We acknowledge NHS funding to the NIHR Biomedical Research Centre. Some of the work compiling this guide was facilitated by funding received from Macmillan Cancer Support.
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Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.