A Lalji

Effectiveness and tolerability of colesevelam hydrochloride for bile-acid malabsorption in patients with cancer: a retrospective chart review and patient questionnaire.

BACKGROUND Commercially available bile-acid sequestrants are not well tolerated by >80% of patients. OBJECTIVE The aim of the present study was to assess the effectiveness and tolerability of colesevelam hydrochloride in patients who developed bile-acid malabsorption after cancer therapy. METHODS The present study comprised 2 parts: a retrospective chart review of the electronic patient records and a patient questionnaire assessing outcome measures. All patients included in this study had a diagnosis of cancer and were being followed up in a cancer clinic at The Royal Marsden Hospital. In addition, all had symptoms of bile-acid malabsorption for >3 months and had been prescribed colesevelam in the gastroenterology clinic at the hospital. The electronic records of patients who were prescribed colesevelam between 2004 and 2007 were obtained from the hospital pharmacy. Those patients who were prescribed colesevelam and did not take any of the prescribed medication or did not return for a follow-up clinical review were excluded. To help further assess outcomes, a questionnaire was mailed to patients who were still residing in the United Kingdom, were not terminally ill, and were not lost to follow-up. The questionnaire comprised questions that assessed medication history (ie, whether patients were still taking colesevelam or not [and the reason for not taking colesevelam]), dosage, effectiveness for symptom relief, and adverse events. RESULTS In total, 45 patients (37 women and 8 men; median age, 58 years [range, 32-89 years]) who received treatment with colesevelam between 2004 and 2007 were included. Of these, 36 were sent a questionnaire and 30 responded. Identifiable causes of bile acid malabsorption in this sample population were pelvic radiotherapy (n = 29), small-bowel resection (12), upper gastrointestinal surgery (2), high-dose chemotherapy (1), and new-onset Crohns disease (1). Of these patients, 67% (30/45) had not previously responded to cholestyramine treatment, but following treatment with colesevelam, this group had a recorded improvement in: diarrhea, 83% (25/30); urgency of defecation, 74% (20/27); frequency of defecation, 72% (21/29); steatorrhea, 71% (12/17); abdominal pain, 68% (15/22); and fecal incontinence, 62% (13/21). Based on the medical chart review and the patient questionnaire, after colesevelam treatment, the following proportions of all 45 patients studied experienced improvement in symptoms: loose stool (diarrhea), 88% (medical chart) and 80% (questionnaire); frequency of defecation, 77% and 83%, respectively; steatorrhea, 76% and 80%; urgency of defecation, 76% and 80%; abdominal pain, 74% and 58%; and fecal incontinence, 69% and 74%. During the study period, 15 patients discontinued colesevelam: ineffectiveness, 5; adverse events, 5 (because >or=1 of the following: bloating, constipation, heartburn, abdominal pain, flatulence, or perianal soreness); and other reasons, 7 (too many tablets or tablets difficult to swallow [3]; symptoms resolved [2]; colesevelam replaced with another medication [1]; and lost to follow-up [1]). Sixty-seven percent (30/45) of patients continued using colesevelam for up to 4 years. CONCLUSION In view of the data found in this retrospective chart review and patient questionnaire, prospective, double-blind, placebo-controlled trials of colesevelam for bile acid malabsorption are warranted.

Evaluating the efficacy of statins and ACE-inhibitors in reducing gastrointestinal toxicity in patients receiving radiotherapy for pelvic malignancies

INTRODUCTION 3-Hydroxy-methylglutaryl coenzyme-a reductase inhibitors (statins) improve survival following pelvic irradiation for cancer. Large studies suggest that patients with hypertension may have reduced gastrointestinal (GI) toxicity. Animal data suggest that statins and ACE inhibitors (ACEi) may protect against normal tissue injury. Their efficacy in humans has not been reported. AIMS/METHODS To evaluate the impact of statins and ACEi on normal tissue toxicity during radical pelvic radiotherapy. GI symptomatology was recorded prospectively before radiotherapy, weekly during treatment and 1 year later using the inflammatory bowel disease questionnaire-bowel (IBDQ-B) subset. Cumulative acute toxicity (IBDQ-B AUC) and worst score were determined. Dose, brand and duration of statin and/or ACEi usage were obtained from General Practitioners. RESULTS Of 308 patients recruited, 237 had evaluable acute drug and toxicity data and 164 had data at 1year. Acutely, 38 patients (16%) were taking statins, 39 patients (16.5%) were taking ACEi and 18 patients (7.6%) were taking statin+ACEi. Mean changes in acute scores were 7.3 points (non-statin users), 7.3 (non-ACEi users) and 7.0 (non-statin+ACEi users) compared to 4.8 points (statin users), 5.0 points (ACEi users) and 4.9 points (statin+ACEi users). Statin use (p=0.04) and combined statin+ACEi use (p=0.008) were associated with reduced acute IBDQ-B AUC after controlling for baseline scores (ANOVA). At 1 year, users maintained higher IBDQ-B scores than non-users in all user subgroups. CONCLUSION Use of statin or statin+ACEi medication during radical pelvic radiotherapy significantly reduces acute gastrointestinal symptoms scores and also appears to provide longer-term sustained protection.

Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy

Gastrointestinal (GI) symptoms during and after cancer therapy can significantly affect quality of life and interfere with treatment. This study assessed whether bile acid malabsorption (BAM) or bile acid diarrhoea (BAD) are important causes of diarrhoea associated with cancer treatment.

The holistic management of consequences of cancer treatment by a gastrointestinal and nutrition team: a financially viable approach to an enormous problem?

There is no national NHS tariff to fund services for patients experiencing long-term bowel and nutritional problems after cancer treatment. In this paper, we report the clinical characteristics and outcomes of patients referred to our service and the estimated cost of a completed episode of care. Patient characteristics, symptom severity, investigations, diagnoses, number of clinic visits and referrals elsewhere were recorded in a prospective cohort study. During 2013-14, 325 patients completed assessment and treatment. The majority of original cancer diagnoses were urological (43%) and gynaecological (21%). A median of six investigations were requested. 62% were found to have three or more new diagnoses including small intestinal bacterial overgrowth (46%), vitamin D deficiency (38%), bile acid malabsorption (28%), gastritis (22%), radiation-induced bleeding (20%), vitamin B12 deficiency (17%), pelvic floor weakness (17%), colorectal polyps (13%) and pancreatic insufficiency (5%). A median of three visits were required and all commonly reported gastrointestinal symptoms improved by discharge. The mean episode of care per patient was costed at £1,563. Effective amelioration of chronic gastrointestinal toxicity after cancer treatment costs substantially less than treating the cancer in the first place and requires an NHS tariff.

Clinical trial: efficacy of a low or modified fat diet for the prevention of gastrointestinal toxicity in patients receiving radiotherapy treatment for pelvic malignancies

BACKGROUND Inflammatory responses to pelvic radiotherapy can result in severe changes to normal gastrointestinal function with potentially severe long-term effects. Reduced or modified fat diets may confer benefit. METHODS This randomised controlled trial recruited patients with gynaecological, urological or lower gastrointestinal malignancy due to receive radical radiotherapy. Patients were randomised to a low fat (20% total energy from long chain triglycerides), modified fat (20% from long chain triglycerides and 20% from medium chain triglycerides) or normal fat diet (40% total energy from long chain triglycerides). The primary outcome was a difference in change in Inflammatory Bowel Disease Questionnaire--Bowel (IBDQ-B) score, from the start to end of radiotherapy. RESULTS A total of 117 patients with pelvic tumours (48% urological; 32% gastrointestinal; 20% gynaecological), with mean (SD) age: 65 (11.0) years, male:female ratio: 79:38, were randomised. The mean (SE) fall in paired IBDQ-B score was -7.3 (0.9) points, indicating a worsening toxicity. Differences between groups were not significant: P = 0.914 (low versus modified fat), P = 0.793 (low versus normal fat) and P = 0.890 (modified versus normal fat). The difference in fat intake between low and normal fat groups was 29.5 g [1109 kJ (265 kcal)] amounting to 11% (of total energy intake) compared to the planned 20% differential. Full compliance with fat prescription was only 9% in the normal fat group compared to 93% in the low fat group. CONCLUSIONS A low or modified fat diet during pelvic radiotherapy did not improve gastrointestinal symptom scores compared to a normal fat intake. An inadequate differential in fat intake between the groups may have confounded the results.

Management of bile acid malabsorption using low-fat dietary interventions: a useful strategy applicable to some patients with diarrhoea-predominant irritable bowel syndrome?

This study evaluates the efficacy of low-fat dietary interventions in the management of gastrointestinal (GI) symptoms due to bile acid malabsorption. In total, 40 patients with GI symptoms and a 7-day (75)selenium homocholic acid taurine (SeHCAT) scan result of <20%, were prospectively recruited and then advised regarding a low-fat dietary intervention. Before and after dietary intervention, patients rated their GI symptoms using a 10-point numerical scale, and recorded their intake in 7-day dietary diaries. After dietary intervention, the median scores for all GI symptoms decreased, with a significant reduction for urgency, bloating, lack of control, bowel frequency (p ≥: 0.01). Mean dietary fat intake reduced to 42 g fat after intervention (p ≥: 0.01). Low-fat dietary interventions in patients with a SeHCAT scan result of <20% leads to clinically important improvement in GI symptoms and should be widely used.

The efficacy of a low-fat diet to manage the symptoms of bile acid malabsorption - outcomes in patients previously treated for cancer

ABSTRACT Dietary fat ingestion triggers bile secretion into the gastrointestinal tract. Bile acid malabsorption affects >1% of the population, causing loose stool and other gastrointestinal symptoms. The diagnosis is frequently missed. Treatments are often considered ineffective. We evaluated low-fat diets for managing gastrointestinal symptoms in these patients. All patients reporting type 6 or 7 stool were offered a selenium-75 homocholic acid taurine (SeHCAT) scan. Prospective data in patients with 7-day scan retention <20% were analysed. Patients requiring a bile acid sequestrant were given this before receiving dietary advice. Patients completed a 7-day food diary before dietetic consultations. Personalised dietary interventions, providing 20% of daily energy from fat, were prescribed. Symptoms were assessed using a modified gastrointestinal symptom rating scale questionnaire before and 4–12 weeks after dietary intervention. A total of 114 patients (49 male, median age 64 years, median body mass index 27 kg/m2) were evaluated. 44% of these patients were taking colesevelam. After dietary intervention, there was statistically significant improvement in abdominal pain and nocturnal defecation (0.2% alpha, p=0.001). Improvement in bowel frequency, urgency, flatulence, belching, borborygmi and stool consistency were seen, but did not reach statistical significance (p⩽0.004–0.031). Dietary intervention is an effective treatment option for patients with symptomatic bile acid malabsorption and should be routinely considered.

Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy

Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P < 0.001). The difference between groups in the change in IBDQ-B scores between the start and nadir was not significant (P = 0.093). However, the change in score between the start and end of radiotherapy was smaller in the high-fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT 01170299.

PTU-128 The efficacy of using low-fat dietary interventions to manage bile acid malabsorption

Introduction Dietary fat ingestion triggers bile secretion into the gastrointestinal (GI) tract. Bile acid diarrhoea (BAD) or malabsorption (BAM) affects 1%–2% of the population. Affected individuals suffer a wide range of GI symptoms in addition to loose stool. The diagnosis is often missed and treatments are often reported to be ineffective. In this study we used SEHCAT scanning to determine treatment options and evaluated the impact of low-fat diets on GI symptoms in these patients. Method This study analysed prospectively collected data in patients with 7 day 75selenium homocholic acid taurine (SeHCAT) scan retention <20%. All patients reporting type 6 or 7 stool were offered a SeHCAT scan. Patients with abnormal scans requiring a bile acid sequestrant were given this before receiving dietary advice. Patients completed a 7 day food diary before consultation with a registered dietitian and personalised low-fat dietary interventions, providing 20% of daily energy from fat were prescribed. Symptoms were assessed using a modified Gastrointestinal Symptom Rating Scale questionnaire before and 4–12 weeks after dietary intervention. Results Between January 2014 to March 2016, 114 patients, 49 men and 65 women, median age of 64 years, median BMI of 27 kg/m2 were evaluated. 50% had previously undergone GI surgery and 45% had additional GI disorders. 44% were taking Colesevelam. After dietary intervention, the frequency with which patients experienced GI symptoms decreased, with a significant reduction in troublesome urgency, flatulence, abdominal pain, nocturnal defaecation, belching and borborygmi (p≤0.01). Stool consistency and stool frequency also improved. Conclusion Dietary intervention is an effective treatment option for patients with symptomatic bile acid malabsorption/diarrhoea and should be routinely considered. The exact fat restriction which is effective, requires further study. Disclosure of Interest None Declared

Holistic needs assessment and care plans for women with gynaecological cancer: do they improve cancer-specific health-related quality of life? A randomised controlled trial using mixed methods

Objectives Holistic needs assessment (HNA) and care planning are proposed to address unmet needs of people treated for cancer. We tested whether HNA and care planning by an allied health professional improved cancer-specific quality of life for women following curative treatment for stage I–III gynaecological cancer. Methods Consecutive women were invited to participate in a randomised controlled study (HNA and care planning vs usual care) at a UK cancer centre. Data were collected by questionnaire at baseline, 3 and 6 months. The outcomes were 6-month change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (version 3), global score (primary) and, in EORTC subscales, generic quality of life and self-efficacy (secondary). The study was blinded for data management and analysis. Differences in outcomes were compared between groups. Health service utilisation and quality-adjusted life years (QALY) (from Short Form-6) were gathered for a cost-effectiveness analysis. Thematic analysis was used to interpret data from an exit interview. Results 150 women consented (75 per group); 10 undertook interviews. For 124 participants (61 intervention, 63 controls) with complete data, no statistically significant differences were seen between groups in the primary endpoint. The majority of those interviewed reported important personal gains they attributed to the intervention, which reflected trends to improvement seen in EORTC functional and symptom scales. Economic analysis suggests a 62% probability of cost-effectiveness at a £30 000/QALY threshold. Conclusion Care plan development with an allied health professional is cost-effective, acceptable and useful for some women treated for stage I–III gynaecological cancer. We recommend its introduction early in the pathway to support person-centred care.