Severe Bile Acid Malabsorption Research Articles

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre.

Simple SummaryBile acid malabsorption is a common albeit a very underdiagnosed gastroenterology condition especially in cancer cohort of patients. Our study, performed at the National leading centre for treatment of cancer, focuses on prevalence and management of bile acid malabsorption in patients reviewed in our specialized clinic. Currently, precise diagnosis and excellent treatments exist for this disease.The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019–January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 females, 66%) were diagnosed with BAM. Mean age was 59 +/− 12 years. The largest group were females with gynaecological cancer (35), followed by haematology group (15), colorectal/anal (13), prostate (9), upper gastrointestinal cancer (6), another previous malignancy (9). Severe BAM was most common in haematology (10/15; 67%) and gynaecological group (21/35; 60%). Medication and low-fat diet were commenced in 65/87 (75%), medication in 10/87 (11%), diet in 6/87 (7%). Colesevelam was used in 71/75 (95%). Symptoms improved in 74/87 (85%) patients. Vitamin D insufficiency/deficiency was diagnosed in 62/87 (71%), vitamin B12 deficiency in 39/87 (45%). BAM is a common condition in this cohort however treatments are highly effective.

TP1.2.1SeHCAT scan as an investigation for chronic diarrhoea; a single trust experience

Abstract Introduction: Recent published (British Society of Gastroenterology) guidelines strongly recommended investigating unexplained chronic loose stools with SeHCAT scans when available rather than empirical treatment. SeHCAT scan was introduced at our trust in 2015. We aimed to audit this locally. Methods All SeHCAT scans that were done at our trust trust from Jan 2015 to March 2020 were included. Patient demographics along with risk factors and duration of symptoms were documented as well as the referred speciality. Results 55 patients were identified. Average age at time of diagnosis was 50y (18-70y). M:F was 1:3.2 . Most scans were requested by the oncology team as part of the “pelvic radiotherapy late effects service” (n = 25), followed by the gastroenterology team (n = 22) and general surgery team (n = 8). The mean duration of symptoms was 4 years. 73% of the scans showed evidence of bile acid malabsorption (BAM) (n = 40) with bile retention <15%, with the majority of them (n = 30) having severe BAM (retention <5%). 60% of the patients had at least one lower GI endoscopy as part of their workup. The majority of patients were found to have type 3 BAM (n = 37). 60% of patients had symptom improvement on either diet alone or with bile-acid sequestrants (n = 23) and were discharged. Conclusion: SeHCAT scan is a useful test to investigate unexplained chronic diarrhoea. It is important to identify patients at risk of developing bile acid malabsorption. It is currently underutilized by our trust, which might be because of funding issues and awareness among clinicians.

New therapeutic options for bile acid malabsorption diarrhea

We have read with great interest the work published recently by Karhus et al . (1) where they describe the efficacy of the glucagon-like peptide-1 (GLP-1) agonist Liraglutide in two patients diagnosed with severe bile acid malabsorption (BAM) by causing a complete remission of symptoms.

Brief report: length of ileal resection correlates with severity of bile acid malabsorption in Crohn's disease.

Bile acid malabsorption (BAM) is a common cause of diarrhoea in Crohn's disease (CD) patients with ileal resection. BAM is usually diagnosed by selenium-labelled homotaurocholic acid test (75SeHCAT) but its availability is limited. Consequently, a large proportion of patients either remain undiagnosed or subject to empirical therapy. There is a paucity of studies examining the correlation between length of ileal resection and severity of BAM, which will be of use to clinicians with no recourse to diagnostic testing for BAM. We tested the correlation between length of resected ileum and percentage retention on 75SeHCAT of all CD patients with a prior surgical resection who underwent 75SeHCAT testing. Response to treatment with bile salt sequestrant and 75SeHCAT retention values was tested using Fisher's exact test. A total of 91 patients were identified with a median age of 47 (IQR 21-80). The median length of resected ileum was 24cm (range 15-165cm) with a median of 1 resection (range 1-4). Overall, 88 patients (97%) had 75SeHCAT retention values of < 10% and 85 (93%) had retention of < 5%. There was a modest correlation between 75SeHCAT retention and length of ileal resection (Spearman's rho - 0.392, P = 0.0001). Data on response to treatment was available for 57 (63%) patients, of who 38 (67%) responded to bile salt sequestrant. There was no difference in 75SeHCAT retention values between responders and non-responders. There was a modest correlation between length of ileal resection and severity of BAM as defined by 75SeHCAT retention values. Response to bile salt sequestrant therapy was not dependent on 75SeHCAT retention values.

PTH-087 Severity of Bile Acid Malabsorption Does Not Correlate with Length of Ileal Resection or Response to Bile Salt Sequestrant Therapy in Crohn’s Disease

Introduction Bile acid malabsorption (BAM) is a common cause of diarrhoea in Crohn’s disease (CD) patients with ileal resection and can lead to complications such as renal and biliary stone disease. BAM is usually diagnosed by selenium labelled homo-taurocholic acid test (75 SeHCAT) but its availability is limited. Thus, large proportions of resected CD patients either remain undiagnosed or subject to empirical therapy. There is a paucity of studies examining the correlation between length of ileal resection and severity of BAM which will be of particular use to clinicians with no recourse to diagnostic testing for BAM. Methods We identified all CD patients with a prior surgical resection who underwent 75 SeHCAT testing at our institute. Testing was based on the treating clinician’s discretion. The length of resected ileum was recorded from histopathology report. Correlation between length of resected ileum and percentage retention on 75 SeHCAT was assessed using a Spearman’s correlation test. Response to treatment with bile salt sequestrant and 75 SeHCAT retention values (using a cut point of 5%) was analysed using Fisher’s exact test. Results A total of 40 patients were identified with a mean age of 45 (SD±13), of which 6 (15%) were men. The median length of resected ileum was 22.8 cms (range 5.8–61.0 cms) with a median of 1 resection (range 1–4). Overall, 38 patients (95%) had 75 SeHCAT retention values of 5% and the remaining 18 (86%) had values Conclusion There was no correlation between length of ileal resection and severity of BAM as defined by 75 SeHCAT retention values. Response to bile salt sequestrant therapy was not dependent on 75 SeHCAT retention values though overall clinical response was good. Disclosure of Interest K. Lo: None Declared, H. Riyat: None Declared, Y. Prasad: None Declared, S. Subramanian Speaker bureau with: MSD, Abbvie, Shire, Ferring, Actavis, Conflict with: Advisory board Boehringer-Ingelheim, Vifor pharma, MSD, Abbvie, Shire

PTH-247 Modern pelvic chemoradiotherapy techniques continue to cause bile acid malabsorption: Abstract PTH-247 Table 1

Introduction During treatment with pelvic radiotherapy 80% of patients will develop diarrhoea. Patients with worse acute toxicity are at risk of developing more severe late bowel effects. It has previously been found that 44–57% of patients develop bile acid malabsorption (BAM) during pelvic radiotherapy. In the context of newer radiotherapy techniques, when there should be less small bowel exposure, we aimed to determine whether BAM remains a significant problem in this cohort of patients. Method This study was part of a trial evaluating the role of a gastrointestinal intervention for patients with cervical and bladder cancer receiving chemoradiotherapy. When patients developed lower gastrointestinal symptoms a SeHCAT scan was performed to detect BAM. Demographic and treatment data was recorded in the trial documentation. Results Twenty patients underwent a SeHCAT scan. Ten patients had cervical cancer and 10 had bladder cancer, of which 9 were male. All patients received 20 fractions of radiotherapy over 4 weeks. See table for full demographics. View this table: Abstract PTH-247 Table 1 Patient demographics SeHCAT was completed a median 25 days following the start of radiotherapy (28 days for cervix group, 24 days for bladder group). Overall the prevalence of BAM was 65% (13/20). SeHCAT was positive in 90% of the cervix group and 40% of the bladder group. Of the 13 patients who had BAM the prevalence of mild (7-day retention 10–15%), moderate (7-day retention 5–10%) and severe BAM (7-day retention <5%) were 23%, 31% and 46% respectively. There were no patients with 7-day retention of 15–20%. The median 7-day retention of all patients with BAM was 5% while for those without BAM it was 36%. Of the 4 patients who had VMAT (a newer technique), 3 had BAM suggesting that this technique is still strongly associated with small bowel effects. Conclusion Despite advances in radiotherapy techniques, we found a similar rate of BAM in this group compared to historical data. However the rate of BAM differed between the 2 patient groups suggesting that treatment factors may play a role and that these patient groups may not be homogeneous. Disclosure of interest K. White Grant/ Research Support from: This poster presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0211–10024. The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR or the Department of Health., C. Henson: None Declared, K. Jenner: None Declared, S. Burden: None Declared, S. Lal: None Declared, S. Davidson: None Declared, J. McLaughlin: None Declared.

OC-058 Bile Acid Malabsorption: “The Unusual Suspect”. A very Frequent Cause for Diarrhoea after Treatment for many different Cancer Types

Introduction Approximately 16,000 patients per year are left with a chronic change in bowel function and gastrointestinal symptoms following treatment for cancer. This can have a significant impact upon quality of life and even compromise on-going cancer therapy. Previous small studies focusing mainly on patients with gynaecological cancers suggest that bile acid malabsorption (BAM) may be an important cause of radiotherapy-induced diarrhoea. This retrospective study aims to elucidate the prevalence of BAM in patients referred to a specialist gastroenterology clinic which treats patients with consequences of cancer treatments. Methods Patients referred to our clinic are managed using a peer reviewed algorithm. If they report diarrhoea, defined as Bristol Stool Chart type 6–7, a routine referral for a SeHCAT (75-selenium homocholic acid taurine) scan is made to exclude BAM. BAM is diagnosed when the SeHCAT 7 day retention is Results Between 2009–2012, 262 patients were referred for a SeHCAT scan. 139 (53.1%) were male (median age 66, range 32–89) and 123 (46.9%) female (median age 61, range 20–86). 79 (37%) patients had been treated for gynaecological, 94 (44%) for urological, 41 (19%) for anorectal and 30 (11%) for upper gastrointestinal tract cancers. A further 18 (7%) were treated for other cancer types (breast, lung and haematological). BAM was diagnosed in 24 patients (25%) treated for urological cancers, with 17% (n = 4) having severe BAM. 46 patients (58%) treated for gynaecological cancers had BAM, severe in 57% (n = 26). BAM was diagnosed in 22 patients (54%) treated for anorectal cancers, with 55% having severe BAM (n = 12). In 15 patients (50%) treated for upper GI cancers, the majority (73%) had severe BAM (n = 11). For patients with other cancer types, BAM was diagnosed in 8 patients (44%) with severe BAM in 2 of these (25%). Conclusion The frequency of severe bile acid malabsorption and its impact on quality of life is poorly appreciated amongst those who treat cancer. BAM is a common problem in patients treated for a wide variety of cancers with a number of different treatment modalities. Given the effectiveness of dietary fat manipulation combined with a new generation of bile acid sequestrants, SeHCAT scanning should be a first line in investigating patients with diarrhoea after cancer therapies. Disclosure of Interest None Declared

Bile Acid Malabsorption After Pelvic and Prostate Intensity Modulated Radiation Therapy: An Uncommon but Treatable Condition

Intensity modulated radiation therapy (IMRT) is a significant therapeutic advance in prostate cancer, allowing increased tumor dose delivery and increased sparing of normal tissues. IMRT planning uses strict dose constraints to nearby organs to limit toxicity. Bile acid malabsorption (BAM) is a treatable disorder of the terminal ileum (TI) that presents with symptoms similar to radiation therapy toxicity. It has not been described in patients receiving RT for prostate cancer in the contemporary era. We describe new-onset BAM in men after IMRT for prostate cancer. Diagnosis of new-onset BAM was established after typical symptoms developed, selenium-75 homocholic acid taurine (SeHCAT) scanning showed 7-day retention of <15%, and patients' symptoms unequivocally responded to a bile acid sequestrant. The TI was identified on the original radiation therapy plan, and the radiation dose delivered was calculated and compared with accepted dose-volume constraints. Five of 423 men treated in a prospective series of high-dose prostate and pelvic IMRT were identified with new onset BAM (median age, 65 years old). All reported having normal bowel habits before RT. The volume of TI ranged from 26-141 cc. The radiation dose received by the TI varied between 11.4 Gy and 62.1 Gy (uncorrected). Three of 5 patients had TI treated in excess of 45 Gy (equivalent dose calculated in 2-Gy fractions, using an α/β ratio of 3) with volumes ranging from 1.6 cc-49.0 cc. One patient had mild BAM (SeHCAT retention, 10%-15%), 2 had moderate BAM (SeHCAT retention, 5%-10%), and 2 had severe BAM (SeHCAT retention, <5%). The 3 patients whose TI received ≥45 Gy developed moderate to severe BAM, whereas those whose TI received <45 Gy had only mild to moderate BAM. Radiation delivered to the TI during IMRT may cause BAM. Identification of the TI from unenhanced RT planning computed tomography scans is difficult and may impede accurate dosimetric evaluation. Thorough toxicity assessment and close liaison between oncologist and gastroenterologist allow timely diagnosis and treatment.

Bile acid malabsorption in inflammatory bowel disease

Bile acid malabsorption (BAM) is a common feature of Crohn's disease (CD). We aimed to determine whether BAM develops only in patients with a resected distal ileum or if it also occurs in patients who have not undergone surgery for CD. The study included 347 patients with CD or ulcerative colitis (UC) and 119 healthy subjects (controls). BAM was assessed by measurement of serum levels of 7α-hydroxycholest-4-en-3-one (C4) and fibroblast growth factor 19 (FGF19). We surveyed members of the European Crohn's and Colitis Organization and International Organization for the Study of Inflammatory Bowel Disease to collect current information about BAM diagnosis. The severity of BAM was associated with resection of the distal ileum. Compared with controls, patients who received moderate or extensive ileal resection had significantly increased levels of serum C4 (12 versus 62 versus 243 μg/L, respectively; P < 0.001). However, BAM was also present in a substantial number of the patients with CD who were not treated by surgery who had ileitis or colitis (14% and 11%, respectively). There was an indirect, proportional relationship between levels of C4 and FGF19 (P < 0.001). The most severe BAM occurs in CD patients after resection of the distal ileum, but BAM can occur in surgically untreated CD patients, regardless of disease localization. Laboratory tests for BAM should become a part of the algorithm for diagnosis of CD to identify patients who might respond to therapies such as bile acid sequestrants. FGF19 appears to be a reliable marker of BAM.

Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea‐predominant irritable bowel syndrome

Recurrent, watery diarrhoea affects one-third of patients diagnosed with irritable bowel syndrome ('IBS-D'). Idiopathic bile acid malabsorption ('I-BAM') may be the cause. To determine the prevalence of I-BAM in patients suffering from IBS-D. A systematic search was performed of publications reporting patients presenting with IBS-D type symptoms, who were subsequently confirmed as having I-BAM by SeHCAT scanning. Eighteen relevant studies, 15 prospective, comprising 1223 patients were identified. Five studies (429 patients) indicated that 10% (CI: 7-13) patients had severe bile acid malabsorption (SeHCAT 7 day retention <5% of baseline value). 17 studies (1073 patients) indicated that 32% (CI: 29-35) patients had moderate bile acid malabsorption (SeHCAT <10%). 7 studies (618 patients) indicated that 26% (CI: 23-30) patients had mild (SeHCAT <15%) bile acid malabsorption. Pooled data from 15 studies showed a dose-response relationship according to severity of malabsorption to treatment with a bile acid binder: response to colestyramine occurred in 96% of patients with <5% retention, 80% at <10% retention and 70% at <15% retention. Idiopathic adult-onset bile acid malabsorption is not rare. International guidelines for the management of irritable bowel syndrome need to be revised so that clinicians become more aware of this possibility.

Improved HPLC Analysis of Serum 7α-Hydroxycholest-4-en-3-one, a Marker of Bile Acid Malabsorption

Serum concentrations of 7α-hydroxycholest-4-en-3-one (cholesten, bile acid synthesis intermediate) have been shown to correlate with the severity of bile acid malabsorption(1)(2). Current techniques for holster quantification require sophisticated instrumentation(3) or solid-phase extraction (SPE) at 64 °C(4). We developed and validated a method for measuring serum cholesten concentrations using routinely available HPLC instrumentation, focusing on the optimization of the SPE step. Cholesten was purchased from Steraloids, and used to prepare serum calibrators containing 0–1000 μg/L. We added 30 ng of internal standard (7β-hydroxycholest-4-en-3-one, Steraloids) dissolved in 80 μL of methanol, to 1 mL of serum. Then 5 mL of chloroform:methanol (2:1, vol/vol, analytical grade, Penta) was added; the mixture was vortex-mixed vigorously, and centrifuged (2000 g , 3 min, ambient temperature). The upper phase was discarded, and 2 mL of 125 mmol/L NaCl in 50% methanol (vol/vol) was added to the sample, vortex-mixed, and centrifuged as above. The lower phase was transferred to another tube and dried at 60 °C under nitrogen, dissolved in 1 mL …

Bile acid malabsorption

Patients with bile acid malabsorption typically present with chronic, watery diarrhea. Bile acids recirculate between the liver and small intestine in the enterohepatic circulation. They are reabsorbed in the distal small intestine, and normally only a small fraction of the bile acid pool is lost to the colon during each cycle. In patients with bile acid malabsorption, a larger amount of bile acids is spilled into the colon, where the acids stimulate electrolyte and water secretion, which results in loose to watery stools. The common causes of bile acid malabsorption are ileal resection and diseases of the terminal ileum (Crohn's disease and radiation enteritis), which result in a loss of bile acid transporters and, consequently, diminished reabsorption. Bile acid malabsorption also has been documented in a small group of patients with chronic, watery diarrhea who have no demonstrable ileal disease (idiopathic bile acid malabsorption). The amount of bile acid loss to the colon determines the clinical presentation. Patients with mild to moderate bile acid malabsorption present with watery diarrhea and generally respond very well to treatment (with abolishment of diarrhea) with bile acid binders such as cholestyramine. Patients with more severe bile acid malabsorption have both diarrhea and steatorrhea. Treatment with cholestyramine is of no benefit in this group of patients and may, in fact, worsen steatorrhea. These patients are best treated with a low-fat diet supplemented with medium-chain triglycerides.

Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea.

Bile acid malabsorption (BAM) has been described in patients with collagenous colitis. There are no similar studies in lymphocytic colitis. The possibility that BAM might not necessarily be part of the microscopic colitis process and that both entities could simply be concomitant has not been evaluated. Our aim was to assess the frequency and severity of BAM in patients with microscopic colitis as well as in patients with previously unexplained functional chronic diarrhea. Likewise, we wanted to investigate the effect of cholestyramine on the induction and maintenance of remission of these conditions. A [75Se]HCAT abdominal retention test was performed in 26 patients with collagenous colitis, 25 with lymphocytic colitis, and 32 with previously unexplained functional chronic diarrhea. Patients with microscopic colitis who had BAM as well as a subgroup of eight collagenous colitis patients without BAM received treatment with cholestyramine. All patients with previously unexplained chronic diarrhea who had BAM were treated with cholestyramine. Twenty-two (43.1%) patients with microscopic colitis and 24 (75%) patients with previously unexplained functional chronic diarrhea presented with BAM. The frequency of BAM was higher in lymphocytic colitis than in collagenous colitis (60% vs 27%; P = 0.025). Cholestyramine induced clinical remission in 19 of 22 patients with microscopic colitis and BAM, none of eight patients with collagenous colitis without BAM, and all patients with previously unexplained chronic diarrhea and BAM. In conclusion, BAM seems to be common in patients with microscopic colitis-mainly in lymphocytic colitis-and in those with previously unexplained functional chronic diarrhea, suggesting that idiopathic BAM and microscopic colitis are often concomitant conditions. In this setting, cholestyramine seems to be highly effective in stopping diarrhea.

Bile acid malabsorption: mechanisms and treatment.

Bile acid malabsorption is often due to a disease or partial resection of the terminal ileum and more rarely a genetic defect in the distal ileum. It is often associated with diarrhoea with or without steatorrhoea, and it may be complicated by gallstone disease and hyperoxaluria. Bile acid malabsorption is rather easily diagnosed using the selenohomocholic acid taurine test. Patients with bile acid induced diarrhoea should be recommended a low-fat diet. Cholestyramine may be recommended in moderate bile acid diarrhoea. In patients with more severe bile acid malabsorption, cholylsarcosine may be used as a replacement therapy.

Effect of replacement therapy with cholylsarcosine on fat malabsorption associated with severe bile acid malabsorption. Studies in dogs with ileal resection.

The efficacy of cholylsarcosine, a synthetic deconjugation-resistant and nonsecretory conjugated bile acid analog for the treatment of fat malabsorption caused by severe bile acid malabsorption, was assessed in an animal model. In two dogs, the ileum and ileocecal valve were resected, causing severe diarrhea, steatorrhea, bile acid malabsorption, and progressive weight loss. Cholylsarcosine was administered as the water-soluble sodium salt by mixing with the dog food. Various doses were explored as well as varying intakes of dog food. Fat absorption was assessed by gravimetric measurement of fecal fat; a nonabsorbable recovery marker (polyethylene glycol mol wt 4000) was used to correct for incomplete fecal collections. Cholylsarcosine caused a 5- to 30-fold increase in fat absorption but had no significant effect on weight loss or fecal weight. Duodenal content was collected during digestion of a meal via a surgically placed Thomas cannula; the aspirates were dilute, acidic, and had a low bile acid concentration. The bile acid concentration increased modestly when cholylsarcosine was administered, but remained below the critical micellization concentration. The results indicate that oral administration of cholylsarcosine improved dietary fat absorption in a canine model of severe bile acid malabsorption with associated steatorrhea and bile acid deficiency in the proximal small intestine. Studies with this compound in patients with nutritional problems because of steatorrhea and severe bile acid malabsorption appear warranted.

Use of the SeHCAT test in the investigation of diarrhoea.

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea.

Imaging and retention measurements of selenium 75 homocholic acid conjugated with taurine, and the carbon 14 glycochol breath test to document ileal dysfunction due to late radiation damage

In order to assess ileal dysfunction in patients with complaints after pelvic radiation therapy, retention measurements and scintigraphic imaging with selenium 75 homocholic acid conjugated with taurine (75Se-HCAT), combined with the carbon 14 glycochol breath test, were evaluated in 39 patients. In 22 patients without ileal resection the results of the 75Se-HCAT test and the breath test differentiated between a normal functioning ileum (both tests negative) and ileal dysfunction as a cause of complaints (one or both tests positive). Among the patients with ileal dysfunction, the combination of both tests permitted those with bacterial overgrowth (breath test positive, 75Se-HCAT negative) to be separated from patients with evidence of bile acid malabsorption (75Se-HCAT positive, breath test positive or negative). In 17 patients with small-bowel resection, the 75Se-HCAT test helped to estimate the severity of bile acid malabsorption with implications for therapy. In this group the breath test was false-negative in 7 cases with abnormal 75Se-HCAT. Additional systematically performed scintigraphic imaging improved the accuracy of the 75Se-HCAT test, revealing cases with prolonged colonic accumulation of the radiopharmaceutical, causing spurious retention values. In conclusion, assessment of ileal dysfunction by nuclear medicine techniques in post-irradiation conditions provides information about the aetiology and therefore the possibility of adjustment in the clinical management.

Biological and Medical Aspects of Active Heal Transport of Bile Acids

The active transport of conjugated bile acids by the ileum is responsible for the enterohepatic circulation of bile acids, a physiological process that ensures an ample supply to the intestine of these key biological surfactants, irrespective of the rate of their biosynthesis from cholesterol. The ileal bile acid transport system is a high capacity, low affinity secondary active Na+ co-transport system that differs in substrate specificity from that present in the hepatocyte. Ileal transport is homeostatically regulated by feedback inhibition of the bile acids that are transported. The enterohepatic circulation is responsible for the concentration profile present in the intestine--high concentrations in the small intestine and low concentrations in the large intestine. Loss of ileal absorption, when mild, leads to a sequence of events that result in increased concentrations in the large intestine causing diarrhea. Severe bile acid malabsorption causes decreased concentrations in the small intestine which in turn lead to fat maldigestion and fat malabsorption. The increased passage of fatty acids into the colon contributes to diarrhea. Fat maldigestion and malabsorption also causes increased absorption of dietary oxalate from the colon which causes hyperoxaluria and contributes to nephrolithiasis. In cholestatic liver disease, inappropriate upregulation of ileal bile acid transport is likely to cause retention of hepatotoxic endogenous bile acids. In familial hypercholesterolemia, efficient bile acid absorption contributes to downregulation of LDL receptors and the maintenance of elevated plasma cholesterol levels; upregulation of bile acid transport during bile acid sequestrant therapy could diminish its efficacy. Efforts are in progress to develop a suitable bile acid analogue to be administered orally for conditions of bile acid deficiency in the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

AUTHOR'S REPLY

<h3>Introduction</h3> Approximately 16,000 patients per year are left with a chronic change in bowel function and gastrointestinal symptoms following treatment for cancer. This can have a significant impact upon quality of life and even compromise on-going cancer therapy. Previous small studies focusing mainly on patients with gynaecological cancers suggest that bile acid malabsorption (BAM) may be an important cause of radiotherapy-induced diarrhoea. This retrospective study aims to elucidate the prevalence of BAM in patients referred to a specialist gastroenterology clinic which treats patients with consequences of cancer treatments. <h3>Methods</h3> Patients referred to our clinic are managed using a peer reviewed algorithm. If they report diarrhoea, defined as Bristol Stool Chart type 6–7, a routine referral for a SeHCAT (75-selenium homocholic acid taurine) scan is made to exclude BAM. BAM is diagnosed when the SeHCAT 7 day retention is &lt; 15% and is graded mild (10–15%), moderate (5–10%) and severe (&lt; 5%). <h3>Results</h3> Between 2009–2012, 262 patients were referred for a SeHCAT scan. 139 (53.1%) were male (median age 66, range 32–89) and 123 (46.9%) female (median age 61, range 20–86). 79 (37%) patients had been treated for gynaecological, 94 (44%) for urological, 41 (19%) for anorectal and 30 (11%) for upper gastrointestinal tract cancers. A further 18 (7%) were treated for other cancer types (breast, lung and haematological). BAM was diagnosed in 24 patients (25%) treated for urological cancers, with 17% (n = 4) having severe BAM. 46 patients (58%) treated for gynaecological cancers had BAM, severe in 57% (n = 26). BAM was diagnosed in 22 patients (54%) treated for anorectal cancers, with 55% having severe BAM (n = 12). In 15 patients (50%) treated for upper GI cancers, the majority (73%) had severe BAM (n = 11). For patients with other cancer types, BAM was diagnosed in 8 patients (44%) with severe BAM in 2 of these (25%). <h3>Conclusion</h3> The frequency of severe bile acid malabsorption and its impact on quality of life is poorly appreciated amongst those who treat cancer. BAM is a common problem in patients treated for a wide variety of cancers with a number of different treatment modalities. Given the effectiveness of dietary fat manipulation combined with a new generation of bile acid sequestrants, SeHCAT scanning should be a first line in investigating patients with diarrhoea after cancer therapies. <h3>Disclosure of Interest</h3> None Declared

Effect of ileal exclusion on lipoprotein sitosterol in familial hypercholesterolaemia

A plant sterol, sitosterol, was quantitated in very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) and related to faecal steroids and cholesterol absorption in heterozygous familial hypercholesterolaemia patients with (n=7) and without ileal bypass (n=6). The latter had resulted in severe bile acid malabsorption but fractional cholesterol absorption was within low control limits. Serum total and LDL cholesterol and apoprotein B levels were reduced, whereas HDL cholesterol, apoprotein A-I, VLDL and HDL sitosterol concentrations were increased by the ileal exclusion, and the increase in LDL and serum total sitosterol levels was insignificant. In terms of mmol/mol of cholesterol or apoprotein B, however, the LDL and total sitosterol contents were higher in the subjects who had undergone operation. For an unknown reason the sitosterol content increased gradually within the lipoprotein particles from the lighter to the heavier lipoproteins, and the enrichment was similar in the two groups. Dietary sitosterol intake, indicated by faecal sitosterol excretion, was similar in the two groups.The contents of serum total and LDL sitosterol were positively correlated with the dietary sitosterol intake in both groups, and with the fractional cholesterol absorption only in the group not subject to operation. These associations were less consistent for sitosterol contents in other lipoproteins.We conclude that normally the serum sitosterol content reflects cholesterol absorption efficiency even in patients with familial hypercholesterolaemia, provided the dietary sitosterol intake is quite constant. In addition, for unknown reasons ileal exclusion leads to an increased lipoprotein sitosterol content.