Orlistat treatment is safe in overweight and obese liver transplant recipients: a prospective, open label trial

Obesity is a frequent complication following liver transplantation and is insufficiently responsive to dietary and life style advice. We studied the safety of orlistat treatment in obese and overweight liver transplant recipients (n = 15) on a stable tacrolimus-based immunosuppressive regimen. For safety reasons, the treatment period was restricted (6 months 120 mg t.i.d., 3 months 120 mg daily). Three patients dropped out, tacrolimus dose was adjusted in six of 12 remaining patients (dose reduction in 4, increase in 2, P = N.S.). All dose adjustments occurred during the 6 months of orlistat 120 mg t.i.d. therapy. No drug intolerance, adverse events or episodes of rejection occurred during the study. Efficacy of orlistat treatment in this population could not be shown, because a formal control population was not included in this safety trial. Moreover, only a significant decrease of waist circumference (P < 0.01 versus start of the study), but not of weight or body mass index, was achieved in the treated group. Orlistat treatment is well tolerated in liver transplant recipients and can be started safely, provided immunosuppressive drug levels and dietary adherence are closely monitored

Improving the well-being of men by Evaluating and Addressing the Gastrointestinal Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for a mixed-method implementation project

Introduction: Radiotherapy treatment for prostate cancer can cause bowel problems, which may lead to severe difficulties for cancer survivors including limiting travel, work or socialising. These symptoms can appear at any time following radiotherapy. This study focuses on the early identification and protocol-based management of effects known to cause long-term, or even permanent, changes to the well-being of prostate cancer survivors. The rationale of this study is to improve the care offered to men and their families following pelvic radiotherapy for prostate cancer. Method and analysis: Implementation research methodology will be used to adopt a multicomponent intervention at three UK centres. The intervention package comprises a standardised clinical assessment of relevant symptoms in oncology outpatient clinics and rapid referral to an enhanced gastroenterological service for patients identified with bowel problems. Gastroenterology staff will be trained to use an expert practice algorithm of targeted gastroenterology investigations and treatments. The evaluation of the intervention and its embedding within local practices will be conducted using a mixed-methods design. The effect of the new service will be measured in terms of the following outcomes: acceptability to staff and patients; quality of life; symptom control and cost effectiveness. Data collection will take place at baseline, 6 months (±2 months), and 12 months (±2 months) after entry into the study. Ethics and dissemination: The study has ethical approval from the North West-Liverpool East Research Ethics Committee and the appropriate NHS governance clearance. All participants provide written informed consent. The study team aim to publish the results of the study in peer-reviewed journals as well as at national and international conferences. Trial registration number: UKCRN1697

Gastrointestinal consequences of cancer treatment and the wider context: A bad gut feeling

<div><p></p><p><b>Background.</b> The percentage of people living with a diagnosis of cancer is rising globally. Between 20% and 25% of people treated for cancer experience a consequence of cancer which has an adverse impact on the quality of their life. Gastrointestinal (GI) symptoms are the most common of all consequences of cancer treatment and have the greatest impact on daily activity.</p><p><b>Pathophysiology of long-term bowel damage after pelvic radiotherapy.</b> Long-term damage to the bowel after radiotherapy is mediated by ischaemic changes and fibrosis. Each fraction of radiotherapy causes a series of repetitive injuries to the intestinal tissue resulting in an altered healing process, which affects the integrity of the repair and changes the architecture of the bowel wall.</p><p><b>The nature of GI symptoms that develop.</b> Patient-reported outcome measures show that diarrhoea, urgency, increased bowel frequency, tenesmus and flatulence are the five most prevalent GI symptoms with a moderate or severe impact on patients’ daily lives after treatment with pelvic radiotherapy. Many patients also experience fatigue, urinary problems and have sexual concerns.</p><p><b>Systematic assessment and management.</b> The complex nature of those symptoms warrants systematic assessment and management. The use of a tested algorithm can assist in achieving this. The most common contributing factors to ongoing bowel problems after pelvic radiotherapy are small intestinal bacterial overgrowth, bile acid malabsorption, pancreatic insufficiency, rectal bleeding and its impact on bone health.</p><p><b>The wider context.</b> Symptom burden, socio-psychosocial impact, memory and cognitive function, fatigue, urinary problems and sexual concerns need to be taken into account when thinking about consequences of cancer treatment.</p><p><b>Conclusion.</b> As our understanding of consequences of cancer treatments continues to emerge and encompass a wide variety of specialties, a holistic, multifaceted and multidisciplinary approach is required to manage those consequences long-term.</p></div

Systematic Review:The Impact of Cancer Treatment on the Gut and Vaginal Microbiome in Women With a Gynecological Malignancy

Background and aim Worldwide, 1,470,900 women are diagnosed yearly with a gynecological malignancy (21,000 in the UK). Some patients treated with pelvic radiotherapy develop chronic changes in their bowel function. This systematic review summarizes current research on the impact of cancer treatment on the gut and vaginal microbiome in women with a gynecological malignancy.Methods The Preferred reporting Items for Systematic Reviews and Meta-analyses guidelines for systematic reviews were used to ensure transparent and complete reporting. Quantitative studies exploring the gut or vaginal microbiome in this patient cohort were included. Animal studies were excluded. There were no language restrictions.Results No studies examined the possible effects of surgery or chemotherapy for gynecological cancers on the gut or vaginal microbiome.Three prospective cohort studies were identified using sequencing of changes in the gut microbiome reporting on a total of 23 women treated for gynecological cancer. All studies included patients treated with radiotherapy with a dosage ranging from 43.0 to 54.0 Gy. Two studies assessed gastrointestinal toxicity formally; 8 women (57%) developed grade 2 or 3 diarrhea during radiotherapy. The outcomes suggest a correlation between changes in the intestinal microbiome and receiving radiotherapy and showed a decrease in abundance and diversity of the intestinal bacterial species. Before radiotherapy, those who developed diarrhea had an increased abundance of Bacteroides, Dialister, and Veillonella (P < 0.01), and a decreased abundance of Clostridium XI and XVIII, Faecalibacterium, Oscillibacter, Parabacteroides, Prevotella, and unclassified bacteria (P < 0.05).Conclusion The limited evidence to date implies that larger studies including both the vaginal and gut microbiome in women treated for a gynecological malignancy are warranted to explore the impact of cancer treatments on the microbiome and its relation to developing long-term gastrointestinal toxicity. This may lead to new avenues to stratify those at risk and explore personalized treatment options and prevention of gastrointestinal consequences of cancer treatments

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

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&ndash;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 +/&minus; 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

Outcomes from treating bile acid malabsorption using a multidisciplinary approach

Background & aimDespite bile acid malabsorption affecting >1 % of the population, the outcomes of treatment are largely unreported. This study evaluated the effectiveness of a structured intervention for this condition.MethodThis was a retrospective evaluation of prospectively recorded patient reported outcome measures in a consecutive cohort of patients diagnosed with bile acid malabsorption seen in a cancer centre gastroenterology clinic. Every patient completed a 7-day food diary, a gastrointestinal symptom rating scale questionnaire and Bristol stool chart before the first clinic appointment and the symptom questionnaire and Bristol stool chart before all subsequent appointments. Patients who reported any episodes of type 6 or 7 stool were referred for a 75Selenium (Se) homocholic acid taurine scan. Abnormal gastrointestinal symptoms were investigated and treated systematically using a peer reviewed management algorithm.ResultsBetween 2011 and 2013, 136 men, 146 women, median age 66 years (range 19–89) underwent a scan. 143 (51 %) had 7-day isotope retention of ≤20 %. 105 (73 %) had previously undergone pelvic radiotherapy and 67 (47 %) GI surgery. 123 (86 %) were treated with low-fat diets, 79 (55 %) with a bile acid sequestrant, 73 (51 %) both. On discharge, 100 (70 %) patients reported an overall symptom improvement (mean −4.2 points, p < 0.0001). In patients who had only bile acid malabsorption and no other gastrointestinal diagnoses, 77 % (41/53) reported a mean improvement of −5.4 points (p < 0.0005). Patients reported a clinically significant improvement in urgency, faecal incontinence, wind, nocturnal defaecation, tiredness, abdominal pain, bloating, and steatorrhoea, (p = <0.0005). Stool frequency was reduced and stool consistency was improved.ConclusionIn this large cohort of complex patients, bile acid malabsorption is common and a multidisciplinary approach to managing gastrointestinal symptoms is effective