Changes in cancer incidence and mortality have been modest during the past several decades, but the number of cancer survivors has almost tripled during the same period. With an increasing cohort of ...cancer survivors, efforts to prevent, diagnose and manage adverse effects of cancer therapy, in general, and those of radiation therapy specifically, have intensified. Many cancer survivors have undergone radiation therapy of tumours in the pelvis or abdomen, thus rendering the bowel at risk of injury. In fact, the current prevalence of patients who have long-term radiation-induced intestinal adverse effects exceeds that of IBD. Considerable progress towards reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which enable precise delivery of the radiation beam. Moreover, new insights into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. This Review discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, presents current management options and outlines priorities for future research. By adding insight into molecular and cellular mechanisms of related bowel disorders, gastroenterologists can substantially strengthen these efforts.
The number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with ...inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed.
A multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments.
Different pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent and may also require specialist input. The largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy. Their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical treatments fail. All endoscopic and surgical interventions after radiotherapy are potentially hazardous as radiotherapy may induce significant local ischaemia. The best current evidence for effective treatment of radiation-induced GI bleeding is with sucralfate enemas and hyperbaric oxygen therapy.
All cancer units must develop simple methods to identify the many patients who need help and establish routine referral pathways to specialist gastroenterologists where patients can receive safe and effective treatment. Early contact with oncologists and/or specialist surgeons with input from the patient's family and friends often helps the gastroenterologist to refine management strategies. Increased training in the late effects of cancer treatment is required.
Treatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions-bile acid diarrhoea ...(BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. 4 databases were searched from 1978 to 2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I
statistics. Seven studies (n = 597) estimated the pooled prevalence for BAD as 41% (95% CI 29-54). 17 studies (n = 5068) estimated that of MC as 3% (95% CI 2-4%). Two studies (n = 478) suggested a rate of 4.6% (range: 1.8-6.1%) for PEI. Using breath testing, 26 studies (n = 6700) and 13 studies (n = 3415) estimated the prevalence of lactose and fructose malabsorption as 54% (95% CI 44-64%) and 43% (95% CI 23-62%); 36 studies (n = 4630) and 22 studies (n = 2149) estimated that of SIBO as 49% (95% CI 40-57%) with lactulose and 19% (95% CI 13-27%) with glucose. Rates of all conditions were significantly higher than in healthy controls. A significant proportion of patients presenting to secondary care with IBS have an organic condition which may account for their symptoms. Failure to exclude such conditions will deny patients effective treatment.
Dietary fiber may favorably influence fermentation, gastrointestinal inflammation, and disease progression in Crohn's disease, ulcerative colitis (UC), and pouchitis and offer an attractive ...therapeutic addition to pharmacological treatment. This systematic review appraised data from randomized controlled trials of fiber in the management of inflammatory bowel disease.
The review followed Cochrane and PRISMA recommendations. Seven electronic databases were searched along with hand searching and contacting experts. Inclusion criteria were randomized controlled trials of the effects of fiber on clinical endpoints (primarily disease activity for treatment or maintenance) or physiological outcomes in patients with inflammatory bowel disease.
In total, 23 randomized controlled trials fulfilled the inclusion criteria (UC, 10; Crohn's disease, 12; and pouchitis, 1) recruiting 1296 patients. In UC, 3/10 studies reported fiber supplementation to benefit disease outcomes. In Crohn's disease, 0/12 studies and in pouchitis 1/1 study reported a benefit on disease activity. Despite this, a number of studies reported favorable intragroup effects on physiological outcomes including fecal butyrate, fecal calprotectin, inflammatory cytokines, microbiota, and gastrointestinal symptom indices. Meta-analysis was not possible.
There is limited weak evidence for the efficacy of fiber in improving disease outcomes in UC and pouchitis. The potential antiinflammatory role of fiber is intriguing and merits further investigation in adequately powered clinical trials. Excluding overt gastrointestinal obstruction, there was no evidence that fiber intake should be restricted in patients with inflammatory bowel disease.
Summary New gastrointestinal symptoms are frequent after pelvic radiotherapy and can greatly affect the quality of life of cancer survivors. The effect of radiation on the intestinal microbiota, and ...the clinical implications of a modified microbial balance after radiotherapy are now beginning to emerge. In this Personal View, we show the importance of the microbiota for intestinal homoeostasis, and discuss the similarity between inflammatory bowel disease, which has been extensively researched, and radiation-induced gastrointestinal toxicity. By use of microbiota profiles for risk assessment and manipulation of the intestinal flora for prevention and treatment of radiation, enteropathy could become a reality and would be of substantial relevance to the increasing numbers of long-term cancer survivors.
Background
The underlying mechanisms of chemotherapy-induced gastrointestinal (GI) symptoms are poorly researched. This study characterised the nature, frequency, severity and treatable causes for GI ...symptoms prospectively in patients undergoing chemotherapy for GI malignancy.
Methods
Patients receiving chemotherapy for a GI malignancy were assessed pre-chemotherapy, then monthly for 1 year using the Gastrointestinal Symptom Rating Scale, a validated patient-reported outcome measure. Patients with new, troublesome GI symptoms were offered investigations to diagnose the cause(s). Their oncologist was alerted when investigations were abnormal.
Results
A total of 241 patients, 60% male, median age 63 years (range 30–88), were enrolled; 122 patients were withdrawn, 93%, because of progressive disease or death. During the study, > 20% patients reported chronic faecal incontinence and > 10% reported moderate or severe problems with taste, dysphagia, belching, heartburn, early satiety, appetite, nausea, abdominal cramps, peri-rectal pain, rectal flatulence, borborygmi, urgency of defecation or tenesmus. Thirty percent reported continuing passage of hard stools and 30% on-going diarrhoea. Moderate or severe fatigue affected 40% participants at its peak and persisted in 15% at 1 year. Toxicity dictated change in chemotherapy for 13–29% patients/month. Common Terminology Criteria for Adverse Events underestimated gastrointestinal morbidity. Pre-chemotherapy screening identified previously undiagnosed pathology: exocrine pancreatic insufficiency (9%), vitamin B
12
deficiency (12%) and thyroid dysfunction (20%). Patients often refused investigations to diagnose their chemotherapy-induced symptoms; however, for every three investigations performed, one treatable cause was diagnosed: particularly small intestinal bacterial overgrowth (54%), bile acid malabsorption (43%), previously not described after chemotherapy, and unsuspected urinary tract infection (17%).
Conclusions
Patients undergoing chemotherapy for GI malignancy commonly have difficult GI symptoms requiring active management which does not occur routinely. The underlying causes for these symptoms are often treatable or curable. Randomised trials are urgently needed to show whether timely investigation and treatment of symptoms improve quality of life and survival.
Trial registration
ClinicalTrials.gov
Identifier: NCT02121626
Cancer survival is improving rapidly due to advances in treatments that will often involve radiotherapy, chemotherapy and novel biological agents in addition to surgery. This comes at the price of ...living with chronic symptoms, of which diarrhoea is particularly common. There is good evidence that for many patients these symptoms become part of everyday life, their “normality” is adjusted and symptoms are tolerated even when limiting activities severely. Clinicians often fail to appreciate the impact of these problems, as the focus of follow up tends to be on cancer recurrence. However, the rapid identification of patients in significant trouble can lead to earlier diagnosis of treatable pathologies and improvement of patients’ symptoms. The aim of this review is to highlight the mechanisms which cause oncology patients to develop diarrhoea and highlight useful investigational and treatment strategies.
Summary Background Chronic gastrointestinal symptoms after pelvic radiotherapy are common, multifactorial in cause, and affect patients' quality of life. We assessed whether such patients could be ...helped if a practitioner followed an investigative and management algorithm, and whether outcomes differed by whether a nurse or a gastroenterologist led this algorithm-based care. Methods For this three-arm randomised controlled trial we recruited patients (aged ≥18 years) from clinics in London, UK, with new-onset gastrointestinal symptoms persisting 6 months after pelvic radiotherapy. Using a computer-generated randomisation sequence, we randomly allocated patients to one of three groups (1:1:1; stratified by tumour site urological, gynaecological, or gastrointestinal, and degree of bowel dysfunction IBDQ-B score <60 vs 60–70): usual care (a detailed self-help booklet), gastroenterologist-led algorithm-based treatment, or nurse-led algorithm-based treatment. The primary endpoint was change in Inflammatory Bowel Disease Questionnaire–Bowel subset score (IBDQ-B) at 6 months, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00737230. Findings Between Nov 26, 2007, and Dec 12, 2011, we enrolled and randomly allocated 218 patients to treatment: 80 to the nurse group, 70 to the gastroenterologist group, and 68 to the booklet group ( figure ). Most had a baseline IBDQ-B score indicating moderate-to-severe symptoms. We recorded the following pair-wise mean difference in change in IBDQ-B score between groups: nurse versus booklet 4·12 (95% CI 0·04–8·19; p=0·04), gastroenterologist versus booklet 5·47 (1·14–9·81; p=0·01). Outcomes in the nurse group were not inferior to outcomes in the gastroenterologist group (mean difference 1·36, one sided 95% CI −1·48). Interpretation Patients given targeted intervention following a detailed clinical algorithm had better improvements in radiotherapy-induced gastrointestinal symptoms than did patients given usual care. Our findings suggest that, for most patients, this algorithm-based care can be given by a trained nurse. Funding The National Institute for Health Research.
Radiotherapy is important in managing pelvic cancers. However, radiation enteropathy may occur and can be dose limiting. The gut microbiota may contribute to the pathogenesis of radiation ...enteropathy. We hypothesized that the microbiome differs between patients with and without radiation enteropathy.
Three cohorts of patients (
= 134) were recruited. The early cohort (
= 32) was followed sequentially up to 12 months post-radiotherapy to assess early radiation enteropathy. Linear mixed models were used to assess microbiota dynamics. The late cohort (
= 87) was assessed cross-sectionally to assess late radiation enteropathy. The colonoscopy cohort compared the intestinal mucosa microenvironment in patients with radiation enteropathy (cases,
= 9) with healthy controls (controls,
= 6). Fecal samples were obtained from all cohorts. In the colonoscopy cohort, intestinal mucosa samples were taken. Metataxonomics (16S rRNA gene) and imputed metataxonomics (Piphillin) were used to characterize the microbiome. Clinician- and patient-reported outcomes were used for clinical characterization.
In the acute cohort, we observed a trend for higher preradiotherapy diversity in patients with no self-reported symptoms (
= 0.09). Dynamically, diversity decreased less over time in patients with rising radiation enteropathy (
= 0.05). A consistent association between low bacterial diversity and late radiation enteropathy was also observed, albeit nonsignificantly. Higher counts of
, and
significantly associated with radiation enteropathy. Homeostatic intestinal mucosa cytokines related to microbiota regulation and intestinal wall maintenance were significantly reduced in radiation enteropathy IL7 (
= 0.05), IL12/IL23p40 (
= 0.03), IL15 (
= 0.05), and IL16 (
= 0.009). IL15 inversely correlated with counts of
and
.
The microbiota presents opportunities to predict, prevent, or treat radiation enteropathy. We report the largest clinical study to date into associations of the microbiota with acute and late radiation enteropathy. An altered microbiota associates with early and late radiation enteropathy, with clinical implications for risk assessment, prevention, and treatment of radiation-induced side-effects.
.
Purpose
There are increasing numbers of patients who have been treated for colorectal cancer (CRC) who struggle with ongoing physical and psychological symptoms. ‘Cancer survivor’ is often used to ...describe these patients but this terminology remains controversial. This study sought to understand the follow-up experience of CRC patients in the UK and identify the terminology they prefer following diagnosis and treatment.
Methods
Purposeful sampling of patients from specialist CRC follow-up clinics was performed until data saturation was achieved. Two 1:1 semi-structured qualitative interviews were performed for each participant. Data were analysed thematically.
Results
Seventeen participants, median age = 62, 53% male were interviewed. Several themes were identified. Of note, fear of cancer recurrence dominates patients’ agendas at follow-up appointments. There are also clinical and administrative barriers to discussing symptoms including being embarrassed, feeling that their symptoms were not relevant or not having enough time to discuss issues. However, there are several methods which may improve this, such as through the use of video consultations and questionnaires. In addition, patients identified inadequate holistic support despite significant psychological and social distress. Our data suggest that labelling a diverse group of patients as ‘cancer survivors’ can be problematic.
Conclusion
It is important that clinicians systematically screen patients for symptoms that are known to occur following treatment. Clinicians and patients should have routine access to pathways and programmes that can support patients in navigating their life after cancer therapy.
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