Incidence, Diagnosis and Management of Malabsorption Following Oesophagectomy: a Systematic Review.

BACKGROUND: Survival following oesophagectomy for cancer is improving, resulting in increased focus on quality of life and survivorship. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM). The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. METHODS: A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until December 2021. RESULTS: Of 464 identified studies, eight studies (n = 7 non-randomised longitudinal studies) were included where patients were identified with malnutrition following oesophagectomy. Studies included a combined sample of 328 (range 7-63) patients. Malabsorption syndromes including EPI, SIBO and BAM occurred in 15.9-100%, 37.8-100% and 3.33-100% over 21 days-60 months, 1-24 months and 1-24 months respectively. There was no consensus definition for EPI, SIBO or BAM, and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin or colesevelam showed improvement in symptoms and weight in all studies, where investigated. CONCLUSIONS: Malabsorption syndromes following oesophagectomy are under-recognised, and thus under-reported. The resultant gastrointestinal symptoms may have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies; however, greater understanding of these conditions, their diagnosis and management is required to further understand which patients will benefit from treatment.

[Assessment of a digestive malabsorption syndrome]. / Vignette diagnostique de l'étudiant. Exploration d'un syndrome de malabsorption digestive.

Malabsorption syndrome is a complex clinical entity that needs to be carefully explored. Patients present frequently chronic diarrhoea associated with weight loss. These symptoms affect patient's quality of life. The assessment of this syndrome requires a detailed anamnesis, a careful clinical exam, the use of biological measurements in both blood and faeces, and, if necessary, other more complex investigations including radionuclide tests. It is important to find the right pathogenesis in order to start effective treatments if possible. First, there are classical bowel pathologies like celiac disease and rarely Crohn disease. Second, biliopancreatic pathologies may also result in a malabsorption syndrome. Of note, this syndrome is very common after abdominal surgery like intestinal resection following mesenteric ischemia, biliopancreatic and gastric surgery. We will use a clinical case of malabsorption after an abdominal surgery to illustrate how to explore these patients who are suffering from malabsorption.

Le syndrome de malabsorption est une entité clinique, rencontrée régulièrement en consultation, qui combine des symptômes digestifs et généraux. Il se caractérise essentiellement par des troubles du transit (diarrhée chronique), associés fréquemment à une perte de poids. Cette symptomatologie altère la qualité de vie des patients, il est donc important de mettre au point le/les mécanisme(s) responsable(s) de la malabsorption afin de pouvoir envisager les différentes possibilités thérapeutiques et améliorer au maximum la qualité de vie du patient. Pour ce faire, nous devons, dans un premier temps, procéder à une anamnèse minutieuse et un examen clinique soigné, ensuite prescrire et exploiter les analyses de laboratoire (sur sang et sur selles) adaptées ainsi que les examens complémentaires de médecine nucléaire, d'imagerie médicale et d'endoscopie digestives. Il existe tout d'abord, une série de pathologies gastro-intestinales qui présentent ce syndrome, telles que la maladie coeliaque dans sa forme classique et, plus rarement, la maladie de Crohn ainsi que les pathologies bilio-pancréatiques. Le syndrome de malabsorption est également très fréquent dans les suites de chirurgies digestives lourdes telles que l'ischémie mésentérique entraînant un syndrome de grêle court, la pancréatectomie partielle ou totale, la gastrectomie totale, ainsi que les chirurgies du système biliaire. Nous allons, au travers d'un cas clinique, illustrer l'approche diagnostique sur le plan anamnestique, clinique et technique d'une malabsorption secondaire à une chirurgie digestive.

The active problem solving of patients dependent on home parenteral nutrition: A qualitative analysis.

BACKGROUND & AIMS: People with chronic, type 3, intestinal failure often require long-term home parenteral nutrition (HPN). People receiving HPN have frequent interactions with their healthcare, due to the need for close monitoring and due to recurrent hospital admissions. Individuals' responses to, and interactions with, their health care service provides are poorly described. We conducted a service evaluation to explore people's experiences of HPN-related healthcare interactions in order to identify how service providers can best meet the individualised needs of patients. METHODS: We interviewed ten people receiving HPN. The participants were asked about their healthcare interactions related to HPN. The data were analysed using a qualitative research method known as interpretive phenomenological analysis. This analytical approach is concerned with the meaning that people ascribe to particular events, in this case their HPN-related healthcare interactions. RESULTS: The participants in this study described a range of psychosocial problems related to their HPN healthcare interactions, including reliance, risk and restrictions. Participants' solutions to these problems included adaptation of their routine, self-guardianship and passivity. Sometimes, these solutions generated secondary problems of their own, including concerns with resource use, negative healthcare interactions and conflicts of responsibility. A range of contextual factors influenced how participants interpreted their healthcare interactions and the solutions available to them. These contextual factors included continuity of healthcare professionals, the attitude of staff, and information and knowledge about HPN. CONCLUSIONS: By attending to the individual meaning ascribed to healthcare events, and the contextual factors that surround these events, we have been able to better understand the decisions made by patients dependent on HPN. This suggests that healthcare professionals may also better understand their patients' decision making by attending to the individual meaning that patients ascribe to healthcare events and to contextual factors. We propose a model to describe the process of problem -> resolution -> problem in which participants are actively engaged.

Assessment of intestinal malabsorption.

Significant efforts have been made in the last decade to either standardize the available tests for intestinal malabsorption or to develop new, more simple and reliable techniques. The quest is still on and, unfortunately, clinical practice has not dramatically changed. The investigation of intestinal malabsorption is directed by the patient's history and baseline tests. Endoscopy and small bowel biopsies play a major role although non-invasive tests are favored and often performed early on the diagnostic algorithm, especially in paediatric and fragile elderly patients. The current clinically available methods and research tools are summarized in this review article.

Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study.

OBJECTIVES: Severe sprue-like enteropathy associated with olmesartan has been reported, but there has been no demonstration of an increased risk by epidemiological studies. AIM: To assess, in a nationwide patient cohort, the risk of hospitalisation for intestinal malabsorption associated with olmesartan compared with other angiotensin receptor blockers (ARB) and ACE inhibitors (ACEIs). DESIGN: From the French National Health Insurance claim database, all adult patients initiating ARB or ACEI between 1 January 2007 and 31 December 2012 with no prior hospitalisation for intestinal malabsorption, no serology testing for coeliac disease and no prescription for a gluten-free diet product were included. Incidence of hospitalisation with a discharge diagnosis of intestinal malabsorption was the primary endpoint. RESULTS: 4 546 680 patients (9 010 303 person-years) were included, and 218 events observed. Compared with ACEI, the adjusted rate ratio of hospitalisation with a discharge diagnosis of intestinal malabsorption was 2.49 (95% CI 1.73 to 3.57, p<0.0001) in olmesartan users. This adjusted rate ratio was 0.76 (95% CI 0.39 to 1.49, p=0.43) for treatment duration shorter than 1 year, 3.66 (95% CI 1.84 to 7.29, p<0.001) between 1 and 2 years and 10.65 (95% CI 5.05 to 22.46, p<0.0001) beyond 2 years of exposure. Median length of hospital stay for intestinal malabsorption was longer in the olmesartan group than in the other groups (p=0.02). Compared with ACEI, the adjusted rate ratio of hospitalisation for coeliac disease was 4.39 (95% CI 2.77 to 6.96, p<0.0001) in olmesartan users and increased with treatment duration. CONCLUSIONS: Olmesartan is associated with an increased risk of hospitalisation for intestinal malabsorption and coeliac disease.

SeHCAT [tauroselcholic (selenium-75) acid] for the investigation of bile acid malabsorption and measurement of bile acid pool loss: a systematic review and cost-effectiveness analysis.

BACKGROUND: The principal diagnosis/indication for this assessment is chronic diarrhoea due to bile acid malabsorption (BAM). Diarrhoea can be defined as the abnormal passage of loose or liquid stools more than three times daily and/or a daily stool weight > 200 g per day and is considered to be chronic if it persists for more than 4 weeks. The cause of chronic diarrhoea in adults is often difficult to ascertain and patients may undergo several investigations without a definitive cause being identified. BAM is one of several causes of chronic diarrhoea and results from failure to absorb bile acids (which are required for the absorption of dietary fats and sterols in the intestine) in the distal ileum. OBJECTIVE: For people with chronic diarrhoea with unknown cause and in people with Crohn's disease and chronic diarrhoea with unknown cause (i.e. before resection): (1) What are the effects of selenium-75-homocholic acid taurine (SeHCAT) compared with no SeHCAT in terms of chronic diarrhoea, other health outcomes and costs? (2) What are the effects of bile acid sequestrants (BASs) compared with no BASs in people with a positive or negative SeHCAT test? (3) Does a positive or negative SeHCAT test predict improvement in terms of chronic diarrhoea, other health outcomes and costs? DATA SOURCES: A systematic review was conducted to summarise the evidence on the clinical effectiveness of SeHCAT for the assessment of BAM and the measurement of bile acid pool loss. Search strategies were based on target condition and intervention, as recommended in the Centre for Reviews and Dissemination (CRD) guidance for undertaking reviews in health care and the Cochrane Handbook for Diagnostic Test Accuracy Reviews. The following databases were searched up to April 2012: MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; the Cochrane Databases; Database of Abstracts of Reviews of Effects; Health Technology Assessment (HTA) Database; and Science Citation Index. Research registers and conference proceedings were also searched. REVIEW METHODS: Systematic review methods followed the principles outlined in the CRD guidance for undertaking reviews in health care and the National Institute for Health and Care Excellence (NICE) Diagnostic Assessment Programme interim methods statement. In the health economic analysis, the cost-effectiveness of SeHCAT for the assessment of BAM, in patients with chronic diarrhoea, was estimated in two different populations. The first is the population of patients with chronic diarrhoea with unknown cause and symptoms suggestive of diarrhoea-predominant irritable bowel syndrome (IBS-D) and the second population concerns patients with Crohn's disease without ileal resection with chronic diarrhoea. For each population, three models were combined: (1) a short-term decision tree that models the diagnostic pathway and initial response to treatment (first 6 months); (2) a long-term Markov model that estimates the lifetime costs and effects for patients initially receiving BAS; and (3) a long-term Markov model that estimates the lifetime costs and effects for patients initially receiving regular treatment (IBS-D treatment in the first population and Crohn's treatment in the second population). Incremental cost-effectiveness ratios were estimated as additional cost per additional responder in the short term (first 6 months) and per additional quality-adjusted life-year (QALY) in the long term (lifetime). RESULTS: We found three studies assessing the relationship between the SeHCAT test and response to treatment with cholestyramine. However, the studies had small numbers of patients with unknown cause chronic diarrhoea, and they used different cut-offs to define BAM. For the short term (first 6 months), when trial of treatment is not considered as a comparator, the optimal choice depends on the willingness to pay for an additional responder. For lower values (between £1500 and £4600) the choice will be no SeHCAT in all scenarios; for higher values either SeHCAT 10% or SeHCAT 15% becomes cost-effective. For the lifetime perspective, the various scenarios showed widely differing results: in the threshold range of £20,000-30,000 per QALY gained we found as optimal choice either no SeHCAT, SeHCAT 5% (only IBS-D) or SeHCAT 15%. When trial of treatment is considered a comparator, the analysis showed that for the short term, trial of treatment is the optimal choice across a range of scenarios. For the lifetime perspective with trial of treatment, again the various scenarios show widely differing results. Depending on the scenario, in the threshold range of £20,000-30,000 per QALY gained, we found as optimal choice either trial of treatment, no SeHCAT or SeHCAT 15%. CONCLUSIONS: In conclusion, the various analyses show that for both populations considerable decision uncertainty exists and that no firm conclusions can be formulated about which strategy is optimal. Standardisation of the definition of a positive SeHCAT test should be the first step in assessing the usefulness of this test. As there is no reference standard for the diagnosis of BAM and SeHCAT testing provides a continuous measure of metabolic function, diagnostic test accuracy (DTA) studies are not the most appropriate study design. However, in studies where all patients are tested with SeHCAT and all patients are treated with BASs, response to treatment can provide a surrogate reference standard; further DTA studies of this type may provide information on the ability of SeHCAT to predict response to BASs. A potentially more informative option would be multivariate regression modelling of treatment response (dependent variable), with SeHCAT result and other candidate clinical predictors as covariates. Such a study design could also inform the definition of a positive SeHCAT result. STUDY REGISTRATION: The study is registered as PROSPERO CRD42012001911. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Semiquantitative assessment of breath hydrogen testing.

BACKGROUND AND AIM: A major use of breath hydrogen testing is to assess absorptive capacity for sugars to assist dietary design for management of gut symptoms. Qualitative reporting takes no account of the vigor of hydrogen response and provides little insight into degrees of malabsorption. This study aimed to describe a semiquantitative reporting method and to compare results with those reported qualitatively. METHODS: In consecutive Caucasian patients with Crohn's disease (n = 87), ulcerative colitis (59), functional gastrointestinal disorders (FGID) (162), and healthy controls (76), area under the curve was calculated for lactulose (15 g). This was compared with that for lactose (50 g) and fructose (35 g). Degree of malabsorption was categorized into arbitrary groups. RESULTS: Semiquantitative results for ≥ 30% (designated "convincing") malabsorption was most similar to those using a qualitative cutoff value of 20 ppm, but in 38% and 21% of patients, the classification of malabsorption (nil or clinically significant) changed for fructose and lactose, respectively. Using a cutoff of 10 ppm, 49% and 5% were classified differently. Crohn's disease had a higher prevalence (42%) of convincing fructose malabsorption than controls (24%) or patients with FGID (33%) (P < 0.02). Highest prevalence of convincing lactose malabsorption (38%) was in ulcerative colitis, greater than controls (18%) and FGID (18%) (P < 0.02). CONCLUSIONS: Semiquantitative assessment provides different results with different clinical implications in more than one third of patients, but disease-related alterations in prevalence are similar to those defined qualitatively. This method may be preferable because it lessens the confounding influence of the vigor of the hydrogen response.

For the assessment of intestinal permeability, size matters.

The purpose of this review is to demonstrate that an intestine leaky to small molecules can be impermeable to large antigenic molecules. The author proposes that the permeability of the epithelium to very small sugar molecules such as lactulose/mannitol-used for the past 50 years to gauge intestinal permeability-does not necessarily correlate with epithelial permeability to macromolecules. This article begins with the history and science behind the use of small sugars to measure permeability, a method developed in 1899. The lactulose/mannitol test may give useful information regarding the overall condition of the digestive tract; however, the author suggests that the test is not indicative of the transport of macromolecules such as bacterial toxins and food antigens, which have the capacity to damage the structure of the intestinal barrier and/or challenge the immune system. This article describes the various mechanisms and physiological transport pathways through which increased antigen uptake may result in immunological reactions to food antigens and bacterial lipopolysaccharides, resulting in the pathogenesis of disease. Finally, the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders. Therefore, more knowledge about the epithelium's permeability to large molecules undoubtedly contributes not only to early detection but also to secondary prevention of many inflammatory autoimmune, neuroimmune, and neurodegenerative disorders.

Clinical assessment of the child with intestinal failure.

The management of the child with intestinal failure is complex, and it is developing into a multispecialty field of its own led by expert teams of both transplant and nontransplant surgeons, gastroenterologists, and dieticians. Patients are at risk for medical, surgical, and nutritional complications that should be anticipated so that they can be prevented or managed appropriately. Catheter associated infections and intestinal failure associated liver diseases are important complications that impact the likelihood of bowel adaptation and long-term survival. The clinical assessment of a pediatric intestinal failure patient should include evaluation of the child within the context of recognized prognostic factors.

Assessment of small intestinal permeability using 1H-NMR spectroscopy.

BACKGROUND: Evaluation of small intestinal permeability (SIP) is based on the estimation of the urinary excretion ratio of a large and a small molecule (lactulose and mannitol, L/M) after oral administration. We evaluated SIP using 1H-NMR spectroscopy. METHODS: In-vitro experiments on known concentration of mannitol and lactulose solutions were performed to measure accuracy and precession of quantification using 1H-NMR spectroscopy. Eighteen patients with malabsorption syndrome (MAS) and 28 healthy subjects (HS) underwent SIP evaluation using L/M excretion ratio over 6-h after oral administration of 15 mL (10g) lactulose and 5 g mannitol using 1H-NMR spectroscopy and trimethyl silyl propionic acid as external reference and for quantification. RESULTS: Median errors of estimation of mannitol and lactulose were 5% (range 1.2 to 5) and 1.3% (range 0.2 to 1.3), respectively in-vitro. Patients with MAS excreted higher quantity of lactulose in urine than HS (median 0.33 mmol vs 0.12, 0 to .676 mmol, p<0.008). There was a trend towards lower urinary excretion of mannitol in patients with MAS than HS (median 3.58, range 0.61 to 15.77 mmol vs. 3.82, 1.34 to 16.42 mmol, p = ns). L/M ratio was higher among patients with MAS as compared to HS (median 0.1172 vs 0.045, p< 0.002). A cut-off value of L/M excretion ratio by receiver-operating characteristic (ROC) curve of 0.049 had a sensitivity and specificity of 72% and 61%, respectively; a cut-off value of 0.078 had a specificity of 90% but low sensitivity (67%). Area under ROC curve was 0.77. CONCLUSION: 1H-NMR spectroscopy is an analytical tool for assessment of SIP with reasonable sensitivity and specificity.

Assessment of phospholipid malabsorption by quantification of fecal phospholipid.

OBJECTIVES: The standard methods for quantifying fat absorption involve extraction of fat from fecal samples with heptane, ether and ethanol. These solvents do not quantitatively recover phospholipids. Malabsorption of dietary and biliary phosphatidylcholine could potentially result in choline deficiency. Therefore, the authors developed a method extracting and quantifying fecal phospholipids. METHODS: Fecal samples were collected for 72 hours from 18 children with cystic fibrosis and 10 control children. Fat was extracted first with hexane/diethyl ether/ethanol and then with chloroform/methanol. Total fat was quantitated gravimetrically. Phospholipids in extracted fat were separated and quantified using high-performance liquid chromatography with evaporative light-scattering detection (HPLC-ELSD). Phospholipid quantification was validated with a phosphomolybdate colorimetric assay. RESULTS: The combination of solvent systems used in this study significantly improved total fat (p < 0.05) and phospholipid (p < 0.001) extraction compared with either hexane/diethyl ether/ethanol or chloroform/methanol alone. Fecal phospholipid measured by HPLC-ELSD was significantly correlated with lipid-soluble phosphorous using the phosphomolybdate assay (r = 0.75, p < 0.001). This method also allows quantification of fecal phosphatidylcholine and lysophosphatidylcholine. CONCLUSIONS: Hexane/diethyl ether/ethanol followed by chloroform/methanol extraction of fecal samples and quantification of phospholipids using HPLC-ELSD is a new method for investigating phospholipid malabsorption.

Yield of laboratory testing to identify secondary contributors to osteoporosis in otherwise healthy women.

Our purpose in this study was to determine the prevalence of undetected disorders of bone and mineral metabolism in women with osteoporosis and to identify the most useful and cost-efficient screening tests to detect these disorders. A cross-sectional study was conducted among 664 postmenopausal women with osteoporosis at the Osteoporosis and Metabolic Bone Disease Program at the Mount Sinai Hospital in New York between January 1992 and June 1996. Women without a history of diseases or medications known to adversely affect bone who completed extensive laboratory testing including complete blood count, chemistry profile, 24-h urinary calcium, 25(OH)vitamin D, and PTH were included. Among 173 women who met the inclusion criteria for the study, previously undiagnosed disorders of bone and mineral metabolism were identified in 55 women (32%). Disorders of calcium metabolism and hyperparathyroidism were the most frequent diagnoses. A testing strategy involving measurement of 24-h urine calcium, serum calcium, and serum PTH for all women and serum TSH among women on thyroid replacement therapy would have been sufficient to diagnose 47 of these 55 women (85%) at an estimated cost of $75 per patient screened. Previously undiagnosed disorders affecting the skeleton are common in otherwise healthy women with low bone density. A simple testing strategy is likely to identify most such disorders.

A preliminary assessment of post prandial unconjugated bile acids in serum of cats with chronic diarrhoea and vomiting.

Increases in serum unconjugated bile acid concentrations have recently been shown to be diagnostic for small intestinal bacterial overgrowth in man. Similar increases in serum unconjugated bile acids were detected in three of nine cats with chronic diarrhoea and vomiting.

Small intestinal malabsorption in the horse: an assessment of the specificity of the oral glucose tolerance test.

Specificity of the oral glucose tolerance test (OGTT) for the diagnosis of small intestinal malabsorption in the horse was assessed by comparing the results of OGTT with the results of a histopathological examination of the small intestine in 42 adult horses affected by chronic weight loss. The horses were assigned to three groups on the basis of the results of the test. Five horses were considered to have a normal OGTT absorption result (Group 1); all the horses had a histologically normal small intestine. Twenty-five horses had a partial malabsorption result (Group 2) seven of which had normal small intestinal morphology, whereas the remaining 18 had a variety of pathological lesions including lymphosarcoma, villous atrophy, granulomatous enteritis and eosinophilic gastroenteritis. Twelve of the 42 horses had a total malabsorption result (Group 3), and all had a severe infiltrative lesion in the small intestinal wall (either lymphosarcoma or granulomatous enteritis).