Efficacy of incremental loads of cow's milk as a treatment for lactose malabsorption in Japan

BACKGROUND Lactose intolerance(LI)is commonly seen in East Asian countries.Several studies showed that lactose or milk loading has been used as a treatment for lactose malabsorption(LM)in Western countries,but there have been no reports regarding this type of treatment in Japan.As lactose or milk loading requires ingestion of large amounts of lactose within a short period,this is considered to be too harsh for Japanese people because of their less habitual milk consumption(175 mL per day in average)than Western people.In this study,we demonstrated lactose tolerance acquisition in a suitable way for Japanese.AIM To examine the efficacy of lactose(cow’s milk)loading treatment in patients with LM.METHODS Individuals with abdominal symptoms induced by milk or dairy products(LI symptoms)were identified with a questionnaire.A 20 g lactose hydrogen breath test(LHBT)was carried out to confirm LM diagnosis and to evaluate co-existence of small intestinal bacterial overgrowth(SIBO).Respondents diagnosed with LM were selected as study subjects and were treated with incremental loads of cow’s milk,starting from 30 mL and increasing up to 200 mL at 4-7 d intervals.After the treatment,changes in symptoms and LM diagnostic value of 20 g LHBT were investigated.Stool samples pre-and post-treatment were examined for changes in intestinal microbiota using 16S rRNA sequencing.Informed consent was obtained prior to each stage of the study.RESULTS In 46 subjects with LI symptoms(10-68 years old,mean age 34 years old)identified with the questionnaire,35(76.1%)were diagnosed with LM by 20 g LHBT,and 6 had co-existing SIBO.The treatment with incremental cow’s milk was carried out in 32 subjects diagnosed with LM(14-68 years old,median age 38.5 years old).The mean period of the treatment was 41±8.6 d.Improvement of symptoms was observed in 29(90.6%;95%confidence interval:75.0%-98.0%)subjects.Although 20 g LHBT indicated that 10(34.5%)subjects had improved diagnostic value of LM,no change was observed in 16(55.2%)subjects.Analysis of the fecal intestinal microbiota showed a significant increase in Blautia in 7 subjects who became symptom-free after the treatment(P=0.0313).CONCLUSION LM was diagnosed in approximately 75%of the subjects who had LI.Incremental loads of cow’s milk is regarded as a useful treatment for LM without affecting everyday life.

Helicobacter pylori infection and drugs malabsorption

Drug absorption represents an important factor affecting the efficacy of oral drug treatment.Gastric secretion and motility seem to be critical for drug absorption.A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori(H.pylori)infection has been proposed.Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H.pylori infection.According to the Maastricht Florence Consensus Report on the management of H.pylori infection,H.pylori treatment improves the bioavailability of both these drugs,whereas the direct clinical benefits to patients still await to be established.Less strong seems the association between H.pylori infection and other drugs malabsorption,such as delavirdine and ketoconazole.The exact mechanisms forming the basis of the relationship between H.pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated.H.pylori infection may trigger a chronic inflammation of the gastric mucosa,and impaired gastric acid secretion often follows.The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption.This minireview focuses on the evidence of H.pylori infection associated with impaired drug absorption.

Four-sample lactose hydrogen breath test for diagnosis of lactose malabsorption in irritable bowel syndrome patients with diarrhea

AIM: To validate 4-sample lactose hydrogen breath testing(4SLHBT) compared to standard 13-sample LHBT in the clinical setting.METHODS: Irritable bowel syndrome patients with diarrhea(IBS-D) and healthy volunteers(HVs) were enrolled and received a 10 g, 20 g, or 40 g doselactose hydrogen breath test(LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h(13 measurements). The detection rates of lactose malabsorption(LM) and lactose intolerance(LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT.RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups(P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT(97%-100%, Kappa 0.815-0.942) with high sensitivity(90%-100%) and specificity(100%) at all three lactose doses in both groups.CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.

Lactose malabsorption and intolerance: What should be the best clinical management?

Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a wellknown cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake. Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.

Phytochemical malabsorption:clinical significance

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Co-occurrence of carbohydrate malabsorption and primary epiploic appendagitis

Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with hydrogen(H2) breath tests and correlated to carbohydrate malabsorption. During performing these H2-breath tests the patient presented with an acute, localized, non-migratory pain in the left lower abdominal quadrant. Primary epiploic appendagitis is a rare cause of abdominal acute or subacute complaints and diagnosis of primary epiploic appendagitis(PEA) is made when computed tomography reveals a characteristic lesion. We report on a patient with cooccurrence of lactose and fructose malabsorption, which was treated successfully with a diet free of culprit carbohydrates, with PEA recovering without medication or surgical treatment within few days. Since the abdominal unspecific symptoms had been present for months, they appeared not to be correlated to the acute localized abdominal pain, therefore we speculate on a random co-occurrence of combined carbohydrate malabsorption and PEA.

Overview on the endoscopic treatment for obesity:A review

Obesity rates have increased,and so has the need for more specific treatments.This trend has raised interest in non-surgical weight loss techniques that are novel,safe,and straightforward.Thus,the present review describes the endoscopic bariatric treatment for obesity,its most recent supporting data,the questions it raises,and its future directions.Various endoscopic bariatric therapies for weight reduction,such as intragastric balloons(IGBs),aspiration therapy(AT),small bowel endoscopy,endoscopic sleeve gastroplasty,endoluminal procedures,malabsorption endoscopic procedures,and methods of regulating gastric emptying,were explored through literature sourced from different databases.IGBs,AT,and small bowel endoscopy have short-term effects with a possibility of weight regain.Minor adverse events have occurred;however,all procedures reduce weight.Vomiting and nausea are common side effects,although serious complications have also been observed.

Postoperative diarrhea in Crohn's disease:Pathogenesis,diagnosis,and therapy

Diarrhea is a frequent symptom in postoperative patients with Crohn’s diseases(CD),and several different mechanisms likely account for postoperative diarrhea in CD.A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.

Role of Helicobacter pylori infection on nutrition and metabolism

Helicobacter pylori(H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world's population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome.

Which factors determine exocrine pancreatic dysfunction in diabetes mellitus?

The exocrine structure is significantly affected by diabetes because of endocrine structure-function disorder within the pancreas. Exocrine pancreatic dysfunction (EPD) is the general name of the malabsorption process resulting from inadequate production, release, decreased activation, and/or insufficient degradation of enzymes required for digestion from pancreatic acinar cells. It is important to diagnose patients early and correctly, since there may be both macro- and micro-nutrient deficiency in EPD. In this paper, EPD, the diabetes- EPD relationship, and the predictive, effective factors affecting the emergence of EPD are briefly explained and summarized with contemporary literature and our experienced based on clinical, lab, and radiological findings.

Chronic pancreatitis:A diagnostic dilemma

Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently-published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland.

Endoscopic tools for the diagnosis and evaluation of celiac disease

Celiac disease(CD)is an autoimmune disease of the small bowel induced by ingestion of wheat,rye and barley.Current guidelines indicate histological analysis on at least four duodenal biopsies as the only way to diagnose CD.These indications are based on the conception of the inability of standard endoscopy to make diagnosis of CD and/or to drive biopsy sampling.Over the last years,technology development of endoscopic devices has greatly ameliorated the accuracy of macroscopic evaluation of duodenal villous pattern,increasing the diagnostic power of endoscopy of CD.The aim of this paper is to review the new endoscopic tools and procedures proved to be useful in the diagnosis of CD,such as chromoendoscopy,Fujinon Intelligent Chromo Endoscopy,Narrow Band Imaging,Optical Coherence Tomography,Water-Immersion Technique,confocal laser endomicroscopy,high-resolution magnification endoscopy,capsule endoscopy and I-Scan technology.

Nutrition in chronic pancreatitis

The pancreas is a major player in nutrient digestion.In chronic pancreatitis both exocrine and endocrine insufficiency may develop leading to malnutrition over time.Maldigestion is often a late complication of chronic pancreatic and depends on the severity of the underlying disease.The severity of malnutrition is correlated with two major factors:(1)malabsorption and depletion of nutrients(e.g.,alcoholism and pain)causes impaired nutritional status;and(2)increased metabolic activity due to the severity of the disease.Nutritional deficiencies negatively affect outcome if they are not treated.Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention.Good nutritional practice includes screening to identify patients at risk,followed by a thoroughly nutritional assessment and nutrition plan for risk patients.Treatment should be multidisciplinary and the mainstay of treatment is abstinence from alcohol,pain treatment,dietary modifications and pancreatic enzyme supplementation.To achieve energy-end protein requirements,oral supplementation might be beneficial.Enteral nutrition may be used when patients do not have sufficient calorie intake as in pylero-duodenalstenosis,inflammation or prior to surgery and can be necessary if weight loss continues.Parenteral nutrition is very seldom used in patients with chronic pancreatitis and should only be used in case of GI-tract obstruction or as a supplement to enteral nutrition.

Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency

The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.

Less common etiologies of exocrine pancreatic insufficiency

Exocrine pancreatic insufficiency(EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases(diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin(CCK); celiac or inflammatory bowel disease(IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery(asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy(PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI(66%-92%). EPI occurs in patients with type 1(26%-57%) or type 2 diabetes(20%-36%) and is typically mild to moderate; by definition, all patients with type 3 c(pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease(4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD(14%-74%) and up to 100% of gastrointestinal surgery patients(47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

Nutritional and health benefits of semi-elemental diets: A comprehensive summary of the literature

AIM:To critically review and summarize the literature on nutritional and health outcomes of semi-elemental formulations on various nutritionally vulnerable patient populations who are unable to achieve adequate nutrition from standard oral diets.METHODS:We conducted a comprehensive literature search of Pubmed and Embase databases.We manually screened articles that examined nutritional and health outcomes(e.g.,growth,disease activity,gastrointestinal impairment,mortality,and economic impact)among various patient groups receiving semi-elemental diets.This review focused on full-text articles of randomized controlled clinical trials and other intervention studies,but pertinent abstracts and case studies were also included.Results pertaining primarily to tolerance,digestion,and absorption were summarized for each patient population in this systematic review.RESULTS:Results pertaining primarily to tolerance,digestion,and absorption were summarized for each patient population.The efficacy of semi-elemental whey hydrolyzed protein(WHP)diet have been reported in various nutritionally high risk patient populations including-Crohn’s disease,short bowel syndrome,acute and chronic pancreatitis,cerebral palsy,cystic fibrosis,cerebrovascular accidents,human immunodeficiency virus,critically ill,and geriatrics.Collectively,the evidence from the medical literature indicates that feeding with a semi-elemental diet performs as well or better than parenteral or amino acid based diets in terms of toler-ance,digestion,and nutrient assimilation measures across various disease conditions.CONCLUSION:Based on this comprehensive review of the literature,patient populations who have difficulty digesting or absorbing standard diets may be able to achieve improved health and nutritional outcomes through the use of semi-elemental WHP diets.

Long-term outcome of pancreatic function following oncological surgery in children:Institutional experience and review of the literature

BACKGROUND Pancreatic neoplasms are uncommon in children and in most cases they are benign or have low malignant potential.Pancreatoblastoma and solid pseudopapillary tumor are the most frequent types in early and late childhood,respectively.Complete resection,although burdened by severe complications,is the only curative treatment for these diseases.Pancreatic surgery may result in impaired exocrine and endocrine pancreatic function.However,limited data are available on the long-term pediatric pancreatic function following surgical resection.AIM To investigate endocrine and exocrine pancreatic function and growth after oncological pancreatic surgery in a pediatric series.METHODS A retrospective analysis of all pediatric patients who underwent surgery for pancreatic neoplasm in our Institution from January 31,2002 to the present was performed.Endocrine and exocrine insufficiency,auxological and fat-soluble vitamin status(A,D,E and clotting tests)were assessed at diagnosis and at every follow-up visit.Exocrine insufficiency was defined as steatorrhea with fecal elastase-1<200μg/g stool,while endocrine insufficiency was identified as onset of Diabetes or Impaired Glucose Tolerance.Growth was evaluated based on body mass index(BMI)z-score trend.RESULTS Sixteen patients(12 girls and 4 boys,mean age 10.7±5.3 years),were included.Nine patients(56%)had a neoplasm in the pancreatic head,4 in the body/tail,2 in the tail and 1 in the body.Histological findings were as follows:Solid pseudopapillary tumor in 10 patients(62.5%),insulinoma in 2 patients,neuroendocrine tumor in 2 patients and acinar cell carcinoma in 2 patients.The most frequent surgery was pancreaticoduodenectomy(50%).Exocrine failure occurred in 4 patients(25%)and endocrine failure in 2 patients(12.5%).Exocrine insufficiency occurred early(within 6 mo after surgery)and endocrine insufficiency later(8 and 10 years after surgery).Mean BMI z-score was 0.36±1.1 at diagnosis and 0.27±0.95 at the last assessment.Vitamin D was insufficient(<30 ng/mL)in 8 of the 16 patients during the follow-up period.Vitamins A,E and clotting test were into the normal ranges in all patients.CONCLUSION Careful and long-term monitoring should follow any pancreatic surgery,to recognize and promptly treat exocrine and endocrine pancreatic insufficiency,which can occur after surgery.

Concise review on short bowel syndrome: Etiology, pathophysiology, and management

Adults have approximately 20 feet of small intestine,which is the primary site for absorbing essential nutrients and water.Resection of the intestine for any medical reason may result in short bowel syndrome(SBS),leading to loss of major absorptive surface area and resulting in various malabsorption and motility disorders.The mainstay of treatment is personalized close dietary management.Here we present SBS with its pathophysiology and different nutritional management options available.The central perspective of this paper is to provide a concise review of SBS and the treatment options available,along with how proper nutrition can solve major dietary issues in SBS and help patients recover faster.

Microscopic enteritis:Bucharest consensus

Microscopic enteritis(ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms,nutrient and micronutrient deficiency.It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy.This work recognises a need to characterize disorders with microscopic and submicroscopic features,currently regarded as functional or non-specific entities,to obtain further understanding of their clinical relevance.The consensus working party reviewed statements about the aetiology,diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment.Following the 5th International Course in Digestive Pathology in Bucharest in November 2012,an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME.A five-step agreement scale(from strong agreement to strong disagreement) was used to score 21 statements,independently.There was strong agreement on all statements about ME histology(95%-100%).Statements concerning diagnosis achieved 85% to 100% agreement.A statement on the management of ME elicited agreement from the lowest rate(60%) up to 100%.The remaining two categories showed general agreement between experts on clinical presentation(75%-95%) and pathogenesis(80%-90%) of ME.There was strong agreement on the histological definition of ME.Weaker agreement on management indicates a need for further investigations,better definitions and clinical trials to produce quality guidelines for management.This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

Diarrhea after bariatric procedures:Diagnosis and therapy

Diarrhea after bariatric procedures, mainly those with malabsorptive elements including Roux-Y Gastric Bypass and Biliopancreatic Diversion, is common and an essential determinant of quality of life and microand macronutrient deficiencies. Bariatric surgery is the only sustainably successful method to address morbid obesity and its comorbidities, particularly gaining more and more importance in the specific treatment of diabetic patients. Approximately half a million procedures are annually performed around the world, with numbers expected to rise drastically in the near future. A multitude of factors exert their influence on bowel habits; preoperative comorbidities and procedure-related aspects are intertwined with postoperative nutritional habits. Diagnosis may be challenging owing to the characteristics of postbariatric surgery anatomy with hindered accessibility of excluded segments of the small bowel and restriction at the gastric level. Conventional testing measures, if available, generally yield low accuracy and are usually not validated in this specific population. Limited trials of empiric treatment are a practical alternative and oftentimes an indispensable part of the diagnostic process. This review provides an overview of causes for chronic post-bariatric surgery diarrhea and details the particularities of its diagnosis and treatment in this specific patient population. Topics of current interest such as the impact of gut microbiota and the influence of bile acids on morbid obesity and especially their role in diarrhea are highlighted in order to provide a better understanding of the specific problems and chances of future treatment in post-bariatric surgery patients.