Micronutrient deficiencies and anemia in the follow-up after gastroesophageal cancer surgery.

Due to insufficient dietary intake and altered digestion and absorption of nutrients, patients after gastroesophageal cancer surgery are at risk of becoming malnourished and consequently develop micronutrient deficiencies. The aim of this study was to determine the prevalence of micronutrient deficiencies and anemia during follow-up after gastroesophageal cancer surgery. This single-center cross-sectional study included patients after resection for esophageal or gastric cancer visiting the outpatient clinic in 2016 and 2017. Only patients without signs of recurrent disease were included. All patients were guided by a dietician in the pre- and postoperative phase. Dietary supplements or enteral tube feeding was prescribed in case of inadequate dietary intake. Blood samples were examined for possible deficiencies or abnormalities in hemoglobin, prothrombin time, iron, ferritin, folic acid, calcium, zinc, vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin D and vitamin E. The percentage of patients with micronutrient deficiencies were scored. Of the 335 patients visiting the outpatient clinic, measurements were performed in 263 patients (221 after esophagectomy and 42 after gastrectomy), resulting in an inclusion rate of 79%. In the esophagectomy group, deficiencies in iron (36%), vitamin D (33%) and zinc (20%) were most prevalent. After gastric resection, deficiencies were most frequently observed in vitamin D (52%), iron (33%), zinc (28%) and ferritin (17%). Low levels of hemoglobin were found in 21% of patients after esophagectomy and 24% after gastrectomy. Despite active nutritional guidance, deficiencies in vitamin D, iron, zinc and ferritin, as well as low levels of hemoglobin, are frequently observed following gastroesophageal resection for cancer. These micronutrients should be periodically checked during follow-up and supplemented if needed.

Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature.

Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle-Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4-6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 µg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 µg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.

Exocrine pancreatic and enterocyte function in patients with advanced pancreatic cancer.

BACKGROUND & AIMS: Exocrine pancreatic function is affected in patients with locally advanced pancreatic cancer (LAPC), clinically leading to steatorrhea. It is unknown whether maldigestion and malabsorption can also be attributed to impaired intestinal enterocyte function. In this exploratory study enterocyte function was assessed in patients with locally advanced pancreatic cancer, treated with Irreversible Electroporation (IRE). METHODS: Enterocyte function was studied by Citrulline Generation Test (CGT). Intestinal absorption capacity of energy and fat was calculated from the differences between nutritional intake (four-days diary) and quantified fecal losses energy and fat in three-days feces collection. RESULTS: Twelve patients were included before IRE, and 5 patients had follow-up measurements. Fasted citrulline [CIT] and glutamine [GLU] levels were below reference levels of healthy subjects ([CIT] 38 ± 8 µmol/L; [GLU] 561 ± 77 µmol/L) both before ([CIT] 25 ± 9 µmol/L; [GLU] 65 ± 35 µmol/L) and after IRE ([CIT] 19 ± 9 µmol/L; [GLU] 53 ± 26 µmol/L) whereas CGT curves were normal, indicating normal enterocyte function (slope 0.21 ± 0.12 and 0.17 ± 0.07 µmol/L/min; [CIT] increment 63 ± 39 and 80 ± 44% respectively). Severe energy/fat malabsorption was present in 6 out of 12 patients with LAPC (mean loss 349 kcal/d, 13 g fat/d) before and in 4 out of 5 patients (mean loss 509 kcal/d, 32 g fat/d) after IRE respectively. CONCLUSIONS: Enterocyte function was generally within reference limits in patients with advanced pancreatic cancer. Severe malabsorption may be explained by exocrine pancreatic insufficiency.

Percentiles for skeletal muscle index, area and radiation attenuation based on computed tomography imaging in a healthy Caucasian population.

BACKGROUND/OBJECTIVES: Muscle mass is a key determinant of nutritional status and associated with outcomes in several patient groups. Computed tomography (CT) analysis is increasingly used to assess skeletal muscle area (SMA), skeletal muscle index (SMI) and muscle radiation attenuation (MRA). However, interpretation of these muscle parameters is difficult since values in a healthy population are lacking. The aim of this study was to provide sex specific percentiles for SMA, SMA and MRA in a healthy Caucasian population and to examine the association with age and BMI in order to define age- and BMI specific percentiles. SUBJECTS/METHODS: In this retrospective cross-sectional study CT scans of potential kidney donors were used to assess SMA, SMI and MRA at the level of the third lumbar vertebra. Sex specific distributions were described and, based on the association between age/BMI and muscle parameters, age, and BMI specific predicted percentiles were computed. The 5th percentile was considered as cut-off. RESULTS: CT scans of 420 Individuals were included (age range 20-82 years and BMI range 17.5-40.7 kg/m2). Sex specific cut-offs of SMA, SMI and MRA were 134.0 cm2, 41.6 cm2/m2 and 29.3 HU in men and 89.2 cm2, 32.0 cm2/m2 and 22.0 HU in women, respectively. Correlations were negative between age and all three muscle parameters, positive between BMI and SMA/SMI and negative between BMI and MRA, resulting in age- and BMI specific percentiles. CONCLUSIONS: This study provides sex specific percentiles for SMA, SMI, and MRA. In addition, age- and BMI specific percentiles have been established.

Assessment of Nutritional Status, Digestion and Absorption, and Quality of Life in Patients with Locally Advanced Pancreatic Cancer.

BACKGROUND AND AIM: To provide a comprehensive quantitative assessment of nutritional status, digestion and absorption, and quality of life (QoL) in patients with locally advanced pancreatic cancer (LAPC). METHODS: Sixteen patients with LAPC were prospectively assessed for weight loss (WL), body mass index (BMI), fat-free mass index (FFMI), handgrip strength (HGS), dietary macronutrient intake, serum vitamin levels, resting and total energy expenditure (REE and TEE, indirect calorimetry), intestinal absorption capacity and fecal losses (bomb calorimetry), exocrine pancreatic function (fecal elastase-1 (FE1)), and gastrointestinal quality of life (GIQLI). RESULTS: Two patients had a low BMI, 10 patients had WL > 10%/6 months, 8 patients had a FFMI < P10, and 8 patients had a HGS < P10. Measured REE was 33% higher (P = 0.002) than predicted REE. TEE was significantly higher than daily energy intake (P = 0.047). Malabsorption (<85%) of energy, fat, protein, and carbohydrates was observed in, respectively, 9, 8, 12, and 10 patients. FE1 levels were low (<200 µg/g) in 13 patients. Total QoL scored 71% (ample satisfactory). CONCLUSION: Patients with LAPC have a severely impaired nutritional status, most likely as a result of an increased REE and malabsorption due to exocrine pancreatic insufficiency. The trial is registered with PANFIRE clinicaltrials.gov NCT01939665.

Lymphoma development and survival in refractory coeliac disease type II: Histological response as prognostic factor.

BACKGROUND: Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). OBJECTIVE: The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies. METHODS: A total of 45 patients were retrospectively analysed. All patients received 2-CdA, after which they were either closely monitored (monotherapy, n = 30) or a step-up approach was used including auSCT (step-up therapy, n = 15). RESULTS: Ten patients (22%) ultimately developed EATL; nine of these had received monotherapy. Absence of histological remission after monotherapy was associated with EATL development (p = 0.010). Overall, 20 patients (44%) died with a median survival of 84 months. Overall survival (OS) within the monotherapy group was significantly worse in those without histological remission compared to those with complete histological remission(p = 0.030). The monotherapy group who achieved complete histological remission showed comparable EATL occurrence and OS as compared to the step-up therapy group (p = 0.80 and p = 0.14 respectively). CONCLUSION: Histological response is an accurate parameter to evaluate the effect of 2-CdA therapy and this parameter should be leading in the decisions whether or not to perform a step-up treatment approach in RCDII.

Preventing complications in celiac disease: our experience with managing adult celiac disease.

Celiac disease is, as we know it, rather than being a rare and incurable disease until the 1950's, both quite common in screening studies and readily treatable. Three conditions are triggered by gluten consumption: celiac disease, the skin rash dermatitis herpetiformis and gluten ataxia. We describe our follow up for out clinic management, as evidence based data about such an approach are lacking in current literature. No food, beverages or medications containing any amount of gluten can be taken. Compliance is often difficult especially when patients are asymptomatic. We control a cohort, in daily practice, of over 700 adult patients. The majority of patients manage the diet without any problems. We describe our follow up in general, for serology, laboratory and histology. Forty percent of our newly diagnosed celiac patients do have a BMI over 25 kg/m(2). An appropriate attitude for this problem is lacking. The problem of slowly weaning off Dapsone over 5-10 years in DH is recognized. The bone density is checked in all newly diagnosed celiac patients. We control, if necessary, by telephone and lab controls done in local cities and see our patients only every two years face-to-face for follow up. The main question is if the adherence to a GFD, quality of life and prevention of complications is improved by visiting a dedicated celiac clinic. We hope to standardize this attitude on evidence data in the years to come.

Bomb calorimetry, the gold standard for assessment of intestinal absorption capacity: normative values in healthy ambulant adults.

BACKGROUND: Intestinal absorption capacity is considered to be the best method for assessing overall digestive intestinal function. Earlier reference values for intestinal function in healthy Dutch adults were based on a study that was conducted in an inpatient metabolic unit setting in a relatively small series. The present study aimed to readdress and describe the intestinal absorption capacity of healthy adults, who were consuming their usual (Western European) food and beverage diet, in a standard ambulatory setting. METHODS: Twenty-three healthy subjects (aged 22-60 years) were included in the analyses. Nutritional intake (energy and macronutrients) was determined with a 4-day nutritional diary. Subsequently, mean faecal losses of energy (by bomb calorimetry), fat, protein and carbohydrate were determined following a 3-day faecal collection. Finally, intestinal absorption capacity was calculated from the differences between intake and losses. RESULTS: Mean (SD) daily faeces production was 141 (49) g (29% dry weight), containing 891 (276) kJ [10.7 (1.3) kJ g(-1) wet faeces; 22.6 (2.5) kJ g(-1) dry faeces], 5.2 (2.2) g fat, 10.0 (3.8) g protein and 29.7 (11.7) g carbohydrates. Mean (SD) intestinal absorption capacity of healthy subjects was 89.4% (3.8%) for energy, 92.5% (3.7%) for fat, 86.9% (6.4%) for protein and 87.3% (6.6%) for carbohydrates. CONCLUSIONS: The present study provides normative values for both stool nutrient composition and intestinal energy and macronutrient absorption in healthy adults on a regular Dutch diet in an ambulatory setting. Intestinal energy absorption was found to be approximately 90%.

Nutritional support in patients with GVHD of the digestive tract: state of the art.

An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD-DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B12 and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies.

Assessment of small bowel function in critical illness: potential role of citrulline metabolism.

Small intestinal function in critically ill patients should ideally be assessed in order to determine the preferred feeding route, timing, and composition of enteral nutrition. Additionally, evaluation of small bowel function may lead to new insights aimed to maintain enterocyte integrity. Critically ill patients are likely to have impaired enterocyte function mainly as a consequence of diminished splanchnic blood flow associated with mucosal hyperpermeability and bacterial translocation, a pathological state believed to be pivotal in the development of sepsis and multiple organ dysfunction syndrome (MODS). However, feasible and validated clinical tools to reliably assess enterocyte function are lacking. This explorative review discusses the promising role of citrulline, a nonprotein amino acid almost exclusively generated by the enterocyte, as a biomarker reflecting enterocyte function in critically ill patients. Citrulline metabolism, its potential as enterocyte biomarker, and literature on citrulline in critically illness will be discussed. Finally, a novel test for enterocyte function, the citrulline generation test (enterocytic citrulline production upon stimulation with enteral or intravenous glutamine) will be considered briefly.

The citrulline generation test: proposal for a new enterocyte function test.

BACKGROUND: The amino acid citrulline is mainly produced by enterocytes from conversion of glutamine. As fasting plasma citrulline proved disappointing as a biomarker for enterocyte dysfunction in clinical practice, we propose a citrulline generation test (CGT) to assess enterocyte function. AIM: To assess the feasibility of a CGT in healthy subjects and patients with decreased enterocyte mass. METHODS: Nineteen healthy subjects, 16 patients with intestinal villous atrophy and nine patients with short bowel syndrome (SBS) were given an oral bolus of 20 g of the dipeptide alanine-glutamine. Subsequent changes in plasma citrulline and other amino acid concentrations were determined using reverse-phase high-performance liquid chromatography. RESULTS: Following the oral bolus of alanine-glutamine, plasma citrulline concentrations showed a time dependent rise in healthy subjects of 44 +/- 13% (38-55 micromol/L, P < 0.0001). The slope from baseline plasma citrulline to peak concentrations was 0.22 +/- 0.08, 0.13 +/- 0.04 and 0.09 +/- 0.04 micromol/L/min in healthy subjects, patients with coeliac disease (CeD) and refractory CeD, respectively (healthy subjects vs. CeD P < 0.05, healthy subjects vs. refractory CeD P < 0.001). In patients with SBS, the CGT was able to distinguish between non-adapted and adapted SBS by means of the incremental area under the CGT curve till 90 min (iAUC T90). The iAUC T90 was 447 +/- 179 and 1039 +/- 178 micromol/L/min in non-adapted and adapted SBS, respectively (P = 0.04). CONCLUSION: An oral bolus of alanine-glutamine induces a time-dependent rise in plasma citrulline concentration to an extent dependent on the existence of villous atrophy or enterocyte hyperplasia in CeD, and adapted SBS, respectively.

Fecal energy losses in enterally fed intensive care patients: an explorative study using bomb calorimetry.

BACKGROUND & AIMS: Early enteral nutrition and tailored supply of nutrients have become standard in most of the intensive care units (ICU). So far little attention has been given to losses of energy in the stools. The purpose of this explorative study was to evaluate the energy losses of patients with loose stools, necessitating the use of a feces-collector device in a tertiary academic ICU. METHODS: In a group of 13 fully enterally fed and mechanically ventilated patients with loose stools, the daily energy loss in feces was determined, using bomb calorimetry. Malabsorption was defined as an absorption capacity of 85% or less. Energy expenditure was determined with indirect calorimetry. RESULTS: Six out of 13 (46%) patients fulfilled the criterion of malabsorption. The mean total energetic absorption capacity was 84.6+/-13.3%. The mean capacity of absorption of fat was 89.7+/-16.3%. The caloric value of energy loss had a mean of 301+/-259 kcal/day. Fecal fat loss proved not to be a good indicator of total fecal energy loss. A total of 4/13 patients (31%) had a net negative energy balance of over 500 kcal/day. A daily feces production of 250 g or more was a good predictor of malabsorption. Energy loss could accurately be predicted by using a factor 4.87 for the combined energetic value of protein and carbohydrates, if dry weight and fecal fat content are known. CONCLUSIONS: In this clinical study on ICU patients with loose stools, malabsorption proved to be a frequently occurring and so far unrecognized problem, contributing strongly to negative energy balances in 1/3 of the patients.

Are malnourished patients complex patients? Health status and care complexity of malnourished patients detected by the Short Nutritional Assessment Questionnaire (SNAQ).

BACKGROUND: This article describes the characteristics of patients identified as malnourished using the Short Nutritional Assessment Questionnaire (SNAQ) in terms of health status (quality of life, functional capacity, and body composition) and care complexity. We expected that by using the quick and easy SNAQ method of screening on malnutrition, inferences could be made about general health status and care complexity. This information can be used for optimal multi-disciplinary treatment of the malnourished patient. METHODS: The research population consisted of a group of 588 patients admitted to internal medicine and surgery wards of the VU university medical center. Patients with a SNAQ score of at least 3 points were considered malnourished. The SNAQ score was compared to the health status, which was determined by serum albumin, hand grip strength, quality of life, body composition, and estimated care complexity. RESULTS: At admission, 172 patients (29%) had a SNAQ score of at least 3 points. These patients had a significantly poorer quality of life, poorer physical functioning, a lower fat free mass index, and higher care complexity. CONCLUSION: These findings confirm our assumption that a considerable proportion of malnourished patients should be considered as complex patients and that malnutrition is an important aspect and indicator of overall health status of the patients. The SNAQ is a simple malnutrition screening tool, applicable in the current complex hospital situation, to identify these complex, malnourished patients.

[Energy losses from a short bowel: not only fat]. / Energetische verliezen uit een korte darm; meer dan alleen vet.

Two adult patients, men aged 43 and 45 years, with Crohn's disease, complicated by high-output small-bowel-stomy and short-bowel syndrome due to several intestinal resections, presented with extreme weight loss. Although both patients followed a high-calorie diet combining solid foods and enteral nutrition by nasogastric tube, containing 16,000 kJ and 21,000 kJ, respectively, weight loss continued. Faecal fat excretion and basal metabolic rate were determined, but these could not explain the caloric deficit. Therefore, faecal bomb calorimetry, a measurement of total faecal energy content, was also performed, revealing a considerably higher faecal energy loss than had been calculated from faecal fat excretion; this indicates that faecal carbohydrate loss plays an important supplementary role. A stable weightwas achieved in both patients by prescribing extra food. Therefore, faecal fat excretion is an insufficient indicator of total faecal calorie loss in patients with high-output stomata and short-bowel syndrome. Bomb calorimetry may be considered as a tool to determine the remaining absorptive capacity in short-bowel patients.

Development and validation of a hospital screening tool for malnutrition: the short nutritional assessment questionnaire (SNAQ).

OBJECTIVE: For the early detection and treatment of malnourished hospital patients no valid screening instrument for the Dutch language exists. Calculation of percentage weight loss and body mass index (BMI) by the nurse at admission to the hospital appeared to be not feasible. Therefore, the short, nutritional assessment questionnaire (SNAQ), was developed. RESEARCH, DESIGN AND METHODS: Two hundred and ninety one patients on the mixed internal and surgery/oncology wards of the VU University medical center were screened on nutritional status and classified as well nourished (<5% weight loss in the last 6 months and BMI>18.5), moderately malnourished (5-10% weight loss in the last 6 months and BMI>18.5) or severely malnourished (>10% weight loss in the last 6 months or >5% in the last month or BMI<18.5). All patients were asked 26 questions related to eating and drinking difficulties, defecation, condition and pain. Odds ratio, binary and multinomial logistic regression were used to determine the set of questions that best predicts the nutritional status. Based on the regression coefficient a score was composed to detect moderately (2 points) and severely (3 points) malnourished patients. The validity, the nurse-nurse reproducibility and nurse-dietitian reproducibility was tested in another but similar population of 297 patients. RESULTS: The questions 'Did you lose weight unintentionally?'. 'Did you experience a decreased appetite over the last month?' and 'Did you use supplemental drinks or tube feeding over the last month?' were most predictive of malnutrition. The instrument proved to be valid and reproducible. CONCLUSION: SNAQ is an easy, short, valid and reproducible questionnaire for early detection of hospital malnutrition.

Screening of nutritional status in The Netherlands.

BACKGROUND AND AIMS: In 2001, the Dutch Dietetic Association conducted a national screening on malnutrition. The goal of this screening was to determine the prevalence of disease-related malnutrition in The Netherlands in all fields of medical care and to investigate the involvement of the dietitian in the treatment of malnutrition. METHODS: Eight thousand five hundred and twenty nine patients were screened of which data of 7606 patients could be analysed. Eighty one per cent (6150) of the patients were hospital patients. Eleven per cent (808) of the patients lived in a nursing home. Seven per cent (533) of the patients were home-care patients, who were measured at home or at the general practitioner's office. The origin of 115 patients (2%) was not registered. Age, height, weight, unintentional weight loss, kind of illness and intervention by a dietitian were registered. Malnutrition was defined as >10% unintentional weight loss during the past 6 months and risk of malnutrition was defined as 5-10% unintentional weight loss during the past 6 months. RESULTS: Twelve per cent (884) of all patients appeared to be malnourished. Thirteen per cent (962) were at risk of malnutrition and 75% (5760) were well nourished. Fifty four per cent of the malnourished patients were referred to a dietitian. Oncological disease was more associated with malnutrition than non-oncological disease (in particular in the head and neck, lung and intestinal areas). Also, non-oncological gastro-intestinal and lung disease patients were often categorised as malnourished. Elderly patients (>75 years) were more at risk of malnutrition. BMI and unintentional weight loss did not correlate well. CONCLUSION: In this national survey conducted by dietitians, including a convenience sample of mainly institutionalised patients, approximately 25% of patients in all medical fields were categorised as moderately or severely malnourished. About half of these patients were seen by a dietitian.