Liquid biopsies and patient-reported outcome measures for integrative monitoring of patients with early-stage breast cancer: a study protocol for the longitudinal observational Prospective Breast Cancer Biobanking (PBCB) study.

INTRODUCTION: Breast cancer is still the most common malignancy among women worldwide. The Prospective Breast Cancer Biobank (PBCB) collects blood and urine from patients with breast cancer every 6 or 12 months for 11 years from 2011 to 2030 at two university hospitals in Western Norway. The project aims to identify new biomarkers that enable detection of systemic recurrences at the molecular level. As blood represents the biological interface between the primary tumour, the microenvironment and distant metastases, liquid biopsies represent the ideal medium to monitor the patient's cancer biology for identification of patients at high risk of relapse and for early detection systemic relapse.Including patient-reported outcome measures (PROMs) allows for a vast number of possibilities to compare PROM data with biological information, enabling the study of fatigue and Quality of Life in patients with breast cancer. METHODS AND ANALYSIS: A total of 1455 patients with early-stage breast cancer are enrolled in the PBCB study, which has a one-armed prospective observational design. Participants consent to contribute liquid biopsies (i.e., peripheral blood and urine samples) every 6 or 12 months for 11 years. The liquid biopsies are the basis for detection of circulating tumour cells, circulating tumour DNA (ctDNA), exosomal micro-RNA (miRNA), miRNA in Tumour Educated Platelet and metabolomic profiles. In addition, participants respond to 10 PROM questionnaires collected annually. Moreover, a control group comprising 200 women without cancer aged 25-70 years will provide the same data. ETHICS AND DISSEMINATION: The general research biobank PBCB was approved by the Ministry of Health and Care Services in 2007, by the Regional Ethics Committee (REK) in 2010 (#2010/1957). The PROM (#2011/2161) and the biomarker study PerMoBreCan (#2015/2010) were approved by REK in 2011 and 2015 respectively. Results will be published in international peer reviewed journals. Deidentified data will be accessible on request. TRIAL REGISTRATION NUMBER: NCT04488614.

Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database.

PURPOSE: Tamoxifen is an important targeted endocrine therapy in breast cancer. However, side effects and early discontinuation of tamoxifen remains a barrier for obtaining the improved outcome benefits of long-term tamoxifen treatment. Biomarkers predictive of tamoxifen side effects remain unidentified. The objective of this prospective population-based study was to investigate the value of tamoxifen metabolite concentrations as biomarkers for side effects. A second objective was to assess the validity of discontinuation rates obtained through pharmacy records with the use of tamoxifen drug monitoring. METHODS: Longitudinal serum samples, patient-reported outcome measures and pharmacy records from 220 breast cancer patients were obtained over a 6-year period. Serum concentrations of tamoxifen metabolites were measured by LC-MS/MS. Associations between metabolite concentrations and side effects were analyzed by logistic regression and cross table analyses. To determine the validity of pharmacy records we compared longitudinal tamoxifen concentrations to discontinuation rates obtained through the Norwegian Prescription database (NorPD). Multivariable Cox regression models were performed to identify predictors of discontinuation. RESULTS: At the 2nd year of follow-up, a significant association between vaginal dryness and high concentrations of tamoxifen, Z-4'-OHtam and tam-NoX was identified. NorPD showed a tamoxifen-discontinuation rate of 17.9% at 5 years and drug monitoring demonstrated similar rates. Nausea, vaginal dryness and chemotherapy-naive status were significant risk factors for tamoxifen discontinuation. CONCLUSIONS: This real-world data study suggests that measurements of tamoxifen metabolite concentrations may be predictive of vaginal dryness in breast cancer patients and verifies NorPD as a reliable source of adherence data.

Adherence to adjuvant endocrine therapy in postmenopausal breast cancer patients: A 5-year prospective study.

PURPOSE: Adjuvant endocrine therapy (ET) in breast cancer reduces recurrence risk and increases overall survival. The aim of the study was to quantify non-adherence and discontinuation to ET in postmenopausal women with breast cancer, and identify possible clinical or social risk factors. METHODS: Women with hormone-receptor positive breast cancer (N = 138), mean age 58 (SD 9.3) years, filled in 4 questionnaires within 1-12, 24, 36 and 48-60 months after surgery; Subjective Health Complaints Inventory (SHC), Functional Assessment of Cancer Therapy-Social Support Subscale (FACT-ES), and Quality of Patient Information Questionnaire (QPI). Adherence to Tamoxifen (Tam) or Aromatase Inhibitors (AI) was examined using self-reported adherence and data from the Norwegian Prescription Database (NorPD) [corrected]. Kaplan-Meier curves and Cox proportional hazards regression models estimated adherence to ET. RESULTS: The estimate of discontinued ET within 60 months was 38%. Self-reported discontinuation was 7% compared with 25% from the NorPD. Being overweight or obese were significantly time dependent factors predictive for discontinuing ET, p = 0.025. CONCLUSION: Closer follow-ups, tailor-made information about the proven benefits of ET, and keeping a normal body mass index (BMI) may improve adherence to ET in postmenopausal women with breast cancer.

Diet in women with breast cancer compared to healthy controls - What is the difference?

PURPOSE: After a cancer diagnosis, patients often change their lifestyle in order to improve health. The aim of this study was to examine whether women with breast cancer had changed their diet two years after the diagnosis, and to compare their diet with that of healthy female blood donors. METHODS: Patients (n = 180), median age 58 years (range 37-78), and 101 controls, median age 57 years (age 43-75) answered questions about consumption of alcohol, 36 different food items, and information like age, body mass index (BMI), marital status, and years of education. RESULTS: Forty patients (22%) had changed their diet. Comparing all patients with controls, significantly more patients avoided alcohol, p = 0.0005, and 3 of 36 food items; smoked food, p = 0.04, and milk and other dairy products, p = 0.02 and p = <0.0001, respectively. Based on BMI, 50% of all the patients reported overweight or obesity. Breast cancer treatment explained 5.7% of the total variance in scores for changing diet, where chemotherapy was the sole significant predictor, p = 0.04. CONCLUSION: Two years after a breast cancer diagnosis, most women (78%) maintained their diet, which was largely similar to the controls. Fifty percent of the patients reported overweight or obesity.

Fatigue, anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls.

BACKGROUND: Women with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls. METHOD: Women with breast cancer (N = 196) filled in 5 questionnaires 1-2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue - Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires. RESULTS: The patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p ≤ 0.001). CONCLUSION: Most women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints.

Illness uncertainty in breast cancer patients: validation of the 5-item short form of the Mishel Uncertainty in Illness Scale.

PURPOSE: Several studies have shown that uncertainty about disease and fear of disease progression affects psychosocial adjustment and quality of life. The purpose of this study was to validate a Norwegian short version of the "The Mishel Uncertainty in Illness Scale" (SF-MUIS) and to examine the impact of uncertainty in illness in breast cancer patients. METHOD AND SAMPLE: 209 patients in breast cancer treatment completed questionnaires for SF-MUIS, Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Cancer Therapy-Breast (FACT-ES), and eight questions concerning quality of the patient information provided (IQP). Relationship between scores on uncertainty in illness and anxiety, depression, social support, emotional well-being, the quality of patient information provided, and age were studied by multiple regression analyses. RESULTS: Ordinal coefficient alpha for the Norwegian version of SF-MUIS was 0.70. Scores on SF-MUIS correlated significantly with scores on HADS (P = 0.001), FACT-ES (P = 0.001), and IQP (P = 0.001) indicating good convergent validity. The patients reported a moderate degree of uncertainty in illness. However, those who had been diagnosed with breast cancer for a year, reported higher scores than those newly diagnosed (P=<0.0001). Information provided was the sole significant predictor of illness uncertainty (P=<0.0001). CONCLUSION: The results of the present study confirm that the Norwegian version of the SF-MUIS is a suitable tool for assessment of uncertainty in breast cancer patients, who reported a moderate degree of uncertainty in illness.

Chronic fatigue in patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome: validation of a Norwegian translation of the Fatigue Impact Scale.

BACKGROUND: Patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome (IBS) suffer from several health complaints, including fatigue. The aim of the present study was to validate a Norwegian translation of the Fatigue Impact Scale (FIS), and to assess the impact of fatigue in patients with self-reported food hypersensitivity and IBS, as compared with healthy controls. METHODS: Thirty-eight patients with unexplained self-reported food hypersensitivity and IBS, who participated in the validation of the FIS completed the following additional questionnaires: the Short Form of Nepean Dyspepsia Index for assessment of quality of life, the Subjective Health Complaint Inventory, and questionnaires for diagnosis and severity of IBS. Impact of fatigue was studied in 43 patients with unexplained self-reported food hypersensitivity, 70% diagnosed with IBS, and 42 healthy controls. RESULTS: Cronbach's α for the FIS was 0.98, indicating excellent agreement between individual items. Scores on the FIS correlated with scores on the Short Form of Nepean Dyspepsia Index (r = 0.50, P = 0.001), indicating good convergent validity, and were higher in patients (median 85.0, interquartile range 36.8-105.3) than in controls (median 14.0, interquartile range 3.0-29.0, P ≤ 0.0001). CONCLUSION: The Norwegian translation of the FIS performed excellently in patients with unexplained self-reported food hypersensitivity and IBS, with patients reporting significantly more impact of chronic fatigue than healthy controls.

Functional bowel symptoms, fibromyalgia and fatigue: a food-induced triad?

OBJECTIVE: Patients with perceived food hypersensitivity typically present with multiple health complaints. We aimed to assess the severity of their intestinal and extra-intestinal symptoms. MATERIALS AND METHODS: In a prospective study, 84 patients referred to our outpatient clinic for investigation of perceived food hypersensitivity were enrolled consecutively. Irritable bowel syndrome (IBS) was diagnosed according to the Rome III criteria. Severity and impact of bowel symptoms, fatigue and musculoskeletal pain were evaluated by using the following questionnaires: The IBS Severity Scoring System (IBS-SSS), the Fatigue Impact Scale (FIS), the FibroFatigue Scale (FFS), and visual analogue scales (VAS) for scoring of musculoskeletal pain. RESULTS: All but one patient were diagnosed with IBS, 58% with severe symptoms. Extra-intestinal symptoms suggestive of chronic fatigue and fibromyalgia were demonstrated in 85% and 71%, respectively. Neither IgE-mediated food allergy nor organic pathology could explain the patients' symptoms. Nevertheless, malabsorption of fat was demonstrated in 10 of 38 subjects. CONCLUSIONS: Perceived food hypersensitivity may be associated with severe, debilitating illness. The comorbid triad of IBS, chronic fatigue, and musculoskeletal pain is striking and may point to a common underlying cause.

Perceived food hypersensitivity: a review of 10 years of interdisciplinary research at a reference center.

Perceived food hypersensitivity is a prevalent, but poorly understood condition. In this review article, we summarize narratively recent literature including results of our 10 years' interdisciplinary research program dealing with such patients. The patients (more than 400) included in our studies were all adults referred to a university hospital because of gastrointestinal complaints self-attributed to food hypersensitivity. Despite extensive examinations, food allergy was seldom diagnosed. The majority of the patients fulfilled the diagnostic criteria for irritable bowel syndrome. In addition, most suffered from several extra-intestinal health complaints and had considerably impaired quality of life. However, psychological factors could explain only approximately 10% of the variance in the patients' symptom severity and 90% of the variance thus remained unexplained. Intolerance to low-digestible carbohydrates was a common problem and abdominal symptoms were replicated by carbohydrate ingestion. A considerable number of patients showed evidence of immune activation by analyses of B-cell activating factor, dendritic cells and "IgE-armed" mast cells. Multiple factors such as immune activation, disturbed intestinal fermentation, enteric dysmotility, post-infectious changes and "local" allergy in the gut as well as psychological disturbances may play a role in the pathophysiology of perceived food hypersensitivity. Hence, our results support the view that management of these patients should be interdisciplinary.

Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study.

Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of life (QoL) in patients with subjective food hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of whom 25 had irritable bowel syndrome (IBS), were included in the present study. Before and after treatment and 1 month posttreatment, patients filled in the Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health complaints (SHC) inventory for nongastrointestinal symptoms in addition to short form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL improved significantly, both at end of treatment and 1 month posttreatment. The consistent improvements following seal oil administration warrant further placebo-controlled trials for confirmation of effect.

Do psychological factors predict symptom severity in patients with subjective food hypersensitivity?

OBJECTIVE: We examined whether psychological factors such as general and gastrointestinal symptom-specific anxiety and depression could predict symptom severity in patients with unexplained, self-reported (subjective) food hypersensitivity. For the purpose, we translated and validated the Visceral Sensitivity Index (VSI). MATERIAL AND METHODS: Seventy consecutive patients completed questionnaires for Hospital Anxiety and Depression Scale, VSI, Irritable Bowel Syndrome Symptom Questionnaire, and Subjective Health Complaints Inventory. Relationship between scores on psychological factors and scores on somatic symptoms were studied by multiple regression analyses. RESULTS: Most patients reported non-gastrointestinal symptoms in addition to their irritable bowel syndrome complaints, but general and symptom-specific anxiety, and depression could not explain a significant amount of the variance in somatic complaints. Gastrointestinal symptom-specific anxiety was a significant predictor of gastrointestinal complaints (p = 0.02), and age was the sole significant predictor of non-gastrointestinal complaints (p = 0.01). Approximately 90% of the total variance in symptom severity remained unexplained by the psychological factors. The Norwegian version of the VSI had satisfactory validity (Cronbach alfa = 0.93). Symptom-specific and general anxiety were significantly correlated (r = 0.48, p < or = 0.0001). CONCLUSIONS: Psychological factors were not major predictors of symptom severity in patients with subjective food hypersensitivity. The Norwegian version of VSI had satisfactory validity.

Anxiety and depression in patients with self-reported food hypersensitivity.

OBJECTIVE: Self-reported food hypersensitivity (SFH) is common. Psychological factors are assumed to be associated. We assessed anxiety and depression in SFH patients, using both questionnaires and interview. METHODS: Consecutive patients (n=130) and randomly selected healthy volunteers (n=75) completed the Hospital Anxiety and Depression Scale (HADS), the neuroticism scale of the Eysenck Personality Questionnaire (EPQ-N) and the General Health Questionnaire (GHQ). Seventy-six of the patients were also interviewed by use of the Mini International Neuropsychiatric Interview and the Montgomery-Aasberg Depression Rating Scale. All patients underwent extensive allergological, gastroenterological and dietary examinations. RESULTS: According to interviews, 57% of patients fulfilled the DSM-IV criteria for at least one psychiatric disorder. Anxiety disorders (34%) and depression (16%) predominated. According to questionnaires, patients scored significantly higher than controls on all psychometric scales except for depression (HADS). We also found an underreporting of depression in HADS compared with interviews (2.5% vs. 16%, P=.001). Food hypersensitivity was rarely confirmed by provocation tests (8%). Eighty-nine percent of the patients had irritable bowel syndrome. CONCLUSIONS: Anxiety and depression are common in patients with IBS-like complaints self-attributed to food hypersensitivity. Anxiety disorders predominate. In this setting, depression may be underreported by HADS.

Subjective health complaints and quality of life in patients with irritable bowel syndrome following Giardia lamblia infection: a case control study.

OBJECTIVE: Irritable bowel syndrome (IBS) is associated with unexplained medical symptoms, and the degree of somatic comorbidity may indicate whether the aetiology of IBS is predominantly psychological or biological in origin. The purpose of this study was to examine the comorbidity and quality of life of patients with IBS following infection with Giardia lamblia. MATERIAL AND METHODS: Sixty-seven consecutive patients with persistent abdominal symptoms, initiated by an acute infection with G. lamblia, completed questionnaires for scoring of subjective health complaints (SHC) and quality of life (Short-form Nepean Dyspepsia Index (SF-NDI)). The scores were compared with corresponding scores in persons from the general population (n=70). RESULTS: Compared with controls, each of the two groups of patients, those with present (n=17) and those with cured (n=50) G. lamblia infection, had significantly higher scores (p<0.0001) on SHC. However, subscores on somatic comorbidity (musculoskeletal pain) were low and similar to those in the general population (OR 1.2 (0.51-2.73)). Quality of life was substantially impaired in the patients; sum scores 30.0+/-8.0 (mean+/-SD) and 31.7+/-9.3 in the patient groups and 13.5+/-6.8 in the general population (p<0.0001). CONCLUSIONS: Patients with post-giardiasis IBS suffer very little somatic comorbidity, suggesting that the aetiology of this form of postinfective IBS is predominantly biological in origin and may thus differ from the more common, non-postinfective forms of IBS. The combination of persisting abdominal symptoms and psychological distress might be a perpetuating factor contributing to low quality of life.

Lifestyle of patients with self-reported food hypersensitivity differ little from controls.

The aim of this study was to examine the lifestyle of adult patients with abdominal discomfort (i.e., diarrhea, bloating, pain, and irregular defecation) self-attributed to food hypersensitivity and compare it with controls to see if the patients had a special lifestyle explaining their symptoms. Forty-six participants in this study were adult ethnic Norwegians referred by general practitioners to the Centre for Occupational and Environmental Allergy at Haukeland University Hospital because of gastrointestinal complaints, which the patients or their doctors suspected could be due to food allergy. They were compared with 70 age- and sex-matched volunteer controls from the general population. All participants filled out an extensive questionnaire focusing on different lifestyle aspects. One hundred percent of the patients and 43% of the controls (p < .0001) reported hypersensitivity to at least one food item. Significantly, fewer patients than controls reported daily consumption of milk (p = .004), coffee (p = .02), and alcohol (p = .008) for the past year. Among consumers, the participants used less milk (P = .002) and coffee (P = .04) than controls. Eating habits, meal patterns, quality of sleep, the amount of exercise, and use of painkillers were similar in both groups. There were small differences in lifestyle between the patients and the controls. Patients with gastrointestinal complaints self-attributed to food hypersensitivity used less milk, coffee, and alcohol, but none of those differences explain their symptoms. Such lifestyle would rather be expected to lessen symptoms, and we postulate that it is the consequence of their food intolerance and not its cause.

Effects of short-term oral administration of dietary marine oils in patients with inflammatory bowel disease and joint pain: a pilot study comparing seal oil and cod liver oil.

BACKGROUND: Very long chain n-3 polyunsaturated fatty acids have modulating effects on inflammatory mechanisms. Seal and fish oils are rich in n-3 polyunsaturated fatty acids, and possibly therefore high doses of nasoduodenally administered seal oil rapidly relieved inflammatory bowel disease (IBD)-associated joint pain in two recent studies. In the present study, we compared the effects of short-term oral administration of seal oil and cod liver oil on IBD-related joint pain, leucotriene B(4) level, serum fatty acid profile and IBD activity. METHODS: Thirty-eight patients with IBD-related joint pain were included in the study; 21 had Crohn's disease and 17 ulcerative colitis. Ten milliters of seal oil (n=18) or cod liver oil (n=20) was self-administered orally 3 times a day for 14 days before meals in a double-blind setting. RESULTS: There were no significant differences between the two intervention groups or between Crohn's disease and ulcerative colitis patients. There was a tendency toward improvement in several joint pain parameters after both seal oil and cod liver oil administration. Further, plasma leucotriene B(4) concentration, serum Sigma n-6 to Sigma n-3, and arachidonic acid (20:4n-6) to eicosapentaenoic acid (20:5n-3) ratios were similarly reduced after administration of seal oil and cod liver oil. CONCLUSION: No significant differences in the two treatment groups were seen; in both groups, the changes in several joint pain parameters, leucotriene B(4) level of plasma, and serum fatty acid profile were putatively favourable.

Short-term duodenal seal oil administration normalised n-6 to n-3 fatty acid ratio in rectal mucosa and ameliorated bodily pain in patients with inflammatory bowel disease.

BACKGROUND: A high dietary intake of n-6 compared to n-3 fatty acids (FAs) may promote the production of pro-inflammatory eicosanoids and cytokines. In two recent studies, short-term (10-day) duodenal administration of n-3 polyunsaturated fatty acid rich seal oil ameliorated joint pain in patients with inflammatory bowel disease (IBD). Using unpublished data from these two studies we here investigated whether normalisation of the n-6 to n-3 FA ratio in blood and tissues by seal oil administration was associated with improved health related quality of life (HRQOL) as assessed by the generic short-form 36 (SF-36) questionnaire. RESULTS: In the first pilot study, baseline n-6 to n-3 FA ratio in rectal mucosal biopsies from 10 patients with IBD (9 of those had joint pain) was significantly increased compared with that in 10 control patients without IBD or joint pain. Following seal oil administration, the n-6 to n-3 FA ratio of the IBD-patients was significantly lowered to the level seen in untreated controls. In the subsequent, randomized controlled study (n = 19), seal oil administration reduced the n-6 to n-3 FA ratio in blood similarly and also the SF-36 assessed bodily pain, while n-6 FA rich soy oil administration had no such effect. CONCLUSION: In these two separate studies, short-term duodenal administration of seal oil normalised the n-6 to n-3 FA ratio in rectal mucosa and improved the bodily pain dimension of HRQOL of patients with IBD-related joint pain. The possibility of a causal relationship between n-6 to n-3 FA ratio in rectal mucosa and bodily pain in IBD-patients warrants further investigations.

Subjective health complaints and modern health worries in patients with subjective food hypersensitivity.

Perceived food hypersensitivity is much more common than food allergy as medically verified. Unexplained symptoms and wrong attribution are typical in subjective health complaints. We hypothesize that subjective health complaints and worries are abnormally prevalent among patients with subjective food hypersensitivity. Forty-six patients with subjective food hypersensitivity and two control groups, one formed by 50 health care workers and one by 70 sex- and age-matched volunteers from the general population, were included in our study. All filled in two questionnaires: Subjective Health Complaints Inventory and Modern Health Worries Scale. None of the patients had IgE-mediated food allergy. The patients scored significantly higher than the controls on sum scores for four domains of subjective health complaints, including gastrointestinal complaints (P < 0.001), musculoskeletal complaints (P < 0.01), "pseudoneurology" (P < 0.001), and allergy (P < 0.001). Sum scores on modern health worries did not differ significantly between groups. The results support our hypothesis of an association between subjective food hypersensitivity and subjective health complaints, corroborating the view that, in the absence of food allergy, the conditions are sharing pathogenetic mechanisms.

Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity.

OBJECTIVE: Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound. MATERIAL AND METHODS: Thirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge. RESULTS: Sonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p = 0.008) and a positive double-blind placebo-controlled food challenge (p = 0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r = 0.50, p = 0.004) or the jejunum (r = 0.42, p = 0.02). Intra- and interobserver variation of the tracing procedure showed low values. CONCLUSIONS: Responses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.

Food hypersensitivity-immunologic (peripheral) or cognitive (central) sensitisation?

Patients with food hypersensitivity suffer poor quality of life and several unexplained health complaints, both abdominal and extra-abdominal. Part of the suffering is due to healthcare providers' neglect and poor insight, allowing a strong position for alternative medicine. Distinguishing food allergy from functional and organic disorders can be extremely difficult. We have found examination of faecal calprotectin and gut permeability to be useful for excluding organic disease, whilst conventional provocation tests for positive diagnosis of food hypersensitivity are cumbersome. Our new ultrasound provocation test has been promising, but we acknowledge that much work remains to be done before its sensitivity and specificity can be finally established. The majority of patients with self-reported food hypersensitivity have a non-allergic hypersensitivity disorder. We suggest that cognitive-emotional sensitisation at the brain level, and not peripheral (immunological) sensitisation, is a major pathogenetic mechanism by which the patients' various abdominal and extra-abdominal health complaints are generated. Extensive activation of cognitive networks might be triggered by peripheral sensory mechanisms, often misinterpreted as 'food allergy'. Clearly, the approach to patients with food hypersensitivity should be interdisciplinary.