Gastrointestinal toxicity of systemic oncology immunotherapy.

BACKGROUND: Systemic anti-cancer immunotherapy provides a substantial progress in options of current oncology treatment. Yet, this therapeutic approach is potentially associated with a significant gastrointestinal toxicity. AIM: The purpose of this paper is to provide a comprehensive review on pathogenesis, clinical features, dia gnostics and therapy of these toxicities. Review of current knowledge: Check-point inhibitors brought a major progress in anti-cancer immunotherapy and improved significantly prognosis of several malignancies (e. g. metastatic malignant melanoma, non-small-cell lung cancer, gastric and colorectal cancers in high-risk population associated with presence of pathogenic mutations, renal cell carcinoma, squamous cell carcinoma of the head and neck and urothelial carcinoma). They include monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4; e. g. ipilimumab, tremelimumab), programmed death-1 receptor (PD-1; e. g. pembrolizumab, nivolumab) and its ligand PD-L1 (e. gatezolizumab, avelumab). Chimeric antigen receptor (CAR) T-cell therapy is another new option for haematological malignancies and metastatic colorectal cancer. Major symptoms of gastrointestinal toxicity caused by systemic immunotherapy include diarrhoea (20-50%), entero-colitis (1-10%) and laboratory or clinical signs of hepatopathy (~10%). Anti-cancer immunotherapy can be also complicated by infections (Clostridium difficile, Mycoplasma and/ or cytomegalovirus). There is no data on other possible complications so far. However, it can be assumed that these will also include bile acid malabsorption as well as small intestinal bacterial overgrowth syndrome. Treatment of gastrointestinal complications of immunotherapy should be graded according to their severity. It includes symptomatic medications (e. g. loperamide), systemic glucocorticoids and anti-TNF monoclonal antibodies (alone or together with mycofenolate mofetil or tacrolimus in the most severe cases). CONCLUSIONS: Awareness of possible complications of systemic anti-cancer immunotherapy is crucial for patients safety. It is mandatory to consider immune-related adverse events, complicating infections, bile acids malabsorption and small intestinal bacterial overgrowth syndrome. Prompt proper dia gnostics and immediate vigorous therapy infl uence the outcome of patients signifi cantly. A strictly individualized approach is indispensable.

High resolution anorectal manometry in patients with anorectal dysfunctions and the therapeutic consequences.

INTRODUCTION: High resolution anorectal manometry (HRAM) is a diagnostic method indicated in patients with anorectal dysfunction. The aim of the study was to evaluate the prevalence of anorectal dysfunctions and to assess therapeutic consequences. METHODS: Retrospective data of consecutive patients referred to HRAM in the period from March 2019 to February 2021 were evaluated. Basic manometric parameters were assessed: resting pressure (RP), maximal squeeze pressure (SP), rectal sensitivity (RS), and dyssynergic defecation (DD). RESULTS: 113 patients with combined fecal incontinence and obstructive defecation syndrome (FI + ODS: 44.2%), fecal incontinence (FI: 26.5%), obstructive defecation syndrome (ODS: 16.8 %), stoma before restoration of intestinal continuity (6.2%), functional pelvic pain (FP: 3.5 %) and controversial cases (2.7%) were analyzed. The average age was 54 years; female patients predominated (72 %). Patients with FI and FI+ODS had lower mean RP (57 mmHg and 53 mmHg) and/or lower SP (160 mmHg and 140 mmHg) compared to baseline. Patients with ODS had normal values of mean RP (75 mmHg) and SP (225 mmHg). DD was noted in most patients (FI: 76.6%, FI + ODS: 88%, ODS: 89.5%, FP: 100%). Conservative therapy with pelvic floor physiotherapy was provided in most cases (FI+ODS: 40%, ODS: 36.8%, FI: 13.3%, FP: 75%). CONCLUSION: In patients with defecation disorders there is a high prevalence of pathological manometric findings that combine with each other. Based on manometric findings, conservative treatment with individual pelvic floor physiotherapy can be initiated.

Pathophysiological Characteristics Linking Type 2 Diabetes Mellitus and Colorectal Neoplasia.

A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention.

Zenkers diverticulum - effectiveness of endoscopic therapy.

Zenkers diverticulum is the most common type of esophageal diverticulum with a prevalence of 0.01 to 0.11 %, usually found in middle-aged and older patients. The prevalent symptoms are dysphagia and regurgitation. Treatment is recommended in symptomatic patients and consists of myotomy of the cricopharyngeal muscle. Both surgical and endoscopic methods are used in the treatment of Zenkers diverticulum. With technical advances, flexible endoscopy has come to the forefront in the treatment of Zenkers diverticulum, especially in older polymorbid patients. Its advantages include lower morbidity and mortality, shorter surgery time, the possibility of performing the procedure without general anesthesia, and a shorter hospital stay, including early oral food intake. In this paper we present our own experience with endoscopic treatment of Zenkers diverticulum and at the same time we provide a review of effectiveness with other methods of treatment.

Update and review of diagnosing functional anorectal disorders - standardized protocol for high-resolution anorectal manometry and the London classification.

Complex anorectal examination including a detailed medical history, physical proctological examination and evaluation of the sensorimotor and structural function of the anorectum is essential for the diagnosis and therapeutic management of functional anorectal dysfunction. The aim of the work is to provide an overview of diagnosing functional anorectal disorders according to the new update and consensus statement of the International Anorectal Physiology Working Group (IAPWG) with a focus on indications, a standardized examination protocol and introduction of the new London classification of anorectal dysfunction. The indications are: fecal incontinence, defecation disorders, functional pelvic (anorectal) pain, evaluation before an anorectal intervention and before planned delivery to assess the function of a previously traumatized anal sphincter. Standardization of the diagnosis and the evaluated data are the basis for multidisciplinary cooperation and determination of a treatment plan for each patient individually.

3D high-resolution anorectal manometry selected case reports.

Presented selected case reports are focused on the individual cases of patients suffering from functional anorectal disorders. During the examination algorithm, the emphasis is on 3D high-resolution anorectal manometry, which is a useful diagnostic technique and helps to understand the pathophysiological mechanisms in the field of functional anorectal disorders. Thanks to a comprehensive examination an individualized treatment plan can be determined for each patient.

Accuracy of EUS and CEH EUS for the diagnosis of pancreatic tumours.

OBJECTIVES: The main objective is to compare the accuracy of EUS and CEH EUS for the diagnosis of pancreatic cancer (PC). The secondary objective is to evaluate the accuracy of EUS FNA and to determine to what extent EUS and CEH EUS findings are affected by endosonographer subjectivity. METHODS: A prospective single-centre study was conducted in patients with pancreatic lesions detected on CT. The patients were examined by EUS, CEH EUS and EUS FNA. The obtained results were compared with the final diagnosis that was based on cytology and further clinical findings and on histopathological findings from subjects who underwent surgery. A second reading of the EUS and CEH EUS images was performed by the endosonographer, who was blinded to clinical data of patients. RESULTS: We examined 116 patients, 73 had a final diagnosis of PC, 14 had NETs and 20 had other tumours. The sensitivity, specificity, NPV, PPV, and accuracy of EUS for diagnosis of PC were 83.1, 62.5, 83.1, 70.7 and 78.6%, for CEH EUS 94.5, 61.7, 84.1, 84 and 84.1% and for EUS FNA 87.6, 91.2, 95.5, 77.5 and 88.8, respectively. The inter-observer agreement for EUS marker of PC was good (κ = 0.75), and that for CEH EUS was average (κ = 0.59 for arterial phase and κ = 0.68 for washout in venous phase). CONCLUSION: CEH EUS is a non-invasive method that allows more accurate identification of PC than EUS. The subjectivity of CEH EUS evaluation is worse than that of EUS but acceptable.

[Current application and future perspectives of capsule colonoscopy]. / Soucasné vyuzití a budoucnost kapslové kolonoskopie.

Colon capsule endoscopy (CCE) is a noninvasive technique for diagnostic imaging of the colon that does not require air insufflation or sedation. CCE can be used in average-risk patients, in patients with incomplete colonoscopy and in patients with contraindications for conventional colonoscopy. In this paper, we review the technical characteristics, current application and possible future development of CCE.Key words: colorectal cancer - screening colon capsule endoscopy.

[Diagnosis of early pancreatic cancer and precursor lesions]. / Diagnostika casného karcinomu pankreatu a prekurzorových lézí.

Pancreatic cancer is a malignancy, which usually carries a poor prognosis; the 5-year survival is less than 6%. Therefore, its early detection in a stage when curable resection can be performed is essential to give the patients the best possible chance for a long-term survival. Despite the use of the most up-to-date diagnostic procedures, an early diagnosis of pancreatic carcinoma is rather unsuccessful. Furthermore, long-term survival rates for pancreatic cancer patients are still unsatisfactory, even when diagnosed early. Nevertheless, alterations occur in biomolecules as early as during the onset of oncogenesis, which can be detected by structure-sensitive spectroscopic methods. These methods provide a potential for detecting a sufficiently specific biomarker of early pancreatic carcinoma. A pilot study using molecular spectroscopy was conducted at the 1st Department of Internal Medicine, 1st Faculty of Medicine, Charles University and Military University Hospital in Prague, Czech Republic, in cooperation with the Department of Analytical Chemistry, University of Chemistry and Technology in Prague, Czech Republic. In the study, we compared the spectral response of blood plasma of patients with pancreatic carcinoma and healthy controls. Molecular spectroscopy provided evidence of significant differences between the two groups as illustrated by the study results. This approach thus might be suitable for detecting a specific biomarker of early pancreatic carcinoma. The findings have forced us to rethink the practical benefits of all potential biomarkers. In the future, we might face a situation where although any given marker is positive in a patient, no convincing morphological correlation can be found using available imaging methods. An important question is thus raised - whether or not to indicate surgical resection only on the basis of the biomarker positivity, and what type of resection to opt for.Key words: pancreatic cancer - early detection - spectroscopy - pancreatectomy.

[Pneumoperitoneum after colonoscopy - "to cut or not to cut"]. / Pneumoperitoneum po kolonoskopii - "to cut or not to cut".

Colon perforation is a very serious complication of colonoscopy. The correct diagnosis and management of therapy improve the prognosis of patients. The treatment can be conservative, endoscopic and surgical. In this case report we present microperforation as a complication of polypectomy in the caecum during colonoscopy, followed by laparoscopic surgery.Key words: colonoscopy - complication -perforation polypectomy.

Propofol-induced acute pancreatitis.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced acute pancreatitis comprises only 0.5%-2% of all cases of acute pancreatitis. Propofol is a potentially dangerous drug that can cause acute pancreatitis, but this complication is extremely rare. CASE SUMMARY: A 57-year-old patient developed acute pancreatitis after a planned thyroidectomy. As the common causes of acute pancreatitis were excluded, we believe that the pancreatitis was drug-induced, in this case by a single dose of propofol administered to the patient during the surgery. WHAT IS NEW AND CONCLUSION: We present a rare case of propofol-induced acute necrotising pancreatitis, which is to the best of our knowledge the first fatal case reported in an adult patient.

DIABETIC KETOACIDOSIS WITH AN ACUTE ABDOMEN AS A FIRST MANIFESTATION OF TYPE 1 DIABETES MELLITUS.

CONTEXT: Diabetic pseudoperitonitis is a very rare complication of the type 1 diabetes mellitus and it is associated with a severe ketoacidosis. The exact pathogenesis of the status is still unclear, the typical presentation is an acute abdomen by the patient. To confirm the diagnosis, it is necessary to make examinations, which exclude other possible reason of an acute abdomen by the patient (laboratory tests, abdominal ultrasound or a CT scan). CASE PRESENTATION: A 46-years old man was admitted to the hospital wih a history of a 10 days epigastric pain. Laboratory tests, abdominal ultrasound, CT scan and upper endoscopy were performed, the reason of the pain remained unclear. Because of the peritoneal signs at the first day of the hospitalisation an acute surgery was indicated, without any pathology at the laparoscopy. A severe metabolic acidosis was recognized only after the surgery, the initial hypoglycaemia rose up after giving a total parenteral nutrition to the patient. The increase of the glycaemia, the severe metabolic acidosis with glycosuria and ketonuria, and the elevation of the glycated haemoglobin brought us to the diagnosis of the new onset of the diabetes. CONCLUSION: Diabetic pseudoperitonitis with the picture of an acute abdomen can occur as a first manifestation of the diabetes. Thinking of this rare complication and recognising it can avoid unnecessary acute surgery by the patient.

[The populations attitudes to colorectal cancer screening in the Czech Republic]. / Prístup populace ke screeningu kolorektálního karcinomu v Ceské republice.

BACKGROUND: The mortality of colorectal cancer (CRC) is significant worldwide. There is good evidence for benefits of the CRC screening in mortality reduction. Since 2009, the population of the Czech Republic have had two CRC screening options from which to choose: a faecal occult blood test (FOBT) at the age of 50 to be repeated every two years or primary screening colonoscopy (PSC) at the age of 55. General practitioners play a crucial role in the CRC screening programme. The CRC screening adherence of the Czech population is poor and does not exceed 25%. MATERIAL AND METHODS: The aims of the study were to analyse the reasons behind the low CRC screening adherence of the Czech population, to classify the populations attitudes, and to identify the barriers. A questionnaire survey was conducted in a Czech energy company with 13,000 employees in 2011-2012. The questionnaire was administered electronically by e-mail or directly at the workplace. RESULTS: The questionnaire response rate was 31.3% (4070). The pool of respondents consisted of 2804 (68.9%) females and 1266 (31.1%) males. Of the respondents, 1345 (33.1%) were aged over 50 years (73.5% women and 26.5% men). Of the cohort aged over 50, 68.65% of women and 63.2% of men took a FOBT. Ten percent of respondents aged over 50 years have never heard of CRC screening and 32.8% of this age category have never participated in CRC screening. The main reasons for not taking a FOBT were feeling well and having no health problems (38.8%) or FOBT not offered the by the general practitioner (27.8%). Other reasons were no time to do so, fear of the result, unsure of the procedure, unawareness of what FOBT is, or uncomfortable about the test procedure. On the other hand, 8.37% of the participants aged between 15 and 39 years and 20.7% of those aged between 40 and 49 years have already taken a FOBT. Overall, 15.4% of respondents prefer the new alternative, PSC, as the CRC screening option. Significant differences in CRC screening adherence are seen between administrative regions of the Czech Republic and between education levels. CONCLUSIONS: From the results, it follows that a considerable proportion of the population of the Czech Republic do not understand the principle of CRC screening and its methods. Enough room has been left to promote education on CRC screening for both the public and general practitioners. On the other hand, a large part of proactive individuals participate in CRC screening before the age of 50.

[Approach to population-based screening in the Czech Republic, methodology and first results of the personalised invitation of citizens to cancer screening programmes]. / Koncepce populacního screeningu v Ceské republice, metodika a první výsledky adresného zvaní obcanu do preventivních onkologických programu

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

[Results of the Czech National Colorectal Cancer screening programme -  faecal occult blood tests]. / Výsledky Národního programu screeningu kolorektálního karcinomu v Ceské republice -  testy na okultní krvácení do stolice.

INTRODUCTION: The nationwide Colorectal Cancer Screening Programme was introduced in the Czech Republic in 2000. The aim of this article is to describe the employment of faecal occult blood tests (FOBTs) by the Czech population within the screening programme, and to provide information on the latest results of the programme. MATERIAL AND METHODS: Data on the development of the colorectal cancer (CRC) burden in the Czech population is obtained from the Czech National Cancer Registry, a database required by the Czech law that has been collecting comprehensive data on cancer patients since 1977. Data on FOBT employment can be obtained from health care payers, and was provided by the Czech National Reference Centre. RESULTS: Around 8,000 patients are diagnosed with colorectal cancer in the Czech Republic each year, and the number of CRC deaths is about 4,000. Despite the ongoing screening programme, significant improvements in the proportional representation of cancer stages (i.e., improvements in early detection of CRC cases) have yet to be seen. Although the number of FOBTs performed in the Czech Republic has significantly grown in the long term (which is accompanied by an increase in coverage by this screening test), the total coverage of the Czech population aged over 50 was only 25.5% in 2012. The Olomouc Region, the Zlin region, and the Usti nad Labem region had the highest coverage rates by CRC screening based on FOBT (over 28%), while the Capital of Prague had the lowest coverage rate (18%). Since 2008, FOBT positivity rates have seen a continuous and significant increase, reaching 6.9% in 2012. Between 13 to 14% of FOBTs in women are performed by practical gynaecologists. CONCLUSION: Despite a significant increase in the participation rate in recent years, which was partially improved by the involvement of practical gynaecologists, the programme unfortunately still covers only a quarter of the eligible population. Implementation of effective measures aimed at getting people interested in preventive examinations (including the recently introduced programme of personalized invitations) is therefore essential; otherwise, the screening programme will not be successful on the population level.

[Results of the Czech National Colorectal Cancer Screening Programme - colonoscopy examinations]. / Výsledky Národního programu screeningu kolorektálního karcinomu v Ceské republice - kolonoskopická vysetrení

INTRODUCTION: Colorectal cancer (CRC) is one of the most common cancers, and the Central European countries have the highest CRC burden worldwide. CRC screening has repeatedly been proven capable of decreasing CRC mortality and incidence rates. The nationwide Colorectal Cancer Screening Programme in the Czech Republic involves the colonoscopic examination as a diagnostic method (for patients with a positive FOBT result -  screening colonoscopy -  SC), or as a screening method (primary screening colonoscopy -  PSC). The aim of this article is to present the results of colonoscopic examinations performed as part of the Czech screening programme. MATERIAL AND METHODS: For the purpose of quality assurance, the Czech programme has been equipped since 2006 with an information system called the Colorectal Cancer Screening Registry, which collects and evaluates data on preventive colonoscopies performed in the colonoscopy screening centres. Performance indicators, as specified in the European Guidelines (and adapted for the Czech programme), are employed to assess preventive colonoscopies performed in the Czech Republic. RESULTS: Since 2006, more than 110,000 SCs and almost 20,000 PSCs were recorded. Approximately 95% of SCs and almost 98% of PSC were classified as total, i.e. examining the entire colonic mucosa up to the caecum. The positive predictive value of FOBT for adenomas has increased slightly and continuously over time, and was 39.7% in 2013. In PSC, the adenoma detection rate (ADR) has recently increased compared to previous years, and was 27.3% in 2013. CRC was detected in 3.7% of individuals undergoing an SC examination and in 1.0% of individuals undergoing a PSC examination. The programme safety is controlled based on the monitoring of complications during colonoscopies; these can occur either during diagnostic colonoscopy (perforation in 0.03% of cases since 2006) or during endoscopic polypectomy (perforation in 0.12% of cases, bleeding in 0.73% of cases since 2006). CONCLUSION: Our results confirm that the quality of colonoscopic examinations corresponds to the international standards and that this is not an obstacle to a positive impact of CRC screening on the Czech population, which has a high colorectal cancer burden.

[Performance indicators in screening programmes]. / Indikátory kvality screeningových programu

Breast, colorectal and cervical cancer screening programmes make it possible to decrease the population mortality rates of these diseases. How-ever, complex standards of the quality of care must be introduced and followed in order to maintain a favourable ratio between the benefits and risks arising from population-wide screening programmes. Such programmes should be organized and population-based, ensuring that quality control is performed at all levels. This review introduces the system of quality control in the Czech cancer screening programmes, and provides specific examples of performance indicators that are usable and/ or being used in these programmes. Cancer screening programmes in the Czech Republic are equipped with a comprehensive information background which involves monitoring of the cancer burden in the population, monitoring of the screening process based on clinical data, and monitoring of the screening process based on administrative data. In particular, the specific performance indicators describe the success rate of take up of the target population, ability of the screening test to reveal (sensitivity) or to exclude (specificity) the screened condition, correct employment of subsequent diagnostic methods or treatment of detected cancers or precancerous lesions where applicable. In the Czech breast cancer screening programme, these indicators are routinely used in order to monitor the individual centres; in both colorectal and cervical cancer screening programmes, these indicators are used to monitor the entire programme, whereas the system of quality control for individual centres is under continuous development. A project of personalized invitations was launched in 2014, and its results are regularly evaluated in cooperation with the Czech National Reference Centre and the Ministry of Health of the Czech Republic.

[New European Information and Communication Platform Striving for Improved Care for Colorectal Cancer Patients - www.crcprevention.eu]. / Nová evropská konferencní a informacní platforma usilující o zlepsení péce o pacienty s kolorektálním karcinomem -  www.crcprevention.eu.

The article introduces a new information and communication platform that focuses on the promotion of colorectal cancer prevention and on the improvement of care for colorectal cancer patients. In addition to the platforms objectives, the article also presents the conclusions of the first year of the "European Colorectal Cancer Days" international conference held annually in Brno since 2012. Further information and news are available at www.crcprevention.eu.

Feedback is the best way to see.

A 60-year-old man with past history of acute mild pancreatitis (AP) in 1997 and 2005, recently with repeated attacks of AP 5 times in last 2 years. Repeated endoscopic ultrasonography (EUS) showed 20 mm cyst in pancreatic body with 5 mm nodule, main pancreatic duct (MPD) 4-6 mm, fine-needle aspiration malignant cell negative, mucin positive. Computed tomography and magnetic resonance imaging of branch duct intraductal papillary mucosal neoplasms with 10 mm branch duct. From 2011 to 2013, the cyst was without progression in size or character. Due to clinical course of repeated AP, endoscopic retrograde cholangiopancreatography was recommended. It revealed dilated MPD 5-7 mm and 15 mm × 13 mm cyst in pancreatic body. Distal pancreatectomy was indicated because of clinical course and "worrisome EUS features" - MPD size and intramural nodule. In terms of having feedback, endosonographer use to examine every resected specimen of pancreas in our hospital just after surgery. The resected body with "sand glass" appearance of the cyst of size 3 cm was totally different from what we saw previously. We rewinded the previous EUS documentation and made a new evaluation. EUS is unique method for pancreatic tumors, but only in combination with real image of specimen makes endosonographer to bow up.

[Gluten induced diseases]. / Choroby zpusobené lepkem.

The introduction of cereals in human nutrition 10 000 years ago caused the occurrence of gluten induced diseases. This protein complex is involved in pathogenesis of wheat allergy, celiac disease, and gluten sensitivity. Wheat allergy and celiac disease are mediated by the system of adaptive immunity. Gluten sensitivity is a recently defined entity induced by innate immune mechanisms. These subjects present various intestinal and particularly extraintestinal symptoms. The differences between celiac disease and gluten intolerance include permeability of the intestinal mucosal barrier, histology of duodenal biopsy, and mucosal gene expression. The symptoms of gluten sensitivity may also have another genetic background of food intolerance independent of the HLADQ2, - DQ8 system and tissue transglutaminase (eg. in some psychiatric disorders). At present, there is no specific bio-marker of gluten sensitivity. The diagnosis is possible only by exclusion of other causes of symptoms and improvement on a glutenfree diet applied in a doubleblind placebo controlled manner with optional sequence of both stages to exclude the placebo effect due to nutritional intervention.