Bouveret syndrome / Bouveret-szindróma.

Összefoglaló. A Bouveret-szindróma egy bilioenteralis fistulán keresztül a vékonybélbe - az esetek 85%-ában a duodenumba - jutó nagy epeko okozta bélelzáródást jelenti. Leggyakrabban idos nok körében fordul elo. Jelen közleményünk célja e kórkép tüneteinek, diagnosztikájának és terápiás lehetoségeinek ismertetése egy esetbemutatás kapcsán. A 79 éves nobeteg felvételi hasi panaszainak hátterében típusos gyomorkimenet-obstrukciós szindrómát okozó, a duodenumban beékelodött epeko, Bouveret-szindróma igazolódott. A diagnózist az elvégzett natív hasi röntgen és hasi ultrahangvizsgálatok már felvetették, de megerosítésére további képalkotó vizsgálatot (hasi CT) és endoszkópos beavatkozást végeztünk. Ezt követoen sebészeti beavatkozás történt, melynek során a cholecystoduodenalis fistula zárása és az epeko eltávolítása után a beteg gyógyultan távozott. Közleményünkben a diagnózisfelállítás idejének fontosságáról, illetve a terápiás lehetoségekrol számolunk be, valamint szeretnénk felhívni a figyelmet az epeko okozta gyomorürülési zavar ezen ritka formájára. Orv Hetil. 2021; 162(49): 1982-1986. Summary. Bouveret syndrome is a rare form of bowel obstruction resulting to the small intestine - in 85% of the cases to the duodenum - caused by a gallstone from a bilioenteral fistula. It occurs most commonly in elderly women. The aim of the present study is to describe the symptoms, diagnostic and therapeutic options of Bouveret syndrome due to our case report. The background of epigastric pain of the 79-year-old woman was the typical gastric outlet obstruction syndrome caused by Bouveret syndrome with an impacted gallstone into the duodenum. This diagnosis was suggested by abdominal X-ray and abdominal ultrasound; however, it was confirmed with abdominal computer tomography and upper gastrointestinal endoscopy. This was followed by surgical intervention to close the cholecystoduodenal fistula and remove the gallstone, finally the cured patient was discharged. In our study, we summarize the importance of timely diagnosis and therapeutic options, respectively, furthermore, draw attention to this rare form of gallstone-caused gastric outlet obstruction syndrome. Orv Hetil. 2021; 162(49): 1982-1986.

Cronkhite­Canada syndrome / Cronkhite-Canada-szindróma.

Összefoglaló. A Cronkhite-Canada-szindróma egy extrém ritka, nem öröklodo, gyomor-bél rendszeri polyposissal, fehérjeveszto enteropathiával és ectodermalis elváltozásokkal járó megbetegedés. A világon eddig összesen körülbelül 500 esetet jegyeztek fel. Az etiológia pontosan nem tisztázott, hátterében elsosorban autoimmun folyamatot feltételeznek. A diagnózis a páciens kórtörténetén, a fizikális vizsgálaton, az endoszkópos képen és a szövettani leleten alapul. A jelen közleményben egy 71 éves férfi beteg esetét mutatjuk be. A klinikai kép és az elvégzett vizsgálatok alapján a tünetek hátterében Cronkhite-Canada-szindrómát igazoltunk, majd a szakirodalomban leggyakrabban alkalmazott kombinált protonpumpagátló, kortikoszteroid és meszalazin adását vezettük be, illetve táplálásterápiát alkalmaztunk. Tudomásunk szerint Cronkhite-Canada-szindrómás beteg esete Magyarországon elsoként kerül ismertetésre. Orv Hetil. 2021; 162(11): 432-438. Summary. Cronkhite-Canada syndrome is an extremely rare, noninherited disease, characterized by gastrointestinal polyposis, protein-losing enteropathy and ectodermal abnormalities. Approximately 500 cases have been reported worldwide. The aetiology is unknown, most probably autoimmune mechanisms may be involved. The diagnosis is based on patient history, physical examination, endoscopic findings and histology. Here we report the case of a 71-year-old male, diagnosed with Cronkhite-Canada syndrome. The treatment consisted of proton-pump inhibitor, corticosteroids, mesalazin and nutritional therapy. To the best of our knowledge, this is the first report of Cronkhite-Canada syndrome in Hungary. Orv Hetil. 2021; 162(11): 432-438.

[One-year persistence of fixed-dose combinations of angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertensive patients]. / Az angiotenzinkonvertálóenzim-gátló/kalciumcsatorna-blokkoló fix gyógyszer-kombinációk egyéves perzisztenciája hypertoniában.

INTRODUCTION: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient's adherence is one of the most important factors in reducing unwanted cardiovascular events. AIM: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients. METHOD: Authors have analysed the prescription database of the National Health Insurance Fund in Hungary on pharmacy claims between October 1, 2012 and September 30, 2013. Those patients were identified who filled prescriptions for FDCs of ACEI and CCBs prescribed for the first time for hypertensive patients and who had not received similar drugs during the year before. Apparatus of survival analysis was used, where 'survival' was the time to abandon the medication. RESULTS: 124 388 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinuation in patients with ramipril/amlodipine FDC was 54% (HR = 1.00, reference), perindopril/amlodipine 47% (HR = 1.30, p<0.0001), lisinopril/amlodipine 36% (HR = 1.79, p<0.0001), ramipril/felodipine 26% (HR = 2.28, p<0.0001) and trandolapril/verapamil 12% (HR = 4.13, p<0.0001). The average survival time of drug limited to 360 days was 270.2 days for ramipril/amlodipine FDC, 242.7 days for perindopril/amlodipine FDC, 211.2 days for lisinopril/amlodipine FDC, 186.3 days for ramipril/felodipine FDC and 125.7 days for trandolapril/verapamil FDC. CONCLUSIONS: The authors demonstrated that the one-year persistence of ACEI/CCB FDCs was significantly different in hypertensive patients. Ramipril/amlodipine FDC was more advantageous for patient adherence. Orv Hetil. 2019; 160(9): 343-348.

[Adverse effects of long-term proton-pump inhibitor therapy on adults]. / A hosszú távú protonpumpagátló kezelés következményei felnotteken.

In the last few decades, proton-pump inhibitors have become the mainstay of the treatment of acid-related disorders. Despite their efficacy, these drugs are not without risks. Recently several articles have been published on their long-term adverse effects. Among these adverse effects, the higher risk of bone fractures, the vitamin B12 and magnesium deficiencies and the higher risk of Clostridium difficile infection may be relevant. As these drugs are prescribed more and more frequently all over the world, the knowledge of the long-term adverse effects is very important not only for the specialists but for the general practitioners as well. In this review, the authors discuss the recent findings in this field, emphasising that the long-term use of these drugs must be based on an adequate and strong indication. Orv Hetil. 2018; 159(19): 735-740.

Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis.

MicroRNAs are short non-protein coding RNA molecules involved in the epigenetic regulation of gene expression. Recently, extracellular microRNAs have been described in body fluids that might enable epigenetic communication between distant tissues. Being highly conserved molecules, exogenous xeno-microRNAs from different species could affect gene expression in the host even in a cross-kingdom fashion. Several data underline the relevance of microRNA-mediated communication between virus and host, and there are some experimental data showing that plant- or animal-derived dietary microRNAs might have gene expression modulating activity in humans. Milk-derived microRNAs might be involved in the "epigenetic priming" of the baby. Exogenous microRNAs might be hypothesized to be implicated in disease pathogenesis, e.g. in tumors. Major questions remain to be addressed including the amount of xeno-microRNAs needed for biological action or routes for microRNA delivery. In this brief review, experimental data and hypotheses on the potential pathogenic inter-species relevance of microRNA are presented.

Diagnostic Relevance of microRNAs in Other Body Fluids Including Urine, Feces, and Saliva.

Beside blood-borne circulating miRNAs, miRNAs have been identified in other body fluid and excrements including stool, bile, saliva, and urine. Given the direct link of these body fluids to certain organs, their analysis for potential diagnostic miRNA markers is plausible. Several independent findings underline the potential utility of stool-derived miRNAs in the diagnosis of colorectal and pancreatic cancer. Given the difficulties in the diagnosis of cholangiocellular cancer, biliary miRNAs might be envisaged as useful markers. Several miRNAs have been identified in the saliva that could be associated with diseases, including tumors of the oral cavity. The urinary pool of miRNAs could be exploited for the diagnosis of urinary tract diseases and some appear to enable early diagnosis. In this chapter, we present findings supporting the potential diagnostic utility of fecal, biliary, salivary, and urinary miRNAs focusing mostly on tumors.

Are Circulating microRNAs Involved in Tumor Surveillance?

By studying literature data and having performed an in silico analysis, the circulating microRNA expression profiles of healthy individuals appear to show an abundance of microRNAs with predominant tumor suppressor activity. We hypothesize that circulating tumor suppressor microRNAs might constitute a sort of continuous tumor surveillance, whereby circulating microRNAs delivering gene expression modulating epigenetic information might halt cell transformation and tumorigenesis. This mechanism might complement the well-known cancer immune surveillance. A further hypothesis is also discussed, supposing that the tissue specific action of microRNAs might represent a putative defense mechanism against the potential tumor-promoting actions of secreted miRNA.

Hypothetic Interindividual and Interspecies Relevance of microRNAs Released in Body Fluids.

MicroRNAs may not only be relevant within the organism, but microRNAs released in body fluids might affect other individuals and hypothetically also other species. Such interindividual and cross-species activity of microRNAs appears to be very interesting, but these actions are largely hypothetic at present warranting extensive experimental validation. Food-derived microRNAs might extend the relevance of food for epigenetic regulation; however, the efficient gastrointestinal transfer of microRNAs needs to be demonstrated. We have raised the hypothesis that the nonprotein coding "dark matter" of the genome containing microRNA genes might be relevant in the regulation of interindividual and interspecies epigenetic communication.

Analysis of Circulating MicroRNAs In Vivo following Administration of Dexamethasone and Adrenocorticotropin.

Purpose. The interaction of hormones of the pituitary-adrenal axis and adrenal cortex-associated circulating microRNAs is mostly unknown. We have studied the effects of dexamethasone and adrenocorticotropin on the expression of five circulating microRNAs (hsa-miR-27a, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, and hsa-miR-503) reported to be related to the adrenal cortex in plasma samples. Methods. Expression of microRNAs was studied in plasma samples of 10 individuals examined by 1 mg dexamethasone suppression test and another 10 individuals stimulated by 250 µg tetracosactide (adrenocorticotropin). Total RNA was isolated and microRNA expression was analyzed by real-time reverse transcription quantitative polymerase chain reaction normalized to cel-miR-39 as reference. Results. Only circulating hsa-miR-27a proved to be significantly modulated in vivo by hormonal treatments: its expression was upregulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Secreted hsa-miR-27a was significantly induced by dexamethasone in vitro in NCI-H295R cells, as well. The expression of hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration. Conclusions. hsa-miR-27a expression is modulated by hormones of the hypothalamic-pituitary-adrenal axis both in vitro and in vivo. The biological relevance of hsa-miR-27a modulation by hormones is unclear, but the responsiveness of circulating microRNAs to hormones of the pituitary-adrenal axis is noteworthy.

Suggested roles for microRNA in tumors.

MicroRNAs are short non-coding RNA molecules encoded by distinct genes involved in the posttranscriptional regulation of gene expression. Forming part of the epigenetic machinery, microRNAs are involved in several aspects of tumorigenesis. Deregulation of microRNA expression is a common feature of tumors. Overexpressed oncogenic and underexpressed tumor suppressor microRNAs have been described in many different tumors. MicroRNAs are released from tumors that might affect other cells within and outside the tumor. Circulating microRNAs might also be involved in a tumor surveillance mechanism. In this short overview, some important aspects of microRNA in tumors are discussed.

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy.

Several lines of evidence support the relevance of microRNAs in both adrenocortical and adrenomedullary (pheochromocytomas) tumors. Significantly differentially expressed microRNAs have been described among benign and malignant adrenocortical tumors and different forms of pheochromocytomas that might affect different pathogenic pathways. MicroRNAs can be exploited as markers of malignancy or disease recurrence. Besides tissue microRNAs, novel data show that microRNAs are released in body fluids, and blood-borne microRNAs can be envisaged as minimally invasive markers of malignancy or prognosis. MicroRNAs might even serve as treatment targets that could expand the rather-limited therapeutic repertoire in the field of adrenal tumors. In this review, we present a critical synopsis of the recent observations made in the field of adrenal tumor-associated microRNAs regarding their pathogenic, diagnostic, and potential therapeutic relevance.

Tumor surveillance by circulating microRNAs: a hypothesis.

A growing body of experimental evidence supports the diagnostic relevance of circulating microRNAs in various diseases including cancer. The biological relevance of circulating microRNAs is, however, largely unknown, particularly in healthy individuals. Here, we propose a hypothesis based on the relative abundance of microRNAs with predominant tumor suppressor activity in the blood of healthy individuals. According to our hypothesis, certain sets of circulating microRNAs might function as a tumor surveillance mechanism exerting continuous inhibition on tumor formation. The microRNA-mediated tumor surveillance might complement cancer immune surveillance.

[Potential relevance of microRNAs in the diagnostics of inflammatory bowel diseases]. / A mikro-RNS-ek szerepe a gyulladásos bélbetegségek diagnosztikájában.

Inflammatory bowel diseases are chronic inflammatory disorders characterized by relapses and remissions. Several factors have been suggested to participate in their development, although their detailed pathogenesis still remains largely unknown. MicroRNAs are single strained, non-coding RNAs, consisting of 18-25 nucleotides that regulate gene expression at the posttranscriptional level. Aberrant expression of microRNAs has been found in several malignant tumors. Recently the role of microRNAs in the pathogenesis of inflammatory-autoimmune disorders (such as inflammatory bowel disease) is being intensively investigated. Beside their pathogenic roles, microRNAs can also be exploited as diagnostic markers, especially in cases where the interpretation of histological data is difficult. In this review the authors discuss recent findings in the field of microRNAs in the diagnosis and pathogenesis of inflammatory bowel diseases.

[Significance of microRNA expression in body fluids in the diagnosis of gastrointestinal tumors]. / A testváladékok mikro-RNS-kifejezodésének jelentosége a gyomor-bél rendszeri tumorok diagnosztikájában.

MicroRNAs are small, non-coding, single strained RNAs that regulate gene expression at the posttranscriptional level. They are involved in all major aspects of cellular functions, such as cell cycle, differentiation, migration, apoptosis etc. The role of microRNAs as potential biomarkers of several malignant diseases is being intensively investigated, since they can be found in the body fluids, too, besides their usual intracellular localisation. MicroRNAs have been detected in blood, saliva, stool, breast milk, urine, bile etc. In this review the authors discuss recent findings in the field of microRNAs in stool, bile and saliva, underlying their potential significance in the diagnosis of gastrointestinal tumors.

[Hereditary tumours of the endocrine pancreas]. / Az endokrin pancreas öröklódó daganatai.

The pathogenesis, diagnosis and therapy of tumours originating from the endocrine pancreas represent one of the most exciting challenges of contemporary medicine. Some of these tumours appear as part of four hereditary syndromes (multiple endocrine neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 and tuberous sclerosis) that are all inherited as autosomal dominant traits and result from mutations of tumour suppressor genes. Considering its clinical relevance, MEN1 appears to be the most important among these four syndromes. Tumours of the endocrine pancreas develop in 30-80% of patients carrying mutations of the MEN1 gene. Gastrinomas are the most frequent functioning tumours in MEN1 patients, followed by insulinomas, whereas other tumors e.g. glucagonoma, VIP-oma, GRF-oma and somatostatinoma occur very rarely. Tumours of the endocrine pancreas are infrequent in patients suffering from VHL, neurofibromatosis and tuberous sclerosis. In this review article, the authors present a synopsis of tumours of the endocrine pancreas related to these hereditary syndromes underlining the clinical characteristics, diagnostical and therapeutical possibilities.