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Given their fundamental physiological importance, their involvement in the immune system, and their close association with the development of intestinal diseases, the interest in intestinal epithelial cells has increased significantly over the past fifteen years. Their close association with intestinal worm and protozoan infections - a significant 2016 discovery - has further stimulated research into uncommon chemosensitive tuft epithelial cells. Although their numbers are relatively low, tuft cells are now recognized as an essential sentinel of the gastrointestinal tract, as their taste receptors for succinate, sweet, and bitter continuously monitor intestinal contents. When stimulated, tuft cells release a number of effector molecules, including immunomodulatory molecules like interleukin 25, prostaglandins E2 and D2, cysteinyl leukotriene C4, acetylcholine, thymic stromal lymphopoietin, and beta-endorphins. Tuft cells have been shown to be crucial for immunity against nematodes and protozoa. The majority of tuft cell research has used the doublecortin-like (microtubule-linked) kinase 1 protein marker on mice; however, the expression of the enzyme cyclooxygenase-1 may help identify human intestinal tuft cells. Few studies have examined the association between tuft cells and intestinal diseases in humans. This article provides an update on intestinal epithelial tuft cells, including their physiology, immunological nodal function, and role in human diseases. We conclude by discussing the potential clinical therapeutic value of tuft cells. Orv Hetil. 2023; 164(44): 1727-1735.

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Colorectal cancer (CRC) is one of the most common types of cancers worldwide. The incidence of sporadic CRC is lower in individuals below 50 years and increases with age, furthermore, it shows typical clinical, macroscopic and molecular differences between females and males. According to the results of epidemiological and molecular biology studies, the estradiol-regulating signaling pathway plays an important role in the development and prognosis of CRC, predominantly through estrogen receptor beta (ERß), which is dominant in the colonic epithelium. Estradiol has multiple gastrointestinal effects, which were confirmed by in vitro and in vivo studies on histologically intact and cancerous cells as well. In contrast to estrogen receptor alpha (ERα), the activation of ERß inhibits cell proliferation and enhances apoptosis, nevertheless, the expression of estrogen receptor beta can change both during physiological ageing and in colorectal disorders. The ERß-mediated antitumour effects of estradiol may be exerted through inhibition of cell proliferation, stimulation of apoptosis, inhibition of metastasis formation and its anti-inflammatory activity. Based on the results of cell culture and animal studies, selective modulators of estrogen receptor beta (selective estrogen receptor modulator [SERM]) and phytoestrogens can be new, additional therapeutic options in the treatment of colorectal diseases characterized by chronic inflammation and uncontrolled cell proliferation. Orv Hetil. 2020; 161(14): 532-543.

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The incidence and mortality of colorectal cancer (CRC) are considerably high in Central European countries, it is the second most common cancer in both men and women in Hungary with 10,000 newly registered patients per year. These data indicate the necessity of new screening methods that are more comfortable for patients, hence the compliance can be increased. Cell-free DNA (cfDNA) level in blood is elevated in certain physiological conditions, such as pregnancy or high physical activity. Furthermore, cfDNA concentration alterations can also be detected in some pathological processes; increased cfDNA amount was observed in autoimmune and inflammatory diseases, as well as in various cancers including CRC. Numerous studies about origin, function, and mechanism of cfDNA can be found in the scientific literature. In this review, we aimed to describe the quantitative and qualitative changes of cfDNA, to present its functions, and to provide an overview of the available diagnostic applications for CRC. CfDNA can be released to the circulatory system via apoptosis, necrosis or by direct secretions by living cells. In cancer patients, cfDNA can originate from healthy and cancer cells, hence genetic (e.g. mutations in APC, KRAS, BRAF) and epigenetic (e.g. methylation in SEPT9, SFRP1) alterations of tumor cells can be examined in cfDNA fraction. Several high-throughput, sensitive and even automated methods are available providing opportunity to perform standardized sample preparation and to analyse biomarker candidates quantitatively. These enhancements can help to develop alternative screening methods that can be easily integrated into the clinical practice and can contribute to early cancer detection. Orv Hetil. 2019; 160(30): 1167-1177.

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Since the therapeutic options for colon cancer are limited, the reinduction of treatments (rechallenge) is part of the therapeutic strategy. Our case is an example for that. A 65-year-old female patient was operated on stenotizing sigmoid cancer. Resectio was performed. Surgically incurable multiple hepatic metastases were proven. The histology revealed adenocarcinoma (grade II, pT3pN1cM1). In the first line, 13 cycles of bevacizumab (BEV) + FOLFOX followed by 2 cycles of BEV + capecitabine and 11 cycles of BEV + 5FU/LV were administered. In the second line, 28 cycles of cetuximab (CET) + FOLFIRI were given. In the third line, due to liver limited disease and based on the preference of the patient, two cycles of transarterial chemoembolisation (doxorubicin + lipiodol) were administered. In the fourth line, four cycles of trifluridine/tipiracil were given. In the fifth line, 13 cycles of BEV + FOLFIRI were given, as a rechallenge, which improved the overall survival by 6,5 months. Orv Hetil. 2018; 159(31): 1284-1290.

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Muir-Torre syndrome is a rare genodermatosis with autosomal dominant inheritance. The syndrome is considered to be a subtype of the hereditary nonpolyposis colorectal cancer (or Lynch-syndrome). In two-third of the cases, it develops as the consequence of germline mutations in mismatch-repair genes--most commonly MutS Homolog-2 and MutL Homolog-1. Its diagnosis can be established if at least one sebaceous tumor (sebaceoma, sebaceous adenoma, epithelioma, carcinoma or basal-cell carcinoma with sebaceous differentiation) and/or keratoacanthoma and at least one internal neoplasm are present. Here the authors present the history of a 52-year-old man with multiple sebaceous carcinomas on his back. Immunohistochemical analysis showed the lack of MutL Homolog-1 protein expression in the tumor cells. Detailed clinical workup in order to identify internal malignancy found malignant coecum tumor. Histopathological evaluation of the sample from the right hemicolectomy revealed mid-grade adenocarcinoma with MutL Homolog-1 and postmeiotic segregation increased-2 deficiency. The detection of the cutaneous sebaceous carcinoma and the application of the modern diagnostic methods resulted in identification of the associated colorectal cancer in an early stage; hence, definitive treatment was available for the patient.

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