Relationship between serum calcium and CA 19-9 levels in colorectal cancer

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n=32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25(OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer

CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells

AIM: The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS: We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS: In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION: These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC

A kettős-ballonos endoszkópia szerepe a vékonybél betegségeinek diagnózisában és kezelésében összehasonlítva a kapszulás endoszkópiával

A legutóbbi évekig csak a vékonybél kezdeti szakasza volt megközelíthetô a diagnosztikus vagy terápiás endoszkópos beavatkozások számára. Egy új, kettôs ballonos (DBE) endoszkópos eljárás, amely nagy felbontású képet szolgáltat, mindkettôre lehetôséget nyújt a gastrointestinalis traktus bármely területén. A tanulmány célja az volt, hogy beszámoljunk a Fujinon EN-T5 terápiás kettôs ballonos enteroszkóppal szerzett tapasztalatainkról, illetve összevessük az eredményeket a korábbi kapszulás endoszkópia eredményével, akinél ez rendelkezésre állt

A gyulladásos bélbetegségek szülészeti-nőgyógyászati vonatkozásai = Obstetrical and Gynecological Relevance of Inflammatory Bowel Disease

Bevezetés: A gyulladásos bélbetegségek élethosszig tartó lefolyást mutatnak, a termékenység viszont időkorlátok közé szorított. Célkitűzés: Gyulladásos bélbetegségben szenvedő nőkben a szülészeti-nőgyógyászati aspektusok pontosabb megismerése. Módszerek: A szerzők kérdőíves felméréssel 100 beteg és 100 egészséges kontroll nő adatait dolgozták fel. Eredmények: Későbbi életkorban kezdődő betegség esetén a menarche korábban jelentkezik (p = 0,03). A bélbetegség aktivitása, a szteroidok és 5-aminoszalicilát készítmények menstruációs zavart okozhatnak. A betegek ritkábban alkalmaznak fogamzásgátló módszereket (p = 0,002), mégis a tervezéstől a teherbe esésig eltelt idő a betegeknél hosszabb. A betegek vérszegényebbek, mint a kontrollok (p<0,001). A bélbetegség tünetei terhesség alatt enyhébbek, mint a betegség kezdetén és a post partum időszakban (p<0,001). A túlsúly kedvezően alakítja a tünetek átlagos súlyosságát, a terhesség alatti tüneteket (p = 0,042) és a szövődmények relatív gyakoriságát. Az újszülötteknél gyakoribb a koraszületés (p = 0,019) és a kis születési súly. Szövődményes gátmetszés gyakrabban fordul elő a betegcsoportban (p = 0,019). Következtetések: A terhesség jótékonyan hat a bélbetegségek tüneteire, amennyiben a fogamzás nyugalmi periódusban történt. Introduction: Inflammatory bowel disease may show a life long persistance, while female fertility is time-limited. Aim: The aim of the authors was to obtain more knowledge about the obstetrical-gynecological aspects of this disorder. Methods: The authors evaluated 100 patients with inflammatory bowel disease and 100 healthy women with a self-composed questionnaire. Results: Menarche occurred significantly earlier in patients than in controls (p = 0,03). Either the activity of the disease, or the therapy itself may initiate irregularities in the menstrual cycle. Patients used contraceptives less frequently than controls (p = 0,002), and the time from family-planning to conception was longer in patients. Symptoms of bowel disease during pregnancy were not as severe as before and after pregnancy (p<0,001). Excess weight had a beneficial effect on symptoms during pregnancy (p = 0,042) and on the frequency of complications. Preterm birth and low birth weight were more frequent in newborns of patients (p = 0,019). Conclusion: Pregnancy has positive effect on the symptoms of inflammatory bowel disease in case gestation occurs in a stable period of the inflammatory bowel disease

Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol

Background : Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. Objective : Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. Methods: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. Results: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. Conclusions: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. Trial Registration: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt

Double-balloon enteroscopy for the diagnosis and treatment of obscure bleeding, inflammatory bowel diseases and polyposis syndromes: we see more but do we know more?

Background/Aims: Our aim was to report our experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope (DBE) in the diagnosis of small bowel diseases. Methodology: Between August 2005 and October 2006, 52 DBE procedures were conducted on 47 consecutive patients (M/F: 22/25, age: 51.6 SD 19.5 years) presenting at our tertiary referral hospital (35 and 7 patients from oral and arial route, respectively; 5 patients from both). All procedures were performed using i.v. anesthesia, at our outpatient clinic. Results: Indication suspected small-bowel bleeding in 28 patients, suspected/known inflammatory bowel syndrome (TBD) in 12 and polyposis/suspected neoplasia in 7. In obscure bleeding small-bowel abnormality was found in 18 patients (64.3%) including angiodysplasias/erosions and one polypoid lesion. In suspected IBD, IBD was diagnosed in 2 out of 8 cases. In patients with polyposis syndromes, polyps were in two Peutz-Jeghers patients, while a further patient with suspected stenosis was diagnosed with primary adenocarcinoma. The average insertion length was app. 213cm. No severe complications were observed. Conclusions: Based on our experience DBE is a safe and useful method for evaluating and treating small bowel disease in selected patients with obscure bleeding, IBD or polyposis syndromes, however the clinical importance of minute lesions still needs to be determined

Verner-Morrison szindróma egy esete [Verner-Morrison syndrome: a case study]

1958-ban Verner és Morrison írta le az elnevezésében a vizes hasmenésre, hypokalaemiára és achlorhydriára utaló szindrómát (watery diarrhea, hypokalaemia, achlorhydria – WDHA). A nagy mennyiségű vazoaktív intestinalis peptidet (VIP) termelő VIPomák rendszerint a hasnyálmirigyből származnak. A tipikus tünetek fontos szerepet játszanak a VIPoma diagnózisában. A hasmenés a diagnózis felismerése előtt évekig perzisztálhat. A kezeletlen WDHA-szindróma a hosszabb ideig fennálló exsiccosis, illetve az elektrolit- és sav-bázis háztartás zavara miatt krónikus veseelégtelenséghez vezethet, ami a betegség lefolyását súlyosbíthatja. Specifikus marker (VIP) meghatározása érzékeny módszer a kórisme felállításához. A felismerésben segítséget nyújt az endoszkópos ultrahang, komputertomográfia, mágneses rezonancia és főleg a szomatosztatinanalógokkal végzett szcintigráfiás vizsgálat. A kezelési lehetőségek közé tartozik a daganat reszekciója, a kemoterápia és a tünetek csökkentése érdekében a szomatosztatinanalógok alkalmazása. A korai diagnózis és kezelés kedvezően hathat a betegek életben maradására. A VIPomák társulhatnak az 1-es típusú multiplex endokrin neoplasia (MEN-1) szindrómához. | Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA) in 1958. VIPomas producing high amounts of vasoactive intestinal peptide (VIP) commonly originate from the pancreas. Typical symptoms play a momentous role in the diagnosis of VIPoma. Diarrhea may persist for years before the diagnosis. Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base metabolism disorders, which may cause chronic renal failure. Assessment of specific marker (VIP) offers high sensitivity in establishing the diagnosis. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogues. Treatment options include resection of the tumor, chemotherapy or the reduction of symptoms with somatostatin analogues. Early diagnosis and management may affect survival of patients favorably. VIPoma cases may be associated with multiple endocrine neoplasia type 1