Gut microflora associated characteristics in children with celiac disease

Aim The over-arching aim of this thesis was to study some metabolic functions of the gut microflora in children with known or screening detected celiac disease (CD) and their first-degree relatives. Materials Study I. A number of 36 untreated CD children, 47 after at least 3 months on glutenfree diet (GFD) and 42 healthy controls (HC). Study II. A number of 76 first-degree relatives to CD children and 93 healthy controls (HC). Study III. A number of 17 screening detected CD children were included to be compared with the untreated children and controls from study I; with exchange of one child in the untreated group, due to low age. Study IV. A comparative study regarding correlation between iso-forms of short chain fatty acids (SCFAs) in humans as well as in animals. Methods Faecal short chain fatty acids were measured in all four studies. Additionally faecal tryptic activity (FTA) was measured in study II. Major findings All groups of CD children demonstrated a similar SCFAs profile, i.e. significantly more total SCFAs and acetic acid and a strong tendency to more iso-butyric and iso-valeric acids compared with HC. The first-degree relatives demonstrated another SCFAs profile, i.e. significantly less total SCFAs and acetic acid and significantly more FTA than HC. Conclusions and future outlook Based upon the strong similarities between all groups of CD children we are allowing ourselves hypothesising that CD children have a celiacogenic flora compared with healthy controls. In a similar way it can be said that the first-degree relatives are harbouring a celiacprotective microflora. Our findings open up for challenging new diagnostic, therapeutic and prognostic possibilities

Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year's gluten-free diet

OBJECTIVE: Recent work indicates that the gut microflora is altered in patients with coeliac disease (CD). Faecal short-chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported a high SCFA output in children with symptomatic and asymptomatic CD at presentation, as well as in CD children on a gluten-free diet (GFD) for less than 1 year, indicating deviant gut microfloral function. In this report, we focus on faecal SCFA production in coeliacs on GFD for more than 1 year. MATERIALS AND METHODS: Faecal samples were collected from 53 children with CD at presentation, 74 coeliac children on GFD for less than 1 year, and 25 individuals diagnosed with CD in childhood and on GFD for more than 1 year. The control group comprised 54 healthy children (HC). The faecal samples were analysed to show the SCFA pattern taken as a marker of gut microflora function. We applied a new fermentation index, reflecting the inflammatory activity of the SCFAs (amount of acetic acid minus propionic acid and n-butyric acid, together divided by the total amount of SCFAs). RESULTS: In coeliacs on GFD for more than 1 year, the individual SCFAs, total SCFA, and fermentation index did not differ significantly from the findings in controls. In contrast, the faecal SCFA level was clearly higher in coeliacs treated with GFD for less than 1 year compared to those more than 1 year. CONCLUSIONS: This is the first study on SCFA patterns in faecal samples from individuals with CD on GFD for more than 1 year. Our study indicates that the disturbed gut microflora function in children with CD at presentation and after less than 1 year of GFD, previously demonstrated by us, is normalised on GFD for more than 1 year

The investigation of the factors related tolymphovascular space invasion in endometrium cancerand, the relation between lymphovascular spaceinvasion and myometrial invasion, lower uterus segmentinvolvement, cervical involvement and lymph nodulmetastasis

YÖK Tez No: 685163Amaç: Endometrium kanserinde lenfovasku?ler saha invazyonu (LVSİ) ile ilgili faktörler ve lenfovasku?ler saha invazyonunun miyometrial invazyon (Mİ), alt uterin segment tutulumu, servikal tutulum ve lenf nodu metastazı ile ilişkisi incelenmiş olup, lenfovasku?ler saha invazyonunun endometrium kanseri için yeni bir prognostik belirteç olarak kullanılıp kullanılamayacağının araştırılması amaçlanmıştır. Gereç ve Yöntem: Kliniğimizde 2015-2021 yılları arasında endometrium kanseri nedeniyle total histerektomi + bilateral salpingooferektomi ± Pelvik ve/veya Paraaortik lenfadenektomi + omentektomi yapılmış 44 hasta çalışmaya dahil edilmiş ve patoloji sonuçlarına göre LVSİ pozitif olan ve olmayan olmak u?zere 2 gruba ayrılmıştır. LVSİ olmayan 29 hasta kontrol grubu ve LVSİ pozitif olan 15 hasta çalışma grubu olarak belirlenmiştir. Hastalar yaş, ameliyat tipi, gravida, parite, menopoz durumu, malignite öyku?su?, ailede malignite öyku?su?, sistemik hastalık, ilaç kullanımı, operasyon öyku?su?, başvuru şikayeti, preop endometrial örnekleme sonucu, yapılan ameliyatlar, patolojik tanısı, cerrahi evreleri ve patoloji sonuçları univaryan ve multivaryan analizler yapılarak karşılaştırılmıştır. Bulgular: Gruplar arasında yaş, gravida, parite, menopoz durumu, malignite öyku?su?, malignite tipi, ailede malignite öyku?su? ve tipi, sistemik hastalık varlığı, başvuru şikayeti, preoperatif endometrial örnekleme sonuçları, ana materyal patoloji, uterus çapı, tu?mör çapı, Mİ varlığı, alt uterin segment tutulumu, servikal tutulum, paraaortik lenf nodu tutulumu, ana materyal batın yıkama sıvında tu?mör varlığı ve prognoz açısından sonuçları karşılaştırılmış ve istatistiksel olarak anlamlı fark bulunamamıştır iv (Sırasıyla p=0,657, p=0,773, p=0,930, p=0,957, p=0,925, p=0,999, p=0,822, p=0,571, p=0,675, p=0,414, p=0,846, p=0,083, p=0,328 ve p<0,05). Her iki grup histolojik grade, nu?kleer grade, Mİ derinliğinin, pelvik lenf nodu tutulumu ve ana material cerrahi evre açısından karşılaştırılmış ve istatistiksel olarak anlamlı bulunmuştur. LVSİ pozitif olan çalışma grubunda ana materyal histolojik ve nu?kleer grade açısından bakıldığında istatistiksel olarak anlamlı olacak şekilde daha fazla oranda grade 3 tu?möre sahip olduğu tespit edilmiştir (p=0,001 ve p<0,05). LVSİ olan çalışma grubunda istatistiksel olarak kontrol grubuna göre ana materyal nu?kleer grade açısından anlamlı sonuç bulunmuştur (p=0,001 ve p<0,05). Mİ varlığı açısından her iki grup arasında istatistiksel olarak anlamlı farklılık bulunamamış (p=0,999 ve p<0,05) olmasına rağmen Mİ varlığında LVSİ pozitif olan çalışma grubunda Mİ derinliğinin anlamlı olarak ½'den daha fazla olduğu tespit edilmiştir (p=0,001 ve p<0,05). Sağ ve sol pelvik lenf nodu tutulumu açısından LVSİ pozitif olan grupta istatistiksel olarak anlamlı sonuç bulunmuştur (Sağ pelvik lenf nodu için p=0,003 ve p<0,005, sol pelvik lenf nodu için p=0,001 ve p<0,05). Her iki grup ana materyal cerrahi evrelendirme açısından karşılaştırıldığında LVSİ pozitif olan grupta daha ileri evre hastalık olduğu istatistiksel olarak anlamlı sonuç bulunmuştur (p=0,009 ve p<0,05). Sonuç: Endometrium kanserinde LVSİ'nin prognostik öneminin yeri birçok çalışmada araştırılmış olmasına rağmen kesin bir fikir birliğine varılamamıştır. Çalışmamızın sonucunda LVSİ varlığının histolojik grade, nu?kleer grade, Mİ derinliği, pelvik lenf nodu tutulumu ve daha ileri evre hastalık açısından istatistiksel olarak anlamlı etkisi olduğunu gözlemledik. Bu konuda daha çok vaka sayılı ve daha uzun takip su?reli çalışmalara ihtiyaç duyulmaktadır.Objective: Having investigated the factors related to lymphovascular space invasion (LVSI) in endometrium cancer and the relations between LVSI and myometrial invasion (MI), lower uterus segment involvement, cervical involvement and lymph nodule metastasis, the purpose of this research is to investigate whether or not LVSI can be used as a new prognostic metric in endometrium cancer. Materials and Methods: 44 patients had gone under hysterectomy + bilateral salpingo-oophorectomy ± pelvic and/or paraaortic lymphadenectomy + omentectomy procedures due to being diagnosed with endometrium cancer between 2015-2021 in our clinic, and according to the pathological results, the patients were divided in to two groups of LVSI positives and negatives. The control group of 29 patients without LVSI and the experimental group of 15 patients with LVSI were identified for the study. The patients were compared according to the analyses done over age, surgery type, gravida, parity, menopause state, malignancy history, malignancy history of family, systematic illnesses, medical drug use, medical operation history, symptomatic complaints, pre-operational endometrial sample analysis results, completed surgeries, pathological diagnosis, surgical stages, pathological results, univariant and multivariant results. Result: The results between the groups were compared according to age, gravida, parity menopause state, malignancy history, malignancy history of family, systematic illnesses, symptomatic complaints, pre-operational endometrial sample analysis results, main material pathology, uterus radius, tumour radius, MI presence, segment involvement of lower uterus, cervical involvement, paraaortic lymph nodule vi involvement, presence of tumour in main material peritoneal cytology and prognosis. According to the statistical analysis no meaningful differences were found (p=0,657, p=0,773, p=0,930, p=0,957, p=0,925, p=0,999, p=0,822, p=0,571, p=0,675, p=0,414, p=0,846, p=0,083, p=0,328 and p<0,05). Two groups were compared with respect to histological grade, nuclear grade, MI depth, pelvic lymph nodule involvement and main material surgical state, and the results were found statistically meaningful. When considered by taking histological and nuclear grade into account, the statistical results showed that the experimental group of patients who had LVSI had a higher rate of grade 3 tumour (p=0,001 and p<0,05). Meaningful statistical results were found with respect to nuclear grade in the LVSI positive patients of the experimental (p=0,001 and p<0,05). Even though no statistically meaningful results were found considering MI presence (p=0,999 and p<0,05), in the presence of MI among the experimental group, the depth of MI is identified to be above ½ (p=0,001 and p<0,05). Likewise, meaningful results were found when the experimental group of LVSI positive patients were considered by taking left and right pelvic nodule involvement into account (for the right pelvic lymph nodule p=0,003 and p<0,005, for the left lymph nodule p=0,001 and p<0,05). Finally, when both groups were compared with respect to the main material surgical staging, it was statistically shown that the LVSI positive patients appeared to have a more mature state of the disease (p=0,009 and p<0,05). Conclusion: Although LVSI's prognostic importance in endometrium cancer was investigated in many research, there is no consensus on its crucial role in the development of endometrium cancer. As a result of our research, we have statistically shown how the presence of LVSI meaningfully impacts histological grade, nuclear grade, MI depth, pelvic lymph nodule involvement and maturity of the disease. Further study with more patients and a longer follow-up period is still needed in this research subject