Morphological characteristics of changes in the squamous epithelium of the upper part of the digestive tract in model organisms in the settings of provoked carcinogenesis

Relevance: Noticeable spreading of malignant neoplasms of upper section of digestive system and the worsening of these patients’ quality of life in case of late diagnostics stimulate the development of protocols for early detection of precancerous changes. The purpose of the study was to investigate the morphological characteristics of changes in the squamous epithelium of the upper part of the digestive tube in model organisms under provoked carcinogenesis when exposed to substances with proven carcinogenic activity. Methods: 40 female nonlinear white rats obtained from the Orekhovo-Zuevsky urban settlement veterinary station were used as model organisms. The rats were divided into 4 equal groups. The first control group was not exposed to any specific influences. In groups 2-4, the rats underwent sedation and mechanical scarification microtraumatization of the oral mucosa. Then, they were applied twice a week by 0.9% NaCl solution (control group 2), 1% aqueous solution of dimethyl sulfoxide (DMSO, Akrikhin, Russia) (control group 3), or 1% aqueous solution of DMSO containing 0.1 mg/ml 4-nitroquinoline-N-oxide (4- NQO, Acros Organics, USA) (experimental group 4). Results: The cytological picture associated with chronic trauma to the mucous membrane of the upper digestive tract was characterized by nonspecific reactions: inflammation, hyper- and parakeratosis, and atrophic changes. There were no statistically significant differences in the frequency of such changes between the experimental and control groups. Specific changes in squamous epithelium towards a precancerous state in the experimental group with chronic exposure to a substance with carcinogenic activity occurred significantly more often than in the control groups (p <0.05), as proven by the results of comparative histological verification. Conclusion: Cytological study can be offered for clinical study as a screening tool for precancerous oropharynx and upper esophagus conditions

From Intrauterine to Extrauterine Life—The Role of Endogenous and Exogenous Factors in the Regulation of the Intestinal Microbiota Community and Gut Maturation in Early Life

Differentiation of the digestive tube and formation of the gut unit as a whole, are regulated by environmental factors through epigenetic modifications which enhance cellular plasticity. The critical period of DNA imprinting lasts from conception until approximately the 1,000th day of human life. During pregnancy, besides agents that may directly promote epigenetic programming (e.g., folate, zinc, and choline supplementation), some factors (e.g., antibiotic use, dietary components) can affect the composition of the mother's microbiota, in turn affecting the fetal microbiome which interacts with the offspring's intestinal epithelial cells. According to available literature that confirms intrauterine microbial colonization, the impact of the microbiome and its metabolites on the genome seems to be key in fetal development, including functional gut maturation and the general health status of the offspring, as well as later on in life. Although the origin of the fetal microbiome is still not well-understood, the bacteria may originate from both the vagina, as the baby is born, as well as from the maternal oral cavity/gut, through the bloodstream. Moreover, the composition of the fetal gut microbiota varies depending on gestational age, which in turn possibly affects the regulation of the immune system at the barrier between mother and fetus, leading to differences in the ability of microorganisms to access and survive in the fetal environment. One of the most important local functions of the gut microbiota during the prenatal period is their exposure to foreign antigens which in turn contributes to immune system and tissue development, including fetal intestinal Innate Lymphoid Cells (ILCs). Additional factors that determine further infant microbiome development include whether the infant is born premature or at term, the method of delivery, maternal antibiotic use, and the composition of the mother's milk, among others. However, the latest findings highlight the fact that a more diverse infant gut microbiome at birth facilitates the proliferation of stem cells by microbial metabolites and accelerates infant development. This phenomenon confirms the unique role of microbiome. This review emphasizes the crucial perinatal and postnatal factors that may influence fetal and neonatal microbiota, and in turn gut maturation.

The latest insights into the innervation of the digestive tube

The question of the innervation of the digestive tube, which is one of the most difficult parts of the autonomic nervous system, has been in the center of attention of biologists for the last decade. Most recently, a number of works have appeared on the "enteric nervous system", as Langley called the Auerbach and Meissner plexus together.

Y-en-Roux reconstruction in abdominal surgery: historical retrospective of operative method’s evolution. Part II

This historical review is more focused on the analysis of highly relevant, unique method proposed by A. Wölfl er, E. Doyen and C. Roux more than 140 years ago. We also try to present main facts and the chronology of Y-reconstruction of the digestive tube concept’s development. Hereby we present historical retrospective of theoretic concept creation, experimental confi rmation and initial clinical experience of Y-shaped reconstruction of the digestive tube on Roux-en-Y-loop, stages of concept evolution and development from the end of the 19th century and continuing into current times. Scientifi c research of surgical gastroenterology, oncology, pancreatology and hepatobiliary surgery founders, expand application of Roux-en-Y-reconstruction from distal resection of the stomach and gastroenterostomy to gastrectomy, repeated operations on the upper part of the digestive tube, the formation of biliary-enteric and pancreatic anastomosis, and the use in the routine practice of bariatric surgery.

Expression of Piwi, MMP, TIMP, and Sox during Gut Regeneration in Holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirotida)

Mesodermal cells of holothurian Eupentacta fraudatrix can transdifferentiate into enterocytes during the regeneration of the digestive system. In this study, we investigated the expression of several genes involved in gut regeneration in E. fraudatrix. Moreover, the localization of progenitor cells of coelomocytes, juvenile cells, and their participation in the formation of the luminal epithelium of the digestive tube were studied. It was shown that Piwi-positive cells were not involved in the formation of the luminal epithelium of the digestive tube. Ef-72 kDa type IV collagenase and Ef-MMP16 had an individual expression profile and possibly different functions. The Ef-tensilin3 gene exhibited the highest expression and indicates its potential role in regeneration. Ef-Sox9/10 and Ef-Sox17 in E. fraudatrix may participate in the mechanism of transdifferentiation of coelomic epithelial cells. Their transcripts mark the cells that plunge into the connective tissue of the gut anlage and give rise to enterocytes. Ef-Sox9/10 probably controls the switching of mesodermal cells to the enterocyte phenotype, while Ef-Sox17 may be involved in the regulation of the initial stages of transdifferentiation.

Case Report: Uncommon Association of ITGB4 and KRT10 Gene Mutation in a Case of Epidermolysis Bullosa With Pyloric Atresia and Aplasia Cutis Congenita

Background: Epidermolysis bullosa is a rare form of genodermatosis produced by different gene mutations. The junctional form of the disease (JEB-PA) can associate pyloric atresia, renal abnormalities, and aplasia cutis congenita.Case Description: A case of a male preterm newborn with suspicion of digestive tube malformation at fetal ultrasound and who was born by cesarian section. At birth, he presented extensive cutaneous aplasia on the lower limbs and bilaterally under ears; outer ear agenesis; nasal septum hypoplasia; micrognathia; multiple blisters on the face, trunk, and limbs; lower limb deformities and absence of toe nails. Pathological examination following a surgical procedure with unfavorable outcome showed pyloric atresia, junctional form of epidermolysis bullosa and aplasia cutis congenita. Homozygous variants in two genes were identified: c.3111+1G&gt;A in ITGB4 (class 5) and c.1498G&gt;T in KRT10 (class 3).Conclusion: The particularity of our case is the novel finding of a coincidental occurrence in the context of consaguinity of two mutations in the ITGB4 and KRT10 genes, and clinical characteristics of epidermolysis bullosa.

Y-en-Roux reconstruction in abdominal surgery: historical retrospective of operative method’s evolution. Part I

Target of this historical review is focused on analysis of highly relevant, unique method proposed by A. Wölfler, E. Doyen and C. Roux more than 140 years ago, also we try to present main facts and chronology of development of concept Y-reconstruction of digestive tube. Hereby we present historical retrospective of theoretic concept creation, experimental verification and initial clinical experience of Y-shaped reconstruction of digestive tube on Roux-en-Y-loop, stages of concept evolution and development till the end of XIX age till our days. The founders’ scientific research onducted in surgical gastroenterology, oncology, pancreatology and hepatobiliary surgery, has expanded application of Roux-en-Y-reconstruction from distal resection of the stomach and gastroenterostomy to gastrectomy, repeated operations on the upper part of the digestive tube, the formation of biliary-digestive and pancreatic anastomoses, as well as the use in the routine practice of bariatric surgery.

PARCELAR GASTRIC RESECTION IN ASSOCIATION WITH BOWEL RESECTIONS AS PART OF DEBULKING SURGERY FOR ADVANCED STAGE OVARIAN CANCER – A CASE REPORT

Ovarian cancer represents one of the most aggressive gynecological malignancies affecting women worldwide, associated with significant rates of cancer related death within the first years after the initial diagnostic. The poor survival rates are usually explained by the presence of disseminated lesions even from the beginning. In such situations, the digestive tube is one of the most commonly involved territory, therefore necessitating extended resections in order to achieve complete cytoreduction. The aim of this paper is to report the case of a 53 year old patient who was diagnosed with peritoneal carcinomatosis from ovarian cancer, presenting multiple levels of digestive tract involvement due to the presence of disseminated tumoral masses. Therefore the patients was submitted to multiple digestive resections represented by parcelar gastrectomy, segmental ileal resection and subtotal colectomy. In order to minimize the risks of developing severe postoperative complications – due to the relatively high number of anastomoses – the continuity of the digestive tract was established by a terminal ileostomy, considering that creation of a ileorectal anastomosis would be too dangerous in the context of multiple digestive resections. The postoperative evolution was simple, the patient being further submitted to adjuvant treatment.