EYUNOGASTROPLASTICА AS AN EFFECTIVE METHOD FOR PREVENTING FUNCTIONAL DISORDERS AFTER PROXIMAL GASTRIC RESECTION

The analysis of the results of treatment of 97 patients who were operated from surgical diseases of the cardiac stomach. Proximal gastric resection (PRG) was performed using isoperistaltic jejunogastroplasty (modified by Merendino-Dillard) (50 people – group I) and with direct esophagogastroanastomosis (47 people – group II). 12 and 24 months after the operation, an X-ray and endoscopic examination of the upper digestive tract was performed, assessing the severity of functional disorders (nutritional status, body weight deficiency, reflux esophagitis, anastomosis) Results. After 2 years or more, 5.9% of patients ate more than 6 times a day in group I, while in group II, 23.3% (p <0.05). 67.6% of patients in group I and 36.7% in group II returned to their previous (as before the illness) diet – 3-4 times a day (p <0.05). After 24 months or more, in group II, the average weight of patients did not exceed preoperative indicators (95.9 ± 0.25%), while in group I, there was an increase in the average weight of 109.9 ± 0.13%. (p <0.05). The frequency of reflux esophagitis was observed in 8 (9.3%) cases: in group I – in 2 (4.5%) and in group II-in 6 (14.3%) (p <0.05) According to the authors, the PRG with the reconstruction of the digestive tract according to Meredino-Dilard creates optimal conditions for a faster and better recovery of functional parameters and demonstrates how significant and effective the performed surgical treatment is.

Ancient role of sulfakinin/cholecystokinin-type signalling in inhibitory regulation of feeding processes revealed in an echinoderm

Sulfakinin (SK)/cholecystokinin (CCK)-type neuropeptides regulate feeding and digestion in protostomes (e.g. insects) and chordates. Here, we characterised SK/CCK-type signalling for the first time in a non-chordate deuterostome – the starfish Asterias rubens (phylum Echinodermata). In this species, two neuropeptides (ArSK/CCK1, ArSK/CCK2) derived from the precursor protein ArSK/CCKP act as ligands for an SK/CCK-type receptor (ArSK/CCKR) and these peptides/proteins are expressed in the nervous system, digestive system, tube feet, and body wall. Furthermore, ArSK/CCK1 and ArSK/CCK2 cause dose-dependent contraction of cardiac stomach, tube foot, and apical muscle preparations in vitro, and injection of these neuropeptides in vivo triggers cardiac stomach retraction and inhibition of the onset of feeding in A. rubens. Thus, an evolutionarily ancient role of SK/CCK-type neuropeptides as inhibitory regulators of feeding-related processes in the Bilateria has been conserved in the unusual and unique context of the extra-oral feeding behaviour and pentaradial body plan of an echinoderm.

Immediate and long-term results of proximal gastric resection depending on the methods of the digestive tract continuity restoring

Proximal gastric resection (PGR) is still one of the most difficult and dangerous surgical interventions, and it is the only method of curative treatment of diseases of the cardiac part of the stomach in many cases. 5 types of gastrointestinal reconstruction are mainly performed after PRG: submerged rectal esophagogastroanastomosis, antireflux interposition of the jejunal segment, interposition of the jejunal segment of the jejunal pocket, interposition of the jejunal segment as a double tract and reconstruction with the formation of a gastric tube. Modern literature includes many works devoted to the development of methods of physiological reconstruction after subtotal and total removal of the stomach; however, none of the existing methods is recognized as optimal. Among the main indicators characterizing the effectiveness of PGR are the frequency and severity of the development of a large group of functional disorders, characterized as «diseases of the operated stomach», or «post-gastro-resection disorders», which significantly worsen the quality of life (QOL) and reduce the working capacity, which causes disability of the operated patients Assessment of QoL after surgery for diseases of the cardiac stomach is a fundamentally important component of monitoring the effectiveness of treatment and, therefore, allows one to determine the indications for certain types of interventions. The available world scientific literature does not provide convincing data on the assessment of QOL in patients after proximal resection for cardiac part of the stomach diseases, since there are no clear criteria for its assessment depending on the chosen methods and methods of reconstruction of gastrointestinal tract (GIT). In this regard, there is a need for further study of proximal resection with reconstruction of the gastrointestinal tract in surgical diseases of the cardiac part of the stomach on the basis of analysis of immediate and long-term results, as well as the quality of life of patients who underwent these surgical interventions.

Analysis of the relative copy numbers of TP63, YAP1 and KMT2D genetic loci and EGFR expression in orthotopic patient-derived xenografts of cardioesophageal cancer in immunodeficient mice.

e15033 Background: Cardioesophageal cancer is a common tumor affecting the cardiac stomach and lower esophagus. Tumor heterogeneity is important, since it can cause the ineffectiveness of chemotherapy and radiotherapy due to individual characteristics of the neoplasm in different patients, as well as the intensification of invasion and metastasis. Our purpose was to analyze the relative copy numbers of TP63, YAP1 and KMT2D genetic loci and EGFR expression in orthotopic patient-derived xenografts of cardioesophageal cancer. Methods: The model of cardioesophageal cancer was created in Balb/c Nude mice with surgical bioptates of adenocarcinoma obtained from donors. The relative copy numbers of TP63, YAP1 and KMT2D genetic loci and EGFR expression were determined by Real-Time qPCR. Results: A PDX model of cardioesophageal cancer was successfully created by transplanting a moderately differentiated adenocarcinoma from a patient diagnosed with infiltrative ulcerative cancer of the lower third of the esophagus with a transition to the cardiac stomach into the distal esophagus of Balb/c Nude mice. The EGFR expression was elevated in patient tumor samples, compared to healthy tissues (p = 0.021) and gastric cancer xenografts (p = 0.07). Molecular genetic analysis demonstrated an association between an increased EGFR expression and changes in the relative copy numbers of TP63, YAP1, and KMT2D in donor samples compared to gastric cancer xenografts (p = 0.02, p = 0.026 and p = 0.042). Conclusions: The relative copy numbers of TP63, YAP1, and KMT2D were associated with intensified EGFR expression and changed with each new generation of orthotopic xenografts.

Correlation of SOX-2 and NOTCH1 copy numbers with vimentin expression in orthotopic patient-derived xenografts of cardioesophageal cancer in immunodeficient mice.

e15034 Background: Cardioesophageal cancer is one of the most common tumors affecting the mucosa of the cardiac stomach and distal esophagus. Despite the variety of treatment strategies and chemotherapy agents, the prognosis for the patients remains poor. The purpose of the study was to analyze the relative copy numbers of SOX-2 and NOTCH1 and vimentin expression in orthotopic patient-derived xenografts of cardioesophageal cancer. Methods: The model of cardioesophageal cancer was created in Balb/c Nude mice with surgical bioptates of moderately differentiated adenocarcinoma obtained from a donor with infiltrative ulcerative cancer of the lower third of the esophagus with a transition to the cardiac stomach into the distal esophagus of Balb/c Nude mice. The index of proliferative activity in the bioptates was assessed by IHC. The relative copy numbers of SOX-2 and NOTCH1 and vimentin expression were determined by Real-Time qPCR. Results: Expression of vimentin was absent in tissues of the donor tumor. The levels of vimentin expression statistically significantly increased in xenografts (1+ and 3+). The SOX-2 and NOTCH1 relative copy numbers were statistically significantly increased in tissues of the donor tumor (0.9 and 0.7), compared to xenografts (1.5±0.03 and 1.7±0.03). Molecular genetic analysis demonstrated an association between an increased vimentin expression and changes in the relative copy numbers of SOX-2 and NOTCH1 (p = 0.013 and p = 0.0001). Conclusions: The relative copy numbers of SOX-2 and NOTCH1 genetic loci was associated with increased expression of the epithelial-mesenchymal transition marker vimentin in tumor tissue samples and changed with each new generation of orthotopic xenografts.

Frequencies of Porphyromonas gingivalis Detection in Oral-Digestive Tract Tumors

Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. In this study, we examined the presence of Porphyromonas gingivalis (P. gingivalis) in oral-digestive tract tumors by immunohistochemistry (IHC) and PCR and analyzed the correlation between P. gingivalis detection and clinicopathological characteristics and prognosis of oral and esophageal carcinoma. The IHC results showed that the positive rates of P. gingivalis were 60.00, 46.00, 20.00, 6.67, and 2.86% in oral, esophagus, cardiac, stomach, and colorectal cancer tissues, respectively. Likewise, PCR results showed rates of 56.00, 42.00, 16.67, 3.33, and 2.86%, respectively. The two methods were consistent, and the kappa value was 0.806, P &lt; 0.001. In addition, P. gingivalis expression was significantly correlated with lymph node metastasis and the clinical stages of oral and esophageal cancer (P &lt; 0.05). The overall survival rate of the P. gingivalis undetected group (86, 50%) was significantly higher than that of the P. gingivalis detected group (57, 14%) for oral and esophageal cancer, respectively. In conclusion, the detection rate of P. gingivalis showed a decreasing trend in oral-digestive tract tumors. Detection with P. gingivalis was associated with poor prognosis for oral and esophageal cancer.

Impacts of near‑future ocean warming on microbial community composition of the stomach of the soft‑bottom sea star Luidia clathrata (Say) (Echinodermata: Asteroidea)

There is growing evidence that environmental changes caused by climate change can impact the microbiome of marine invertebrates. Such changes can have important implications for the overall health of the host. In the present study we investigated the impact of chronic exposure to an ambient (28°C) and a predicted mid- (30°C) and end-of-century (32°C) seawater temperature on microbiome modification in tissues of the cardiac stomach of the abundant predatory sea star Luidia clathrata collected in September 2018 from Apalachee Bay, Florida (29°58’N, 84°19’W) in the northern Gulf of Mexico (GOM). Diversity (Shannon index) was lowest among the microbial community of stomach tissue when compared to the microbiome of the artificial sea star feed, and aquarium sand and seawater across all three experimental temperature treatments. Moreover, the stomach microbial community composition was distinct between each of the four sample types. Exposure to the highest experimental temperature treatment (32°C) resulted in a significant modification of the composition of the microbial community in stomach and sand samples, but not in seawater samples when compared to those from the current mean ambient GOM temperature (28°C). Importantly, at the most elevated temperature the stomach microbiome shifted from a Vibrio sp. dominated community to a more diverse community with higher proportions of additional taxa including Delftia sp. and Pseudomonas sp. This microbiome shift could impact the digestive functionality and ultimately the health of L. clathrata, a key soft-bottom predator in the northern GOM.

Evolutionarily ancient role of cholecystokinin-type neuropeptide signalling as an inhibitory regulator of feeding-related processes revealed in an echinoderm

Cholecystokinin (CCK) / sulfakinin (SK)-type neuropeptides regulate feeding and digestion in chordates and protostomes (e.g. insects). Here we characterised CCK/SK-type signalling for the first time in a non-chordate deuterostome - the starfish Asterias rubens (phylum Echinodermata). In this species, two neuropeptides (ArCCK1, ArCCK2) derived from the precursor protein ArCCKP act as ligands for a CCK/SK-type receptor (ArCCKR) and are expressed in the nervous system, digestive system, tube feet and body wall. Furthermore, ArCCK1 and ArCCK2 cause dose-dependent contraction of cardiac stomach, tube foot and body wall apical muscle preparations in vitro and injection of these neuropeptides in vivo triggers cardiac stomach retraction and inhibition of the onset of feeding in A. rubens. Thus, an evolutionarily ancient role of CCK/SK-type neuropeptides as inhibitory regulators of feeding-related processes in the Bilateria has been conserved in the unusual and unique context of the extra-oral feeding behaviour and pentaradial body plan of an echinoderm.

Molecular and functional characterization of somatostatin-type signalling in a deuterostome invertebrate

Somatostatin (SS) and allatostatin-C (ASTC) are structurally and evolutionarily related neuropeptides that act as inhibitory regulators of physiological processes in mammals and insects, respectively. Here, we report the first molecular and functional characterization of SS/ASTC-type signalling in a deuterostome invertebrate—the starfish Asterias rubens (phylum Echinodermata). Two SS/ASTC-type precursors were identified in A. rubens (ArSSP1 and ArSSP2) and the structures of neuropeptides derived from these proteins (ArSS1 and ArSS2) were analysed using mass spectrometry. Pharmacological characterization of three cloned A. rubens SS/ASTC-type receptors (ArSSR1–3) revealed that ArSS2, but not ArSS1, acts as a ligand for all three receptors. Analysis of ArSS2 expression in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed stained cells/fibres in the central nervous system, the digestive system (e.g. cardiac stomach) and the body wall and its appendages (e.g. tube feet). Furthermore, in vitro pharmacological tests revealed that ArSS2 causes dose-dependent relaxation of tube foot and cardiac stomach preparations, while injection of ArSS2 in vivo causes partial eversion of the cardiac stomach. Our findings provide new insights into the molecular evolution of SS/ASTC-type signalling in the animal kingdom and reveal an ancient role of SS-type neuropeptides as inhibitory regulators of muscle contractility.