Mucosal Cancer Research Articles

Cervical metastasis of undetermined origin: evaluation and criteria for management

<p class="abstract"><strong>Background:</strong> Cervical metastatic cancer of undetermined primary site is described as the presence of metastasis in the cervical lymph node(s) without any identifiable primary site, despite detailed clinical and investigative evaluations. Identification of primary origin is still a big challenge even in the phase of modern diagnostic options. This review was meant to lay open the challenges and offer options of evaluation and managing these cases in a resource limited environment.</p><p class="abstract"><strong>Methods:</strong> The literature search was carried out to retrieve relevant published articles, books, guidelines. The search was limited to articles in English while unpublished literatures were excluded. </p><p class="abstract"><strong>Results:</strong> The process of metastasis might begin before the obvious growth of the primary mass, making detection of primary site of a malignant tumour difficult to determine. There is no current worldwide consensus for evaluation and treatment of cervical metastasis of undetermined primary; however, the primary purpose for management should be towards cure along with locoregional control. This is always based on a well-studied natural history of the mucosal squamous cell cancers of the upper aerodigestive tract.</p><p class="abstract"><strong>Conclusions:</strong> The first step in the work up remains thorough clinical evaluation and the minimum evaluation should include computed tomography scan of the head and neck, core needle biopsy of the metastatic cervical lymph node(s) for histological analysis, panendoscopy and biopsies from suspicious sites in the upper airway. Treatment modalities can be classified into modified radical neck dissection with or without adjuvant radiotherapy, radiotherapy alone, and combination of surgical intervention and chemoradiation.</p>

Final Analysis of Diagnostic Endoscopic Resection Followed by Selective Chemoradiotherapy for Stage I Esophageal Cancer: JCOG0508

Final Analysis of Diagnostic Endoscopic Resection Followed by Selective Chemoradiotherapy for Stage I Esophageal Cancer: JCOG0508

S460 Safety of Powered Non-Thermal Endoscopic Ablation Device for Barrett’s Esophagus: A Systematic Review and Meta-Analysis

Introduction: Endoscopic mucosal resection (EMR) is utilized for removing preneoplastic or neoplastic lesions from the gastrointestinal tract. EMR is recommended for patients with a high risk of mucosal cancer, but the use of various thermal ablation techniques is associated with post-therapeutic stenosis. EndoRotor is a non-thermal device that suctions target epithelium into a small catheter where a spinning knife resects the mucosa, which reduces the risk of scarring and stenosis. Therefore, we performed a systematic review and meta-analysis to evaluate the safety of EndoRotor for non-thermal ablation of Barrett’s esophagus. Methods: A systematic review of the literature was performed using Medline, Embase, Web of Science, and the Cochrane library database until June 2022 to identify all studies that evaluated the safety of non-thermal endoscopic resection devices for the ablation of Barrett's esophagus. Other outcomes of interest included rates of intraoperative bleeding, post-procedural bleeding, perforation, post-procedural stenosis, and post-procedural pain or discomfort. All analyses were conducted using comprehensive meta-analysis software. Results: Five studies, including 70 patients, were included in the final analysis. There were four observational studies and one randomized controlled trial. The pooled rate of intraoperative bleeding was 39% (95% CI: 25.4-54.5%, I2=0) and post-procedural bleeding was 7.5% (95% CI: 2.6%-19.6%, I2=0). The pooled rate of perforation was 4.1% (1.3%-11.9%, I2=0), post-procedural follow-up stenosis was 11.2% (4.7%-24.2%, I2=0), and post-procedural pain or discomfort was 54.2% (95% CI: 41.5%-66.4%, I2=9.2%). The efficacy of EndoRotor was not evaluated given the lack of data reported in the included studies. Conclusion: The new EndoRotor resection device could be a viable alternative to existing ablative therapies for Barrett's esophagus. However, our study revealed significant adverse events, and therefore, larger randomized control trials are warranted to evaluate the risks and benefits of this novel device.

The Effect of Radiation Therapy on the Success of the Use of Submental Flap in the Reconstruction of Oral Cavity Defects

Purpose: To evaluate the effect of previously performed radiation therapy on the successful use of a submental flap in oral reconstruction. Material and methods: The study included 52 patients who underwent reconstruction of oral cavity defects using a submental flap between February 2015 and January 2021. Radiation therapy was performed in 13 patients in the preoperative period at different time periods and in different doses. Results: From February 2015 to August 2021, to 52 patients submental flap was used to reconstruct oral cavity defects after surgical treatment of oral mucosal cancer. 13 patients received radiation therapy before surgical treatment compared to 39 who did not. In eleven cases, partial flap necrosis occurred, of which 3 underwent radiation therapy to two in a radical dose before surgical treatment. In two cases, there was a discrepancy of sutures in the oral cavity, one in each group, which did not require surgical intervention and were closed with conservative treatment. Two patients who underwent radiation therapy developed a fistula communicating with the oral cavity and neck healed spontaneously with conservative management. Marginal mandibular nerve palsy developed in three patients, one in the group with radiation therapy, the rest without a history of radiation therapy. Conclusions: Total flap necrosis was not observed in any group. Thus, preoperative radiation therapy is not a contraindication to the use of a submental flap to reconstruct oral cavity defects with relatively acceptable complications. The submental flap is easy to harvest, reliable, universal flap to reconstruct oral cavity defects.

Nur77 promotes invasion and migration of gastric cancer cells through the NF-κB/IL-6 pathway

To analyze the association of Nur77 with overall survival of gastric cancer patients and investigate the role of Nur77 in invasion and migration of gastric cancer cells. Oncomine database was used to analyze the expression of Nur77 in gastric cancer and gastric mucosa tissues, and the distribution characteristics of Nur77 protein between gastric cancer and normal tissues were compared using Human Protein Atlas. GEPIA2 was used to analyze the relationship of Nur77 expression and the patients' survival. The expression of Nur77 in gastric cancer cell lines GES-1, AGS and MKN-45 were detected by Western blotting. The regulatory interactions between IL-6 and Nur77 were verified by transfecting the cells with specific Nur-77 siRNA and Nur-77-overexpressing plasmid. The changes in migration ability of the cells following Nur-77 knockdown were assessed with scratch assay. The effect of Nur-77 overexpression or IL-6 knockdown, or their combination, on migration and invasion of the gastric cancer cells were examined using Transwell assay. The effect of Nur77 expression level on NF-κB/IL-6 pathway activation was analyzed using Western blotting. Oncomine database showed that gastric cancer tissues expressed a significantly higher level of Nur77 mRNA than normal tissues (P < 0.05). Nur77 expression was detected mostly in the nucleus, and a high Nur77 expression was associated with a poor survival outcome of the patients (P < 0.05). In gastric cancer cells, the high expression of Nur77 participated in the regulation of IL-6. Nur77 silencing significantly lowered the migration ability of the cells (P < 0.05), and IL-6 silencing significantly attenuated the enhanced migration caused by Nur77 overexpression (P < 0.05). Nur77 participates in the activation of NF-κB/IL-6 signaling pathway by regulating the expression of p-p65, p65, p-Stat3 and Stat3. A high Nur77 expression is strongly correlated with a poor prognosis of gastric cancer patients. Nur77 promotes the invasion and migration of gastric cancer cells possibly by regulating the NF-κB/IL-6 signaling pathway.

Clinicopathological Significance and Molecular Mechanism of AKT/GSK3β Pathway-based Fibrillin-1 Expression in Gastric Cancer Progression.

This research was developed to explore the significance of fibrillin-1 (FBN1) in the progression of gastric cancer and its relationship with the activation of the AKT/glycogen synthase kinase-3beta (GSK3β) pathway. For this aim, immunohistochemical assays were adopted to detect FBN1 expression in chronic superficial gastritis, chronic atrophic gastritis, gastric cancer, and normal mucosa. The expression of FBN1 in gastric cancer and adjacent tissue samples was detected by reverse transcription-quantitative (RT-q) PCR and Western blot, and the relationship between FBN1 and the clinicopathological features of gastric cancer patients was analyzed. Lentivirus was utilized to construct SGC-7901 gastric cancer cell lines stably overexpressing and silencing FBN1, and the effects on cell proliferation, colony formation, and apoptosis were analyzed. AKT, GSK3β, and their phosphorylated proteins were detected by Western blot. Results showed that the positive expression rate of FBN1 increased successively in chronic superficial gastritis, chronic atrophic gastritis, and gastric cancer. FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of tumor invasion. Overexpression of FBN1 promoted the proliferation and colony formation of gastric cancer cells, inhibited apoptosis, and promoted the phosphorylation of AKT and GSK3β. Silencing FBN1 expression inhibited the proliferation and clonal formation of gastric cancer cells, promoted apoptosis, and inhibited the phosphorylation of AKT and GSK3β. In conclusion, FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of gastric tumor invasion. FBN1 silencing inhibited the progression of gastric cancer through the AKT/GSK3β pathway.

Automatic optical biopsy for colorectal cancer using hyperspectral imaging and artificial neural networks.

Intraoperative identification of cancerous tissue is fundamental during oncological surgical or endoscopic procedures. This relies on visual assessment supported by histopathological evaluation, implying a longer operative time. Hyperspectral imaging (HSI), a contrast-free and contactless imaging technology, provides spatially resolved spectroscopic analysis, with the potential to differentiate tissue at a cellular level. However, HSI produces "big data", which is impossible to directly interpret by clinicians. We hypothesize that advanced machine learning algorithms (convolutional neural networks-CNNs) can accurately detect colorectal cancer in HSI data. In 34 patients undergoing colorectal resections for cancer, immediately after extraction, the specimen was opened, the tumor-bearing section was exposed and imaged using HSI. Cancer and normal mucosa were categorized from histopathology. A state-of-the-art CNN was developed to automatically detect regions of colorectal cancer in a hyperspectral image. Accuracy was validated with three levels of cross-validation (twofold, fivefold, and 15-fold). 32 patients had colorectal adenocarcinomas confirmed by histopathology (9 left, 11 right, 4 transverse colon, and 9 rectum). 6 patients had a local initial stage (T1-2) and 26 had a local advanced stage (T3-4). The cancer detection performance of the CNN using 15-fold cross-validation showed high sensitivity and specificity (87% and 90%, respectively) and a ROC-AUC score of 0.95 (considered outstanding). In the T1-2 group, the sensitivity and specificity were 89% and 90%, respectively, and in the T3-4 group, the sensitivity and specificity were 81% and 93%, respectively. Automatic colorectal cancer detection on fresh specimens using HSI, using a properly trained CNN is feasible and accurate, even with small datasets, regardless of the local tumor extension. In the near future, this approach may become a useful intraoperative tool during oncological endoscopic and surgical procedures, and may result in precise and non-destructive optical biopsies to support objective and consistent tumor-free resection margins.

Clinicopathological and molecular characterization of early gastric adenocarcinoma in Helicobacter pylori-uninfected patients: emphasis on differentiated gastric adenocarcinoma.

Recently, Helicobacter pylori (HP)-uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP-uninfected gastric cancer have not been elucidated. We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS). Among 968 primary early gastric carcinomas, 64 (6.6%) were HP-uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n = 39), differentiated gastric adenocarcinoma (DGA, n = 16), and signet-ring cell carcinoma (SRCC, n = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously (n = 5), and a gastric phenotype (n = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP-uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%). Overall, HP-uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP-uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.

Passive Immunization with a Single Monoclonal Neutralizing Antibody Protects against Cutaneous and Mucosal Mouse Papillomavirus Infections.

We have established a mouse papillomavirus (MmuPV1) model that induces both cutaneous and mucosal infections and cancers. In the current study, we use this model to test our hypothesis that passive immunization using a single neutralizing monoclonal antibody can protect both cutaneous and mucosal sites at different time points after viral inoculation. We conducted a series of experiments involving the administration of either a neutralizing monoclonal antibody, MPV.A4, or control monoclonal antibodies to both outbred and inbred athymic mice. Three clinically relevant mucosal sites (lower genital tract for females and anus and tongue for both males and females) and two cutaneous sites (muzzle and tail) were tested. At the termination of the experiments, all tested tissues were harvested for virological analyses. Significantly lower levels of viral signals were detected in the MPV.A4-treated female mice up to 6 h post-viral inoculation compared to those in the isotype control. Interestingly, males displayed partial protection when they received MPV.A4 at the time of viral inoculation, even though they were completely protected when receiving MPV.A4 at 24 h before viral inoculation. We detected MPV.A4 in the blood starting at 1 h and up to 8 weeks postadministration in some mice. Parallel to these in vivo studies, we conducted in vitro neutralization using a mouse keratinocyte cell line and observed complete neutralization up to 8 h post-viral inoculation. Thus, passive immunization with a monoclonal neutralizing antibody can protect against papillomavirus infection at both cutaneous and mucosal sites and is time dependent. IMPORTANCE This is the first study testing a single monoclonal neutralizing antibody (MPV.A4) by passive immunization against papillomavirus infections at both cutaneous and mucosal sites in the same host in the mouse papillomavirus model. We demonstrated that MPV.A4 administered before viral inoculation can protect both male and female athymic mice against MmuPV1 infections at cutaneous and mucosal sites. MPV.A4 also offers partial protection at 6 h post-viral inoculation in female mice. MPV.A4 can be detected in the blood from 1 h to 8 weeks after intraperitoneal (i.p.) injection. Interestingly, males were only partially protected when they received MPV.A4 at the time of viral inoculation. The failed protection in males was due to the absence of neutralizing MPV.A4 at the infected sites. Our findings suggest passive immunization with a single monoclonal neutralizing antibody can protect against diverse papillomavirus infections in a time-dependent manner in mice.

Short-term outcomes of three rare cases of intramucosal Epstein-Barr virus-associated gastric cancer treated with endoscopic submucosal dissection.

Epstein–Barr virus-associated gastric cancer (EBVaGC) is a subtype of gastric cancer morphologically characterized by massive lymphocyte infiltration. We herein report the short-term outcomes of three rare cases of intramucosal EBVaGC treated with endoscopic submucosal dissection (ESD). Histologically, the lesions exhibited poorly to moderately differentiated tubular adenocarcinoma without lymphovascular invasion, and in situ hybridization revealed EBV-encoded small RNA. Helicobacter pylori infection was not found in any of the lesions. During the 3 to 12 months of follow-up following ESD, none of the ESD-treated patients showed evidence of local recurrence or distant metastases. Essential characteristics of intramucosal EBVaGC may include lymphocyte infiltration into the mucosal stroma or cancer nests as well as the presence of a lace pattern. We believe that ESD might be a safe and suitable treatment method for intramucosal EBVaGC that avoids needless surgery, particularly in patients with severe comorbidities or a high operational risk.

Artificial intelligence for diagnosing gastric lesions under white-light endoscopy.

The ability of endoscopists to identify gastric lesions is uneven. Even experienced endoscopists may miss or misdiagnose lesions due to heavy workload or fatigue or subtle changes in lesions under white-light endoscopy (WLE). This study aimed to develop an artificial intelligence (AI) system that could diagnose six common gastric lesions under WLE and to explore its role in assisting endoscopists in diagnosis. Images of early gastric cancer, advanced gastric cancer, submucosal tumor, polyp, peptic ulcer, erosion, and lesion-free gastric mucosa were retrospectively collected to train and test the system. The performance of the system was compared with that of 12 endoscopists. The performance of endoscopists with or without referring to the system was also evaluated. A total of 29,809 images from 8947 patients and 1579 images from 496 patients were used to train and test the system, respectively. For per-lesion analysis, the overall accuracy of the system was 85.7%, which was comparable to that of senior endoscopists (85.1%, P = 0.729) and significantly higher than that of junior endoscopists (78.8%, P < 0.001). With system assistance, the overall accuracies of senior and junior endoscopists increased to 89.3% (4.2%, P < 0.001) and 86.2% (7.4%, P < 0.001), respectively. Senior and junior endoscopists achieved varying degrees of improvement in the diagnostic performance of other types of lesions except for polyp. The diagnostic times of senior (3.8 vs 3.2s per image, P = 0.500) and junior endoscopists (6.2 vs 4.6s per image, P = 0.144) assisted by the system were both slightly shortened, despite no significant differences. The proposed AI system could be applied as an auxiliary tool to reduce the workload of endoscopists and improve the diagnostic accuracy of gastric lesions.

Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer.

IgGFc-binding protein (FCGBP) is a mucin first detected in the intestinal epithelium. It plays an important role in innate mucosal epithelial defense, tumor metastasis, and tumor immunity. FCGBP forms disulfide-linked heterodimers with mucin-2 and members of the trefoil factor family. These formed complexes inhibit bacterial attachment to mucosal surfaces, affect the motility of pathogens, and support their clearance. Altered FCGBP expression levels may be important in the pathologic processes of Crohn’s disease and ulcerative colitis. FCGBP is also involved in regulating the infiltration of immune cells into tumor microenvironments. Thus, the molecule is a valuable marker of tumor prognosis. This review summarizes the functional relevance and role of FCGBP in immune responses and disease development, and highlights the potential role in diagnosis and predicting tumor prognosis.

The Morphological Analysis of the Collagen Fiber Straightness in the Healthy Uninvolved Human Colon Mucosa Away From the Cancer

The morphological method—based on the topology and singularity theory and originally developed for the analysis of the scattering experiments—was extended to be applicable for the analysis of biological data. The usefulness of the topological viewpoint was demonstrated by quantification of the changes in collagen fiber straightness in the human colon mucosa (healthy mucosa, colorectal cancer, and uninvolved mucosa far from cancer). This has been done by modeling the distribution of collagen segment angles by the polymorphic beta-distribution. Its shapes were classified according to the number and type of critical points. We found that biologically relevant shapes could be classified as shapes without any preferable orientation (i.e. shapes without local extrema), transitional forms (i.e. forms with one broad local maximum), and highly oriented forms (i.e. forms with two minima at both ends and one very narrow maximum between them). Thus, changes in the fiber organization were linked to the metamorphoses of the beta-distribution forms. The obtained classification was used to define a new, shape-aware/based, measure of the collagen straightness, which revealed a slight and moderate increase of the straightness in mucosa samples taken 20 and 10 cm away from the tumor. The largest increase of collagen straightness was found in samples of cancer tissue. Samples of healthy individuals have a uniform distribution of beta-distribution forms. We found that this distribution has the maximal information entropy. At 20 cm and 10 cm away from cancer, the transition forms redistribute into unoriented and highly oriented forms. Closer to cancer the number of unoriented forms decreases rapidly leaving only highly oriented forms present in the samples of the cancer tissue, whose distribution has minimal information entropy. The polarization of the distribution was followed by a significant increase in the number of quasi-symmetrical forms in samples 20 cm away from cancer which decreases closer to cancer. This work shows that the evolution of the distribution of the beta-distribution forms—an abstract construction of the mind—follows the familiar laws of statistical mechanics. Additionally, the polarization of the beta-distribution forms together with the described change in the number of quasi-symmetrical forms, clearly visible in the parametric space of the beta-distribution and very difficult to notice in the observable space, can be a useful indicator of the early stages in the development of colorectal cancer.

Outer Membrane Vesicles From The Gut Microbiome Contribute to Tumor Immunity by Eliciting Cross-Reactive T Cells.

A growing body of evidence supports the notion that the gut microbiome plays an important role in cancer immunity. However, the underpinning mechanisms remain to be fully elucidated. One attractive hypothesis envisages that among the T cells elicited by the plethora of microbiome proteins a few exist that incidentally recognize neo-epitopes arising from cancer mutations (“molecular mimicry (MM)” hypothesis). To support MM, the human probiotic Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA-E.coli Nissle) and orally administered to C57BL/6 mice. The treatment with OVA-E.coli Nissle, but not with wild type E. coli Nissle, induced OVA-specific CD8+ T cells and inhibited the growth of tumors in mice challenged with B16F10 melanoma cells expressing OVA. The microbiome shotgun sequencing and the sequencing of TCRs from T cells recovered from both lamina propria and tumors provide evidence that the main mechanism of tumor inhibition is mediated by the elicitation at the intestinal site of cross-reacting T cells, which subsequently reach the tumor environment. Importantly, the administration of Outer Membrane Vesicles (OMVs) from engineered E. coli Nissle, as well as from E. coli BL21(DE3)ΔompA, carrying cancer-specific T cell epitopes also elicited epitope-specific T cells in the intestine and inhibited tumor growth. Overall, our data strengthen the important role of MM in tumor immunity and assign a novel function of OMVs in host-pathogen interaction. Moreover, our results pave the way to the exploitation of probiotics and OMVs engineered with tumor specific-antigens as personalized mucosal cancer vaccines.

Short-term outcomes of patients undergoing endoscopic submucosal dissection for colorectal lesions.

ObjectivesEndoscopic submucosal dissection (ESD) of colorectal lesions was invented in Japan, but postoperative management including hospital stay has not been reconsidered due to the Japanese insurance system. To explore appropriate postoperative management after colorectal ESD, we reviewed short‐term outcomes after ESD in non‐selected consecutive patients.MethodsPatients who underwent colorectal ESD from April 2013 to September 2020 in one institution were reviewed. The primary outcome measure was the occurrence of adverse events stratified by the Clavien‐Dindo classification with five grades. A logistic regression model with the Firth procedure was applied to investigate predictors of severe (grade III or greater) adverse events.ResultsA total of 330 patients (female 40%, male 60%; median 72 years; IQR 65–80 years) with colorectal lesions (median 30 mm, IQR 23–40 mm; colon 77%, rectum 23%; serrated lesion 4%, adenoma 47%, mucosal cancer 30%, invasive cancer 18%) was evaluated. The en bloc resection rate was 97%. The median dissection time was 58 min (IQR: 38–86). Intraprocedural perforation occurred in 3%, all successfully treated by endoscopic clipping. No delayed perforations occurred. Postprocedural bleeding occurred in 3% on days 1–10 (median day 2); all were controlled endoscopically. Severe adverse events included only delayed bleeding. In analyzing severe adverse events in a multivariate logistic regression model with the Firth procedure, antithrombotic agent use (p = 0.016) and rectal lesions (p = 0.0010) were both significant predictors.ConclusionsNo serious adverse events occurred in this series. Four days of hospitalization may be too long for the majority of patients after ESD.

Meta-analysis of mucosal microbiota reveals universal microbial signatures and dysbiosis in gastric carcinogenesis

The consistency of the associations between gastric mucosal microbiome and gastric cancer across studies remained unexamined. We aimed to identify universal microbial signatures in gastric carcinogenesis through a meta-analysis of gastric microbiome from multiple studies. Compositional and ecological profiles of gastric microbes across stages of gastric carcinogenesis were significantly altered. Meta-analysis revealed that opportunistic pathobionts Fusobacterium, Parvimonas, Veillonella, Prevotella and Peptostreptococcus were enriched in GC, while commensals Bifidobacterium, Bacillus and Blautia were depleted in comparison to SG. The co-occurring correlation strengths of GC-enriched bacteria were increased along disease progression while those of GC-depleted bacteria were decreased. Eight bacterial taxa, including Veillonella, Dialister, Granulicatella, Herbaspirillum, Comamonas, Chryseobacterium, Shewanella and Helicobacter, were newly identified by this study as universal biomarkers for robustly discriminating GC from SG, with an area under the curve (AUC) of 0.85. Moreover, H. pylori-positive samples exhibited reduced microbial diversity, altered microbiota community and weaker interactions among gastric microbes. Our meta-analysis demonstrated comprehensive and generalizable gastric mucosa microbial features associated with histological stages of gastric carcinogenesis, including GC associated bacteria, diagnostic biomarkers, bacterial network alteration and H. pylori influence.

Artificial intelligence-assisted staging in Barrett's carcinoma.

Artificial intelligence (AI) is increasingly being used to detect neoplasia and interpret endoscopic images. The T stage of Barrett's carcinoma is a major criterion for subsequent treatment decisions. Although endoscopic ultrasound is still the standard for preoperative staging, its value is debatable. Novel tools are required to assist with staging, to optimize results. This study aimed to investigate the accuracy of T stage of Barrett's carcinoma by an AI system based on endoscopic images. 1020 images (minimum one per patient, maximum three) from 577 patients with Barrett's adenocarcinoma were used for training and internal validation of a convolutional neural network. In all, 821 images were selected to train the model and 199 images were used for validation. AI recognized Barrett's mucosa without neoplasia with an accuracy of 85 % (95 %CI 82.7-87.1). Mucosal cancer was identified with a sensitivity of 72 % (95 %CI 67.5-76.4), specificity of 64 % (95 %CI 60.0-68.4), and accuracy of 68 % (95 %CI 64.6-70.7). The sensitivity, specificity, and accuracy for early Barrett's neoplasia < T1b sm2 were 57 % (95 %CI 51.8-61.0), 77 % (95 %CI 72.3-80.2), and 67 % (95 %CI 63.4-69.5), respectively. More advanced stages (T3/T4) were diagnosed correctly with a sensitivity of 71 % (95 %CI 65.1-76.7) and specificity of 73 % (95 %CI 69.7-76.5). The overall accuracy was 73 % (95 %CI 69.6-75.5). The AI system identified esophageal cancer with high accuracy, suggesting its potential to assist endoscopists in clinical decision making.

Differences in serological profiles of Epstein-Barr virus infection in patients with head and neck tumors and lymphomas.

e18055 Background: Epstein-Barr virus (EBV) is associated with the development of various cancers, including nasopharyngeal carcinoma (NPC), gastric cancer, and lymphomas. The use of EBV serological markers in screening and monitoring of NPC has been shown to be valuable. The significance of serological markers in the diagnosis of other head and neck cancers is poorly described. The aim of this study was to analyze the serological profiles of EBV infection in patients with head and neck tumors. Methods: The main group included 24 patients with laryngeal cancer (n = 12) and oral mucosa cancer (n = 12). Keratinizing squamous cell carcinoma was registered in 22 (91.7%) patients, and adenoid cystic cancer in 2 (8.3%) patients. The control group included 44 lymphoma patients. Antibodies to EBV proteins were determined in the blood serum by ELISA and Western blot (WB) tests. Results: ELISA detected antibodies of the A, M and/or G classes against various EBV proteins in 100% of patients in the main group and 97.7% of controls. IgA VCA in patients with head and neck cancer were determined 2.7 times more often (50% vs 18.2%, p = 0.034) than in patients with lymphomas, IgG EA - 2.1 times more often (58.3% vs 27.3%, p = 0.049), and the complex of acute infection markers (IgA VCA, IgM VCA, IgG EA in various combinations) was determined 2.0 times more often (66.7% vs 34.1%, p = 0.045). Atypical profile (only VCA IgG+) was determined only in patients with lymphomas (4.5%). The profile characteristic of immunosuppression (IgG VCA+, IgG EA+, NA IgG±) was determined 1.8 times more often in patients with head and neck cancer than in patients with lymphomas (25% vs 13.6%, p &gt; 0.05). According to WB tests, patients of the main group more often demonstrated IgM EBNA-1p79 (16.7%), VCA p65 (16.7) and p22 (16.7%), while controls – VCA p22 (27.8%), EA-R p93 (16.7%) and VCA p33 (16.7%). IgG in the main group was more often determined to EBNA-1 p79 (91.7%), VCA p22 (91.7%) and VCA p33 (66.7%), in the control group to VCA p40 (87.5%), EBNA-1 p79 (75%) and VCA p22 (62.5%). Statistically significant differences were found only for VCA p42 (0% in the experimental group and 37.5% in controls, p = 0.049), VCA p40 (25% and 87.5%, p = 0.009) and p27 (0% and 37.5%, p = 0.049). EA-D p45 was determined only in patients with lymphoma. Conclusions: The vast majority of patients in both groups were previously infected with EBV. Serological profiles of EBV infection in patients with head and neck cancer and lymphomas were significantly different. Markers of acute infection were more often determined in patients with head and neck cancer; the range of individual proteins in the main group was narrower than in the control group. The biological meaning of the differences in the detection rates of antibodies to individual EBV proteins in patients of the two groups remains to be elucidated.

PECULIARITIES OF COVID-19 SUSCEPTIBILITY IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

Polycystic ovary syndrome (PCOS) is the most common endocrinological disease among women of reproductive age, the prevalence of which reaches up to 15% in the world depending on the study population and the diagnostic criteria used. Purpose: analysis of existing medical research on the increased susceptibility to Covid-19, its form and features among women with PCOS, coverage of research on this topic to raise awareness of Ukrainian physicians in building proper prevention, modernizing approaches to diagnosis, treatment and avoidance of Covid-19 complications in women with PCOS and to disseminate material and further in form PCOS patients about possible risks of Covid-19. Results and discussion. Women with PCOS are characterized by a higher incidence of cardiovascular disease, kidney damade, non-fatty steatohepatitis, achieving a body mass index over 30 kg/m2 , diabetes and endometrial mucosal cancer. Metabolic syndrome characterized by hypertension, obesity, insulin resistance and dyslipidemia is found in 22.7% of women with PCOS. Given the high prevalence of various risk factors for PCOS, which coincide with the severity of Covid-19, it can be argued that women with PCOS are a critical group of patients with a potentially higher risk of adverse effects of Covid-19. Conclusions. Despite their young age and gender, women with PCOS are at increased risk for Covid-19. Women with cardiovascular and metabolic diseases in PCOS are a group of patients with a potentially higher risk of complications from Covid-19. Women with PCOS should first be informed about the need for vaccination and preventive measures during the Covid-19 pandemic, monitoring the treatment of existing pathologies and prompt medical attention for SARS-CoV-2 infection.

Prevalence, Cell Tropism, and Clinical Impact of Human Parvovirus Persistence in Adenomatous, Cancerous, Inflamed, and Healthy Intestinal Mucosa.

Parvoviruses are single-stranded DNA viruses, infecting many animals from insects to humans. Human parvovirus B19 (B19V) causes erythema infectiosum, arthropathy, anemia, and fetal death, and human bocavirus (HBoV) 1 causes respiratory tract infections, while HBoV2-4 are enteric. Parvoviral genomes can persist in diverse non-permissive tissues after acute infection, but the host-cell tropism and the impact of their tissue persistence are poorly studied. We searched for parvoviral DNA in a total of 427 intestinal biopsy specimens, as paired disease-affected and healthy mucosa, obtained from 130 patients with malignancy, ulcerative colitis (UC), or adenomas, and in similar intestinal segments from 55 healthy subjects. Only three (1.6%) individuals exhibited intestinal HBoV DNA (one each of HBoV1, 2, and 3). Conversely, B19V DNA persisted frequently in the intestine, with 50, 47, 31, and 27% detection rates in the patients with malignancy, UC, or adenomas, and in the healthy subjects, respectively. Intra-individually, B19V DNA persisted significantly more often in the healthy intestinal segments than in the inflamed colons of UC patients. The highest loads of B19V DNA were seen in the ileum and colon specimens of two healthy individuals. With dual-RNAscope in situ hybridization and immunohistochemistry assays, we located the B19V persistence sites of these intestines in mucosal B cells of lymphoid follicles and vascular endothelial cells. Viral messenger RNA transcription remained, however, undetected. RNA sequencing (RNA-seq) identified 272 differentially expressed cellular genes between B19V DNA-positive and -negative healthy ileum biopsy specimens. Pathway enrichment analysis revealed that B19V persistence activated the intestinal cell viability and inhibited apoptosis. Lifelong B19V DNA persistence thus modulates host gene expression, which may lead to clinical outcomes.