Malignant Gastrointestinal Diseases Research Articles

A review of wrist mechanism design and the application in gastrointestinal minimally invasive surgery of multi-degree-of-freedom surgical laparoscopic instruments.

This paper aims to comprehensively review current designs of Multi-degree-of-freedom (Multi-DOF) wrist mechanisms and the applications of Multi-DOF surgical instruments in gastrointestinal minimally invasive surgery (MIS). By reviewing the advantages and limitations of traditional laparoscopic and robotic surgical instruments, we present the development of Multi-DOF surgical instruments. Then, we summarize the Multi-DOF wrist mechanisms, delineating their pros and cons. Finally, the surgical outcomes and efficiency of Multi-DOF surgical instruments are reviewed. The utilization of Multi-DOF surgical instruments for both benign and malignant gastrointestinal diseases demonstrates perioperative outcomes comparable to traditional laparoscopic and robotic surgeries. In certain aspects, it exhibits advantages such as shorter operative times and faster gastrointestinal function recovery. Further research is needed to effectively combine these driving mechanisms to achieve a new type of transmission mechanism with high rigidity and precision, ample working space, and decoupled degrees of freedom. Multi-DOF surgical instruments offer the advantages of high flexibility and lower costs, displaying good feasibility and safety in practical clinical applications within gastrointestinal surgery. Their promotion in primary care hospitals could benefit a larger patient population. However, more extensive sample-sized multicenter studies are still warranted to elucidate such surgical instruments' advantages further.

Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with a high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although NDUFA4L2 has high expressions in various tumors and affects tumor progression, its role in COAD remains unclear. The role of NDUFA4L2 in COAD was analyzed utilizing datasets available from public databases including The Cancer Genome Atlas, The Genotype-Tissue Expression (GTEx), Gene Expression Omnibus, Alabama Cancer Database (UALCAN), and The Human Protein Atlas databases. The prognostic value of NDUFA4L2 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NDUFA4L2 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NDUFA4L2 expression and immune cell infiltration levels was examined through single-sample gene set enrichment analysis (ssGSEA). The NDUFA4L2 expression levels in COAD patients and cell lines were validated through immunohistochemistry, immunofluorescence, qRT-PCR, and Western blot. Wound healing assay was also performed to evaluate the effect of NDUFA4L2 on COAD metastasis. Furthermore, the NDUFA4L2 mediated competing endogenous RNA (ceRNA) regulatory network was predicted and constructed through a variety of databases. The comprehensive pan-cancer analysis showed that NDUFA4L2 possesses diagnostic and prognostic value in many cancers, especially in COAD. GO-KEGG and GSEA analyses indicated that NDUFA4L2 was associated with multiple biological functions including epithelial-mesenchymal transition and adaptation to hypoxia. The ssGSEA analysis showed that NDUFA4L2 expression was associated with immune infiltration. In vitro experiments confirmed upregulation of NDUFA4L2 in COAD tissues and cell lines, and NDUFA4L2 overexpression significantly promoted migration of COAD cells. In addition, the C9orf139 /miR-194-3p axis was speculated as the possible upstream regulators of NDUFA4L2 in COAD. This study demonstrated that NDUFA4L2 upregulation was correlated with tumor progression, relapsed prognosis and aggressive migration of COAD, suggesting that NDUFA4L2 can act as an effective prognostic biomarker and a promising therapeutic target for COAD treatment.

SLC12A8 upregulation promotes colorectal cancer progression and chemoresistance.

Colorectal cancer (CRC), a prevalent gastrointestinal malignant disease, causes substantial morbidity and mortality. Identification of novel prognostic biomarkers and therapeutic targets is critically needed to improve patient outcomes. Although solute carrier family 12 member 8 (SLC12A8) has high expression in various tumors and affects tumor progression, its role in CRC remains unclear. The aim of this study was to investigate the functions of SLC12A8 in CRC. SLC12A8 expression and its association with clinical significance in CRC patients were explored via multiple public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Human Protein Atlas (HPA), The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and Kaplan-Meier plotter. The effects of SLC12A8 on the CRC cell apoptosis, epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS) production, and sensitivity to oxaliplatin were verified by in vitro experiments. SLC12A8 expression was upregulated in CRC tissues compared with normal colorectal tissues. Furthermore, high expression of SLC12A8 was associated with poorer prognosis in CRC patients. Pathway enrichment analyses revealed SLC12A8 involvement in oxidative stress and transforming growth factor-beta (TGF-β) signaling. Experiments in CRC cells showed that SLC12A8 upregulation promoted apoptosis resistance, EMT, and inhibited ROS production. Moreover, SLC12A8 knockdown enhanced the sensitivity of CRC cells to oxaliplatin chemotherapy. Our integrative analyses identify SLC12A8 as a candidate biomarker for CRC progression. Targeting SLC12A8 may improve patient responses to oxaliplatin-based treatment regimens.

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although neurexophilin 4 (NXPH4) has been investigated in several tumors, its role in COAD remains unclear. The aim of this study was to explore the prognostic value and potential functions of NXPH4 in COAD. The expression of NXPH4 in COAD were analyzed using The Cancer Genome Atlas (TCGA) and datasets from the Gene Expression Omnibus (GEO) database. The prognostic value of NXPH4 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NXPH4 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NXPH4 expression and immune cell infiltration levels was examined thorough single-sample gene set enrichment analysis (ssGSEA). Furthermore, the competing endogenous RNA (ceRNA) regulatory network that may be involved in NXPH4 in COAD was predicted and constructed through a variety of databases. NXPH4 expression was significantly higher in COAD tissue compared with normal colon tissues. Meanwhile, high expression of NXPH4 was associated with poor prognosis in COAD patients. GO-KEGG and GSEA analyses indicated that NXPH4 was associated with glycolysis and hypoxia pathway, and may promote COAD progression and metastasis by modulating metabolic reprogramming. ssGSEA analysis demonstrated that NXPH4 expression also associated with immune infiltration. Furthermore, we identified various microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) as upstream regulators of NXPH4 in COAD. The present study revealed that high expression of NXPH4 is associated with tumor progression, metabolic reprogramming, and immune infiltration. These findings suggest that NXPH4 could serve as a reliable prognostic biomarker and a promising therapeutic target in COAD.

Clinical Impact of Exosomes in Colorectal Cancer Metastasis.

Cancer is a complex deadly disease that has caused a global health crisis in recent epochs. Colorectal cancer (CRC) is the third most common malignant gastrointestinal disease. It has led to high mortality due to early diagnostic failure. Extracellular vesicles (EVs) come with promising solutions for CRC. Exosomes (a subpopulation of EVs) play a vital role as signaling molecules in CRC tumor microenvironment. It is secreted from all active cells. Exosome-based molecular transport (DNA, RNA, proteins, lipids, etc.) transforms the recipient cell's nature. In CRC, tumor cell-derived exosomes (TEXs) regulate multiple events of CRC development and progression such as immunogenic suppression, angiogenesis, epithelial-mesenchymal transitions (EMT), physical changes in the extracellular matrix (ECM), and metastasis. Biofluid-circulated tumor-derived exosomes (TEXs) are a potential tool for CRC liquid biopsy. Exosome-based colorectal cancer detection creates a great impact in CRC biomarker research. The exosome-associated CRC theranostics approach is a state-of-the-art method. In this review, we address the CRC and exosomes complex associated with cancer development and progression, the impact of exosomes on CRC screening (diagnostic and prognostic biomarkers), and also highlight several exosomes with CRC clinical trials, as well as future directions of exosome-based CRC research. Hopefully, it will encourage several researchers to develop a potential exosome-based theranostic tool to fight CRC.

Clostridioides difficile Infection in a Japanese Tertiary Children's Hospital.

PurposeToxins produced by Clostridioides difficile infection (CDI) can cause enteritis and diarrhea. Although the number of pediatric CDI cases is increasing, the clinical management of pediatric CDI, including patient characteristics and prognosis, remains unclear. This study aimed to elucidate the background and clinical course of patients with CDI and evaluate the reliability of diagnostic tests in a tertiary pediatric hospital in Japan.MethodsWe retrospectively analyzed the clinical data of children diagnosed with CDI between 2011 and 2021 at the Saitama Children’s Medical Center in Saitama, Japan.ResultsDuring the study period, 1,252 C. difficile antigen/toxin tests were performed, and 37 patients were diagnosed with CDI. The main underlying diseases among the patients were hematological and malignant disorders and gastrointestinal diseases, including inflammatory bowel disease (IBD) (59.4%). Two patients (5.4%) had an unremarkable medical history. Among the 37 patients, 27 (73.0%) were immunocompromised, 25 (67.6%) had a history of antibiotic use within the past two months, and 6 (16.2%) were negative on the initial test but were positive on the second test. Finally, 28 patients (75.7%) required primary antibiotic therapy only, and two patients with IBD required additional antibiotic therapy as secondary treatment.ConclusionThe number of pediatric patients with CDI is increasing. Both a comprehensive interview, including underlying diseases and history of antibiotic use, and an understanding of the features of clinical examinations should be emphasized to appropriately diagnose and treat CDI.

Prognostic significance of Notch3 immunoreactivity patterns in Caucasian colon adenocarcinoma patients

IntroductionColon cancer is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory.AimTo investigate the prognostic role of Notch3, an immunohistochemical study was performed on samples of colon adenocarcinoma tissues and adjacent non-pathological mucosa in Caucasian patients.Material and methodsParaffin-embedded colon adenocarcinoma samples were assessed immunohistochemically for Notch3 protein. Connections between Notch3 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated.ResultsThe level of the Notch3 immunohistochemical reactivity was correlated with the grade of the histological differentiation (p < 0.001). A strong expression of Notch3 protein was detected more frequently in patients with G3 tumours than in patients with G1 tumours. Moreover, the significant difference was also detected between the patients with G1 tumour and those with G2. In the G2 patients a strong reactivity was described more frequently. The Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with a low expression level of Notch3 was significantly greater than that for patients with a moderate or strong level of Notch3 immunoreactivity (p < 0.001). A multivariate analysis demonstrated that the grade of tumour differentiation (p = 0.001) and Notch3 expression (p < 0.001) were independent risk factors for worse survival.ConclusionsThe high level of Notch3 immunoexpression was demonstrated to be associated with malignancy-related clinicopathological factors and 5-year overall survival of patients.

Diagnostic value of circulating microRNAs for esophageal cancer: a meta-analysis based on Asian data.

esophageal cancer (EC) is one of the most common gastrointestinal malignant diseases. We conducted a comprehensive meta-analysis to explore the clinical applicability of circulating microRNA for the diagnosis of EC. as of September 10, 2021, a comprehensive literature search was conducted on PubMed, Embase, Web of Science, Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to evaluate the test performance. The potential sources of heterogeneity were analyzed by subgroup analysis. Deeks' funnel plot was used to assess publication bias. 85 studies from 50 articles were included in the current meta-analysis. The overall pooled sensitivity was 0.82 (95 % CI, 0.79-0.84), specificity was 0.84 (95 % CI, 0.81-0.86), PLR was 4.9 (95 % CI, 4.2-5.9), NLR was 0.22 (95 % CI, 0.19-0.25), DOR was 22 (95 % CI, 17-29) and AUC was 0.89 (95 % CI, 0.86-0.92), respectively. Subgroup analysis suggested that miRNA clusters with a large sample size showed better diagnostic accuracy. Publication bias was not found. circulating miRNAs can be used as a potential non-invasive biomarker for the diagnosis of EC in Asian populations.

Dysbiosis of the duodenal microbiota as a diagnostic marker for pancreaticobiliary cancer.

BACKGROUNDPancreaticobiliary cancer (PB Ca) is a lethal disease, and a useful diagnostic marker is urgently needed. A correlation between the human microbiota and malignant gastrointestinal diseases was recently reported.AIMTo investigate the efficacy of the duodenal microbiota for diagnosing PB Ca.METHODSWe recruited 22 patients with benign pancreaticobiliary diseases (benign group) and 12 patients with PB Ca (malignant group). The duodenal microbiota of each patient was analyzed by the 16S rDNA terminal restriction fragment length polymorphism method. Patient characteristics, tumor markers, and relative abundances of the duodenal microbiota were compared between the benign and malignant groups.RESULTSCancer antigen 19-9 (CA19-9), Bifidobacterium, Clostridium cluster XVIII, and Prevotella levels differed significantly between the benign and malignant groups. Clostridium cluster XVIII had the greatest area under the receiver operating characteristic curve (AUC) among the four factors with respect to diagnosing PB Ca (cutoff value: 3.038%; sensitivity: 58.3%; specificity: 95.2%; AUC: 0.81). The combination of Clostridium cluster XVIII (cutoff value: 3.038%) and CA19-9 Levels (cutoff value: 18.8 U/mL) showed 91.7% sensitivity and 71.4% specificity for diagnosing PB Ca.CONCLUSIONThe duodenal microbiota may be useful for PB Ca screening.

Peritoneal surface malignancy spread reoperations after cytoreductive surgery + HIPEC.

Peritoneal malignancies (PM) are observed in about 1030% of patients suffering from gastrointestinal malignant diseases, both in connection with the primary surgical management or as metachronous metastases due to cancer recurrence. In the 1980s a new method of cytoreductive surgery (CRS) + HIPEC (hyperthermic intraperitoneal chemotherapy) was introduced. Today, we consider this method to be the gold standard for treatment of pseudomyxoma peritonei and peritoneal mesothelioma. The method increases overall survival (OS) of patients diagnosed with colorectal cancer, primary peritoneal and ovarian cancers. However, the disease recurs after this demanding treatment in the certain group of patients, approximately in 2544% of patients treated for pseudomyxoma peritonei, and in 40% and up to 82% of those treated for mesothelioma and colorectal cancer, respectively. Based on literary data (PubMed-Medline, last 5 years) and our own experience we present the basic factors associated with tumor recurrence, possibility of treatment using repeated CRS + HIPEC, data regarding second-look operations, and as applicable, prophylactic HIPEC. The method CRS + HIPEC provides an effective treatment of peritoneal carcinomatosis even in cases of recurrence. The second-look operations and prophylactic HIPEC may favorably affect the prognosis after primary R0 resections.

Prevalence of Helicobacter pylori infection and the incidence of the associated malignant and peptic ulcer disease (PUD) at Nelson Mandela Academic Hospital: a retrospective analysis

Background H. pylori infection is associated with both benign and malignant gastrointestinal diseases. However, no studies have been conducted locally describing the prevalence of H. pylori and its associated GIT diseases. The objectives of this study are to determine the prevalence of H. pylori, and the incidence of PUD and gastric malignancies among patients who are infected with H. pylori or who have the stigmata of previous exposure to H. pylori. Material and methods Data was collected retrospectively from files of adult patients with upper gastro-intestinal symptoms from January to December, 2012. The gastric mucosal biopsy specimens were analyzed for the presence of H. pylori, chronic gastritis, PUD, and gastric malignancies. Results Of 156 records there were 70 (45%) males and 86 (55%) females, with a median age of 56.5. The prevalence of H. pylori was 54.5%; 95% of 156 had chronic gastritis (CG). Ninety-sever percent of the 85 H. pylori positive and 93% of the 71 H. pylori negative patients had CG. However, the difference was not statistically significant (97% vs 93%, p = 0.322). The incidence of PUD was 16% and 10 (6.4%) had gastric malignancies, of which four (2.7%) and three (2%) were antral intestinal-type and proximal diffuse types, respectively. Three (2%) had gastric MALT lymphoma. The risk of both gastric malignancies and PUD was demonstrated to increase with advancing age. Discussion and conclusion The prevalence of H. pylori was equivalent to the global prevalence; however, high prevalence of CG may be indicative of high local infection rate. The incidence of H. pylori and/or chronic gastritis-associated intestinal-type gastric adenocarcinoma, MALT lymphoma, and PUD is equivalent to that reported globally. Advancing age and active H. pylori infection or stigmata of past exposure thereto are associated with increased risk of peptic ulcers and malignant gastric diseases.

Assessment of Fecal Calprotectin level in Inflammatory, Infectious and Malignant Gastrointestinal Diseases

Background: Calprotectin is a marker of inflammation as it is a cytosolic protein in the neutrophilic granulocytes. Objectives: We aimedto assess fecal calprotectin (FC) in the inflammatory, infectious and malignant gastrointestinal (G.I.T) diseases. Patients and Methods: 169 patients presented with G.I.T symptoms and proved with inflammatory, infectious or malignant condition by histopathological examination of the G.I.T endoscopic specimens were recruited. Symptomatic subjects with normal findings were considered as a non-organic; comparable group. Complete blood count, E.S.R, C.R.P, liver function tests, kidney function tests and stool analysis followed by endoscopic examination and multiple biopsies were taken for histopathological examination. FC was measured for all subjects. Results: Out of 169 patients; 79 patients (53.7%) showed inflammatory/infectious lesions (34 of them were inflammatory bowel disease (I.B.D)), 68 (46.3%) were malignant lesions and, 22 of them showed non-organic lesions (13%). FC levels (median, IQR; interquartile range) were significantly higher in inflammatory, infection group and malignant group than in the non-organic group (145 (53-2467) and 136 (45-212) versus 17 (10-57) respectively, P value =0.000). Patients with I.B.D showed significantly higher values for FC than in those with non I.B.D, P value= 0.000. Colorectal cancer patients showed higher FC values than gastric or esophageal cancer, P value= 0.000. Conclusions: FC is a useful marker in the diagnosis of G.I.T inflammatory, infectious and malignant conditions especially in I.B.D and colorectal cancer.

A potential prognostic prediction model of colon adenocarcinoma with recurrence based on prognostic lncRNA signatures

BackgroundColon adenocarcinoma (COAD) is one of the common gastrointestinal malignant diseases, with high mortality rate and poor prognosis due to delayed diagnosis. This study aimed to construct a prognostic prediction model for patients with colon adenocarcinoma (COAD) recurrence.MethodsDifferently expressed RNAs (DERs) between recurrence and non-recurrence COAD samples were identified based on expression profile data from the NCBI Gene Expression Omnibus (GEO) repository and The Cancer Genome Atlas (TCGA) database. Then, recurrent COAD discriminating classifier was established using SMV-RFE algorithm, and receiver operating characteristic curve was used to assess the predictive power of classifier. Furthermore, the prognostic prediction model was constructed based on univariate and multivariate Cox regression analysis, and Kaplan-Meier survival curve analysis was used to estimate this model. Furthermore, the co-expression network of DElncRNAs and DEmRNAs was constructed followed by GO and KEGG pathway enrichment analysis.ResultsA total of 54 optimized signature DElncRNAs were screened and SMV classifier was constructed, which presented a high accuracy to distinguish recurrence and non-recurrence COAD samples. Furthermore, six independent prognostic lncRNAs signatures (LINC00852, ZNF667-AS1, FOXP1-IT1, LINC01560, TAF1A-AS1, and LINC00174) in COAD patients with recurrence were screened, and the prognostic prediction model for recurrent COAD was constructed, which possessed a relative satisfying predicted ability both in the training dataset and validation dataset. Furthermore, the DEmRNAs in the co-expression network were mainly enriched in glycan biosynthesis, cardiac muscle contraction, and colorectal cancer.ConclusionsOur study revealed that six lncRNA signatures acted as an independent prognostic biomarker for patients with COAD recurrence.

Influence of Indoleamine-2,3-Dioxygenase and Its Metabolite Kynurenine on γδ T Cell Cytotoxicity against Ductal Pancreatic Adenocarcinoma Cells.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant gastrointestinal disease. The enzyme indoleamine-2,3-dioxgenase (IDO) is often overexpressed in PDAC and its downstream metabolite kynurenine has been reported to inhibit T cell activation and proliferation. Since γδ T cells are of high interest for T cell-based immunotherapy against PDAC, we studied the impact of IDO and kynurenine on γδ T cell cytotoxicity against PDAC cells. Methods: IDO expression was determined in PDAC cells by flow cytometry and Western blot analysis. PDAC cells were cocultured with γδ T cells in medium or were stimulated with phosphorylated antigens or bispecific antibody in the presence or absence of IDO inhibitors. Additionally, γδ T cells were treated with recombinant kynurenine. Read-out assays included degranulation, cytotoxicity and cytokine measurement as well as cell cycle analysis. Results: Since IDO overexpression was variable in PDAC, IDO inhibitors improved γδ T cell cytotoxicity only against some but not all PDAC cells. γδ T cell degranulation and cytotoxicity were significantly decreased after their treatment with recombinant kynurenine. Conclusions: Bispecific antibody drastically enhanced γδ T cell cytotoxicity against all PDAC cells, which can be further enhanced by IDO inhibitors against several PDAC cells, suggesting a striking heterogeneity in PDAC escape mechanisms towards γδ T cell-mediated anti-tumor response.

The clinical significance of Notch1 immunoexpression in Caucasian patients with colorectal adenocarcinoma

IntroductionColorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory.AimTo investigate the clinicopathological and prognostic roles of Notch1 expression, the immunohistochemical investigation was performed in samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients.Material and methodsParaffin-embedded adenocarcinoma samples were assessed immunohistochemically for Notch1 protein and scored according to the percentage of cells with a positive reaction combined with staining intensity. Connections between Notch1 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated.ResultsThe level of the Notch1 immunohistochemical reactivity was correlated with the grade of the histological differentiation, size of the primary tumour, regional lymph node involvement, and perineural invasion (all p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of Notch1 was significantly longer than that for patients with moderate or strong level of Notch1 immunoreactivity (p < 0.001).ConclusionsThe enhanced level of Notch1 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients.

Cell-free DNA testing: future applications in gastroenterology and hepatology.

The application of next-generation sequencing in clinical practice is increasing as accuracy and interpretation have improved and the cost continues to decline rapidly. Cell-free DNA is a unique source for next-generation sequencing that could change routine clinical practice in gastroenterology and hepatology. Testing of cell-free DNA in blood and fecal samples is an easy, rapid, and noninvasive method to assess for premalignant, malignant, metabolic, infectious, inflammatory, and autoimmune gastrointestinal and liver diseases. In this review, we describe cell-free DNA technologies, current applications of cell-free DNA testing, and proposed cell-free DNA targets for gastrointestinal and hepatic diseases, with a specific focus on malignancy. In addition, we provide commentary on how cell-free DNA can be integrated into clinical practice and help guide diagnosis, prognosis, disease management, and therapeutic response.

The clinical and prognostic evaluation of GRP94 immunoexpression in Caucasian patients with colorectal adenocarcinoma.

IntroductionColorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still unsatisfactory.AimTo investigate the clinicopathological and prognostic roles of GRP94 expression, the immunohistochemical investigation was performed on samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients.Material and methodsParaffin-embedded adenocarcinoma samples were assessed immunohistochemically for GRP94 protein and scored according to the percentage of cells with positive reaction combined with staining intensity. Connections between GRP94 immunoexpression and clinicopathological factors including the overall survival (OS) were evaluated.ResultsThe level of the GRP94 immunohistochemical reactivity was correlated with the grade of the histological differentiation (H (2.92) = 25.906; p < 0.001), size of the primary tumour (Z = –4.010; p < 0.001), regional lymph node involvement (Z = –6.547; p < 0.001), and perineural invasion (Z = –6.235; p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of GRP94 was significantly longer than that for patients with a moderate or strong level of GRP94 immunoreactivity (p < 0.001).ConclusionsAn enhanced level of GRP94 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients. However, a multivariate analysis demonstrated that GRP94 was not revealed as an independent risk factor for CRC prognosis.

Microbiome and Colorectal Cancer.

The trillions of microbes collectively referred to as the human microbiota, inhabit the human body and establish a beneficial relationship with the host. It is clear however that dysbiosis impacting microbial diversity in the gut, may lead to development of inflammatory and malignant gastrointestinal diseases including colorectal cancer (CRC). We provide a literature review of the recent influx of information related to the alterations in gut microbiota composition that influences CRC incidence and progression. A growing body of evidence implicates altered gut microbiota in the development of CRC. Profiles of CRC associated microbiota have been shown to differ from those in healthy subjects and bacterial phylotypes vary depending on the primary tumor location. The compositional variation in the microbial profile is not restricted to cancerous tissue however and is different between cancers of the proximal and distal colons, respectively. More recently, studies have shed light on the "driver-passenger" model for CRC wherein, driver bacteria cause inflammation, increased cell proliferation and production of genotoxic substances to contribute towards mutational acquisition associated with adenoma-carcinoma sequence. These changes facilitate gradual replacement of driver bacteria by passengers that either promote or suppress tumor progression. Significant advances have also been made in associating individual bacterial species to consensus molecular subtypes (CMS) of CRC and this remarkable development is expected to galvanize scientific community into advancing therapeutic strategies for CRC. Increasing evidence suggests a link between the intestinal microbiota and CRC development although the mechanisms through which the bacterial constituents of the microbiome contribute towards CRC are complex and yet to be fully fathomed. Thus, more exhaustive and mechanistic studies are needed to identify key interactions amongst diet, microbial community and metabolites that help facilitate the adenoma-carcinoma sequence evolution in CRC. It is expected that development of therapeutics based on microbial association with CMS will likely facilitate the translation of molecular subtypes into the clinic for CRCs and potentially other malignancies.

PS02.010: ESTABLISHMENT OF THE UPPER GI INTERNATIONAL ROBOTIC ASSOCIATION (UGIRA)

Abstract Background Robot-assisted surgery is increasingly performed for both benign and malignant upper gastro-intestinal disease. However, no global consensus exists regarding exact techniques and implementation methods of robotic esophageal and gastric surgery. To facilitate the effective implementation and advancement of these procedures, evidence based guidelines should be generated. In this context, the ‘Upper GI International Robotic Association’ (UGIRA) was established in 2017. Until now, 20 experienced robotic surgeons from 10 different countries in Europe (The Netherlands, Germany, United Kingdom, Denmark), Asia (Japan, Hong Kong, North-Korea, Taiwan), North-America (United States of America), and South-America (Brazil) have confirmed to become a member of the UGIRA. By means of an oral presentation, we would like to announce the establishment of the UGIRA and to introduce its primary aims, which are: To set up a web-based registry for international data collection.An international registry is created to enable international collaboration on research. Data collection should especially focus on the robotic elements of upper gastro-intestinal surgery, such as trocar positions, anastomotic technique, conduit stapling technique, and conduit diameter in esophagectomy.To establish guidelines for robotic upper gastro-intestinal surgical procedures.The approach to robotic upper gastro-intestinal surgical procedures should be standardized by formulating step-by-step guidelines. These guidelines will encompass robotic surgery for both benign (i.e. hiatal hernia, fundoplication) and malignant disease (i.e. esophageal and gastric cancer), with the exception of bariatric procedures.To form effective training programs that involve proctoring by experienced surgeons.In order to safely implement robotic surgery, training pathways that involve proctoring should be followed. The UGIRA will serve as the core platform to establish these training pathways and to appoint proctors in all continents. Completion of the training pathway will result in UGIRA credentialing. Methods Not applicable. Results Not applicable. Conclusion The UGIRA was recently established to facilitate the effective implementation and advancement of robotic esophageal and gastric surgery worldwide. To this end, the primary aims include setting up a web-based international registry, establishing guidelines for robotic upper gastro-intestinal procedures, and forming effective training pathways that involve proctoring. Disclosure All authors have declared no conflicts of interest.

Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer.

The tumor necrosis factor–related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other members of the TNF ligand superfamily, its role as a biomarker in pancreatic cancer is currently unknown. We analyzed serum levels of A proliferation-inducing ligand (APRIL) and TWEAK in 134 patients with pancreatic cancer. Results were compared with 50 healthy controls and correlated with clinical data. Intratumoral expression of APRIL and TWEAK in pancreatic cancer was analysed using the datasets made available by the TCGA-LIHC project. APRIL serum levels were significantly elevated in patients with pancreatic cancer compared to healthy controls, which is in line with previous findings. Notably, the diagnostic accuracy of circulating APRIL levels was similar to CA19-9, an established tumor marker for pancreatic cancer. In contrast, serum concentrations of TWEAK were decreased in pancreatic cancer patients. Interestingly, no differences in TWEAK concentrations became apparent between different clinical subgroups of pancreatic cancer. Moreover, within our cohort of patients, TWEAK levels did not correlate with the patients’ prognosis and the diagnostic as well as prognostic potential of TWEAK was lower than CA 19-9, when analyzed in this setting. Finally, using data from the TCGA-LIHC project, we demonstrate that expression levels of TWEAK and APRIL represent prognostic markers for patients’ survival according to Kaplan-Meier curve analyses. TWEAK and APRIL serum concentrations are regulated differently in patients with pancreatic cancer, highlighting diverse roles of variant TNF ligands in this type of cancer.