Digestive System Tumors Research Articles

Extrahepatic malignant neoplasms after liver transplantation: the experience of a single transplant center

Objective: to evaluate the incidence of de novo malignant neoplasms (MN) after liver transplantation (LT) and compare with indicators among the general Russian population. Materials and methods. The study included 182 patients who had at least a 6-month follow-up period after LT and had no extrahepatic malignancies before LT. All data were analyzed retrospectively. Statistical processing of the results was carried out using the Statistica program for Windows v.10. Results. MN incidence was 5.5% (10 of 182 patients). The average period from transplantation to diagnosis of de novo neoplasm was 47.8 months (8 to 144 months). The patients were 3 men and 7 women. Types of de novo tumors included digestive system tumor (2 out of 10), hematologic malignant tumor (3 out of 10), skin cancer – melanoma (1 out of 10), urologic cancer (1 out of 10), gynecological (2 out of 10) and base of tongue cancer (1 out of 10). Five patients (50.0%) died, mortality was higher than in other LT patients (Z = –2.6; p = 0.009). The average follow-up period after detection of neoplasms was 18.8 months. Incidence of malignant neoplasms following LT was 10 times higher than among the general Russian population. No significant differences were found in the incidence of late acute rejection between 10 patients with MN and other 172 patients (Z = 0.18, p = 0.8). Among surviving patients, 2 patients with lymphomas received tacrolimus immunosuppression monotherapy, while 3 had everolimus-based immunosuppression. Conclusion. Incidence of de novo extrahepatic malignancies after LT is significantly higher than in the general population. To reduce the incidence of neoplasms in the future, patients should undergo regular screening, proliferative signal blockers should be prescribed, although their effectiveness requires further research.

Rspos and malignant tumors of digestive system.

Roof plate specific spondins (Rspos) are important activators of the Wnt signaling pathway discovered recently. Rspos include four secreted proteins: Rspo1, Rspo2, Rspo3, and Rspo4.They are mainly involved in the regulation of cell proliferation and differentiation via regulating the canonical Wnt/β-catenin signaling pathway.The physiological functions of Rspos include regulating sex selection, limb development, organ formation and development. Rspos are involved in the pathogenesis of some malignant tumors, and the roles of Rspos vary in different types of tumors.

Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.

Background5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells.MethodsCell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay.ResultsIn this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the pro-apoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model.ConclusionWe found that the downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.

Interpretation of the development of neoadjuvant therapy for gastric cancer based on the vicissitudes of the NCCN guidelines.

Gastric cancer is one of the most common digestive system tumors in China, and locally advanced gastric cancer (LAGC) accounts for a high proportion of newly diagnosed cases. Although surgery is the main treatment for gastric cancer, surgical excision alone cannot achieve satisfactory outcomes in LAGC patients. Neoadjuvant therapy (NAT) has gradually become the standard treatment for patients with LAGC, and this treatment can not only achieve tumor downstaging and improve surgical rate and the R0 resection rate, but it also significantly improves the long-term prognosis of patients. Peri/preoperative neoadjuvant chemotherapy and preoperative chemoradiotherapy are both recommended according to a large number of studies, and the regimens have also been evolved in the past decades. Since the NCCN guidelines for gastric cancer are one of the most authoritative evidence-based guidelines worldwide, here, we demonstrate the development course and major breakthroughs of NAT for gastric cancer based on the vicissitudes of the NCCN guidelines from 2007 to 2019, and also discuss the future of NAT.

Comparative peptidome profiling reveals critical roles for peptides in the pathology of pancreatic cancer.

Pancreatic cancer is a digestive system tumour disease with a notably poor prognosis and a 5-year survival rate of less than 10 %. In recent years, peptide drugs have shown great clinical value in antitumour applications. We aim to identify differentially expressed peptides by using peptidomics techniques to explore the mechanisms involved in the development and pathology of pancreatic cancer. We performed peptidomic analysis of pancreatic cancer and paired paracancerous tissues by using ITRAQ labelling technology and conducted in-depth bioinformatics analysis and functional studies on differentially expressed peptides. A total of 2,881 peptides were identified, of which 133 were differentially expressed (116 were upregulated and 17 were downregulated). By using GO analysis, the differentially expressed peptides were found to be closely related to the tumour microenvironment and extracellular matrix. KEGG enrichment analysis revealed that precursor proteins were closely related to the T2DM and RAS signalling pathways. The endogenous peptide P1DG can significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells. P1DG and its precursor GAPDH may be closely related to the proliferation, migration and invasion of pancreatic cancer. Peptidomics can aid in understanding the pathogenesis of pancreatic cancer more comprehensively.

The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors.

Transfer RNA-derived small RNA(tsRNA) is a type of non-coding tRNA undergoing cleavage by specific nucleases such as Dicer. TsRNAs comprise of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Based on the splicing site within the tRNA, tRFs can be classified into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. TiRNAs can be classified into 5′-tiRNA and 3′-tiRNA. Both tRFs and tiRNAs have important roles in carcinogenesis, especially cancer of digestive system. TRFs and tiRNAs can promote cell proliferation and cell cycle progression by regulating the expression of oncogenes, combining with RNA binding proteins such as Y-box binding protein 1 (YBX1) to prevent transcription. Despite many reviews on the basic biological function of tRFs and tiRNAs, few have described their correlation with tumors especially gastrointestinal tumor. This review focused on the relationship of tRFs and tiRNAs with the biological behavior, clinicopathological characteristics, diagnosis, treatment and prognosis of digestive system tumors, and would provide novel insights for the early detection and treatment of digestive system tumors.

245例消化系统神经内分泌肿瘤的内镜表现及病理特征分析

245例消化系统神经内分泌肿瘤的内镜表现及病理特征分析

Hepatocellular carcinoma: new provisions of the WHO classification, 5th edition, 2019

The WHO Classification of Digestive System Tumors (WHO, 5th Edition, 2019) presents new provisions on the morphological, molecular genetic, and therapeutic aspects of hepatocellular carcinoma (HCC). This classification versus the 2010 edition underwent substantial changes. Undifferentiated carcinoma (ICD-0: 8020/3) was excluded. The TNM staging system introduces additional gradations. Based on new evidence, HCC types and subtypes (scirrhous, clear cell, steatohepatic, and others) were identified depending on gene mutations according to ICD-11. The classification changes are of not only important theoretical, but also applied significance. These are valuable for oncologists and pathologists.

Metastasis immune-based scores predict patient survival

ABSTRACT Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. A comprehensive analysis of all metastases of each patient revealed the heterogeneity of the colorectal metastatic disease and its clinical impact. Complex tumor-immune interrelations shape the metastatic landscape. Adaptive immune cells and Immunoscore quantified in a random metastatic biopsy predict clinical outcome and their evaluation in the tumor microenvironment of the least infiltrated metastasis most accurately predict long-term survival. The adaptive immune cell infiltration was more informative than tumor regression and pathological response to predict long-term survival. These results highlight the clinical utility of Immunoscore for patient management. The immune response within the tumor microenvironment is an essential diagnostic criterion for colorectal cancer that has recently been integrated into the international WHO classification of Digestive System Tumors.

Calcifying Nested Stromal-Epithelial Tumour of the Liver: case report and review of literature

Abstract Calcifying nested stromal-epithelial tumour (CNSET) of the liver is a rare tumour, recently included in the WHO Classification of Digestive system Tumours 2019. Its hallmark is the nested proliferation of epithelial and spindle

Insulin-like growth factor I (IGF-I) and its present significance in digestive system diseases

Insulin-like growth factor I (IGF-I) is a main mediator of growth hormone’s (GH) action. Under physiological conditions, IGF-I is responsible for growth and development of organism through influence on proliferation and differentiation of cells. IGF-I is produced in almost all tissues of organism and its activity is determined by interaction with specific receptors (IGF-IR, IGF-IIR) and IGF-binding proteins (IGFBP-1 - IGFBP-6), and by proteases hydrolyzing IGFBPs as well. Currently, a surge of interest on insulin-like growth factor I as a potential factor contributing to the development of neoplasms, including neoplasms of digestive system, is observed. IGFBPs and IGF-IR may also be of importance in etiology and pathogenesis of cancer. It is assumed that high serum concentration of IGF-I may increase the risk of cancer development whereas high serum concentration of IGFBP-3 may inhibit the progression of the disease. Until recently, attempts of modulating the concentration of IGF-I with the use of pharmacological agents of diverse mechanisms of action under innovative anti-cancer therapies, have been made. Lately, it is pointed to the possibility of application of IGF-I in the management of certain diseases of digestive system. It was observed that IGF-I not only contributes to the maintenance of normal structure and function of epithelium in the gastrointestinal tract but also stimulates repair processes in damaged mucosa. Results of preliminary studies on the treatment of short bowel syndrome, gastric ulcer disease, enteritis induced by chemo- and radiotherapy, and inflammatory bowel disease with the use of exogenous IGF-I are encouraging.

Incidence of Canine Digestive System Tumours in Baghdad Province

Tumours in pets occur naturally are as common in dogs as they are in humans. Tumours of the alimentary system have been reported in animals, although less frequently. Food patterns and specific diet components could have a big role in such tumour occurrence. Therefore, the aim of this study was to investigate the clinical signs and inspect the neoplasm lesions of the gastrointestinal (GI) tract grossly and histopathologically in dogs in Baghdad, Iraq, and to see whether pet diets had any tumourigenic effect. Throughout two years sixteen dogswere referred to Teaching Animal Hospital and private clinics at Baghdad city had masses in (GI) tract. Males and the large sizes breeds were more likely to be affected with GI tumours. Half of the cases aged 5-10 years and belonged to German Shepherd, while the other half involved the other breeds (i.e. Belgian Malinois, Labrador, Pointer GSP and Terrier) equally. Biopsies were taken from the tumour tissues for histological examination. Clinically, the animals presented general signs of digestive system abnormalities like difficulty defecating, bloody stool, lethargy and weight loss. Grossly, the tumours varied in their sizes from <3 cm to >5 cm in diameter, and the most frequent site of occurrence (10 out of 16 cases) was in the large intestine. Histologically, the most tumours reported were malignant, and included adenocarcinomas (6/16) followed by leiomyosarcoma (4/16), and 2/16 belonged to carcinoid tumour. However, lipoma and viral papilloma (4/16) were also registered as the benign tumours. Inconclusion,tumours of canine digestive system do exist but rare. The healthy nutrition of dog may be prevent this type of tumour when dog consume enough amount of raw meat, little of artificial food like kibble with small of some vegetables and fruits. Additionally, the information gained from dogs could be used to suspect and test the effect on humans as they have strong pathophysiology similarities

Targeted Sequencing of Mixed Neuroendocrine- Non-neuroendocrine Neoplasm of the Gallbladder Suggests a Monoclonal Origin: A Case Report

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the gallbladder is a rare tumor that is defined in the World Health Organization (WHO) 2019 digestive system tumor classification as the presence of a neuroendocrine neoplasm admixed with a non-neuroendocrine carcinoma, each component constituting at least 30% of the neoplasm. The exact pathogenesis of MiNENs remains unclear. We present a case of a 74-year-old Filipino woman who presented with nonspecific clinical and radiologic findings and subsequently underwent cholecystectomy. Histopathologic and immunohistochemical evaluation of the gallbladder confirmed the diagnosis of a mixed well-differentiated adenocarcinoma (30%) and large cell neuroendocrine carcinoma (70%). The adenocarcinoma and neuroendocrine carcinoma components were separately microdissected and submitted for targeted 15-gene sequencing using the Illumina Trusight Tumor 15 (TST15) panel. NGS identified a TP53 missense mutation leading to a stop codon in both components. The finding of similar molecular signatures in the two morphologically distinct components supports the hypothesis that MiNEN arises from a common precursor stem cell capable of divergent phenotypic differentiation.

Analysis of autophagy-related genes and associated noncoding RNAs and transcription factors in digestive system tumors.

Aim: To investigate the autophagy-related gene (ATG) expression and the associated noncoding RNAs (ncRNA) and transcription factors (TF) in digestive system tumors (DST). Methods: We systematically investigated the ATG expression in DST by weighted gene correlation network analysis, crosstalk connection, functional analysis and Pivot analysis. Results: ATGs were clustered into six modules with co-expression in DST. Functional analysis revealed that six ATG-related modules were enriched in biological pathways involved in tumorigenesis. Pivot analysis identified key ncRNAs and TFs, which are essential for the pathogenesis, clinical diagnosis and treatment of DST. Conclusion: Our study highlights the crucial roles of ncRNA and TFs in the identification of potential biomarkers or therapeutic targets for DST.

Early Detection of Oncological Diseases of the Digestive System (Guidelines of the Russian Gastroenterological Association and the Russian Association of Oncologists for Primary Care Physicians)

Aim. The present guidelines intended for primary care physicians are aimed at facilitating early diagnosis of malignant tumours of the digestive system, which can significantly improve the immediate and long-term results of their treatment.General provisions. The guidelines comprise sections devoted to esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, hepatocellular carcinoma and extrahepatic bile duct and gall bladder cancer, as well as pancreatic cancer. Each section contains information on risk factors and precancerous diseases, which allows a physician to identify whether a particular patient falls into the risk group of digestive system neoplasms. It is shown how digestive system cancers can be suspected on the basis of patients’ complaints and past medical history, as well as data obtained both from a direct examination and laboratory instrumental studies. Each section offers practical algorithms in cases of suspected esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, hepatocellular carcinoma and extrahepatic bile duct and gallbladder cancer, as well as pancreatic cancer.Conclusion. The knowledge of clinical manifestations and risk factors in the development of digestive system neoplasms allows a physician to suspect cancer and devise a timely and adequate diagnostic strategy, including laboratory and instrumental studies at specialised clinical centres.

The progress and advances of biliary tract carcinoma chemotherapy

Compared with other tumors of digestive system such as colorectal cancer, the overall survival for advanced biliary tract carcinoma has not been prolonged greatly although some progress has been made on the optimization of the treatment. One of the reasons is that there is no effective chemotherapy for biliary tract cancer yet. In this review, we summarized the recent research findings on chemotherapy for BTC , thereby providing guidance on clinical practice. Key words: Biliary tract neoplasms; Antineoplastic combined chemotherapy protocols; Review

The 2019 WHO classification of tumours of the digestive system.

The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of the digestive system (Table ​(Table1).1). For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, in most instances histopathological classification remains the gold standard for diagnosis. The WHO classification of tumours series is designed to be used worldwide, including those settings where a lack of tissue samples or of specific technical facilities limits the pathologist's ability to rely on molecular testing. Table 1 Selected changes within the new classification of tumours of the digestive system

LncRNA TDRG1 promotes the aggressiveness of gastric carcinoma through regulating miR-873-5p/HDGF axis

Gastric carcinoma (GC) is still one of the most common digestive system neoplasms and the primary reason for malignant cancer-associated death. Long non-coding RNAs (lncRNAs) have been reported to play critical roles in GC progression. In this study, we demonstrated that lncRNA testis development-related gene 1 (TDRG1) is markedly upregulated in clinical GC tissues and GC cells. High level of lncRNA TDRG1 correlates with the metastasis and prognosis of patients with GC. Overexpression of lncRNA TDRG1 promotes GC growth and metastatic-related traits in vitro and in vivo, and silencing TDRG1 causes opposite results. We future find that TDRG1 is inversely associated with miR-873-5p and positively modulates the expression of hepatoma-derived growth factor (HDGF), a functional target gene of miR-873-5p. Finally, lncRNA TDRG1 regulates the progression of GC through regulating miR-873-5p/HDGF pathway. Taken together, our data uncover the crucial function of TDRG1-miR-873-5p-HDGF axis in human gastric cancer.

Screening and validating the core biomarkers in patients with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PAAD) is one of the most common malignant tumors in digestive system. To find the new therapeutic targets and explore potential mechanisms underlying PAAD, the bioinformatics has been performed in our study. The PAAD gene expression profile GSE28735 was chosen to analyze the differentially expressed genes (DEGs) between PAAD carcinoma tissues and normal adjacent tissues from 45 patients with PAAD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, a protein-protein interaction (PPI) network was also constructed to help us screen the top 20 hub genes in this profile and demonstrated the underlying interactions among them. The Gene Expression Profiling Interactive Analysis (GEPIA) was further performed in order to valid the mRNA levels of top5 up-regulated and top5 down-regualted DEGs, apart from exploring their association with survival rate as well as tumor stage. Finally, Q-PCR was further employed to valid the top5 up-regulated and top5 down-regulated genes in patients with PAAD. In our study, there were a total of 444 DEGs captured (271 up-regulated genes and 173 down-regulated genes). Among these DEGs, the top5 up-regulated genes were CEACAM5, SLC6A14, LAMC2, GALNT5 and TSPAN1 while the top5 down-regulated genes were GP2, CTRC, IAPP, PNLIPRP2 and PNLIPRP1. GO analysis disclosed that the DEGs were predominantly enriched in cell adhesion, lipid metabolism, integrin binding, proteolysis and calcium ion binding. KEGG analysis disclosed that the enriched pathway included pancreatic secretion, protein digestion and absorption, fat digestion and absorption, ECM-receptor interaction, focal adhesion and PI3K-Akt signaling pathway. Survival analysis unveiled that the high expression levels of SLC6A14, GALNT5 and TSPAN1 may correlate with the poor prognosis while high expression levels of IAPP may contribute to a better prognosis in patients with PAAD. Additionally, the levels of CEACAM5, SLC6A14, LAMC2 and GALNT5 were also associated with tumor stage. Furthermore, according to the connectivity degree of these DEGs, we selected the top20 hub genes, namely ALB, FN1, EGF, MMP9, COL1A1, COL3A1, FBN1, CXCL12, POSTIN, BGN, VCAN, THBS2, KRT19, MET, MMP14, COL5A2, GCG, MUC1, MMP1 and CPB1, which were expected to be promising therapeutic targets in PAAD. Collectively, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of PAAD.

Practical membrane anatomy of en bloc mesogastrium excision in lymph node dissection of gastric cancer

Gastric cancer is a common malignant tumor of digestive system. D2 procedure is recognized as the standard operation for advanced gastric cancer at present. However, controversies still exist in the standardization and quality control of surgical procedures. Total mesorectal excision (TME) and complete mesocolic excision (CME) based on the membrane anatomy perfectly solve these problems in the treatment for colorectal cancer. However, the complexity of mesogastrium determines that TME and CME cannot be easily transplanted to the treatment of gastric cancer. The practical membrane anatomy in gastric cancer surgery is just emerging and its impact on the treatment of gastric cancer is immeasurable. By reviewing the evolution and embryonic development of digestive system, and combining with actual operation, this paper analyzes and redefines several key issues such as traditional Toldt space, Gerota fascia and complete mesenteric excision. On this basis, we propose a novel and feasible surgical procedure named regional en bloc mesogastrium excision (rEME) for distal gastric cancer. The concept of en bloc mesogastrium excision (EME) based on membrane anatomy may have some influences on the lymph node grouping from the 'Japanese Classification of Gastric Carcinoma'. Performance of EME may reduce the controversies about the group of lymph nodes and their borders. EME in the infra-pyloric region weakens the significance of subdivision of No.6 lymph nodes into No.6a, No.6v and No.6i. More studies are needed in the construction of a mature theoretical system for practical membrane anatomy in gastric surgery.