Common Gastrointestinal Cancer Research Articles

Gastrointestinal Cancer Patient Derived Organoids at the Frontier of Personalized Medicine and Drug Screening.

Cancer is a leading cause of death worldwide. Around one-third of the total global cancer incidence and mortality are related to gastrointestinal (GI) cancers. Over the past few years, rapid developments have been made in patient-derived organoid (PDO) models for gastrointestinal cancers. By closely mimicking the molecular properties of their parent tumors in vitro, PDOs have emerged as powerful tools in personalized medicine and drug discovery. Here, we review the current literature on the application of PDOs of common gastrointestinal cancers in the optimization of drug treatment strategies in the clinic and their rising importance in pre-clinical drug development. We discuss the advantages and limitations of gastrointestinal cancer PDOs and outline the microfluidics-based strategies that improve the throughput of PDO models in order to extract the maximal benefits in the personalized medicine and drug discovery process.

Curcumin Inhibits the Development of Pancreatic Cancer by Targeting the circ_0079440/miR-522-3p/EIF4A1 Pathway.

Pancreatic cancer (PC) is a common gastrointestinal cancer with high invasiveness and high mortality. Curcumin is a natural polyphenol with anti-tumor activity against different cancers, including PC. Curcumin has been verified to mediate the expression of circular RNAs (circRNAs) to inhibit tumor development. This study aimed to explore the function and regulatory mechanism of curcumin on circ_0079440 in PC. PC cells were treated with different concentrations of curcumin (0, 5, 10 or 15 μM) for 24 h. Gene expression in PC cells and tissues was detected using RT-qPCR. Cell malignant phenotypes were determined by functional assays. The levels of EMT-related proteins were tested using western blot. RNA interaction was determined using RNA pulldown assay, luciferase reporter assay and RIP assay. The results showed that curcumin suppressed cell proliferative, migratory, and invasive capabilities, and weakened epithelial-mesenchymal transition (EMT) in a concentration-dependent way. Circ_0079440 was expressed at a high level in PC and its level was reduced via curcumin administration in PC cells. Rescue assays showed that circ_0079440 overexpression reversed the suppressive effects of curcumin on PC cell malignant phenotypes. Furthermore, in the xenograft mouse models, curcumin treatment inhibited tumor growth and metastasis, and circ_0079440 upregulation reversed the function of curcumin. Additionally, circ_0079440 was revealed to bind to miR-522-3p to upregulate eukaryotic initiation factor 4A1 (EIF4A1) expression in PC cells. EIF4A1 expression was also downregulated by curcumin, and EIF4A1 overexpression abolished the suppressive functions of curcumin. Moreover, EIF4A overexpression or miR-522-3p inhibition counteracted the anti-tumor effects of circ_0079440 depletion on PC development. To sum up, curcumin suppresses PC development by targeting the circ_0079440/miR-522-3p/EIF4A1 pathway, which might provide novel therapeutic targets for treatment of PC.

Exploring disparities in palliative care utilization among hospitalized patients with hepatocellular carcinoma: A retrospective cohort study.

1616 Background: Hepatocellular carcinoma is one of the common gastrointestinal cancers, and its advanced stage requires palliative care due to its inferior prognosis and mortality. Palliative care significantly improves the burden of HCC on patients and the healthcare system. Despite the evidence of its use, reported utilization could have been better. This study aims to investigate the disparities in utilization of palliative care in hospitalized patients with HCC and examine related factors. Methods: This retrospective cohort study used data from the 2018-2020 National Inpatient Sample (NIS) database. Patients aged 18 or above with hepatocellular carcinoma were studied to determine how their utilization of palliative care varied based on their race and other identifiable risk factors. Palliative care utilization encompasses palliative care/ comfort care or under the care of a palliative care physician or referral. We examined these patients' demographics, All Patient Refined Diagnosis Related Group (APR-DRG) risk of mortality, and their relationship with palliative care utilization. Results: This study identified 128,140 patients with hepatocellular carcinoma (HCC), of whom 26,730 (20.9%) had utilized palliative care. The majority of study participants were White and male. The palliative care utilization (PCU) group comprised mainly White patients, with 50% of the group having extreme APR-DRG risk of mortality. Compared to Whites, Blacks had increased odds of palliative care utilization in both unadjusted (OR=1.08; 95% CI: 0.99-1.18) and adjusted models (aOR=1.11; 95% CI: 1.01-1.22). Hispanics had reduced odds in both unadjusted (OR=0.83; 95% CI: 0.75-0.91) and adjusted models (aOR=0.84; 95% CI: 0.76-0.93). Moreover, over 50% of study participants were in large, bed-sized hospitals and on Medicare insurance. Conclusions: Our study showed significant disparities in palliative care utilization among hospitalized patients with hepatocellular carcinoma. While the majority of patients were White and male, Black patients had increased odds of palliative care utilization, and Hispanics had reduced odds. Additionally, patients in large, bed-sized hospitals and on Medicare insurance comprised over 50% of the study population. The racial disparities in utilization might stem from differences in socio-cultural beliefs and practices alongside other factors. Efforts are needed to address these disparities and ensure equitable care for all patients, particularly vulnerable populations. Further research and quality improvement initiatives are essential to explore and address these disparities and contributing factors, enhancing outcomes for patients with HCC.

Translational Utility of Organoid Models for Biomedical Research on Gastrointestinal Diseases.

Organoid models have recently been utilized to study 3D human-derived tissue systems to uncover tissuearchitecture and adultstem cellbiology. Patient-derived organoids unambiguously provide the most suitable in vitro system to study disease biology with the actual genetic background. With the advent of much improved and innovative approaches, patient-derived organoids can potentially be used in regenerative medicine. Various human tissues were explored to develop organoids due to their multifold advantage over the conventional in vitro cell line culture approach and in vivo models. Gastrointestinal (GI) tissues have been widely studied to establish organoids and organ-on-chip for screening drugs, nutraceuticals, and other small molecules having therapeutic potential. The function of channel proteins, transporters, and transmembrane proteins was also explained. The successful application of genome editing in organoids using the CRISPR-Cas approach has been reported recently. GI diseases such as Celiac disease (CeD), Inflammatory bowel disease (IBD), and common GI cancers have been investigated using several patient-derived organoid models. Recent advancements on organoid bio-banking and 3D bio-printing contributed significantly in personalized disease management and therapeutics. This article reviews the available literature on investigations and translational applications of patient-derived GI organoid models, notably on elucidating gut-microbial interaction and epigenetic modifications.

CBC-1 as a Cynanbungeigenin C derivative inhibits the growth of colorectal cancer through targeting Hedgehog pathway component GLI 1

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT–PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting glioma‑associated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.

Role of Nano Enzyme in Diagnosis, Prognosis and Treatment of Gastrointestinal Tract (GIT) Cancer

Background:The most common life-threatening problem in population is gastrointestinal tract (GIT) cancer and its mortality rate is very high. Now a days Nanotechnology is a modern way of diagnosis and treatment. Nano-enzymes showed best diagnosis efficacy of treatment and disease progression Aims and objectives: The aims and objectives of current review were a comprehensive overview of Nano-enzymes in the diagnosis, prognosis, and treatment of gastrointestinal tract cancer. Practical Implications:Through Nano-enzymes different types of cancer may be diagnosis, prognosis, and treated. While the treatment of gastrointestinal tract cancer with Nano-enzymes showed best results. In this review, we outlined the many types of nanoparticles used to treat esophageal cancer. Conclusion:A common gastrointestinal cancer with a poor prognosis and a high fatality rate is esophageal cancer. Despite the development of multiple therapy approaches, patients with esophageal cancer still have a low 5-year survival rate. Traditional methods of delivering anti-cancer medications have some drawbacks, including no targeted administration and general toxicity. For the treatment of Esophageal cancer, nanoparticles offer a viable platform for drug delivery since they have a number of outstanding benefits, including less side effects, a longer circulation duration, and a preference for accumulating at the tumor site. These include polymers, micelles, liposomes, inorganic nanoparticles, and organic nanoparticles. In this review, we outlined the many types of nanoparticles used to treat esophageal cancer.

Abstract 4049: The beta-carboline Harmine sensitives microsatellite stable colorectal cancer mouse model to anti-PD-1 through upregulating MHC-I dependent antigen presentation machinery and improving the infiltration of CD8 T cells into the tumor microenvironment

Abstract Colorectal cancer (CRC) is the most common gastrointestinal cancer and the third leading cause of cancer-related death in both sexes. Mismatch repair deficient/microsatellite instability-high (MSI) colorectal cancer patients benefit from immune checkpoint blockades (ICBs)-based immunotherapy; however, this benefit has not been translated into microsatellite stable (MSS) colorectal cancer. It has been proposed that the loss of major histocompatibility complex class I (MHC-I) in tumor cells limits the use of ICB in colorectal cancer. Harmine displays a number of biological and pharmacological properties affecting the immune response and tumor phenotype. Here, we assessed the impact of combining harmine, also referred to as ACB1801 molecule, on improving the responsiveness of ICB in the mouse MSS CRC model. Our results showed that combining ACB1801 significantly improves the therapeutic benefit of anti-PD-1 in the CT26 CRC mouse model by decreasing tumor growth and improving the survival of tumor-bearing mice. The improvement of anti-PD-1-based therapy by combining ACB-1801 was associated with a modification of the immune landscape of tumors as evidenced by an increase in the CD8+ T cells and a decrease in the Treg infiltrations into the tumor microenvironment. By profiling the cytokine/chemokine network, we showed that ACB1801 induced the expression and the release of the proinflammatory chemokine CXCL10 by CRC tumor cells in vitro, which could be responsible for driving CD8+ T cells to the tumor microenvironment. Mechanistically, we showed that ACB1801 increased the expression of MHC-I genes, including TAP1 and TAPASIN, and improved the antigen loading on MHC-I in CRC cells in vitro. Overall, our study highlights the value of combining ACB1801 and anti-PD-1 as a therapeutic opportunity to convert MSS colorectal cancer into an “immune hot” cancer, which may define the future treatment paradigm of colorectal cancer for which there is a great unmet need. Citation Format: Ruize Gao, Kris Van Moer, Coralie Pulido, Anaïs Oudin, Diane Murera, Teresa L. Ramos, Margaux Poussard, Andreas Schläpfer, Annette Ives, Christian Auclair, Bassam Janji. The beta-carboline Harmine sensitives microsatellite stable colorectal cancer mouse model to anti-PD-1 through upregulating MHC-I dependent antigen presentation machinery and improving the infiltration of CD8 T cells into the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4049.

Simultaneous Expression of CD70 and POSTN in Cancer-Associated Fibroblasts Predicts Worse Survival of Colorectal Cancer Patients.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide, with high morbidity and mortality rates. The evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) that modulate cancer cell proliferation, invasion, metastasis, and tumor immunity, including in CRC, has been attracting attention. The present study examined the expression status of CD70 and POSTN in CRC and analyzed their association with clinicopathological features and clinical outcomes. In the present study, in total 15% (40/269) and 44% (119/269) of cases exhibited CD70 and POSTN expression on CAFs, respectively. Co-expression of CD70 and POSTN was detected in 8% (21/269) of patients. Fluorescent immunohistochemistry identified the co-expression of CD70 and POSTN with FAP and PDPN, respectively. ACTA2 was not co-expressed with CD70 or POSTN in CRC CAFs. CRC with CD70+/POSTN+ status in CAFs was significantly associated with distant organ metastasis (p = 0.0020) or incomplete resection status (p = 0.0011). CD70+/POSTN+ status tended to associate with advanced pT stage (p = 0.032) or peritoneal metastasis (p = 0.0059). Multivariate Cox hazards regression analysis identified CD70+/POSTN+ status in CAFs [hazard ratio (HR) = 3.78] as a potential independent risk factor. In vitro experiments revealed the activated phenotypes of colonic fibroblasts induced by CD70 and POSTN, while migration and invasion assays identified enhanced migration and invasion of CRC cells co-cultured with CD70- and POSTN-expressing colonic fibroblasts. On the basis of our observations, CD70 and POSTN immunohistochemistry can be used in the prognostication of CRC patients. CRC CAFs may be a promising target in the treatment of CRC patients.

Descriptive Epidemiology of Early-Onset Gastrointestinal Cancers in Iran, 2014-2018.

We aim to present incidence rates and geographical distribution of most common early-onset gastrointestinal cancers (EOGICs), including early-onset esophageal cancer (EOEC), gastric cancer (EOGC) and colorectal cancer (EOCRC) in Iran, 2014-2018. Data on new cases of EOEC, EOGC and EOCRC were obtained from publicly available annual reports of the Iranian National Population-based Cancer Registry (INPCR). Incidence rates were calculated using the population data available from the Statistical center of Iran. We considered the World standard population for calculation of age-standardized incidence rates (ASR). We also calculated 95% confidence intervals (CIs) for ASR. All rates are presented per 100000 person-years. Overall, 19,679 new cases of EOGIC were registered by the INPCR between 2014 and 2018. The ASRs (95% CI) of EOEC, EOGC and EOCRC were 0.49 (95% CI: 0.47-0.51), 1.67 (1.63-1.71), and 3.07 (3.01-3.13) per 100,000 person-years, respectively. Our findings indicate decreasing and constant trends in the ASR of EOEC and EOGC during the study period, 2014-2018. There was an increasing trend in the ASR of EOCRC. We also found geographical disparities in the incidence rates of EOGICs across provinces of Iran, suggesting the highest ASRs of EOEC in Golestan (1.3), EOGC in Ilam (2.99) and EOCRC in Ilam (4.49). Our findings suggested that the incidence rate of EOCRC is consistently increasing. We also found variations in the incidence of EOGICs among different provinces. Further investigations are recommended to clarify the time trends and risk factors of EOGICs in Iran.

Tissue sampling and histopathological limitations in esophageal cancer

Esophageal adenocarcinoma is a common gastrointestinal cancer. Esophagogastroduodenoscopy with biopsy and immunohistochemistry are used to detect the neoplasm at an early stage. Definitive diagnosis requires not only highly specialized equipment but also the skills of the endoscopist and pathologist. We report the case of a 35-year-old man with progressive dysphagia caused by gastroesophageal cancer. Numerous esophagogastroduodenoscopy studies, computed tomography, and barium X-ray swallow revealed an extensive esophageal lesion; however, pathomorphologic examinations did not confirm malignancy within a year. Histological studies showed pyloric gland adenoma and adenoma from parietal or oncocytic cells with high-grade dysplasia. Esophagogastroduodenoscopy with targeted biopsy at a specialized center confirmed the tumor malignancy. This clinical case demonstrates the importance of summing clinical symptoms and using additional instrumental methods to make a definitive diagnosis if biopsy results are ambiguous.

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy.

Colorectal cancer is one of the most common gastrointestinal cancers and the second leading cause of cancer-related death. Although colonoscopy screening has greatly improved the early diagnosis of colorectal cancer, its recurrence and metastasis are still significant problems. Tumour cells usually have the hallmark of metabolic reprogramming, while fatty acids play important roles in energy storage, cell membrane synthesis, and signal transduction. Many pathways of fatty acid metabolism (FAM) are involved in the occurrence and development of colon cancer, and the complex molecular interaction network contains a variety of genes encoding key enzymes and related products. Clinical information and RNA sequencing data were collected from TCGA and GEO databases. The prognosis model of colon cancer was constructed by LASSO-Cox regression analysis among the selected fatty acid metabolism genes with differential expression. Nomogram for the prognosis model was also constructed in order to analyze its value in evaluating the survival and clinical stage of the colon cancer patients. The differential expression of the selected genes was verified by qPCR and immunohistochemistry. GSEA and GSVA were used to analyze the enrichment pathways for high- and low-risk groups. CIBERSORT was used to analyze the immune microenvironment of colon cancer and to compare the infiltration of immune cells in the high- and low-risk groups. The "circlize" package was used to explore the correlation between the risk score signature and immunotherapy for colon cancer. We analysed the differential expression of 704 FAM-related genes between colon tumour and normal tissue and screened 10 genes with prognostic value. Subsequently, we constructed a prognostic model for colon cancer based on eight optimal FAM genes through LASSO Cox regression analysis in the TCGA-COAD dataset, and its practicality was validated in the GSE39582 dataset. Moreover, the risk score calculated based on the prognostic model was validated as an independent prognostic factor for colon cancer patients. We further constructed a nomogram composed of the risk score signature, age and American Joint Committee on Cancer (AJCC) stage for clinical application. The colon cancer cohort was divided into high- and low-risk groups according to the optimal cut-off value, and different enrichment pathways and immune microenvironments were depicted in the groups. Since the risk score signature was significantly correlated with the expression of immune checkpoint molecules, the prognostic model might be able to predict the immunotherapy response of colon cancer patients. In summary, our findings expand the prognostic value of FAM-related genes in colon cancer and provide evidence for their application in guiding immunotherapy.

Investigation of CBL-b, c-CBL expressions in colorectal cancer patients and their relationship with clinicopathological characteristics

Introduction: Colorectal cancer (CRC) is the most common gastrointestinal cancer and a major cause of cancer-related mortality worldwide. Molecular indicators of pathogenic factors that regulate CRC, which are known as oncogenes, are desirable for response to treatment and improvement of CRC patient management. Several risk factors play a role in the development of this disease, which can occur genetically, familial, or sporadically. CRC tumorigenesis is stimulated by the proto-oncogene β-catenin (wnt/β-catenin). Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through an unknown mechanism that affects nuclear β-catenin. The current objective of this study is to evaluate the expression levels of Cbl-b and c-Cbl genes to determine if their transcripts can be used as suitable diagnostic indicators. Additionally, we aim to investigate the correlation between clinicopathological information of CRC patients and the levels of Cbl-b and c-Cbl. Materials and Methods: Quantitative Real-Time PCR (qRT-PCR) method was used to evaluate the expression levels of Cbl-b and c-Cbl in 45 colorectal tumor tissues and 45 adjacent control tissues. Furthermore, we analyzed the diagnostic power of Cbl-b and c-Cbl by plotting receiver operating characteristic (ROC) curves. Results: Our results showed that the expression levels of Cbl-b and c-Cbl were significantly increased in CRC patients compared to the adjacent control group (P<0.003, P<0.004). Analysis of clinicopathological features of CRC patients revealed that the expression of Cbl-b and c-Cbl was associated differently with TMN stage, LVI+ (P<0.0003, P<0.0001) (P<0.003, P<0.07). Conclusion: These results indicate that the levels of Cbl-b and c-Cbl may serve as potential diagnostic indicators for CRC.

PATIENT ADVOCACY-01 WHY IS NEURO- ONCOLOGY MISSING FROM CIVIL SOCIETY CANCER ADVOCACY AGENDA?

Abstract BACKGROUND Cancer civil society and patient groups across Africa play a major role in pressuring governments to develop, fund, and implement national cancer control plans and to keep their commitments to international declarations. Additionally, community cancer awareness is mainly driven by lay cancer advocates and cancer survivors. The cancer policy and legislation landscape in Kenya has largely been shaped by the civil society through consistent advocacy OBJECTIVE Explore barriers and enablers to meaningful engagement of cancer civil society advocates in advancing neuro-oncology in Africa. METHODOLOGY This is a desk review of current developments and literature in advocacy for neuro-oncology with insights and perspectives of practicing oncology nurses and civil society cancer advocates in Kenya. FINDINGS Cancer advocacy in Kenya has traditionally focused on creating awareness on the more common cancers, breast, cervical prostate and Gastro-intestinal cancers. Over the last 10 years’ attention has gradually shifted to access and cost of care. Cancers of the central nervous system such as gliomas, neuroblastomas and meningiomas, though not uncommon do not feature prominently in advocacy discourses. This is due the fact that they are perceived as ‘rare’, complex, difficult to explain and with poor outcomes. DISCUSSION AND IMPLICATIONS There is a growing appreciation of the need to develop a framework through which civil society can contribute to the development of quality neuro oncology services. Cancer civil society organizations, neurosurgeons, neurologists, oncologists, academicians, and other healthcare professionals must work together to overcome structural barriers so that neuro oncology is not left behind in the national cancer plans. Stakeholders will need to establish guidelines with well defined mechanism for engaging, involving and acknowledging the contribution of cancer advocates in advancing neuro-oncology. This will require a cultural shift from neuro-oncology professionals to accommodate the input of lay civil society advocates.

Synchronous Upper GIT Malignancy in an Elderly Patient

Previously thought that, synchronous colonic cancers are relatively common but synchronous upper gastrointestinal cancers are relatively uncommon. But now a days, frequency of synchronous esophageal cancers, gastric cancers or duodenal cancers is increasing due to availability of the upper GI endoscopy, and the prolonged life span of the general population. Here we discussed anelderly malewho presented with features of gastric outlet obstruction and dysphagia and finally diagnosed as simultaneous esophageal squamous cell carcinoma and gastric adenocarcinoma.
 Bangabandhu Sheikh Mujib Med. Coll. J. 2022;1(2):107-109

Investigation of the effect of CA IX enzyme inhibition on the EZH2 gene and histone 3 modifications

Abstract Objectives Colon cancer is the most common gastrointestinal cancer worldwide with high morbidity and mortality rates. The main purpose of our study is to elucidate the interaction mechanism of the H+ ion concentration effect in the CO2/HCO3 − buffer system of tumor-associated carbonic anhydrase IX (CA IX) enzyme inhibition in the HT-29 colon cancer cell line on cell epigenetic modifications. Methods Cell culture was performed using the human colon cancer cell line HT-29. CA IX enzyme inhibitor Acetazolamide (AZA) was administered. The results of the cell viability test and inhibition were evaluated. Extracellular pH measurements were performed. Total histone protein isolation was performed and Histone H3 modifications were analyzed by ELISA method. After RNA isolation, complementary DNA (cDNA) synthesis was carried out. RT-PCR was performed to determine the gene expression levels of hypoxia-inducible factor 1A (HIF1A), enhancer of zeste homolog 2 (EZH2) and CA IX. Results CA IX enzyme inhibition in the HT-29 cell line decreased the expression of CA IX (p<0.05) and HIF1A (p<0.01) genes and increased the expression of the EZH2 (p<0.05). There was a significant decrease in the expression of CA IX (p<0.05) and HIF1A genes as a result of inhibition with AZA performed under hypoxic conditions. It was observed that CA IX enzyme inhibition increases the expression of the EZH2 gene by more than 3 times (p<0.01). As a result of AZA inhibition, methylation levels were observed to increase in normoxic conditions, while methylation levels were observed to decrease in hypoxic conditions. Conclusions Observing the changes in the H3 modifications and changes in the expression of CA IX, HIF1A and EZH2 genes in this study supports that CA IX enzyme inhibition plays an active role in epigenetic modifications.

ThTP4.5 Outcomes of colorectal cancers can be improved - 10 year Results from a South Asian Tertiary Center

Abstract Introduction Colorectal cancers are the most common gastrointestinal cancers and continue to rise in numbers. We aimed to compare the outcomes of all colorectal cancers after a five year period of change in practice. Methods We compared the demographic, clinical, treatment, and outcomes parameters of all rectal cancer patients registered at our hospital in the year 2013 to those in 2018. A total of 1442 patients, 511 in 2013 and 931 in 2018 were included. Results Median age reduced from 46 years to 40 years, with the proportion of young rectal cancers (≤45 years) increasing from 49% to 70% in 2018. A shift towards low rectal cancers, poorly differentiated and signet-ring cell histology was also observed in 2018. More patients in 2018 presented with advanced T and N stage with similar rates of distant metastatic disease at initial diagnosis. Curative intent treatment was offered to 1179 patients, and neoadjuvant radiation was offered to similar proportions with an increasing use of short-course radiation in 2018. Higher default and progression rates were observed in 2018 (30.2% vs 40.8%), and fewer patients could receive definitive surgery. At a median follow up of 96 months for the 2013 group and 32 months for the 2018 cohort, the 3-year OS was 47.5% and 73.3% for the 2013 and 2018 registered patients, respectively. Conclusions The increase in survival for every stage of rectal cancer in five years interval despite more advanced and aggressive tumours, suggest the augmentation and improvement in services offered at the colorectal unit.

Diagnostic application of circulating CDH17 biomarker for screening GI malignancies.

3058 Background: Colorectal cancer (CRC) is the most common and treatable gastrointestinal (GI) cancer, yet it remains the second leading cause of cancer associated deaths globally. Cadherin-17 (CDH17) is a biomarker for GI cancers characterized by its overexpression in stomach, liver, and colorectal cancers but controlled expression in normal tissues from healthy adults. Although an improvement in the detection strategy of CDH17 is essential to apply it for large scale CRC screening. We have developed a novel diagnostic immunoassay using a panel of highly specific antibodies (PCT/US2019/032752) that unveiled CDH17 as a potential diagnostic maker with high detection sensitivity and specificity in CRC. Methods: The study recruited 150 patients (Retrospective specimens - 50 colorectal adenomas and 100 colorectal cancer) and 50 asymptomatic 18-80 years old blood donors (prospective specimens). CDH17 expression levels were measured within the individual blood-plasma samples using an enzyme-linked immunoassay. Results: The novel CDH17 diagnostic assay showed a wide operating dynamic range extending from 90ng to a lower limit of detection at 123pg. Using the assay, we observed a progressive and a significant increase in the plasma CDH17 concentration from the asymptomatic individuals to the colorectal adenoma group, while the CRC patients showed the highest expression of the circulating protein (median: 2.5ng/mL vs 4.5ng/mL vs 8.0ng/mL, P<0.0001). Within the CRC group, a higher CDH17 expression was associated with advanced tumor invasion, occurrence of nodal or distant metastases, as well as a clinical presentation of an advanced stage disease. The diagnostic power of the assay in terms of ROC AUC values was higher than 0.9 with an overall sensitivity of 82% that extended to 100% for metastatic CRC, while the specificity was at 94% for all stages combined (P<0.0001). Plasma CDH17 outperformed the clinically applied CEA and CA19-9 markers in differentiating the CRC patients from the asymptomatic population. Conclusions: The CDH17 immunoassay is potentially a diagnostics tool aid for the detection of CDH17 within blood samples prompting the early diagnosis of CRC. [Table: see text]

Prognosis value and positive association of Rab1A/IL4Rα aberrant expression in gastric cancer

Gastric cancer (GC) is the most common gastrointestinal cancer and the leading cause of worldwide cancer-associated mortality. Several GC patients are diagnosed at the advanced stage with an unsatisfactory 5-year survival rate. Rab1A was significantly associated with IL4Rα expression in non-small cell lung cancer. However, their potential correlation in expression and prognosis remains largely unknown in GC. In this study, Rab1A/IL-4Rα was significantly increased in GC than in para-cancerous tissues, and Rab1A/IL-4Rα overexpression caused poor prognosis among GC patients. Rab1A expression was significantly correlated with IL-4Rα expression in GC tissues, as determined by IHC analysis. In addition, the mRNA expression of Rab1A was closely linked with the IL-4Rα mRNA expression in GC tissue expressed by qPCR. Furthermore, the Kaplan–Meier analysis demonstrated that the group with negative Rab1A and IL-4Rα expression had longer 5-year survival rates than the other group. Besides, the group with positive Rab1A and IL-4Rα expression had a worse prognosis than the other group. Finally, nomograms revealed the overall 3 and 5-year survival determined crucial roles of Rab1A/IL-4Rα expression in predicting the prognosis of GC patients. Therefore, Rab1A/IL-4Rα is vital in GC, providing a novel perspective on targeted GC therapy.

The Novel Use of IL-28 as an Effective Radiosensitizer in Pancreatic Cancer.

Pancreatic cancer is the second most common gastrointestinal cancer in the world, yet the five-year survival outcome rate of less than 5% urges for improvement in medical interventions of pancreatic cancer. Currently, high dose radiation therapy (RT) is used as an adjuvant treatment; however, the high level of RT required to treat advanced neoplasms leads to high incidence rates of side effects. In recent years, the utilization of cytokines as radiosensitizing agents has been studied, in order to reduce the amount of radiation required. However, few studies have examined IL-28 regarding its potential as a radiosensitizer. This study is the first to utilize IL-28 as a radiosensitizing agent in pancreatic cancer. MiaPaCa-2, a widely used pancreatic cancer cell line was used in this study. Clonogenic survival and cell proliferation assays were used to evaluate growth and proliferation of MiaPaCa-2 cells. Caspase-3 activity assay was used to evaluate apoptosis of MiaPaCa-2 cells and RT-PCR was used to study the possible molecular mechanisms. Our results showed that IL-28/RT enhanced RT-induced inhibition of cell proliferation and promoted apoptosis of MiaPaCa-2 cells. Furthermore, compared to RT alone, we found that IL-28/RT up-regulated the mRNA expression of TRAILR1 and P21, while down-regulating mRNA expression of P18 and survivin in MiaPaCa-2 cells. IL-28 has the potential to be used as a radiosensitizer for pancreatic cancer and warrants further investigation.

Sister Marie-Joseph's Nodule Revealing A Pancreatic Adenocarcinoma: About A Case with Review of the Literature

The Sister Marie-Joseph nodule (SMJ) is an umbilical cutaneous metastasis of a cancer of the gastrointestinal tract or of the gynecological sphere [1]. Stomach and colon are the common gastrointestinal cancers associated with the SMJ nodule. The pancreas is a rare primary site of umbilical metastasis [1]. In pancreatic cancer, the Sister Mary Joseph nodule is a sign of advanced disease associated with a poor prognosis [2].