Invasive Adenocarcinoma Of Colon Research Articles

Appendiceal Mucosal Schwann Cell Proliferation Associated with Incidentally Detected Goblet Cell Adenocarcinoma of Appendix in a Case of Invasive Adenocarcinoma of Sigmoid Colon- A Case Report

Abstract Introduction/Objective Appendiceal mucosal Schwann cell proliferation has been suggested to be a putative histologic marker of appendiceal diverticular disease. Appendiceal Goblet cell adenocarcinoma, (GCA) is amongst the most rare appendiceal tumors with a reported incidence of 0.05 cases per 100,000 population per year in United States. They have features of both neuroendocrine tumors and adenocarcinomas, but behave more similarly to adenocarcinomas. Methods/Case Report Herein, we report a case of appendiceal mucosal schwann cell proliferation associated with incidentally detected Goblet cell adenocarcinoma of appendix in a known case of invasive adenocarcinoma of sigmoid colon. A 75-year-old female presented with sigmoid colon obstruction. Intraoperatively, she was found to have gangrenous and perforated colon, as well as a large obstructing sigmoid mass, and underwent total abdominal colectomy with end-ileostomy. On gross examination, a tan bosselated tumor (up to 3.5 cm) was seen in proximal sigmoid colon. Microscopic examination showed Invasive adenocarcinoma, moderately-differentiated. Appendix was unremarkable on gross examination. Incidentally, the appendix microscopically demonstrated “Goblet cell adenocarcinoma”, histologic grade 1 out of 3 (pathologic stage pTis pN0), present in multiple foci within lamina propria of the distal third of appendix over an area measuring 1.5 cm. Additionally, there were foci of SOX10-positive bland- looking spindle cell proliferation in lamina propria of the appendix. This proliferation is rendered as “Schwann cell proliferation”. Results (if a Case Study enter NA) NA Conclusion One study found that “Schwann cell proliferation” is seen in 42% of appendiceal diverticula cases. It has never been reported in association with “Appendiceal GCA” before. Here we report an intriguing case of Schwann cell proliferation associated with this rare entity of GCA for the first time in literature. Therefore, awareness of such coexistence of these pathologic entities in the same appendix is essential to alert the pathologist to look for GCA, whenever Schwann cell proliferation is encountered in random section of an appendix. This case also emphasizes the importance of being vigilant of the possible presence of other tumors in a specimen with a known tumor.

PER3 promoter hypermethylation correlates to the progression of pan-cancer

BackgroundMalignant cells exhibit reduced period circadian regulator 3 (PER3) expression. However, the underlying mechanisms of variations in PER3 expression in cancers and the specific function of PER3 in tumor progression remain poorly understood.ResultsWe explored multiple public databases, conducted bioinformatics analyses, and performed in vitro and in vivo experiments for validation. We found PER3 expression was decreased in most types of cancers, and PER3 downregulation was associated with a poor prognosis in 8 types of cancer. PER3 promoter methylation levels were increased in 11 types of cancer. Promoter hypermethylation (CpG islands [CGIs] cg12258811 and cg14204433) correlated with decreased PER3 expression in six cancers (breast invasive carcinoma, colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma [KIRP], lung adenocarcinoma [LUAD], and uterine corpus endometrial carcinoma). CGI cg12258811 hypermethylation was associated with reduced survival time and advanced cancer stages. Moreover, the bisulfite pyrosequencing assay confirmed CGI cg12258811 hypermethylation and its negative correlation with PER3 expression. In vitro and in vivo experiments demonstrated that PER3 inhibited KIRP and LUAD progression. Decitabine enhanced PER3 expression and inhibited KIRP cell functions by reducing promoter (cg12258811) methylation level.ConclusionsOur findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.

Comprehensive Analysis Reveals Epithelial Growth Factor Receptor as a Potential Diagnostic Biomarker in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a highly aggressive tumor of the central nervous system, is the most common malignant brain tumor and poses a significant risk to life. GBM patients have a low survival rate owing to their aggressive nature, poor prognosis, genomic variations among patients, and histopathological differences. In this study, we used several bioinformatics platforms, namely Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases, Kaplan-Meier plotter, and cBioPortal, to conduct a comprehensive analysis to highlight the expression of epithelial growth factor receptor (EGFR) in patients with GBM. Our study highlights EGFR as a potential diagnostic and prognostic marker. According to the TIMER database, EGFR was upregulated in five cancers, including GBM, head and neck squamous cell carcinoma, kidney renal cell carcinoma, kidney renal cell papillary cell carcinoma, and lung squamous cell carcinoma, whereas it was downregulated in breast invasive carcinoma, colon adenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, rectum adenocarcinoma, and uterine corpus endometrial carcinoma. Our investigation highlighted the expression of EGFR in various clinicopathological parameters, which include age, sex, gender, and TP53 mutation status in patients with GBM. We found that EGFR was upregulated in middle-aged and older adults compared to normal tissues, while it was not significantly downregulated in young adults and older adults. EGFR was upregulated in Caucasians compared to normal tissue, whereas it was downregulated in Asian and African American populations, but this was not statistically significant. In terms of gender, EGFR was upregulated in the male population compared to the female population. Furthermore, EGFR was upregulated in patients with TP53 mutations compared to normal tissues. We also examined the correlation between EGFR gene expression and immune cell infiltration in GBM patients and the impact of EGFR mutations on patient prognosis. Our results revealed a significant positive correlation between EGFR, B cells, and macrophages, but this was not significant for other cell types. This study signified that upregulation of EGFR was associated with a poor prognosis in patients with GBM validated by the GEPIA and UALCAN databases.

P43-7 Synchronous invasive breast cancer and colon adenocarcinoma in a 57-year-old Filipino male

P43-7 Synchronous invasive breast cancer and colon adenocarcinoma in a 57-year-old Filipino male

CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications.

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target. Our approach encompassed data collection from diverse knowledge resources, gene function analysis, differential gene expression profiling, immune cell infiltration assessment, and strategic prioritization of target indications. Our findings revealed strong correlations between CCR8 and specific cancers, notably Breast Invasive Carcinoma (BRCA), Colon Adenocarcinoma (COAD), Head and Neck Squamous Cell Carcinoma (HNSC), Rectum adenocarcinoma (READ), Stomach adenocarcinoma (STAD), and Thyroid carcinoma (THCA). This research advances our understanding of CCR8 as a potential target for anti-cancer drug development, bridging the gap between molecular insights and creating opportunities for personalized treatment of solid tumors.

Evaluation of annexin A1 expression in lung, breast, colon, and prostatic adenocarcinomas and in tumor microenvironment

Objectives: Annexin A1 (ANXA1) which plays a role in tumor development and metastasis has been reported to be an effective regulator for tumor stroma and interacts with different components in the tumor microenvironment. The role of ANXA1 in tumorigenesis has not been fully understood. One of the main reasons for this is the great variability of ANXA1 expression in malignant tumors across different tumor types. Materials and Methods: Archived hematoxylin-eosin stained preparations of lung adenocarcinoma, breast invasive ductal carcinoma, colonic adenocarcinoma, and prostatic acinar carcinoma were re-evaluated and tumor regions to be analyzed with the tissue microarray method were determined. The ANXA1 expressions between the tumors and tumor microenvironment were evaluated immunohistochemically. Results: ANXA1 expression was decreased in the lung, breast, colon, and prostate adenocarcinomas. The most prominent staining was seen in lung adenocarcinoma cases. There was no statistically significant difference between the tumors in terms of ANXA1 staining (P > 0.05). ANXA1 was shown to be a more stained tumor microenvironment than in the tumor. Statistically significant staining with ANXA1 between within tumor and tumor microenvironment was observed in breast adenocarcinomas (P < 0.05). Our study showed differences between ANXA1 expression in different cancers, in tumor cells, and tumor microenvironment. Conclusion: Considering the effects of ANXA1 on tumor development and metastasis, a potential use as a biomarker may be suggested. Particularly, in breast adenocarcinomas, the high expression of ANXA1 in the tumor microenvironment supports the notion that it could induce the tumor stroma response.

Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2.

Solute carrier family 35 member A2 (SLC35A2), which belongs to the SLC35 solute carrier family of human nucleoside sugar transporters, has shown regulatory roles in various tumors and neoplasms. However, the function of SLC35A2 across human cancers remains to be systematically assessed. Insights into the prediction ability of SLC35A2 in clinical practice and immunotherapy response remains limited. We obtained the gene expression and protein levels of SLC35A2 in a variety of tumors from Molecular Taxonomy of Breast Cancer International Consortium, The Cancer Genome Atlas, Gene Expression Omnibus, Chinese Glioma Genome Atlas, and Human Protein Atlas databases. The SLC35A2 level was validated by immunohistochemistry. The predictive value for prognosis was evaluated by Kaplan-Meier survival and Cox regression analyses. Correlations between SLC35A2 expression and DNA methylation, genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and tumor microenvironment were performed using Spearman's correlation analysis. The possible downstream pathways of SLC35A2 in different human cancers were explored using gene set variation analysis. The potential role of SLC35A2 in the tumor immune microenvironment was evaluated via EPIC, CIBERSORT, MCP-counter, CIBERSORT-ABS, quanTIseq, TIMER, and xCell algorithms. The difference in the immunotherapeutic response of SLC35A2 under different expression conditions was evaluated by the tumor immune dysfunction and exclusion (TIDE) score as well as four independent immunotherapy cohorts, which includes patients with bladder urothelial carcinoma (BLCA, N = 299), non-small cell lung cancer (NSCLC, N = 72 and N = 36) and skin cutaneous melanoma (SKCM, N = 25). Potential drugs were identified using the CellMiner database and molecular docking. SLC35A2 exhibited abnormally high or low expression in 23 cancers and was significantly associated with the prognosis. In various cancers, SLC35A2 expression and mammalian target of rapamycin complex 1 signaling were positively correlated. Multiple algorithmic immune infiltration analyses suggested an inverse relation between SLC35A2 expression and infiltrating immune cells, which includes CD4+T cells, CD8+T cells, B cells, and natural killer cells (NK) in various tumors. Furthermore, SLC35A2 expression was significantly correlated with pan-cancer immune checkpoints, TMB, MSI, and TIDE genes. SLC35A2 showed significant predictive value for the immunotherapy response of patients with diverse cancers. Two drugs, vismodegib and abiraterone, were identified, and the free binding energy of cytochrome P17 with abiraterone was higher than that of SLC35A2 with abiraterone. Our study revealed that SLC35A2 is upregulated in 20 types of cancer, including lung adenocarcinoma (LUAD), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). The upregulated SLC35A2 in five cancer types indicates a poor prognosis. Furthermore, there was a positive correlation between the overexpression of SLC35A2 and reduced lymphocyte infiltration in 13 cancer types, including BRCA and COAD. Based on data from several clinical trials, patients with LUAD, LUSC, SKCM, and BLCA who exhibited high SLC35A2 expression may experience improved immunotherapy response. Therefore, SLC35A2 could be considered a potential predictive biomarker for the prognosis and immunotherapy efficacy of various tumors. Our study provides a theoretical basis for further investigating its prognostic and therapeutic potentials.

METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.

N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms. We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression. Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression. These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.

A Transcriptomic and Reverse-Engineering Strategy Reveals Molecular Signatures of Arachidonic Acid Metabolism in 12 Cancers.

Cancer and arachidonic acid (AA) have important linkages. For example, AA metabolites regulate several critical biological functions associated with carcinogenesis: angiogenesis, apoptosis, and cancer invasion. However, little is known about the comparative changes in metabolite expression of the arachidonic acid pathway (AAP) in carcinogenesis. In this study, we examined transcriptome data from 12 cancers, such as breast invasive carcinoma, colon adenocarcinoma, lung adenocarcinoma, and prostate adenocarcinoma. We also report here a reverse-engineering strategy wherein we estimated metabolic signatures associated with AAP by (1) making deductive inferences through transcriptome-level data extraction, (2) remodeling AA metabolism, and (3) performing a comparative analysis of cancer types to determine the similarities and differences between different cancer types with respect to AA metabolic alterations. We identified 77 AAP gene signatures differentially expressed in cancers and 37 AAP metabolites associated with them. Importantly, the metabolite 15(S)-HETE was identified in almost all cancers, while arachidonate, 5-HETE, PGF2α, 14,15-EET, 8,9-EET, 5,6-EET, and 20-HETE were discovered as other most regulated metabolites. This study shows that the 12 cancers studied herein, although in different branches of the AAP, have altered expression of AAP gene signatures. Going forward, AA related-cancer research generally, and the molecular signatures and their estimated metabolites reported herein specifically, hold broad promise for precision/personalized medicine in oncology as potential therapeutic and diagnostic targets.

S2251 A Case of Invasive Colonic Adenocarcinoma in a Patient With E. faecalis Bacteremia

S2251 A Case of Invasive Colonic Adenocarcinoma in a Patient With E. faecalis Bacteremia

S2246 FIT or Unfit: Advanced Colon Cancer Screening

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer related mortality worldwide. The U.S. Preventative Services Task Force guidelines recommend screening for average risk patients at age 45, and modalities include stool-based or direct visualization tests. We report a presentation of Stage IV colorectal adenocarcinoma in the setting of 3 annual negative fecal immunochemical testing (FIT) tests. Case Description/Methods: A 67-year-old woman presented with shortness of breath, unintentional weight loss, and abdominal pain. She denied hematochezia or melena. Physical exam was notable for pallor and right upper quadrant pain. Initial laboratory data showed normocytic anemia with a hemoglobin 10.1 g/dL, alkaline phosphatase 610 U/L, aspartate aminotransaminase 116 U/L, alanine aminotransaminase 67 U/L. Computed tomography of the chest, abdomen, and pelvis revealed a normal colon and extensive metastatic disease in the liver and lungs with bilateral subsegmental pulmonary emboli. Chart review was notable for negative FIT tests in 2017, 2018, and 2020, performed within a year of this presentation. Further workup was significant for elevated carcinogenic embryonic antigen 1470 ng/mL, and normal alpha-fetoprotein and cancer antigen 19-9 levels. Colonoscopy revealed an infiltrating, ulcerated, semi-circumferential mass at the ileo-cecal valve and ascending colon (Figure). Pathology demonstrated moderately differentiated invasive colonic adenocarcinoma with malignant glands infiltrating a desmoplastic stroma. Immunohistochemistry did not show any microsatellite instability changes. Discussion: One study showed FIT testing was 73.8% sensitive for detecting Stage I-III CRC, however, sensitivities dropped with advanced precancerous lesions and sessile serrated polyps to 23.8% and 5.1% respectively. Another retrospective cohort looking at 6 consecutive rounds of FIT testing demonstrated lower accuracy of detecting proximal colon cancers compared to distal cancers (0.45 vs 0.73; P< 0.001). Lower cut off values of qualitative FIT correlated with better sensitivities, however, specificity declined. Although FIT testing is able to detect the majority of colorectal cancers, it has decreased accuracy and sensitivity in advanced precancerous lesions, sessile serrated polyps, and proximal (right) colon lesions. Colonoscopy is considered gold standard and further guidelines should recommend a standardized cut off value to help improve screening efficacy.Figure 1.: Large fungating mass in the ascending colon and ileo-cecal valve.

Pancancer Analysis of the Oncogenic and Prognostic Role of NOL7: A Potential Target for Carcinogenesis and Survival.

Despite growing evidence suggesting the critical function of NOL7 in cancer initiation and development, a systematic pancancer analysis of NOL7 is lacking. Herein, we present a comprehensive study of NOL7 which aimed to explore its potential role and detailed mechanisms across 33 human tumors based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CATPAC) databases. As a result, both gene and protein levels of NOL7 were found to be increased in various tumor tissues, including breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and head and neck squamous cell carcinoma (HNSC) as compared with corresponding normal tissues. Meanwhile, dysregulated NOL7 expression was found to be closely related to pathological stage and prognosis in several cancers, including LIHC, ovarian serous cystadenocarcinoma (OV), and bladder urothelial carcinoma (BLCA). The DNA methylation level of NOL7 was found to be decreased in most cancers and to be negatively associated with NOL7 expression. Furthermore, NOL7 expression was determined to be significantly associated with levels of infiltrating cells and immune checkpoint genes, including HMGB1. Analysis of NOL7-related genes revealed that RNA metabolism pathways, including “ribosome biogenesis”, “spliceosome”, and “RNA transport”, were mainly involved in the functional mechanism of NOL7 in human cancers. In summary, this pancancer study characterized the relationship between NOL7 expression and clinicopathologic features in multiple cancer types and further showed its potential regulatory network in human cancers. It represents a systemic analysis for further functional and therapeutic studies of NOL7 and highlights its predictive value with respect to the carcinogenesis and prognosis of various cancers, especially LIHC.

New Insights Into PTBP3 in Human Cancers: Immune Cell Infiltration, TMB, MSI, PDCD1 and m6A Markers.

Polypyrimidine tract binding protein 3 (PTBP3) plays a critical role in post-transcriptional regulation. The role of PTBP3 in various human tumours was explored and analysed in this study based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PTBP3 was highly expressed in most tumours, such as breast invasive carcinoma, colon adenocarcinoma and hepatocellular carcinoma. PTBP3 overexpression generally predicts poor overall survival and disease-free survival in patients with adrenocortical carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. However, low PTBP3 expression predicts poor prognosis in kidney renal clear cell carcinoma. We also explored PTBP3 genetic alterations in different tumour tissues. The result found that the frequency of PTBP3 alteration (>4%) was the highest in uterine tumours with “mutation” as the primary type. Furthermore, we found a significant correlation between PTBP3 expression and tumour mutational burden and microsatellite instability in various human tumours, and found that PTBP3 expression was positively correlated with TMB in ACC, STAD, PAAD, LUAD, and SARC. Two enhanced phosphorylation levels of S30 and S426 in colon cancer, ovarian cancer, and uterine corpus endometrial carcinoma were found. Further analysis indicated that PTBP3 expression was positively correlated with the cancer-associated fibroblasts for most tumour types. This study also found a relationship between immune checkpoints and N6-methyladenosine-related markers and PTBP3 expression. Moreover, the “mRNA surveillance pathway” and “RNA degradation” were involved in the functional mechanisms of PTBP3. These results provide new insights for molecular studies, and integrative analysis provided a framework for determining the predictive, prognostic, and therapeutic relevance of PTBP3 in cancer patients.

S3611 Double Trouble: Primary Lung and Colon Cancer in a Patient With Crohn’s Disease

Introduction: This vignette highlights the development of localized rectal adenocarcinoma and concomitant metastatic large cell neuroendocrine tumor of the lung in a patient with longstanding Crohn’s disease (CD) on Vedolizumab (VDZ). Case Description/Methods: A 61 year old male with a 2 year history of severe, uncontrolled colonic inflammatory CD presented to the ED with weakness, loss of appetite, and a 30lb weight loss over a 1 month period. He had been on VDZ 300mg every 8 weeks for 1 year. A CT chest showed a new 2cm pulmonary nodule with increasing mediastinal and perihilar lymphadenopathy. Bronchoscopy and endobronchial ultrasound were performed for lymph node sampling and revealed a large cell neuroendocrine tumor, which was later found to be metastatic to the brain. The patient was discharged with plans to optimize the VDZ therapy and start cancer treatment. Anticipating the use of immunotherapy, a colonoscopy was performed and revealed active inflammation in the sigmoid colon. Incidentally, an 18mm Is (sessile) polyp was found in the rectum and removed by piecemeal snare polypectomy. Pathology was consistent with invasive colonic adenocarcinoma. A colonoscopy one year earlier had been negative for malignancy. After a careful discussion in the GI tumor board, the decision was made to treat the lung cancer first. Unfortunately, the patient developed sepsis after his first chemotherapy dose and passed away. Discussion: This case illustrates the challenges with CD therapy during active malignancy. CD patients are at increased risk for both colonic adenocarcinoma and pulmonary malignancy. There have been isolated cases linking CD to premalignant diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, suggesting a possible correlation between CD and the highly aggressive large cell neuroendocrine tumor of the lung seen, though data is limited. VDZ has been associated with 24%-31% clinical remission of CD after induction. It was shown to be well tolerated and had a low risk of malignancy in patients with and without a history of prior malignancy. Data is limited on the use of VDZ concurrently with active chemotherapy, though it is presumed have a favorable safety profile given the gut-selective nature of the drug. The development of malignancies in this case is thought to be possibly related to CD and likely unrelated to VDZ. With limited data available, a multidisciplinary discussion between oncology and GI is ideal to develop a tailored treatment plan for CD patients with active malignancy.

S2332 Finding a Needle Outside a Haystack: Duodenal Perforation by IVC Filter

Introduction: Deep venous thrombosis (DVT) is a common medical problem that can cause significant morbidity and mortality. For patients who cannot tolerate systemic anticoagulation, placement of an inferior vena cava (IVC) filter is frequently performed and usually well-tolerated. Complications can occur, particularly in filters with prolonged indwelling time, though perforations are historically rare. Here, we present a case of an IVC filter causing asymptomatic duodenal perforation. Case Description/Methods: An 80-year-old female presented to the hospital with generalized weakness. Her past medical history included asthma, chronic back pain, and DVT diagnosed 11 years ago for which she had an IVC filter inserted 6 years ago. She was started on low molecular weight heparin for a deep venous thrombosis discovered on venous ultrasound for leg swelling. During her workup, laboratory studies revealed microcytic anemia, though she denied any abdominal pain and signs of gastrointestinal blood loss including hematemesis, hematochezia, and melena and never had upper endoscopy or colonoscopy before. During esophagogastroduodenoscopy (EGD), a long, thin, metallic foreign body was encountered in the second portion of the duodenum that appeared to be poking through a small non-bleeding ulceration (Figure 1A). Computed tomography confirmed extraluminal presence of an IVC strut perforating into the duodenum (Figure 1B). Colonoscopy was significant for a large fungating and easily friable mass partially obstructing the ascending colon lumen (Figure 1C). Biopsies of the mass resulted as invasive adenocarcinoma. She underwent right hemicolectomy with ileocolonic anastomosis and was discharged to a skilled nursing facility. Discussion: This patient presented with weakness and microcytic anemia. Bidirectional endoscopy revealed invasive colonic adenocarcinoma which was the likely etiology of her symptoms. EGD demonstrated perforation of the duodenum by IVC filter; this is a rare complication that usually presents with severe abdominal pain or gastrointestinal hemorrhage. However, this patient was asymptomatic, and the decision was made to manage the filter conservatively particularly in the setting of her need for urgent surgical management of her colon cancer.Figure 1.: IVC filter incidentally found in duodenum on endoscopy (A), demonstrated on imaging (B). Large colonic mass (C) found on colonoscopy was the more likely cause of patient's anemia.

Surgical outcomes and survival rates of colon cancer in children and young adults

IntroductionColon cancer in children and young adults is rare. We sought to compare outcomes and survival between patients ≤and>25 years of age with colon cancer. MethodsUsing the National Cancer Database, patients with colon cancer between 2004 and 2016 were identified. We included patients with histological codes consistent with invasive colon adenocarcinoma and excluded those missing data about treatment. Post-surgical outcomes and survival were compared. ResultsOf 531,462 patients meeting criteria, 947 were ≤25 years. Patients ≤25 had more advanced disease (stage III:44.4%vs33.4%, stage IV:27.5%vs.15.3%) and higher rates of total colectomy (8.9%vs.2.7%) and proctocolectomy (5.0%vs.0.0%) than those >25 years. Stage for stage, 5-year survival was higher in patients ≤25 than those >25years. On multivariate regression, age was not associated with increased risk of mortality while male sex and uninsured status were. ConclusionsDespite presenting with more advanced disease, patients ≤25 years with colon cancer had better survival than those >25 years.

GenHITS: A network science approach to driver gene detection in human regulatory network using gene’s influence evaluation

Cancer is among the diseases causing death, in which, cells uncontrollably grow and reproduce beyond the cell regulatory mechanism. In this disease, some genes are initiators of abnormalities and then transmit them to other genes through protein interactions. Accordingly, these genes are known as cancer driver genes (CDGs). In this regard, several methods have been previously developed for identifying cancer driver genes. Most of these methods are computational-based, which use the concept of mutation to predict CDGs. In this research, a method has been proposed for identifying CDGs in the transcription regulatory network using the concept of influence diffusion and by modifying the Hyperlink-Induced Topic Search algorithm based on the diffusion concept. Due to the type of these networks and the processes of abnormality progression in cells and the formation of cancerous tumors, high-influence genes can be the most likely considered as the driver genes. Therefore, we can use the influence diffusion concept as an acceptable theory to identify these genes. Recently, a method has been proposed to detect CDGs with the concept of the influence maximization. One of the challenges in these types of networks is finding the power of regulatory interaction between genes. Moreover, we have proposed a novel method to calculate the weight of regulatory interactions, based on the concept of diffusion. The performance of the proposed method was compared with other seventeen computational and network tools. Correspondingly, three cancer types were used as benchmarks as follows: breast invasive carcinoma (BRCA), Colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). In addition, to determine the accuracy of the detected drivers using each method, CGC (Cancer Gene Census) and Mut-driver gene lists were utilized as gold standard. The results show that GenHITS performs better compared to the most of the other computational and network methods. Besides, it is also able to identify genes that have been identified by none of the other methods yet.

Finding prognostic gene pairs for cancer from patient-specific gene networks

BackgroundMolecular characterization of individual cancer patients is important because cancer is a complex and heterogeneous disease with many possible genetic and environmental causes. Many studies have been conducted to identify diagnostic or prognostic gene signatures for cancer from gene expression profiles. However, some gene signatures may fail to serve as diagnostic or prognostic biomarkers and gene signatures may not be found in gene expression profiles.MethodsIn this study, we developed a general method for constructing patient-specific gene correlation networks and for identifying prognostic gene pairs from the networks. A patient-specific gene correlation network was constructed by comparing a reference gene correlation network from normal samples to a network perturbed by a single patient sample. The main difference of our method from previous ones includes (1) it is focused on finding prognostic gene pairs rather than prognostic genes and (2) it can identify prognostic gene pairs from gene expression profiles even when no significant prognostic genes exist.ResultsEvaluation of our method with extensive data sets of three cancer types (breast invasive carcinoma, colon adenocarcinoma, and lung adenocarcinoma) showed that our approach is general and that gene pairs can serve as more reliable prognostic signatures for cancer than genes.ConclusionsOur study revealed that prognosis of individual cancer patients is associated with the existence of prognostic gene pairs in the patient-specific network and the size of a subnetwork of the prognostic gene pairs in the patient-specific network. Although preliminary, our approach will be useful for finding gene pairs to predict survival time of patients and to tailor treatments to individual characteristics. The program for dynamically constructing patient-specific gene networks and for finding prognostic gene pairs is available at http://bclab.inha.ac.kr/pancancer.

Filiform polyposis with sigmoid colon adenocarcinoma: a case report

BackgroundFiliform polyposis is a rare form of inflammatory polyposis, which is occasionally formed in the colon of patients with history of inflammatory bowel disease (IBD). It is characterized by presence of several to hundreds of slender, worm-like polyps in the colon lined by histologically normal colonic mucosa and often coalesce, resulting in a tumor-like mass. Filiform polyposis is most frequently associated with a post-inflammatory reparative process in patients with IBD history, and only cases of filiform polyposis occurring in patients without IBD history have been reported. Filiform polyposis has been considered as a benign inflammatory polyposis without any risk of dysplasia, while the possibility of carcinogenesis of inflammatory polyps is not fully excluded. To date, only three cases of filiform polyposis coexisting with dysplasia have been reported.Case presentationA 59-year-old male patient with no past medical history of IBD underwent laparoscopic sigmoidectomy for obstructive filiform polyposis, which was associated with sigmoid colon adenocarcinoma. Based on the histological findings of the resected specimen, invasive sigmoid colon adenocarcinoma was surrounded by filiform polyposis, and adenocarcinoma also scattered uniformly on the surface of filiform polyposis. In immunohistochemistry, abnormal p53 expression was observed in adenocarcinoma, while it was not shown in mucosa on filiform polyposis.ConclusionsThis is the fourth case of filiform polyposis that is closely associated with colon dysplasia or adenocarcinoma based on histological findings. However, immunohistochemical findings did not support the theory that inflammation initiates adenocarcinoma in filiform polyposis like IBD. Hence, further immunohistochemical and genetic analyses are needed to clarify the association between filiform polyposis and carcinogenesis.

Rate of colorectal neoplasia in patients with Hodgkin lymphoma

Survivors of Hodgkin lymphoma (HL) are at increased risk of breast, lung, thyroid, stomach, pancreatic and colon cancer. There is limited information on the utility of endoscopic screening for colon cancer. We aimed to describe the adenoma detection rate (ADR) in patients with HL to determine the appropriate timing of colonoscopy screening. We retrospectively studied patients with HL who underwent colonoscopy between 2000 and 2017. A total of 251 patients underwent colonoscopy. Eighty (32%) patients had 151 colonic polyps. Thirty per cent of the polyps exhibited high-grade dysplasia, and invasive colon adenocarcinoma was found in 10 patients. Patients with the nodular sclerosing subtype of HL had a significantly lower ADR than others (P=0.002). The ADR was 5% in patients younger than 35years (n=64), 23% in patients between 35 and 40years of age (n=22), 39% in patients between 40 and 50years of age (n=51) and 46% in patients older than 50years (n=114).