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Pathologica Feb 2021Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most recent WHO classification as neuroendocrine tumors (NET), neuroendocrine... (Review)
Review
Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most recent WHO classification as neuroendocrine tumors (NET), neuroendocrine carcinomas (NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNENs). NECs and MiNENs are aggressive neoplasms requiring multimodal treatment strategies. By contrast, NETs are, in most cases, indolent lesions occurring as incidental findings in the appendix or as polyps in the rectum. While most appendiceal and rectal NETs are considered relatively non-aggressive neoplasms, a few cases, may show a more aggressive clinical course. Unfortunately, clinical/pathological characteristics to select patients at high risk of recurrence/metastases are poorly consolidated. Diagnosis is generally easy and supported by the combination of morphology and immunohistochemistry. Differential diagnostic problems are for NECs/MiNENs with poorly differentiated adenocarcinomas, when immunohistochemical neuroendocrine markers are not obviously positive, whereas for NETs they are represented by the rare appendiceal tubular and clear cell variants (which may be confused with non-neuroendocrine cancers) and rectal L-cell tumors which may be chromogranin negative and prostatic marker positive.
Topics: Appendix; Carcinoma, Neuroendocrine; Colon; Humans; Infant, Newborn; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Rectum
PubMed: 33686307
DOI: 10.32074/1591-951X-230 -
Gastroenterology Sep 2019Many genetic and environmental factors, including family history, dietary fat, and inflammation, increase risk for colon cancer development. Peroxisome...
BACKGROUND & AIMS
Many genetic and environmental factors, including family history, dietary fat, and inflammation, increase risk for colon cancer development. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that regulates systemic lipid homeostasis. We explored the role of intestinal PPARα in colon carcinogenesis.
METHODS
Colon cancer was induced in mice with intestine-specific disruption of Ppara (Ppara), Ppara (control), and mice with disruption of Ppara that express human PPARA (human PPARA transgenic mice), by administration of azoxymethane with or without dextran sulfate sodium (DSS). Colons were collected from mice and analyzed by immunoblots, quantitative polymerase chain reaction, and histopathology. Liquid chromatography coupled with mass spectrometry-based metabolomic analyses were performed on urine and colons. We used molecular biology and biochemical approaches to study mechanisms in mouse colons, primary intestinal epithelial cells, and colon cancer cell lines. Gene expression data and clinical features of patients with colorectal tumors were obtained from Oncomine, and human colorectal-tumor specimens and adjacent normal tissues were collected and analyzed by immunohistochemistry.
RESULTS
Levels of Ppara messenger RNA were reduced in colon tumors from mice. Ppara mice developed more and larger colon tumors than control mice following administration of azoxymethane, with or without DSS. Metabolomic analyses revealed increases in methylation-related metabolites in urine and colons from Ppara mice, compared with control mice, following administration of azoxymethane, with or without DSS. Levels of DNA methyltransferase 1 (DNMT1) and protein arginine methyltransferase 6 (PRMT6) were increased in colon tumors from Ppara mice, compared with colon tumors from control mice. Depletion of PPARα reduced the expression of retinoblastoma protein, resulting in increased expression of DNMT1 and PRMT6. DNMT1 and PRMT6 decreased expression of the tumor suppressor genes Cdkn1a (P21) and Cdkn1b (p27) via DNA methylation and histone H3R2 dimethylation-mediated repression of transcription, respectively. Fenofibrate protected human PPARA transgenic mice from azoxymethane and DSS-induced colon cancer. Human colon adenocarcinoma specimens had lower levels of PPARA and retinoblastoma protein and higher levels of DNMT1 and PRMT6 than normal colon tissues.
CONCLUSIONS
Loss of PPARα from the intestine promotes colon carcinogenesis by increasing DNMT1-mediated methylation of P21 and PRMT6-mediated methylation of p27 in mice. Human colorectal tumors have lower levels of PPARA messenger RNA and protein than nontumor tissues. Agents that activate PPARα might be developed for chemoprevention or treatment of colon cancer.
Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Case-Control Studies; Cell Cycle Proteins; Cell Transformation, Neoplastic; Colon; Colonic Neoplasms; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Databases, Genetic; Disease Models, Animal; Fenofibrate; Gene Expression Regulation, Neoplastic; Humans; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins; PPAR alpha; Protein-Arginine N-Methyltransferases; Signal Transduction
PubMed: 31154022
DOI: 10.1053/j.gastro.2019.05.057 -
Annals of Oncology : Official Journal... Nov 2019A high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our... (Observational Study)
Observational Study
BACKGROUND
A high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our treatment decisions, there are no biomarkers determining minimal residual disease (MRD) and patients are at risk of being undertreated or even overtreated with chemotherapy in this setting. Circulating-tumor DNA (ctDNA) can to be a useful tool to better detect risk of relapse.
PATIENTS AND METHODS
One hundred and fifty patients diagnosed with localized CC were prospectively enrolled in our study. Tumor tissue from those patients was sequenced by a custom-targeted next-generation sequencing (NGS) panel to characterize somatic mutations. A minimum variant allele frequency (VAF) of 5% was applied for variant filtering. Orthogonal droplet digital PCR (ddPCR) validation was carried out. We selected known variants with higher VAF to track ctDNA in the plasma samples by ddPCR.
RESULTS
NGS found known pathological mutations in 132 (88%) primary tumors. ddPCR showed high concordance with NGS (r = 0.77) for VAF in primary tumors. Detection of ctDNA after surgery and in serial plasma samples during follow-up were associated with poorer disease-free survival (DFS) [hazard ratio (HR), 17.56; log-rank P = 0.0014 and HR, 11.33; log-rank P = 0.0001, respectively]. Tracking at least two variants in plasma increased the ability to identify MRD to 87.5%. ctDNA was the only significantly independent predictor of DFS in multivariable analysis. In patients treated with adjuvant chemotherapy, presence of ctDNA after therapy was associated with early relapse (HR 10.02; log-rank P < 0.0001). Detection of ctDNA at follow-up preceded radiological recurrence with a median lead time of 11.5 months.
CONCLUSIONS
Plasma postoperative ctDNA detected MRD and identified patients at high risk of relapse in localized CC. Mutation tracking with more than one variant in serial plasma samples improved our accuracy in predicting MRD.
Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Circulating Tumor DNA; Colectomy; Colon; Colonic Neoplasms; DNA Mutational Analysis; Disease-Free Survival; Female; Follow-Up Studies; Gene Frequency; High-Throughput Nucleotide Sequencing; Humans; Kaplan-Meier Estimate; Male; Mutation; Neoplasm Recurrence, Local; Neoplasm, Residual; Postoperative Period; Prospective Studies
PubMed: 31562764
DOI: 10.1093/annonc/mdz390 -
Asian Journal of Surgery Oct 2022
Topics: Adenocarcinoma; Colon; Humans; Male; Prostate; Prostatic Neoplasms
PubMed: 35523607
DOI: 10.1016/j.asjsur.2022.04.106 -
Annals of Surgery May 1972
Topics: Adolescent; Adult; Aged; Carcinoma; Caustics; Child; Child, Preschool; Colon; Esophageal Neoplasms; Esophageal Stenosis; Esophageal and Gastric Varices; Esophagitis; Esophagoplasty; Female; Hemorrhage; Hernia, Diaphragmatic; Humans; Infant; Male; Middle Aged; Postoperative Complications
PubMed: 5028488
DOI: 10.1097/00000658-197205000-00014 -
World Journal of Surgical Oncology Jul 2020Hepatocellular carcinoma (HCC) is a malignant tumor with frequent intrahepatic metastases; extrahepatic metastases are not rare but less frequent compared to... (Review)
Review
BACKGROUND
Hepatocellular carcinoma (HCC) is a malignant tumor with frequent intrahepatic metastases; extrahepatic metastases are not rare but less frequent compared to intrahepatic ones. The most frequent sites of extrahepatic metastases are the lungs, followed by the lymph nodes, bones, and adrenal glands. Case report covering gastrointestinal (GI) tract involvement from HCC is limited.
CASE PRESENTATION
A 60-year-old man was referred to us in May 2019 with a diagnosis of sigmoid colon tumor. The patient had a history of HCC and had received two stages of open resections for the primary and the abdominal metastasis successively and many times of transcatheter arterial chemoembolization (TACE). The sigmoid colon tumor received Hartmann procedure after abdominal enhanced computerized tomography (CT) scan and colonoscopy, while postoperative pathology and immunohistochemistry identified it as extrahepatic colonic metastasis from HCC.
CONCLUSIONS
The ratio of extrahepatic metastasis to the digestive tract was very low, and the majority was upper gastrointestinal involvement because of direct invasion or intraperitoneal implantation. TACE may be the risk factor of retrograde hematogenous metastasis to the downstream colon.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Colon; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis
PubMed: 32723336
DOI: 10.1186/s12957-020-01960-2 -
Molecular Medicine Reports Oct 2021Colon carcinoma is one of the most common cancers worldwide. Epidemiological studies have revealed that colon cancer is the third leading cause of cancer‑related...
Colon carcinoma is one of the most common cancers worldwide. Epidemiological studies have revealed that colon cancer is the third leading cause of cancer‑related deaths, which is due to the increased incidence and mortality rates. However, the treatment strategies for colon cancer remain unsatisfactory for patients, especially for those with advanced or recurrent colon cancer. Dysregulated microRNAs (miRNAs) are considered to influence tumor development and metastasis. However, the molecular mechanism through which miRNAs affect cancer progression is not yet completely understood. The aim of the present study was to investigate the expression levels of has‑miR‑15a‑5p and its molecular mechanism in colon cell carcinoma. In the present study, the expression levels of hsa‑miR‑15a‑5p were found to be decreased in colon tumor tissues and cancer cell lines. Hsa‑miR‑15a‑5p overexpression inhibited colon cell proliferation and migration. Mechanistically, the G1/S‑specific cyclin‑D1 (CCND1) gene was predicted as a target of hsa‑miR‑15a‑5p, as evidenced by bioinformatics and dual‑luciferase reporter assay analyses. CCND1 overexpression significantly increased the progression of colon cancer. Furthermore, CCND1 was demonstrated to mediate the effects of hsa‑miR‑15a‑5p on colon cancer cells. The present study demonstrated that hsa‑miR‑15a‑5p alleviated the proliferation, migration and invasion of colon cancer by targeting the CCND1 gene, which represents a potential molecular target for the diagnosis and treatment of colon cancer.
Topics: Adult; Aged; Carcinoma; Cell Proliferation; China; Colon; Colonic Neoplasms; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Male; MicroRNAs; Middle Aged
PubMed: 34414457
DOI: 10.3892/mmr.2021.12375 -
Cancer Letters Mar 2016Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive... (Review)
Review
Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ERβ/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ERβ selective agonists, can activate or upregulate ERβ in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ERβ may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.
Topics: Adenocarcinoma; Adenomatous Polyps; Animals; Anticarcinogenic Agents; Cell Transformation, Neoplastic; Colon; Colonic Polyps; Colorectal Neoplasms; Estrogen Receptor Antagonists; Estrogen Receptor beta; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Risk Factors; Signal Transduction
PubMed: 26708506
DOI: 10.1016/j.canlet.2015.12.009 -
The American Journal of Case Reports Sep 2022BACKGROUND Sarcomatoid carcinoma is a rare tumor that can occur in different organs and anatomical locations. Colonic sarcomatoid carcinoma, also known as... (Review)
Review
BACKGROUND Sarcomatoid carcinoma is a rare tumor that can occur in different organs and anatomical locations. Colonic sarcomatoid carcinoma, also known as carcinosarcoma, is an extremely rare tumor, with only 32 cases reported world-wide. The pathogenesis and guidelines for treatment are poorly understood due to the rarity and invasiveness of the disease. CASE REPORT A 77-year-old woman presented with worsening lower abdominal pain and associated fever after having initially been diagnosed with stump appendicitis and associated phlegmon 3 weeks prior, which was treated with antibiotics. Repeat imaging revealed an extraluminal versus perforated colonic mass with associated phlegmon. The patient's condition continued to worsen, with development of obstructive-like symptoms, resulting in operative intervention involving a R2 right hemicolectomy, stapled ileo-colostomy, and partial omentectomy. The patient had an uneventful remainder of her hospitalization other than continued lower abdominal pain. After initial discharge, the patient presented to an outside hospital due to continued deterioration of health, with findings of an additional mass, likely secondary to the previous lymphadenopathy. Ultimately, goals of care were discussed, and the decision was made to provide palliative care, and the patient died due to her illness 32 days after the initial procedure. CONCLUSIONS Carcinosarcoma is an extremely rare tumor with scant research guiding treatment guidelines. Current guidelines gathered from previous case reports suggest treating colorectal carcinosarcoma as adenocarcinoma. Additional research and studies are needed to establish appropriate therapeutic guidelines for carcinosarcoma.
Topics: Abdominal Pain; Aged; Anti-Bacterial Agents; Carcinoma; Carcinosarcoma; Cellulitis; Colon, Ascending; Female; Humans
PubMed: 36176184
DOI: 10.12659/AJCR.937548 -
International Journal of Oncology Jul 2018Developing rapidly from the cecal diverticulum in a 5-week-old embryo, the cecum, which is developed from the caudal limb of the midgut loop, is different from the...
Developing rapidly from the cecal diverticulum in a 5-week-old embryo, the cecum, which is developed from the caudal limb of the midgut loop, is different from the ascending colon. The aim of this study was to analyze the different clinicopathological and biological characteristics of patients with carcinoma of the cecum and ascending colon. We accessed data for 59,035 patients with adenocarcinomas of the cecum and ascending colon from the Surveillance, Epidemiology and End Results database to explore the potential associations between the clinicopathological characteristics and overall survival. Furthermore, we analyzed the differences in gene expression between the two segments in the Gene Expression Omnibus database. The results were validated in The Cancer Genome Atlas database, as well as with another independent dataset from the First Affiliated Hospital of Xi'an Jiaotong University. The results of this study revealed the potential prognostic differences between adenocarcinoma of the cecum and ascending colon, which may be caused by the differential expression levels of the SLCO1B3 gene. When including the expression levels of SLCO1B3 in intraoperatively examined lymph nodes, 8 factors were found able to predict the prognosis of patients with carcinomas of the cecum and ascending colon. As regards the surgical therapeutic strategies, the resection of >15 local lymph nodes is appropriate for improving the prognosis of patients.
Topics: Adult; Aged; Carcinoma; Cecum; Colon, Ascending; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Lymph Nodes; Male; Middle Aged; Prognosis; Proteome; Solute Carrier Organic Anion Transporter Family Member 1B3
PubMed: 29658575
DOI: 10.3892/ijo.2018.4366