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World Journal of Gastrointestinal... Nov 2023The prevalence of multiple primary malignant neoplasms (MPMNs) is increasing in parallel with the incidence of malignancies, the continual improvement of diagnostic...
BACKGROUND
The prevalence of multiple primary malignant neoplasms (MPMNs) is increasing in parallel with the incidence of malignancies, the continual improvement of diagnostic models, and the extended life of patients with tumors, especially those of the digestive system. However, the co-existence of MPMNs and duodenal adenocarcinoma (DA) is rarely reported. In addition, there is a lack of comprehensive analysis of MPMNs regarding multi-omics and the tumor microenvironment (TME).
CASE SUMMARY
In this article, we report the case of a 56-year-old man who presented with a complaint of chest discomfort and abdominal distension. The patient was diagnosed with metachronous esophageal squamous cell carcinoma and DA in the Department of Oncology. He underwent radical resection and chemotherapy for the esophageal tumor, as well as chemotherapy combined with a programmed death-1 inhibitor for the duodenal tumor. The overall survival was 16.6 mo. Extensive evaluation of the multi-omics and microenvironment features of primary and metastatic tumors was conducted to: (1) Identify the reasons responsible for the poor prognosis and treatment resistance in this case; and (2) Offer novel diagnostic and therapeutic approaches for MPMNs. This case demonstrated that the development of a second malignancy may be independent of the location of the first tumor. Thus, tumor recurrence (including metastases) should be distinguished from the second primary for an accurate diagnosis of MPMNs.
CONCLUSION
Multi-omics characteristics and the TME may facilitate treatment selection, improve efficacy, and assist in the prediction of prognosis.
PubMed: 38111767
DOI: 10.4240/wjgs.v15.i11.2627 -
International Journal of Cancer Apr 2024Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal...
Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal cancer, and gastric and duodenal ulcer and a randomly selected subcohort of ~2000 individuals within the China Kadoorie Biobank study of >0.5 million adults. We used a bead-based multiplex serology assay to measure antibodies against 19 pathogens (total 43 antigens) in baseline plasma samples. Associations between pathogens and antigen-specific antibodies with risks of site-specific cancers and ulcers were assessed using Cox regression fitted using the Prentice pseudo-partial likelihood. Seroprevalence varied for different pathogens, from 0.7% for Hepatitis C virus (HCV) to 99.8% for Epstein-Barr virus (EBV) in the subcohort. Compared to participants seronegative for the corresponding pathogen, Helicobacter pylori seropositivity was associated with a higher risk of non-cardia (adjusted hazard ratio [HR] 2.73 [95% CI: 2.09-3.58]) and cardia (1.67 [1.18-2.38]) gastric cancer and duodenal ulcer (2.71 [1.79-4.08]). HCV was associated with a higher risk of duodenal cancer (6.23 [1.52-25.62]) and Hepatitis B virus was associated with higher risk of duodenal ulcer (1.46 [1.04-2.05]). There were some associations of antibodies again some herpesviruses and human papillomaviruses with risks of gastrointestinal cancers and ulcers but these should be interpreted with caution. This first study of multiple pathogens with risk of gastrointestinal cancers and ulcers demonstrated that several pathogens are associated with risks of gastrointestinal cancers and ulcers. This will inform future investigations into the role of infection in the etiology of these diseases.
Topics: Adult; Humans; Cohort Studies; Duodenal Ulcer; Ulcer; Duodenal Neoplasms; Seroepidemiologic Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Cardia; Gastrointestinal Neoplasms; Hepatitis C; Helicobacter Infections; Helicobacter pylori
PubMed: 38108203
DOI: 10.1002/ijc.34814 -
Endoscopy Dec 2023
Topics: Humans; Colonic Polyps; Colonoscopy; Neuroendocrine Tumors; Adenoma; Duodenal Neoplasms
PubMed: 38092057
DOI: 10.1055/a-2209-9924 -
Cell Reports Dec 2023The carcinogenesis and progression of hepatocellular carcinoma (HCC) are closely related to viral infection and intestinal bacteria. However, little is known about...
The carcinogenesis and progression of hepatocellular carcinoma (HCC) are closely related to viral infection and intestinal bacteria. However, little is known about bacteria within the HCC tumor microenvironment. Here, we showed that intratumoral Mycoplasma hyorhinis (M. hyorhinis) promoted the initiation and progression of HCC by enhancing nuclear ploidy. We quantified M. hyorhinis in clinical tissue specimens of HCC and observed that patients with high M. hyorhinis load had poor prognosis. We found that gastrointestinal M. hyorhinis can retrogradely infect the liver through the oral-duodenal-hepatopancreatic ampulla route. We further found that the increases in mononuclear polyploidy and cancer stemness resulted from mitochondrial fission caused by intracellular M. hyorhinis. Mechanistically, M. hyorhinis infection promoted the decay of mitochondrial fusion protein (MFN) 1 mRNA in an m6A-dependent manner. Our findings indicated that M. hyorhinis infection promoted pathological polyploidization and suggested that Mycoplasma clearance with antibiotics or regulating mitochondrial dynamics might have the potential for HCC therapy.
Topics: Humans; Mycoplasma; Carcinoma, Hepatocellular; Liver Neoplasms; Mycoplasma hyorhinis; Mycoplasma Infections; Tumor Microenvironment
PubMed: 38088929
DOI: 10.1016/j.celrep.2023.113563 -
Indian Journal of Pathology &... 2023
Topics: Humans; Female; Teratoma; Ovarian Neoplasms
PubMed: 38084562
DOI: 10.4103/ijpm.ijpm_913_21 -
The American Journal of Surgical... Feb 2024Small bowel adenocarcinoma (SBA) is rare, and scant data exist regarding its molecular and clinicopathologic characteristics. This study aimed to clarify the correlation...
Small bowel adenocarcinoma (SBA) is rare, and scant data exist regarding its molecular and clinicopathologic characteristics. This study aimed to clarify the correlation between immunophenotypes, DNA mismatch repair status, genomic profiling, and clinicopathologic characteristics in patients with SBA. We examined 68 surgical resections from patients with primary SBA for immunohistochemical analyses of CK7, CK20, CD10, CDX2, MUC1, MUC2, MUC4, MUC5AC, and MUC6 expression as well as mismatch repair status. Genomic profiling was performed on 30 cases using targeted next-generation sequencing. Tumor mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null based on MUC2, MUC5AC, MUC6, and CD10 immunostaining. The expression of these proteins was categorized into 3 classifications according to their relationship to: (1) tumor location: CK7/CK20, MUC4, and MUC6; (2) histologic type: mucinous adenocarcinoma was positive for MUC2 and negative for MUC6; and (3) TNM stage: CD10 was downregulated, whereas MUC1 was upregulated in advanced TNM stages. CDX2 was a specific marker for SBA generally expressed in the small intestine. MUC1 and MUC4 expression was significantly associated with worse prognosis. MUC2 expression correlated with better prognosis, except for mucinous adenocarcinoma. Although the difference was not statistically significant, gastric-type tumors were more frequently located in the duodenum and were absent in the ileum. APC and CTNNB1 mutations were not found in the gastric-type tumors. The SBA immunophenotype correlated with tumor location, biological behavior, and genomic alterations. Our results suggest that the molecular pathway involved in carcinogenesis of gastric-type SBA differs from that of intestinal-type SBA.
Topics: Humans; Mucin-2; Genetic Profile; Biomarkers, Tumor; Adenocarcinoma; Adenocarcinoma, Mucinous; Intestine, Small; Duodenal Neoplasms
PubMed: 38062562
DOI: 10.1097/PAS.0000000000002161 -
Scientific Reports Dec 2023Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric...
Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to αGlcNAc. We recently demonstrated that αGlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for αGlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. αGlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced αGlcNAc and TFF2 expression. The ratios of αGlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P < 0.001). Co-expression of αGlcNAc-glycosylated MUC6 and TFF2 in PGA suggests the existence of αGlcNAc/TFF2 form complex in PGA cells, a finding consistent with our observations in non-neoplastic Brunner's gland cells. The decreased αGlcNAc and TFF2 expression are associated with high grade atypical cells, indicative of the malignant potential of PGA.
Topics: Humans; Glycosylation; Mucin-6; Trefoil Factor-2; Biomarkers, Tumor; Duodenum; Gastric Mucosa; Adenoma
PubMed: 38062108
DOI: 10.1038/s41598-023-49040-1 -
Endoscopy Dec 2023
Topics: Humans; Ascites; Pancreatic Neoplasms; Endosonography; Endoscopic Ultrasound-Guided Fine Needle Aspiration
PubMed: 38052422
DOI: 10.1055/a-2208-5363 -
Clinical and Translational... Jan 2024We aimed to evaluate the natural course of sporadic nonampullary duodenal adenomas (SNDAs) and determine the risk factors of progression.
INTRODUCTION
We aimed to evaluate the natural course of sporadic nonampullary duodenal adenomas (SNDAs) and determine the risk factors of progression.
METHODS
We retrospectively analyzed the follow-up outcomes of patients with biopsy-diagnosed SNDA between April 2010 and March 2016 at 13 institutions. All initial biopsy specimens were centrally evaluated. Only those diagnosed with adenomas were included. Mucinous phenotypes were classified into pure intestinal and non-pure intestinal phenotypes. Cumulative incidence rates of carcinoma and tumor enlargement were evaluated. Tumor enlargement was defined as a ≥25% or 5-mm increase in tumor size.
RESULTS
Overall, 121 lesions were analyzed. Within a median observation period of 32.7 months, 5 lesions were diagnosed as carcinomas; the cumulative 5-year incidence of carcinoma was 9.5%. Male sex ( P = 0.046), initial lesion size ≥10 mm ( P = 0.044), and non-pure intestinal phenotype ( P = 0.019) were significantly associated with progression to carcinoma. Tumor enlargement was observed in 22 lesions, with a cumulative 5-year incidence of 33.9%. Initial lesion size ≥10 mm ( P < 0.001), erythematous lesion ( P = 0.002), high-grade adenoma ( P = 0.002), Ki67 negative ( P = 0.007), and non-pure intestinal phenotype ( P = 0.001) were risk factors of tumor enlargement. In a multivariate analysis, an initial lesion size ≥10 mm ( P = 0.010) and non-pure intestinal phenotype ( P = 0.046) were independent and significant risk factors of tumor enlargement.
DISCUSSION
Lesion size ≥10 mm and non-pure intestinal phenotype on initial biopsy are risk factors of cancer progression and tumor enlargement in cases with SNDA. Thus, management effectiveness may be improved by focusing on lesion size and the mucinous phenotype.
Topics: Humans; Male; Retrospective Studies; Adenoma; Duodenal Neoplasms; Carcinoma; Phenotype
PubMed: 37991249
DOI: 10.14309/ctg.0000000000000649 -
BMC Cancer Nov 2023Duodenal papilla carcinoma (DPC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study...
Development and validation of web calculators to predict early recurrence and long-term survival in patients with duodenal papilla carcinoma after pancreaticoduodenectomy.
BACKGROUND
Duodenal papilla carcinoma (DPC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop web calculators to predict early recurrence (ER) (within two years after surgery) and long-term survival in patients with DPC after PD.
METHODS
Patients with DPC after radical PD were included. Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Two web calculators were developed based on independent risk factors in the training cohort and then tested in the validation cohort.
RESULTS
Of the 251 patients who met the inclusion criteria, 180 and 71 patients were enrolled in the training and validation cohorts, respectively. Multivariate logistic regression analysis revealed that tumor size [Odds Ratio (OR) 1.386; 95% confidence interval (CI) 1070-1.797; P = 0.014]; number of lymph node metastasis (OR 2.535; 95% CI 1.114-5.769; P = 0.027), perineural invasion (OR 3.078; 95% CI 1.147-8.257; P = 0.026), and tumor differentiation (OR 3.552; 95% CI 1.132-11.152; P = 0.030) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.759 and 0.729 in predicting ER in the training and the validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with single variable.
CONCLUSIONS
This study developed and validated two web calculators that can predict ER and long-term survival in patients with DPC with high degree of stability and accuracy.
Topics: Humans; Pancreaticoduodenectomy; Duodenum; Duodenal Neoplasms; Pancreatectomy; Carcinoma; Chronic Disease; Nomograms
PubMed: 37985973
DOI: 10.1186/s12885-023-11632-5