CONCLUSIONS: Herein, the expression profiles, oncogenic roles, regulators and inhibitors of DNMT1 in PDACs are presented and discussed. DNMT1 is overexpressed in PDAC cases compared with non-cancerous pancreatic ducts, and its expression gradually increases from pre-neoplastic lesions to PDACs. DNMT1 plays oncogenic roles in suppressing PDAC cell differentiation and in promoting their proliferation, migration and invasion, as well as in induction of the self-renewal capacity of PDAC cancer stem cells. These effects are achieved via promoter hypermethylation of tumor suppressor genes, including cyclin-dependent kinase inhibitors (e.g., p14, p15, p16, p21 and p27), suppressors of epithelial-mesenchymal transition (e.g., E-cadherin) and tumor suppressor miRNAs (e.g., miR-148a, miR-152 and miR-17-92 cluster). Pre-clinical investigations have shown the potency of novel non-nucleoside DNMT1 inhibitors against PDAC cells. Finally, phase I/II clinical trials of DNMT1 inhibitors (azacitidine, decitabine and guadecitabine) in PDAC patients are currently underway, where these inhibitors have the potential to sensitize PDACs to chemotherapy and immune checkpoint blockade therapy.
METHODS: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates.
RESULTS: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84).
CONCLUSIONS: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary.
CASE REPORT: We report a case of a 75-year-old man who presented with symptoms of obstructive jaundice. Ultrasonography and computed tomography (CT) showed an ill-defined lobulated soft tissue lesion at the head/uncinate process of the pancreas measuring 4.5 x 4.9 x 5.8 cm. The patient underwent pancreaticoduodenectomy for suspected pancreatic head/uncinate process carcinoma. Histopathology and immunohistochemical assessment of the pancreatic lesion established the diagnosis of a low-grade follicular lymphoma.
DISCUSSION: Clinical and imaging features of primary pancreatic lymphoma may often overlap with pancreatic carcinoma. There is a value of obtaining preoperative tissue diagnosis such as tissue biopsy and fine needle aspiration (FNA) cytology with or without flow cytometry to make an accurate diagnosis of non-Hodgkin lymphoma and alleviate the need of more radical surgery in pancreatic lymphoma.
METHODS: This was an international, multicenter, prospective, randomized controlled study. After providing informed consent, consecutive adult patients referred for EUS-FNTA for solid lesions larger than 2 cm were randomized to a MOSE arm or to a conventional arm without ROSE. A designated cytopathologist from each center performed all cytopathological examinations for that center and was blinded to the randomization results. The primary outcome measure was the diagnostic yield, and the secondary outcomes included sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and the rate of procedure-related complications.
RESULTS: 244 patients (122 conventional, 122 MOSE) were enrolled during the study period. No significant differences between the two arms were found in procedure time or rate of procedure-related adverse events. The diagnostic yield for the MOSE technique (92.6 %) was similar to that for the conventional technique (89.3 %; P = 0.37), with significantly fewer passes made (median: conventional 3, MOSE 2; P
METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).
RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.
CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.