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Simple Summary: The available chemotherapeutic regimens for metastatic pancreatic ductal adenocarcinoma (mPDAC) in Romania include FOLFIRINOX (FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem). The purpose of our study was to compare the efficacy of FFX, GB, and Gem in patients with mPDAC in real-world scenarios. Our research revealed that the overall survival (OS) of patients receiving FFX or GB was comparable, twice as long as that of patients receiving Gem, and the progression-free survival (PFS) was highest for patients receiving FFX as first-line chemotherapy (L1). Male gender, Eastern Cooperative Oncology Group Performance (ECOG-PS) 0/1, the FFX regimen, and neutrophil-to-lymphocyte ratio (NLR) > 4.15 were all independently linked to a longer OS. L1 with FFX improved both OS and PFS for second-line chemotherapy (L2). Purpose: To assess the efficacy of FOLFIRINOX(FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: This is a retrospective study that included 83 patients with mPDAC treated with first-line chemotherapy (L1) with either FFX, GB or Gem between 2015 and 2017. Progression-free survival (PFS) for L1 and second-line chemotherapy (L2) (PFS-L1 and PFS-L2) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Median PFS-L1 for FFX, GB and Gem groups was 9 months (95% (Confidence Interval) CI 2.76–15.24), 5 months (95%CI 3.44–6.56), and 5 months (95%CI 3.76–6.24), respectively (p = 0.04). OS was 14 months (95%CI 11.16–16.85), 12 months (95%CI: 9.44–11.56), and 7 months (95%CI: 5.7–8.3) for patients treated with FFX, GB, and Gem, respectively (p = 0.0001). ECOG-PS (0/1) (Hazard Ratio (HR) 6.74, p = 0.002), age > 70 years (HR 0.25, p = 0.04), body tumors (HR 2.8, p = 0.048), CA19–9 > 39 U/mL (HR 0.26, p = 0.02), and neutrophil-to-lymphocyte ratio (NLR) > 4.15 (HR 6.76, p = 0.001) were independent prognostic factors for PFS-L1. Male gender (HR 3.02, p = 0.026), ECOG-PS (0/1) (HR 4.21, p = 0.003), L1 with FFX (HR 0.255, p = 0.007), and NLR > 4.15 (HR 2.65, p = 0.04) were independent prognostic factors of OS. PFS-L2 (HR 6.91, p = 0.013) and OS-L2 (HR 6.95, p = 0.037) were significantly higher in patients first treated with FFX. Conclusions: The OS of patients who receive FFX or GB is comparable. The best PFS-L1 belongs to the FFX group. Male gender, ECOG-PS 0/1, the FFX regimen, and NLR > 4.15 were independent predictors of OS. PFS-L2 and OS-L2 were favorably impacted by L1 with FFX. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10−10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18 , whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10–6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms. [ABSTRACT FROM AUTHOR]

Background. Endoscopic ultrasound (EUS) in association with fine needle aspiration (FNA) it is considered to be the standard of pancreatic mass lesions diagnosis. Our aim was to determine which ultrasound features, including a particular hypoechoic rim aspect can predict a pancreatic neuroendocrine tumor (pNET) diagnosis. Methods. The EUS examinations performed for solid pancreatic lesions from 2015 to 2019 in a Tertiary Gastroenterology Center were evaluated in a prospective study. There were 175 cases analyzed, out of which pNET diagnosis was established by FNA in n= 19 (10.8%). Mean age of patients with pNETs was 56.1 ± 10.3 years, significantly lower than all cases in the study group and 52.7% of which were females. We studied the following EUS characteristics by univariate and multivariate analysis: well defined margins, hypoechoic EUS aspect, homogeneous pattern, the presence of internal vascularization, stiff elastographic appearance, the presence of multiple lesions, the internalization of large vessels, Wirsung duct dilation and the presence of a hypoechoic rim delimiting the interior margin of the lesion. Results. The following EUS features were significantly associated with EUS diagnosis of pNET: well defined margins (63.1% vs 35.7% p=0.02), homogeneous pattern (36.8% vs 16.9%, p=0.03), the presence of internal vascularisation (63.1% vs 24.3%, p=0.0004), blue on elastography (89.4% vs 64.2%, p=0.03) and the presence of a hypoechoic rim (47.3% vs 2.5%, P< 0.0001). In the multivariate logistic regression analysis only the presence of a hypoechoic rim was independently associated with the pNET diagnosis (p< 0.0001). Conclusions. EUS appearance can suggest the diagnosis of a pNET. The presence of a hypoechoic rim delimiting the interior margin of the lesion is an independent predictor of pNET diagnosis. [ABSTRACT FROM AUTHOR]

Introduction. Acute pancreatitis (AP) is among the most common causes of emergency admissions in gastroenterology departments. Although AP etiology comprises mainly gallstones, alcohol abuse, and hyperlipidemia, there is a strong, bidirectional association between AP and pancreatic cancer (PC). Case presentation. We present the case of a 76-year-old woman, smoker (15 pack-years), nondrinker, without relevant personal/family medical history, admitted in another unit for intense epigastric pain irradiated to the back, nausea and vomiting for 10 days prior to hospitalization. She also reported unintentional weight loss - 10 kilograms in six months. At that time - there were no remarkable clinical findings, the blood tests showed high amylase (2 times the upper normal limit(2xULN)), moderate inflammation, mild hyperglycemia, normal liver function tests, and triglycerides. She was diagnosed with acute pancreatitis (AP). The supportive treatment (hydration, pain killers) lead to symptoms decrease. One week afterward a contrast enhanced abdominal CT (CECT) scan was performed revealing a pancreatic head mass (55 mm), invading the duodenum, lesser gastric curvature, in contact with the superior mesenteric artery (SMA), also common bile duct and Wirsung duct dilation and small fluid pericefalic collections. She was referred to our hospital for further investigations. At admission (one month after symptoms onset) the pain persisted, the blood test showed - high - amylase (2xUN) and lipase (5xULN), cholestasis (GGT-5xUNL, ALP - 1.5xUNL, normal BB), moderate inflammation, hyposideremia (22ug/dL). Endoscopic ultrasound (EUS) was performed describing a voluminous pancreatic head cystic lesion compressing the gastric wall - drainage was considered unsafe. She was further referred to abdominal MRI performed 3 months after disease onset that showed a locally advanced pancreatic head tumor, complete regression of the pseudocyst. The patient became jaundiced (total BB of 7 mg/dL) and continued to lose weight. EUS tissue acquisition (EUS-TA) was performed. The pathology results established the diagnosis of high-grade pancreatic adenocarcinoma. Discussion. This was a case of AP caused by PC diagnosed at 2 months after AP onset by EUS-TA after AP remission. The tumor had otherwise a typical course with weight loss, abdominal pain, and jaundice A biliary stent will be placed and chemotherapy will be started. Conclusion: Although rare clinicians must be aware of the PC etiology of AP - especially in older patients, with presumably idiopathic AP etiology, weight loss, and concomitant new-onset diabetes. To this end, a follow-up CECT must be performed during the first year after AP in selected cases. [ABSTRACT FROM AUTHOR]

[Display omitted] • The methods for pancreatic cancer monitoring have a latency in indicating disease progression. • Cell-free DNA is the most extensively studied type of liquid biopsy in pancreatic adenocarcinoma. • Circulant tumor DNA indicates increased aggressiveness of resectable or unresectable tumors and if detected during treatment. • Associations of KRAS mutations and prognosis in unresectable cases is to be determined. This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined. [ABSTRACT FROM AUTHOR]