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Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank p = 0.011), and an elevated ccfDNA concentration (≥25.79 ng/mL) was strongly associated with shorter OS (4 vs. 8 months; log rank p = 0.009). According to the results of the multivariable Cox regression analysis, the baseline concentration of ccfDNA was an independent prognostic factor for OS (HR 0.45, 95% CI 0.21-0.97, p = 0.041). Furthermore, the combination of ccfDNA levels with NLR greatly enhanced the prognostic accuracy of PDAC patients. Our study demonstrates that ccfDNA concentration and NLR are independent predictors of survival in PDAC. Subsequent studies should validate this combination as a prognostic indicator in PDAC patients and assess its utility for guiding therapeutic decisions.

Background: Genetic tests are increasingly performed for the management of unresectable pancreatic cancer. For genotyping aimed samples current guidelines recommend using core specimens, although based on moderate quality evidence. However, in clinical practice among the endoscopic ultrasound (EUS) guided tissue acquisition methods, fine needle aspiration (FNA) is the most widely performed., Aim: To assess the adequacy for next generation sequencing (NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma (PDAC) samples., Methods: Between November 2018 and December 2021, 105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology center. Either 22 gauge (G) or 19G FNA needles were used. One pass was dedicated to DNA extraction. DNA concentration and purity (A260/280, A260/230) were assessed by spectrophotometry. We assessed the differences in DNA parameters according to needle size and tumor characteristics (size, location) and the adequacy of the extracted DNA for NGS (defined as A260/280 ≥ 1.7, and DNA yield: ≥ 10 ng for amplicon based NGS, ≥ 50 ng for whole exome sequencing [WES], ≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and t -test respectively. Moreover, we compared DNA purity parameters across the different DNA yield categories., Results: Our cohort included 49% male patients, aged 67.02 ± 8.38 years. The 22G needle was used in 71% of the cases. The DNA parameters across our samples varied as follows: DNA yield: 1289 ng (inter quartile range: 534.75-3101), A260/280 = 1.85 (1.79-1.86), A260/230 = 2.2 (1.72-2.36). DNA yield was > 10 ng in all samples and > 100 ng in 93% of them (one sample < 50 ng). There were no significant differences in the concentration and A260/280 between samples by needle size. Needle size was the only independent predictor of A260/230 which was higher in the 22G samples ( P = 0.038). NGS adequacy rate was 90% for 19G samples regardless of NGS type, and for 22G samples it reached 89% for WGS adequacy and 91% for WES and amplicon based NGS. Samples with DNA yield > 100 ng had significantly higher A260/280 (1.89 ± 0.32 vs 1.34 ± 0.42, P = 0.013). Tumor characteristics were not corelated with the DNA parameters., Conclusion: EUS-FNA PDAC samples yield DNA adequate for subsequent NGS. DNA amount was similar between 22G and 19G FNA needles. DNA purity parameters may vary indirectly with needle size., Competing Interests: Conflict-of-interest statement: All authors confirm they have no conflict of interest in relation to this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background/aim: Locally advanced pancreatic head cancer remains an aggressive malignancy with a low likelihood of achieving resectability after neoadjuvant chemotherapy. Resection is even more difficult if anatomical variations of the blood supply are present., Case Report: We present the case of a 62-year-old male diagnosed with locally advanced pancreatic cancer in the presence of an aberrant right hepatic artery originating from the superior mesenteric artery. After completing six cycles of neoadjuvant chemotherapy consisting of irinotecan and oxaliplatin, resectability was achieved, the patient being submitted to pancreatoduodenectomy. Intraoperatively, the presence of an aberrant right hepatic artery originating from the superior mesenteric artery was confirmed. The postoperative course was uneventful, the patient being discharged on the eight postoperative day, while the histopathological studies confirmed the negativity of the resection margins., Conclusion: Resectability can be achieved after neoadjuvant chemotherapy for locally advanced pancreatic cancer. However, attention should be focused on the possibility of the presence of anatomical variations of the pancreatic and liver blood supply., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Pancreatic cancer remains asymptomatic for a long period of time, being frequently diagnosed when vascular invasion is already present. Such cases are widely known as borderline lesions. The aim of this study was to identify the effectiveness of vascular resection in this subgroup of patients., Patients and Methods: Fifteen such cases were submitted to surgery with curative intent., Results: Eight cases were diagnosed with borderline resectable lesions with portal vein invasion and were submitted to per primam resection and seven cases were initially diagnosed with arterial invasion and had been initially submitted to neoadjuvant chemotherapy followed by resection. In all cases portal vein resection was needed while in other four cases association of superior mesenteric artery resection was performed. Postoperatively, five patients developed complications requiring reoperation, three of whom died at the end of the first postoperative month. The histopathological studies confirmed the completeness of resection in all cases., Conclusion: Vascular resections in pancreatic cancer resections remain demanding procedures, and are reserved for cases in which a radical resection is feasible., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Invasion of portal vein (PV)/ superior mesenteric vein (SMV) in pancreatic ductal adenocarcinoma (PDAC) is no longer a contraindication for resection when reconstruction is technically feasible. However, the literature data reached conflicting conclusions regarding the early and long-term outcomes of patients with venous resection and pancreatectomies for PDAC. The study aims to present the outcomes in a large series of patients with pancreatectomies and associated PV/ SMV resection for PDAC, in a single center experience. Patients Methods: The data of 100 patients with pancreatectomies and PV and/ or SMV resection performed between 2002 and 2016 (February, 1st) were retrospectively analyzed from a prospectively maintained electronic database, which included 474 pancreatectomies for PDAC. Only patients with a final pathological diagnosis of PDAC were included in the present study. Results: Overall, 21.1% of patients with pancreatectomies for PDAC required a venous resection (100 patients out of 474 patients). Segmental resection was performed in 77 patients (out of 100 patients with pancreatectomies and venous resection - 77%), while 23 patients (23%) have had tangential venous resection. In the group of patients with segmental venous resection, reconstruction was made by end-to-end anastomosis in 53 patients (out of 77 patients - 68.8%), while in 24 patients (out of 77 patients - 31.2%) a graft interposition was necessary. Negative resections margins were obtained in 63 patients (63%). Histological tumor invasion of the resected vein was confirmed in 64 patients (64%). Postoperative complications occurred in 47 patients (47%), with severe complications (i.e., Dindo-Clavien grade III-V) in 19 patients (19%). Postoperative pancreatic fistulae, delayed gastric emptying and post-pancreatectomy hemorrhage rates were 9%, 20% and 15%, respectively. PV/ SMV thrombosis occurred in 5 patients (5%). The 90-day mortality rate in the group of patients with venous only resection, without any associated procedures, was 8%. Adjuvant treatment was performed in 63 patients (63%), while only 2 patients (2%) underwent neoadjuvant chemotherapy. Median follow-up time was 105 months (range, 3 - 186 months), with a median overall survival time of 13 months (range, 3 - 186 months). In the group of patients with negative resection margins, the median overall survival time was 16 months (range, 3 - 186 months). Conclusions: PV/ SMV resection during pancreatectomies for PDAC is technically feasible, and grafts are rarely required for venous reconstruction. However, venous resection is associated with high postoperative complications rates, and the mortality rate is not neglectable. The main goal of such complex procedure is to obtain negative resection margins, a situation associated with encouraging survival rates., (Celsius.)

Unlabelled: Background/ Aim: Chronic hepatitis B virus (HBV) infection is sometimes considered a risk factor for pancreatic cancer (PDAC), but the prognostic value of its presence has only rarely been investigated. The present study aimed to explore the impact of HBV after resection for PDAC., Materials and Methods: According to HBV surface antigen seroreactivity, 343 patients were classified as having non-viral or HBV-related cases of PDAC. Clinicopathological data and outcomes were comparatively assessed between the groups., Results: Chronic HBV infection was observed in 16 patients (4.5%). No significant differences between the HBV and non-viral cases of PDAC were observed. Tumor diameters (3.4 vs. 3.0, p=0.092) and stages at diagnosis (31 vs. 14% T1-T2, p=0.082) tended to differ between the groups, albeit without reaching significance. Completion of adjuvant therapy (63 vs. 54%, p=0.612), as well as median overall survival (15 vs. 17 months, p=0.346) was similar in the HBV and non-viral PDAC groups., Conclusion: HBV-positive and virus-free patients with PDAC generally shared the same demographic, clinical and pathological profiles. HBV did not appear to have a detrimental effect on either early or long-term outcomes after resection for PDAC. Future studies searching for occult infection might, however, shed a different light on the role of HBV in PDAC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Pancreatic cancer is one of the most lethal malignancies and is associated with a very poor overall survival. However, it seems that the only curative option remains an aggressive surgical approach capable of obtaining a radical resection. Unfortunately, this desiderate is even harder to be obtained when it comes to pancreatic tumors with vascular invasion., Case Report: We present the case of a 65-year-old patient who was diagnosed with a cephalopancreatic tumor invading both the portal vein and the superior mesenteric artery., Results: Whipple procedure was performed with portal and superior mesenteric artery resection; the continuity of the portal vein was established by an end-to-end anastomosis, while the superior mesenteric artery was re-implanted in the infra-renal aorta., Conclusion: Due to improvements of surgical techniques and postoperative management, the postoperative morbidity and early mortality significantly decreased and enabled the surgeon to perform ultra-radical surgery with better outcome., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

In this study, we focus our interest on some peculiar infrastructural abnormalities detected in an insulinoma case. Tumor pancreatic endocrine cells proliferated detrimental to exocrine counterpart, so that extensive areas of prevalent β-tumor cells can be seen. Two phenotypes of β-tumor cells can be identified: (1) β-tumor cells with full euchromatic and nucleolated nuclei and (2) β-tumor cells with heterochromatic and shrink nuclei. Because of stroma alteration, including basement membrane, cell-extracellular matrix junctions are also compromised. The mostly striking and important finding in this report for a case of insulinoma is the high fragility of plasma membrane of both two phenotypes of β-tumor cells. Cell-cell junctions, especially desmosomal junctions are severely altered, almost missing, plasma membranes showed shedding membrane vesicles and extensive dissolutions leading to pseudo-syncytia formation. Extravasated blood cells, including inflammatory cells contribute to the dramatic and extensive destructive areas of epithelial cells as well as stroma counterpart. Moreover, also the inner cell cytomembranes exhibit abnormalities: many β-tumor cells have excessive dilatations of nuclear envelope and endoplasmic reticulum. All above severe infrastructural abnormalities, especially down regulation of cell-cell and cell-extracellular matrix adhesions and plasma membranes fragility might result in aberrant cell behavior and, consequently, much care should be taken for the postoperatory patient evolution.

The assessment of caveolin-1 (Cav-1) as a marker of tumor aggressiveness in pancreatic ductal adenocarcinoma (PDAC). In this study, we examined the expression of Cav-1 in 34 human PDAC tissue samples and the associated peritumoral tissues by immunohistochemistry and western blot. Additionally, we correlated Cav-1 expression with other tissue (Ki-67, p53) and serum (CA 19-9) tumor markers. In the tumor-derived tissue, both tumor cells and blood vessels expressed Cav-1. In contrast, in peritumoral tissue, Cav-1 expression was confined mainly to blood vessels and was only occasionally expressed in ductal or parenchymal cells. Western blot analysis confirmed the overexpression of Cav-1 in pancreatic tumors compared with peritumoral tissue. Cav-1 expression in tumor tissues was correlated with both the Ki-67 LI (r = 0.95, P < 0.0001) and p53 expression (chi2 = 9.91, P < 0.005). Overexpression of Cav-1 was associated with tumor size, grade and stage and Cav-1 expression in tumors was correlated with an increased serum level of CA 19-9 (r = 0.795, P < 0.001). Based on the results of this study, the inclusion of Cav-1 in a putative panel of biomarkers predicting pancreatic cancer aggressiveness is warranted.

In this study, we addressed the hypothesis that transcriptional suppression of erythroblastosis virus E26 oncogene homolog 1 (ETS-1) is an efficient therapeutic approach to pancreatic adenocarcinoma by investigating the effect of ETS-1 suppression in human pancreatic cancer cells. We accomplished this by using an adenoviral vector encoding only the DNA-binding domain of wild-type ETS-1 (ETS-1 dominant negative, ETS-1-DN). ETS-1-DN decreases ETS-1-binding by competing for its binding to DNA. Adenoviral-mediated transfer of ETS-1-DN (adenoviral ETS-1-DN construct, AdETS-1-DN) into pancreatic tumor cell lines did not affect their proliferation rate in vitro but did significantly inhibit their in vivo growth in nude mice. Furthermore, to test the efficacy of ETS-1-DN in vivo, we injected the AdETS-1-DN into established human pancreatic adenocarcinomas grown in nude mice. This treatment significantly reduced tumor size as compared to saline injection, without any detectable side effects. Microvessel density in mouse xenografts displayed significantly lower values in tumors in which ETS-1 was downregulated. In addition, expression of the ETS-1-DN in the pancreatic cancer cells resulted in downregulation of urokinase-type plasminogen activator (u-PA) and metalloproteinase-1 (MMP-1) expression. Taken together, these data suggest that transcriptional inactivation of ETS-1 is able to significantly affect angiogenesis and growth of pancreatic cancer. This effect may be due in part to downregulation of MMP-1 and u-PA expression. Our results suggest that ETS-1-DN is a promising candidate for antiangiogenic gene therapy in pancreatic cancer.

Introduction: Pancreatic involvement in metastatic melanoma is not an uncommon feature in disseminated disease, but isolated metastasis to the pancreas is a rare entity. Management of the pancreatic metastatic melanoma is controversial and the role of surgery is poorly defined. Most of the resectable pancreatic metastases were treated by standard pancreatectomies, and the role of limited resections (as central pancreatectomy) was not yet established., Case Report: A 43-years old woman with previously right eye enucleation for primary melanoma (4 years ago) developed three metastases (one located into the body of pancreas and two into the right inferior pulmonary lobe). The diagnosis of the pancreatic metastasis was done by endoscopic ultrasound -fine needle aspiration biopsy. A two step operation was performed: first a central pancreatectomy for pancreatic metastasis and after three weeks a right inferior pulmonary lobectomy for lung metastases., Results: The postoperative outcome after central pancreatectomy was complicated by a bleeding from distal pancreatic stump, requiring a re-laparotomy for hemostasis and a pancreatic fistula conservatively treated. At 12 months after operation the patient is asymptomatic, with no clinical and imaging signs of recurrence., Conclusion: Surgical resection remains the single hope for cure for patients with metastatic melanoma. Central pancreatectomy could be an optimal choice for metastatic malignant melanoma to the body of the pancreas only if a complete resection of the tumor can be achieved and can be accomplished by other surgical procedures for other sites of metastatic melanoma.