Dimitrios Karavias

Giant malignant insulinoma

Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed.

Pancreatic mediastinal pseudocyst presenting as a posterior mediastinal mass with recurrent pleural effusions: a case report and review of the literature

IntroductionA rare complication of chronic pancreatitis is the formation of single or multiple mediastinal pseudocysts, which are fueled from the pancreas through anatomical openings of the diaphragm. We present a rare case with a difficult diagnosis, treatment and potentially catastrophic complications.Case presentationA 53-year-old Caucasian man was referred to our hospital for further investigation and treatment of a large heterogeneous mass situated in the posterior mediastinum, and bilateral pleural effusions which had developed after recent multiple episodes of pancreatitis. He had a history of chronic alcoholism. Laboratory and imaging modalities established the diagnosis of a pancreatic mediastinal pseudocyst.ConclusionsDespite successful initial conservative treatment, our patient had a relapse and underwent emergency surgical intervention due to internal hemorrhage. We present his diagnostic and imaging workup, along with the multidisciplinary intervention, and a literature review referring to the diagnosis and treatment of mediastinal pancreatic pseudocysts.

Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming

Objective Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis. Design DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo. Results We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2D-induced changes in cellular, metabolic and proliferative rates. Conclusion Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.

Performing Intraoperative Computer Assisted Risk Analysis for Oncologic Liver Surgery in Clinical Practice

Oncologic liver surgery offers the only reasonable chance to cure liver cancer. Selection of patients is essential for effective treatment and in order to minimize perioperative complications. The hepatic surgeon has to achieve complete resection of the tumor(s) including devascularized liver segments and leave a sufficient future liver remnant volume (FLR). Computer assisted risk analysis can provide useful information regarding resectability, anatomical relations, risk areas and volumetric measurements. However, additional findings from the intraoperative ultrasound may modify the resection plan. The aim of this prospective study was to evaluate the intraoperative computer assisted risk analysis for oncologic liver surgery in clinical practice using a novel liver segmentation and surgery planning solution. Fourteen consecutive patients at our institution, undergoing elective major liver resections from August 2014 to July 2015 were enrolled in this prospective study. Additional intraoperative findings were incorporated on-site in the preoperative 3D models of five patients (35%). Mean intraoperative risk analysis time was 4.6min/case SD±0.9. Intraoperative virtual liver resections were designed in less than 2 minutes in all cases (mean 1.4min SD±0.4. The preoperative plan was finally changed in three patients (21%). Intraoperative computer assisted risk analysis provided rapid and reliable reevaluation of the preoperative plan and helped surgeons to select a safe approach for liver oncologic surgery.

Abstract 4528: Chromatin regulation by ING3 leads to tumor suppressive effects in pancreatic cancer through distinct signaling pathways

Background: Despite our increased knowledge of the molecular events underlying the multi-step development of pancreatic cancer (PanCa), clinically meaningful improvement in survival rates has not yet been achieved. A growing body of evidence supports that pancreatic tumorigenesis is not only led by genetic alterations but also aberrant epigenetic regulation. Identification of epigenetic drivers of the clinical disease is of major importance, as it could potentially offer a means to interfere with novel targets in PanCa therapy. Methods: Gene expression microarrays were employed in PanCa tissues and adjacent uninvolved tissues. mRNA and protein levels were assessed by qRT-PCR and immunohistochemical analysis of tissue microarrays in extended cohorts of patients. RNAi interference assays or lentiviral expression vector systems were applied for knockdown/overexpression experiments, as evidenced by qRT-PCR and Western Blot Analysis. Molecular analysis, cell proliferation, invasion and colony formation assays were conducted in genetically modified cells. Subcutaneous xenograft mouse models were used to evaluate tumor growth in vivo. Immunoprecipitation followed by mass-spectroscopy analysis was used to evaluate protein-protein interactions. Histone H4 at lysine 16 acetylation (H4K16ac) levels were assessed by Western Blot analysis, while chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq) was performed for mapping protein-DNA interactions. Results: Differential expression analysis of chromatin regulators in PanCa versus normal tissues shows that 27 epigenetic molecules are significantly deregulated (>1.5 fold, P Conclusions: Conclusively, we provide evidence that PanCa is characterized by loss of the chromatin regulator ING3 and we elucidated the tumor suppressive role of the latter in PanCa cell growth and invasion in vitro and in vivo. Citation Format: Marina Koutsioumpa, Maria Hatziapostolou, Christos Polytarchou, Angelos Oikonomopoulos, Swapna Mahurkar-Joshi, Sara Huerta-Yepez, Belen Tirado-Rodriguez, Dimitrios Karavias, Helen Kourea, George A. Poultsides, David W. Dawson, Timothy R. Donahue, Dimitrios Iliopoulos. Chromatin regulation by ING3 leads to tumor suppressive effects in pancreatic cancer through distinct signaling pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4528.