Background: Surgical resection is considered to be the only potentially curative option for patients with pancreatic neuroendocrine tumors (pNETs). High risk rates of perioperative complications make minimally invasive ablative techniques a novel perspective and alternative treatment option for pancreatic neuroendocrine tumors. This study aims to present the first experience of using a microwave ablation in management of pNETs.Methods: Sechenov University has an experience of treating more than 400 patients with hormoneproducing tumors of the pancreas, 7 of which were treated by microwave ablation (MWA).Results: In all patients that underwent MWA, a regression of hormonal symptomatic was achieved. Two patients required readmission a month later for draining of pseudocyst and abscess. Conclusions:The exact role of microwave ablation in the treatment of non-metastatic pancreatic neuroendocrine tumors has not been defined yet. There is a lack of large prospective randomized studies and the reason for this is that local tumor destruction is indicated in selected cases only, thus making it difficult to analyze a large group of patients and assess long-term results of the treatment. However, microwave ablation allows to take a better control of symptoms in patients with hormone overproduction and in those with high risk of postoperative complications.

Objectives: Blood-based tests have been shown to be an effective strategy for colorectal cancer (CRC) detection in screening programs. This study was aimed to test the performance of 20 blood markers including tumor antigens, inflammatory markers, and apolipoproteins as well as their combinations. Methods: In total 203 healthy volunteers and 102 patients with CRC were enrolled into the study. Differences between healthy and cancer subjects were evaluated using Wilcoxon rank-sum test. Several multivariate classification algorithms were employed using information about different combinations of biomarkers altered in CRC patients as well as age and gender of the subjects; random sub-sampling cross-validation was done to overcome overfitting problem. Diagnostic performance of single biomarkers and multivariate classification models was evaluated by receiver operating characteristic (ROC) analysis. Results: Of 20 biomarkers, 16 were significantly different between the groups (p-value ≤ 0.001); ApoA1, ApoA2 and ApoA4 levels were decreased, whereas levels of tumor antigens (e.g. carcinoembriogenic antigen) and inflammatory markers (e.g., C-reactive protein) were increased in CRC patients vs. healthy subjects. Combinatorial markers including information about all 16 significant analytes, age and gender of patients, demonstrated better performance over single biomarkers with average accuracy on test datasets ≥95% and area under ROC curve (AUROC) ≥98%. Conclusions: Combinatorial approach was shown to be a valid strategy to improve performance of blood-based CRC diagnostics. Further evaluation of the proposed models in screening programs will be performed to gain a better understanding of their diagnostic value.

BACKGROUND Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors. METHODS Twenty‐one formalin‐fixed, paraffin‐embedded specimens (15‐tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger—Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19. RESULTS Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %). CONCLUSIONS Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin. Cancer 2003. © 2003 American Cancer Society.

Insulinomatosis is characterized by monohormonality of multiple macro-tumors and micro-tumors that arise synchronously and metachronously in all regions of the pancreas, and often recurring hypoglycemia. One of the main characteristics of insulinomatosis is the presence of insulin-expressing monohormonal endocrine cell clusters that are exclusively composed of proliferating insulin-positive cells, are less than 1 mm in size, and show solid islet-like structure. It is presumed that insulinomatosis affects the entire population of β-cells. With regards to molecular genetics, this phenomenon is not related to mutation in MEN1 gene and is more similar to sporadic benign insulinomas, however, at the moment molecular genetics of this disease remains poorly investigated. NGS sequencing was performed with a panel of 409 cancer-related genes. Results of sequencing were analyzed by bioinformatic algorithms for detecting point mutations and copy number variations. DNA copy number variations were detected that harbor a large number of genes in insulinoma and fewer genes in micro-tumors. qPCR was used to confirm copy number variations at ATRX, FOXL2, IRS2 and CEBPA genes. Copy number alterations involving FOXL2, IRS2, CEBPA and ATRX genes were observed in insulinoma as well as in micro-tumors samples, suggesting that alterations of these genes may promote malignization in the β-cells population.

Иммуногистохимическое определение экспрессии рецепторов к соматостатину 1, 2А, 3 и 5-го типов в нейроэндокринных опухолях различной локализации и степени злокачественности Актуальность. У пациентов с нейроэндокринными опухолями (НЭО) очень важно еще до начала лечения аналогами соматостатина прогнозировать его клинический эффект. Данных по иммуногистохимическому исследованию экспрессии рецепторов к соматостатину (ССР) разных типов, полученных на больших выборках НЭО различной локализации, функциональной активности и степени злокачественности, накоплено недостаточно, что и определило цель настоящего исследования. Материал и методы. Проводили иммуногистохимическое исследование с антителами к ССР 1, 2А, 3 и 5-го типов. Материалом исследования послужили тканевые образцы диагностических и операционных биопсий 399 НЭО: 168 поджелудочной железы, 120 желудочно-кишечного тракта (желудка -48, тонкой кишки -39, из которых опухолей двенадцатиперстной кишки -14, аппендикса -6, толстой и прямой кишки -15 и 12), 84 легких, 6 тимуса / средостения и 21 метастазов НЭО с неизвестной первичной локализацией. Результаты. Очень высокий уровень экспрессии ССР 2А, которые преимущественно связывают аналоги соматостатина, используемые сегодня в клинической практике, выявлен в НЭО Ключевые слова: рецепторы к соматостатину, нейроэндокринные опухоли, иммуногистохимия

The incidence of pancreatic neuroendocrine tumors has significantly increased for the last decades. Patients with multiple pancreatic neuroendocrine tumors require special attention to the diagnosis and treatment algorithms. The aim is to show possible treatment approaches for patients with multiple pancreatic neuroendocrine tumors. Materials and methods. 26 patients with multiple pancreatic neuroendocrine tumors were managed in the abdominal surgery department of Sechenov University for the last 20 years. Results. The rate of multiple tumors was 9% for sporadic tumors and 36.5% among patients with MEN-1. Sensitivity of the imaging techniques was significantly lower than in solitary insulinomas. Most patients underwent parenchymasparing procedures. Total pancreatectomy was performed only in two cases. Conclusion. Accurate imaging and identification of hormone-secreting tumors allows to offer patients parenchyma-sparing surgery and to provide more personalized approach to the treatment of patients with multiple pancreatic neuroendocrine tumors.

The aim of the study was to assess the efficiency of the method for registration of video fluorescence of 5-ALA-induced protoporphyrin IX in stomach and esophagus diseases, to adapt it for clinical conditions, i.e. for conducting differential diagnosis and detecting precancer conditions, and to formulate recommendations on the best photosensitizer doses and time of application in order to make the diagnostic procedure for these diseases more accurate. Materials and Methods. Registration of fluorescence for diagnostic purposes was performed on 57 patients with gastropathology (mainly with stomach cancer) with the help of single-channel (n=50) and dual-channel (n=7) laser video fluorescence registration systems. The study was performed using 5-aminolevulinic acid (5-ALA) (Alasens). 39 endoscopic, 18 intraoperative/laparoscopic investigations, and 7 studies on the macropreparation have been performed. Results. When both systems were used, no fluorescence was registered in cases of stomach ulcer, chronic gastritis, massive tumor necrosis and blood admixture in the stomach as well as in the patient with subcompensated stenosis and a stented output section of the stomach without serous membrane invasion and low 5-ALA concentration. In all other cases, a distinct fluorescence was recorded, the data of which may be used for establishing exact diagnosis and choosing further treatment tactics. Conclusion. Laser video fluorescence technique is a promising method for differential diagnosing and definition of the tumor extension process in the stomach and esophagus which can be used as an express method in diagnostically complex cases.

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