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Introduction: The development of new highly accurate, inexpensive and accessible methods for the detection of lower-extremity peripheral artery disease (LE-PAD) in diabetic patients is required. The aim of this study was to evaluate the accuracy of a new incoherent optical fluctuation flowmetry (IOFF) method in detecting legs with hemodynamically significant stenoses compared to ankle brachial index (ABI) and transcutaneous oximetry (TcPO2) in patients with diabetes mellitus (DM)., Materials and Methods: Patients were recruited into 2 groups. Group 1 included patients with DM without LE-PAD and/or diabetic foot syndrome; Group 2 included patients with DM and LE-PAD. All patients underwent the following measurements: ultrasound (reference method), ABI, TcPO2, and the new IOFF method., Results: The new IOFF method showed a sensitivity of 79.5% and a specificity of 89.8% in detecting limbs with hemodynamically significant stenosis (AUC 0.890, CI 0.822-0.957). TcpO2 allows the diagnosis of LE-PAD with 69.2% sensitivity and 86.2% specificity (AUC 0.817, CI 0.723-0.911). Using a standard ABI cut-off of less than 0.9, the sensitivity and specificity for this parameter were 34.5% and 89.7%, respectively. Increasing the diagnostic cut-off of the ABI on the study group to 0.99 improved sensitivity to 84.6% and specificity to 78% (AUC,0.824 CI 0.732-0.915)., Conclusions: The new IOFF technique has demonstrated high sensitivity and specificity in the detection of LE-PAD in patients with DM. The high accuracy, rapid measurement, and potential availability suggest that the new IOFF method has a high potential for clinical application in the detection of PAD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(1) Background: To date, there are no studies evaluating the ability of the incoherent optical fluctuation flowmetry (IOFF) method to assess foot tissue perfusion. The aim of this study was to evaluate the correlation between perfusion values measured by IOFF and TcPO2 in patients with diabetes-related lower-extremity complications. (2) Methods: This was an observational, cross-sectional, two-center study. Diabetic patients with peripheral artery disease and/or diabetic foot ulcers were studied (n = 27, examinations were carried out on 54 legs). Perfusion in the foot tissues was assessed using TcPO2 (reference standard for this study) and the IOFF method. (3) Results: High correlation coefficients of all perfusion parameters measured by IOFF with TcPO2 (Rs 0.7 to 0.76) were shown. The study demonstrated that the IOFF method allows, with a sensitivity of 85.7% and a specificity of 90.0%, the identification of patients with a critical decrease in TcPO2 < 20 mmHg. (4) Conclusions: The high correlation of IOFF parameters with TcPO2 and the moderately high sensitivity and specificity in detecting patients with severe ischemia of foot tissues shows the promise of the method for assessing a tissue perfusion in patients with diabetes-related lower-extremity complications.

Introduction: Pancreatic tumors (PT) usually occur after age 60 and almost never in children and young patients (pts). Little is known concerning frequency, morphological and immunohistochemical (IHC) characteristics of PTs in children and young pts. Aim(s): To assess the incidence and prevalence of PT in children and young pts. Materials and methods: five-hundred and forty-eight PTs were verified by IHC, including 358 neuroendocrine neoplasms (pNEN), 53 solid-pseudopapillary (SPT), 129 ductal tumors, and eight other types of PT. 98 (17.8%) of these pts were at the age of 2 to 30 yrs. Results: pNEN were identified in 61.2% (60198) young pts: 32 female, 28 male, at mean age of 21.6 (2-30) yrs. pNENs in 10% pts (6/60) were malignant and sporadic with regional or distant metastases. Four of them at age of 11, 16, 16, 28 yrs with two insulinomas, gastrinoma and somatostatinoma died within 2-5 years because of disease progression. Fifty-one pts presented with hypoglycemia, four - Zollinger-Ellison syndromes (SM). The other cases had nonfunctioning pNENs. Sixteen (26.7%) of 60 pts with pNENs had hereditary SM: 13 (21.7%) - MEN-1, two - VHL, one - tuberous sclerosis. Nine (69.2%) of 13 MEN-1 pts had multiple (2 to 8) pNENs. SPT were identified in 35.7% (35198) young pts and mainly occurred in young females (F/M ratio=1:7.8), at mean age of 17.6 (9-30) years. No SPT had signs of malignancy. Conclusion: Predominant types of pancreatic tumors in children and young pts are pNEN and SPT. Young pts with MEN-1 syndrome often have multiple pNENs. [ABSTRACT FROM AUTHOR]

Introduction: Defining localization and potential ACTH-producing extrapituitary neuroendocrine neoplasms (ACTH-epNEN) is important for clinical practice. Aim(s): To assess CK19 expression in ACTH-epNEN of different localization. Materials and methods: CK19 (clone RCK108) and Ki-67 (clone MIB-1) expression were evaluated immunohistochemically (IHC) in 37 ACTH-epNEN specimens: 19 lung (L-NEN) (51.3%); eight thymus (T-NEN) and two mediastinal (M-NEN) (27.2%); six gastrointestinal (GI): three pancreatic (Pn-NEN), one ampulla Vater's (AV-NEN), one appendical (A-NEN), one rectal (R-NEN) (16.2%); two medullary thyroid carcinomas (MTC) (5.4%); in 13 men and 25 women, at mean age 42.1 (16-67 yrs). Results: Clinical presentation of ACTH-ectopic syndrome was diagnosed in 30 (81.1%) patients (pts) at early stage, in three (8.1%) pts at late stage of the disease (Pn-NEN, AV-NEN, R-NEN). Four tumors (10.8%) were asymptomatic (2 L-NEN, Pn-NEN, M-NEN). Twenty of 37 (54.1%) ACTH-epNEN had CK19 expression: in 9/10 T-NEN and M-NEN (90%), 2/2 MTC (100%), 4/6 GI-NEN (66.7%) and 5/19 L-NEN (26.3%). All CK 19-positive ACTH-epNENs of GI and thyroid, mediastinum, thymus and three tumors of the lung were malignant (with metastases or recurrences). We got a strong correlation between CK19 expression in ACTH-epNE and an increased level of Ki-67 (Spearman r=0,75, p<0.001). Conclusion: CK19 expression in ACTH-epNEN is an important criteria for malignancy potential. Especially for L-NEN, this can be used to predict recurrence and metastases. [ABSTRACT FROM AUTHOR]

Introduction: Aim(s): To compare the clinical manifestations of the various causes of hypoglycemia and determine biochemical and instrumental predictors of the severity of hypoglycemia. Materials and methods: Thirty patients with complaints similar to hypoglycemia referred to our clinic over the past 10 years. Twenty-four of them - 18 women, six men, the average age - 43 years. A 72-hour fasting test and imaging methods were performed on all patients. Results: In only 15 patients was insulinoma confirmed (Group A). The remaining 15 patients (Group B) revealed other causes of hypoglycemia (gastrointestinal diseases - six patients, functional hypoglycemia - three liver failure, two anorexia nervosa, one affective disorders, one inadequate treatment of diabetes mellitus. There were no differences by gender and age between groups. Group A patients were more likely to have convulsions, coma, difficulty awaking in the morning (p<0.05). The duration of the fasting test was: in Group A - less than 24 hours (from 4 to 22 hours), in Group B -72 hours. In Group A, the test was stopped because of severe hypoglycemia symptoms (glucose-1.46 mmol / I), and in Group B - because there were no symptoms and no hypoglycemia for 72 hours. We did not find a reliable correlation between the test duration and the tumor size or C-peptide. Conclusion: In patients with insulinomas, symptoms of hypoglycemia were more severe. The lack of correlation between clinical manifestations and hypoglycemia and characteristics of the tumor were probably associated with a small number of patients. [ABSTRACT FROM AUTHOR]

Introduction: A 39 y.o. man with renal insufficiency (GFR 34 ml/min) due to autosomal-dominant polycystic disease (in the liver and kidney) and ACTH-ectopy (AES). Aim(s): Materials and methods: Results: The first signs of hypercortisolism were only high blood pressure. Suspected kidney disease. Hypercortisolism symptoms gradually progressed and steroid diabetes mellitus and osteopenia diagnosed. AES suspected (HDDST - negative, 23.00 ACTH -20.2 pmol / 1 (N<5), pituitary MRI-normal, CT-scan -- thymic lesion found). The potassium level was on upper limit of normal probably because of kidney disease. BIPSS with desmopressin stimulation confirmed AES (Pit/Perif gradient of ACTH<3). CgA and tumormarkers were in normal ranges. Thymectomy performed. Histologically it was thymic cyst without ACTH-secreting cells. Ketokonazol was prescribed. Colonoscopy, pituitary MRI, CT chest and abdomen, bronchoscopy revealed no tumor six months thereafter. Because of hypercortisolism progression unilateral adrenalectomy was done. Immunohistochemically the adrenal medulla cells were positive for synaptophysin, CgA and ACTH. Annual examination failed to reveal any tumor. He is on ketokonazol (600 mg/d) now. No signs of hypercortisolism and no diabetes melitus. Conclusion: The source of AES is still unknown. But the hypercortisolism is well-controlled by ketokonazol. [ABSTRACT FROM AUTHOR]

Simple Summary: Individualized diagnostics approaches in modern cancer therapy require predictive and prognostic biomarkers that are easily accessible and stratify patients for optimal and individualized treatment. Pancreatic ductal adenocarcinoma (PDAC) is still a life-threatening disease mainly because of its late diagnosis in advanced stages or rapid progress even in patients with curative resection of the primary tumor. Moreover, patients with liver metastases exhibit an even worse prognosis. Hence, this retrospective multi-center study aims to identify biomarkers in perioperative serum of PDAC patients predicting early liver metastasis. A highly sensitive biomarker analysis was performed using two different methodological approaches. Olink® analysis, which was also used to validate LEGENDplexTM results, identified significant differences in proteins involved in chemotaxis and migration of immune cells as well as cell growth in serum of patients with early versus late onset of liver metastasis. Further studies with larger cohorts are required to validate these findings for clinical translation. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with poor survival rates. Only 20% of the patients are eligible for R0-surgical resection, presenting with early relapses, mainly in the liver. PDAC patients with hepatic metastases have a worse outcome compared to patients with metastases at other sites. Early detection of hepatic spread bears the potential to improve patient outcomes. Thus, this study sought for serum-based perioperative biomarkers allowing discrimination of early (EHMS ≤ 12 months) and late hepatic metastatic spread (LHMS > 12 months). Serum samples from 83 resectable PDAC patients were divided into EHMS and LHMS and analyzed for levels of inflammatory mediators by LEGENDplexTM, which was validated and extended by Olink® analysis. CA19-9 serum levels served as control. Results were correlated with clinicopathological data. While serum CA19-9 levels were comparable, Olink® analysis confirmed distinct differences between both groups. It revealed significantly elevated levels of factors involved in chemotaxis and migration of immune cells, immune activity, and cell growth in serum of LHMS-patients. Overall, Olink® analysis identified a comprehensive biomarker panel in serum of PDAC patients that could provide the basis for predicting LHMS. However, further studies with larger cohorts are required for its clinical translation. [ABSTRACT FROM AUTHOR]

Abstracts from the 13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease held in Barcelona, Spain on March 9-11 2016 are presented including "Are elFs Ingredients for Neuroendocrine Tumorigenesis?" by N. Gantenbein and colleagues, "The MEN2B Due to de Novo Mutation M918T at Algiers" by A. Chikouche and "Neuroendocrine Cancer Patient Experience Survey" by C. Bouvier and colleagues.

Introduction: Bronchial carcinoids (BCs), originating from endocrine cells dispersed in the respiratory epithelium, can be divided into typical (TBC) and atypical (ABC). TBC are less aggressive, smaller, and much less likely to metastasize, while ABC are more aggressive and metastasize, roTOR has a central role in regulating cell growth, metabolism, and apoptosis. A differential roTOR activation in BCs has been previously demonstrated, suggesting that mTOR pathway might play a predictive role in patients eligible for mTOR-targeted therapies. Aim(s): To evaluate the effects of roTOR inhibitors on human BCs cell lines. Materials and methods: NCIH720 (ABC) and NCIH727 (TBC) cells were treated with Everolimus or with NVP-BEZ 235, a dual PI3K/mTOR inhibitor. Cell viability, caspase activity and cell cycle progression were evaluated after 72 h. Results: Everolimus inhibits cell viability in both cell lines with more pronounced effects on NCIH720, does not activate apoptosis but determines G1/G0 accumulation. NVPBEZ235 had similar effects to Everolimus in terms of cell viability in NCIH727, but was more potent in NCIH720 cells. Caspase activity was not induced by NVP-BEZ 235 in NCIH727, but was enhanced in NCIH720. Western blot and Q-PCR were performed to assess whether this differential effect is due to variations in roTOR expression in BCs cell lines, mTOR expression is 1.5-fold higher in NCIH720 compared to NCIH727. Conclusion: These data demonstrate that mTOR inhibitors affect BCs cell lines differently depending on mTOR expression. [ABSTRACT FROM AUTHOR]

The article presents abstracts presented at the 9th Annual European Neuroendocrine Tumor Society (ENETS) Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, including "Expression of UCH-L1 in PETs and Its Implications," "Activation of Hedgehog Pathway in Neuroendocrine Tumor," and "Alterations of Global and Gene-Specific DNA Methylation in Midgut Carcinoids."

Abstracts of studies presented at the 8th Annual ENETS Conference for the diagnosis and treatment of neuroendocrine tumor disease are presented, including "Chromogranin B is a Prognostic Marker in NETs," "A Novel Missense Mutation of the TMEM127 Gene That Leads to Pheochromocytoma Phenotype" and "Challenges in the Management of VIPoma Patients."

An author index for the journal "Neuroendocrinology" is presented.

The article presents abstracts of medical topics which include the clinical-morphology correlation in diagnostics and evaluation of surgery results of pancreatic insulinoma and nesidiobastosis, the transarterial chemoembolization (TACE) of liver metastasis from pancreatic well-differentiated endocrine carcinoma, and the somatostatin receptors 1-5 expression in a large series of well-differentiated neuroendocrine tumors.

In the period from 2013 to 2015 the 2-clinic of Tashkent Medical Academy for examination and treatment were 46 patients with adrenal tumors. Simultaneous operations were performed in 6 patients, of whom 4 women and 2 men. A morphological study of adrenal tumors, we found: 2 -- aldosteroma (33.3%), 1 -- pheochromocytoma (16.6%), 1 -- adrenal cyst (16.6%), 2 -- cortex adenoma (33.3%). Of these, 50% patients were with intsidentaloma (2 cortical adenoma and 1 adrenal cyst). Indications for simultaneous operations were a combination of adrenal tumors with cholelithiasis and umbilical hernia. At the same time in 4 (66.6%) patients simultaneously conducted operations -- right-sided laparoscopic adrenalectomy, and laparoscopic cholecystectomy, in 1 patient (16.6%) -- a left laparoscopic adrenalectomy and laparoscopic cholecystectomy and 1 (16.6%) patient's after adrenalectomy surgery hernia repair is made to the type of allopath «on lay». In postoperative period complications were not observed. On the next day after surgery drains removed and all patients are activated. Average bed day was 4 ± 1.71. Thus, the analysis of these patients treatment results showed that the duration of surgery and hospital stay do not differ from similar parameters specific to patients with isolated surgical pathology. Treatment simultaneously several surgical diseases liquidate of need for repeated operations and its risk of possible complications. All of the above underscores the feasibility and cost-effectiveness of performing simultaneous operations in patients with concomitant surgical pathology. [ABSTRACT FROM AUTHOR]

Objective: Fas is a cell-surface receptor responsible for induction of apoptosis in human thyrocytes upon interaction with Fas Ligand. Fas protein expression on thyroid cells and Fas-mediated apoptosis is decreased in multinodular goiter (MNG) resulting in thyroid cell proliferation. The soluble form of Fas (sFas) produced by alternative mRNA splicing may inhibit Fas-Fas Ligand binding and apoptosis. The aim of this study was to examine whether sFas is differentially expressed in multinodular goiter (MNG), which is associated with decreased Fas-mediated apoptosis. Method: We determined serum sFas levels using enzyme-linked immunosorbent assay (ELISA) in 42 patients with MNG and 23 normal controls. Results: Serum sFas levels were increased in patients with MNG (7.47 ± 2.55 ng/ml) compared to normal controls (2.26 ± 0.9 ng/ml). Levels of sFas were not significantly correlated with age, sex or clinical parameters, such as serum levels of FT4 or TSH. Discussion: Increased sFas in MNG may indicate increased expression of alternatively spliced Fas mRNA variant and decreased expression of cell-surface Fas protein, and may enhance thyroid cell proliferation by protecting thyroid cells from Fas-mediated apoptosis. [ABSTRACT FROM AUTHOR]