Sporadic pancreatic neuroendocrine neoplasms : A retrospective clinicopathological and outcome analysis from a Latvian study group

Publisher Copyright: 2023 Ptasnuka, Truskovs, Ozolins, Narbuts, Sperga and Plaudis.BACKGROUND: Although pancreatic neuroendocrine neoplasms (PNEN) are rare, there has been a constant increase in incidence. Furthermore, PNEN present unique clinical behaviors and long-term survival can be expected even in the presence of metastases as compared with ductal adenocarcinoma of the pancreas. Determining the best therapeutic approach and proper timing of therapy requires knowledge of reliable prognostic factors. Therefore, the aim of this study was to explore clinicopathological features, treatment, and survival outcomes of patients with PNEN based on Latvian gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) registry data. METHOD: Patients with confirmed PNEN at Riga East Clinical University Hospital and Pauls Stradins Clinical University Hospital, between 2008 and 2020, were retrospectively analyzed. Data were collected and included in EUROCRINE, an open-label international endocrine surgical registry. RESULTS: In total, 105 patients were included. The median age at diagnosis was 64 years (IQR 53.0-70.0) for males and 61 years (IQR 52.5-69.0) for females. In 77.1% of patients, tumors were hormonally nonfunctional. Among those with functioning PNEN, 10.5% of patients presented with hypoglycemia and were diagnosed with insulinoma, 6.7% of patients presented with symptoms related to carcinoid syndrome; 30.5% of patients showed distant metastases at the time of diagnosis, and surgery was performed in 67.6% of patients. Notably, for five patients with nonfunctional PNEN <2 cm, a "watch and wait" approach was used; none of the patients developed metastatic disease. The median length of hospital stay was 8 days (IQR 5-13). Major postoperative complications were found in 7.0% of patients, and reoperation was conducted for 4.2% of patients, due to postpancreatectomy bleeding (2/71) and abdominal collection (1/71). The median follow-up period was 34 months (IQR 15.0-68.8). The OS at the last follow-up was 75.2% (79/105). The observed 1-, 5- and 10-year survival rates were 87.0, 71.2 and 58.0, respectively. Seven of the surgically treated patients had tumor recurrence. The median time of recurrence was 39 months (IQR 19.0-95.0). A univariable Cox proportional hazard analysis provided evidence that a nonfunctional tumor, a larger tumor size, the presence of distant metastases, a higher tumor grade, and the tumor stage were strong, negative predictors of OS. CONCLUSION: Our study represents the general trends of clinicopathological features and treatment of PNEN in Latvia. For PNEN patients, tumor functionality, size, distant metastases, grade, and stage may be useful to predict OS and must be confirmed in further studies. Furthermore, a "surveillance" strategy might be safe for selected patients with small asymptomatic PNEN.publishersversionPeer reviewe

Sporadic pancreatic neuroendocrine neoplasms: A retrospective clinicopathological and outcome analysis from a Latvian study group

BackgroundAlthough pancreatic neuroendocrine neoplasms (PNEN) are rare, there has been a constant increase in incidence. Furthermore, PNEN present unique clinical behaviors and long-term survival can be expected even in the presence of metastases as compared with ductal adenocarcinoma of the pancreas. Determining the best therapeutic approach and proper timing of therapy requires knowledge of reliable prognostic factors. Therefore, the aim of this study was to explore clinicopathological features, treatment, and survival outcomes of patients with PNEN based on Latvian gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) registry data.MethodPatients with confirmed PNEN at Riga East Clinical University Hospital and Pauls Stradins Clinical University Hospital, between 2008 and 2020, were retrospectively analyzed. Data were collected and included in EUROCRINE, an open-label international endocrine surgical registry.ResultsIn total, 105 patients were included. The median age at diagnosis was 64 years (IQR 53.0–70.0) for males and 61 years (IQR 52.5–69.0) for females. In 77.1% of patients, tumors were hormonally nonfunctional. Among those with functioning PNEN, 10.5% of patients presented with hypoglycemia and were diagnosed with insulinoma, 6.7% of patients presented with symptoms related to carcinoid syndrome; 30.5% of patients showed distant metastases at the time of diagnosis, and surgery was performed in 67.6% of patients. Notably, for five patients with nonfunctional PNEN &lt;2 cm, a “watch and wait” approach was used; none of the patients developed metastatic disease. The median length of hospital stay was 8 days (IQR 5–13). Major postoperative complications were found in 7.0% of patients, and reoperation was conducted for 4.2% of patients, due to postpancreatectomy bleeding (2/71) and abdominal collection (1/71). The median follow-up period was 34 months (IQR 15.0–68.8). The OS at the last follow-up was 75.2% (79/105). The observed 1-, 5- and 10-year survival rates were 87.0, 71.2 and 58.0, respectively. Seven of the surgically treated patients had tumor recurrence. The median time of recurrence was 39 months (IQR 19.0–95.0). A univariable Cox proportional hazard analysis provided evidence that a nonfunctional tumor, a larger tumor size, the presence of distant metastases, a higher tumor grade, and the tumor stage were strong, negative predictors of OS.ConclusionOur study represents the general trends of clinicopathological features and treatment of PNEN in Latvia. For PNEN patients, tumor functionality, size, distant metastases, grade, and stage may be useful to predict OS and must be confirmed in further studies. Furthermore, a “surveillance” strategy might be safe for selected patients with small asymptomatic PNEN

Immunohistochemical expression of HBME-1, E-cadherin, and CD56 in the differential diagnosis of thyroid nodules

Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background and Objective. Distinction between benign and malignant thyroid tumors is essential for proper clinical management. The aim of this study was to evaluate the diagnostic potential of a set of 3 molecular markers in the differential diagnosis of thyroid tumors. Material and Methods. Immunohistochemistry for HBME-1, E-cadherin (E-CAD), and CD56 was carried out in 36 follicular adenomas, 77 colloid goiters, 36 papillary thyroid carcinomas, and 14 follicular carcinomas. Sixty-eight thyroid fine needle aspiration(FNA) cases confirmed by subsequent surgical resection specimens were selected. Immunocytochemistry for HBME-1, E-CAD, and CD56 was performed in these cases, including 25 papillary thyroid carcinomas, 1 follicular carcinoma, 22 follicular adenomas, and 20 colloid goiters. Results. PTC was characterized by a decreased expression of E-CAD and CD56 contrary to the surrounding benign thyroid tissues. There was no HBME-1 expression in benignthyroid tissues, but it was high in papillary thyroid carcinomas and weak in follicular adenomas. The expression of E-CAD and CD56 was significantly higher in follicular adenomas than in the surrounding thyroid tissues. Analyzing the FNA material, HBME-1 expression was documented in 96% of papillary thyroid carcinomas, but there was no expression in the benign lesions. E-CAD and CD56 expression was significantly weakened in papillary thyroid carcinomas, but enhanced in follicular adenomas. Conclusions. HBME-1 was found only in malignant lesions and can be considered the most sensitive, specific single marker in papillary thyroid carcinomas. CD56 and E-CAD can assist in the decision-making on thebenign and malignant nature of the nodule. Immunocytochemistry is of value as an ancillary test to enhance the diagnostic accuracy of thyroid FNA samples.publishersversionPeer reviewe

Can We Predict Differentiated Thyroid Cancer Behavior? : Role of Genetic and Molecular Markers

Funding Information: Funding: This work was supported by Riga Stradins University Grant to Non-invasive diagnostic and predictive biomarkers for bladder tumor early diagnosis and prediction. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Thyroid cancer is ranked in ninth place among all the newly diagnosed cancer cases in 2020. Differentiated thyroid cancer behavior can vary from indolent to extremely aggressive. Currently, predictions of cancer prognosis are mainly based on clinicopathological features, which are direct consequences of cell and tissue microenvironment alterations. These alterations include genetic changes, cell cycle disorders, estrogen receptor expression abnormalities, enhanced epithelial-mesenchymal transition, extracellular matrix degradation, increased hypoxia, and consecutive neovascularization. All these processes are represented by specific genetic and molecular markers, which can further predict thyroid cancer development, progression, and prognosis. In conclusion, evaluation of cancer genetic and molecular patterns, in addition to clinicopathological features, can contribute to the identification of patients with a potentially worse prognosis. It is essential since it plays a crucial role in decision-making regarding initial surgery, postoperative treatment, and follow-up. To date, there is a large diversity in methodologies used in different studies, frequently leading to contradictory results. To evaluate the true significance of predictive markers, more comparable studies should be conducted.Peer reviewe

Validity of multiplex biomarker model of 6 genes for the differential diagnosis of thyroid nodules

<p>Abstract</p> <p>Background</p> <p>Currently the cytological examination of fine needle aspiration (FNA) biopsies is the standard technique for the pre-operative differential diagnosis of thyroid nodules. However, the results may be non-informative in ~20% of cases due to an inadequate sampling and the lack of highly specific, measurable cytological criteria, therefore ancillary biomarkers that could aid in these cases are clearly needed. The aim of our study was to evaluate the mRNA expression levels of 8 candidate marker genes as the diagnostic biomarkers for the discrimination of benign and malignant thyroid nodules and to find a combination of biomarkers with the highest diagnostic value.</p> <p>Materials and methods</p> <p>mRNA expression levels of eight candidate marker genes - <it>BIRC5, CCND1, CDH1, CITED1, DPP4, LGALS3, MET </it>and <it>TFF3 </it>was measured by real-time RT-PCR in paired nodular and surrounding normal thyroid tissue specimens of 105 consecutive patients undergoing thyroid surgery and compared between different types of thyroid lesions.</p> <p>Results</p> <p>Significant differences in the mRNA expression levels between the normal and malignant thyroid tissues and between benign and malignant nodules were found for <it>BIRC5, CCND1, CITED1, DPP4, LGALS3, MET </it>and <it>TFF3</it>, but not <it>CDH1</it>. On a single gene basis, relative quantity (RQ) of <it>LGALS3 </it>had the highest diagnostic value for the discrimination of malignant and benign thyroid nodules (AUC = 0.832, P < 0.0001 and 90.9% sensitivity and 65.6% specificity at the optimal cut-off on ROC curve). The only two-marker set that outperformed <it>LGALS3 </it>was RQ sum of <it>LGALS3 </it>and <it>BIRC5 </it>(AUC = 0.841, P < 0.0001). An application of multivariate logistic regression analysis resulted in the generation of a multiplex biomarker model based on <it>LGALS3, BIRC5, TFF3, CCND1, MET </it>and <it>CITED1 </it>that had considerably higher specificity than a single marker or two marker gene-based models (AUC = 0.895, P < 0.0001, 70.5% sensitivity and 93.4% specificity).</p> <p>Conclusions</p> <p>This study confirmed that mRNA expression levels of 7 out of 8 candidate genes analysed have a diagnostic value for the distinction of benign and malignant thyroid nodules. The multiplex biomarker model based on 6 genes outperformed a single marker or two marker-based models and warrants feasibility studies on FNA biopsies and the validation in a larger cohort of patients.</p

Large Parathyroid Tumor 8 Years after Thyroid Surgery : A Case Report

Funding Information: This case report was funded by the Fundamental and Useful Research Project (FLPP) within the project “Multiparametric ultrasound correlation with morphology in patients with primary hyperparathyroidism [Nr. lzp-2020/2-0297].” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 S. Karger AG. All rights reserved.This report represents an unusually large parathyroid carcinoma (PC) mimicking thyroid nodule recurrence after hemithyroidectomy. PC is a rare endocrine malignancy accounting for less than 1% of hyperparathyroidism cases. This is the first case report where contrast-enhanced ultrasound (CEUS) was performed on a PC. A 63-year-old female presented with an enlarged mass on the left side of the neck. In 2012, left-side hemithyroidectomy was done due to a benign goiter. In 2020, laboratory analysis showed markedly elevated parathyroid hormone and calcium. Multiparametric neck ultrasonography was performed including B-mode, color Doppler, shear wave elastography, and CEUS. Computed tomography revealed an irregular mass in proximity to the trachea, esophagus, and dislocation of the common carotid artery. Perifocal fatty tissue appeared normal. Scintigraphy displayed a suspected parathyroid tumor or a suspected left lobe nodule of thyroid. Based on the biochemical diagnosis of primary hyperparathyroidism and radiological examinations, a suspected parathyroid tumor was considered. Intraoperative findings demonstrated an unusually large 9 × 6 cm tumor (84 g) adjacent to the common carotid artery anterolaterally and the recurrent laryngeal nerve medially. Pathohistological examination revealed a tumor solid in structure, with focal necrosis penetrating the capsule. Immunohistochemical analysis was positive for chromogranin, CD56, and Ki-67 (8–10%) and negative for CK20 and CK7. The morphological and immunohistochemical results correspond to PC. PC is a challenging diagnosis requiring a multidisciplinary approach, especially in the case of previous neck surgery. The only curative treatment for PC is radical surgery. Lifelong monitoring of PCs is mandatory due to the high recurrence rate.publishersversionPeer reviewe

Contrast-Enhanced Ultrasound Qualitative and Quantitative Characteristics of Parathyroid Gland Lesions

Funding Information: Funding: This research received funding from Latvian Science Funding, project number Izp-2020/2-0297, Multiparametric ultrasound correlation with morphology in patients with primary hyperparathyroidism. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background and Objectives: preoperative differentiation of enlarged parathyroid glands may be challenging in conventional B-mode ultrasound. The aim of our study was to analyse qualitative and quantitative characteristics of parathyroid gland lesions, using multiparametric ultrasound protocol—B-mode, Colour Doppler (CD), and contrast-enhanced ultrasound (CEUS)— and to evaluate correlation with morphology in patients with hyperparathyroidism (HPT). Materials and Methods: consecutive 75 patients with 88 parathyroid lesions and biochemically confirmed HPT prior to parathyroidectomy were enrolled in the prospective study. B-mode ultrasound, CD, and CEUS were performed with the subsequent qualitative and quantitative evaluation of acquired data. We used 1 mL or 2 mL of intravenous ultrasound contrast agent during the CEUS examination. Correlation with post-surgical morphology was evaluated. Results: seventy parathyroid adenomas were hypoechoic and well contoured with increased central echogenicity (44.3%), peripheral-central vascularization (47%), and polar feeding vessel (100%). Twelve hyperplasias presented with similar ultrasound appearance and were smaller in volume (p = 0.036). Hyperplasias had a tendency for homogenous, marked intense enhancement vs. peripherally enhanced adenomas with central wash-out in CEUS after quantitative analysis. No significant difference was observed in contrasting dynamics, regardless of contrast media volume use (1 mL vs. 2 mL). We achieved 90.9% sensitivity and 72.7% specificity, 93% positive predictive value (PPV), 87.3% negative predictive value (NPV), and 87.3% accuracy in the differentiation of parathyroid lesions prior to post-processing. In a quantitative lesion analysis, our sensitivity increased up to 98%, specificity 80%, PPV 98%, and NPV 80% with an accuracy of 96.4%. Conclusions: CEUS of parathyroid lesions shows potential in the differentiation of adenoma from hyperplasia, regardless of the amount of contrast media injected. The quantitative analysis improved the sensitivity and specificity of differentiation between parathyroid lesions. Hyperplasia was characterized by homogeneous enhancement, fast uptake, and homogeneous wash-out appearance; adenoma—by peripheral uptake, central wash-out, and reduced hemodynamics. The use of CEUS quantification methods are advised to improve the ultrasound diagnostic role in suspected parathyroid lesions.publishersversionPeer reviewe

Immunohistoc.hemical Expression of HBME-1, E-cadherin, and CD56 in the Differential Diagnosis of Thyroid Nodules

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