The Epidemiological and Clinical Findings from the Latvian Registry of Primary Congenital Glaucoma and Evaluation of Prognostic Factors.

Background and objectives: primary congenital glaucoma (PCG) is a rare, potentially blinding disease that affects children worldwide. The aim of the study was to describe the epidemiological and clinical characteristics, outcomes for newly diagnosed patients with PCG, as well as evaluate the prognostic factors that are related to the outcomes. Materials and Methods: a retrospective cohort study was conducted at a tertiary referral centre among patients diagnosed with PCG. Evaluation of the clinical data was performed preoperatively at three, six, and 12 months after the surgery and at the last follow-up. Results: during the 15 years of follow-ups, 24 eyes of 18 patients were diagnosed with PCG. Unilateral and bilateral PCG constituted 50% of cases each. A slight male predominance was observed (55.6% vs. 44.4%), with a relative risk of 1.3. The incidence of PCG was 1:19,033 live births. The mean age of the patients at the time of diagnosis was 10.1 ± 10.0 months, with a diagnostic delay of 2.0 ± 1.9 months. Furthermore, 75% of patients indicated an enlargement of an eyeball, followed by excessive tearing (58.3%) and corneal opacity (41.7%). After 85.9 ± 51.2 months, the mean intraocular pressure (IOP) value was 14.6 ± 4.9 mmHg. Surgical treatment provided sufficient IOP control in 75% of PCG cases at the last follow-up visit. The only prognostic factor that was related to the outcome of IOP control that was statistically significant was axial length at the time of diagnosis. Conclusions: the incidence of PCG in Latvia was 5.3 patients per 100,000 live births. PCG was more common among males than females with a relative risk of 1.3. The enlargement of an eyeball was the leading clinical sign.

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

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.

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

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.

Epidemiological Data and Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: Insights From Tertiary Referral Hospitals in Latvia.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are rare, heterogeneous group which tend to rise in incidence. Epidemiological profile and outcomes of GEP-NEN may vary among countries. The aim of study was to provide baseline clinical and histopathological features of patients with GEP-NEN from tertiary referral hospitals in Latvia. METHODS: A retrospective study of patients with histologically confirmed diagnosis of GEP-NEN treated between 2006 and 2018. Joinpoint regression modeling was used to estimate annual percentage change (APC) for incidence trends. Overall survival (OS) rate was obtained by Kaplan-Meier method. RESULTS: In total, 205 patients were included. The median age at diagnosis was 61.0 (IQR 52.0-70.5) years, 69.3% were females. The age-adjusted incidence per 100 000 inhabitants increased from 0.03 in 2006 to 0.67 in 2018 with APC of 24.1%, p < 0.005. The most common primary tumor site was pancreas (30.7%), followed by stomach (24.9%) and small intestine (20.5%). Non-functional tumors are present in 83.4%, while carcinoid syndrome in 7.8%. Stage IV metastatic disease was present in 27.8% tumors. The majority of patients (82%) received an operation with radical or palliative intent. The 1- and 3-year OS rate were 88.0% (95% CI 83.3-92.7) and 77.1% (95% CI 70.4-83.8), respectively. Increasing tumor grade, stage and the presence of distant metastases were associated with significantly worse OS. CONCLUSION: Our study highlights increasing incidence of GEP-NEN in Latvia. The most common primary site was pancreas and surgery considered as main modality of treatment. Registry and long-term data collection are necessary to develop GEP-NEN management concept in Latvia.

Evaluation of malignant parathyroid tumours in two European cohorts of patients with sporadic primary hyperparathyroidism.

PURPOSE: Parathyroid carcinoma (PC) is remarkable for its rare occurrence and challenging diagnostics. PC accounts for 0.1-5 % cases of primary hyperparathyroidism (PHPT). The differentiation from benign tumours is difficult even by morphological criteria. To address these issues, we assessed the PC frequency in two separate European PHPT cohorts and evaluated the demographic, clinical, morphological and molecular background. METHODS: A retrospective study was carried out, using continuously maintained database (2005-2014) of PHPT patients from two tertiary referral university hospitals in Europe. The demographic, clinical data and frequency of PC among surgically treated PHPT was detected. Immunohistochemistry (IHC) was performed to detect parafibromin, representing protein product of HRPT2 gene and proliferation marker Ki-67. RESULTS: Both PHPT cohorts were characterised by close mean age values (58.6 and 58.0 years) and female predominance. The frequency of PC differed significantly between the cohorts: 2.1 vs. 0.3 %; p = 0.004. PC was characterised by invariable complete loss of parafibromin contrasting with parathyroid adenomas. The proliferation fraction was similar in both PC cohorts (10.6 and 11.0 %). PC showed significantly higher proliferation fraction than typical parathyroid adenomas (1.6 %), atypical adenomas (1.6 %) or adenomas featuring focal loss of parafibromin (2.2 %). CONCLUSIONS: PC frequency can range significantly between the two European cohorts. The differences can be attributable to selection bias of patients referred for surgery and are not caused by discordant definition of malignant parathyroid histology. Diffuse loss of parafibromin and increased proliferation fraction by Ki-67 are valuable adjuncts in PC diagnostics due to significant differences with various clinical and morphological subtypes of adenoma.

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

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.

Neuroendocrine Carcinoma of the Extrahepatic Bile Ducts: A Case Report.

BACKGROUND Neuroendocrine tumors (NETs) primarily originating from the extrahepatic biliary (EB) tree are a medical rarity, accounting for less than 100 recorded instances globally. This case report outlines an encounter with this uncommon condition, demonstrating the complexities of diagnosis and management. CASE REPORT A 42-year-old woman presented at our Emergency Department with a 3-week history of itching and symptoms of obstructive jaundice. Initial laboratory tests showed hyperbilirubinemia and elevated liver transaminases. Abdominal ultrasonography indicated choledocholithiasis. Magnetic resonance imaging suggested either Mirizzi syndrome or a proximal common bile duct neoplasm. Abdominal computed tomography showed cholestasis, suggesting choledocholithiasis or cholangiocarcinoma (type-1). An endoscopic retrograde cholangiopancreatography with biliary and pancreatic duct stenting was performed for drainage, with brush cytology confirming adenocarcinoma. The patient was referred for surgical resection of the bile duct tumor, involving extrahepatic bile duct resection, en bloc cholecystectomy, lymphadenectomy, Roux-en-Y anastomosis, and biliary drainage. Histopathology identified a neuroendocrine carcinoma. Following surgery, the patient underwent eight cycles of FOLFOX6 chemotherapy, with no disease relapse post-treatment. CONCLUSIONS This case emphasizes multidisciplinary teamwork importance in managing rare diseases like EB bile duct NETs. These tumors' rarity and symptom ambiguity necessitate histological examination for accurate diagnosis. This report aims to guide healthcare professionals facing similar future cases.

Surgical Treatment of Hepatocellular Carcinoma with a Tumor Thrombus Invading the Right Atrium: A Case Report.

Up to 3% of all hepatocellular carcinomas (HCCs) present with a tumor thrombus (TT) in the inferior vena cava (IVC) and right atrium (RA). Extensive growth of HCC into the IVC and the RA is associated with a particularly poor prognosis. This clinical condition is related to a high risk of sudden death due to pulmonary embolism or acute heart failure. Therefore, a technically challenging treatment undergoing hepatectomy and cavo-atrial thrombectomy is necessary. We report a 61-year-old man presenting with right subcostal pain, progressive weakness, and periodic shortness of breath for 3 months. He was diagnosed with advanced HCC with a TT extending from the right hepatic vein into the IVC and RA. A multidisciplinary meeting with cardiovascular and hepatobiliary surgeons, oncologists, cardiologists, anesthesiologists, and radiologists was held to determine the best treatment approach. Initially, the patient underwent right hemihepatectomy. As follows, the cardiovascular stage using cardiopulmonary bypass was successfully performed, removing the TT from the RA and ICV. In the early postoperative period, the patient remained stable and was discharged on the 8th postoperative day. A morphological examination revealed grade 2/3 HCC, a clear cell variant with microvascular and macrovascular invasion. Immunohistochemical staining was positive for HEP-1, CD10, whereas negative for S100. The morphological and immunohistochemical results corresponded to HCC. The treatment of such patients requires the cooperation of various specialties. Although the approach of the surgery is extremely complex including specific technical support, as well as high perioperative risks, the result offers favorable clinical outcomes.

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

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 benign thyroid 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 the benign and malignant nature of the nodule. Immunocytochemistry is of value as an ancillary test to enhance the diagnostic accuracy of thyroid FNA samples.

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

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.

Acute Appendicitis in the Elderly: A Literature Review on an Increasingly Frequent Surgical Problem.

With increased life expectancy and the growing total population of elderly patients, there has been rise in the number of cases of acute appendicitis in elderly people. Although acute appendicitis is not the most typical pathological condition in the elderly, it is not uncommon. Most of these patients require surgical treatment, and as with any acute surgical pathology in advanced age, treatment possibilities are affected by comorbidities, overall health status, and an increased risk of complications. In this literature review we discuss differences in acute appendicitis in the elderly population, with a focus on clinical signs, diagnostics, pathogenesis, treatment, and results.

Diagnostic utility of immunohistochemical panel in various thyroid pathologies.

BACKGROUND: For management of thyroid nodules, distinction between benign and malignant tumours is essential. The study was performed to evaluate the diagnostic value of molecular markers in different thyroid tumours. MATERIALS AND METHODS: Immunohistochemistry for CD56, HBME-1, COX-2, Ki-67, p53 and E-cadherin (E-CAD) was performed in 113 benign and 35 malignant thyroid lesions including 36 follicular adenomas (FA), 77 colloid goitres, 26 papillary thyroid carcinomas (PTC) and 9 follicular carcinomas (FC). The results were scored semiquantitatively by staining intensity (0-3 scale) and percentage of positive cells. RESULTS: PTC was characterised by decreased E-CAD and CD56 expression in contrast to surrounding benign thyroid tissues. HBME-1 expression was absent in benign thyroid tissues but was notably high in PTC and occasionally in FC. The expression of E-CAD and CD56 in FA was significantly higher than in the surrounding thyroid tissues. No expression of p53 was found in any group. The expression of COX-2 was low in all lesions. The proliferation activity by Ki-67 was generally low; however, it was significantly higher in cancers. CONCLUSIONS: The panel consisting of three markers, HBME-1, E-CAD and CD56, can be recommended as an adjunct to morphology criteria. HBME-1 is found in malignant lesions only and is the most sensitive and specific single marker in PTC. Decreased expression of E-CAD and CD56 distinguishes PTC from FA and FC. Both FA and FC are characterised by high expression of E-CAD and CD56. The practical use of Ki-67 is difficult due to low values. The role of adhesion factors in thyroid malignancies may be superior in comparison with cell proliferation.

Fibrinolytic System Changes in Liver Surgery: A Pilot Observational Study.

Introduction: Bleeding occurs frequently in liver surgery. Unbalance between tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations might increase bleeding. Our aim was to analyze perioperative fibrinolytic changes during liver surgery. Materials and Methods: We evaluated 15 patients for inclusion into a prospective pilot study of liver surgery. We assessed fibrinolysis by plasma PAI-1 and t-PA: before surgery (T1), before Pringle maneuver (PM;T2), at the end of surgery (T3) and 24 h postoperatively (T4), and registered demographic and laboratory data, extent and duration of surgery, hemodynamic parameters, blood loss, and transfused volumes of blood products. Data presented as mean ± SD. Significance at P < 0.05. Results: After exclusion of six patients only undergoing biopsies, we included six women and three men aged 49.1 ± 19.6 years; two patients with liver metastases of colorectal cancer and hepatocellular carcinoma, respectively, two with focal nodular hyperplasia, two with hepatic hemangioma, and one with angiomyolipoma. Six patients underwent PM. PAI-1 plasma concentration (n = 9) rose from 6.25 ± 2.25 at T1 through 17.30 ± 14.59 ng/ml at T2 and 28.74 ± 20.4 (p = 0.007) and 22.5 ± 16.0 ng/ml (p = 0.04), respectively, at T3 and T4. Correspondingly, t-PA plasma concentration (n = 9) increased from 4.76 ± 3.08 ng/ml at T1 through 8.00 ± 5.10 ng/ml (p = 0.012) at T2 and decreased to 4.25 ± 2.29 ng/ml and 3.04 ± 3.09 at T3 and T4, respectively. Plasma t-PA level at T2 was significantly different from those at T1, T3, and T4 (p < 0.004). In PM patients, t-PA levels increased from T1, peaked at T2 (p = 0.001), and subsequently decreased at T3 and T4 (p = 0.011 and p = 0.037), respectively. Mean blood loss was 1,377.7 ± 1,062.8 ml; seven patients received blood products. Patients with higher PAI-1 levels at T3 received more fresh frozen plasma (r = 0.79; p = 0.01) and red blood cells (r = 0.88; p = 0.002). Conclusions: During liver surgery, fibrinolysis increased, as evidenced by rises in plasma PAI-1and t-PA, especially after start of surgery and following PM. Transfused volumes of blood products correlated with higher plasma concentrations of PAI-1. Confirming this tendency requires a larger cohort of patients.