Chromogranin A Levels Research Articles

Low sensitivity of chromogranin A in the diagnosis of insulinoma: a single-center study

Background: Insulinoma is a neuroendocrine tumor (NET), with its main clinical manifestation being the hypoglycemic syndrome. The symptoms of hypoglycemia are nonspecific, and therefore, in most cases, the diagnosis is made untimely. The Russian clinical guidelines for the diagnosis and treatment of NET suggest as a diagnostic test that the universal circulating marker of all NET, chromogranin A (CgA) be determined. However, the literature data on the sensitivity of CgA in the diagnosis of insulinoma are contradictory. Aim: To evaluate the diagnostic effectiveness of the CgA test in the diagnosis of insulinoma. Materials and methods: This was a hospital-based single-center, cross-sectional comparative (first step) and prospective non-comparative (second step) study conducted from 2016 to 2022. During the first part of the study, we determined serum CgA in 120 patients with suspected non-diabetic hypoglycemia and compared its levels in the patients with and without confirmed insulinoma (n = 87 and n = 33, respectively). During the second study step, CgA was measured in the insulinoma patients at 6 [4.0; 7.0] months after surgery. The CgA levels at baseline and post-surgery were analyzed in 74 patients (those with recurring non-diabetic hypoglycemia were excluded from the analysis). Results: In the study subjects without insulinoma, the median CgA level was 0.7 [0.5; 1.1] (range, 0.1 to 2.0) nmol/l and the difference (with Bonferroni adjustment) from its levels in the patients with insulinoma before surgery was non-significant (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, р = 0.045). The CgA concentration in the insulinoma patients after surgery was 0.9 [0.7; 1.2], range, 0 to 1.9 nmol/l and significantly differed from that at baseline (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, p = 0.012, Wilcoxon test). In the patients with insulinoma before surgery the CgA levels exceeding the generally accepted reference range ( 2 nmol/l) was found in 11.5% (n = 10), with its median level of 2.5 [2.3; 4.1], range 2.3 to 8.5 nmol/l. There were no significant associations between the CgA levels and localization, tumor numbers, their size and malignization grade, insulin and proinsulin values, and duration of fasting. The sensitivity and specificity of the CgA test were 12% [95% confidence interval [CI]: 6%–20%] and 100% [95% CI: 97%–100%], respectively. The prognostic value of a positive result (PVPR) was 100% [95% CI: 69%–100%] and the prognostic value of a negative result (PVNR) 30% [95% CI: 28%–32%]. Conclusion: As a diagnostic test, CgA has high specificity and prognostic value of a positive result. However, the uncertainty of the prognostic value of a negative result is unacceptably high. A special study is required to clarify the operational characteristics of CgA in insulinoma.

Searching for New Biomarkers of Neuroendocrine Tumors: A Comparative Analysis of Chromogranin A and Inflammatory Cytokines in Patients with Neuroendocrine Tumors.

Neuroendocrine neoplasms (NENs) present a diagnostic challenge due to their heterogeneous nature and non-specific clinical manifestations. This study aimed to explore novel biomarkers for NENs. Serum chromogranin A (CgA) levels and a panel of 48 inflammatory cytokines were analyzed in a cohort of 84 NEN patients and 40 healthy controls using enzyme-linked immunosorbent assay (ELISA) and multiplex ELISA. Significant alterations in cytokine levels were observed in the NEN patients compared to the controls, including elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), and reduced levels of angiogenic factors like platelet-derived growth factor-BB (PDGF-BB) and tumor necrosis factor beta (TNF-β). Notably, cytokines such as growth-regulated alpha protein (GRO-α) and TNF-β demonstrated strong potential as diagnostic markers, with receiver operating characteristic (ROC) curve analyses showing high sensitivity and specificity. Additionally, a positive correlation was found between CgA levels and several inflammatory cytokines, suggesting their synergistic role in tumor progression. These findings highlight the limited reliability of CgA alone as a diagnostic marker and underscore the importance of a multi-marker approach in diagnosing and monitoring NENs. Further research on a larger cohort is necessary to validate these biomarkers and their potential clinical applications.

Trans-arterial embolization versus chemoembolization for neuroendocrine liver metastases: a propensity matched analysis

IntroductionLocoregional therapies are a mainstay of treatment for patients with neuroendocrine liver metastases (NELM), yet the optimal transarterial approach remains undefined and recent studies have raised concern over the safety of transarterial chemoembolization (TACE). MethodsPatients with NELM who underwent TACE or transarterial embolization (TAE) at a single institution between 2000–2022 were retrospectively reviewed. Propensity score matching (PSM) controlling for age, sex, bilateral disease, tumor size, lobar embolization, grade, and extrahepatic disease was utilized to compare short- and long-term outcomes. ResultsAmong 412 patients with NELM, 329 underwent TACE and 83 TAE. Mean age was 60.7 ± 11.1 years. Patients primarily presented with synchronous (69.2%), bilateral (84.2%), and G1 disease (48.8%) and underwent staged procedures (55.8%). Following PSM, TACE was associated with slightly worse post-procedure laboratory values, but no difference in complications compared to TAE (23.3%vs29.3%, p = 0.247). TACE was associated with improved mean PFS (21.8vs10.7 months, p = 0.002), but no difference in radiographic size, chromogranin level, or median overall survival (50.0 months vs not met, p = 0.833). ConclusionAmong patients with NELM, TACE was associated with similar short-term outcomes and improved PFS, but no difference in OS compared to TAE. These findings highlight the need for additional research on the optimal locoregional therapy for NELM.

Chromogranin A (CgA) Deficiency Attenuates Tauopathy by Altering Epinephrine-Alpha-Adrenergic Receptor Signaling.

Our previous studies have indicated that insulin resistance, hyperglycemia, and hypertension in aged wild-type (WT) mice can be reversed in mice lacking chromogranin-A (CgA-KO mice). These health conditions are associated with a higher risk of Alzheimer's disease (AD). CgA, a neuroendocrine secretory protein has been detected in protein aggregates in the brains of AD patients. Here, we determined the role of CgA in tauopathies, including AD (secondary tauopathy) and corticobasal degeneration (CBD, primary tauopathy). We found elevated levels of CgA in both AD and CBD brains, which were positively correlated with increased phosphorylated tau in the frontal cortex. Furthermore, CgA ablation in a human P301S tau (hTau) transgenic mice (CgA-KO/hTau) exhibited reduced tau aggregation, resistance to tau spreading, and an extended lifespan, coupled with improved cognitive function. Transcriptomic analysis of mice cortices highlighted altered levels of alpha-adrenergic receptors (Adra) in hTau mice compared to WT mice, akin to AD patients. Since CgA regulates the release of the Adra ligands epinephrine (EPI) and norepinephrine (NE), we determined their levels and found elevated EPI levels in the cortices of hTau mice, AD and CBD patients. CgA-KO/hTau mice exhibited reversal of EPI levels in the cortex and the expression of several affected genes, including Adra1 and 2, nearly returning them to WT levels. Treatment of hippocampal slice cultures with EPI or an Adra1 agonist intensified, while an Adra1 antagonist inhibited, tau hyperphosphorylation and aggregation. These findings reveal a critical role of CgA in regulation of tau pathogenesis via the EPI-Adra signaling axis.

Age and Sex-related Chromogranin A Gene Polymorphisms and its Association with Metabolic Syndrome Components.

The purpose of this study was to determine the possible differences in genetic polymorphisms and serum levels of chromogranin A (CgA), according to age and sex, in subjects with and without metabolic syndrome (MetS). The genotyping and serum level of CgA and biochemical parameters were measured by the T-ARMS-PCR and PCR-RFLP and ELISA and spectrophotometer methods, respectively. A comparison of males with and without MetS showed significantly lower high-density lipoprotein-cholesterol (HDL-C) levels than those of females.At ages 30-70 years, both sexes showed significant differences in triglycerides (TG), fasting blood sugar (FBS), CgA levels and waist circumference (WC) when compared to the two groups. Both sexes with MetS indicated significant differences in systolic blood pressure (SBP) at ages 40-70 years, while at ages 40-59 years, there was a significant difference in HDL-C level in males.There was a significant correlation between serum levels of FBS, TG, SBP and WC (in both sexes), and CgA in subjects with MetS. Significant correlation was found between HDL-C level and diastolic blood pressure (DBP), and CgA level in males and females, respectively. CgA genotype frequency (T-415C and C+87T polymorphisms) showed no significant differences between males and females with and without MetS, while there was only a significant difference in frequency of the genotypes T-415C when compared to males with and without MetS. The CgA appears to be strongly associated with MetS components in both sexes. Variation in CgA gene expression may affect the T-415C polymorphism in males. This may mean that the structure of CgA genetics differs in different ethnic groups. Differences in the serum level and expression of CgA gene may show valuable study results that it may be expected a relationship between these variables and the MetS.

STUDY OF PHYSIOLOGICAL AND BIOCHEMICAL VARIATIONS IN POPULATION GROUPS UNDERGOING ACUTE OR CHRONIC STRESS

Objective: Stress arises from derangements of personal and professional activities. The basic reason is changes in lifestyle and psychosocial adaptations. Life becomes demanding, complicated, mechanical, and devoid of health. In today’s modern world, occupational stress has become the major factor for loss of health and peacefulness of mind. Methods: This is an observational descriptive study which was conducted in a group of 84 people between 25 and 60 years of age to study the association of acute stress on salivary amylase level and effect of chronic stress on lipid profile, glycosylated hemoglobin and certain inflammatory markers in people representing different forms of stress. Three groups of the population were studied. Group 1 (n=20) - Patients undergoing any elective surgery (abdominal/genitourinary) or an invasive diagnostic procedure (upper GI endoscopy, lymph node biopsy) Group 2 (n=32) – High/middle socio-economic male or female working for ≥8 h/day with or without stress. Group 3 (n=32) – Low socioeconomic male or female earning <100 Rs/day with or without stress. Salivary alpha-amylase and chromogranin A (CgA) levels are good markers of stress. Results: There was increased levels of cortisol (p<0.0001), alpha amylase (p<0.01), and decreased levels of CgA (p<0.001) pre-procedure period as a marker of acute stress. In the chronic stress group of low income as well as high-income status, glycosylated hemoglobin, and blood lipid profile in both males and females were significantly deranged. Plasma malondialdehyde (MDA) levels and interleukin (IL)-1 and IL-2 were significantly raised in both groups. Serum ferritin level was low in the low socioeconomic group but normal in the high socioeconomic group. Conclusion: Salivary amylase level was raised in acute stress and there is a direct correlation of chronic stress with high low-density lipoprotein/ high-density lipoprotein ratio, raised glycosylated Hemoglobin, serum MDA, IL-1, 2 levels irrespective of economic group.

Optimal follow-up with somatostatin receptor PET/CT imaging in patients with small intestinal neuroendocrine tumours.

Somatostatin receptor positron emission tomography with computerised tomography imaging (SRI) has a high sensitivity for the detection of small intestinal neuroendocrine tumors (siNET), which makes it ideal for follow-up. The aim of the present study was to investigate whether follow-up with SRI in patients with siNET led to any change in the treatment of the patient and if patient and/or tumour factors were associated with such change. Adults with siNET who had undergone at least two SRI scans between 2013 and 2021 were identified. Data on age, sex, comorbidities, tumour stage, grade, and most recent levels of serum Chromogranin A (CgA) and 24-h urine 5-hydroxyindoleacetic acid (5-HIAA) before each SRI scan were obtained. The major change was defined as new treatment previously not received or discontinuation of ongoing treatment. Univariate and multivariate mixed models logistic regression on variables with a presumed biological relationship with major change and with backwards stepwise exclusion of variables with p > .1 was performed. A total of 164 patients with siNET diagnosis had undergone 570 SRI scans. The median follow-up was 3.1 years. Only 82 of 570, 14%, of SRI scans led to a major change in treatment. Female sex, age below 75 years, elevated or missing CgA, elevated or missing urine 5-HIAA, progress on last SRI scan and distant extrahepatic disease were all independently associated with increased odds ratios for major change after follow-up with SRI. A small proportion of SRI scans (14%) led to a major change in treatment. Six independent risk factors with increased odds of major change, all available before each SRI scan, were identified. While validation of these risk factors is needed in a separate cohort, these findings could help clinicians individualise follow-up for siNET patients in the future.

The Use of Coffee Aroma for Stress Reduction in Postgraduate Dental Students

ObjectivesThis study aimed to investigate the measure to reduce academic stress of graded oral presentation in postgraduate dental students using coffee aromatherapy. MethodsHealthy postgraduate dental students in a seminar class were divided into coffee (n = 32) or control (n = 26) group. There were three modes of aroma distribution: personal distribution with a coffee pad attached to a lanyard, a lanyard plus a personal fan for ventilation of the aroma, and the typical method of the diffuser to spread the aroma in the ambient air. The levels of salivary alpha-amylase (sAA), cortisol (sCort), and chromogranin A (sCgA) represented stress biomarkers. Pulse rates were also measured. ResultsThe levels of sAA increased 176.62 ± 30.26% between pre- and post-presentation in the control group. Inhaling coffee aroma during the presentation period significantly ameliorated sAA increase at 81.02 ± 14.90% (p = 0.015). sCort levels tended to decrease in the coffee group but not significantly. Surprisingly, sCgA levels actually increased more in the coffee group. Also, pulse rates decreased in the coffee group (-2.07 ± 2.81 bpm) and increased in the control group (6.90 ± 3.22 bpm; p = 0.035). Subgroup analysis did not reveal differences in salivary markers among three aroma distribution modes. ConclusionsCoffee aroma could have anxiolytic effect on postgraduate dental students as evidenced by sAA levels and pulse rates. Personal aroma distribution was also a useful and effective mode of aromatherapy.

Robot therapy aids mental health in patients with hematological malignancy during hematopoietic stem cell transplantation in a protective isolation unit

Patients with hematological malignancy experience physical and psychological pain, such as a sense of isolation and confinement due to intensive chemotherapy in a protective isolation unit (PIU). We examined whether the intervention of a robotic puppy, aibo (manufactured by Sony), could improve patients' mental health as an alternative therapy for pet therapy, which is not feasible in PIU. This study included 21 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (n = 16) or autologous HSCT (n = 5). The patients were randomly divided into the aibo and control groups. Psychological effects were regularly assessed by measuring the levels of salivary stress hormone chromogranin A (CgA), serum oxytocin, and serum cortisol and the quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores. The aibo group demonstrated a significant decrease in CgA level, while the control group showed the opposite trend. In addition, changes in serum oxytocin and cortisol levels indicated that aibo helped reduce stress. There was no significant difference in the QIDS-SR scores between the two groups; however, the psychomotor activity in the aibo group improved significantly. These findings suggest that aibo intervention during a stay in a PIU can improve the mental health of patients with hematological malignancies who have undergone HSCT.

Determination of an Acclimation Period for Swine in Biomedical Research.

Swine are widely used models in biomedical research due to their physiologic and anatomic similarities to humans. During transport from vendors to research facilities, pigs are subject to a number of stressors, including environmental, social, and stress as a result of deprivation from food and water. As stress can have a number of adverse psychologic and physiologic effects, an acclimation period, defined as the period of time that an animal has to adjust and stabilize in a new environment, is recommended. The literature indicates that swine should be conditioned to their new facility for 5 to 7 d prior to undergoing survival surgery; however, to date, there is no published scientific evidence to support this or any specific acclimation period for swine. To investigate whether a certain length acclimation period leads to decreased stress in swine, we measured 2 stress biomarkers, cortisol and chromogranin A (CgA), from the saliva of 12 naive Yorkshire swine (n = 6 males and 6 females) arriving at our facility for use in research protocols. Noninvasive saliva collection was performed on days 1, 3, 5, 7, 10, and 14 after arrival from the vendor (representing different acclimation periods). We hypothesized that longer acclimation periods would result in reduced levels of both cortisol and CgA, indicating reduced stress. Our data revealed that there was no statistical difference in cortisol levels over time (P = 0.8200), nor between the sexes (P = 0.9886) or individual animals (P = 0.6280). CgA, similarly to cortisol, showed no overall effect of time (P = 0.2017) or sex (P = 0.6598). For this analyte, individual animal was significant (P < 0.0001), which suggests high interanimal variation. Furthermore, there was a significant decrease (P = 0.0077) in salivary CgA from day 1 compared with day 14, suggesting that swine may benefit from an acclimation period of at least 14 d.

Angiogenic biomarkers of response to treatment with peptide receptor radionuclide therapy in neuroendocrine tumours.

Neuroendocrine tumours (NETs) are a heterogeneous group of tumours, which is characterized by rich vascularization. The role of angiogenesis in NETs has been widely researched. Peptide receptor radionuclide therapy (PRRT) is an effective treatment method for patients with disease progression in NETs. Due to the heterogeneousness of NETs, the response to treatment varies. Currently, the finding of efficient markers helpful in assessing the response to treatment in NETs is crucial. The aim of this study was to assess chromogranin A (CgA) and angiogenic factors in gastro-entero-pancreatic (GEP) and broncho-pulmonary (BP) NET patients treated with PRRT. The study group included 40 patients with GEP NETs and BP NETs who completed four cycles of PRRT. Serum levels of CgA and angiogenic factors such as vascular endothelial growth factor (VEGF), its receptors (VEGF-R1, VEGF-R2, VEGF-R3), were assessed before and after four cycles of PRRT. All tests were determined using ELISA. The concentration of CgA, VEGF-R1 and VEGF-R2 decreased significantly, whereas VEGF-R3 increased significantly after PRRT. PRRT did not affect VEGF, it was similar before and after the radioisotope treatment. Based on AUROC, only for VEGF-R1 AUC was a consequence of 0.7 which can be considered as a good response to PRRT treatment. VEGF-R1 may be a potential biomarker useful in assessing the effectiveness of PRRT in NET patients.

Carcinoid tumorlet/typical carcinoid of the lung: An incidental bronchoscopic finding and cytological dilemma

Carcinoid tumors of the lung are low-grade neuroendocrine tumors with the potential to progress to high-grade tumors. Diagnosing a typical carcinoid of the lung/tumorlet is a tough nut to crack, especially in their early stages when there is no well-defined lesion in the imaging. Besides, differentiating a carcinoid from low-grade adenocarcinomas of the lung cytologically is quite challenging due to their similar morphology. We report a case of typical carcinoid of lung/tumorlet in a 42-year-old male who presented with hemoptysis. Flexible fibreoptic bronchoscopy revealed a bump in the right middle bronchus. Bronchial biopsy showed a cellular smear with a monotonous round to oval bland-looking cells distributed in singles and in acini, having a high nuclear-cytoplasmic ratio, scant cytoplasm, regular round nuclei, and inconspicuous nucleoli. No atypical mitotic figures or necrosis were seen. With these features, a cytological diagnosis of a typical carcinoid was made. Biopsy was not attempted again due to the small size of the lesion and inaccessibility. Serum chromogranin levels were elevated, confirming the diagnosis. The PET scan was unremarkable. The patient was referred to medical oncology for further management. This report will create awareness about diagnosing early carcinoid/tumorlet, especially with the increasing use of bronchoscopy and cytological diagnostic caution of overdiagnosis of malignancy.

THU526 Long-term Follow-up Of A Functional Gastroenteropancreatic Tumor Secreting Both Somatostatin And Gastrin

Abstract Disclosure: R. Zafar: None. J. Syeda: None. K. Rajamani: None. Introduction: There have been fewer than 200 cases of somatostatinoma reported since 1977. We report a case of a functional Gastroenteropancreatic neuroendocrine tumor (GEP-NET) secreting both somatostatin and gastrin. Clinical Case: A 55-year-old male with diabetes mellitus, chronic diarrhea, gastric ulcer, and cholelithiasis was referred to the endocrinology clinic for poorly controlled diabetes mellitus. He had a history of B-cell lymphoma of the thyroid treated by chemotherapy and radiation. He was found to have two paraduodenal masses by PET CT scan during surveillance for recurrence of lymphoma. Laboratory evaluation revealed elevated levels of insulin, glucagon, gastrin, somatostatin, and chromogranin A on multiple occasions both fasting and random. Ultrasound-guided endoscopic biopsy of the paraduodenal nodules was initially read as a neuroendocrine tumor. Subsequent immunohistochemical staining was positive for both somatostatin and gastrin. The stains were negative for glucagon and insulin. The Ki-67 proliferation index was less than 1%. The patient declined surgical treatment of the paraduodenal tumors. He underwent cholecystectomy for cholelithiasis. Gastric ulcers resolved with the use of proton pump inhibitors. His blood glucose was well controlled with insulin. Sequential CT/PET scans showed no change in the size of paraduodenal masses over a follow-up period of 14 years. Conclusion: GEP-NETs may secrete more than one type of hormone simultaneously. This case highlights a functional GEP-NET with clinical manifestations due to elevated levels of somatostatin and gastrin. Characterization of GEP-NETs by immuno-histochemical staining and hormonal analysis may help direct clinical management. Although many GEP-NETs are managed surgically, this case suggests that the Ki-67 proliferation index and sequential PET or CT scans may guide the nonsurgical management of functional GEP-NETs.

Exploring the spectrum of incidental gastric polyps in autoimmune gastritis.

Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa. We investigate the incidence of gastric polyps in CAAG patients. This is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded. A total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668vs 893 pg/ml p=0.0237, 146vs 207ng/ml p=0.0027, respectively). CAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG.

Diagnostic dilemma in a patient with history of medullary thyroid carcinoma and abnormal serum liver enzymes; a case report with six years follow up

BackgroundMedullary thyroid carcinoma (MTC) is a neuroendocrine tumor that originates from parafollicular C-cells. Calcitonin (Ctn) and carcinoembryonic antigen (CEA) are useful biomarkers for monitoring MTC cases.Case presentationHere, we describe a 48-year-old woman, who presented in 2014 with bilateral thyroid nodules. Report of fine needle aspiration was suspicious for MTC; initial laboratory evaluation showed serum Ctn level of 1567 pg/mL. After excluding type 2 multiple endocrine neoplasia syndrome clinically, total thyroidectomy and neck lymph node dissection were performed. The final histopathological diagnosis was right lobe MTC with neither vascular invasion nor lymph node involvement. On regular follow-up visits, Ctn and CEA levels have been undetectable, and repeated cervical ultrasonographic exams were unremarkable from 2014 to 2021. As liver enzymes became elevated in 2016, the patient was further evaluated by a gastroenterologist. Abdominopelvic ultrasonography revealed a coarse echo pattern of the liver parenchyma with normal bile ducts. A liver fibroscan showed a low fibrosis score (7kPa). The patient was recommended to use ursodeoxycholic acid. According to the progressive rise of liver enzymes with a cholestatic pattern in October 2020, a liver biopsy was performed that showed tiny nests of neuroendocrine-like cells with a background of primary biliary cholangitis (PBC). Immunohistochemical stainings were positive for chromogranin A (CgA), and synaptophysin and negative for Ctn, CEA, and thyroglobulin. Further imaging investigations did not reveal any site of a neuroendocrine tumor in the body. Considering normal physical exam, imaging findings, as well as normal serum levels of Ctn, CEA, CgA, and procalcitonin, the patient was managed as a PBC.ConclusionIn follow-up of a patient with MTC, we reported progressively increased liver enzymes with a cholestatic pattern. Liver biopsy revealed nests of neuroendocrine-like cells with a background of PBC, the findings that might suggest acquiring neuroendocrine phenotype by proliferating cholangiocytes.

Qinghua decoction improves chronic nonbacterial prostatitis possibly regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors.

To explore the mechanism by which Qinghua decoction regulates neuroendocrine inflammation in chronic nonbacterial prostatitis (CNP) model rats and provide an experimental basis for clinical treatment. The rats were randomly divided into six groups: normal control, model, Qianlie Tongyu capsule, low-dose Qinghua decoction, medium-dose Qinghua decoction, and high-dose Qinghua decoction group with six rats in each group. Rats in each group were sacrificed on the 29th day of treatment, and blood and prostate tissues were collected. Serum levels of tumor necrosis factor-alpha and interleukins 1-beta, 6, 8, and 10 (TNF-α and IL-1β, -6, -8, and -10, respectively) were measured using enzyme-linked immunosorbent assay. The pathological changes in the rat prostate tissue in each group were observed under a light microscope. The expression levels of chromogranin A (CgA), nerve growth factor (NGF), and tyrosine kinase A (TrkA) were detected using reverse transcription quantitative polymerase chain reaction. Western blotting was used to detect protein expression of CgA, NGF, and TrkA. In the model group, the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels. TNF-α, IL-1β, -6, and -8, CgA, NGF, and TrkA levels increased, whereas the content of IL-10 decreased, which was statistically significant compared to that in the normal control group ( < 0.05). Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration. When compared with the model group, the high-dose Qinghua decoction group showed a significant improvement in these indices ( < 0.05). Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP, regulation of inflammatory cytokine expression, and inhibition in the expression of CgA, NGF, and TrkA. This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.

Successful use of biotherapy with somatostatin analogues in the treatment of a patient with multiple endocrine neoplasia type 1

The syndrome of multiple endocrine neoplasia type I, MEN-1, or Wermer’s syndrome, occupies a separate place in the group of neuroendocrine tumors. Being a genetic, family-determined disease and having a transmission rate of 50%, it is manifested by multiple neoplasms of various malignant potential in many organs. Given the trend towards personalization of treatment, specialists in various fields are constantly looking for improved diagnostics and new methods of treatment. We present our own experience in the treatment of MEN-1 syndrome with somatostatin analogues. The patient, born in 1972, was observed by an endocrinologist at the age of 22, when a pituitary microadenoma was detected. After 18 years, a pancreatic tumor was detected, which was successfully removed. Histological and immunohistochemical studies verified a Grade 1 neuroendocrine tumor. Control computed tomography revealed multiple masses in the head and tail of the pancreas. Given the condition, patients since 2013 have been prescribed biotherapy with an analogue of somatostatin – octreotide. However, taking the drug was not regular, and the patient noted a deterioration in her condition. In 2019, by decision of the council, biotherapy with Lanreotide was prescribed. Even taking into account irregular examinations due to absenteeism, the control examination in 2022 showed normalization of the levels of chromogranin A and serotonin, the absence of new tumor foci and the progression of those present during Positron emission tomography. Thus, a multidisciplinary approach and the appointment of adequate therapy helps to improve the quality of life and stabilize patients with MEN-1 syndrome.

Pro-Gastrin-Releasing Peptide as a Biomarker in Lung Neuroendocrine Neoplasm.

There is a lack of effective biomarkers for diagnosing lung neuroendocrine neoplasms (LNENs). A known small cell lung cancer (SCLC) biomarker is a pro-gastrin-releasing peptide (ProGRP), but not for all LNENs, especially for bronchopulmonary carcinoids. This study aimed to evaluate the diagnostic value of ProGRP and chromogranin A (CgA) in diagnosing LNENs. The ProGRP and CgA levels in 290 cases of LNENs and 54 healthy controls (HCs) were measured. The median ProGRP concentration in the group of LNEN patients was 136.4 pg/mL, higher than that of HCs at 6.5 pg/mL. Most of the LNEN cohort was well-differentiated tumors (typical and atypical carcinoids, n = 262, 91.7% of all LNENs). The sensitivity, specificity, and area under the curve (AUC) of ProGRP when distinguishing LNENs vs. HCs were 94.8%, 100%, and 0.995. CgA (AUC = 0.375) could not determine LNENs vs. HCs. Therefore, based on these results, ProGRP may be considered as an effective marker for diagnosing LNENs.

Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting

Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity.&#x0D; Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease.&#x0D; Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers.&#x0D; Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient.&#x0D; In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p 0.05) and chromogranin А (elevation to 31.3 g/L [13.9; 90.7]; p 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 mol/L [32.95; 43.51]; p 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile.&#x0D; Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.

The Role of &lt;sup&gt;68&lt;/sup&gt;Ga-DOTATATE PET/CT in the Follow-Up of Patients with Pancreatic Neuroendocrine Tumors: a Retrospective Study

Purpose: To study the impact of 68Ga-DOTATATE PET/CT on the treatment tactics of metastatic pancreatic neuroendocrine tumors (pNETs).Material and methods: 208 68Ga-DOTATATE PET/CTs enrolled in 50 patients. Each patient underwent 68Ga-DOTATATE PET/CT two to ten times (median 4.2Դ2.2). At the time of the first study, the diagnosis of pNET was confirmed histologically and immunohistochemically in all patients. CT and MRI, as well as assessment of biochemical recurrence (serotonin and chromogranin-A levels exceeding the reference intervals) performed in all patients within one month before the next PET/CT. The results of all the listed studies in the detection of recurrent metastatic pNETs compared.Results: At the first 68Ga-DOTATATE PET/CT, metastases were detected in 46 patients out of 50 (92 %). At the same time, prior to the first PET/CT, CT and MRI revealed tumor foci only in 34 patients (68 %). Thus, compared with routine imaging methods, additional tumor foci detected in 12 patients (24 %). Among all 208 PET/CT examinations, 166 results were positive (79.8 %). According to the results of all CT and MRI studies, tumor foci diagnosed in 117 cases (56.3 %). Compared to CT and MRI, additional tumor foci detected in 49 studies (23.6 %). Metastases on PET/CT detected in 43 studies, despite the absence of biochemical recurrence. On PET/CT, pNETs recurrence was detected in six patients versus three on CT and MRI. Tumor progression — in 10 patients versus five on CT and MRI.Conclusion: We revealed the influence of 68Ga-DOTATATE PET/CT on the management of patients in the absence of other signs of disease recurrence or progression. 68Ga-DOTATATE PET/CT in combination with CT and MRI contributes to earlier diagnosis of recurrent metastatic pNETs.