[Surgical treatment of pheochromocytoma].

This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The main component of preoperative preparation is the use of alpha-blockers. The need to prescribe them to all patients is increasingly disputed, especially for patients without severe hypertension. An increasing number of publications demonstrate positive results of treatment without the use of alpha-blockers, advocating an individual approach and the use of the drug according to certain indications. Minimally invasive endoscopic techniques of adrenalectomy have become widespread in surgical treatment. They are represented by laparoscopic and retroperitonescopic technic, including using their single-port modifications. The earliest possible intersection of the central vein in the past was considered the most important aspect of adrenalectomy for pheochromocytoma, currently, due to the development of surgical techniques and anesthesiological manuals, this has ceased to be a mandatory rule of successful surgery. Despite the significant influence of the intersection of this vessel on intraoperative hemodynamics, surgical tactics with its later intersection have their own justifications and do not lead to a deterioration in treatment results. The standard volume of surgical intervention for pheochromocytomas is total adrenalectomy, however, in the presence of hereditary syndromes, such as multiple endocrine neoplasia type 2 syndrome, neurofibomatosis type 1, von Hippel-Lindau syndrome, it is possible to perform cortical-sparing adrenalectomy.

[Corticotropin-producing pheochromocytoma in multiple endocrine neoplasia type 1].

A clinical case of a man 66 y.o. who was diagnosed with hormone-inactive pituitary macroadenoma complicated by corneal erosion and partial atrophy of the optic nerve of the left eye due to exophthalmos. The increase in prolactin level was regarded due to a «stalk-effect¼. The patient underwent a transnasal pituitary adenomectomy with subsequent regression of symptoms. After 4 years, against the background of a new coronavirus infection, increasing general weakness, headaches, a crisis increase in blood pressure and tachycardia attacks appeared. Computed tomography (CT) accidentally revealed an adrenal incidentaloma, in laboratory tests - hypercortisolism, elevated ACTH levels, hypokalemia, hyperglycemia, increased levels of metanephrine and normetanephrine. The patient developed acute steroid psychosis, after which an adrenalectomy with a tumor was performed, a pheochromocytoma was histologically confirmed. After surgery, there was a regression of symptoms, the development of adrenal insufficiency with reduced levels of ACTH and cortisol. Upon further examination, a polynodose euthyroid goiter was established, the biopsy of the nodes - Hashimoto's thyroiditis (Bethesda II). Meanwhile, primary hyperparathyroidism was detected. According to ultrasound, scintigraphy with Ts99m-Technetril and CT revealed an increase of left parathyroid gland. A bilateral revision of the neck, removal of the right upper and left upper parathyroid adenomas were performed. In the postoperative period, the levels of calcium and parathyroid hormone were normalized. Given the presence of a combination of multiple tumors of the endocrine system (primary hyperparathyroidism, corticotropin-producing pheochromocytoma, hormone-inactive pituitary macroadenoma, polynodose euthyroid goiter), the MEN1 syndrome was clinically established. The study of 2 and 10 exons of the MEN1 gene revealed no mutations, which does not exclude the presence of a hereditary syndrome. The patient continues observation. In the available literature in Russian and English languages the case of ACTH pheochromocytoma as part of the MEN type 1 syndrome have not been found. Therefore, we consider the presented case to be the first one.

[Metastatic risk factors in pheochromocytoma/paraganglioma].

Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic¼ and «non-metastatic¼. Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15-20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.

[Comparison of the effectiveness of various methods for determining the level of metanephrines in the diagnosis of pheochromocytomas].

BACKGROUND: Pheochromocytoma (PHEO) is a tumor from the chromaffin tissue of the adrenal medulla, capable of hyperproduction of catecholamines. The increased production of hormones by the tumor leads to catecholamine crises, which have a pathological effect on all organs and systems. In the primary diagnosis of pheochromocytomas, it is important to determine the level of the metabolite of catecholamines - metanephrines. Currently, in clinical practice, various methods are used to determine the level of this metabolite: in blood plasma or in urine, total or only free form, fractionated analysis or unfractionated. AIM: Comparison of the effectiveness of various methods for determining the level of metanephrines for the diagnosis of pheochromocytomas. MATERIALS AND METHODS: A retrospective single-center cohort study was conducted on a sample of patients who were initially operated on for adrenal neoplasm at the Pirogov St. Petersburg State University High Medical Technology Clinic from November 2007 to December 2022 and who passed analysis to determine the level of blood or urine metanephrins before surgical treatment. The results of tests for metanephrine and tumor size were evaluated. RESULTS: 1088 patients with adrenal neoplasms who underwent surgical treatment were examined, of which 348 had histologically confirmed the presence of pheochromocytoma. Four types of metanephrine assays were compared: free fractionated plasma metanephrines (232 patients), unfractionated daily urine metanephrines (431 patients), fractionated total daily urine metanephrines (427 patients) and fractionated free daily urine metanephrines (178 patients). The greatest sensitivity was demonstrated by the analysis of free fractionated plasma methanephrines (95.4%). Unlike others, the sensitivity of this analysis did not decrease in the group of patients with small pheochromocytomas (3 cm or less). The greatest specificity was demonstrated by the analysis of unfractionated metanephrines in daily urine (97.8%), with the lowest sensitivity among all tests (67.6%). The study of fractionated total daily urine metanephrins showed good results of sensitivity and specificity, only slightly inferior to the best indicators, and the analysis of free daily urine metanephrins demonstrated unexpectedly low efficiency. There is a positive correlation between the level of metanephrine in the blood and the size of the tumor. CONCLUSION: Based on the data obtained, the preferred assays for the primary diagnosis of pheochromocytoma can be considered the determination of fractionated free plasma metanephrines and fractionated total daily urine metanephrines, which is consistent with relevant clinical recommendations. It was found that the size of the tumor correlates with the severity of an increase in the level of metanephrins determined by any of the described methods.

[Diagnostic value of ct in examination of patients with adrenal cancer].

BACKGROUND: In most cases adrenal tumours are detected by accident while performing medical imaging tests for other diseases. These findings are treated as adrenal incidentaloma. Prevalence of incidentalomas detected on CT scans is up to 4%. According to different authors, 4-12% of all adrenal tumours are adrenocortical carcinomas. As for today, the most significant medical imaging technique is CT scan with bolus IV injection of contrast agent and assessment of tumour's density. The analysis of the results of CT imaging in 67 patients with ACC was carried out according to a single protocol. The main signs characteristic of this disease are described. It is very important to evaluate typical signs of ACC on CT scans for risk assessment of ACC before surgical treatment. If malignant tumour is suspected during preoperative examination, it is extremely important to choose the right surgical treatment strategy. AIM: To evaluate the significance of CT as the main method of preoperative diagnosis in patients with malignant tumors of the adrenal cortex. Studying CT semiotics of adrenocortical cancer in a large group of patients using a single standard imaging protocol. Find the main radiological symptoms characteristic of adrenocortical cancerMATERIALS AND METHODS: Here are the results of retrospective study of CT scans performed on 67 patients with adrenocortical carcinoma who received treatment in the Department of Endocrine Surgery of Saint-Petersburg State University N.I. Pirogov Clinic of High Medical Technologies during 2012-2020. The diagnostic significance of CT in patients with ACC was assessed. RESULTS: The most common features of ACC: tumour heterogeneity (84.3%), tumour's size 3-9 cm (75%), signs of invasion into surrounding structures (10%), pre-contrast density above +30 HU (75%), absolute contrast washout less than 60% (68.8%), relative contrast washout less than 40% (64.6%)CONCLUSION: CT scan with IV contrast was not able to show any definitive pathognomonic signs of ACC. Nevertheless, CT scan should be performed in all patients with suspected (or confirmed using other medical imaging technique) adrenal tumour according to standard protocol. Bolus injection of contrast agent should be performed in all patients with tumour's pre-contrast density above +5 HU.

Carbon dioxide embolism during posterior retroperitoneal adrenalectomy.

We report a case of massive carbon dioxide embolism associated with injury to the inferior vena cava, during posterior retroperitoneoscopic adrenalectomy. The presenting clinical features were tachycardia, rapid oxygen desaturation and severe respiratory acidosis, without evidence of bleeding. The patient was resuscitated by increasing the fraction of inspired oxygen, administering intravenous fluid and converting to an open procedure to suture the vein. This case demonstrates that gas embolism due to vessel injury during posterior retroperitoneal adrenalectomy may arise without evidence of bleeding, severe hypotension or an abrupt increase in end-tidal carbon dioxide. Using a high carbon dioxide insufflation pressure in the retroperitoneal space enhances visualisation of the surgical field by decreasing small-calibre vessel bleeding. However, it can contribute to, and delay recognition of, carbon dioxide embolism. Knowledge of the clinical features of carbon dioxide embolism, careful monitoring and vigilance for intra-operative surgical challenges can assist with the detection of this rare but potentially fatal complication.

Age-Related Features of Ketanserin Effects in Experimental Liver Cirrhosis.

The effect of ketanserin on inflammation, liver fibrosis, and microviscosity of the plasma and mitochondrial membranes of hepatocytes was studied on young (3 months) and old (9 months) male Wistar rats with experimental liver cirrhosis. Ketanserin reduced inflammation, area of the connective tissue, and liver damage and improved serum biochemical parameters in rats of both age groups; in old rats, the effects were more pronounced than in young animals. In old rats, ketanserin reduced polarity of hepatocyte plasma and mitochondrial membranes in the area of protein-lipid contacts, which determined higher effectiveness of ketanserin during the treatment of liver cirrhosis in aged animals.

[Clinical and laboratory features of hereditary pheochromocytoma and paraganglioma].

The widespread introduction of genetic testing in recent years has made it possible to determine that more than a third of cases of pheochromocytomas and paragangliomas (PPPGs) are caused by germline mutations. Despite the variety of catecholamine-producing tumors manifestations, there is a sufficient number of clinical and laboratory landmarks that suggest a hereditary genesis of the disease and even a specific syndrome. These include a family history, age of patient, presence of concomitant conditions, and symptoms of the disease. Considering that each of the mutations is associated with certain diseases that often determine tactics of treatment and examination of a patient, e.g. high risk of various malignancies. Awareness of the practitioner on the peculiarities of the course of family forms of PPPGs will allow improving the tactics of managing these patients.The article provides up-to-date information on the prevalence of hereditary PPPGs. The modern views on the pathogenesis of the disease induced by different mutations are presented. The main hereditary syndromes associated with PPPGs are described, including multiple endocrine neoplasia syndrome type 2A and 2B, type 1 neurofibromatosis, von Hippel-Lindau syndrome, hereditary paraganglioma syndrome, as well as clinical and laboratory features of the tumor in these conditions. The main positions on the necessity of genetic screening in patients with PPPGs are given.

Peculiarities of the Functional State of Mitochondria of Peripheral Blood Leukocytes in Patients with Acute Myocardial Infarction.

We studied the rate of oxygen consumption by mitochondria isolated from peripheral blood leukocytes of patients with acute myocardial infarction and healthy volunteers. It was found that leukocyte mitochondria in patients with acute myocardial infarction were characterized by significantly lower rate of oxygen consumption and lower level of coupling of oxidation and phosphorylation processes in comparison with mitochondria from healthy volunteers.

[Effect of benzimidazole derivative with hypoglycemic activity on reproduction processes in females rats].

Toxicological experiments showed that the new benzimidazole derivative with hypoglycemic action--diabenol--influences the sexual activity and processes of female fertilization. The estrous cycle, sexual activity and quality of fertilization were activated at females upon the administration of diabenol in a therapeutic dose of 5 mg/kg. It is established that the drug administration in a toxic dose of 160 mg/kg suppresses the sexual activity and, at the same time, does not affect the estrous cycle and quality of fertilization in females.