[Ectopic acromegaly due to bronchial neuroendocrine tumors: the first description in Russia of three clinical cases].

 Acromegaly is a neuroendocrine disorder caused by excessive production of growth hormone (GH). In the majority of cases the cause of acromegaly is a pituitary tumor producing GH. Cases of ectopic acromegaly are much rarer. Ectopic acromegaly occurs in cases of tumors which produce growth hormone-releasing hormone (GHRH) or extrapituitary tumors which produce GH. The main sources of excessive GHRH production are neuroendocrine tumors (NETs) of the lung or pancreas. Treatment of ectopic acromegaly consists of surgical removal of the source of GHRH hyperproduction and in cases where surgery is not an option, somatostatin analogues, pegvisomant, chemotherapy, immunotherapy or radiation therapy are used.In this article three cases of ectopic acromegaly due to GHRH-producing lung NETs are presented, each of them being notable for a number of features. In the first two cases, clinical symptoms were mild, besides in the second case ectopic acromegaly was accompanied by primary hyperparathyroidism. In the third case ectopic acromegaly was accompanied by pituitary macroadenoma, and after surgical removal of the lung NET remission of acromegaly was not achieved. In all three cases, lung NETs were detected incidentally on radiologic chest screening for other conditions.

[Survival predictors in patients with ectopic acth syndrome].

AIM: To determine significant factors affecting the survival of patients with ectopic ACTH syndrome (EAS). MATERIALS AND METHODS: A multi-center, observational study with a retrospective analysis of patients with EAS. The end point of the study was the fatal outcome of patients from various causes. In order to identify predictors of survival or mortality, univariate and multifactorial Cox regression analyses were carried out. ROC-analysis was used to determine the prognostic threshold values of individual predictors. The survival analysis was carried out using the Kaplan-Mayer method. Statistical data processing was carried out by using IBM SPSS Statistics 23. RESULTS: The age of patients at the time of diagnosis ranged from 12 to 76 years (Me 40 years [28;54]). The age of the studied population was 55 years [38; 64] for women and 42 years [32; 54] for men. The median period of observation was 50 months [13;91], with a maximum follow-up of 382 months. 92 patients (60,9%) had bronchopulmonary NET, 17 (11,3%) - thymic carcinoid, 8 - pancreatic NET, 5 -pheochromocytoma, 1- cecum NET, 1- appendix carcinoid tumor, 1 - medullary thyroid cancer and 26 (17,2%) patients had an occult NET. The primary tumor was removed in 101 patients (66,9%). Bilateral adrenalectomy was performed in 42 (27,8%) cases. Metastases were revealed in 23,2% (n=35) of patients. Relapse of the disease was observed in 24,4%, long-term remission was preserved in 64 patients (74,4%). Death occurred in 42 patients (28%). The average age of survivors was 47,0±15,2 versus 53,5±15,6 years for the deceased (p=0,022). The average survival time from diagnosis for the deceased was 32 months, Me 16,5 months [7;54]. Multivariate analysis revealed that the following factors have a direct impact on survival: age of diagnosis ≥51 years (OR 4,493; 95% CI 2,056-9,818, p<0,001), bronchopulmonary neuroendocrine tumor (NET) (OR 0,281; 95% CI 0,119-0,665, p=0,004), the presence of distant metastases (OR 2,489; 95% CI 1,141-5,427, p=0,022), late-night salivary cortisol (LNSC) ≥122,2 nmol/L (OR 2,493; 95% CI 1,014-6,128, p=0,047). CONCLUSION: The prognosis of patients with EAS is influenced by the age of diagnosis, NET localization, distant metastases and level of LNSC. The most common cause of ectopic ACTH syndrome was bronchopulmonary NET which was associated with the best survival rate.

[Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization].

AIM: To study the clinical, biochemical characteristics, treatment results and follow-up of patients with ectopic ACTH syndrome EAS (ACTH adrenocorticotropic hormone ). MATERIALS AND METHODS: A retrospective, observational, single-center study of 130 patients with EAS. Demographic information of patients, medical history, results of laboratory and instrumental investigations at the pre- and postoperative stages and follow-up of EAS were analyzed. RESULTS: The mean age at the diagnosis ranged from 12 to 74 years (Me 40 years [28; 54]). The duration of the disease from the onset of symptoms to the verification of the diagnosis varied from 2 to 168 months (Me 17.5 months [7; 46]). Eighty-one (62,3%) patients had bronchopulmonary NET, 9 thymic carcinoid, 7 pancreatic NET, 5 pheochromocytoma, 1 cecum NET, 1 appendix carcinoid tumor, 1 medullary thyroid cancer and 25 (19.2%) had an occult source of ACTH. The median follow-up period of patients was 27 months [9.75; 61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.1%) patients, bilateral adrenalectomy was performed in 23 (18%) patients, in 16 of them there was an occult source of ACTH-producing NET and in 7 patients in order to control hypercortisolism after non-successful surgical treatment. Regional and distant metastases were revealed in 25 (19.2%) patients. At the time of the last observation 59 (72%) patients were exhibited a full recovery, 12 (14.6%) had relapse of the disease and 26 (20%) died from multiple organ failure (n=18), pulmonary embolism (n=4), surgical complications (n=2), disseminated intravascular coagulation syndrome (n=1) or COVID-19 (n=1). CONCLUSION: In our cohort of patients bronchopulmonary NET are the most frequent cause of EAS (62.3%). Surgical treatment leads to remission of hypercortisolism in 72% cases; the proportion of relapse (14.6%) and fatal outcome (20%) remains frequent in EAS.

[Bronchopulmonary ACTH-producing tumors].

Neuroendocrine tumors have the ability to produce the hormones and vasoactive peptides. Excess of these hormones leads to different symptoms and syndromes because of organs' injuries. Detection of ACTH origin by using of modern diagnostic methods is not always possible. Lungs and bronchi are one of the most frequent localization of ACTH-producing tumors. It is considered that carcinoids with bronchopulmonary localization like a benign tumors in the clinical course. But at the same time carcinoid tends to metastasize, so timely diagnostics and treatment improve quality of life significant and increase the life expectancy of patients. The modern state of diagnostics and surgical treatment problem of ACTH-producing tumors with bronchopulmonary localization is presented in the article. It was described the brief historical background, clinical symptoms, instrumental and biochemical methods of diagnosis. The principles of surgical treatment are presented in the article.

Cellular and molecular phenotypes of proliferating stromal cells from human carcinomas.

BACKGROUND: Stromal cells are a functionally important component of human carcinomas. The aim of this study was to obtain and characterise primary cultures of stromal cells from human carcinomas and the corresponding surrounding normal tissue. METHODS: Primary stromal cell cultures from tumours of lung, oesophagus and pancreas were obtained using a mild tissue dissociation method and a medium for culturing mesenchymal cells. Immunofluorescence staining and western blotting were used to analyse the expression of differentiation markers and selected known oncoproteins in the cell cultures obtained. RESULTS: A panel of stromal primary cultures was prepared from different human tumours and from matched normal cancer-free tissues. The in vitro proliferative potential of tumour-associated fibroblasts was shown to be higher than that of matched normal stromal cells. A mutational analysis of the TP53 and KRAS2 genes in a number of stromal cultures did not reveal known mutations in most cells of the cultures studied. Western blot analysis showed that stromal cells of lung tumours were characterised by a statistically significantly lower expression level of the p16 protein as compared with that in normal lung stromal cells. An important finding of our study was that, according to immunofluorescence assay, a fraction of fibroblast-like vimentin-positive cells in some tumour and normal stromal cell cultures expressed an epithelial marker - cytokeratins. CONCLUSIONS: Proliferating stromal cells from the carcinomas studied proved to be genetically normal cells with altered expression profiles of some genes involved in carcinogenesis, as compared with normal stromal cells. Epithelial-mesenchymal transition may lead to the emergence of transdifferentiated fibroblast-like cells in tumour stroma and in the tumour-surrounding tissue.

[1318 nm YAG-ND laser in surgery of lung metastases]. / Neodimovyi YAG-lazer s dlinoi volny 1318 nm v khirurgii metastazov legkikh.

YAG laser with 1318 nm wave was used in the treatment of 23 patients with peripheral lesions of the lungs, 7 of them had multiple lung metastases. Advantage of YAG laser over electric knife was demonstrated. In diagnosis of lung metastases it is necessary to consider not only results of computed tomography but also ones of intraoperative palpation that requires a wide surgical approach for hand manipulation in the pleural cavity. This method permits one to detect more metastases. Lateral thoracotomy with or without rib resection creates optimal conditions for use of YAG laser in surgery of multiple lung metastases.

[Ultrasonic diagnosis of focal damages in thoracoscopic operations]. / Ul'trazvukovaia diagnostika ochagovykh porazhenii legkogo pri torakoskopicheskikh operatsiiakh.

5-year experience of developed in PAMS A.V. Vishnevsky Institute of Surgery RAMS ultrasonic examination (USE) of the lung in thoracoscopic operations for focal lung lesions (FLL) is presented. Pilot experience of ultrasonic topical and differential diagnosis of FII opens a new page in diagnosis of respiratory diseases. Over 5 years 74 USE of FLL were performed. FLL were found in 91% cases. Detailed topical diagnosis of allows to design the lung resection with the best functional result. In postoperative X-ray examination neither atelectases nor zones of stable hypoventilation were detected. Normal echographic picture of lung tissue and echosemiotics of different focal lesions are descubed. The experience of diagnosis by echographic signs of FLL shows teasibility of differentiation of hamartomas from tuberculomas and focal metastatic lesions. The payential of differential diagnosis is illustrated. Differential diagnosis supported enucleation in superficial hamartomas and resection in suspected malignant tumor or tuberculosis. Use of intraoperative USE in the majority of cases of focal lesions located both in depth of lung tissue and subpleurally warrants the success of operation in thoracoscopic variant.

[Videothoracoscopy in diagnosis and treatment of small peripheral pulmonary masses]. / Videotorakoskopiia v diagnostike i lechenii malykh perifericheskikh obrazovanii legkikh.

This study was devoted to examination of efficacy of modern methods of diagnosis and surgical treatment of patients with small peripheral pulmonary masses (SPPM) with the use of videothoracoscopy. The results of examination and treatment of 126 patients with SPPM (80 patients underwent videothoracoscopy) were analysed. This study demonstrated high-quality of modern complex of clinicoradiological investigations for diagnosis of SPPM. The reliability of the complex is 91%. The necessity of immediate elective operation of the patients with SPPM is shown for verification of the process and adequate surgery. Videothoracoscopic surgery is effective method of treatment in patients with SPPM.

[Ultrasonic study in thoracoscopic operations]. / Ul'trazvukovoe issledovanie pri torakoskopicheskikh operatsiiakh.

Intraoperative ultrasound diagnosis (IOUSD) was made in several thoracoscopic interventions in 15 patients: diagnostic thoracoscopies (3) in patients with lymphogranulomatosis, carcinoid and peripheral lung cancer, enucleation and atypical resection of the lung (4) in patients with hamartochondromas, in excision of lung cyst (1), in removal of foreign body of the lung (1), in removal of celomic cysts (2) and in ablation of neurofibroma of the mediastinum (1), in atypical resection of the lung and enucleation of tuberculomas (2). Video thoracoscopy in combination with intraoperative ultrasound examination provides possibility for precisional diagnosis of focal disease of the lung and mediastinal organs, including local masses of small sizes, and is rather informative method of diagnosis. IOUSD allows to define the diagnosis more exactly and to determine the extent of pathological process, to prevent complications and locate intraparenchymal masses and foreign bodies in lung tissues, and thus enables to complete operation without thoracotomy.