[Retrosternal goiter in thoracic surgical practice]. / Zagrudinnyi zob v torakal'noi khirurgicheskoi praktike.

OBJECTIVE: To evaluate and optimize surgical approaches to the management of retrosternal goiter. MATERIAL AND METHODS: A cohort retrospective single-center study included 56 patients aged 68.3±9.8 years with retrosternal goiter who underwent surgery between 2004 and 2019. Right-sided goiter was diagnosed in 16 cases, left-sided goiter in 21 patients, bilateral goiter in 19 patients. Palpable neck mass was found in 17 (30.4%), stridor in 16 (28.6%), thyrotoxicosis in 4 (7.1%) and recurrent laryngeal nerve palsy in 2 (3.6%) cases. X-ray signs of tracheal compression were detected in 43 (76.8%) patients, deviation in 26 (46.4%) patients. Resection through cervical collar incision was performed in 40 (71.4%) patients. Additional sternotomy was required in 11 (19.6%) patients, 1 (1.8%) patient required collar incision and right anterior mediastinotomy. Right-sided posterolateral thoracotomy without collar incision was performed in 1 (1.8%) patient with a suspected mediastinal teratoma. Three patients underwent median sternotomy only because of preoperative diagnosis of teratoma in one and thymoma in two patients. RESULTS: There was no perioperative mortality. Transient vocal changes occurred in 3 (5.4%) patients, recurrent laryngeal nerve palsy in 3 (5.4%), atrial fibrillation in 2 (3.6%), wound complications in 2 (3.6%), left phrenic nerve palsy in 1 (1.8%), transient hypocalcaemia in 1 (1.8%) and persistent hypothyroidism in 1 (1.8%) patient. Hospital-stay ranged from 2 to 12 (5.5±2.0) days. Multinodular goiter was found in 53 (94.6%) patients, diffuse goiter in 1 (1.8%), ectopic thyroid in 1 (1.8%) and oncocytic tumor in 1 (1.8%) patient. One (1.8%) patient underwent simultaneous resection of RSG via a collar incision and right-sided VATS upper lobectomy for primary lung cancer. One (1.8%) patient also underwent simultaneous resection of RSG via collar incision and right-sided VATS subcarinal lymph node biopsy for coexistent lymphoma. Mean vertical length of goiter in the collar incision group was 7.6 cm compared to 10.6 cm in the sternotomy group. Mean weight of specimens was 162.3 g in patients with collar incisions and 312.5 g in the sternotomy group. Sternotomy was required in 14 (25%) patients. CONCLUSION: Resection of retrosternal goiter is more commonly performed via cervical collar incision with mandatory availability of sternotomy. Radiological measurement of craniocaudal length may predict the need for sternotomy. Surgical outcomes are not affected by surgical approach. Simultaneous thoracic interventions for a coexistent pathology in patients with RSG may be considered. Further research of minimally invasive interventions for RSG resection is required.

The matrix-dependent 3D spheroid model of the migration of non-small cell lung cancer: a step towards a rapid automated screening.

In vitro 3D cell culture systems utilizing multicellular tumor spheroids (MCTS) are widely used in translational oncology, including for studying cell migration and in personalized therapy. However, early stages of cellular migration from MCTS and cross-talk between spheroids are overlooked, which was addressed in the current study. Here, we investigated cell migration from MCTS derived from human non-small cell lung cancer (NSCLC) cell line A549 cultured on different substrates, collagen gel or plastic, at different time points. We found that migration starts at 4-16 h time points after the seeding and its speed is substrate-dependent. We also demonstrated that co-culture of two NSCLC-derived MCTS on collagen gel, but not on plastic, facilitates cell migration compared with single MTCS. This finding should be considered when designing MCTS-based functional assays for personalized therapeutic approach and drug screenings. Overall, our work characterizes the in vitro 3D cell culture model resembling NSCLC cell migration from the clusters of CTCs into surgical wound, and describes microscopy-based tools and approaches for image data analysis with a potential for further automation. These tools and approaches also might be used to predict patterns of CTCs migration based on ex vivo analysis of patient biopsy in a 3D culture system.

[Anti-viral activity of a complex of the glycyrrhizic acid-alpha-glutamyltryptophan against the experimental lethal influenza infection in white mice caused by the oseltamivir-resistant strain of the virus].

Influenza virus is a leading causing factor of infectious respiratory human pathology. The search and development of novel anti-influenza drugs with a wide spectrum of activity is an important goal for medical science. In addition to specific anti-viral activity of the compound, its way of application is of great importance. In this work, we present the results of the study of the activity of a combination of glutamyl-tryptophan with glycirrhyzic acid (GTGA) against oseltamivir-resistant strain of the virus A/Vladivostok/2/09 (H1N1) at per os application on the model of the lethal influenza infection in white mice. The application of the GTGA was shown to decrease the specific mortality of animals (index of protection 43-50%), to increase the mean day of death to 2.5-3.9 days, and to reduce the infectious titer of the virus in the lung tissue to 1.5-1.9 Ig EID50/20 mg. The corresponding values for the reference compound oseltamivir were 14-25%, 1.1-1.9 days and 0.7 Ig EID50/20 mg, respectively, depending on the dose of the virus. The use of the GTGA also led to a reliable increase of the titers of interferon in the blood from 44.3 to 66.3 ME/mL. Morphological analysis revealed that GTGA lead to normalization of the structure of the lung tissue restricting the level of the cytodestruction and inflammation. The results obtained in this work allow the combination studied to be suggested as a promising anti-influenza drug that is active against the drug-resistant virus strains and can be applied orally.

[The anti-viral activity of the complex glycyrrhizic acid-alpha-glutamyl-tryptophan against experimental lethal influenza infection in white mice caused by oseltamivir-resistant strain of the virus].

Influenza virus is a leading causing factor of infectious respiratory human pathology. The ability to implement the antigenic drift and development of drug resistance makes it important to develop novel anti-influenza drugs of wide spectrum of activity. In this work, we present the results of the study of the activity of a combination of glycyrrhizic acid with dipeptide alpha-glutamyl-tryptophan against oseltamivir-reistant strain of the virus Al Vladivostok/2/09 (H1 N1) on the model of lethal influenza infection in white mice. Application of Orvilax was shown to decrease the specific mortality of animals (index of protection 39-67% depending on the dose of the virus and drugs combination), to increase the mean day of death to 3.7-5.0 days and decrease the infectious titer of the virus in lung tissue to 1.3 Ig EID50/20 mg. The corresponding figures for the reference compound Tamiflu were 8-11%, 0.5-1.5 days, and 0.6 Ig EID50/20 mg. The use of Orvilax also led to reliable increase of the titers of interferon in the blood from 30.4 to 56.5 ME/mL. The results obtained allow the drug to be considered as a promising anti-influenza remedy that is active against the drug-resistant virus strains.

[Problems of microbiological diagnosis of tuberculosis].

Objective methods of confirmation the diagnosis of tuberculosis are bacteriological (detection and isolation of Mycobacterium tuberculosis) and histological (detection of specific elements of granulomatous inflammation in the tissues). To improve the quality of microbiological examination of patients are needed equip clinical diagnostic laboratory fluorescent microscopes, modern flyuorohromnymi dyes and related training.

[Regulation of proliferation and viability of tumor cells in vitro by alloferon-1 and allostatin-1].

Alloferon-1 (AF) and allostatin-1 (AS) cytotoxic and growth modulating activities have been compared. AF is cationic oligopeptide isolated from the hemolymph of experimentally infected blow fly Calliphora vicina. AS is AF synthetic analog that differs from the parent molecule in two amino acids substituted. It has been shown that both AF and AS have no direct cytotoxic activity in concentrations ranging from 1 x 10(-1) to 10 microg/ml, however, the peptides demonstrated significant effect on tumor cells proliferation in vitro. Both peptides displayed growth modulating activity in mass cell cultures and boosted growth inhibiting activity of doxorubicin in the course of P388D1 cells cloning, although AS potentated doxorubicin cytostatic activity to a greater extent. Similarly, AS boosted anti-clonogenic activity of cyclophosphamide applied in a subthreshold concentration. Experiments with peptide-fluorescein complex have demonstrated that AF and AS belong to the group of cell-penetrating peptides. Moreover, the experiments displayed AF ability to bind with chromosomes.

Horner's syndrome in a patient presenting with a spontaneous pneumothorax.

Spontaneous pneumothoraces are a common thoracic problem presenting to an Accident and Emergency (A&E) department. The symptoms and signs are well described and a chest x-ray examination is usually diagnostic. However the neurological signs, specifically a Horner's syndrome on the ipsilateral side, are not widely recognised. This case illustrates the association and emphasises that when assessing a patient with a suspected spontaneous pneumothorax, an ipsilateral Horner's syndrome supports the clinical diagnosis. Further, its presence makes a tensioning pneumothorax, or as in this case a pneumothorax with significant collapse and apical adhesions, more likely. No previous case reporting the association has had the opportunity for thorascopic assessment and demonstration of likely cause.

Membrane type matrix metalloproteinases (MMPs) show differential expression in non-small cell lung cancer (NSCLC) compared to normal lung: correlation of MMP-14 mRNA expression and proteolytic activity.

Improved understanding of the involvement of matrix metalloproteinases (MMPs), including membrane-type MMPs (MT-MMPs), in human tumours has potential diagnostic, prognostic and therapeutic implications. We assessed the relationship between MT-MMP expression and clinicopathological parameters in human non-small cell lung cancer (NSCLC) and histologically normal lung tissue by quantitative Real Time PCR (qRT-PCR). All MT-MMPs (MMPs 14-17, 24 and 25) were detected by qRT-PCR with significantly higher MMP-14, -15 and -17 expression observed in tumour relative to normal lung specimens. MMP-16 was undetectable in normal lung but expressed in 8% tumours. MMP-15 demonstrated significant overexpression in adenocarcinomas relative to squamous cell carcinomas and normal lung tissue. MMP-14 mRNA expression strongly correlated to MMP-14 proteolytic activity in preclinical tumour models, indicating that qRT-PCR may predict MMP-14 activity levels in NSCLC. These data suggest that MMP-14, -15 and -17 may be good markers of disease, or therapeutic targets for treatment of human NSCLC.

[Non-specific resistance and immune responsiveness in patients with ischemic heart disease and cardiac arrhythmias]. / Nespetsificheskaia rezistentnoct' organizma i immunologicheskaia reaktivnost' u bol'nykh ishemicheskoi bolezn'iu serdtsa s narusheniiami serdechnogo ritma.

Nonspecific resistance (peripheral leukogram, integral leukocytic indices, types of adaptive responses, and phagocytosis) and immunological responsiveness (T- and B-immunity systems) were studied in 30 patients with chronic coronary heart disease (CHD) concurrent with various cardiac arrhythmia. In the patients, there was an increase in the relative counts of band neutrophils and lymphocytes, a decrease in the counts of segmented granulocytes and monocytes. A number of integral leukocytic indices (leukocytic index, lymphocytic-and-granulocytic index, total index, and deviation index) were increased and the neuthrophil/lymphocyte ratio was decreased. A higher frequency of a reactivation response and a lower frequency of a training response were revealed in the structure of their adaptive reactions. The patients with CHD concurrent with arrhythmia were also found to have increased granulopectic and phagocytic indices and higher tetrazolium nitroblue test values than healthy individuals. Their immunological responsiveness was characterized by a reduction in the absolute and relative counts of theophylline-sensitive T lymphocytes and an elevation of immunoglobulins A concentrations.

Pharyngo-laryngo-oesophagectomy and gastric pull-up for post-cricoid and cervical oesophageal squamous cell carcinoma.

Pharyngo-laryngo-oesophagectomy and gastric pull-up (PLOGP) is a complex and relatively uncommon procedure. The aim of this study is to analyse the results of PLOGP in patients with post-cricoid and cervical oesophageal squamous cell carcinomas. This study was a retrospective review of 26 patients (11 males + 15 females, mean age 63.5 years) who underwent PLOGP from 1988 to 1997. Eighteen (69 per cent) patients were staged as T(3) and eight (31 per cent) T(4). Eighteen (69 per cent) patients had N(0), seven (27 per cent) N(1) and one (four per cent) N(2) disease. Multiple primary tumours were recorded in three (11.5 per cent) patients. Four (15 per cent) patients had pre-operative radiotherapy with poor response and two (eight per cent) required emergency tracheotomy prior to surgery. Feeding jejunostomy was performed on 19 (73 per cent) and neck lymph node dissection in eight (31 per cent) patients. The mean duration of surgery was five hours (range 3.5 to 7.5) with a mean blood loss of 840 ml (range 160 to 1800), a mean stay in ICU of 4.2 days and hospital stay ranged from nine to 84 days (mean 34). Three (11.5 per cent) patients died (pneumonia - one, congestive heart failure - one, pulmonary embolus - one) in the early post-operative period. Eight (31 per cent) patients remain alive from 30 to 136 months (mean 58 months). Two (eight per cent) patients died with no evidence of disease. Thirteen (50 per cent) patients died of their disease between two to 51 months (mean 17.3 months) post-operatively. Kaplan-Meier survival estimates for one year was 65 per cent, for three years 35 per cent and for five years 26 per cent (see Figure 1). Median survival in the whole series was 18 months. Post-operative speech was with an electrolarynx in 16 (62 per cent). One patient (four per cent) used gastric speech and one patient (four per cent) used a Blom-Singer valve effectively. Five (19 per cent) patients had no speech post-operatively. All patients maintained oral feeding. Gastric transposition constitutes a safe and reliable method of restoring the continuity of the upper digestive tract following pharyngo-laryngo-oesophagectomy.

Antiviral and antitumor peptides from insects.

Insects can rapidly clear microbial infections by producing a variety of immune-induced molecules including antibacterial and/or antifungal peptides/polypeptides. In this report, we present the isolation, structural characterization, and biological properties of two variants of a group of bioactive, slightly cationic peptides, referred to as alloferons. Two peptides were isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina (Diptera), with the following amino acid sequences: HGVSGHGQHGVHG (alloferon 1) and GVSGHGQHGVHG (alloferon 2). Although these peptides have no clear homologies with known immune response modifiers, protein database searches established some structural similarities with proteins containing amino acid stretches similar to alloferon. In vitro experiments reveal that the synthetic version of alloferon has stimulatory activities on natural killer lymphocytes, whereas in vivo trials indicate induction of IFN production in mice after treatments with synthetic alloferon. Additional in vivo experiments in mice indicate that alloferon has antiviral and antitumoral capabilities. Taken together, these results suggest that this peptide, which has immunomodulatory properties, may have therapeutic capacities. The fact that insects may produce cytokine-like materials modulating basic mechanisms for human immunity suggests a source of anti-infection and antitumoral biopharmaceuticals.

[Role of the interferon system in the course of neglected forms of colorectal cancer]. / Rol' interferonovoi sistemy v techenii zapushchennykh form kolorektal'nogo raka.

Operations for neglected forms of colorectal carcinoma were performed on 66 patients. The interferon status was determined before the operation, on the 1st, 7th and 14th days after the operative intervention. "Viferon-2" was given to 18 patients (starting from 2 days before the operation) with the daily dose 1,000,000 IU. The investigation has shown that deep inhibition of production of interferon (alpha and beta by leukocytes increased risk of the development of postoperative pyo-inflammatory complications. Using the preparation "Viferon-2" is highly effective for prevention of such complications.

[Cycloferon in treating duodenal ulcers in rats]. / Tsikloferon v terapii iazvy dvenadtsatiperstnoi kishki u krys.

The possibility of using cycloferon (interferon inductor) for a complex treatment (in combination with the main drug solcoseryl possessing pronounced therapeutic properties) of duodenum ulcers was experimentally studied in male rats. The experiments showed a considerable difference in the interferon status of animals with model duodenum ulcers treated with cycloferon, solcoseryl, their combination, and placebo (control). The healing effect of solcoseryl administered in combination with cycloferon exceeded that of each component administered separately.

[Effect of probucol on cardiac electrophysiology in anginal patients with hyperlipidemia and diabetes mellitus type II]. / Vliianie probukola na élektrofiziologicheskie parametry serdtsa u bol'nykh stenokardiei, sochetaiushcheisia s giperlipidemiei i sakharnym diabetom tipa 2.

AIM: To investigate effects of a hypolipidemic drug with antioxidant action probucol on electrophysiological parameters of the heart in patients with ischemic heart disease (IHD), stable angina (SA), hyperlipoproteinemia (HLP) and diabetes mellitus (DM) type II. MATERIAL AND METHODS: The trial entered 48 IHD patients (11 males and 37 females) aged 47-73 years with SA functional class II and III (39.4 and 60.6%, respectively), secondary HLP (mean group total cholesterol 6.5 +/- 0.17 mmol/l), DM type II (mean fast glucose 7.7 +/- 1.8 mmol/l) and obesity (mean body mass index 29.7 +/- 2.2 kg/m2). Transesophageal pacing of the left ventricle was conducted in all the patients before probucol treatment and 18 hours, 1 month and 3 months after it. RESULTS: Probucol (a single dose 500 mg) significantly reduced the time of recovery of sinus node function. Three months of probucol administration in a dose 1000 mg/day enhanced pacemaker activity of the sinus node. CONCLUSION: In addition to a beneficial effect on lipid metabolism (a decrease of total cholesterol by 13.4%, LDLP cholesterol by 15.2%, triglycerides by 15.8%), probucol enhanced pacemaker activity of the sinus node. This makes it perspective in patients with sinus node dysfunction. Caution is necessary in prescribing probucol to patients with supraventricular tachycardia caused by re-entry mechanism.

Total thoracic oesophagectomy for oesophageal carcinoma: has it been worth it?

OBJECTIVE: Anastomotic recurrence is a major cause of late mortality following oesophago-gastrectomy (OG) for carcinoma of the oesophagus and oesophago-gastric junction using either the Ivor Lewis or left thoraco-abdominal approach with intra-thoracic anastomosis. The aim of this study was to determine whether the more extensive total thoracic oesophagectomy (TTO) with cervical anastomosis would reduce the anastomotic recurrence rate while maintaining acceptable operative morbidity and mortality. METHODS: From January 1988 to December 1996, 108 total thoracic oesophagectomies and 66 oesophago-gastrectomies were performed with curative intent in 174 patients (125 males, mean age 62.4 years) with carcinoma (squamous cell carcinoma in 34 and adenocarcinoma in 140) of the middle (31 patients) and lower (44 patients) oesophagus and oesophago-gastric junction (99 patients). RESULTS: Minor complications occurred in 37 (34%) total thoracic oesophagectomy and 18 (27%) oesophago-gastrectomy patients, major complications in 15 (14%) and 5 (8%) and peri-operative death in 5 (4.6%) and 7 (11%) patients, respectively. Anastomotic leakage occurred in 10 (9%) total thoracic oesophagectomy and 5 (8%) oesophago-gastrectomy patients, and was fatal in 1 (1%) and 4 (6%). There was no incidence of tumour at or within 5 mm of the proximal limit in the total thoracic oesophagectomy group and this was reflected in the complete absence of anastomotic recurrence. In the oesophago-gastrectomy group there was a positive proximal resection margin in 13 (20%) and 13 anastomotic recurrences (22% of peri-operative survivors). The 5-year survival (including operative mortality) was 29% for total thoracic oesophagectomy compared with 21% for the other techniques (P = 0.028 log rank test). Median survival was 25.2 months after total thoracic oesophagectomy and 15.8 after oesophago-gastrectomy. CONCLUSIONS: Total thoracic oesophagectomy can be performed in oesophageal cancer patients with comparable morbidity to that of lesser resections. Incomplete proximal resection and anastomotic recurrence did not occur in this series of 108 total thoracic oesophagectomies and this is reflected in an increased medium term survival. The improved survival is most apparent for tumours of the oesophago-gastric junction.

[Dipyridamole (curantil) treatment of anginal patients: results of treatment for many years]. / Mnogoletnii opyt lecheniia bol'nykh stenokardiei dipiridamolom (kurantilom).

AIM: To assess effect of curantil optimal doses on clinical condition, coronary reserves, systemic microcirculation and peripheral hemodynamics in patients with stable angina pectoris (AP) given a course or continuous treatment. MATERIALS AND METHODS: A 2-month treatment with curantil with a gradual increase of the daily dose to 0.45 g was given to 261 patients with AP. After that the treatment was continued to 3 years in 38 patients. The coronary reserves were examined with bicycle exercise tests, peripheral hemodynamics and microcirculation were investigated with tachooscillography and conjunctival biomicroscopy. RESULTS: The 2-month curantil treatment was effective in 81% of the patients with AP functional class II-III and 60% of those with AP class 4. Exercise tolerance increased in AP of functional class II-III and IV by 50 and 24%, respectively. Ischemic depression of ECG ST segment induced by the exercise shortened. Prolongation of the treatment to 1 year resulted in further regression of AP and provided a 57% increase in muscular performance. The 3-year treatment maintained the 1-year effectiveness which was associated with lowering of postload and improvement of microcirculation, in particular, a 2-fold decrease in manifestations of sludge. CONCLUSION: The antianginal effect of optimal daily doses of curantil is more potent in angina of effort, grows step-by-step and reaches maximum if continued for a year. A hemodynamic effect of curantil manifests with lowering of postload and improvement of microcirculation. This allows to recommend curantil in combined treatment of chronic coronary heart disease.