[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.

[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.

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.

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.

Perioperative neutron brachytherapy with californium-252.

Between 1973 and 1988, 495 patients were treated with Cf-252 neutron brachytherapy. Cf-252 neutron therapy sources developed in the USSR has been used in the trial. A numerical reconstruction method for localization of Cf-252 cell coordinates by projections on orthogonal radiographs has been designed and used for treatment planning. Eight (1.6%) patients with recurrent and persistent head and neck tumors and ages from 32 to 48 years (mean age 43 years) were treated with Cf-252 perioperative neutron brachytherapy. There were three patients with oral cavity, one with oropharynx, three with parotid gland cancers, and one with a skin tumor. The dose rate ranged fro 3.2 cGy/h to 11.1 cG/h, the minimal peripheral dose ranged from 3 Gy to 8 Gy. Initial local control was achieved in all patients. Local recurrence developed in two cases. Three patients died in first year after therapy. Three patients died during the second year. Two patients are long term cures, one patient more than nine years and one eight years, that is 25% of the treated patients.

Neutron brachytherapy in the treatment of melanoma.

PURPOSE: The use of Cf-252 for treatment of cutaneous malignant melanoma is presented. METHODS AND MATERIALS: From 1975 to 1992, plaque Cf-252 applicator neutron brachytherapy was performed in nine patients with skin malignant melanoma of head and neck or chest wall. Neutron brachytherapy alone was applied in six patients; two patients received neutron brachytherapy before and one after photon teletherapy. Tumor neutron brachytherapy doses ranged from 3.9-11.5 Gy. Four patients underwent surgical resection of the primary tumor and in six cases, regional lymph node dissection was done. RESULTS: The patients survival times ranged from 3 months to 12 years; 2-year survival was 50% and 30% of the patients lived 3 years. The mean survival time was 39 months. All but 1 patients died because of distant metastases. Local tumor control was achieved in all cases. CONCLUSION: The clinical study shows the relative sensitivity of melanoma to the neutron irradiation and offer new possibilities in Cf-252 brachytherapy.

Total thoracic esophagectomy for esophageal cancer.

BACKGROUND: Many current methods of esophageal resection have drawbacks that result in inadequate proximal resection, inadequate lymphadenectomy, and difficult gastric and splenic access. We describe a technique that allows reliable and safe access to the chest, abdomen, and neck. STUDY DESIGN: From 1988 to 1995, 113 patients (82 men; mean age 65.3 +/- 4.5 years) with carcinoma of the esophagus or esophagogastric junction (middle third in 34, lower third in 41, and cardia in 38) underwent total thoracic esophagectomy. The histology was adenocarcinoma in 71 (62.8%), squamous cell carcinoma in 32 (28.3%), and undifferentiated carcinoma in 10 (8.9%) of the patients; 57 tumors (50.5%) were stage III. The esophagus and stomach were mobilized through a left thoracoabdominal incision. After completion of the esophageal resection, the fundus of the stomach was sutured to the esophageal stump to allow later delivery of the stomach into the neck. The esophagogastric anastomosis was performed with continuous single-layer absorbable suture through a left oblique cervical incision. RESULTS: The mean duration of the operation was 309.2 +/- 47.9 minutes. Hospital stay ranged from 5 to 49 days (median, 12 days). The perioperative mortality rate was 4.4%. Anastomotic leak occurred in six patients (5.3%), one of whom died. The proximal resection margin was microscopically free of tumor in all cases, and with a minimum followup period of 18 months, there has been no anastomotic recurrence in any patient. Actuarial survival at 1 year was 63.4% +/- 4.9%, at 3 years 41.4% +/- 5.9%, and at 5 years 22.7% +/- 6.3%. CONCLUSIONS: Total thoracic esophagectomy through the left chest with a separate left cervical incision allows clear access to the esophagus and stomach and good tumor clearance. This procedure may be performed with a low rate of anastomotic leakage, a very low mortality rate, and no anastomotic tumor recurrence.

Management of a patient with synchronous squamous cell cancers of the oesophagus and stomach.

Synchronous tumours of the oesophagus and stomach are relatively rare and principles of diagnostics and treatment are still the matter of discussion. Either primary tumours or primary and metastatic lesions in the oesophagus and stomach have been described. The difficulty of diagnosing the gastric lesion and necessity of fast decision making during surgery are reasons to discuss this case.

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.

Simultaneous cardiac surgery with pulmonary resection: presentation of series and review of literature.

BACKGROUND: The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature. METHODS: Thirteen patients (male ten, female three; mean age 65 years) underwent simultaneous cardiac surgery and pulmonary resection. Lung pathology consisted of primary lung carcinoma (n = 10), benign disease (n = 2) and carcinoid (n = 1). Lung resections included pneumonectomy (n = 3), lobectomy (n = 4), segmentectomy (n = 1) and local excision (n = 5). Cardiac procedures consisted of coronary artery bypass grafting (CABG) in 11, aortic valve replacement in one and mitral valve repair with CABG in one patient. In all but one case the lung resection was performed prior to heparinization and cardiopulmonary bypass (CPB). In two patients, with suitable coronary anatomy, myocardial revascularization without CPB was performed to reduce morbidity. RESULTS: There was no hospital mortality. Postoperative blood loss and ventilation requirements were reduced in the patients who were operated on without CPB. Prolonged ventilatory support was required in two cases. All patients with benign pathology are alive. In the lung cancer group there have been five late deaths: disseminated metastatic disease (n = 3), anticoagulant related haemorrhage (n = 1) and broncho-pleural fistula (n = 1). Of the remaining five patients four are alive and disease free 7-23 months post-operatively; one patient has recurrent disease 40 months post-operatively. CONCLUSIONS: Simultaneous pulmonary resection and cardiac surgery is associated with acceptable operative morbidity and mortality. In patients with lung carcinoma long-term survival was determined by tumour stage. The avoidance of CPB may be advantageous by decreasing blood loss and ventilation requirements.

Subcutaneous jugulofemoral bypass: a simple surgical option for palliation of superior vena cava obstruction.

BACKGROUND: Percutaneous placement of an intraluminal stent is usually a successful intervention for the disabling symptoms of Superior Vena Cava (SVC) obstruction. However, on occasion this may not be feasible and, as malignant disease is responsible for 90% of cases, the morbidity associated with median sternotomy or thoracotomy usually precludes surgical bypass. OBJECTIVE: To achieve good palliation of the symptoms of SVC obstruction by surgical bypass without performing sternotomy or thoracotomy. PATIENTS: Two patients with SVC obstruction secondary to lung cancer and a third after radiochemotherapy for malignant mediastinal teratoma. In all patients intraluminal stenting was considered but was not possible. METHODS: Jugulofemoral bypass was performed using long saphenous vein which was tunnelled subcutaneously from the femoral to the jugular vein. RESULTS: One patient required wound exploration for haemorrhage. Good palliation was achieved in all patients. One patient died 3 months post-operatively from lung cancer and the remaining two are alive without symptoms at 13 months and 6 weeks postoperatively. CONCLUSIONS: Though the majority of patients with SVC obstruction can be treated with non-surgical methods, subcutaneous jugulofemoral bypass may provide good palliation if these are not feasible.

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.

[Results of a long-term follow-up of exercise test indicators in patients with various courses of stenocardia]. / Rezul'taty mnogoletnego nabliudeniia za pokazateliami veloérgometricneskoi proby u bol'nykh s razlichnym techeniem stenokardii.

The study was undertaken to examine the natural history of stable angina in 295 patients who had been followed up for an average of 5.4 years. The results showed that among them the survival rate was 77%. Out of 217 survivors, 47.5% exhibited no changes in the manifestations of coronary heart disease, only 7.8% showed improvement and increase in exercise performance, in 44.7%, their status became worse as manifested by more frequent anginal attacks and significantly diminished exercise tolerance; 3.2% developed congestive heart failure, there were marked ECG cardiac arrhythmias or scarry changes due to sustained myocardial infarction in 3.2% and 11.1%, respectively.

[Electrocardiography in women with angina pectoris during physical exertion]. / Elektrokardiogramma u zhenshchin, bol'nykh stenokardiei, vo vremia fizicheskoi nagruzki.

Comparative study was conducted of ECG changes during an attack of angina pectoris induced by physical exertion on a bicycle ergometer in 74 females and 100 males suffering from angina pectoris. It is shown that with a similar clinically determined severity of angina pectoris, tolerance to physical exertion is significantly lower in females than in males. Essential differences were also revealed in the ECG changes during an anginose attack. The data obtained are evidence that the approach to the appraisal of the results of load tests in ischemic disease of the heart in females should evidently differ from that in males.

[Chronotropic reserve of the heart in stenocardia]. / O khronotropnom rezerve serdtsa u bol'nykh stenokardiei.

The rate of cardiac contractions was studied prior to and during the bicycle ergometry test and in the period of restitution in 140 patients with angina pectoris of various severity as compared to practically healthy males. In distinction to healthy individuals, patients with angina pectoris reacted to physical exertion of equal force by a higher rate of cardiac rhythm which returned back to normal more slowly in the period of restitution. They were also marked by more rapid "uneconomical" expenditure of the cardiac chronotropic reserves. In angina pectoris, the capacity of the heart to maximum increase in the rate of contractions was limited. With the growth in the severity of chronic coronary insufficiency, the attack of angina induced by muscular exertion developed at a lesser frequency of the cardiac rhythm (p is less than 0.001).