Neutrophils are the most abundant population of leukocytes, which constitute the defense against pathogens. Released by neutrophils the proteolytic enzymes and reactive oxygen species help in eliminating infections, but also cause extensive tissue damage. Neutrophil apoptosis plays an essential role in cell homeostasis and resolution of inflammation. It is mediated by a complex network of intracellular apoptotic/survival signaling pathways and can be modulated by a variety of extracellular stimuli such as hypoxia. Here, we review recent studies on the mechanisms of neutrophil death and survival accentuating on neutrophil apoptosis under hypoxic conditions. Neutrophils possess components of both extrinsic and intrinsic apoptotic routes. However in neutrophils this mechanism has special features. The involvement of death receptors, caspases, mitochondria, and Bcl-2 proteins are discussed. Both the transcription factor NF-kappaB and p38MAPK regulate the neutrophil apoptotic program. Despite that reactive oxygen species (ROS) can directly promote and/or adjust apoptosis, there is no consensus about the role of ROS on neutrophil lifespan. Thus both the type of ROS involved and the site of their generation may be important for neutrophil apoptosis. Finally, hypoxia can activate several signaling pathways. The possible differences between the effects of sustained and intermittent hypoxia are also addressed.

The article presents a draft of clinical recommendations for the diagnosis and treatment of differentiated thyroid cancer in adult patients, which provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches.

The article presents a draft of clinical recommendations for the diagnosis and treatment of medullary thyroid cancer in adult patients, which provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches.

СПОСОБ УСТРАНЕНИЯ ДЕФЕКТА ПОЛОСТИ РТА И ЯЗЫКА СЛОЖНОСОСТАВНЫМ СВОБОДНЫМ «ХИМЕРНЫМ» РЕВАСКУЛЯРИЗИРОВАННЫМ, РЕИННЕРВИРОВАННЫМ КОЖНО-МЫШЕЧНЫМ ЛОСКУТОМ ПОСЛЕ ТОТАЛЬНОЙ ГЛОССЭКТОМИИ

The study objective is to demonstrate the difficulties associated with treatment of HPV-negative oropharyngeal cancer.Material and methods. A 52-year-old male patient visited a doctor in P.A. Herzen Moscow Oncology Research Institute in January 2017 with complaints of pain in the right part of the oropharynx irradiating to the right ear and difficulties with swallowing food and liquids. The patient was diagnosed with stage IVA oropharyngeal cancer (cT3N2bM0).Results. The patient underwent a course chemoradiotherapy (CRT); as a result, the tumor in the area of the right tonsil became indeterminable 2 weeks later. Three months after completing the course of CRT, the patient underwent modified radical right-sided lymph node dissection. Histological examination revealed metastases from poorly differentiated squamous cell carcinoma in 3 lymph nodes (LNs) with an invasion into adjacent adipose tissue. In October 2017, we received a histological confirmation of ongoing tumor growth in the area of the tongue root and LN metastases in the left side of the neck (yrpT4aN2cM0). We performed resection of the mandible, tongue, soft tissues of the oral floor, and right side of the oropharynx with installation of an oropharyngeal stoma, extended radical left-sided neck lym-phadenectomy with excision of soft tissues (levels I—V), defect repair using an autologous pectoral musculocutaneous flap, and tracheostomy. In March 2018, the patient was found to have continuing tumor growth in the area of the epiglottis and floor of the oral cavity. The patient underwent laryngectomy with oropharyngeal resection and end tracheostomy. In July 2018, we again received a histological confirmation of tumor growth in soft tissues of the anterior neck. We performed resection of the tumor and soft tissues with subsequent plastic reconstruction of the defect. In October 2018, the patient presented with multiple metastases in both lungs. He received a course of immune therapy. Positron emission tomography revealed neoplastic foci with pathological metabolic activity in the area of the alveolar process of the mandible (left side), soft tissues of the neck, lungs, left-sided axillary LNs, and mediastinal LNs. It was decided to continue immune therapy.Conclusion. HPV-negative oropharyngeal cancer requires an optimized treatment algorithm and, possibly, more aggressive therapeutic measures, such as increased radiation doses. Both overall management strategy and recommended standard scheme of CRT should be revised; the role of surgical and chemotherapeutic components of treatment should also be reassessed. We believe that surgical intervention should be considered regardless of the effect of radiation therapy, while the duration of follow-up after CRT should be reduced.

Squamous cell carcinoma (SCC) is the second most common skin cancer after basal cell carcinoma. Usually, antitumor treatment is sufficiently effective: recovery rate is about 90 %. Primary SCC is characterized by variable growth rate, as well as by involvement of regional lymph nodes (from 1 % for well differentiated tumors to 10 % for poorly differentiated tumors, size 3 cm and /or invasion depth 4 mm). In case of SCC development near post-burn scar, the rate of regional metastasis is 10-30 %. A relatively small possibility of distant metastasis also exists, with overall mortality of 2-3 %. In SCC of the head and neck, both hematogenic and perineural advancement into the CNS are possible. Total rate of local recurrences is 25 %. The main factors of local and regional recurrences are location (head and neck), size (tumor diameter 2 cm), invasion depth (4 mm), tumor differentiation, perineural involvement, patient's immune status and previous treatment. Tumors in areas that weren»t subjected to solar radiation and tumors in the areas of pervious irradiation, thermal damage, scarring or chronic ulcers are more prone to recurrences and metastasis. Poorly differentiated and anaplastic SCC is more likely to metastasize compared to well differentiated tumors. Medially located SCC is the area of the face mask and lip is more prone to neural invasion. Multidisciplinary approach with involvement of all specialists in antitumor treatment is necessary for development of treatment tactics.