Photodynamic therapy in a patient with perianal extramammary Paget's disease.

Extramammary Paget's disease is a rare neoplasm of apocrine gland-bearing areas of the skin. One of the most common localizations of such a tumor is the perianal area. Surgery is the most frequently reported therapy. However, it is an invasive procedure and complicated by a high recurrence rate. An alternative to surgical treatment may be non-invasive photodynamic therapy. We describe in this article the case of a 69-year-old patient with extramammary Paget's disease (a large tumor in the perianal area 22 × 18 cm) successfully treated with chlorin e6 photodynamic therapy.

[Metastatic solid pseudopapillary tumor in the perinephric fat without a primary identified focus]. / Metastaz solidnoi psevdopapillyarnoi opukholi v paranefral'nuyu kletchatku bez pervichno vyyavlennogo ochaga.

Solid pseudopapillary tumor of the pancreas is an extremely rare neoplasm of the exocrine portion of this organ, which affects mostly young women and is characterized by a low malignancy potential and a relatively benign clinical course. According to the literature, even in disease progression as metastases, the overall 5-year survival rate is more than 95%. The paper describes a clinical case of a female patient with a solid pseudopapillary pancreatic tumor regarded as a metastatic neoplasm in the retroperitoneal space after surgical treatment previously performed in 2001.

[Endolaryngeal resection of the larynx for adenocystic cancer]. / Endolaringeal'naya rezektsiya gortani pri adenokistoznom rake.

Adenocystic carcinoma accounts for 3-5% of all malignant neoplasms of the head and neck organs. Due to the rarity of detecting this cancer in the larynx, treatment options are still controversial: surgery with postoperative radiation therapy or surgery alone. Patient A., 64 years old, turned to the City Clinical Oncological Hospital No. 1 in October 2019 with complaints of moderate pain when swallowing, sensation of a foreign body. Fibrolaryngoscopy revealed an exophytic form of growth bright red color formation with a small tuberous surface up to 12 mm in size in the area of the free left edge of the epiglottis. There was a thickening of the pharyngeal-epiglottis fold. Histological examination revealed adenocystic cancer. Diagnosed with Laryngeal cancer with cT1N0M0. On December 23, 2019, endolaryngeal resection of the larynx was performed using an operating microscope in the volume R0. This observation is of interest both in morphological terms (extremely rarely detected cancer of the larynx) and in terms of treatment (an organ-preserving operation was performed - endolaryngeal resection of the larynx).

[Solitary fibrous tumor of pleura (symptoms, diagnosis, treatment)]. / Solitarnaya fibroznaya opukhol' plevry (klinika, diagnostika, lechenie).

OBJECTIVE: Optimization of diagnosis and treatment of patients with solitary fibrous tumor of pleura, analysis of overall survival and disease-free survival, predictors of recurrence. MATERIAL AND METHODS: There were 66 patients with solitary fibrous tumor of pleura (26 men and 40 women) aged 57.6 years (range 26-80 years). Asymptomatic course was found in 29 (44%) patients, various symptoms - in 37 (56%) patients. Thoracotomy was applied in 36 patients, thoracoscopy - in 30 patients. Immunohistochemical examination included analysis of definition of Stat6 expression. RESULTS: Benign variant of SFT was diagnosed in 50 (75.7%) patients, malignant variant - in 16 (24.3%) patients. STAT6 expression was observed in all cases. Postoperative morbidity was 9%, mortality - 1.6%. Recurrence was diagnosed in 2 (4%) patients with benign variant of disease and in 5 (31.2%) patients with malignant variant (2 of them died from progression of disease). Progression-free survival was 89.4%, overall survival - 95.4%. Predictors of recurrence are tumor dimension over 10 cm, necrosis and/or hemorrhagic component of tumor, mitotic count of at least four per 10 high-power fields. CONCLUSION. S: Olitary fibrous tumor of pleura is a rare mesenchymal fibroblastic neoplasm growing from submesothelial layer. Differential and preoperative morphological diagnosis of SFT is difficult and demands a special immunohistochemical examination with analysis of Stat 6 expression. Surgery is preferred for tumor de novo and recurrent neoplasm.

[Expression of ganglioside GD2 on colorectal adenocarcinoma cells]. / Ékspressiia gangliozida GD2 na kletkakh kolorektal'noi adenokartsinomy.

Using flow cytometry GD2 ganglioside expression was evaluated both on colorectal adenocarcinoma cell lines and on tumor tissue samples from colorectal cancer patients. The marker was found on EpCAM-positive tumor cells in 6 of 12 patients' samples but not on the HT29 and CaCo-2 cell lines. GD2 expression was not an exceptional feature of cancer stem cells, since its expression level was similar on CD133-positive and CD133-negative tumor cells. Thus, the presence of GD2 ganglioside was revealed on colorectal adenocarcinoma cells for the first time. This finding makes it possible to use targeted therapy to treat this disease.

[Adenoid cystic carcinoma of the larynx: a case report]. / Nabliudenie adenokistoznogo raka gortani.

Adenoid cystic carcinoma is one of the rare pathological conditions affecting the larynx. It is known to develop from the glandula elements present in this organ. The authors report a clinical observation of adenoid cystic carcinoma in the form of an exophytic tumour of the pale pink colour having a smooth surface and the well-pronounced vascular patterns at the base. The neoplasm is localized in the arytenoid and retroarytenoid cartilage regions. Being of 3.5-4 cm in size, the tumour causes the narrowing of the larynx in its posterior portions and restricts its mobility. Bearing in mind the considerable extension of the neoplastic process, we undertook laryngectomy including the resection of the orolaryngopharynx and the cervical portion of the oesophagus, the subtotal resection of the thyroid gland and the simultaneous reconstruction of the orolaryngopharynx.

[Modern approaches to the diagnosis of precancerous pathology and early lung cancer]. / Sovremennye podkhody k diagnostike predopukholevoi patologii i rannego raka legkogo.

AIM: To assess the possibilities of modern diagnostic techniques to diagnose precancerous pathology and early central lung cancer. MATERIAL AND METHODS: Analysis of Russian and foreign publications for precancerous pathology and early lung cancer, results and comparison of various diagnostic techniques. RESULTS: Central lung cancer has a stepwise development with transformation of normal bronchial epithelium to hyperplastic followed by focal metaplasia, dysplasia, cancer in situ (CIS) and microinvasive cancer. Fluorography, chest X-ray, computed tomography, magnetic resonance imaging and sputum cytology examination are used to diagnose lung cancer. However, endoscopy plays a leading role in diagnosis of early central lung cancer which rapidly and effectively detects changes of tracheobronchial tree mucosa at the initial stages of carcinogenesis thanks to the use of modern techniques (spectral, autofluorescent and ZOOM - endoscopy).

Changes in the functional activity of mitochondria isolated from the liver of rat that passed the preadaptation to ultra-low deuterium concentration.

The incubation in deuterium-depleted medium of mitochondria isolated from the liver of rats that consumed drinking diet with depleted deuterium (46 ppm) revealed a higher (by 35%) generation of hydrogen peroxide in comparison with the mitochondria (isolated from the liver of rats that consumed drinking diet with 152 ppm deuterium) incubated in medium that contained 152 ppm deuterium. Succinate addition to the reaction system led to an increase in the production of hydrogen peroxide in isolated mitochondria by 44-81%, whereas the difference in the generation of H2O2 between the organelles incubated in mediums 46 and 152 ppm was reduced by 14%. The revealed change in the functional activity of mitochondria suggests the ability of the organism to adapt to the deuterium-depleted drinking diet, which is probably due to the formation of the D/H isotope transmembrane gradient.

[Biomarkers of prostate cancer sensitivity to the Sendai virus].

Metastatic prostate cancer is often associated with either primary or intractable castration-resistant prostate cancer (CRPC), thus justifying the search for entirely new ways of treatment. Oncolytic viruses are able to selectively induce the death of tumor cells without affecting normal cells. A murine Sendai virus has potential to be used as an oncolytic agent. However, tumors vary in their sensitivity to different viruses, prompting us to attempt to identify corresponding biomarkers that reflect the interaction of cancer cells and the virus. Here, we show that the sensitivity of primary prostatic adenocarcinoma cell lines to Sendai virus strain (SeVM) vary substantially. Using quantitative PCR, we evaluated expression levels of genes that encode RIG-1-like and Toll-like receptors (TLRs) in cell lines and showed that the levels of mRNAs that encode TLR3 and TLR7 correlate with a degree of sensitivity of the cells to Sendai virus. The lines with lower levels of TLR3 and TLR7 expression are more sensitive to the virus.

[The difficulties of cytologic diagnostic of breast diseases based on trepanobiopsy samples.]

The article analyses, on the basis of scientific publications and original data, the causes of erroneous cytological conclusion concerning samples of trepanobiopsies of mammary gland. The most prevalent benign affections that are characterized by most frequent hyper diagnostic of cancer are fibro-adenoma with proliferation of epithelium and sclerosing adenosis. At the same time, certain modifications of lobular carcinoma of mammary gland, tubular, papillary cancer as well as highly differentiated invasive carcinoma of nonspecific type from cells with ulterior nuclear atypism sometimes it is difficult to diagnose at the cellular level. The sensitivity of cytological diagnostic of pathology of mammary gland using samples of trepanobiopsies makes up 97.5%, specificity - 98.5%. The number of false positive cytological conclusions about presence of malignant tumor makes up to 0.6%, false negative - 1.5%. The reliability of cytological analysis makes up to 97.4%, efficiency - 96.3%.

[The application of automated system of evaluation of morphology of cells for diagnostic of Hodgkin's lymphoma in education process of course of clinical oncocytology].

The analysis of cytological analysis data demonstrated that cytological diagnosis of Hodgkin's lymphoma was established properly in exact and estimated form in 92.8%. The cytological reports mentioned no alternatives. The cytological analysis system Vision Cyto® was applied to analyze cellular content by micro photos of cytological samples of 119 patients with established morphologic (histological and cytological) diagnosis of Hodgkin's lymphoma. On the basis of the received data training programs were developed concerning cytological diagnostic and detection of forms of disease. The gallery was organized concerning pictures of tumor and background cells playing key role in cytological diagnostic. The distinctive differential diagnostic indications of various forms of Hodgkin's lymphoma were established.

[THE TECHNOLOGY "CELL BLOCK" IN CYTOLOGICAL PRACTICE].

The article presents summary information concerning application of "cell block" technology in cytological practice. The possibilities of implementation of various modern techniques (immune cytochemnical analysis. FISH, CISH, polymerase chain reaction) with application of "cell block" method are demonstrated. The original results of study of "cell block" technology made with gelatin, AgarCyto and Shadon Cyoblock set are presented. The diagnostic effectiveness of "cell block" technology and common cytological smear and also immune cytochemical analysis on samples of "cell block" technology and fluid cytology were compared. Actually application of "cell block" technology is necessary for ensuring preservation of cell elements for subsequent immune cytochemical and molecular genetic analysis.

[Molecular genetic mechanisms of drug resistance in prostate cancer].

The major problem in prostate cancer treatment is the development of drug resistance and especially important, cross-resistance. The mechanisms of drug resistance, which are divided into ligand-dependent (requiring the presence of androgens in the cell) and independent (not requiring the presence of androgens) are reviewed. The mechanisms are mainly represented with mutations of the androgen receptor and expression of aberrant constitutively active splice variants, as well as up-regulation of genes involved in androgens synthesis.

[ENDOCYTOSCOPY--NEW TYPE OF ENDOSCOPIC EXAMINATION OF LOWER GASTROINTESTINAL AND RESPIRATORY TRACT].

Majority of published data describing endocytoscopic examination of upper gastrointestinal tract mucosa, but in recent publications, it is reported, that endocytoscopy is suitable for small bowel, colon, respiratory tract and even peritoneum "optical biopsy". In number of articles possibilities of celiac sprue diagnostics with endocytoscopy is discussed, but small-bowel endocytoscopy is limited, due to absence of endocytoscopes, compatible with enteroscopes. More widely endocytoscopy is used in colon, mostly in lateral-spreading adenomas diagnostics. Prof. S-E. Kudo developed endocytoscopic classification of colonic mucosa changes, used for differential diagnostics and lesion mapping, describing hyperplasia, adenomas with different grades of intraepithelial neoplasia, non-invasive and invasive cancer. Some authors reported about good possibilities of endocytoscopy in inflammatory bowel disease diagnostics. Most of data, related to respiratory tract endocytoscopic examination, focused on precancerous conditions and early pharyngeal and lung cancer, and the preliminary results are promising, but, unfortunately, for now, endocytoscopy in bronchial tree is limited, due to lack of thin endocytoscopes. According to some article data, it is possible to use endocytoscopy not only in gastrointestinal and respiratory tract, but also in optical confirmation of peritoneal tumor dissemination in gastric and ovarian cancer patients, and--in bladder mucosa examination.

[ENDOCYTOSCOPY--NOVEL ENDOSCOPIC DIAGNOSTICS APPROACH: PRINCIPLES AND PROCEDURE].

Endocytoscopy is one of the most novel endoscopic diagnostic procedures, providing optical magnification up to 1150 times of gastrointestinal and respiratory tract mucosa. Such approach allows real-time tissue and cellular structure visualization. Endocytoscopy, along with confocal laser endomicroscopy, can be considered as "optical biopsy" in vivo. Of course, endocytoscopy currently is experimental diagnostic method, all available endocytoscopes are prototypes. According to published data, endocytoscopy can be used in precancerous conditions and early intramucosal cancer diagnostics in esophagus, stomach, colon and bronchial tree. Different types of endocytoscopes are used for examinations: some of them are baby-scopes, with fixed magnification 570-1150 times, introduced into accessory channel of the therapeutic parent-endoscope, others--are integrated type, providing scalable magnification from 80 to 380 times. As for traditional pathology ex vivo, for endocytoscopy mucosal cell nuclei stain is needed. For vital staining during endocytoscopy methylene blue, toluidine blue and crystal violet in different concentrations are more often used. In cases of squamous-cell dysplasia or cancer, it is recommended to use 1% methylene blue solution, whereas in intestinal type metaplasia, dysplastic changes and cancer (Barrett's esophagus, P. Correa precancerous cascade, colon adenomas), 1% toluidine blue is preferred. With endocytoscopy, after vital staining, we can visualize and estimate mucosa tissue and cell characteristics: papillae, crypt and gland shapes and sizes, their integrity (tissue markers); cell nuclei size and shape, polarity and nuclear dye intensity (cell markers).

[Downregulation of OGDHL expression is associated with promoter hypermethylation in colorectal cancer].

Cell metabolic reprogramming is one of the cancer hallmarks. Glycolysis activation, along with suppression of oxidative phosphorylation and, to a lower extent, the TCA cycle, occurs in the majority of malignant tumors. A bioinformatics search for the glucose metabolism genes that are differentially expressed in colorectal cancer (CC) was performed using the data of The Cancer Genome Atlas (TCGA) Project. OGDHL for an oxoglutarate dehydrogenase complex subunit, which is involved in the TCA cycle and is indirectly responsible for the induction of apoptosis, was identified as one of the most promising candidates. A quantitative PCR analysis showed, on average, an eightfold downregulation of OGDHL in 50% (15/30) of CC samples. Based on the TCGA data, promoter hypermethylation was assumed to be a major mechanism of OGDHL inactivation. Bisulfite sequencing identified the OGDHL promoter region (+327 ... +767 relative to the transcription start site) that is often methylated in CC samples with downregulated ODGHL expression (80%, 8/10) and is possibly crucial for gene inactivation. Thus, frequent and significant OGDHL downregulation due to hypermethylation of a specific promoter region was demonstrated for CC. The OGDHL promoter methylation pattern was assumed to provide a marker for differential diagnosis of CIMP+ (CpG island methylator phenotype) tumors, which display dense hypermethylation of the promoter region in many genes.

[Effect of water isotopic composition on Rhodococcus erythropolis biomass production].

The effect of water isotopic composition on concentration of oil-oxidizing actinobacteria Rhodococcus erythropolis VKM Ac-2017D cellular biomass is observed during cultivation in liquid nutrient media. The value for the effect was determined by experimental conditions, including consecutive use of hydrophilic and hydrophobic nutritious substrates--saccharose and hexadecane. It is shown, that when Rhodococcus erythropolis VKM Ac-2017D cells, cultivated in media with sucrose and 71 and 98 ppm deuterium content in water were inoculated into the similar in mineral and isotopic composition media with hexadecane, a considerable increase in cellular biomass production is observed if compared to a control sample in which water with 150 ppm deuterium concentration was used.

[Diagnosis and treatment for Paget's breast cancer: state of the art].

Breast cancer is the most common cancer in women. According to WHO experts in the world each year there are revealed from 800,000 up to 1 million new cases of breast cancer. In the structure of malignant tumors morbidity among female population, in Russia in 2012 breast cancer ranked the first place (20.7%) and remained the leading malignant pathology in women. Paget's breast cancer is a rare form of breast cancer that occurs in the mouth of the excretory ducts of the nipple, which characterized by lesion of the nipple and large ducts, often with the formation of tumor in the breast. This rare abnormality occurs in 0.5-5% of all cases of breast cancer.

[Confocal laser endomicroscopy principles and performing algorithm in gastric mucosa examination].

Accuracy of endoscopic examination in early gastric cancer and precancerous conditions diagnostics for many years depended only on quality of biopsy. That's why, risk of overlooking gastric focal carcinoma, particularly-- multiple, was relatively high. Last couple of years new endoscopic method--confocal laser endomicroscopy (CLE) was released for commercial use. This approach provides real-time information about morphology of gastric mucosa during endoscopic examination. CLE is a variation of confocal microscopy--morphologic technique, providing examination of thick specimens or live tissue. CLE system is a single-channel fluorescence microscope, used in endoscopy, where confocal probe incorporated into endoscope or mounted into accessory channel. For proper results of CLE intravenous administration of fluorescence agent is needed. In our study in P.A. Herzen Moscow Cancer Research Institute we have used 10% fluorescein sodium, due to acriflavine use is prohibited in Russian Federation. In 157 patients with suspected early gastric cancer mean time of CLE was 24 ± 3.5 min. In all cases descriptive images were acquired. Mean amount of endomicrosocpic images in one patient was as high as 162 ± 8.3.

[Early gastric cancer and precancerous conditions diagnostics with confocal laser endomicroscopy].

AIM: To develop endomicroscopic criteria of early gastric cancer and precancerous conditions METHODS: 157 suspected for early gastric cancer patients were included in our study. In all cases complex endoscopic examination (narrow-band imaging NBI-HD endoscopy, endosonography (EUS) and endoscope-based confocal laser endomicroscopy (CLE) with precise biopsy) was performed. CLE images compared to pathology data. RESULTS: Precise criteria of intestinal metaplasia in CLE was presence of oval gray goblet cells in epithelium. Gastric adenoma with moderate dysplasia appeared on CLE images as glandular structures in mucosa surface layers. The signs of high-grade dysplastic changes in adenoma were appearing of different shape and size cells with lost polarity. Well-differentiated carcinoma featured destruction of some glands and forming dark cell clusters. Revealed criteria of poor-differentiated carcinoma was total disintegration of glandular structures. Overall accuracy of CLE in early gastric cancer and precancerous conditions diagnostics reached 95,6% (P < 0.001). Selected accuracy in different condition was: 100% in intestinal metaplasia identifying, 86.1%--in adenoma with moderate dysplasia, 96.2% in high-grade dysplasia and cancer in situ, and 100%--in poor-differentiated gastric carcinoma types). CONCLUSION: As the result of our study we have developed precise endomicroscopic criteria of intestinal metaplasia in stomach, gastric adenoma with moderate and high-grade dysplasia and early gastric cancer--as well-differentiated, as poor-differentiated.