Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

[The effect of applying clinical organizational telemedicine technology management of anti-tuberculous care on dynamics of tuberculosis morbidity and mortality].

The tuberculosis is the most important medical and social problem among globally dangerous epidemiological phenomena. the tuberculosis ranks 9th place in the structure of mortality and disability of population and 1st place among causes of death from single infectious agent.The purpose of the study was to analyze dynamics of total morbidity and mortality because of tuberculosis against the background of the implementation of telemedicine clinical organizational technology in phthisiology care 2007-2021.The official Regional and Federal data of Rosstat for 2007-2021 were used. The indicators of total morbidity and mortality of population caused by tuberculosis in the Sverdlovsk Oblast were established. The research methods were content analysis, dynamic series analysis, graphical analysis, statistical differences analysis.In the Sverdlovsk Oblast, the morbidity and mortality of tuberculosis exceeded national average indicators by 1.2-1.5 times. In 2007-2021, as a result of implementation of clinical organizational telemedicine technology in managing phthisiology care, total morbidity and mortality of population caused by tuberculosis decreased up to 2.275 and 2.97 times respectively. The rate of decrease of analyzed epidemiological indicators generally correlated with national average data with statistical validity of difference t≥2.In regions with unfavorable epidemiological indicators of tuberculosis, application of innovative technologies in management of clinical organizational processes is required. The development and implementation of clinical organizational telemedicine technology for managing regional phthisiology care contributes to significant reduction of morbidity and mortality of tuberculosis and optimizes sanitary and epidemiological well-being.

[Morphologic structure and immunohistochemical analysis of vaginal wall in women with pelvic organ prolapse].

AIM: to study a correlation between clinical stage of pelvic organ prolapse (POP), a histological structure and results of immunohistochemical study of the vaginal wall were evaluated. MATERIALS AND METHODS: A total of 60 peri- and postmenopausal women (average age 61.9+/-8.4 years) with POP of stage II-IV, according to the POP-Q classification, or with stress urinary incontinence and cystocele of stage I-II, who undergone to surgical treatment, were included in the study. During a procedure, a biopsy from the anterior vaginal wall was taken. Depending on the stage of POP, patients was divided into two groups. In the group 1, 30 patients with stage I and II of POP were included, while group 2 included 30 women with POP of stage III and more. The control group (group 3) consisted of 20 patients without POP (mean age 63.4+/-11.0 years) who underwent a hysterectomy due to to other indications. A histological and immunohistochemical studies of vaginal wall tissue was performed in order to determine the tissue content of collagen type I and III; matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), vimentin and smooth muscle actin. RESULTS: In contrast to two other groups, in group 2 there were significant changes in the connective tissue. Collagen has a form of fibrous mass with areas of reduced content. In addition, scarring areas with an increase in the content of type III collagen, a decrease in the amount of type I collagen and elastic fibers with significant fragmentation, were seen. Moreover, in patients with severe POP (III-IV), degradation of collagen fibers with a decrease in connective tissue strength and elasticity was detected. Women with POP had a low ratio of type I:III collagen. Analysis of the collagen content in the vaginal wall in patients with mild POP (I-II) revealed a significant increase in the level of collagen type I (p=0.0003) and a decrease in the content of type III (p=0.045), compared to patients with more severe POP (III-IV). The level of MMP-1 and MMP-2 in women with POP was higher, than in control group by 1.7 times (p<0.05). The content of TIMP-1 in the group 1 was significantly lower by 1.5 and 2.2 times, compared to group 2 and 3, respectively. An analysis of MMP-1 and MMP-2 concentration in patients of groups 1 and 2 revealed a significant (p=0.04) decrease in their activity in severe POP (III-IV). In women of the group 2, biopsy of the vaginal wall showed that expression of vimentin and smooth muscle actin in the connective tissue was significantly higher, than in group 1 and 3 (p<0.05). Vimentin expression in the group 2 was 1.4 and 2.6 times higher than in the group 1 and 3, respectively. In the control group, the expression of these markers in the vaginal wall was minimal and focal. CONCLUSION: Our data indicate that fibrosis and degradation of the connective tissue in the vaginal wall predominate in POP, and these changes are a consequence, but not a cause of PG. The aggravation of degenerative changes in the connective tissue leads to the progression of POP.

[Pancreatoduodenectomy: learning curve within single multi-field center]. / Pankreatoduodenal'naia rezektsiia: krivaia obucheniia na primere odnogo mnogoprofil'nogo tsentra.

AIM: To analyze learning curve by using of immediate results of pancreatoduodenectomy at multi-field oncology institute. MATERIAL AND METHODS: For the period 2010-2016 at Abdominal Oncology Department of Herzen Moscow Oncology Research Institute 120 pancreatoduodenal resections were consistently performed. All patients were divided into two groups: the first 60 procedures (group A) and subsequent 60 operations (group B). Herewith, first 60 operations were performed within the first 4.5 years of study period, the next 60 operations - within remaining 2.5 years. RESULTS: Learning curves showed significantly variable intraoperative blood loss (1100 ml and 725 ml), surgery time (589 min and 513 min) and postoperative hospital-stay (15 days and 13 days) in group A followed by gradual improvement of these values in group B. Incidence of negative resection margin (R0) was also significantly improved in the last 60 operations (70 and 92%, respectively). CONCLUSION: Despite pancreatoduodenectomy is one of the most difficult surgical interventions in abdominal surgery learning curve will differ from one surgeon to another.

[Female genital prolapse surgery using ultra lightweight polypropylene mesh].

AIM: To compare the results of female genital prolapse (FGP) surgery via vaginal access using lightweight and ultra-lightweight polypropylene mesh. MATERIALS AND METHODS: From 2007 to 2011, 93 women aged from 46 to 71 years with II-IV stage FGP (POP-Q classification) were examined and underwent the vaginal extra-peritoneal colpopexy using polypropylene implants in the Department of Urology. Patients were divided into 2 groups. In patients of group 1 (n=50) the surgery was performed according to a newly developed technique using perforated ultra-lightweight (surface density 19 g/m2) domestically manufactured polypropylene implant. In group 2, a standard trocar set with light (surface density of 42.7 g/m2) foreign-made polypropylene implants was used. RESULTS AND DISCUSSION: Long-term follow-up was from 1 to 5 years. General surgical complications (urinary bladder injury, blood loss over 300 ml, perineal and vaginal hematomas) were detected in 2 (4%) patients of group 1 and in 7 (16.3%) patients of group 2. The most common specific mesh-related complication was the vaginal wall erosion, which was observed in 4 (9.3%) patients of group 2 and in 1 (2%) patient of group 1. FGP recurrence was diagnosed in 5 (10%) patients of group 1 in the non-treated part and in 8 (18.6%) patients of group 2. Three patients (7%) in group 2 developed recurrent cystocele due to the shrinkage of the mesh implant which was not observed in group 1. At 12 month follow-up, the results of FGP surgical treatment were estimated as good (full functional recovery and no FGP recurrence) in 41 (82%) and 32 (74.4%) patients of groups 1 and 2, respectively. CONCLUSION: We have developed a method of vaginal extra-peritoneal colpopexy using a perforated ultra-lightweight polypropylene implant. This technique has resulted in the absence of recurrence in the treated part of FGP, and 4.1, 4.2 and 4.7 fold reductions in the incidence of general surgical complications, vaginal wall erosions and perineal and vaginal hematomas, respectively, compared with FGP patients undergoing the placement of the lightweight polypropylene implant using the standard trocar set.

[Radical nephrectomy in a left pelvic dystopic kidney in a patient with renal cell carcinoma].

The incidence of the renal cell carcinoma in Russia and worldwide remains high. Current literature reports isolated cases of patients who were diagnosed and treated for malignant neoplasms of dystopic kidneys. In addition, the absence of patient complaints and the paucity of non-specific symptoms of pelvic dystopic kidneys lead to late diagnosis of this anomaly and the kidney diseases. This article presents a case study of a radical nephrectomy in a patient with renal cell carcinoma of the left pelvic dystopic kidney.

[TREATMENT OF AGE-RELATED ANDROGEN DEFICIENCY IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA].

This paper reports the results of a comparative study evaluating the safety and efficacy of testosterone therapy in 44 patients with BPH and age-related androgen deficiency. All patients received α-blockers. The findings of the study showed a substantial improvement in the quality of life of patients in the study group that received testosterone therapy, compared with the control group treated with only α-blockers.

[Surgical treatment of simple cysts of the kidney in multiphasic hospital].

The presented work is based on an analysis of survey results and surgical treatment of 418 patients with simple renal cysts during the period from 1995 to 2010. The volume of the cysts ranged from one to 2500 ml. The average volume of the operated cysts was 360.2 +/- 306.7 ml. The abilities of the multiphasic hospital, equipping it with the modern diagnostic and medical equipment, the long experience of work enabled the authors to develop the algorithm of inspection and surgical treatment of the patients with simple renal cysts and to develop practical recommendations, presenting them in logical schemes.

[Palliative therapy of locally-advanced prostate cancer following radical treatment].

Both radical and combined radiotherapy for locally-advanced prostate cancer may be followed by complications involving the upper and lower urinary tracts. Such conditions are generally reversible but still they may turn chronic and even call for surgery. Our study used the data gathered in the course of examination and treatment of 107 patients with prostate cancer T3-4N0-1M0, some of them suffering from post-radical treatment complications.

[Assessment of mucosal injury in stage T1-T2NOMO bladder cancer after radiation or intravesical chemotherapy].

The report reviews the experience gained with radio- and chemotherapy-related injuries suffered by bladder cancer patients. It corroborates the opinion of most European specialists that indications for radical cystectomy be extended with due considerations of up-to-date potential in anesthesiology, extensive care and pharmacology. Possible untoward side effects of radiation and intravesical chemotherapy as well as means of solution of the problem are discussed. It is urgent considering the constantly growing number of such patients, their age and associated somatic problems.

[Use of flow cytometry in diagnosis of urinary bladder cancer].

Urinary bladder cancer ranks 11th (10-15 cases per 100,000 annually) in the oncological morbidity registry. Morphological diagnosis is generally confirmed by cytological assay of urinary sediment or lavage liquid. Yet, the method is effective only with low-differentiated cell tumor. Flow cytometry was used at the Center's Clinic (2005-2006) to test urinary sediment from 32 patients diagnosed with bladder cancer. In addition, all patients were tested 3 times by the standard cytological procedure using a mix of azure and eosin (Pappenheim). The sensitivity of the latter method proved to be 31.3% as compared with 65.62% for flow cytometry.

[An evaluation of damage caused by radiation and chemical drugs to urinary bladder mucosa in stage T1-T2N0V0 cancer].

An evaluation of damage caused by radiation and chemical drugs to urinary bladder mucosa in stage T1-T2N0V0 cancer is presented and therapeutic modalities are discussed. The authors summarize their experience and offer recommendations for optimal treatment of the disease. Also, suggestions are made how to work out indications and contraindications in dealing with a specific urinary bladder cancer vis-avis stage and possible complications.

[Potential of modern urology in palliation of cancer].

The paper deals with certain issues in present-day oncology and introduction of the most efficient endourological procedures to improve quality of life. Most cancer patients suffer urological cancer-related and postoperative complications. Oncologists are often confronted with such problems as disturbed passage of urine in colorectal and gynecological cancers, radiation injury and surgery-induced impairment of the urinary tract and urolithiasis in cancer patients. Diagnostic and therapeutic potential of modern urology and novel approaches intended to improve quality of life in cancer patients with urological complications are discussed.

[Use of radiofrequency ablation in palliative therapy of renal cancer].

New methods in management of renal cancer promising better quality-of-life outcomes have been introduced for the past 10-15 years. They offer more opportunity of early detection of cancer, differential diagnosis and more accurate staging. Yet, there is a sizeable percentage of patients who cannot undergo surgery for general health reasons, multiple tumor involving both kidneys or involvement of a single kidney. Such patients may be given radio frequency ablation which causes a.c.-charged intracellular structures to vibrate leading to coagulation of tumor. Being unable of complete cure, the procedure is well tolerated. It gives the feeling of comfort, improves quality of life and is often followed by survival times comparable to postoperative ones.