[Texture analysis of 3D models for the prediction of the grade of clear cell renal cell carcinoma of the kidney (pilot study)].

AIM: To evaluate the possibilities of textural analysis of 3D models in differentiating the degree of nuclear dysplasia of the clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The specimens after surgical treatment of 190 patients with ccRCC were analyzed. In all cases, nephron-sparing surgery (NSS) was performed through laparoscopic access. The clinical characteristics were evaluated, including age, gender, tumor localization (side, surface and segments), absolute tumor volume, Charlson comorbidity index, body mass index, nephrometry scores (RENAL, PADOVA, C-index). Patients were divided into 2 groups. In group 1, there were 119 patients with the ccRCC of Grade 1 or 2, while group 2 consisted of 71 patients with ccRCC of Grade 3 and 4. All patients underwent 3D virtual planning of procedure using the 3D modeling program "Amira". At the first stage, two experienced radiologists performed manual segmentation of 3D models of kidney parenchyma tumors. At the second stage, the tumor shape was analyzed with a mathematical calculation of three indicators and more than 300 textural features of statistics of types 1-2 were extracted. Further, an intellectual analysis was carried out. For the evaluation of tumor grade according to Furman system, the classification problem was solved using the machine learning algorithm Stochastic Gradient Descent and cross-validation k=5. RESULTS: The accuracy of classification for the two groups of Grade 1 or 2 and Grade 3 or 4 on the F1 metric was 72.2. To build the model, the following parameters were selected: the absolute tumor volume, the Charlson comorbidity index, "Energy", the first quartile and the second decile of the pixel intensity distribution. CONCLUSION: The texture analysis of 3D models for the prediction of Fuhrman grade in ccRCC demonstrated satisfactory quality for two groups of Grade 1 or 2 and Grade 3 or 4 nuclear dysplasia.

[Expression of markers of epithelial-mesenchymal transition in breast cancer]. / Ekspressiya markerov epitelial'no-mezenkhimal'nogo perekhoda pri rake molochnoi zhelezy.

OBJECTIVE: To study of the expression of epithelial-mesenchymal transition markers in various molecular subtypes of cancer and in benign breast diseases with different risks of malignant transformation. MATERIAL AND METHODS: An immunohistochemical study of the expression of E-cadherin, collagen II, integrin 1ß, cyclin D1 was carried out in breast tissue samples: 58 with invasive breast carcinoma of no special type and 17 with benign breast diseases with a high and low risk of malignant transformation. RESULTS: Patients with a triple negative molecular subtype are characterized by lower expression of collagen II compared with individuals with luminal A and B+ subtypes. A distinctive feature of patients with the HER2+ subtype was increased expression of cyclin D1 compared with the luminal A subtype, and in patients with the luminal B+ subtype, the expression of integrin 1ß is higher than in the luminal B- and HER2+ subtypes. The expression of cyclin D1 in patients of both groups with benign diseases was lower than in all groups with invasive carcinoma, but at the same time, in patients with a low risk of malignant transformation, the expression of cyclin D1 was higher than in those with an increased risk. CONCLUSION: The study revealed the relationship between the expression of markers and molecular subtypes of breast tumors, in addition, some patients with benign diseases were found who need further more careful monitoring and may be at risk for the development of malignancy.

[Early urethral catheter removal after robot-assisted radical prostatectomy].

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a widely used treatment method for patients with clinically localized prostate cancer. Posterior reconstruction of urethrovesical anastomosis (UVA) is one of the techniques that provides early recovery of urinary continence after surgery. Changes in the technique of performing posterior reconstruction of UVA may contribute to further improvement of functional results. AIM: To evaluate the functional results of early removal of the urethral catheter (after 3 days) after RARP using a modified surgical technique of performing posterior reconstruction of UVA compared with the standard catheterization time (7 days after surgery). MATERIALS AND METHODS: Patients who underwent RARP were randomly assigned to early catheter removal (3 days after surgery, main group, n=15) and standard catheterization time (7 days after surgery, control group, n=15). RARP was performed using the Da Vinci Si system. The primary end point was the rate of spontaneous voiding after catheter removal. Secondary endpoints were the incidence of urine leakage into the paravesical tissue during retrograde cystography, as well as complications according to the Clavien-Dindo system. The frequency and severity of stress urinary incontinence after catheter removal was assessed using the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF). RESULTS: There were no significant differences between groups in terms of baseline and perioperative parameters. After removal of the catheter, no acute urinary retention was observed in both groups. Also, there were no cases of urine leakage into the paravesical tissue during retrograde cystography. The ICIQ-UI SF questionnaire showed no significant differences between the groups at 1, 3, 6, and 12 months after surgery. CONCLUSIONS: The method of modified posterior reconstruction allows to remove the urethral catheter 3 days after RARP. Early removal of the urethral catheter did not adversely affect the early recovery of urinary continence, the quality of UVA, and did not increase the incidence of acute urinary retention. Further studies with longer follow-up periods are needed.

[Two-layer posterior reconstruction of the vesicourethral anastomosis during robotic-assisted radical prostatectomy].

AIM: To study the influence of the technique of posterior reconstruction of the vesicourethral anastomosis (VUA) on the prevention of urinary incontinence after robotic-assisted radical prostatectomy (RARP). MATERIAL AND METHODS: A total of 67 patients (mean age 63 years) with localized prostate cancer were included in the study. All patients were divided into two groups. In the group 1 (n=32) the standard technique of the VUA was used, while in the group 2 (n=35) the two-layer posterior reconstruction was done. The impact of urinary incontinence on the quality of life was analyzed using the ICIQ-SF questionnaire 1, 3 and 6 months after operation. On postoperative days 5-7, all patients underwent cystography to assess the tightness of the VUA. RESULTS: One month after RARP in the group 1 the mean score of ICIQ-SF questionnaire was 6.72, compared to 4.57 in group 2 (p=0.04). After 3 and 6 months the respective values were 3.8 vs. 2.3 (p=0.09) and 1.94 vs. 1.2 (p=0.23), respectively. Cystography revealed no extravasation of the contrast. CONCLUSION: The results of a retrospective comparative study suggest that a two-layer posterior reconstruction of the VUA during RARP, being a simple method, provides better continence rate one month postoperatively compared to standard technique, although larger randomized clinical trials are needed.

[Influence of the HLDF differentiation factor on the production of cytokines by bio-tissues of breast tissue in its non-malignant diseases and in invasive carcinoma of a non-specific type]. / Vliianie faktora differentsirovki HLDF na produktsiiu tsitokinov bioptatami tkani molochnoi zhelezy pri ee nezlokachestvennykh zabolevaniiakh i pri invazivnoi kartsinome nespetsificheskogo tipa.

We studied the effect of the HLDF differentiation factor on production of cytokines by biopsy samples of nonmalignant breast diseases (ND) and invasive breast carcinoma of no special type (IBC-NST), in the absence and presence of lymphogenic metastasis: IBC-NST patients werw subdivided into groups on the prognostic protocol of the 8th edition of the AJCC committee. Group IA consisted of patients with T1-T2 tumor sizes, and predominantly with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-); it also included one patient with the HER2+ (ER-/PR-/HER2+) molecular subtype. The IB group was mainly composed of patients with T2 tumor size, with the presence of lymphogenic metastasis (in 8 out of 10) patients and with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-) and it also included three patients with the HER2+ (ER-/PR-/HER2+) molecular subtype. Group IIA consisted of patients with T1-T2 tumor sizes, mainly with no metastases in the lymph nodes (in 11 out of 12 patients) and with a triple negative molecular subtype. Group IIB included patients with T2 tumor size, the presence of nodal metastasis and the expression of markers of ER-/PR-/HER2 - and ER-/PR-/HER2+. Group IIIA consisted of patients with tumor size T1-T3, with the presence of nodal metastasis and the expression of markers of ER-/PR+/HER2+ and ER-/PR-/HER2+. Group IIIC consisted of patients with T3 tumor size, lymphogenic metastasis, and expression of ER-/PR-/HER2-markers (triple negative molecular subtype). Due to a limited number of patients in the groups IIB, IIIA and IIIC, as well as due to more severe clinical and pathological stages, according to the prognostic Protocol of the 8th edition of the AJCC Committee, they were pooled into group III. Concentrations of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 were assayed in supernatants of biopsy specimens of breast tissue. Results have shown that with IBC-NST, a statistically significantly higher level of spontaneous production (SP) by biopsy specimens of IL-17, IL-18, IFN-γ and VEGF, and a lower level of SP IL-6 as compared with ND. Patients of all clinical and pathological groups showed a high VEGF spontaneous production as compared with ND, while statistically significant differences from patients with ND were not found in IL-17 spontaneous production in group IB patients, and IL-18 spontaneous production were absent in group IA. Only in patients with IA and IB, the IL-6 spontaneous production was lower as compared to ND, and the IL-8 spontaneous production was lower in the IA group. IFN-γ spontaneous production was higher in patients with IBC-NST group IIA as compared with ND. Under the influence of the HLDF differentiation factor, it was found that the parameters of IBC-NST patients were statistically significantly higher in the production of IL-1Ra, IL-17, IL-18 and VEGF, and statistically significantly lower in the production of IL-6 as compared to ND. HLDF had a higher impact on the content of IL-18 in IBC-NST patients than in ND. After HDLF sublimation IL-6 values were lower in patients of groups IA and IB, and HLDF-induced IL-17 production was higher only in patients of group IA. Statistically significant differences in the index of influence of HLDF (IVHLDF), representing ratio of the cytokine concentration in the supernatants of a biopsy specimen stimulated by HLDF to spontaneous cytokine production, were found between ND and IBC-NST in the case of on IFN-γ production, and also in the case of IL-4 production (between patients in the absence and presence of lymphogenic metastasis). IVHLDF for production of IL-6, IL-8 and TNF-α was lower in group IIA patients compared to group IA, and IVHLDF for production of GM-CSF and MCP-1 was lower in group IIA as compared to group III, in addition IVHLDF for MCP-1 products was lower in group IIA as compared to ND. The HLDF effect on the cytokine production by the tumor and its microenvironment was different in ND patients and IBC-NST patients. HDLF suppressed IFN-γ production in the pooled group of IBC-NST patients; HLDF mainly had a suppressive effect on the production of IL-6, IL-8, TNF-α, GM-CSF and MCP-1 in IBC-NST patients of group IIA.

[Simultaneous laparoscopic procedures in patients with synchronous multiple primary gastric and kidney cancer]. / Odnomomentnye laparoskopicheskie operatsii u bol'nykh s pervichno-mnozhestvennym sinkhronnym rakom zheludka i pochki.

OBJECTIVE: To evaluate an effectiveness of simultaneous laparoscopic procedures in patients with synchronous multiple primary cancer (SMPC). MATERIAL AND METHODS: We observed 3 patients (2 men and 1 woman) aged 61-78 years with synchronous multiple primary gastric and kidney cancer. Gastric tumors were localized in the lower third of the body (1) and the antrum (2), histological structure corresponded to adenocarcinoma G1 (1) and G2 (2). Kidney tumors were verified as light cell carcinoma and localized in the upper segment of the left kidney in 2 patient and right kidney in one patient. Mean dimension of tumor scheduled for resection was 4.65 cm, nephrectomy - 10.3 cm. Complexity of resection according to the RENAL scale was equal to 8 and 10. RESULTS: Three patients underwent laparoscopic Billroth-I distal gastrectomy, 2 - kidney resection and one patient - nephrectomy. Mean surgery time was 265±37 min, blood loss - 175±29 ml. There were no conversion and redo interventions within 30 days after surgery. Mean hospital-stay was 11±2 days. CONCLUSION: Minimally invasive technologies in patients with SMPC reduces blood loss, ICU- and hospital-stay. Earlier rehabilitation ensures the next stage of treatment in early postoperative period, while quality of life is better in comparison with traditional interventions.

Influence of Internal and External Factors on the Production of Cytokines by Peripheral Blood Cells in Breast Cancer.

The article focuses on the influence of human leukemia differentiation factor (HLDF), carcinoembryonic antigen (CEA), and polyclonal activators (PA) on cytokine production by peripheral blood cells in breast cancer and benign breast diseases. It was found that the influence of internal factors on the production of cytokines by the peripheral blood cells is associated with lymphatic metastasis (CEA: IL-10; HLDF: IL-6, IL-1ß, TNF-α, and G-CSF). One special circumstance was that there were no differences between the production of cytokines by peripheral blood cells in the patients with breast cancer compared to the patients with benign breast diseases with a high risk of malignant transformation. This is evidence of the functional similarity of peripheral blood cells in patients with these conditions. Cytokine production under the influence of PA was different only in case of TNF-α in all study groups.

[Proteins and immunohistochemical markers of breast diseases]. / Belkovye i immunogistokhimicheskie markery zabolevanii molochnoi zhelezy.

In this work, we have compared malignant and non-malignant diseases of the mammary gland using 8 proteins: HRG, MUC1, PAI-1, HSP90αA1, CDH1, ERα, PGR and IL-12. Their concentrations in the supernatants of blood cells and breast biopsies were compared in terms of spontaneous production, induced by a polyclonal activator and after exposure to biopsy samples of the HLDF differentiation factor, as well as the indices of the effect of the polyclonal activator and HLDF on the protein production. In addition, the correlation relationships of the above indicators with the expression of markers of the epithelial-mesenchymal transition: collagen type II (CII), ß-1 integrin (CD29) and cadherin-E (CDH1) were studied. The study revealed statistically significant differences in the concentration of HRG in the supernatant of blood cells, IL-12 during spontaneous production by biopsy specimens, PGR production of biopsy specimens induced by the polyclonal activator, CDH1 and IL-12 production biopsy specimens exposed to HLDF. According to the influence index of the polyclonal activator and HLDF, statistically significant differences were found for CDH1production. Comparison of non-specific invasive carcinoma biopsy specimens and non-malignant breast diseases by means of the markers of the epithelial-mesenchymal transition revealed statistically significant differences in CD29 expression and the lack of differences in the expression of CDH1 and CII. This indicates the presence of cell atypia in samples of non-malignant breast diseases; it is confirmed by the recognized correlation between the production of certain proteins and the expression of the epithelial-mesenchymal transition markers.

Personalized Approach to Determination of Histidine-Rich Glycoprotein and E-Cadherin in Supernatants of Immunocompetent Blood Cells and Breast Biopsy Specimens in Breast Malignant and Non-Malignant Disease.

The material of patients with invasive carcinoma of no special type (ICNT) and nonmalignant diseases (ND) of the mammary gland was studied. When comparing the concentrations of histidine-rich glycoprotein (HRG) and E-cadherin (CDH1), statistically significant differences between ICNT and ND by HRG in the supernatant of blood cells and its spontaneous production by biopsies and by CDH1 at its induced production, as well as by influence indices of polyclonal activators on the production of CDH1 were found. When comparing the expression of immunohistochemical markers, no statistically significant differences between ICNT and ND were obtained.

[Relationship between supernatant cytokines and expression of markers of epitelial-mesenchymal transition of invasive breast carcinoma of non-specific lymphynosis type]. / Vzaimosviaz' mezhdu tsitokinami supernatantov i ékspressiei markerov épitelial'no-mezenkhimal'nogo perekhoda bioptatov invazivnoi kartsinomy molochnoi zhelezy nespetsificheskogo tipa pri limfogennom metastazirovanii.

The relationship between the content of supernatant cytokines and the expression of non-specific type of markers of epithelial-mesenchymal transition markers in the presence (group II) and the absence of lymphogenous metastasis (group I) were studied in biopsy specimens of mammary invasive breast carcinoma. The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), ß-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that patients of these groups statistically significantly differed in spontaneous production of IL-18 and G-CSF, in terms of the index of the effect of the polyclonal activator on G-CSF production. There was a correlation between the parameter of CII expression in tumor tissue and the production of cytokines by tumor biopsy specimens; it was characteristic of all patients with invasive carcinoma of a non-specific type, and correlations, both direct and reverse between the expression indices of CDH1, CD29 and cytokine production varied depending on the presence or the absence of lymphogenous metastasis. The study revealed the features of the correlation between the production of cytokines by the tumor, its microenvironment and the expression of IHC markers of the epithelial-mesenchymal transition in patients with invasive non-specific breast carcinoma in the presence and absence of lymphogenous metastasis.