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Cancer Urology

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Vol 14, No 2 (2018)
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https://doi.org/10.17650/1726-9776-2018-14-2

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

15-25 1491
Abstract

Objective: to develop an effective and safe surgical technique for the treatment of patients with renal cell carcinoma with invasive tumor venous thrombosis of the inferior vena cava (IVC).

Materials and methods. The study included 75 patients underwent surgical treatment at the N.N. Blokhin Russian Cancer Research Center between 1995 and 2017. The median age of patients was 57 years (range: 32–72 years). All patients were diagnosed with RCC with invasive tumor venous thrombosis levels II–IV; of them, 55 patients (73.3 %) had complete IVC obstruction and mature venous collaterals. Twenty- seven patients (26.0 %) were diagnosed with regional, 37 (49.3 %) – with distant metastases. Prior nephrectomy was performed in 5 (6.7 %) cases. Surgical treatment included nephrectomy (n = 70; 93.3 %), thrombectomy with IVC resection (n = 75; 100 %), and metastasectomy in solitary distant lesions (n = 11; 14.7 %). Partial IVC resection was demanded in 18 patients (24.0 %): with infrarenal IVC plication – 14 (18.7 %), with reconstruction of IVC with synthetic patch – 4 (5.3 %). Fifty-seven patients (76.0 %) underwent circular IVC resection (with left renal vein (LRV) ligation – 35 (46.7 %)). The IVC was replaced with ePTFE grafts in 4 (5.3 %) patients, IVC reconstruction was not required in 53 (70.7 %) patients. IVC grafting was considered to be justified in patients without mature venous collaterals. Twenty-two patients (29.3 %) received systemic antitumor therapy. Median follow-up was 32.3 months (range: 1–226 months).

Results. Median operative time was 237.5 min (range: 135–580 min); median blood loss – 7000 mL (range: 1200–27 000 mL). The post- operative complications rate was 52.1 % (grades III–V – 31.5 %). Hospital mortality was 13.3 % (10 of 75 patients). Thirty-two months overall, cancer-specific, and recurrence-free survival were 42.4 %, 49.5 %, and 61.2 % respectively. At 19 months all prosthesis were patent. None of the patients had glomerular filtration rate <60 ml/min/1.73 m2 after LRV ligation. No patients developed disabling chronic venous insufficiency of the lower limbs after IVC ligation/resection without grafting.

Conclusion. Nephrectomy, thrombectomy, and IVC resection is the only effective method of treatment for RCC with invasive tumor venous thrombosis. The development of IVC and LRV venous collaterals allows performing circular IVC resection with LRV ligation without graft replacement.

27-32 985
Abstract

Background. There is a category of patients with renal masses, due to severe concomitant diseases, can not perform the operation or may be associated with a threat to life. In addition, many patients with small tumor sites are extremely concerned about their disease and are negative about the tactics of active observation and insist on treatment. These patients can be offered alternative methods of treatment of renal cell carcinoma (RCC), the leading of which is cryoablation.

Objective: to evaluate the effectiveness and safety of percutaneous cryoablation of the kidney tumor under ultrasound control.

Materials and methods. In the Urology Clinic of the I.M. Sechenov First Moscow State Medical University during the period from 2015 to 2017 performed 23 percutaneous cryoablation of RCC, 7 (men – 4, women – 3) of which were performed under local anesthesia. In 4 patients due to severe concomitant diseases, general anesthesia was associated with an extremely high risk. Three patients refused from dynamic observation and from traditional surgical treatment; preferred an alternative treatment in the form of a percutaneous cryoablation under local anesthesia. In 4 cases, the formations were located in the lower segment along the posterior surface of the kidney, in 3 – along the lateral surface in the middle segment. The size of the formations was not used 4 cm (T1a). The age of the patients was 62.3 years (51 to 83 years). Right-sided localization of the tumor was noted in 3 patients, left-sided – in 4. One patient had a single kidney.

At the preoperative stage and 6 months after the operation, all patients underwent ultrasound with dopplerography, multislice computerized tomography with contrast, and computer 3D modeling, which helped to clearly assess the size of the tumor, clarify the prevalence of the tumor process and the spatial ratio of the internal surface of the tumor node to the elements of the bowl-and-pelvis system. In all the observations, the formations were located along the posterior or lateral surface of the kidney; in the lower or middle segment; without invasion of the sine. We used a 3rd generation cryomash machine SeedNet gold (Galil Medical), cryoprobes IceSeed and IceRod. Intraoperative, immediately before cryoablation, a tumor biopsy was performed, the presence of RCC in all patients was confirmed morphologically.

Results. According to the ultrasound examination with echodopplerography at 6 months after the operation, the size of the tumor node’s formations decreased on average by 6–8 mm, while there was no blood flow in them. When multislice computerized tomography with 3D modeling was performed, the formation was reduced and the accumulation of the contrast preparation was completely absent or their accumulation gradient did not exceed 10 HU (initially it was about 200 HU). There were no intraoperative complications. In 1 observation, a postoperative hematoma measuring 7 × 3 cm was resolved conservatively and did not require surgical treatment.

Conclusions. Percutaneous cryodestruction under local anesthesia using ultrasound guidance seems to be an effective and safe technique for treating patients with stage T1a RCC with localization in the posterior or lateral surface in the lower or middle segments without invasion of the renal sinus and surrounding tissues. It is planned to continue monitoring patients to assess the long-term effectiveness of cryoablation.

33-42 942
Abstract

Background. Acute renal failure (ARF) in the postoperative period increases the risk of complications and death. Estimating the risk of ARF prior to surgery is particularly important, because it allows modifying the treatment in high-risk patients.

Objective: to develop prognostic models for evaluating the risks of ARF in patients undergoing resection of a solitary kidney by measuring preoperative parameters.

Materials and methods. The study included 136 patients with tumors in a solitary kidney that underwent surgical treatment in the N.N. Alexandrov National Cancer Center of Belarus in the last 16 years.

Results. Biochemical blood tests demonstrated that 28 patients (20.6 %) had ARF in the early postoperative period. The multivariate model for assessing the risk of ARF included the following three covariates: tumor size, multifocality, and serum potassium level. We identified the cut-off points of tumor size (3.6 and 5.2 cm) and potassium level (4.4 and 4.8 mmol/L) that ensured maximum predictive accuracy. Using the multivariate model, we developed a nomogram that allows graphical calculation of the ARF probability in the postoperative period by measuring preoperative parameters.

Conclusion. Our model enables preoperative assessment of the risk of developing ARF after resection of a solitary kidney with an accuracy (С-index) of 85.1 % (95 % confidence interval: 79.3–89.7 %).

44--53 1090
Abstract

Objective: analysis of results of the outcomes of surgical treatment for renal tumors in the Saint Petersburg City Hospital No. 40 over the last 5 years and determination the trends.

Materials and methods. The study included 293 patients that underwent 296 surgeries for renal tumors. The majority of patients (87.84 %) were diagnosed with localized cancer, whereas locally advanced and metastatic forms were detected in 4.39 and 7.77 % of cases respectively. We performed radical nephrectomy (RNE) or nephron sparing (NS) via open or minimally invasive route (videoendoscopic or robot-assisted surgery using the da Vinci Surgical System).

Results. Organ-preserving surgeries were performed in 52.36 % of patients, RNE – in 47.64 % of patients; minimally invasive and open surgeries were conducted in 95.95 and 4.05 % respectively. In individuals with stage cT1a cancer, NS and RNE were performed in 87 and 13 % of cases respectively; in patients with stage cT1b cancer, NS and RNE were performed in 50.82 and 49.18 % of cases respectively. The majority (90.2 %) of patients with renal tumors >7 cm underwent minimally invasive surgeries, primarily RNE. The incidence of severe postoperative complications after NS and RNE was comparable: 5.75–8.06 and 1.67–15.38 % respectively (р = 0.64).

Conclusion. Minimally invasive NS is the method of choice for stage сT1 tumors; however, in some cases, we should also consider it for tumors >7 cm. Videoendoscopic surgery is the most preferable option for these patients, whereas robot-assisted techniques should be used for organpreserving surgeries and RNE in difficult cases.

54-67 2500
Abstract

Kidney cancer is a heterogeneous group of malignant tumors that develop from cells of the proximal convoluted tubules of the kidney. In Russia renal cell carcinoma holds the 2nd place after prostate cancer among tumors of genitourinary system. The main method of renal cell carcinoma treatment is radical nephrectomy, at the same time, high resistance of kidney cancer to chemotherapy and a weak response to hormone treatment are noted, and the effectiveness of cytokine therapy (interleukin 2, interferon alfa) does not exceed 18–20 %. The introduction into clinical practice of modern immune system affecting drugs has changed the disease prognosis for many patients with various malignant neoplasms. Currently, active development of immunotherapeutic drugs directed against inhibitory receptors of T-cells, the so-called “immunity control points” takes place, the most studied among these drugs are anti-CTLA-4 (cytotoxic T-lymphocyte associated protein 4) and anti-PD-1 (рrogrammed cell death pathway 1)/PD-L1 (programmed death ligand 1) monoclonal antibodies. In this review a detailed description of the PD-1 receptor and its PD-L1 ligand, as well as the prognostic and predictive significance of their expression in various types of renal cell carcinoma and the role in suppressing the antitumor T-cell immune response are presented. Blockade of PD-1/PD-L1 enhances antitumor immunity reducing the amount and/or immunosuppressive activity of regulatory T-cells (suppressors) and restoring the activity of effector T-cells that leads to an enhancement of the antitumor immune response. The blockade of PD-1 also stimulates proliferation of memory B-cells. In this regard, drugs that suppress the function of PD-1 are now widely used in the treatment of cancer including kidney cancer. The authors provide a list of promising drugs acting on PD-1/PD-L1 system used in renal cell carcinoma: nivolumab, pembrolizumab and some others. The results of clinical studies se of immunotherapeutic drugs in kidney cancer are analyzed.

68-78 700
Abstract
Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies worldwide. Approximately 25–30 % of newly diagnosed patients have metastatic RCC (mRCC), whereas in 20–30 % of cases, dissemination occurs after radical surgical treatment. The development of targeted and immunooncological agents in recent years significantly increased survival in patients with mRCC. However, clinicians faced a problem of choosing an optimal therapeutic regimen to achieve maximum effectiveness of the treatment. This article discusses the choice of second-line drugs for mRCC, advantages of axitinib and its optimal dosage, and efficacy of sunitinib depending on the disease prognosis.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

88-99 2615
Abstract

The review is devoted to loop-mediated isothermal amplification (LAMP) – a novel molecular diagnostic method that has recently become increasingly popular. Unlike polymerase chain reaction, LAMP does not require thermal cycling; DNA or RNA amplification occurs at a constant temperature (about 65 °C) with 4 or 6 primers. This is a fast, highly-sensitive, and highly specific method, which does not require expensive equipment, where visual detection of the reaction products is performed by the unaided eye. LAMP is successfully used for the diagnosis of multiple viruses, bacteria, and other pathogens (including those in food). Moreover, it can be applied for the detection of singlenucleotide polymorphisms. Recently, a modified LAMP assay – one-step nucleic acid amplification (OSNA) – was validated for metastasis detection. OSNA was demonstrated to have almost the same sensitivity and specificity as standard diagnostic methods (sometimes even higher). Particular attention is paid to the mechanism of LAMP, primer design, and diagnostics of cancer using OSNA.

102-108 949
Abstract

Background. Pelvic floor muscle exercises are used as a first-line treatment for urinary incontinence after radical prostatectomy. Their efficacy is still being investigated. The use of biofeedback when teaching pelvic floor muscle exercises to patients increases the effectiveness of therapy.

Objective: to assess the efficacy of biofeedback-assisted pelvic floor muscle training in patients with urinary incontinence after laparoscopic and robot-assisted radical prostatectomy and to compare the results of teaching.

Materials and methods. A total of 64 patients with urinary incontinence after nerve sparing prostatectomy underwent biofeedback-assisted pelvic floor muscle rehabilitation. Radical laparoscopic surgery was performed in 48 (75 %) patients, whereas robot-assisted surgery was performed in 16 (25 %) patients. The patients started their training 2 months postoperatively. We used two-channel electromyography with the Neurotrack ETS system (United Kingdom) to teach the patients isolated pelvic floor muscle contractions. After achieving a minimum activity of abdominal muscles during pelvic floor muscle contractions, the patients started exercises.

Results. There was no significant difference in age between patients who underwent laparoscopic and robot-assisted radical prostatectomy (р = 0.79). Fifty-five patients (85.9%) acquired the skill of isolated pelvic floor muscle contractions and could perform training on their own. The remaining 9 patients (14.1 %) required regular support from healthcare professionals at an outpatient unit (1–2 biofeedback-assisted trainings per month). Thus, the type of surgery did not affect the process of training. The type of radical prostatectomy had no impact on the acquisition of the pelvic floor muscle contraction skill.

Conclusion. The time for restoration of urinary continence by biofeedback-assisted pelvic floor muscle training did not vary between patients after laparoscopic and robot-assisted radical prostatectomy.

109-121 1501
Abstract

Mass prostatic specific antigen (PSA) testing (population-based PSA screening) has remained controversial, nevertheless there are men cohorts likely to benefit from PSA screening. Heritable factors contribute to 60 % risk for developing familial prostate cancer. Despite the fact that its clinical application is challenging due to polygenic inheritance, advances in new generation sequencing technologies permit identifying highly penetrant germline mutations in genes BRCA1, BRCA2, CHEK2, HOXB13 and MMR associated with tremendous increase in risk of developing the prostate cancer. Several germline mutations are associated with clinically aggressiveness of disease and shortened survival. Targeted screening that is based on family history and genomic aberrations should be the next step towards the precision medicine. Men at elevated risk should been performed for early detection are those with familiar history of prostate cancer, or BRCA1, BRCA2, CHEK2, HOXB13 and MMR pathogenic germline mutation carriers, or first line relatives diagnosed with certain types of cancer. Systematic PSA testing in 1–2 years among germline mutation carriers men beginning at age 45 years would contribute to increase in early detection of localized prostate cancer resulting in more chance of curative treatment and improve survival rates

122-129 2026
Abstract

Background. In the last decade, we observed a significant increase in the number of patients undergoing radiotherapy for prostate cancer (PC). It became possible with the development of new equipment that can significantly increase radiation efficiency and reduce the frequency and severity of side effects. Active investigation of new fractionation regimens led to the development of stereotactic radiotherapy (StR) technique. In this article, we describe our own experience of using StR in patients with localized PC.

Material and methods. The study included 48 patients treated with CyberKnife robotic radiosurgery system. The patients received a total dose of 36.25 Gy delivered in 5 fractions.

Results. At a median follow-up of 24 months, the estimated four-year prostate-specific antigen (PSA) relapse-free survival rate was 95.8 %. The median PSA nadir was 0.48 ng/mL. We observed no grade III–IV side effects (either early or late).

Conclusion. Our results suggest that the use of StR allows achieving good biochemical control comparable to that achieved by other methods and demonstrates comparable and sometimes even lower toxicity.

130-141 922
Abstract

Prostate cancer is one of the most common causes of death from oncological diseases in men. Taxanes (including docetaxel and cabazitaxel) are microtubule-stabilizing agents which block mitotic cell division leading to apoptosis. Past data have shown promise and good tolerability for different regimens. Recent studies demonstrated that taxanes prolonged the survival both metastatic (hormone sensitive and castrationresistant) locally advanced prostate cancer. In this article, we describe current treatments for рrostate cancer in different stages with taxanes.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

142-154 1078
Abstract

Background. Viral infection is a major factor in virus-associated carcinogenesis.

Objective: to evaluate the expression of growth factors and markers of apoptosis, proliferative activity, and angiogenesis in patients with viral DNA-positive bladder cancer.

Materials and methods. The study included 100 bladder cancer patients (72 males and 28 females) aged between 38 and 90 years (mean age 65 ± 10). Tumor tissue samples were tested by polymerase chain reaction to detect DNA of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2 respectively), high-risk human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein—Barr virus (EBV). Immunohistochemical analysis was performed in 32 patients and included the following markers: proliferation marker Ki-67, p63, apoptosis regulator Bcl-2, p53, angiogenesis marker CD31, adhesion protein CD44, and epidermal growth factor receptor (EGFR).

Results. Viral DNA in tumor tissue was detected in 34 patients; of them, 50 % had poorly-differentiated tumors. Twenty-seven patients were found to have EBV DNA in their tumor tissue; 6 patients had CMV DNA; 5 patients had high-risk HPV DNA (types 16, 39, 45, 52, and 59); 1 patient had HSV1 and HSV2 DNA. Four out of 34 participants had mixed infections (1 case of HPV 59 + EBV; 2 cases of EBV + CMV; 1 case of CMV + EBV + HPV 31 and 52). We observed a strong correlation between the presence of EBV DNA and levels of CD31 and Ki-67 expression as well as between high-risk HPV DNA and Bcl-2 expression. High levels of antibodies against EBV capsid antigen were associated with EGFR and Ki-67 expression, whereas the level of antibodies against EBV nuclear antigen correlated with CD44 expression. We evaluated specific characteristics of expression of the markers analyzed depending on the tumor stage, grade of anaplasia, and recurrence. We also assessed morphological characteristics of changes in lymphocytic and plasma cell infiltrates.

Conclusion. We found a correlation between the presence of viral DNA in bladder cancer tissue and markers of proliferative activity, angiogenesis, and apoptosis. Viral infection is likely to increase proliferative activity and suppression of apoptosis, which may cause tumor progression. Further studies are needed to assess this correlation.

REVIEW

162-170 1017
Abstract

Bladder cancer is one of the most common malignant diseases involving the urinary system. Accurate prediction of the disease course and outcome is crucial for choosing an appropriate treatment strategy in these patients. Currently, there are several prognostic models for predicting non-muscle invasive bladder cancer outcomes. The scoring systems developed by the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) are the most widely used prognostic models for bladder cancer. Despite the undeniable merits of these scales, they need to be supplemented. Since the prognostic score has a direct impact on the treatment strategy, intensity and costs of postoperative follow-up, and outcome, its accuracy should be higher than it is now. Identifying the additional parameters that would increase the robustness of these models is one of the major challenges for researchers.

The molecular and genetic characteristics of the tumor, that can be estimated after the first surgery, are probably the best candidates for this role. The main limitation of these prognostic models lies in the fact that they assess only morphological properties of the tumor, while the most important molecular characteristics are neglected. These scoring systems do not evaluate clinical factors, concomitant diseases, and iatrogenic complications occurring during the treatment of relapses. The assessment of molecular mechanisms and clinical characteristics underlying the development of non-muscle-invasive bladder cancer as well as identification of key molecular markers, that could complement the currently existing risk assessment models, are the most important goals for researchers dealing with bladder cancer. It will significantly improve predictive capabilities of these models, ensuring the choice of an optimal treatment strategy.

UROLOGICAL COMPLICATIONS IN CANCER PATIENTS

156-161 852
Abstract

Background. Radiation cystitis is a severe late consequence of radiation therapy of pelvic malignancies. Destruction of glycosaminoglycan’s protective barrier (GAG-layer) plays key role in pathogenesis of radiation cystitis. Hence, GAG-replenishment therapy could be a promised method of treatment the radiation cystitis.

The objective is to evaluate the effectiveness of glycosaminoglycan replacement therapy of chronic radiation cystitis using bladder instillation.

 Materials and methods. 23 female patients with radiation cystitis participated in the retrospective study. They have been randomized divided on two groups. Patients of the 1st group have been treated with intravesical administration of 0,08 % sodium hyaluronate alone, 2nd group – with intravesical sodium hyaluronate in combination with oral sodium hyaluronate and chondroitin sulfate.

Results. Patients of both groups demonstrated less frequency and pain after treatment as well as increased bladder volume. Intravesical administration of glycosaminoglycans in combination with oral administration was more effective than intravesical therapy alone.

Conclusions. GAG-replenishment therapy is a promised treatment options of radiation cystitis. Oral and intravesical GAG-replenishment therapy is more effective in comparison with only intravesical therapy.

CLINICAL CASE

171-175 1588
Abstract

The article describes a successful experience of using high-dose rate brachytherapy (192Ir) in patients with local recurrence of hormone-resistant prostate cancer. High-dose rate brachytherapy allowed to achieve local biochemical control of prostate cancer without toxicity to pelvic organs, thus, maintaining the quality of life.

CONGRESSES AND CONFERENCES

177-182 883
Abstract

From 16 th to 20 th of March, 2018, the 33 rd Annual Congress of the European Association of Urology took place in Copenhagen. Doctors from 78 countries participated in the event. 4,381 abstracts were submitted, 1,338 of which were selected for poster sessions. Prostate cancer, kidney cancer, and bladder cancer were the most studied topics and constituted about a half of all accepted abstracts. In this article, a review of the most significant and interesting reports on cancer urology from the EAU Congress in 2018 is presented.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. ADRENAL CANCER

79-87 14335
Abstract

Background. The adrenal glands are one of the most common sites of metastases in malignant disease, particularly lung cancer. The frequency of adrenal metastasis in patients with breast cancer and lung cancer reaches 39 and 35 % respectively.

Materials and methods. A total of 156 patients with adrenal tumors underwent surgical treatment in the Siberian State Medical University between December 1998 and July 2017. The study included 16 (10.2 %) patients (9 males and 7 females) with adrenal metastases. The mean age of study participants was 57.6 years (range: 44–73 years).

Results. By the moment of surgery, the mean metastatic adrenal tumor size was 4.9 ± 3.0 cm (range: 1.0–10.2 cm). Thirteen out of 16 patients had adrenal metastases from renal cell carcinoma, one patient – from colon cancer, one patient – from lung cancer, and one patient – from breast cancer. Nine patients had left-sided adrenal metastases, whereas six patients had right-sided adrenal metastases. Synchronous adrenal metastasis was detected in two cases: one patient had adrenal metastasis at the side of the renal tumor; the other one had bilateral renal cell carcinoma with both adrenal glands affected.

We identified three main variants of the disease course according to prevailing clinical manifestations of adrenal metastasis: no manifestations, pain syndrome, and arterial hypertension.

Seven participants had no clinical manifestations; of them, 6 patients had renal cell carcinoma, whereas 1 patient had breast cancer. The mean time between surgical removal of the primary tumor and detection of adrenal metastases was 24.1 months; the mean tumor size was 4.5 cm.

Pain syndrome was observed in 5 patients. In three of them, adrenal metastases derived from renal cell carcinoma, in one patient – from lung cancer, and in one patient – from colon cancer. The mean time between removal of the primary tumor and detection of adrenal metastases was 19.8 months; the mean tumor size was 5.4 cm.

Arterial hypertension was diagnosed in four patients. The mean time between removal of the primary tumor and identification of adrenal metastases was 27.3 months; the mean tumor size was 4.1 cm. The five-year overall survival rate in operated patient was 47.8 %.

Conclusion. Regular examinations of patients after surgical treatment of malignant tumors are needed to detect adrenal metastases; surgery can extend the patient’s life.

 can extend the patient’s life.



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ISSN 1726-9776 (Print)
ISSN 1996-1812 (Online)
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