Evaluation of response to tyrosine kinase inhibitors in renal cell carcinoma patients based on expression of miR-99b, -144, -210, -222, -302а and -377 in tumor tissue.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common solid tumors in adults highly resistant to conventional therapies. The expression profile of a number of miRNAs correlates with RCC response to chemotherapeutic agents. AIM: To identify the association of tumor miRNAs expression with neoadjuvant treatment response in patients with RCC. MATERIALS AND METHODS: We analyzed the expression levels of tumor miR-99b, -144, -155, -210, -222, -302а, -377 in 93 RCC patients who received pazopanib or sunitinib in neoadjuvant regimen using RT-PCR. RNU48 was used as a reference miRNA. RESULTS: The levels of expression of miR-99b and -377 are associated with the RCC response to pazopanib, and microRNA-210 and -377 to sunitinib. The characteristic expression profile of miR-99b, -144, -222, -377, and miR-302a determined in 90% of cases was delineated in pazopanib responders as opposed to nonresponders. Similarly, the characteristic expression profile of miR-210, -222, -302a and -377 was suggested for sunitinib responders. CONCLUSIONS: Levels of miR-99b, -210 and -377 expression in RCC tumor tissue might be used as a basis for future predictive panel intended for the assessment of the sensitivity to the regimens of neoadjuvant RCC treatment.

Efficacy of Neoadjuvant Targeted Therapy in Treatment of Patients with Localised Clear-Cell Renal Cell Carcinoma.

AIM: This study aimed to evaluate the efficacy of neoadjuvant targeted therapy (TT) in patients with localised clear-cell renal cell carcinoma (RCC). MATERIALS AND METHODS: A special randomised trial was planned and conducted by the Research Department of Plastic and Reconstructive Oncology in the National Cancer Institute of Ukraine for testing the clinical efficacy of neoadjuvant TT in the treatment of clear-cell localised RCC, and the primary endpoint was tumour response evaluation after TT. The secondary endpoints included evaluation of dependence between the use of neoadjuvant TT and the probability of partial nephrectomy and the correlation between tumour size, stage, remaining functioning parenchyma volume, and response to systemic therapy. RESULTS: Overall, 118 patients met the inclusion criteria and were randomly assigned to receive combined treatment or surgery alone. The percentage of tumour regression ranged from 0% to 60%, and the median was (95% confidence interval) 20.5 ± 14.3 (16.8-24.3%). Most of the patients had a slightly positive response to TT (3%-29% decrease in tumour size); n = 44 (76.9%) cases. Partial response by the Response Evaluation Criteria in Solid Tumours, version 1.1, was observed in 14 (24.1%) patients and reached a maximum of 60% regression. Tumour reduction in the neoadjuvant TT group allowed kidney preservation in 53 (91.4%) patients. In the control group, the number of organ-sparing procedures was significantly lower (n = 20, 33.3%). The statistical difference was relevant (x 2 = 42.1; p < 0.001). CONCLUSION: The positive results of neoadjuvant TT obtained in our study indicate the clinical validity of combined treatment in patients with localised RCC.

Quality of life in patients after radical cystectomy with modified ureterocutaneostomy and Bricker urinary diversion.

BACKGROUND: Radical cystectomy (RC) has been used for over 100 years as an effective treatment of muscle invasive bladder cancer (MIBC). However, the main surgical challenge is not only to remove an affected organ but also to replace its functional component - urine diversion. The aim of our work is to study the efficacy of the modified ureterocutaneostomy technique by estimating the quality of life in post-RC patients with MIBC. MATERIALS AND METHODS: A retrospective analysis of the cases of 40 patients was provided. Two groups were delineated depending on urinary diversion: 20 patients with urinary derivation by the modified ureterocutaneostomy method, and 20 patients - with Bricker conduit. All patients were matched by mean age, gender, American Society of Anesthesiologists status, disease stage and duration. 16 (80%) and 15 (75%) patients from the study and control groups, respectively, passed 3 courses of standard preoperative polychemotherapy with gemcitabine-cisplatin. Quality of life was assessed using the health survey SF-36 form (developed at the US Medical Research Institute), adapted at the National Cancer Institute (Ukraine). RESULTS: Comparing patients after ureterocutaneostomy or Bricker surgery, no statistical discrepancy was noted before surgery and after 3 months. A statistical difference in perioperative parameters was noted only when comparing the surgery duration and length of stay in hospital. CONCLUSIONS: The modified ureterocutaneostomy technique contributes to performing surgery faster and more effectively since an intestinal stage is skipped in surgery. Our findings indicate that ureterocutaneostomy technique may be used as a standard of care for post-RC patients with MIBC.

[PECULIARITIES OF METHOD AND RESULTS OF PLASTY, USING INTESTINAL SEGMENT, FOR IATROGENIC INJURY OF URETER].

Basing on analysis of the examination and treatment results in 53 patients, suffering iatrogenic injury of ureter (IIU), the indications for ureteric reconstruction using intestinal segment were the ureter long irreversible changes, while renal function preserved. A segmental ureteric plasty was done in 8 (15.1%) patients, a subtotal one--in 16 (30.2%), total--in 14 (26.4%), and bilateral--in 15 (28.3%). With the objective to prevent the bladder-intestinal reflux occurrence a distal part of the intestinal transplant was modeled. In 35 (66%) patients 2 - 3 cm of distal part of intestinal mucosa were turned out with the wrap formation. In 18 (34%) patients the creation of antireflux wrap was added by its modeling in a kind of intraileal plasty with formation of two separate channels in the intestinal-bladder anastomosis region. While performance of intraileal plasty of the bladder-intestinal reflux have occurred in 2 (11.1%) patients, and after procedure with the wrap formation--in 13 (37.1%).

[Application of nephrometry for choice of the treatment tactics in patients, suffering nephrocellular cancer].

Most significant nephrometric parameters, impacting the operative procedure choice, basing on analysis of examination and treatment of 903 patients, suffering localized nephrocellular cancer (NCC), were determined a residual volume of kidney parenchyma, maximal size and localization of tumor. The authors elaborated the estimation system for tumor affection of kidney (NCIU-nephrometry), what give possibility to determine the tactics of operative treatment of NCC. While localization of tumor in the kidney pole or its lateral segment a threshold value of the functioning parenchyma volume, in which the conduction of resection of kidney (RK) is indicated, must be over 55%. While localization of tumor in the kidney medial segment the indication for RK is a maximal size of tumor up to 4 cm. Introduction of the elaborated system into clinical practice would permit to make objective indications for RK and nephrectomy conduction.

[NEOADJUVANT TARGET THERAPY IN A RENAL-CELL CANCER].

There were observed 30 patients (32 tumors), to whom preoperatively for renal-cell cancer (ROC) a neoadjuvant target therapy (NATTH) was conducted. In 19 (66.7%) of them a pazopanib (800 mg per os once a day through 2 mo) was applied, and in 10 (33.3%)--sunitinib (50 mg per os once a day through 28 days, the gap--14 days, repeated course--28 days). The indications for the NATTH conduction were: in 7 (21.9%) patients--a locally--spread RCC with the objective to localize a tumor and to search a further possibility of radical surgical intervention performance, and in 25 (78.1%)--the tumor reduction and searching possibility of the organpreserving treatment conduction. The NATTH conduction in the patients, suffering RCC, have guaranteed a primary pathological focus reduction in 90% of observations, and a partial regression in accordance to the RECIST criteria--in 28.1%. A tumor reduction by (22.9 ± 17.8)% at average have permitted to perform a renal resection in 75% of observations, concerning localized RCC, when indication of preservation of enough functioning renal parenchyma was secured.

[CRITERIA OF ESTIMATION AND RESULTS OF TREATMENT OF IATROGENIC INJURIES OF URETERS IN ONCOLOGICAL PATIENTS].

Clinical analysis was conducted in 74 oncological patients, in whom 103 iatrogenic injuries of ureter (IIU) were revealed and for which they were treated in Scientific-nvestigative Department of Plastic and Reconstructive Oncourology. Restoration of renal and ureteric function were noted in terms up to 6 mo, in these terms were revealed all complications, caused by recurrence of obstruction. Late follow-up results of III were positive in 95.2% patients, unsatisfactory result was revealed in 3 (4.8%) patients, what have demanded conduction of surgical secondary correction of urodynamics. Quality of life after restoration operative treatment have improved in 31.70%patients in comparison of such before the operation.

[TACTICS OF TREATMENT OF PATIENTS FOR ONCOLOGICAL DISEASES IN IATROGENIC INJURY OF UPPER URINARY WAYS].

Results of examination and treatment of 119 patients for oncological diseases were analyzed, in whom iatrogenic injury of ureter (IIU) have occurred. Remission of oncological diseases plastic operations were performed in 48 (40.3%) patients, reconstructive - in 23 (19.3%), restoration - in 3 (2.5%); while a progress - palliative nephrostomy in 41 (34.5%) patients. In 4 (3.4%) patients dynamical observation was conducted. The method of operative treatment was selected, taking into account efficacy of treatment of oncological diseases; mechanism of IIU; level of obstruction and irreversibility of changes in wall of ureter; character of injury (one-sided, bilateral, injury of ureter of a single kidney); anatomo-functional changes of upper and lower urinary ways; the patient state severity.