Yulian Mytsyk, Yuriy Borys, Lesia Tumanovska, Dmytro Stroy, Askold Kucher, Katarina Gazdikova, Luis Rodrigo, Peter Kruzliak, Robert Prosecky, Peter Urdzik, Victor Dosenko
Clin Exp Med (2019) 19: 515. https://doi.org/10.1007/s10238-019-00574-7
https://link.springer.com/article/10.1007%2Fs10238-019-00574-7
None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan–Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E − 03 ± 3.11E − 03 RU (p < 0.001). Overexpression of miR-15a was strongly associated with poor histologic prognostic features of ccRCC. Poorly differentiated tumors tend to have more pronounced upregulation of miR-15a compared to highly differentiated lesions: Mean expression values were 4.57 ± 3.19 RU for Fuhrman grade 4 versus 0.02 ± 0.01 RU for Fuhrman grade 1 (p < 0.001). The metastatic involvement of the regional lymphatic nodules (N +) was associated with significantly upregulated miRNA-15a in comparison with N − cases: Mean expression values were 4.92 ± 2.80 RU versus 1.10 ± 2.29 RU, respectively (p < 0.001). In patients with miR-15a expression in RCC tissues ≤ 0.10 RU, mean 5-year CSS was significantly longer compared to patients with expression levels above this threshold: 92.31% (mean duration of survival—59.88 ± 0.12 months) versus 54.8% (mean duration of survival—49.74 ± 2.16 months), respectively (p < 0.001). The tissue expression of miR-15a could be used as a potential prognostic molecular biomarker for conventional RCC.
Yulian Mytsyk, Victor Dosenko, Michał Andrzej Skrzypczyk, Yuriy Borys, Yuriy Diychuk, Askold Kucher, Vasyl Kowalskyy, Serhyi Pasichnyk
Cent European J Urol. 2018; 71(3): 295–303. Published online 2018 Jul 2. doi: 10.5173/ceju.2018.1618
Renal cell carcinoma (RCC) accounts for 3% of adult malignancies and more than 90% of kidney neoplasms. High rates of undiagnostic percutaneous kidney biopsies and difficulties in reliable pre-operative differentiation between malignant and benign renal tumors using contemporary imaging techniques result in large numbers of redundant surgeries. Absence of specific biomarkers for early detection and monitoring complicates on-time diagnosis of the disease and relapse. For the patients followed up after having a nephrectomy, a noninvasive and sensitive biomarker enabling early detection of disease relapse would be extremely useful.
The study is a review of recent knowledge regarding potential clinical applications of microRNAs (miRNAs) as biomarkers of RCC.
MicroRNAs are essential regulators of various processes such as cell proliferation, differentiation, development and death; they have been implicated in diverse biological and pathological processes in RCC. There is a class of miRNAs that promote RCC development (oncomirs) and a class of miRNAs that negatively regulate oncogenes, suppress tumor growth and invasion, and thus could be considered treatment agents (anti-oncomirs). Separate miRNAs and specific miRNAs expression profiles have been identified, enabling early detection of the disease, prediction of response to systemic therapy, or prognostication of biological behavior of the disease.
The miRNA network analysis and gene profiling may help to identify the most sensible molecular signatures of RCC that can be used for diagnostic purposes, as well as poor prognosis signatures and poor therapeutic response signatures in patients who undergo systemic therapy.
Yulian Mytsyk, Victor Dosenko, Yuriy Borys, Askold Kucher, Katarina Gazdikova, Dietrich Busselberg, Martin Caprnda, Peter Kruzliak, Ammad Ahmad Farooqi
Int Urol Nephrol (2018) 50: 851. https://doi.org/10.1007/s11255-018-1841-x
Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker.
In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n = 22), papillary RCC (pRCC, n = 16), chromophobe RCC (chRCC, n = 14), oncocytoma (n = 8), papillary adenoma (n = 2) and angiomyolipoma (n = 5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control.
We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E−01 ± 2.72E−01 vs 1.32E−03 ± 3.90E−03 vs 3.36E−07 ± 1.04E−07 RFU, respectively, p < 0.01). There was no difference in miR-15a expression between ccRCC, pRCC and chRCC (p > 0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient—0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p < 0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E−06 RFU, with AUC—0.955.
MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.
V. S. Fedevych, Yu.O. Mytsyk, Yu.B. Borys
JMBS 2019, 4(5): 202–207 https://doi.org/10.26693/jmbs04.05.202
Despite the recent advances in the diagnostic and therapeutic tactics of patients with bladder cancer, the relevance of this oncological problem remains problematic up to now. Angiogenesis is one of the main factors in the survival and spread of tumor cells. At the moment, there is a wealth of evidence confirming the involvement of growth factors, in particular, VEGF (vascular endothelial growth factor) and TNF (tumor necrosis factor) responsible for the mitogenic activity of cells in the development and progression of malignancies and, therefore, are promising targets when using targeted therapy. The purpose of the study was to determine the molecular markers of VEGF, TNF-α and TNF-β in the urine of patients with bladder cancer stage T3N0M0 and to establish their relation to the degree of G neoplasia. Material and methods. The study included 47 patients with bladder cancer stage T3N0M0 (main group). There were 27 men and 20 women among them. The age of men was 58.1±7.8 and women – 59.4 ±1.3 years. Clinical data from 30 healthy individuals were used as control group data. Results and discussion. According to the results of the statistical analysis, patients with bladder cancer stage T3N0M0 had the average level of VEGF in urine 245.65±7.90 pg / ml which significantly exceeded this indicator in the control group, which was 131.23±7.80 pg / ml. However, this difference was statistically significant (p = 0.04). When studying the level of VEGF in the urine of patients with degrees of neoplasia G1, G2, G3, we found out that in the mentioned subgroups of patients, its average value was 239.59± 9.84 pg / ml, 246.84± ±8.79 pg / ml and 251.57±7.22 pg / ml, respectively. We observed a low degree of G1 neoplasia more frequently. It was detected in 19 of 47 patients, accounting for 40.43%. G1 was diagnosed in 34.04% of patients, and G3 in 25.53% of bladder cancer patients in stage T3N0M0. It should be emphasized that due to the retrospective nature of the study, the above data did not fully reflect the actual epidemiological situation regarding the incidence of T3N0M0 stage bladder neoplasia. The data obtained during the study on the levels of TNF-a in the urine of patients with bladder cancer in stage T3N0M0 had no fundamental differences from the results obtained in the study of stages T1 and T2: the average level of TNF-a in the urine was 361.51±6.76 pg / ml and 352.68±6.75 pg / ml in the control group. This difference was not statistically significant (p> 0.05). When determining TNF-a level in patients with different degrees of neoplasia, we found out that in subgroups of patients with G1, G2, G3, the mean values of this marker in the urine were 360.04±5.97 pg / ml, 361.92±6.89 pg / ml and 363.07±7.50 pg / ml, respectively. In patients with stage 3 T3N0M0 bladder cancer, the average level of TNF-β in the urine was 38.27±4.68 pg / ml, with this indicator in the control group being 33.82±4.62 pg / ml, but this difference did not was statistically significant (p> 0.05). In patients with bladder cancer and the degree of G1 neoplasia, the average level of TNF-β in the urine was 37.01±4.46 pg / ml, at the degree of G2 it was 38.30±4.49 pg / ml, and at the degree of neoplasia of the tumor G3 it equaled 40.01±4.83 pg / ml. Our study had the purpose to determine the molecular markers of VEGF, TNF-α and TNF-β in the urine of patients with bladder cancer stage T3N0M0 and establish their relationship with the degree of neoplasia G, and showed that the average level of VEGF in the urine was 245.65±7.90 pg / ml and significantly exceeded this indicator in the control group, which amounted to 131.23±7.80 pg / ml. However, this difference was statistically significant. In the diagnosis of bladder cancer, the sensitivity and specificity of urinary TNF-α levels were low and were 30% and 20%, respectively, and TNF-β levels they were even lower – 25% and 20%, respectively, which is not representative for the disease. Conclusion. Thus, the determination of the molecular markers of VEGF, TNF-α and TNF-β in the urine of patients with bladder cancer in stage T3N0M0 may serve the basis for the development of new methods for early diagnosis of the disease, as well as predicting the course and evaluating the effectiveness of treatment.
Mytsyk Yu.O., Borys Yu.B., Dosenko V. et al.
Experimental and Clinical Physiology and Biochemistry. ECPB 2017, 80(4): 9–12 https://doi.org/10.25040/ecpb2017.04.009
Renal cell carcinoma (RCC) is relatively common pathology that is found roughly in 3 % of all cases of malignant neoplasia in adults and approximately in 90 % of malignant tumors arising because of a kidney. Associations between imaging features and genomic landscape of RCC have been recently investigated in order to characterize better tumor diagnosting more precisely, staging and establishing more accurate prognosis comparing to classic histopathologic approach. Such integration of imaging and molecular biomarkers has led to novel concept of “radiogenomics”. In our previous work we have already described usefulness of expression of mi-R-15a measured in urine during RCC diagnostics. Moreover, high miR-15a expression values have been significantly associated with poor survival rates in patients with RCC.
The purpose. The goal of the study is investigation of the associations between cross-sectional imaging features of RCC and urine expression levels of miR-15a.
Materials and methods. 52 adult patients with RCC according to clinical and imaging data have been engaged into study. In all patients’ multiphase CT or MRI imaging with contrast enhancement has been performed prior to surgical treatment using standard abdominal protocols.
Urine collecting and miR-15a expression measuring has been performed using quantitative polymerase chain reaction. Associations between miR-15a expression and such RCC imaging features as necrosis, renal vein invasion, presence of intratumoral calcifications, definition of tumor margin and architecture, presence of collecting system invasion, intratumoral hypervascularity, homogeneous or nodular tumor enhancement pattern on nephrographic phase images have been assessed. All patients have been treated surgically with the following pathologic analysis.
Results. RCC cases have been classified concordantly to AJCC cancer staging manual: T1aN0M0 (n = 13, 25,0 %), T1bN0M0 (n = 15, 28,85 %), T2aN0M0 (n = 12, 23,08 %), T2bN0M0 (n = 5, 9,62 %), T3aN0M0 (n = 4, 7,69 %), T3aN1M0 (n = 3, 5,77 %). RCCs have been classified according to histologic subtypes – clear cell RCC (n = 22), papillary RCC (n = 16), chromophobe RCC (n = 14). Simplified two-tiered Fuhrman grading system has been used, in which grades I and II (low grade, n = 12) and grades III and IV (high grade, n = 10) have been combined.
The expression values of miR-15a in urine of patients with RCC have varied from 91,35 to 5,52 relative fluorescence units (RFU), mean – 54,58 ± 37,76 RFU. High expression levels of miR- 15a (> 25 RFU) in patients with RCC have been associated with necrosis (p < 0,05), ill-defined margins of the lesion (p < 0,05) and intratumoral hypervascularity (p < 0,01). Lower miR-15a expression levels (< 25 RFU) have been associated with imaging evidence of renal vein (p < 0,05) and collecting system (p < 0,05) invasion, nodular tumor enhancement pattern (p < 0,05) and multicystic tumor architecture (p < 0,05). There has been no significant association between miR- 15a expression and presence of intratumoral calcifications on cross-sectional images (p>0,05). Conclusions. Radiogenomic analysis may provide valuable information for predicting of emiR-15a expression levels in urine of patients with RCC. In clinical conditions under which there is no possibility to perform genetic assay, imaging features of RCC can be used as surrogates of miR-15a expression to perform prognostication of disease biologic behavior.
Mytsyk Y. , Borys Y., Pasichnyk S., el al.
European Journal of Medical Technologies. 2019, 2(23). P.24-29.
Renal artery embolization (RAE) is used for preparation of patients with renal
cell carcinoma (RCC) of large size or significant vascularization to surgical treatment.
Currently there is no accurate method of prediction of intraoperative
blood loss in patients with RCC after RAE, that may give possibility for more adequate
pre – and postoperative patient management and to define the indications
for re-embolization. The goal of the study was to evaluate the possibility of
application of apparent diffusion coefficient (ADC) for the prediction of the estimated
intraoperative blood loss (EIBL) during the open radical nephrectomy in
patients with RCC and after RAE. The study enrolled 35 patients (main group, 20
males and 15 females) with solid RCC according to clinical and radiologic data
and with the indications to selective RAE with subsequent radical nephrectomy.
In all patients with RCC in the same day or day before RAE and 7 days after
the RAE MRI with additional DWI sequence with b-value=0.800 was performed.
Subsequent measuring of the ADC over the tumor region was done in all cases. ADC values of the normal renal parenchyma for control were achieved during
the examination of 15 healthy volunteers. In all patients with RCC 7-8 days after
the RAE open radical nephrectomy with simultaneous EIBL measurement was
executed. In patients with EIBL less than 500 ml and with no episodes of the hemotransfusions
mean ADC value decreased by 18.4-31.9% in comparison with
initial ADC value. In patients with EIBL more than 500 ml (with hemotransfusions)
mean ADC value increased by 4.91-65.64% compared to baseline value.
In main group of patients in whom no hemotransfusions were required in postop
period (n=29, 82.86%) there was significant (р<0.05) difference in mean
ADC values before and after RAE (decrease by 20.25%): 1.63±0.31×10−3 mm2/s
vs 1.30±0.19×10−3 mm2/s. In main group patients with hemotransfusions
in post-op period this value increased by 28.83%: 1.63±0.31×10−3 mm2/s vs
2.10±0.47×10−3 mm2/s (р<0.05). Conclusions. Application of MRI and its imaging
biomarker ADC can be valuable clinical instrument for prediction of the EIBL
volume during the open radical nephrectomy in patients with RCC after RAE
and need of the hemotransfusion in postoperative period.
Mytsyk, Y., Dutka, I., Yuriy, B. et al.
Int Urol Nephrol (2018) 50: 197. https://doi.org/10.1007/s11255-017-1761-1
Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5–33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM.
Adult patients (n = 158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n = 15). All participants underwent MRI with DWI sequence included.
Mean ADC values of solid RCC (1.65 ± 0.38 × 10−3 mm2/s) were lower than healthy renal parenchyma (2.47 ± 0.12 × 10−3 mm2/s, p < 0.05). There was no difference between mean ADC values of ccRCC, pRCC and chRCC (1.82 ± 0.22 × 10−3 vs 1.61 ± 0.07 × 10−3 vs 1.46 ± 0.09 × 10−3 mm2/s, respectively, p = ns). An inverse relationship between mean ADC values and Fuhrman grade of nuclear atypia of solid ccRCCs was observed: grade I—1.92 ± 0.11 × 10−3 mm2/s, grade II—1.84 ± 0.14 × 10−3 mm2/s, grade III—1.79 ± 0.10 × 10−3 mm2/s, grade IV—1.72 ± 0.06 × 10−3 mm2/s. This was significant (p < 0.05) only between tumors of I and IV grades. Significant difference (p < 0.05) between mean ADC values of solid RCCs, benign renal tumors and renal cysts was observed (1.65 ± 0.38 × 10−3 vs 2.23 ± 0.18 × 10−3 vs 3.15 ± 0.51 × 10−3 mm2/s, respectively). In addition, there was a significant difference (p < 0.05) in mean ADC values between benign cysts and cystic RCC (3.36 ± 0.35 × 10−3 vs 2.83 ± 0.21 × 10−3 mm2/s, respectively).
ADC maps with b values of 0 and 800 s/mm2 can be used as an imaging biomarker, to differentiate benign SRM from malignant SRM. Using ADC value threshold of 1.75 × 10−3 mm2/s allows to differentiate solid RCC from solid benign kidney tumors with 91% sensitivity and 89% specificity; ADC value threshold of 2.96 × 10−3 mm2/s distinguishes cystic RCC from benign renal cysts with 90% sensitivity and 88% specificity. However, the possibility of differentiation between ccRCC histologic subtypes and grades, utilizing ADC values, is limited.
Mytsyk, Y., Dutka, I., Borys, Y. et al.
Int Urol Nephrol (2017) 49: 215. https://doi.org/10.1007/s11255-016-1460-3
Renal cell carcinoma (RCC) represents the most common malignant epithelial neoplasm of the kidney. Accurate assessment of the renal masses, defining the histologic subtype and the grade of differentiation of the tumor, is vital to ensure an adequate case management as well as for staging and prognosis. Recently, diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) tends to be increasingly appealing for the clinicians as an imaging procedure of choice for the diagnosis and staging of the RCC, which is predetermined by several advantages over CT. The goal of the survey was to assess the applicability of the apparent diffusion coefficient (ADC) of the DWI MRI for the differential diagnostics, histologic subtyping, and defining the grade of differentiation of the RCC.
The study enrolled 288 adult patients with renal lesions: 188 patients with solid RCC—126 patients with clear cell subtype (ccRCC), 32 patients with papillary RCC (pRCC), 30 patients with chromophobe RCC (chRCC); 27 patient with cystic form or RCC (Bosniak cyst, category IV); 32 patients with renal angiomyolipoma (AML); 25 patients with renal oncocytoma (OC); and 16 patients with the renal abscess (AB). In total, 245 lesions were pathologically verified. As a reference, 19 healthy volunteers were included into the study. All patients underwent MRI of the kidneys, involving DWI with subsequent evaluation of the ADC.
There was a reliable difference (p < 0.05) in mean ADC values between the normal renal parenchyma (NRP), solid RCC of different histologic subtypes and grades, cystic RCC, and benign renal lesions. The mean ADC values obtained in the result of the study were (×10−3 mm2/s): 2.47 ± 0.12 in NRP, 1.63 ± 0.29 in all solid RCCs, 1.82 ± 0.22 in solid ccRCC (1.92 ± 0.11—Fuhrman grade I, 1.84 ± 0.14—Fuhrman grade II, 1.79 ± 0.10—Fuhrman grade III, 1.72 ± 0.06—Fuhrman grade IV), 1.61 ± 0.07 in pRCC, 1.46 ± 0.09 in chRCC, 2.68 ± 0.11 in cystic RCC, 2.13 ± 0.08 in AML, 2.26 ± 0.06 in OC, and 3.30 ± 0.07 in AB.
The data received in our study demonstrate a substantial restriction of diffusion of hydrogen molecules in tissues of ccRCC in comparison with the healthy renal parenchyma preconditioned by the greater density of tumor. A statistically significant difference in mean ADC values of ccRCC with different grades of nuclear pleomorphism by Fuhrman was observed: Low-grade tumors showed higher mean ADC values compared to high-grade tumors. The modality of the MRI DWI along with ADC measurement allows to reliably differentiate between the solid RCC of main histologic subtypes and grades, cystic RCC, and the benign renal lesions.
Yulian Mytsyk, Yuriy Borys, Iryna Komnatska, Ihor Dutka, Iryna Shatynska-Mytsyk
Pol J Radiol. 2014; 79: 290–295. doi: 10.12659/PJR.890604
Diffusion-weighted imaging (DWI) is an MRI modality using strong bipolar gradients to create a sensitivity of the signal to the thermally-induced Brownian motions of water molecules and in vivo measurement of molecular diffusion. The apparent diffusion coefficient (ADC) is a quantitative parameter calculated from DWI images which is used as a measure of diffusion. DWI allows to obtain comprehensive information on morphological and functional state of the kidney during a single examination without contrast medium administration. The purpose of the study was to evaluate the value of DWI in differentiating benign and malignant solid kidney tumors based on the initial stage of the study.
The study included 19 adult patients with pathologically verified renal tumors: 9 patients with clear cell subtype of the renal cell carcinoma, 5 patients with oncocytoma and 5 patients with angiomyolipoma (AML). In addition, 5 healthy volunteers with completely normal findings according to kidney ultrasound were included into this study and set as reference. All patients underwent renal MR imaging which included DWI with subsequent ADC measurement. MR imaging was performed with a 1.5 T body scanner using an eight-channel phased-array body coil.
The mean ADC value of ccRCC was significantly lower than that of normal renal parenchyma (2.11±0.25×10−3 mm2/s vs. 3.36±0.41×10−3 mm2/s, p<0.01). There was a significant difference in ADC between the malignant and benign renal lesions: in patients with angiomyolipoma the ADC value was 2.36±0.32×10−3 mm2/s vs. 2.11±0.25×10−3 mm2/s; p<0.05 and in patients with oncocytoma – 2.75±0.27×10−3 mm2/s vs. 2.11±0.25×10−3 mm2/s; p<0.05. The difference in ADC values in patients with high and low ccRCC grades was observed.
DWI can be used to characterize renal lesions; the ADC of a renal lesion can be potentially used as an additional parameter to help determine the appropriate clinical management.
Mytsyk Y., Borys Y., Dutka I., Komnatska I. et al.
European Urology Supplements. – 2015. – V. 14, №2. – P.419.
doi: 10.1016/S1569-9056(15)60412-2
Introduction & objectives:
The diffusion-weighted imaging (DWI) allows to obtain comprehensive information on morphologic and functional state of the kidney during single examination without contrast medium administration. The apparent diffusion coefficient (ADC) and exponential apparent diffusion coefficient (EADC) are the quantitative parameters calculated from DWI images used as a measure of the diffusion. The objective of the survey was to assess the value of the DWI, ADC and EADC in the differential diagnostics of the malignant and benign renal lesions.
Materials & methods:
The study enrolled 84 adult patients with 95 renal lesions: 33 patients with clear cell subtype of the renal cell carcinoma (ccRCC) - 25 patients with solid form and 8 patients with cystic form of the ccRCC, 12 patients with papillary RCC (pRCC) and 9 patients with chromophobe RCC (chRCC), 9 patients with the renal angiomyolipoma (AML), 6 patients with the renal oncocytoma and 15 patients with the renal cysts. In 64 patients the diagnosis was confirmed by pathomorphological examination. In addition, 5 healthy volunteers with completely normal findings were included into this study and set as reference. All patients were assessed by renal MR imaging on 1.5 T body scanner involving standard protocol from the manufacturer and DWI (b value=0,800) with consequent ADC and EADC measurement. Functool 4.5 software was used for ADC and EADC map generation and measurements. Statistical significance was considered when P value was <0.05.
Results:
There was a reliable difference in mean ADC values between the subtypes of the renal cell carcinoma (RCC): in patients with the solid form of ccRCC it was 1,82±0.31×10−3mm2/s (1,92±0.25×10−3mm2/s in tumors grade I according to the Fuhrman gradation system, 1,84±0.31×10−3mm2/s in tumors grade II, 1,79±0.28×10−3mm2/s in tumors grade III and 1,73±0.22×10−3mm2/s in tumors grade IV), in patients with pRCC it was 1,61±0.23×10−3mm2/s and 1,48±0.21×10−3mm2/s in patients with chRCC.
The mean ADC value of the benign renal lesions was reliably different from malignant: 1,58±0.31×10−3mm2/s in patients with AML and 2,02±0.25×10−3mm2/s in patients with the renal oncocytoma. The mean ADC value of the cystic form of ccRCC was 2,08±0.25×10−3mm2/s while mean ADC of the non-malignant cysts was 3,41±0.24×10−3mm2/s, 3,11±0.21×10−3mm2/s and 2,62±0.28×10−3mm2/s in patients with cysts category I, II and III respectively (according to Bosniak classification). The mean ADC value of the normal renal parenchyma was 2,15±0.24×10−3mm2/s. Measurements of the mean EADC showed no significant advantages and difference from the ADC levels but EADC map showed better background suppression than ADC.
Conclusion
Diffusion-weighted imaging along with ADC and EADC measurements of the renal lesions provides valuable and statistically reliable data the can be used for the differential diagnostics between the malignant and benign renal lesions and for the prediction of the grade and histologic subtype of the RCC.
Yulian Mytsyk, Serhiy Pasichnyk, Ihor Dutka, Ihor Dats, Dmytro Vorobets, Michał Skrzypczyk, Yerzhan Uteuliyev, Andrea Botikova, Katarina Gazdikova, Peter Kubatka, Peter Urdzik & Peter Kruzliak
Clinical and Experimental Medicine volume 20, pages277–287(2020)
https://link.springer.com/article/10.1007%2Fs10238-020-00612-9
Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration—7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05–11.61), 7.40 ± 2.50 months (95% CI = 5.61–9.19) and 4.20 ± 1.99 months (95% CI = 2.78–5.62) accordingly (p < 0.05). There was no difference in change of main lesions’ longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35–25.87) and by 7.66 ± 6.72% (95% CI = 2.86–12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.
Yuriy Kobilnyk, Yulian Mytsyk, Yuriy Borys, Ihor Dutka, Volodymyr Dmytriv, Roman Zahorujko
Materials of the 49 Congress of Polish Society of Urology. - 12-15.06.2019. - Katowice, Poland. - P.90