Non-metastatik berrak hücreli renal karsinomalı hastalarda De Ritis oranı (aspartat aminotransaminaz/ alanin aminotransaminaz) ve sistemik inflamatuar belirteçlerin prognostik değeri

Öz

Amaç: Bu çalışmada cerrahi olarak tedavi edilen nonmetastatik berrak hücreli renal hücreli karsinom (bhRHK) olgularının preoperatif aspartat aminotransaminaz/alanin aminotransaminaz (De Ritis Oranı - DRO) değerinin prognozu etkileyip etkilemediği ve histopatolojik değişkenlerle ilişkisi değerlendirilmiştir. İkinci amaç da, aynı grup hastalarda nötrofil lenfosit oranı (NLO), trombosit lenfosit oranı (PLO) ve lenfosit monosit oranı (LMO) değerleri ile prognoz ve progresyonsuz sağkalım (PS) arasındaki ilişkiyi değerlendirmekti. Gereç ve Yöntemler: Kliniğimizde 2009-2019 yılları arasında parsiyel veya radikal nefrektomi uygulanan 118 metastatik olmayan bhRHK vakasının tıbbi kayıtları incelenerek çalışmaya alındı. DRO, NLO, PLO ve LMO ve gruplar arasındaki progresyon farkını değerlendirmek için log-rank testleri ile Kaplan-Meier analizi yapıldı. Ayrıca, progresyon öngörücülerini belirlemek için tek ve çok değişkenli Cox regresyon analizleri yapıldı. Bulgular: Hastaların %22,9'unda metastaz ve %6'sında lokal nüks saptandı. Ortanca takip süresi 26 aydı. Tek değişkenli Cox regresyon analizi, tümör boyutunun, invazyon (varlığı), patolojik evre (3+4) ve NLO seviyesinin (≥ 1,98) PS için istatistiksel olarak anlamlı öngörücüler olduğunu gösterdi. Ancak DRO, PS için istatistiksel olarak anlamlı bir öngörücü değildi (p>.05). Tartışma ve Sonuç: bhRHK prognozunda prediktif parametre olarak DRR değeri için anlamlı bir değer bulamadık. Ancak, NLO'deki artış kötü prognoz ile ilişkili bulundu. Bu nedenle prediktif nomogramlarda NLO kullanımı prognozun belirlenmesine olumlu katkı sağlayabilir.

Anahtar Kelimeler

• De Ritis oranı
• Berrak hücreli
• Renal hücreli kanser
• Böbrek kanseri

Prognostic value of De Ritis Ratio (aspartate aminotransaminase/ alanine aminotransaminase) and Systemic Inflammatory Markers in patients with non-metastatic clear cell renal cell carcinoma

Öz

Aim: This study evaluates whether the preoperative aspartate aminotransaminase/ alanine aminotransaminase (De Ritis Ratio - DRR) value affects the prognosis and has a relationship with histopathological variables of non-metastatic clear cell renal cell carcinoma (ccRCC) cases surgically treated. The second aim was to assess the association between neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and lymphocyte monocyte ratio (LMR) values with prognosis, and progression-free survival (PFS) in the same group of patients. Materials and Methods: We reviewed the medical records of 118 non-metastatic ccRCC cases that underwent partial or radical nephrectomy (2009-2019). Kaplan-Meier analysis with log-rank tests was performed to evaluate the difference in progression between DRR, NLR, PLR, and LMR and groups. Moreover, univariate and multiple Cox proportional hazard analyses were performed to identify the predictors of progression. Results: Metastases and local recurrence were detected in 22.9% and 6% of the patients, respectively. Our median follow-up period was 26 months. The univariate Cox regression analysis was showed that the tumor size, invasion (presence), pathological stage (3+4), and NLR level (≥ 1.98)) were statistically significant predictors for PFS. However, DRR was no statistically significant predictor for PFS (p>.05). Conclusion: We did not find any significant value for the DRR value as a predictive parameter in ccRCC prognosis. The increase in NLR is associated with a poor prognosis. Therefore, the use of NLR in predictive nomograms may contribute positively to the determination of prognosis.

Anahtar Kelimeler

• De Ritis ratio; clear cell; renal cell cancer; kidney cancer; prognosis

Kaynakça

1. 1. Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur Urol. 2019;75:799–810.
2. 2. Roxburgh CSD, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncology. 2010;6:149-63.
3. 3. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.
4. 4. Wang H, Fang K, Zhang J, et al. The significance of De Ritis (aspartate transaminase/alanine transaminase) ratio in predicting pathological outcomes and prognosis in localized prostate cancer patients. Int Urol Nephrol. 2017;49:1391–8.
5. 5. Gu L, Ma X, Xie Y, et al. Pretreatment lymphocyte to monocyte ratio is an independent prognostic factor in metastatic clear cell renal cell carcinoma. Clin Genitourin Cancer. 2017;15:e369–77.
6. 6. Son S, Hwang E-C, Jung S-I, et al. Prognostic value of preoperative systemic inflammation markers in localized upper tract urothelial cell carcinoma: a large, multicenter cohort analysis. Minerva Urol Nefrol. 2018;70:300–9.
7. 7. Semeniuk-Wojtaś A, Lubas A, Stec R, et al. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and c-reactive protein as new and simple prognostic factors in patients with metastatic renal cell cancer treated with tyrosine kinase ınhibitors: a systemic review and meta-analysis. Clin Genitourin Cancer. 2018;16:e685–93.
8. 8. Barua SK, Singh Y, Baruah SJ, et al. Predictors of progression-free survival and overall survival in metastatic non-clear cell renal cell carcinoma: a single-center experience. World J Oncol. 2019;10:101–11.

9. 9. Albisinni S, Pretot D, Al Hajj Obeid W, et al. The impact of neutrophil-to-lymphocyte, platelet-to-lymphocyte and haemoglobin-to-platelet ratio on localised renal cell carcinoma oncologic outcomes. Prog en Urol J l’Association Fr d’urologie la Soc Fr d’urologie. 2019;29:423–31.
10. 10. Hutterer GC, Stoeckigt C, Stojakovic T, et al. Low preoperative lymphocyte-monocyte ratio (LMR) represents a potentially poor prognostic factor in nonmetastatic clear cell renal cell carcinoma. Urol Oncol. 2014;32:1041–8.
11. 11. Park JY, Tae BS, Jeong CW, et al. Development of the clinical calculator for mortality of patients with metastatic clear cell type renal cell carcinoma: An analysis of patients from Korean Renal Cancer Study Group database. Investig Clin Urol. 2020;61:260–8.
12. 12. Botros M, Sikaris KA. The de ritis ratio: The test of time. Clin Biochem Rev. 2013;34:117–30.
13. 13. Ha H, Chung J-W, Ha Y-S, et al. Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy. Investig Clin Urol. 2019;60:447–53.
14. 14. Wu J, Chen L, Wang Y, Tan W, Huang Z. Prognostic value of aspartate transaminase to alanine transaminase (De Ritis) ratio in solid tumors: a pooled analysis of 9,400 patients. Onco Targets Ther. 2019;12:5201–13.
15. 15. Bezan A, Mrsic E, Krieger D, et al. The Preoperative AST/ALT (De Ritis) ratio represents a poor prognostic factor in a cohort of patients with nonmetastatic renal cell carcinoma. J Urol. 2015;194:30–5.
16. 16. Ishihara H, Kondo T, Yoshida K, et al. Evaluation of preoperative aspartate transaminase/alanine transaminase ratio as an ındependent predictive biomarker in patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy: a propensity score matching study. Clin Genitourin Cancer.2017;15:598–604.
17. 17. Canat L, Ataly HA, Agalarov S, Alkan I, Altunrende F. The effect of AST/ALT (De Ritis) ratio on survival and its relation to tumor histopathological variables in patients with localized renal cell carcinoma. Int Braz J Urol. 2018;44:288–95.
18. 18. Kang M, Shin SJ, Sung HH, et al. Clinical significance of pre-to-postoperative dynamics of aspartate transaminase/alanine transaminase ratio in predicting the prognosis of renal cell carcinoma after surgical treatment. Dis Markers. 2020;2020:8887605.
19. 19. Lee H, Lee SE, Byun S-S, et al. De Ritis ratio (aspartate transaminase/alanine transaminase ratio) as a significant prognostic factor after surgical treatment in patients with clear-cell localized renal cell carcinoma: a propensity score-matched study. BJU Int. 2017;119:261–7.
20. 20. Kim SH, Park EY, Joo J, Chung J. The de ritis and neutrophil-to-lymphocyte ratios may aid in the risk assessment of patients with metastatic renal cell carcinoma. J Oncol. 2018;2018 :1953571.
21. 21. Laukhtina E, Pradere B, D Andrea D, et al. Association of preoperative serum De Ritis ratio with oncological outcomes in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma. Urol Oncol. 2020;38:936.e7-936.e14.
22. 22. Gu L, Wang Z, Chen L, et al. A proposal of post-operative nomogram for overall survival in patients with renal cell carcinoma and venous tumor thrombus. J Surg Oncol. 2017 ;115:905–12.
23. 23. Kim SH, Joung JY, Seo HK, Lee KH, Chung J. Baseline chronic kidney disease and ıschemic method of partial nephrectomy are ımportant factors for the short- and long-term deterioration in renal function for renal cell carcinoma staged t1-t2: a retrospective single center study. Biomed Res Int. 2016;2016:5398381.
24. 24. Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6:655–63.
25. 25. Kim TW, Lee JH, Shim KH, et al. Prognostic significance of preoperative and follow-up neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with non-metastatic clear cell renal cell carcinoma. Investig Clin Urol. 2019;60:14–20.
26. 26. Ikeda T, Ishihara H, Takagi T, et al. The De Ritis (Aspartate Transaminase/Alanine Transaminase) ratio as a prognosticator in patients with end-stage renal disease-associated renal cell carcinoma. Clin Genitourin Cancer. 2020;18:236-240.e1.
27. 27. Ohno Y. Role of systemic inflammatory response markers in urological malignancy. Int J Urol .2019;26:31–47.
28. 28. Pichler M, Hutterer GC, Stoeckigt C, et al. Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer. 2013;108:901–7.
29. 29. Viers BR, Houston Thompson R, Boorjian SA, et al. Preoperative neutrophil-lymphocyte ratio predicts death among patients with localized clear cell renal carcinoma undergoing nephrectomy. Urol Oncol. 2014;32:1277–84.
30. 30. Li J, Cheng Y, Ji Z. Prognostic value of pretreatment lymphocyte-to-monocyte ratio in patients with urologic tumors: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 2019;98:e14091.