Urologic Oncology: Seminars and Original Investigations
Original articleDe Ritis (aspartate transaminase/alanine transaminase) ratio as a significant predictor of recurrence-free survival in patients with upper urinary tract urothelial carcinoma following nephroureterectomy
Introduction
Upper urinary tract urothelial carcinoma (UUTUC) is a rare disease that accounts for approximately 5% of all tumors derived from the urothelium [1]. Although nephroureterectomy with bladder cuff removal is currently considered as the gold standard treatment for localized UUTUC, high incidences of postoperative systemic disease recurrence in patients with UUTUC have been reported [2], [3]. Therefore, it is important to precisely predict the clinical course following surgery in counseling to determine the best treatment and follow-up strategies for individual patients with UUTUC. However, it remains challenging to guide physicians and patients in the management of UUTUC based on high-quality data for several reasons, such as the low incidence of this disease, the varied UUTUC biology and associated prognosis, and the presence of different therapeutic options [4].
Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are enzymes released from liver cells into the blood stream, representing hepatocellular damage; thus, these are recognized as a part of the commonly requested panel, assessing the liver function [5]. In 1957, the ratio of the serum activities of AST and ALT was initially described by De Ritis, and has been known as the De Ritis ratio [6]. Although originally being proposed as a characteristic of viral hepatitis, this ratio has subsequently been shown to be a useful biomarker for other hepatic diseases [7]. In recent years, there have been several studies showing that different levels of aminotransaminases, including the De Ritis ratio, could be useful prognostic biomarkers in patients with certain types of malignant tumor [8], [9], [10], [11]. For example, Bezan et al. [11] reported that the preoperative De Ritis ratio was an independent prognostic factor in patients with nonmetastatic renal cell carcinoma. To our knowledge, however, the prognostic significance of aminotransaminases in UUTUC remains largely unknown. Considering these findings, we retrospectively reviewed clinicopathologic data from a total of 109 consecutive Japanese patients with clinically localized UUTUC who underwent nephroureterectomy, focusing on the prognostic significance of aminotransaminases in this cohort of patients.
Section snippets
Materials and methods
Of consecutive patients who were newly diagnosed with clinically localized UUTUC and subsequently underwent nephroureterectomy without any neoadjuvant therapies between 2005 and 2014 at our institution, this study included a total of 109 patients fulfilling the following criteria: (1) pure UUTUC was pathologically confirmed, (2) clinical T stage was less than T3, (3) neither nodal nor distant metastasis was found by any diagnostic imaging modality, (4) patients did not have a history of
Results
In this study, 1.30 was selected as an optimal threshold value for the De Ritis ratio using the Youden Index (Fig. 1A). Based on this cutoff value, receiver operating characteristics analysis was conducted to evaluate the association between the De Ritis ratio and eRFS, and the AUC of this case was 0.55 (Fig. 1B). Table 1 shows the clinicopathological characteristics of 109 patients with clinically localized UUTUC who underwent nephroureterectomy according to the preoperative values of AST,
Discussion
Nephroureterectomy is widely recognized as a standard treatment of patients with clinically localized UUTUC. Despite this definitive surgical treatment, UUTUC is characterized by a high risk of postoperative systemic disease recurrence that has been reported to occur in approximately 30%-40% of patients with UUTUC undergoing nephroureterectomy [2], [3]. A number of studies, therefore, have been performed to identify parameters precisely predicting the clinical course of UUTUC following
References (19)
- et al.
Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature
Eur Urol
(2012) - et al.
The current state of serum biomarkers of hepatotoxicity
Toxicology
(2008) - et al.
An enzymic test for the diagnosis of viral hepatitis: the transaminase serum activities
Clin Chim Acta
(1957) - 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) - et al.
Liver metastases from breast cancer: the relationship between clinical, biochemical and pathological features, and survival
Eur J Cancer
(1990) - et al.
Cancer cell metabolism: Warburg and beyond
Cell
(2008) - et al.
Evidence-based sex-related outcomes after radical nephroureterectomy for upper tract urothelial carcinoma: results of large multicenter study
Urology
(2009) - et al.
Ureteral and multifocal tumours have worse prognosis than renal pelvic tumours in urothelial carcinoma of the upper urinary tract treated by nephroureterectomy
Eur Urol
(2011) - et al.
Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973–2005
BJU Int
(2011)
Cited by (32)
Anti-PADI4 antibody suppresses breast cancer by repressing the citrullinated fibronectin in the tumor microenvironment
2022, Biomedicine and PharmacotherapyCitation Excerpt :The ALT level significantly increased the risk of primary liver cancer [31]. A high pretreatment AST/ALT ratio (De Ritis ratio, DRR) was significantly associated with worse overall survival [32–42]. EMT is an important index of tumorigenesis [43].
Aspartate transaminase/alanine transaminase (De Ritis ratio) predicts survival in major burn patients
2022, BurnsCitation Excerpt :Initially, the De Ritis ratio was a valuable indicator for the diagnosis of viral hepatitis. However, previous studies have reported that the De Ritis ratio is also an independent predictor of poor outcomes in patients with acute ischemic stroke, cardiac surgery, non-metastatic renal cell carcinoma, and upper urinary tract urothelial carcinoma [7–10]. Considering that a rise in ALT mainly reflects liver-specific dysfunction while a rise in AST is reflective of kidney, skeletal muscle, and even cerebral ischemic cells, the De Ritis ratio may indicate ischemic organs during the acute phase of severe burns [11].
Prognostic role of preoperative De Ritis ratio in upper tract urothelial carcinoma treated with nephroureterectomy
2020, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :However, after being adjusted for standard pathologic prognostic factors in UTUC, the De Ritis ratio did not retain its statistical significance. Most of the previous studies reported, however, an independent predictive value for RFS, CSS, and OS [15–20]. The discrepancies between these studies and our findings could be explained by several reasons.
The De Ritis (Aspartate Transaminase/Alanine Transaminase) Ratio as a Prognosticator in Patients With End-stage Renal Disease–associated Renal Cell Carcinoma
2020, Clinical Genitourinary CancerCitation Excerpt :AST widely expresses in several organs such as the kidney, muscles, and hepatocellular cells, and increased AST enzymes are identified as an indicator of various diseases including cancer. Recently, the prognostic impact of the AST/ALT ratio (ie, the De Ritis ratio) has been reported in several types of cancers, including urologic malignancies.10-14 Furthermore, in RCC, the association between the AST/ALT ratio and prognosis was reported.12-15
De Ritis Ratio: a Potent Marker in Cancer
2023, Clinical Laboratory