Tag Archive for: letter to the editor

Sir,

We read with great interest the paper by Bedke et al. [1], which showed that using C-reactive protein (CRP) as a biomarker, with 0.25mg/dL as a threshold, did not improve predictive accuracy in a clear-cell RCC model. In certain clinical settings where traditional variables, such as TNM stage, grading and performance status are assessed objectively, a prognostic model for clear-cell RCC consisting of such variables would be helpful, especially if it did not require additional variables such as biomarker measurements and blood data.

The model presented by Bedke et al. includes several subjective variables (Fuhrman grade and performance status). It is worth noting that the evaluation of these subjective variables might be affected by interobserver variation [2]. By contrast, CRP is a serum variable which can be measured objectively. If the subjective variables in the Bedke model could be replaced with objective ones that are routinely available at most institutions, this predictive model would become more consistent and more easily generalizable. We have shown that the predictive model known as TNM-C, which includes CRP instead of subjective variables such as Fuhrman nuclear grade, yields an acceptable level of predictive ability [3].

Yet should the utility of a biomarker be evaluated based only on its discriminative accuracy? Although one of the main motivations for identifying biomarkers is the possibility of incorporating them into prognostic models, biomarkers should be evaluated not only for their utility in discrimination but also with regard to other statistical metrics.

Bedke et al. [1] investigated the prognostic impact of CRP as a biomarker, but only in preoperative settings and using a single cohort without external validation, although many studies have shown that CRP is a powerful predictor of outcomes in RCC [3]. Furthermore, many investigators have reported that the availability of CRP data is linked to improved RCC outcomes in a variety of clinical settings. Several papers have indicated that, in advanced disease states, CRP still has prognostic impact in a postoperative setting [4]. Moreover, CRP is useful not only as a static indicator of prognosis, but also as an indicator of change: measuring dynamic changes in CRP concentration permits the observation of the pharmacological response to therapeutic intervention in RCC [5]. Serial measurements of CRP concentration can be used to monitor the response to therapy at any time during treatment, even during surgery or systemic cytokine therapy. These findings show that CRP can serve as a biomarker for RCC in daily practice [6].

Although a single study showed that CRP did not add significant prognostic value to an established prognostic model, the significance of CRP cannot be dismissed in the clinical treatment of RCC.

Junichiro Ishioka, Kazutaka Saito and Kazunori Kihara
Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan

References

1. Bedke J, Chun FK, Merseburger A et al. Inflammatory prognostic markers in clear cell renal cell carcinoma – preoperative C-reactive protein does not improve predictive accuracy. BJU Int 2012; 110: E771-7.
2. Novara G, Martignoni G, Artibani W,  Ficarra V. Grading systems in renal cell carcinoma. J Urol 2007; 177: 430-6.
3. Iimura Y, Saito K, Fujii Y et al. Development and external validation of a new outcome prediction model for patients with clear cell renal cell carcinoma treated with nephrectomy based on preoperative serum C-reactive protein and TNM classification: the TNM-C score. J Urol 2009; 181: 1004-12.
4. Tatokoro M, Saito K, Iimura Y, Fujii Y, Kawakami S, Kihara K. Prognostic impact of postoperative C-reactive protein level in patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy. J Urol 2008; 180: 515-9.
5. Saito K, Tatokoro M, Fujii Y et al. Impact of C-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma. Eur Urol 2009; 55: 1145-53.
6. Saito K, Kihara K. C-reactive protein as a biomarker for urological cancers. Nat Rev Urol 2011; 8: 659-66.

Sir,

We read the recent publication on clinical and sonographic features predicting testicular torsion in children with great interest [1]. Boettcher et al. identified a variety of clinical predictors, such as short pain duration, nausea or vomiting, abnormal ipsilateral cremasteric reflex, scrotal skin changes and high position of the testicle, as being associated with an increased likelihood of testiscular torsion. They showed that a clinical scoring system based on these clinical factors would have identified all cases of testicular torsion and would have reduced the negative exploration rate by 55%, and concluded that a reliable torsion diagnosis could not be obtained based on ultrasonography alone.

The authors are to be congratulated for their study, because they have identified important clinical variables for predicting testicular torsion and developed a simple and quick scoring system that will reduce the number of patients with acute scrotum undergoing scrotal exploration. We know that colour Doppler sonography (CDS) is the imaging method of choice for the evaluation of acute scrotum, with 63.6–100% sensitivity and 97–100% specificity [2,3]; however, it can show a misleading arterial flow in the early phases of torsion [3]. Furthermore, this imaging technique is operator-dependent and can be difficult to perform in prepubertal children. Other imaging methods, such as scintigraphy and dynamic MRI of the scrotum, provide a sensitivity and specificity similar to that of CDS [3], but these techniques are time-consuming and may also delay diagnosis. Differential diagnosis of testiscular torsion, therefore, remains a clinical diagnosis, and clinical variables such as short duration of pain, nausea and vomiting, high position of testis, skin changes and abnormal ipsilateral cremasteric reflex, deserve to play a more important role in surgical decision-making [4,5].

We believe that CDS, if performed correctly with modern equipment, is an important examination device for the assessment of children with acute scrotum; however, information from CDS should be supported by clinical findings and a physical examination of the patients. A clinical scoring system combined with CDS would be helpful for patient evaluation and to avoid unnecessary scrotal explorations.

Mustafa Resorlu, Yusuf Ziya Tan*, Fatma Uysal, Murat Tolga Gulpinar^†, Gurhan Adam and Huseyin Ozdemir
Departments of Radiology, *Nuclear Medicine and  ^†Urology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, Turkey  

References

1. Boettcher M, Krebs T, Bergholz R, Wenke K, Aronson D. Clinical and sonographic features predict testicular torsion in children: a prospective study. BJU Int 2013 [Epub ahead of print], doi:10.1111/bju.12229.
2. Kalfa N, Veyrac C, Lopez M et al. Multicenter assessment of ultrasound of the spermatic cord in children with acute scrotum. J Urol 2007; 177: 297-301.
3. Tekgül S, Riedmiller H, Dogan HS et al. EAU Guidelines on paediatric urology p17, 2013. Available at: https://www.uroweb.org/gls/pdf/22%20Paediatric%20Urology_LR.pdf.
4. Ciftci AO, Senocak ME, Tanyel FC et al. Clinical predictors for differential diagnosis of acute scrotum. Eur J Pediatr Surg 2004; 14: 333-8.
5. Beni-Israel T, Goldman M, Bar Chaim S, Kozer E. Clinical predictors for testicular torsion as seen in the pediatric ED. Am J Emerg Med 2010; 28: 786-9.