Urine metabolomic analysis in clear cell and papillary renal cell carcinoma: A pilot study.

Renal cell carcinoma (RCC) is one of the most lethal type of tumors and is twice more frequent in men than in women. Initial symptoms are unspecific and belated thus increasing mortality. Moreover, current diagnostic and monitoring tools are harmful for the patient and unspecific in low-grade tumors. Therefore, novel minimally-invasive markers are needed to diagnose and monitor RCC patients. Urine represents the ideal sample source of non-invasive biomarkers for RCC. In our study we aimed to identify a urine metabolomic profile characteristic of RCC patients with diagnostic purposes and also to identify a profile with prognostic value. By an UPLC-Q-ToF MS untargeted metabolomic analysis, we compared the metabolomic profile of 23 RCC patients (14 clear cell RCC and 9 papillary RCC) before surgery and that of 23 healthy controls. Additionally, for the first time, we compared the metabolomic profile of these RCC patients pre-nephrectomy and 3 months and one year post-nephrectomy. We identified the dysregulated metabolomic variables by querying their exact mass against those presented in the Metlin and Human Metabolome Database. Next, we experimentally confirmed their identity. Both RCC subtypes showed similar metabolomic patterns at all stages. 51 metabolomic variables were significantly increased in RCC compared to controls and, among them, 4 were selected as potential discriminant metabolites between groups. We could experimentally confirm the identity of p-cresol glucuronide thus describing for the first time an increase in this metabolite in urine of RCC patients (fold change = 2.922, P = .012). Additionally, we confirmed that no metabolomic differences occur 3 months post-nephrectomy in RRC, while 188 variables were significantly increased one year post-nephrectomy. Of the 15 most discriminant metabolomic variables, we could experimentally confirm the identity of isobutyryl-l-carnitine (fold change = 2.098, P = .004) and l-proline betaine (fold change = 3.328, P = .004), for the first time. In summary, we have identified urine p-cresol glucuronide as potential diagnostic marker for RCC and isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. When confirmed in an independent cohort of RCC patients, these markers may improve the diagnosis and monitoring of RCC patients thus reducing current harmful diagnostic procedures. SIGNIFICANCE: The high-radiation dose of current imaging techniques available to diagnose and monitor renal cell carcinoma (RCC) are harmful for the patient and unspecific in low-grade tumors. Our untargeted metabolomic analysis carried out in urine samples from RCC patients and healthy individual reveals p-cresol glucuronide as potential diagnostic marker for RCC. Additionally, the analysis of RCC urine samples one year post-nephrectomy reveals isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. These novel non-invasive urine biomarkers may improve RCC management thus reducing the use of current harmful diagnostic techniques.

Evaluation of Adult Acute Scrotum in the Emergency Room: Clinical Characteristics, Diagnosis, Management, and Costs.

OBJECTIVE: To evaluate the clinic characteristics, diagnosis, management, and costs of the adult acute scrotum in the emergency room (ER). Acute scrotum is a syndrome characterized by intense, acute scrotal pain that may be accompanied by other symptoms. It is usual in children and commonly found as well in adults, with different causal pathologies between these groups. METHODS: Between November 2013 and September 2014, 669 cases of adult acute scrotum who presented to our ER were prospectively analyzed. Patients under 15 years of age were excluded. Patient age, reason for consultation, investigations performed, final diagnosis, management, and costs were evaluated. For the statistical analysis, the Mann-Whitney, Kruskal-Wallis U, and chi-square tests were used. RESULTS: A total of 669 cases of acute scrotum were analyzed. The mean age at presentation was 40.2 ± 17.3 years. The most presented diagnoses were orchiepididymitis (28.7%), epididymitis (28.4%), symptoms of uncertain etiology (25.1%), and orchitis (10.3%). Diagnostic tests were carried out in 57.8% of cases. Most cases were treated as outpatients (94.2%), with 5.83% admitted and 1% undergoing surgical treatment. Overall, 13.3% of patients represented to the ER. Abnormal results in blood and urine tests were more common among older patients and infectious pathologies. The average cost generated by an acute scrotum ER consult was 195.03€. CONCLUSION: Infectious pathologies are the most common causes of acute scrotum at ER. Abnormal blood and urine tests are unusual and are more common in older patients and infectious pathologies.