Prognostic role of the immunohistochemical expression of proteins related to the renin-angiotensin system pathway in nonmetastatic clear cell renal cell carcinoma.

INTRODUCTION: Stage migration has been observed in renal cell carcinoma (RCC) in recent decades; however, mortality rates have continuously increased in some countries. Tumoral factors have been characterized as major predictors of RCC. Nonetheless, this concept can be improved by combining these tumoral factors with other variables, including biomolecular factors. PURPOSE: This study aimed to assess the immunohistochemical (IHC) expression and prognostic value of renin (REN), erythropoietin (EPO), and cathepsin D (CTSD), and to evaluate whether the concomitant expression of these markers can influence the prognostic outcomes in patients without metastasis. MATERIAL AND METHODS: In total, 729 patients with clear cell RCC (ccRCC) who underwent surgical treatment between 1985 and 2016 were evaluated. All the cases in the tumor bank were reviewed by dedicated uropathologists. The IHC expression patterns of the markers were assessed using a tissue microarray. REN and EPO were classified as "positive" or "negative" expression. CTSD was grouped into "absent or weak expression" or "strong expression." Associations between clinical and pathological variables and the studied markers, in addition to 10-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival rates, were described. RESULTS: REN and EPO expressions were positive in 70.6% and 86.6% of patients, respectively. Absent or weak and strong expressions of CTSD were observed in 58.2% and 41.3% of the patients, respectively. EPO expression had no impact on survival rates even when assessed concomitantly with REN. Negative REN expression was associated with advanced age, preoperative anemia, larger tumors, perirenal fat, hilum or renal sinus infiltration, microvascular invasion, necrosis, high nuclear grade, and clinical stages III to IV. In contrast, strong CTSD expression was associated with poor prognostic variables. The expression patterns of REN and CTSD were unfavorable predictors of the 10-year OS and CSS. In particular, the combination of negative REN and strong CTSD expression had a negative impact on these rates, including a higher risk of recurrence. CONCLUSION: Loss of REN expression and strong CTSD expression were independent prognostic factors in nonmetastatic ccRCC, particularly when the concomitant expression pattern of both markers was present. EPO expression did not influence survival rates in this study.

Simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion: step-by-step video-illustrated technique

ABSTRACT Introduction: One of the most remarkable characteristics of urothelial carcinomas is multifocality. However, occurrence of synchronous bladder cancer and upper urinary tract urothelial cancer (UTUC) is exceptional. Minimally invasive approach for these synchronous tumors was just occasionally reported (1-4). The aim of this video article is to describe step-by-step the technique for simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion (ICUD). Patients and methods: A 66-year-old female presented with synchronous BCG refractory non-muscle invasive bladder cancer and a right-side UTUC. She was a former smoker and had previously been submitted to multiple transurethral resections of bladder tumor, BCG and right distal ureterectomy with ureteral reimplant. We performed a simultaneous laparoscopic right nephroureterectomy and robot-assisted anterior pelvic exenteration with totally intracorporeal ICUD. Combination of robot-assisted and pure laparoscopic approaches was proposed focusing on optimization of total operative time (TOT). Results: Surgery was uneventful. TOT was of 330 minutes. Operative time for nephroureterectomy, anterior pelvic exenteration and ICUD were 48, 135, 87 minutes, respectively. Estimated blood loss was 150mL. Postoperative course was unremarkable and patient was discharged after 7 days. Histopathological evaluation showed a pT1 high grade urothelial carcinoma plus carcinoma in situ both in proximal right ureter and bladder, with negative margins. Twelve lymph nodes were excised, all of them negative. Conclusion: In our preliminary experience, totally minimally invasive simultaneous nephroureterectomy and cystectomy with intracorporeal ICUD is feasible. Pure laparoscopic approach to upper urinary tract may be a useful tactic to reduce total operative time.