Steven Sterious

Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma

To compare overall and cancer‐specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron‐sparing measures (NSM) using a large population‐based dataset.

Opioid antagonists differ according to negative intrinsic efficacy in a mouse model of acute dependence

1 The purpose of the present study is to compare the capacity of opioid antagonists to elicit withdrawal jumping in mice following two acute pretreatment doses of the opioid agonist morphine. Antagonists that precipitate vigorous withdrawal jumping across both morphine treatment doses are hypothesized to be strong inverse agonists at the μ‐opioid receptor, whereas antagonists that elicit withdrawal jumping in mice treated with the high but not the low dose of morphine are hypothesized to be weak inverse agonists. 2 Male, Swiss‐Webster mice (15–30 g) were acutely treated with 56 or 180 mg kg−1 morphine 4 h prior to injection with naloxone, naltrexone, diprenorphine, nalorphine, or naloxonazine. Vertical jumping, paw tremors, and weight loss were recorded. Naloxone, naltrexone, and diprenorphine produced withdrawal jumping after 56 and 180 mg kg−1morphine pretreatment. Nalorphine and naloxonazine produced moderate withdrawal jumping after 180 mg kg−1 morphine pretreatment, but failed to elicit significant withdrawal jumping after 56 mg kg−1 morphine pretreatment. Nalorphine and naloxonazine blocked the withdrawal jumping produced by naloxone. All antagonists produced paw tremors and weight loss although these effects were generally not dose‐dependent. 3 Taken together, these findings reveal a rank order of negative intrinsic efficacy for these opioid antagonists as follows: naloxone=naltrexonediprenorphine>nalorphine=naloxonazine. Furthermore, the observation that nalorphine and naloxonazine blocked the naloxone‐induced withdrawal jumping provides additional evidence that nalorphine and naloxonazine are weaker inverse agonists than naloxone.

Pathological concordance and surgical outcomes of sporadic synchronous unilateral multifocal renal masses treated with partial nephrectomy.

PURPOSE Patients with unilateral synchronous multifocal renal masses represent a unique population with renal cell carcinoma. While pathological concordance rates have been studied for bilateral cases, limited data exist on unilateral multifocal disease. We characterized pathological concordance rates in this population and evaluated the outcomes of nephron preservation. MATERIALS AND METHODS Patients who underwent surgery from 2000 to 2012 for unilateral synchronous multifocal renal masses were identified from a prospectively maintained database. Demographic, surgical and pathological outcomes of this cohort were analyzed. Malignant concordance rates were defined as agreement of all malignant tumor types in a single renal unit. Histological concordance was defined as agreement of all resected mass histologies, eg all clear cell carcinomas. Nuclear grade was considered concordant if all tumors excised were low (Fuhrman 1 or 2, type 1) or high (Fuhrman 3 or 4, type 2) grade. RESULTS Using our institutional database of 2,569 patients with renal tumors we identified 97 with unilateral synchronous multifocal renal masses. Malignant and benign concordance rates were 77.2% and 48.6%, and histological and grade concordance rates were 58.8% and 51.5%, respectively. In this cohort we identified 76 patients (76.3% male) with a median age of 62.5 years who had a total of 241 unilateral synchronous multifocal renal masses and underwent nephron sparing surgery. Median mass size was 2.0 cm (IQR 1.1-3.1), there was a median of 3 tumors per patient and median followup was 24 months (IQR 13-40). Identified renal cell carcinoma histologies included clear cell in 49.4% of cases, papillary in 33.5%, mixed in 4.5% and chromophobe in 2.8%. CONCLUSIONS In what is to our knowledge the largest published report of unilateral synchronous multifocal renal masses we document low pathological concordance rates. As such, percutaneous biopsy of a single renal mass in these patients may not help inform treatment decisions. Nephron sparing surgery may be performed with acceptable oncological and functional results in patients with unilateral synchronous multifocal renal masses.