INTRODUCTION: We conducted this study to characterize the incidence, clinical features, treatment, and outcomes of immune checkpoint inhibitor (ICI) hepatotoxicity. METHODS: Patients who received ICIs (with either single-agent or combination regimens) from January 1, 2010, to March 31, 2018, were identified. Hepatotoxicity was defined as alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN), in the absence of an alternate cause, and categorized as grade 3 (ALT 5–20× ULN) or grade 4 (ALT >20× ULN), according to Common Terminology Criteria for Adverse Events 4.03. RESULTS: Among 5,762 patients, 100 (2%) developed hepatotoxicity, occurring in a higher proportion of recipients of combination therapy (9.2%) compared with monotherapy (up to 1.7%, P < 0.001). ICIs were discontinued permanently in 69 and temporarily in 31 patients. Sixty-seven patients received steroids, 10 of whom (14%) had recurrent hepatotoxicity after the steroid taper. Thirty-one patients resumed ICIs after ALT improvement, 8 of whom (26%) developed recurrent hepatotoxicity. Characteristics of liver injury, response to steroids, and outcomes were similar between 38 individuals with and 62 without possible pre-existing liver disease. The severity and outcome of hepatotoxicity due to combination therapy were not significantly different from monotherapy. There were 36 deaths. Two had liver failure at the time of death, both with progression of liver metastases and grade 3 hepatotoxicity. DISCUSSION: Clinically significant ICI-related hepatotoxicity was uncommon but led to permanent ICI discontinuation in the majority. ICIs were restarted in a sizable proportion of patients, most of whom did not experience recurrent hepatotoxicity.

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Collecting duct carcinoma (CDC) is a rare and aggressive form of renal cell carcinoma (RCC) arising from the principal cells of the collecting duct. One third of cases present with metastatic disease, but many present in a manner similar to conventional RCC or urothelial carcinoma (UC). We discuss a case of CDC which presented as a small mass at the cortico-medullary junction, and was discovered at robotic partial nephrectomy (RPN) to be grossly involving the collecting system. A 62-year-old man presented with a small renal mass suspicious for RCC, which was found on computed tomography (CT) after an episode of gross hematuria. After thorough workup, RPN was attempted; however, intraoperatively the mass was found to be involving the collecting system. Radical nephroureterectomy was performed, and the pathology report revealed CDC. CDC is a rare and aggressive form of RCC. While many cases are metastatic at diagnosis, most patients present with the incidental finding of a small renal mass. There are no reports of a CDC involving the collecting system at RPN after negative ureteroscopy preoperatively. The adjuvant therapeutic options for CDC are limited, and long term survival is poor.