No abstract

Programmed cell death protein-1 (PD-1) blockade therapy has improved outcomes in the treatment of advanced cancers. The therapy is well-tolerated, although it occasionally causes immune-related adverse events (irAEs). Thyroid dysfunction is one of the most common irAEs seen. Our aim was to clarify the clinical characteristics of thyroid dysfunction induced by PD-1 blockade and its association with the therapeutic effect of the treatment in advanced cancers. A total of 174 patients who received nivolumab or pembrolizumab for metastatic or unresectable advanced cancers were included in this retrospective study. The patients were divided into two groups: The thyroid dysfunction group and the euthyroid group. In the present study, the clinical characteristics, the association with anti-thyroid antibodies, as well as the progression-free survival (PFS) and overall survival (OS) were estimated. An adjusted Cox proportional hazard regression model was used to evaluate prognostic factors for OS and PFS. This study showed that 25 out of 150 patients (16.7%) developed immune-related thyroid dysfunction. Hypothyroidism occurred in the early stage of the clinical course (median: 12 weeks); subsequently, 9 of the 25 patients underwent a transient period of hyperthyroidism, all with mild symptoms. The presence of positive anti-thyroid antibodies at baseline was significantly higher in the thyroid dysfunction group (13/22) than in the euthyroid group (18/100, P=0.0002). Moreover, PFS (median: 66 vs. 27 weeks, hazard ratio (HR): 0.50, 95% CI: 0.26-0.89, P=0.02) and OS (median 156 vs. 59 weeks, HR: 0.34, 95% CI: 0.13-0.75, P=0.01) were significantly longer in the thyroid dysfunction group than in the euthyroid group. Multivariable analysis also revealed that thyroid dysfunction was an independent prognostic factor for OS (HR: 0.42, 95% CI: 0.16-0.97, P=0.04). These findings may enable the early recognition and appropriate management of thyroid dysfunction, and help in maximizing the therapeutic effect of PD-1 blockade.

Objective: Patients with upper urinary tract urothelial carcinoma (UUT-UC) without a history of bladder cancer have a different natural history of intravesical recurrence after nephroureterectomy compared with those with a history of bladder cancer. The aim of this study was to identify predictive factors for post-operative intravesical recurrence in patients with non-metastatic upper urinary tract-localized urothelial carcinoma without a history of bladder cancer and who were not taking medication during the perioperative period. Methods: This retrospective study included 133 patients who were treated between 1995 and 2012. Univariate and multivariate analyses were used to evaluate the clinical and pathological factors associated with the cumulative incidence of bladder cancer. Results: Of the 133 patients, 51 (38.3%) developed intravesical recurrence during a median follow-up of 71 months (range, 0.8-210.8). In the multivariate analysis, multifocality (P = 0.03) and high tumour grade (P = 0.007) were significantly associated with the cumulative incidence of bladder cancer. We constructed a prediction classification model on the basis of the total number of risk factors. The 2-year cumulative incidence rates were 5.6, 34.8 and 50.0% in individuals with no, one and two risk factors, respectively. There was a significant difference between patients with no risk factors and those with two risk factors (P = 0.01). Conclusions: Although this retrospective study had several limitations, tumour multifocality and tumour grade were found to be potential risk factors for intravesical recurrence in our cases.

Introduction Horseshoe kidney has unique anatomical features, such as a complex blood supply. We report a patient with renal cell carcinoma in a horseshoe kidney, who underwent tumor resection by robot‐assisted laparoscopic partial nephrectomy based on preoperative three‐dimensional computed tomography. Case presentation A 66‐year‐old man was referred to our hospital with a 2‐cm enhancing mid‐pole mass in the left moiety of a horseshoe kidney. The clinical diagnosis was renal cell carcinoma cT1aN0M0 (R.E.N.A.L. nephrometry score: 1 + 2 + 3 + 3 = 9p). Robot‐assisted laparoscopic partial nephrectomy was performed with selective clamping based on reconstructed three‐dimensional images. The warm ischemia time was 13 min. Pathologic examination confirmed a diagnosis of pT1a clear cell renal cell carcinoma with negative surgical margins. At 6 months postoperatively, computed tomography showed no local recurrence or metastasis and renal function was intact. Conclusion Robot‐assisted laparoscopic partial nephrectomy with preoperative three‐dimensional computed tomography may have advantages for resection of tumors in patients with horseshoe kidney.

Nivolumab, a programmed death-1 checkpoint inhibitor, is worldwide available for metastatic renal cell carcinoma (mRCC). Limited data exist on the response to vascular endothelial growth factor receptor-tyrosine kinase inhibitor (TKI) therapy after administration of nivolumab. In this case study, we report on a patient with tumor lysis syndrome (TLS), which was induced by pazopanib after the administration of nivolumab. A 69-year-old woman with a primary diagnosis of mRCC received pazopanib as a fourth-line therapy, after sunitinib, axitinib, and nivolumab as first-, second-, and third-line therapies, respectively. Two weeks after the administration of pazopanib, she presented to the emergency room of our institution, complaining of fatigue associated with nausea and diarrhea. Her laboratory results showed hyperphosphatemia, hyperuricemia, hypocalcemia, and possible acute kidney injury; the results were consistent with TLS. Our case report highlights TLS as a potential reaction to pazopanib following nivolumab; and we consider careful observation is necessary when administering TKI after immune checkpoint inhibitors.