Complete response to combination therapy using nivolumab and ipilimumab for metastatic, sarcomatoid collecting duct carcinoma presenting with high expression of programmed death-ligand 1: a case report.

BACKGROUND: Collecting duct carcinoma and sarcomatoid renal cell carcinoma are tumors with poor prognosis. Immune checkpoint inhibitors have been established as the standard treatment for advanced renal cell carcinoma. Some cases of remission of collecting duct carcinoma and sarcomatoid renal cell carcinoma have been reported using immune checkpoint inhibitor interventions. Specifically, sarcomatoid renal cell carcinoma expresses high levels of programmed death-ligand 1, an immune checkpoint protein, and immune checkpoint inhibitors have been reported to be highly effective for treating sarcomatoid renal cell carcinoma. CASE PRESENTATION: We describe the case of a 70-year-old Japanese male who underwent radical right nephrectomy for a right renal mass identified on computed tomography. The pathological examination demonstrated that the renal mass was urothelial carcinoma and collecting duct carcinoma with sarcomatoid changes, and programmed death-ligand 1 was highly expressed with a tumor proportion score of more than 10%. There was no evident submucosal connective tissue invasion in the urothelial carcinoma component, and collecting duct carcinoma was diagnosed as primary cancer. The tumor-node-metastasis classification was pT3aN0, venous invasion 1, lymphovascular invasion 0, and Fuhrman nuclear grade 4. Two months after the nephrectomy, multiple metastases were observed in both lungs, the right hilar lymph node, and the S6 segment of the right liver lobe. We initiated first-line combination therapy with nivolumab (240 mg, fixed dose) and ipilimumab (1 mg/kg). One day after administration, the patient developed drug-induced interstitial pneumonia, thus we applied steroid injections. After one administration of immunotherapy, the metastatic lesion showed complete response within 6 months, which was maintained after 3 years. CONCLUSION: We report the first case of complete response to a single dose of combination therapy with nivolumab and ipilimumab for metastatic collecting duct carcinoma with sarcomatoid changes and high expression of programmed death-ligand 1. This case suggests high expectations for immune checkpoint inhibitors as treatment for sarcomatoid-transformed renal carcinoma tumors that express high levels of programmed death-ligand 1.

Undifferentiated pleomorphic sarcoma of the retroperitoneum mimicking a cortisol- and catecholamine-secreting adrenal tumor.

Introduction: Retroperitoneal tumors with endocrine abnormalities are suspected to be functional adrenal tumors. Retroperitoneal soft tissue sarcomas are rare tumors, without endocrine potential. Case presentation: A 60-year-old male was referred for a 15 cm mass in the left suprarenal space. His plasma cortisol and catecholamine levels were elevated. He underwent open left adrenalectomy with radical nephrectomy and his endocrinological abnormalities were improved. Pathological findings suggested that it had originated from the retroperitoneal fat tissue, and a diagnosis of undifferentiated pleomorphic sarcoma was made based on the results of immunohistochemical analysis and fluorescence in situ hybridization. Interestingly, neither cortisol nor catecholamine was elevated when, 6 months after surgery, local recurrence developed. Conclusion: This is the first reported case of undifferentiated pleomorphic sarcoma accompanied by high levels of cortisol and catecholamine. We should keep in mind the possibility of tumors like retroperitoneal soft tissue sarcomas inducing endocrine abnormalities.

[A CASE REPORT OF VESICAL CALCULUS FORMATION WITH CHROMIC CATGUT AT THE URETEROVESICAL ANASTOMOTIC SITE 28 YEARS AFTER RENAL TRANSPLANTATION].

A 69-year-old man underwent renal transplantation due to chronic renal failure of unknown cause in 1991. Furthermore, in 2012 he again underwent renal transplantation due to renal graft dysfunction with focal segmental glomerulosclerosis. After the second renal transplantation, his renal function has been stable. In 2019, he presented to the urology department with gross hematuria. Cystoscopy revealed a 2 cm vesical calculus at the dome of the bladder near the right lateral wall. Therefore, we performed transurethral lithotripsy using the holumium laser method. The vesical calculus was crushed, revealing a suture at the center, suggesting the suture as the cause. We tried to remove the suture during operation, however, it was impossible. Although the remaining suture posed a risk for calculus development, there has been no recurrence of a calculus for 6 months after the operation. This case reports a vesical calculus at the ureterovesical anastomotic site, wherein the core was an absorbable suture used during the initial renal transplantation. It should be taken into consideration that there is a possibility of anastomotic calculus occurrence with absorbable sutures, even long after renal transplantation.

mDia1/3 generate cortical F-actin meshwork in Sertoli cells that is continuous with contractile F-actin bundles and indispensable for spermatogenesis and male fertility.

Formin is one of the two major classes of actin binding proteins (ABPs) with nucleation and polymerization activity. However, despite advances in our understanding of its biochemical activity, whether and how formins generate specific architecture of the actin cytoskeleton and function in a physiological context in vivo remain largely obscure. It is also unknown how actin filaments generated by formins interact with other ABPs in the cell. Here, we combine genetic manipulation of formins mammalian diaphanous homolog1 (mDia1) and 3 (mDia3) with superresolution microscopy and single-molecule imaging, and show that the formins mDia1 and mDia3 are dominantly expressed in Sertoli cells of mouse seminiferous tubule and together generate a highly dynamic cortical filamentous actin (F-actin) meshwork that is continuous with the contractile actomyosin bundles. Loss of mDia1/3 impaired these F-actin architectures, induced ectopic noncontractile espin1-containing F-actin bundles, and disrupted Sertoli cell-germ cell interaction, resulting in impaired spermatogenesis. These results together demonstrate the previously unsuspected mDia-dependent regulatory mechanism of cortical F-actin that is indispensable for mammalian sperm development and male fertility.