No abstract

Locally advanced or metastatic urothelial cancer is an aggressive form of cancer with high recurrence rates and low survival. Nectin-4 is a cell adhesion molecule commonly expressed in several tumors, including high expression in urothelial cancer. Enfortumab vedotin is an antibody-drug conjugate composed of an anti-Nectin-4 humanized monoclonal antibody linked to the microtubule disrupting agent, monomethyl auristatin E. In this phase I study (NCT03070990), Japanese patients with locally advanced/metastatic urothelial cancer treated with prior chemotherapy, or ineligible for cisplatin, were randomized 1:1 to receive 1.0 mg/kg (Arm A) or 1.25 mg/kg (Arm B) enfortumab vedotin on Days 1, 8, and 15 of each 28-day cycle. Assessing the pharmacokinetic and safety/tolerability profiles of enfortumab vedotin were primary objectives; investigator-assessed antitumor activity (RECIST v1.1) was a secondary objective. Seventeen patients (n = 9, Arm A; n = 8, Arm B) received treatment. Pharmacokinetic data suggest a dose-dependent increase in enfortumab vedotin maximum concentration and area under the concentration-time curve at Day 7. Enfortumab vedotin was well tolerated across both doses. Dysgeusia and alopecia (n = 9 each) were the most common treatment-related adverse events. Regardless of attribution, grade ≥ 3 adverse events occurring in ≥2 patients were anemia and hypertension (n = 2 each). One patient achieved a confirmed complete response (Arm A) and five achieved confirmed partial responses (n = 3, Arm A; n = 2, Arm B). Objective response and disease control rates were 35.3% and 76.5%, respectively. In Japanese patients with locally advanced/metastatic urothelial cancer, enfortumab vedotin is well tolerated with preliminary antitumor activity and a pharmacokinetic profile consistent with prior reports.

Anti-CD20/MMF desensitization is safe and allows successful ABO-I kidney transplantation without splenectomy.

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare kidney neoplasm that almost exclusively occurs in perimenopausal women, and long-term estrogen replacement is relevant to its pathogenesis. Herein is described an atypical case of MESTK uncovered in a 12-year-old premenarcheal girl without a history of prior estrogen use. On surgical specimen it was found that the well-circumscribed tumor measuring 14 cm arose from the lower pole of the right kidney, showing solid and fibrous-cystic areas. Microscopically, it was composed both of epithelial structures similar to renal tubules and stroma comprising non-specific spindle cells. Some intratumoral tubules showed affinities to distal-nephron-specific lectins, and those immunoreactive for proximal-tubule-specific CD15 were also present. In addition, primitive ductal structures were reactive both for CD15 and lectins, but immature epithelial elements typical of nephroblastoma were absent. Spindle cells were positive for actin, desmin and vimentin, and expressed progesterone and estrogen receptors. The tumor was comparable with MESTK, although some epithelia were associated with the immunophenotype of proximal tubules. The patient was free of disease postoperatively for 40 months. In the present case, remnants of the primitive periductal mesenchyme might be promoted to neoplastic cells by a sex-steroid surge during puberty.

Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) antigens, and characterization of tumor-infiltrating mononuclear cells (TIM) were examined immunohistologically in 10 specimens of seminoma. ICAM-1 and MHC antigens were not detected on normal spermatogenic cells. ICAM-1 and MHC class I antigens were variably expressed in 7 and 9 seminomas, respectively, whereas class II antigens were not detected. Although the degree of expression of ICAM-1 and MHC antigens was not correlated with any clinical or histopathological factors, neither of the antigens was detected on an anaplastic seminoma. Various numbers of TIM were detected in all of the seminoma, and comprised mainly T cells bearing the lymphocyte function-associated antigen (LFA)-1. No significant correlation was noticed between the degree of lymphocyte infiltration and ICAM-1 or MHC antigen expression. Although ICAM-1 and MHC class I antigens were expressed in seminoma, possibly facilitating an anti-tumor reaction of host, their expression remained low in several cases, despite marked lymphocyte infiltration within the tumor.