Biliary drainage is essential for patients with malignant hilar biliary obstruction (MHBO) to relieve obstructive jaundice and cholangitis and improve survival and quality of life. Uncovered metal stents (MS) are recommended for unresectable cases because of their superior duration of patency; however, their removal is technically difficult once an occlusion occurs. Plastic stents (PS) have regained attention owing to being easily removable, particularly as advances in antitumor therapies have led to prolonged survival and increased need for reintervention; however, their patency remains limited. Recently, slim fully covered MS (FCMS) have been reported to reduce the risk of side branch occlusion and may combine long-term patency with removability. This trial aims to evaluate the efficacy and safety of suprapapillary stent-by-stent (SBS) deployment of slim FCMS compared with PS deployment in patients with unresectable MHBO. This is a multicenter, randomized, open-label, parallel-group study. Patients with unresectable MHBO classified as Bismuth type II or higher are eligible for inclusion. After informed consent is obtained, the patients will be randomized (1:1) to undergo suprapapillary SBS deployment (placement above the duodenal papilla) with either a slim FCMS or PS. The slim FCMS that will be used in this study have a 6-mm diameter, and both the FCMS and PS are equipped with a distal retrieval string to facilitate stent removal during reintervention. The primary endpoint is the rate of non-recurrent biliary obstruction (RBO) at 6 months following the intervention. Secondary endpoints include the time to RBO, overall survival, procedure success rate, clinical success rate, procedure time, adverse events, and reintervention outcomes. The target sample size is 70 patients (35 patients per group). Suprapapillary SBS deployment using slim FCMS may provide longer stent patency while preserving the feasibility of reintervention, potentially establishing a new standard biliary drainage method for unresectable MHBO. Japan Registry of Clinical Trials: jRCT1040250073 registered on August 5, 2025. (https://jrct.mhlw.go.jp/en-latest-detail/jRCT1040250073).
Intraplacental choriocarcinoma (ICC) is a rare gestational trophoblastic tumor that is often difficult to diagnose and is occasionally associated with fetomaternal hemorrhage (FMH). A 28-year-old woman presented with decreased fetal movements at 38 weeks of gestation. Due to a nonreassuring fetal heart rate pattern, an emergency cesarean section was performed. Severe neonatal anemia (3.2 g/dL) and markedly elevated maternal serum alpha-fetoprotein levels suggested FMH, despite normal maternal hemoglobin F levels. Initial placental pathology was unremarkable. Thirteen days postpartum, the patient developed massive vaginal bleeding requiring uterine artery embolization (UAE). Elevated serum β-hCG levels and multiple pulmonary nodules led to a clinical diagnosis of choriocarcinoma. Placental re-evaluation confirmed ICC. Chemotherapy with methotrexate, etoposide, and actinomycin D resulted in complete remission. In conclusion, ICC should be considered in cases of unexplained FMH or postpartum hemorrhage. UAE did not appear to impair the efficacy of subsequent chemotherapy in this case.
BACKGROUND A durable complete response, or sustained disappearance of measurable malignancy, can occur in selected patients with metastatic renal cell carcinoma after systemic therapy. Clear cell renal cell carcinoma is the most common renal cell carcinoma subtype. Lenvatinib is a multikinase inhibitor with antiangiogenic activity, and pembrolizumab is an anti-programmed death-1 immune checkpoint inhibitor. Although this combination can induce deep extracranial responses, central nervous system relapse after prolonged complete response remains incompletely characterized. This report describes a 73-year-old man with late isolated brain metastasis of clear cell renal cell carcinoma after durable complete response to lenvatinib-pembrolizumab and deferred cytoreductive nephrectomy. CASE REPORT A 73-year-old man presented with right flank pain. Computed tomography showed a right renal tumor, level II inferior vena cava tumor thrombus, and multiple pulmonary metastases. Baseline brain computed tomography showed no intracranial metastasis. He received lenvatinib plus pembrolizumab, resulting in marked regression of the primary tumor, inferior vena cava thrombus, and lung metastases. Deferred cytoreductive nephrectomy with thrombectomy was then performed, and pathology confirmed clear cell renal cell carcinoma with extensive treatment effect. Lenvatinib was discontinued because of renal dysfunction, and pembrolizumab monotherapy was continued. The patient maintained complete extracranial radiographic remission for more than 2 years. He later developed headache, and brain magnetic resonance imaging revealed a solitary left occipital metastasis without systemic recurrence. Stereotactic body radiotherapy achieved local control. CONCLUSIONS This case shows that late isolated central nervous system relapse can occur despite durable extracranial complete response after lenvatinib-pembrolizumab and deferred cytoreductive nephrectomy. New neurological symptoms in long-term responders should prompt brain magnetic resonance imaging, because intracranial progression may occur even when systemic imaging remains negative.
e14508 Background: Immune checkpoint blockade is an important cancer treatment, but its therapeutic efficacy varies among patients. In the tumor microenvironment, PD-1 blockade reactivates PD-1+CD8+ T cells while simultaneously enhancing immunosuppression by PD-1+ regulatory T cells (Tregs); therefore, the balance between these populations has been proposed as a useful response biomarker. Because Tregs are also key therapeutic targets, multiple clinical trials using Treg depletion therapy have been conducted worldwide, but therapeutic efficacy has yet to be confirmed. In this context, we profiled the selectivity and expression intensity of representative Treg-depleting target candidates [CD25, T-lymphocyte antigen-4 (CTLA-4), C-C chemokine receptor 4 (CCR4), and CCR8] on effector Treg (eTreg), and investigated which molecules and combinations are more effective as therapeutic targets. Methods: A retrospective study was conducted on 24 patients with oral squamous cell carcinoma who underwent surgery. Peripheral blood lymphocytes (PBLs) were isolated from 24 patients and tumor infiltrated lymphocytes (TILs) from 24 patients respectively. eTreg fraction (CD4+CD45RA-FOXP3hi) was determined by flow cytometric analysis. eTreg frequency in each site and expression of CCR4, CCR8, CD25, CTLA-4 and PD-1 on the eTregs were analyzed. And PD-1 expression on CD8+ T cells was also assessed. The distribution of Tregs within the tissues was also analyzed using multi-fluorescence immunohistochemistry. Results: PD-1 expression on CD8+ T cells (mean [SD], %) was 7.9 [3.4] in PBL and 26.1 [9.2] in TIL (p < 0.001). PD-1 expression on eTregs was 1.7 [0.8] in PBL and 19.8 [9.1] in TIL (p < 0.001). The PD-1+CD8+ T cell/PD-1+eTreg ratio was 8.4 [14.6] in PBL and 1.8 [1.3] in TIL (p = 0.038), and this ratio varied across patients. CCR4 expression on eTregs was higher in PBL than in TIL (93.6 [6.6] vs 61.2 [14.0], p < 0.001), whereas CCR8 expression was higher in TIL than in PBL (61.3 [23.0] vs 23.6 [13.8], p < 0.001); accordingly, the CCR4/CCR8 balance on TIL eTregs was heterogeneous among patients. CD25 was highly expressed in both sites with slightly higher expression in TIL (PBL vs TIL: 80.5 [6.6] vs 85.8 [6.6], p = 0.008). CTLA-4 expression on eTregs was higher in TIL than in PBL (26.1 [9.5] vs 6.4 [3.2], p < 0.001). In the 5 cases of immunostaining, the PD-1+CD8+ T cell/PD-1+ Treg ratio was 11.7 [14.7] in Tumor area and 7.0 [8.9] in Stroma area (p = 0.52). Conclusions: These results suggest that for optimal Treg targeting strategies in oral cancer, it may be desirable to select different target molecules in the tumor and peripheral blood. Furthermore, because the expression of each molecule varies between patients, the optimal target molecule may differ for each patient.
