Evaluation of Retrospective Patient Preference on Extent of Resection of Nonfunctioning Pituitary Adenomas.

BACKGROUND: Neurosurgeons treat nonfunctioning pituitary adenomas by surgical resection. Based on the adherence of the tumor to the normal pituitary gland, operative risks may include hormone replacement therapy for postoperative hypopituitarism with gross total resection that injures the gland or recurrent tumor with subtotal resection and purposeful avoidance of gland manipulation. None of the patients presented in this article had a preoperative preference regarding extent of resection. This study aimed to evaluate postoperative patient preferences regarding extent of resection. METHODS: Adult patients who underwent resection of adenomas between 2015 and 2023 were retrospectively reviewed and surveyed. After surgery, participating patients were asked for their preference regarding 100% tumor resection with lifelong daily hormone replacement therapy versus 90% tumor resection with a chance of recurrence in the hypothetical situation where the neurosurgeon encounters tumor adherent to the normal gland. RESULTS: Of the 73 patients included, 54 (74.0%) responded to the survey, with the majority (36 [66.7%]) preferring 90% resection with the chance of tumor recurrence. Tumor recurrence (odds ratio 2.3, 95% confidence interval 2.1-2.5, P = 0.03) and steroid avoidance (odds ratio 2.2, 95% confidence interval 2.0-2.4, P = 0.04) were the 2 variables that were significant predictors of patient preference in multivariate regression analysis. CONCLUSIONS: Although patients may not have the preoperative insight or experience to have a strong conviction regarding the extent of adenoma resection, the consequences following surgery clearly influence their preference. Most patients in our study, including patients with gross total resection and especially patients who experienced side effects of steroid therapy, preferred subtotal resection with the chance of tumor recurrence over hormone replacement therapy.

Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis.

Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma-supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in multiple myeloma cells. Silencing EPHB1 or EPHB4 in ECs suppressed multiple myeloma growth in coculture. Similarly, loss of EFNB2 in multiple myeloma cells blocked multiple myeloma proliferation and survival in vitro, abrogated multiple myeloma engraftment in immune-deficient mice, and increased multiple myeloma sensitivity to chemotherapy. Administration of an EFNB2-targeted single-chain variable fragment also suppressed multiple myeloma growth in vivo. In contrast, overexpression of EFNB2 in multiple myeloma cells increased STAT5 activation, increased multiple myeloma cell survival and proliferation, and decreased multiple myeloma sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in multiple myeloma cells increased multiple myeloma cell death and sensitivity to chemotherapy and abolished multiple myeloma growth in vivo. Complementary analysis of multiple myeloma patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls multiple myeloma pathogenesis and can be therapeutically targeted to improve multiple myeloma outcomes. SIGNIFICANCE: Ephrin B2 reverse signaling mediated by endothelial cells directly regulates multiple myeloma progression and treatment resistance, which can be overcome through targeted inhibition of ephrin B2 to abolish myeloma.