by
Hal Scherz;
Caroline Jansen;
Roshan Prabhu;
Meghana Pagadala;
Prasanthi Chappa;
Subir Goyal;
Chengjing Zhou;
Stewart Neill;
Nataliya Prokhnevska;
Maria Cardenas;
Kimberly Hoang;
Jim Zhong;
Mylin Torres;
Suzanna Logan;
Jeffrey Olson;
Edjah Nduom;
Luke Del Balzo;
Kirtesh Patel;
Stuart Burri;
Anthony Asher;
Scott Wilkinson;
Ross Lake;
Krisitin Higgins;
Pretesh Patel;
Vishal Dhere;
Adam Sowalsky;
Mohammad Khan;
Haydn Kissick;
Zachary Buchwald
The CD8 + T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1 + TCF1 + stem-like CD8 + T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS’s impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8 + T cells at 3 days. However, CD8 + T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1 + stem-like population.
Purpose: Endoscopic dextranomer/hyaluronic acid (Dx/HA) injection is a common treatment for vesicoureteral reflux (VUR) with excellent reported short-term clinical success rates. Long-term outcomes are less well-defined. We assessed long-term outcomes and parental satisfaction after Dx/HA injection for primary VUR with >5-year follow-up.
Materials and Methods: Families of all patients who underwent Dx/HA injection for primary VUR at our institution between 2008 and 2012 were contacted for telephone interview. Data collected by phone included parental satisfaction and presence and severity of UTIs pre-operatively and post-operatively. Patient demographics, radiographic VUR data, need for secondary surgery, and surgical indications were obtained through chart review.
Results: Five hundred and seventy-five patients underwent Dx/HA injection for primary VUR between 2008 and 2012. Ninety-nine (17.2%) of these patients’ parents were successfully contacted and interviewed. Median follow-up time from surgery to survey was 8.4 (IQR 6.8–9.6) years. Secondary surgery was performed in 13/99 (13.1%), most commonly repeat Dx/HA injection. Seven patients (7.1%) underwent secondary Dx/HA injection for persistent VUR without UTIs at a median of 0.35 (IQR 0.33–0.77) years post-operatively. Five patients (5.1%) underwent Dx/HA injection (n = 3) or ureteral reimplantation (n = 2) for VUR with febrile UTIs (fUTIs) at a median of 2.2 (IQR 1.3–5.1) years. One patient had ureteral reimplantation for symptomatic obstruction 2.8 years after initial surgery. Only 3/99 (3.0%) required open or laparoscopic surgery after Dx/HA injection. Eighty-three families (84.7%) reported ≥1 fUTIs pre-operatively. Of these, only 9/83 (10.8%) reported fUTIs post-operatively, for an overall clinical success rate of 89.2%. Clinical success was 93.1% in patients whose pre-operative fUTIs were treated outpatient and 80.0% in those hospitalized at least once for fUTI treatment pre-operatively. Ninety-four percent of parents were highly satisfied, 2.4% partially satisfied, and 3.5% dissatisfied.
Conclusions: Endoscopic injection with Dx/HA for primary VUR appears to have good long-term clinical success rates and high parental satisfaction, mirroring our previously reported short-term results. Post-operative ureteral obstruction is rare but may occur years post-operatively, justifying initial sonographic surveillance, and repeat imaging in symptomatic patients.