Four Cycles of Etoposide plus Cisplatin for Patients with Good-Risk Advanced Germ Cell Tumors.

BACKGROUND: The National Comprehensive Cancer Network recommends either three cycles of bleomycin, etoposide, and cisplatin or four cycles of etoposide and cisplatin (EPx4) as initial chemotherapy for the treatment of good-risk germ cell tumors (GCTs). To assess the response, toxicity, and survival outcomes of EPx4, we analyzed our experience. MATERIAL AND METHODS: Response and survival outcomes, selected toxicities, and adherence to chemotherapy dose and schedule were assessed in patients with good-risk GCT who received EPx4 at Memorial Sloan Kettering Cancer Center between 1982 and 2016. The results were compared with our past results and published data. RESULTS: Between 1982 and 2016, 944 patients with GCT were treated with EPx4, 289 who were previously reported plus 655 treated between January 2000 and August 2016. A favorable response was achieved in 928 of 944 patients (98.3%). Five-year progression-free, disease-specific, and overall survival rates were 93.9%, 98.6%, and 97.9%, respectively. Median follow-up was 7.3 years (range, 2.8 months to 35.5 years). Viable, nonteratomatous malignant GCT was present in 3.5% of 432 postchemotherapy retroperitoneal lymph node dissection specimens from patients with nonseminomatous GCT. Febrile neutropenia and thromboembolic events occurred in 16.0% and 8.9%, respectively, with one treatment-related death. In the more recent 655-patient cohort, full-dose EPx4 was administered to 631 (96.3%), with deviations from planned treatment driven mainly by vascular (n = 13), hematologic (n = 11), renal (n = 7), or infectious (n = 5) events. CONCLUSION: EPx4 is highly effective and well tolerated in patients with good-risk GCTs and remains a standard of care. IMPLICATIONS FOR PRACTICE: Four cycles of etoposide and cisplatin (EPx4) is a standard-of-care regimen for all patients with good-risk germ cell tumors with a favorable response rate and disease-specific survival of 98%. Full-dose administration of etoposide and cisplatin and complete resection of residual disease lead to optimal outcomes. EPx4 should be the recommended regimen in active smokers, patients with reduced or borderline kidney function, and patients aged 50 years or older, which are patient groups at increased risk for bleomycin pulmonary toxicity. Because of a risk of acquired severe pulmonary illness, EPx4 may also be favored for patients who vape or use e-cigarettes and during ongoing transmission of severe acute respiratory syndrome coronavirus 2.

Digital health technology utilization is associated with enhanced patient perspectives of care.

BACKGROUND: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores measure patient experience and perspectives on care. Novel health information technologies facilitate communication between patients and healthcare teams. Playback Health is a health information technology that incorporates multimedia for providers to communicate health information to patients, their support network, and their healthcare teams. We hypothesized implementing Playback Health may enhance patient perspectives on care. METHODS: HCAHPS scores were obtained retrospectively from a neurosurgical practice located in a metropolitan area between 2020 and 2022 for seven providers. Of these, four providers utilized Playback Health, and three did not. Individual providers' scores were compared between domains using two tailed t-tests at a significance level of p < 0.05. RESULTS: Playback Health use was associated with higher HCAHPS scores across varying domains from 2020 through 2022 as well as overall scores. In 2020, the mean overall score of HCAHPS users was higher than non-users (89.65 vs. 87.28, p = 0.0095). In 2021, again higher mean overall scores were observed in users as compared to non-users (89.11 vs. 87.79, p 0.0266). In 2022, Playback Health users maintained higher scores across communication domains and overall scores (p < 0.00001). Comparisons within domains between Playback Health users and non-users revealed no domains in which non-users had a significantly higher score than users. CONCLUSION: The addition of Playback Health multimedia health information technology was associated with improved patient satisfaction scores. When used as an adjunct to existing patient care, multimedia health information technologies may improve patient perceived care.

Troubleshooting the bypass: intraoperative management of initially failed anastomosis in direct cerebral revascularization surgery.

OBJECTIVE: Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during the case, but only after the recirculation stage, making management crucial at that time of the procedure. In this study, the authors sought to describe troubleshooting of the technical errors encountered in initially failed bypass cases. METHODS: A retrospective analysis describing a single-surgeon, single-institution experience between 2014 and 2021 was performed, based on operative reports and videos, including a 30-day follow-up period. Initially failed bypass was defined if the bypass was not patent or had a significant leak after recirculation, irrespective of the final result. RESULTS: One hundred thirty-eight bypass cases were reviewed for complex aneurysms (n = 49), moyamoya disease (n = 59), and atherosclerosis (n = 30). Fifty-one initially failed anastomoses were identified; 43 of these were the result of a technical error. Etiologies of these failed anastomoses included a clot (n = 14), vessel kinking (n = 4), spasm (n = 5), suture-related cause (n = 5), inappropriate donor or recipient (n = 3), or lack of demand (n = 8). A major leak was attributed to an uncoagulated side branch (n = 4), vessel injury due to suture/clip placement (n = 1), or inadequate suture line coverage (n = 7). Thirty-seven (86%) of 43 cases were troubleshot successfully, as salvage maneuvers included papaverine vessel massage, donor repositioning, re-anastomosis for occlusion in select cases, local hemostatic agents, and suturing or coagulating side branches in a leak. Thirty-day follow-up revealed similar rates of patency between successfully troubleshot patients (35/37) and the rest of the cases (80/87, p = 0.6). CONCLUSIONS: Three major patterns of a noncompatible bypass were found: a major leak, an acute occlusion, or a delayed occlusion. Based on the authors' experience, salvage strategies proved successful, showing an eventual high patency rate. The authors suggest a gradual, structured algorithm to address this stage in surgery that may contribute specifically to cerebrovascular neurosurgeons at the beginning of their careers.

Tranexamic Acid Dosing in Craniosynostosis Surgery: A Systematic Review with Meta-analysis.

This study aimed to compare operative time, blood loss, and transfusion requirement in patients receiving a high tranexamic acid (TXA) dose of greater than 10 mg/kg versus those receiving a low dose of 10 mg/kg or less. Methods: PubMed, Cochrane Central, and Embase were queried to perform a systematic review with meta-analysis. Studies reporting outcomes of TXA use in craniosynostosis surgery were included. TXA dosing, operative time, blood loss, and transfusion requirement were the primary outcomes studied. Other variables studied included age and types of craniosynostosis. Results: In total, 398 individuals in the included articles received TXA for craniosynostosis surgery. TXA loading doses ranged from 10 mg/kg to 50 mg/kg. Overall, administration of TXA was not associated with changes in operative time, but was associated with decreased blood loss and transfusion requirement on meta-analysis. Comparison of high dose TXA (>10 mg/kg) versus low dose (10 mg/kg or less) showed no statistical differences in changes in operative time, blood loss, or transfusion requirement. Conclusions: Overall, TXA reduced blood loss and transfusion requirement in patients undergoing surgery for craniosynostosis. There was no difference in outcomes between high dose and low dose regimens amongst those receiving TXA. Low dose TXA appears adequate to achieve clinical efficacy with a low adverse event rate.

Hearing Preservation Surgery in the Sitting Position for Grade 3B Hannover Classification Vestibular Schwannoma: 3-Dimensional Operative Video.

Surgical treatment of large vestibular schwannomas is challenging. Both facial and cochlear nerves should be preserved in patients who have no neurological deficit preoperatively. In this 3-dimensional video, we present a 35-yr-old patient who presented with documented increase in the size of a known vestibular schwannoma over the span of 3 yr. Surgery was favored among all treatment options due to his young age and the tumor size. Informed consent was obtained. Semisitting surgery allowed for bimanual microdissection of the tumor capsule from the surrounding arachnoid and cranial nerves with 2 micro dissectors. The precision of microdissection is enhanced in the sitting position. Facial nerve stimulation remained stable at 0.05 mA. The auditory evoked potential remained unchanged during the surgery. Complete resection of the tumor and preservation of facial and cochlear nerves was achieved. The patient had a stable hearing grade B and a normal facial nerve function at 3-mo follow-up.

Treatment with dimethyl fumarate reduces the formation and rupture of intracranial aneurysms: Role of Nrf2 activation.

Oxidative stress and chronic inflammation in arterial walls have been implicated in intracranial aneurysm (IA) formation and rupture. Dimethyl fumarate (DMF) exhibits immunomodulatory properties, partly via activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway which reduces oxidative stress by inducing the antioxidant response element (ARE). This study evaluated the effects of DMF both in vitro, using tumor necrosis factor (TNF)-α-treated vascular smooth muscle cells (VSMC), and in vivo, using a murine elastase model to induce aneurysm formation. The mice were treated with either DMF at 100 mg/kg/day P.O. or vehicle for two weeks. DMF treatment protected VSMCs from TNF-α-induced inflammation as demonstrated by its downregulation of cytokines and upregulation of Nrf2 and smooth muscle cell markers. At higher doses, DMF also inhibited the pro-proliferative action of TNF-α by increasing apoptosis which protected the cells from aponecrosis. In mice, DMF treatment significantly decreased the incidence of aneurysm formation and rupture, at the same time increasing Nrf2 levels. DMF demonstrated a neuroprotective effect in mice with a resultant inhibition of oxidative stress, inflammation, and fibrosis in the cerebrovasculature. This suggests a potential role for DMF as a rescue therapy for patients at risk for formation and rupture of IAs.

Final Results of the Prospective Multicenter Excimer Laser-Assisted High-Flow Bypass Study on the Treatment of Giant Anterior Circulation Aneurysms.

BACKGROUND: Both conventional bypass utilizing temporary recipient vessel occlusion and the excimer laser-assisted nonocclusive anastomosis (ELANA) bypass technique are possible strategies in the treatment of giant aneurysms. These treatments have only been studied in single institutional retrospective studies. The potential advantage of the ELANA technique is the absence of temporary occlusion of major arteries, decreasing the risk of intraoperative ischemia. OBJECTIVE: To investigate the risks and potential benefits of high-flow bypass surgery for giant and complex aneurysms of the anterior cerebral circulation. In addition, the effectiveness of the ELANA bypass procedure in the treatment of these aneurysms is determined. METHODS: A total of 37 patients were included in 8 vascular neurosurgical centers in the United States, Canada, and Europe. A 30-d postoperative bypass follow-up was studied by using digital subtraction angiography and/or magnetic resonance angiography and computed tomography angiography to assess patency as well as by clinical monitoring in all patients. RESULTS: In 35 patients, an ELANA high-flow bypass was performed and the aneurysm treated. Four patients had remaining neurological deficits after 30 d caused by stroke (11.4%). These strokes were not related to the ELANA anastomosis device. CONCLUSION: This study does not prove that the ELANA technique has an advantage over conventional bypass techniques, but it appears to be an acceptable alternative to conventional transplanted high-flow bypass in this very-difficult-to-treat patient group, especially in select patients whom cannot be bypassed using conventional means in which temporary occlusion is considered to be not recommended.

Adjuvant Chemotherapy With Etoposide Plus Cisplatin for Patients With Pathologic Stage II Nonseminomatous Germ Cell Tumors.

PURPOSE: The relapse rate after primary retroperitoneal lymph node dissection (RPLND) for patients with pathologic stage (PS) IIA nonseminomatous germ cell tumors (NSGCTs) is 10%-20% but increases to ≥ 50% for PS IIB disease. We report our experience with 2 cycles of adjuvant etoposide plus cisplatin (EP×2) after therapeutic primary RPLND. PATIENTS AND METHODS: All patients with PS II NSGCT seen at Memorial Sloan Kettering Cancer Center from March 1989 to April 2016 and who were planned to receive EP×2 were included. Each cycle consisted of cisplatin 20 mg/m2 and etoposide 100 mg/m2 on days 1 through 5 at 21-day intervals. Demographic characteristics, histopathologic features, therapeutic and survival outcomes were recorded. RESULTS: Of 156 patients, 30 (19%) had pathologic N1, 122 (78%) had pathologic N2 (pN2), and 4 (3%) had pathologic N3 (pN3) disease. The median number of involved lymph nodes was 3 (range, 1-37 nodes), and the median size of the largest involved node was 2.0 cm (range, 0.4-7.0 cm); extranodal extension was present in 69 patients (45%). Embryonal carcinoma was the most frequent RPLND histology, present in 143 patients (92%). One hundred fifty patients (96%) received EP×2, five received EP×1 and one received EP×4. With a median follow-up of 9 years, 2 patients (1.3%; 1 patient each with pN2 and pN3 disease) experienced relapse; both patients remain continuously disease free at more than 5 and 22 years after salvage chemotherapy. Three patients died, all unrelated to NSGCT, yielding 10-year disease-specific, relapse-free, and overall survival rates of 100%, 98%, and 99%, respectively. CONCLUSION: Adjuvant EP×2 for PS II NSGCT is highly effective, has acceptable toxicity, and incurs less drug cost than 2 cycles of bleomycin, etoposide, and cisplatin. Inclusion of bleomycin in this setting is not necessary.

Effectiveness of Dural Sealants in Prevention of Cerebrospinal Fluid Leakage After Craniotomy: A Systematic Review.

OBJECTIVE: Cerebrospinal fluid (CSF) leakage is one of the most challenging complications in neurosurgery. We sought to evaluate the efficacy of dural sealants in preventing CSF leakage after cranial surgery. METHODS: A literature search was performed in the PubMed, Embase, and Cochrane databases. The inclusion criteria were defined to include articles describing regular cranial procedures combined with the use of any dural sealant reporting CSF leakage. The primary outcome was CSF leakage (pseudomeningocele formation or incisional CSF leakage), secondary outcomes were pseudomeningocele formation, incisional CSF leakage, and surgical-site infection. RESULTS: Twenty articles were included. Ten of these were comparative studies (sealant vs. no sealant) including 3 randomized controlled trials. In the 20 articles, a total of 3682 surgical procedures were reported. The number of CSF leakages in general did not differ between the sealant group (8.2%) and control group (8.4%), risk ratio (RR) 0.84 (0.50-1.42), I2 = 56%. Exclusion of non-randomized controlled trials did not alter the results. Meta-analyses for secondary outcomes showed no difference between number of incisional CSF leakage, RR 0.30 (0.05-1.59), I2 = 38%. Also, no difference was found in the pseudomeningocele formation, RR 1.50 (0.43-5.17), I2 = 0%. Surgical-site infection was seen less in the sealant group (1.0%) compared with the control group (5.6%), RR 0.25 (0.13-0.48), I2 = 0%. CONCLUSIONS: This systematic review showed that dural sealants did not reduce the number of CSF leaks in general, the number of incisional CSF leaks alone, or the number of pseudomeningocele formations alone. However, dural sealants reduced the risk of surgical-site infection.

Trends in Cerebral Revascularization in the Era of Pipeline and Carotid Occlusion Surgery Study.

BACKGROUND: In the past, microsurgical bypass was the best option for revascularization of cerebrovascular lesions that required flow replacement or flow augmentation. Over the last 2 decades with advancements in the field of neuroendovascular surgery, especially with the revolution of flow diverting stents as well as the results of the Carotid Occlusion Surgery Study, indications for microvascular bypass have significantly decreased. The purpose of this study was to evaluate trends in cerebral revascularization over the past 8 years. METHODS: We retrospectively reviewed patients with cerebral revascularization surgery during the years 2006-2014 in a single surgeon's practice. All patients who had undergone cerebral revascularization for any indication were included in the study. RESULTS: We identified 106 patients who had undergone cerebral bypass; 2 patients were excluded. Of 104 patients, 60% were female and 40% were male. Indications for surgery were giant aneurysm in 48 patients, arterial occlusion in 30 patients, and moyamoya disease in 26 patients. In all indications except for moyamoya disease, case number per year declined. A marked decrease was noted in revascularization for treatment of giant aneurysm or occlusion. CONCLUSIONS: This study demonstrates the impact that both scientific inquiry and technologic advances have had on a challenging and valuable technique in cerebrovascular surgery. Indications for both flow replacement and augmentative bypass remain. However, the marked decline in indications may have an indelible impact on maintenance of surgical proficiency as well as the ability for young neurosurgeons to develop this valuable skill set.