ABSTRACT
PURPOSE: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. METHODS: A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. RESULTS: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n = 13; 31.7%), followed by posterior fossa (n = 7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. CONCLUSION: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.
Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Down Syndrome , Germinoma , Neoplasms, Germ Cell and Embryonal , Pineal Gland , Sepsis , Teratoma , Brain Neoplasms/pathology , Central Nervous System Neoplasms/pathology , Central Nervous System Neoplasms/therapy , Child , Down Syndrome/complications , Female , Germinoma/pathology , Humans , Male , Neoplasms, Germ Cell and Embryonal/complications , Neoplasms, Germ Cell and Embryonal/therapy , Pineal Gland/pathology , Retrospective Studies , Testicular NeoplasmsABSTRACT
Wnt-activated medulloblastoma (MB) confers an excellent prognosis. However, specific treatment strategies for patients with relapsed Wnt-MB are unknown. We report two patients with recurrent beta-catenin nucleopositive Wnt-MB successfully treated by incorporating marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue (HDCx/AuHPCR). We also present a review of the literature for previously reported cases of relapsed Wnt-MB. We propose that patients with recurrent Wnt-MB may be treated using a multi-disciplinary approach that includes HDCx/AuHPCR with or without re-irradiation.
Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Bone Marrow , Brain Neoplasms/therapy , Cerebellar Neoplasms/diagnostic imaging , Cerebellar Neoplasms/therapy , Hematopoietic Stem Cells , Humans , Medulloblastoma/diagnostic imaging , Medulloblastoma/therapyABSTRACT
OBJECTIVE: To evaluate the availability and breadth of information provided by program-created pediatric otolaryngology fellowship websites as well as the American Society of Pediatric Otolaryngology (ASPO) program directory. METHODS: Program-created pediatric otolaryngology fellowship websites and the ASPO directory were evaluated for 16 key criteria deemed to be relevant to fellowship applicants. RESULTS: All 36 ACGME-accredited pediatric otolaryngology fellowship programs had websites that were readily available by Google search, and the ASPO program directory contained direct links to 17 (47.2 %) program-created websites. On average, program-created websites fulfilled 6.9 (43.1 %, range 1-11) and the ASPO directory fulfilled 6.9 (43.1 %, range 3-11) of the 16 key criteria. When utilizing both resources, the average increased to 8.3 (51.2 %) - criteria included program description (94.4 %), location description (30.4 %), fellowship director contact information (94.4 %), program coordinator contact information (72.2 %), teaching responsibilities (68.6 %), call responsibilities/schedule (41.7 %), operative volume (80 %), breadth of surgical exposure (94.4 %), research opportunities (72.2 %), research expectations (63.9 %), current fellow(s) (42.9 %), post-fellowship placement (28.6 %), fellow clinic (28.6 %), medical missions/outreach (20 %), and resident coverage (36.1 %). CONCLUSION: Pediatric otolaryngology fellowship websites as well as program-specific data sheets from ASPO lack many key criteria that would otherwise be valuable to applicants. Inclusion of these criteria could help applicants make a more well-informed decision when applying into pediatric otolaryngology fellowship.
Subject(s)
Fellowships and Scholarships , Internet , Otolaryngology , Pediatrics , Humans , Otolaryngology/education , Pediatrics/education , United States , Education, Medical, Graduate , Internship and ResidencyABSTRACT
OBJECTIVE: The objective of this study was to develop a nomogram to predict long-term facial nerve (FN) function after vestibular schwannoma (VS) resection. METHODS: A retrospective cohort study of two tertiary academic skull base referral centers was performed. Consecutive adults > 18 years of age with sporadic unilateral VS who underwent resection between September 2016 and May 2021 were included. FN function in the immediate postoperative period and at the most recent evaluation was measured. RESULTS: A total of 306 patients (mean age 49 years, 63% female) were included, with a mean follow-up of 18 months. The mean maximum tumor diameter was 19 mm (range 1-50 mm), and 80 (26.1%) tumors were > 25 mm. Overall, 85% of patients showed good immediate postoperative FN function (House-Brackmann [HB] grade I or II) and 89% maintained good FN function at > 12 months of follow-up. An intraoperative FN electromyographic (EMG) response ≥ 100 µV to 0.05 mA of stimulation (OR 18.6, p < 0.001) was the strongest predictor of good HB grade in the immediate postoperative period. EMG response ≥ 100 µV (OR 5.70, p < 0.001), tumor size ≤ 25 mm (OR 3.09, p < 0.05), and better immediate postoperative HB grade (OR 1.48, p = 0.005) predicted good long-term FN function on multivariable analysis. A point-of-care nomogram based on these data predicted long-term FN function with a sensitivity of 89% and specificity of 69%. CONCLUSIONS: Better immediate postoperative HB grade, intraoperative FN EMG response ≥ 100 µV, and tumor size ≤ 25 mm strongly predicted good long-term FN function after VS resection. A point-of-care nomogram based on these variables could serve as a useful tool for postoperative counseling and prognosis of long-term FN recovery.
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OBJECTIVE: To evaluate clinical and audiometric outcomes of adult and pediatric patients implanted with a semi-implantable transcutaneous active bone-conduction implant. STUDY DESIGN: Retrospective chart review. SETTING: Two tertiary referral centers. PATIENTS: Subjects implanted with the semi-implantable transcutaneous active bone-conduction implant called BoneBridge. INTERVENTION: Implantation of the BoneBridge and audiometric evaluations. MAIN OUTCOME MEASURES: Audiometric, clinical, and surgical outcomes as well as complications. RESULTS: Forty-two adults and 20 children were implanted for conductive or mixed hearing loss as well as single-sided deafness. Implantation significantly improved mean air-conduction pure-tone average from 72.8 ± 22.3 to 35 ± 9 dB in adults and from 65.7 ± 24.3 to 19.6 ± 8.2 dB in children (both p < 0.001). Word recognition score improved from 63.7 ± 38.8% to 85.6 ± 10.6% in adults and 57.8 ± 38% to 89.3 ± 10.1% in children (both p < 0.05). The rate of revision surgery was 11.3%, with four patients (6.5%) undergoing removal for device-related complications, two (3.2%) for complications associated with implantation, and one (1.6%) for device failure secondary to external trauma. CONCLUSIONS: In a large retrospective series consisting of both pediatric and adult patients, implantation with a transcutaneous active bone-conduction implant was found to be a reliable aural rehabilitation option for a variety of hearing loss etiologies.
Subject(s)
Hearing Aids , Hearing Loss , Speech Perception , Humans , Adult , Child , Retrospective Studies , Hearing Loss/surgery , Hearing Loss/complications , Audiometry , Prostheses and Implants/adverse effects , Bone Conduction , Hearing Loss, Conductive/surgery , Hearing Loss, Conductive/etiology , Hearing Aids/adverse effects , Treatment OutcomeABSTRACT
OBJECTIVES: The influence of apnea- and hypopnea-predominance on hypoglossal nerve stimulation therapy outcomes (HGNS) is still poorly defined. We assessed the significance of apnea- and hypopnea-predominance in HGNS outcomes. STUDY DESIGN: Case series with chart review. SETTING: Single-institution tertiary care center. METHODS: A total of 216 subjects were included, all of which had undergone drug-induced sleep endoscopy (DISE) and HGNS implantation. Demographic and polysomnographic data were collected. The 4% apnea-hypopnea criteria were used to calculate apnea-hypopnea index (AHI). Central apneas were omitted. Univariate logistic and linear regression were used to study the association between these data and apnea-predominance and hypopnea-predominance. Kruskal-Wallis rank sum test was used to compare medians between groups for DISE collapse patterns. RESULTS: Sixty-three patients were apnea-predominant, and 153 patients were hypopnea-predominant. These 2 groups were similar demographically (p > .20). There was no significant difference in HGNS outcomes between the groups assessed using Sher20 criteria at the 1-year mark using all-night, single-setting polysomnography or home sleep studies. Apnea index (AI)/AHI and reduction in AHI from preoperative to titration were significantly associated (p = .046). The median preoperative hypopnea index was significantly lower (p = .033) in subjects with no oropharyngeal collapse than patients with partial or complete oropharyngeal collapse. There were no significant relationships between AI/AHI and the different degrees of collapse at the velopharynx, oropharynx, tongue base, or epiglottis. CONCLUSIONS: In line with CPAP, tonsillectomy, and mandibular advancement therapy studies, we found there was largely no significant difference in DISE anatomy or in HGNS treatment outcomes between apnea- and hypopnea-predominant individuals.
Subject(s)
Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/surgery , Hypoglossal Nerve , Endoscopy , Polysomnography , Treatment OutcomeABSTRACT
BACKGROUND: Diffuse midline gliomas (DMG) are highly invasive brain tumors with rare survival beyond two years past diagnosis and limited understanding of the mechanism behind tumor invasion. Previous reports demonstrate upregulation of the protein ID1 with H3K27M and ACVR1 mutations in DMG, but this has not been confirmed in human tumors or therapeutically targeted. METHODS: Whole exome, RNA, and ChIP-sequencing was performed on the ID1 locus in DMG tissue. Scratch-assay migration and transwell invasion assays of cultured cells were performed following shRNA-mediated ID1-knockdown. In vitro and in vivo genetic and pharmacologic [cannabidiol (CBD)] inhibition of ID1 on DMG tumor growth was assessed. Patient-reported CBD dosing information was collected. RESULTS: Increased ID1 expression in human DMG and in utero electroporation (IUE) murine tumors is associated with H3K27M mutation and brainstem location. ChIP-sequencing indicates ID1 regulatory regions are epigenetically active in human H3K27M-DMG tumors and prenatal pontine cells. Higher ID1-expressing astrocyte-like DMG cells share a transcriptional program with oligo/astrocyte-precursor cells (OAPCs) from the developing human brain and demonstrate upregulation of the migration regulatory protein SPARCL1. Genetic and pharmacologic (CBD) suppression of ID1 decreases tumor cell invasion/migration and tumor growth in H3.3/H3.1K27M PPK-IUE and human DIPGXIIIP* in vivo models of pHGG. The effect of CBD on cell proliferation appears to be non-ID1 mediated. Finally, we collected patient-reported CBD treatment data, finding that a clinical trial to standardize dosing may be beneficial. CONCLUSIONS: H3K27M-mediated re-activation of ID1 in DMG results in a SPARCL1+ migratory transcriptional program that is therapeutically targetable with CBD.
Subject(s)
Brain Neoplasms , Glioma , Animals , Humans , Mice , Brain/pathology , Brain Neoplasms/genetics , Calcium-Binding Proteins , Extracellular Matrix Proteins/genetics , Glioma/genetics , Histones/genetics , Inhibitor of Differentiation Protein 1/genetics , Mutation , Signal TransductionABSTRACT
Sentinel lymph node mapping in patients with axillary breast carcinoma is technically challenging and poorly described in the literature. We report a patient with primary ectopic breast carcinoma of the axilla in whom concurrent peri-tumoral and intra-tumoral injection of radionuclide tracer allowed for identification and biopsy of sentinel lymph nodes.
ABSTRACT
Background: There is increasing evidence that students are completing medical school with insufficient surgical education. Near-peer tutoring and flipped classroom formatting may be used to enhance learning while simultaneously relieving faculty burden of teaching. Here, we qualitatively evaluate a 3-month course that integrates the use of near-peer teaching and flipped classroom formatting, with the goal of increasing first-year medical students' self-perceived confidence in performing basic sutures and knot-ties as well as interest in surgery. Methods: Twenty-one first-year medical students participated in a suturing and knot-tying course led by senior medical students. The course consisted of 2-h sessions held every 2 weeks for a total of five sessions. Students were sent publicly available videos prior to each session by which to learn the upcoming techniques and received live feedback from instructors during sessions. Questionnaires were completed pre-course and post-course. Results: Compared to pre-course ratings, post-course ratings of self-perceived confidence to perform various knot-ties and sutures all increased significantly (p < 0.05). All students stated that the course strengthened their desire to pursue a career in surgery. Student feedback of the course was overall positive. Conclusions: Near-peer teaching can be used in conjunction with flipped classroom to increase first-year medical students' self-perceived confidence in surgical suturing and knot-tying as well as interest in surgery. This curriculum may serve as an outline for student-led courses at other institutions.