Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction.

PURPOSE: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Patients with GEJ adenocarcinoma (cT1-3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. RESULTS: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS < 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1-expressing EVs was significantly associated with higher pCR. CONCLUSIONS: Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.

Pattern of cochlear obliteration after vestibular Schwannoma resection according to surgical approach.

OBJECTIVES/HYPOTHESIS: To investigate the prevalence and course of cochlear obliteration according to microsurgical approach to inform clinical decision making regarding optimal timing of cochlear implantation. STUDY DESIGN: Retrospective radiologic review and chart review. METHODS: Patients who underwent microsurgical resection of vestibular schwannoma (VS) with a minimum of two available postoperative magnetic resonance imaging (MRI) scans were analyzed. The prevalence and timing of cochlear and labyrinthine obliteration was classified using relevant MRI sequences. RESULTS: MRI studies in 60 patients were analyzed: 20 translabyrinthine (TL), 20 retrosigmoid, and 20 middle fossa (MF) cases. The first and last postoperative MRI was obtained a median of 3.4 months (interquartile range (IQR), 3.0-3.7 months) and 35 months (IQR, 27-83 months) after surgery, respectively. At the time of the first postoperative MRI, 21 (35%) patients had partial basal turn obliteration, and none of the patients had complete basal turn obliteration. At the time of the last postoperative MRI, six (10%) patients had partial basal turn obliteration and 17 (28%) patients had complete basal turn obliteration. The pattern of partial or complete basal turn obliteration differed significantly among all three surgical approaches (P < .001). Specifically, the risk of partial or complete obliteration of the basal turn was highest in the TL cohort and lowest in the MF cohort. CONCLUSIONS: The prevalence and timing of cochlear obliteration after VS microsurgery varies significantly according to surgical approach. The risk of early and complete obliteration is highest in the TL group and lowest in the MF cohort. These data may inform clinical decision making regarding optimal timing of cochlear implantation in patients with advanced hearing loss after microsurgical resection. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:474-481, 2020.

Retrosigmoid Approach for Resection of Medium-Sized Vestibular Schwannoma.

Objectives This video was aimed to describe the relevant anatomy and key surgical steps of retrosigmoid approach for gross total resection of a medium-sized vestibular schwannoma (VS). Design The procedure is described in a surgical instructional video. Setting The surgery took place at a tertiary skull base referral center. Participant Patient is a 63-year-old woman who reported with nonserviceable hearing (Pure Tone Average 60 dB Hearing level, Word Recognition Score 45%), occasional tinnitus, and a VS in the left cerebellopontine angle (CPA), extending into internal auditory canal (IAC), measuring 1.7 cm parallel to the petrous temporal bone. Main Outcome Measures The VS was resected by retrosigmoid approach. Results The surgery results gross total resection of the VS with postoperative House-Brackmann grade 1 facial nerve function and no postoperative complications. Conclusion The retrosigmoid approach is a good strategy to remove VS involving the CPA and the IAC. The link to the video can be found at: https://youtu.be/B6K_UkrKitg .

Retrosigmoid Approach for Resection of Large Cystic Vestibular Schwannoma.

Objectives This video was aimed to describe the surgical indications, relevant anatomy, and surgical steps of retrosigmoid approach for resection of a large cystic vestibular schwannoma (VS). Design The operative steps are described in a surgical instructional video. Setting The surgery took place at a tertiary skull base referral center. Participant Patient is a 62-year-old man who reported with right sided profound hearing loss with no word recognition, progressive dizziness and tinnitus, excruciating burning pain in the V2 distribution of right trigeminal nerve, wide-based gait, and a right cerebellopontine angle (CPA) cystic VS measuring 3.3 cm. Main Outcome Measures The large cystic VS was resected through retrosigmoid approach. Results The surgery resulted in removal of the large cystic VS with initial delayed facial weakness that completely resolved (House Brackmann grade 1) by 3 month follow-up. The patient had no other postoperative complications and is convalescing well from the procedure. Conclusion Cystic VS presents some unique challenges compared with their solid counterparts. The cystic tumor capsule may be very adherent to the adjacent structures, and distinguishing thin cyst walls from the arachnoid of the CPA, can be quite challenging. The retrosigmoid approach provides adequate surgical exposure for VS tumor resection. The link to the video can be found at: https://youtu.be/sFNvRWG465Q .

Translabyrinthine Approach for Resection of Vestibular Schwannoma.

Objectives This video describes the surgical indications, relevant anatomy, and surgical steps of routine translabyrinthine surgery for gross total resection of sporadic vestibular schwannoma. Design The procedure is presented through a surgical instructional video. Setting The surgery took place at tertiary skull base referral center. Parcipant A 47-year-old patient reported with nonserviceable hearing, frequent episodes of vertigo, recurrent severe headache, and a small unilateral right sided vestibular schwannoma. Results Gross total resection with preservation of facial nerve function was achieved. Conclusion This instructional video documents the surgical steps and relevant anatomy for translabyrinthine resection of vestibular schwannoma. The link to the video can be found at: https://youtu.be/CJ2vKMLs7aI .

Expansile Traumatic Neuroma of the Intratemporal Facial Nerve.

Objectives To present a rare case of traumatic facial neuroma involving the geniculate ganglion and review relevant literature. Patient Thirty-year-old man. Intervention Microsurgical resection via combined mastoid-middle fossa approach with great auricular nerve interpositional graft. Main Outcome Measures Patient demographics and pre- and postoperative facial nerve function. Results A 30-year-old man with a reported history of prior Bell's palsy developed progressive complete (House-Brackmann VI) right facial paralysis following blunt trauma. Imaging was strongly suggestive of a geniculate ganglion hemangioma. As the patient had no spontaneous improvement in his poor facial function over the course of 9 months, he underwent resection of the facial nerve lesion with great auricular nerve graft interposition via a combined mastoid-middle fossa approach. Histopathology demonstrated disorganized fascicles, with axonal clustering reminiscent of sprouting/regeneration following trauma. No cellular proliferation or vascular malformation was present. Conclusion Traumatic facial nerve neuromas can occur following temporal bone trauma and can closely mimic primary facial nerve tumors. Akin to the management of geniculate ganglion hemangioma and schwannoma, preoperative facial function largely dictates if and when surgery should be pursued.