Anatomical determinants of occipitocervical fusion in skull base chordoma resection: a systematic review of the literature with illustrative cases.

OBJECTIVE: Skull base chordomas are rare, locally osseo-destructive lesions that present unique surgical challenges due to their involvement of critical neurovascular and bony structures at the craniovertebral junction (CVJ). Radical cytoreductive surgery improves survival but also carries significant morbidity, including the potential for occipitocervical (OC) destabilization requiring instrumented fusion. The published experience on OC fusion after CVJ chordoma resection is limited, and the anatomical predictors of OC instability in this context remain unclear. METHODS: PubMed and Embase were systematically searched according to the PRISMA guidelines for studies describing skull base chordoma resection and OC fusion. The search strategy was predefined in the authors' PROSPERO protocol (CRD42024496158). RESULTS: The systematic review identified 11 surgical case series describing 209 skull base chordoma patients and 116 (55.5%) who underwent OC instrumented fusion. Most patients underwent lateral approaches (n = 82) for chordoma resection, followed by midline (n = 48) and combined (n = 6) approaches. OC fusion was most often performed as a second-stage procedure (n = 53), followed by single-stage resection and fusion (n = 38). The degree of occipital condyle resection associated with OC fusion was described in 9 studies: total unilateral condylectomy reliably predicted OC fusion regardless of surgical approach. After lateral transcranial approaches, 4 studies cited at least 50%-70% unilateral condylectomy as necessitating OC fusion. After midline approaches-most frequently the endoscopic endonasal approach (EEA)-at least 75% unilateral condylectomy (or 50% bilateral condylectomy) led to OC fusion. Additionally, resection of the medial atlantoaxial joint elements (the C1 anterior arch and tip of the dens), usually via EEA, reliably necessitated OC fusion. Two illustrative cases are subsequently presented, further exemplifying how the extent of CVJ bony elements removed via EEA to achieve complete chordoma resection predicts the need for OC fusion. CONCLUSIONS: Unilateral total condylectomy, 50% bilateral condylectomy, and resection of the medial atlantoaxial joint elements were the most frequently described independent predictors of OC fusion in skull base chordoma resection. Additionally, consistent with the occipital condyle harboring a significantly thicker joint capsule at its posterolateral aspect, an anterior midline approach seems to tolerate a greater degree of condylar resection (75%) than a lateral transcranial approach (50%-70%) prior to generating OC instability.

Extreme lateral infracondylar approach for internal jugular vein compression syndrome: A case series with preliminary clinical outcomes.

BACKGROUND AND OBJECTIVES: Internal jugular vein (IJV) stenosis is associated with several neurological disorders including idiopathic intracranial hypertension (IIH) and pulsatile tinnitus. In cases of extreme bony compression causing stenosis in the infracondylar region, surgical decompression might be necessary. We aim to examine the safety and efficacy of surgical IJV decompression. METHODS: We retrospectively reviewed patients who received surgical IJV decompression via the extreme lateral infracondylar (ELI) approach between July 2020 and February 2022. RESULTS: Fourteen patients with IJV stenosis were identified, all with persistent headache and/or tinnitus. Six patients were diagnosed with IIH, three of whom failed previous treatment. Of the eight remaining patients, two failed previous treatment. All underwent surgical IJV decompression via styloidectomy, release of soft tissue, and removal of the C1 transverse process (TP). Follow-up imaging showed significant improvement of IJV stenosis in eleven patients and mild improvement in three. Eight patients had significant improvement in their presenting symptoms, and three had partial improvement. Two patients received IJV stenting after a lack of initial improvement. Two patients experienced cranial nerve paresis, and one developed a superficial wound infection. CONCLUSION: The ELI approach for IJV decompression appears to be safe for patients who are not ideal endovascular candidates due to bony anatomy. Confirming long-term efficacy in relieving debilitating clinical symptoms requires longer follow-up and a larger patient cohort. Carefully selected patients with symptomatic bony IJV compression for whom there are no effective medical or endovascular options may benefit from surgical IJV decompression.

Cranial transposition and revascularization of autologous omentum: a novel surgical technique for resection of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

Viral markers in nasopharyngeal carcinoma: A systematic review and meta-analysis on the detection of p16INK4a, human papillomavirus (HPV), and Ebstein-Barr virus (EBV).

PURPOSE: This study aimed to conduct a meta-analysis to investigate the distribution of EBV and HPV stratified according to histological NPC type. MATERIALS & METHODS: We performed a meta-analysis to produce pooled prevalence estimates in a random-effects model. We also performed calculations for attributable fractions of viral combinations in NPC, stratified according to histological type. RESULTS: There was a higher prevalence of HPV DNA in WHO Type I (34.4%) versus WHO Type II/III (18.4%). The attributable fractions of WHO Type I NPC was predominantly double negative EBV(-) HPV(-) NPC (56.4%), and EBV(-) HPV(+) NPC (21.5%), in contrast to the predominant infection in WHO Type II/III which was EBV(+) HPV(-) NPC (87.5%). Co-infection of both EBV and HPV was uncommon, and double-negative infection was more common in WHO Type I NPC. CONCLUSION: A significant proportion of WHO Type I NPC was either double-negative EBV(-)HPV(-) or EBV(-)HPV(+).

The prognostic effect of anatomic subsite in HPV-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Since most HPV-associated disease occurs in the tonsillar-related areas (TRA) - palatine and lingual tonsils, the effect of HPV on survival in non-tonsillar oropharyngeal subsites (nTRA) is not well established. The objective of this study was to use a large population-based cohort to investigate the survival impact of HPV in nTRA subsites versus TRA subsites. METHODS: This SEER database study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. RESULTS: HPV-positive squamous cell cancer was significantly more common in TRAs (73%) compared to nTRAs (31.2%, p < 0.001). After controlling for age, treatment, stage, race, and income, patients with HPV-positive disease in nTRAs had a worse cause-specific survival (CSS) than individuals with HPV-positive disease in TRAs (HR = 2.16, 95% CI 1.20-3.86, p = 0.01). CONCLUSION: Patients with HPV-positive OPSCC in nTRAs had poorer survival outcomes compared to patients with HPV-positive OPSCC in TRAs.

HPV status in patients with nasopharyngeal carcinoma in the United States: A SEER database study.

PURPOSE: To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC). MATERIALS AND METHODS: Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models. RESULTS: 180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group. CONCLUSIONS: The clinical implications of HPV in NPC are further elucidated but require more investigation. LEVEL OF EVIDENCE: IV.

Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis.

PURPOSE: The objective of this study was to investigate the prognostic role of three inflammatory markers: the neutrophil to lymphocyte ratio (NLR), the lymphocyte to monocyte ratio (LMR), and the platelet to lymphocyte ratio (PLR) as prognostic indicators in squamous cell carcinoma of the head and neck (HNSCC). METHODS: Patients with HNSCC treated with primary surgery, with or without adjuvant radiochemotherapy were enrolled. The preoperative NLR, LMR, and PLR were recorded. Confounding variables were also recorded: age, sex, BMI, comorbidities, performance status, AJCC T and N stage and HPV status. Endpoints were overall survival (OS) and event-free survival (EFS). Survival analysis was performed using Kaplan-Meier analysis, and multivariable analysis was performed using Cox proportional hazards regression. Survival models were evaluated using Harrell's concordance index (c-index). RESULTS: NLR (p = 0.2413), PLR (p = 0.1593), and LMR (p = 0.0552) were not significantly associated with OS in the multivariable analysis. With regard to EFS, low LMR (HR = 2.95, 95% CI 1.54-5.65, p = 0.001), high PLR (HR = 2.68, 95% CI 1.42-5.09, p = 0.003), and high NLR (HR = 3.37, 95% CI 1.7-6.69, p < 0.001) were associated with EFS. The multivariable c-index was highest for LMR (0.762), followed by NLR (0.761) and PLR (0.739). CONCLUSION: The LMR, PLR, and NLR were not associated with OS, but were associated with EFS in HNSCC. These markers are easily obtainable, and in the age of individualized patient care and precision medicine, they might represent further risk stratification tools for HNSCC patients.

Is human papillomavirus and p16 expression associated with survival outcomes in nasopharyngeal cancer?: A systematic review and meta-analysis.

INTRODUCTION: Human papillomavirus (HPV) is a known prognostic indicator in oropharyngeal cancer. Not much is known about the prognostic role of HPV in Nasopharyngeal cancer (NPC). Here, we performed a systematic review and meta-analysis of the literature to investigate if HPV status was a prognostic factor for NPC. METHODS: PubMed (via the web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled Hazard Ratios (HR) for Overall Survival (OS). RESULTS: A total of 7 studies from 2014 to 2018, reporting data on 2646 patients (range 43-1328) were included in this meta-analysis. The pooled data showed that HPV/p16 status was not associated with OS in NPC with HR of 0.77 (95% CI: 0.55-1.09, p = 0.14). The test for heterogeneity showed little to no heterogeneity of results (I2 = 4%, p = 0.38). Subgroup analysis showed that in large sample sizes, HPV was significantly associated with survival. CONCLUSION: Despite the finding in the pooled HR, we could not draw a definitive conclusion as to the prognostic significance of HPV in NPC. Recommendations for future research are given.

The red cell distribution width as a prognostic indicator in upper aerodigestive tract (UADT) cancer: A systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to investigate the relationship between the Red Cell Distribution Width (RDW) and prognosis in upper aerodigestive tract (UADT) cancer. METHODS: PubMed (via the web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled hazard ratios (HR) for overall survival (OS), disease specific survival (DSS), and recurrence free survival (RFS). RESULTS: Our analysis included the results of 4200 patients in 8 cohorts. The pooled data demonstrated that an elevated RDW was associated with significantly poorer OS (HR: 1.44, 95% CI: 1.13-1.83), RFS (HR: 1.43, 95%CI: 1.13-1.82). The DSS result had high heterogeneity and 95% CI was not pooled. CONCLUSIONS: An elevated RDW may be an indicator of poor prognosis in UADT cancers in certain populations. Further research is needed to confirm this effect.

Evaluation of the prognostic utility of the hemoglobin-to-red cell distribution width ratio in head and neck cancer.

PURPOSE: Hemoglobin is a known prognostic marker in many cancers, including head and neck cancer (HNC). There is some evidence that the red cell distribution width, which is an index of variation in size of red blood cells (RBCs), might be associated with prognosis as well. Recently, a novel prognostic biomarker has been reported-the ratio of the hemoglobin-to-red cell distribution width (Hb/RDW). Our objective was to evaluate the prognostic utility of the pretreatment Hb/RDW in HNC, controlled with known prognostic indices. METHODS: Retrospective cohort study in a tertiary academic hospital setting. Patients diagnosed with HNC treated with curative-intent surgery were eligible. Metastatic disease was excluded. The variables collected were age, sex, BMI, alcohol/tobacco exposure, performance scores, ACE-27, tumor characteristics, adjuvant treatment, and lab values. The primary endpoints were event-free survival (EFS) and overall survival (OS). OS was defined as time from start of treatment to death from any cause, and EFS was defined as time from start of treatment to any progression, recurrence, or death from any cause. Univariate and multivariate survival analysis was performed on the primary endpoints. RESULTS: A total of 205 patients were enrolled from 2010 to 2016. In multivariate analysis, the factors independently associated with EFS were BMI (p = 0.0364), advanced T stage (p = 0.001), and low Hb/RDW ratio (p = 0.017). The factors independently associated with OS were ECOG score (p = 0.042), advanced T stage (p < 0.0001), positive nodes (p = 0.0195), and Hemoglobin (0.0134). CONCLUSION: A low Hb/RDW ratio was associated with poorer EFS (HR = 2.02, 95% CI 1.13-3.61, p = 0.017), but was not associated with OS. This is the first study reporting the prognostic utility of Hb:RDW in head and neck cancer.

The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to investigate the relationship between the pre-treatment lymphocyte-to-monocyte ratio (LMR) and prognosis in HNC. METHODS: PubMed (via the Web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS). RESULTS: Our analysis included the results of 4260 patients in seven cohorts. The pooled data demonstrated that an elevated LMR was associated with significantly improved OS (HR 0.5; 95% CI 0.44-0.57), and DFS (HR 0.70; 95% CI 0.62-0.80). Of note, there was no detectable heterogeneity in either OS (I2 = 0%) or DFS (I2 = 0%). CONCLUSIONS: An elevated LMR may be an indicator of favorable prognosis in HNC. However, our results should be interpreted with some degree of caution due to the retrospective nature of cohort studies. Further research with high-quality prospective studies is needed to confirm the effect of LMR in HNC prognosis.

Intra-arterial cetuximab for the treatment of recurrent unresectable head and neck squamous cell carcinoma†.

IMPORTANCE: Management of recurrent head and neck squamous cell carcinoma is a common and challenging clinical problem in head and neck oncology. OBJECTIVE: Here we present the first reported case of super-selective intra-arterial (SSIA) microcatheter based local delivery of cetuximab for head and neck cancer. This technical report describes the techniques used to deliver the SSIA dose of cetuximab, as well as the patient outcome. DESIGN: This technical report is part of an ongoing Phase I Clinical Trial. SETTING: The New York Head and Neck Institute (NYHNI) is a full-service otolaryngology and neurosurgery department at Lenox Hill Hospital, part of the Northwell Health System. The NYHNI serves a diverse patient population with a wide range of head and neck diseases in a tertiary hospital setting. INTERVENTION: SSIA Cetuximab. PARTICIPANT: A patient presents to our clinic with recurrent unresectable squamous cell carcinoma of the nasopharynx. He is recruited into the first cohort of a phase I clinical trial to assess the safety of SSIA cetuximab, dose starting at 100mg/m2. Adjuvant chemo-radiation therapy is also given. MEASURES: Safety, as measured by toxicity of SSIA cetuximab. RESULTS: SSIA Cetuximab has been demonstrated to be a safe and feasible procedure in this technical report. CONCLUSIONS: This case illustrates technical feasibility and a very preliminary assessment of the safety of a novel delivery of a biologic agent for squamous cell carcinoma of the head and neck, which is part of an ongoing phase I clinical trial. TRIAL REGISTRATION: NCT02438995.

Endovascular palliation of multivessel blowout syndrome in the setting of a nonresectable neck sarcoma.

Carotid blowout syndrome is a rare life-threatening complication of head and neck malignancy. Current literature has focused exclusively on the carotid system and associated branches. We present a unique case of multivessel blowout in the setting of a large nonresectable neck sarcoma requiring various endovascular techniques for palliation.

Revising large scars.

Large scars in the head and neck are often the cause of significant emotional distress to patients, and often present unique challenges to the plastic and reconstructive surgeon undertaking their revision. The primary goal of scar revision is to eliminate compromise of function that may have resulted from scar contracture; a secondary goal is to improve the appearance of the scar. Special techniques for the revision of large scars include serial partial excision, rapid intraoperative or prolonged tissue expansion, split- and full-thickness skin grafting, regional flaps, and free microvascular tissue transfer. Recent research has investigated the use of artificial skin and autologous fat grafting for large scar revision.

Anatomical subsite modifies survival in oropharyngeal squamous cell carcinoma: National Cancer Database study.

BACKGROUND: Oropharyngeal squamous cell carcinomas (OPSCC) can occur in either tonsillar related areas (TRA) or nontonsillar areas (nTRA). The prognostic differences between these sites are unclear. This study investigated this question using the National Cancer Database (NCDB), controlling for other confounders including human papillomavirus (HPV) status. METHODS: This NCDB study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. Kaplan Meier survival analysis was stratified according to HPV status, and further analysis was conducted using multivariable Cox regression. RESULTS: A total of 23 297 patients were included in this study. In the multivariable cox regression analysis, OPSCC subsite was found to be an independent prognostic factor for survival (TRA vs nTRA HR: 0.76, 95% CI: 0.67-0.86, P < .0001). CONCLUSION: In this large cohort, OPSCC subsite was found to be an independent prognostic factor for survival.

The Prognostic Role of Programmed Death-Ligand 1 in Nasopharyngeal Carcinoma.

OBJECTIVES: Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that may be a useful prognostic biomarker in nasopharyngeal cancer (NPC). The purpose of this systematic review and meta-analysis was to investigate the relationship between PD-L1 expression and survival in NPC. METHODS: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched from inception to present. A predefined inclusion and exclusion criteria were used to select articles. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS), and disease metastasis-free survival (DMFS). RESULTS: Eleven studies published from 2014 to 2018 were included, with 1,356 total participants. PD-L1 expression was not associated with OS (HR = 1.10, 95% CI: 0.79-1.55), DFS (HR = 1.66, 95% CI: 0.68-4.03), or DMFS (HR = 1.18, 95% CI: 0.44-3.20). CONCLUSIONS: The prognostic role of PD-L1 in NPC remains unsubstantiated. Future research is needed. Laryngoscope, 130:2598-2606, 2020.

Internal Maxillary to Middle Cerebral Artery Bypass Using an Anterior Tibial Artery Graft, Performed Using a 3-Dimensional Exoscope: 2-Dimensional Operative Video.

Fusiform aneurysms remain challenging entities to treat, as maintenance of flow and prevention of branch occlusion are concerns. Use of endovascular stents may risk nearby branch occlusion. We present a 31-yr-old male with a prior subarachnoid hemorrhage from a left middle cerebral artery (MCA) M1 aneurysm. Informed consent for use of the operative video and information was obtained from the patient. Initially, open clipping was performed with noted residual because of risk of nearby branches. On angiography, a growing fusiform segment distal to the initial aneurysm was noted. The patient was referred to our institution for this finding, and a multidisciplinary team reviewed the case. Endovascular treatment was felt to be risky, as stenting could jail nearby MCA branches. Clipping would also risk occlusion because of scaring from previous hemorrhage. Sufficient flow would be needed, and because the ipsilateral superficial temporal artery was sacrificed in the initial craniotomy, the internal maxillary artery (IMAX) was chosen as the bypass source. A cerebrovascular neurosurgeon, skull base otolaryngologist, and vascular surgeon worked together to perform a left-side IMAX to MCA bypass using an anterior tibial artery graft under 3-dimensional exoscopic visualization. Specifically, a 9-0 nylon suture on a BV-130 needle along with straight and tying forceps were used along with heparinized saline. The bypass was noted to be of robust flow, and the patient did very well on postoperative follow-up. The utilization of an anterior tibial artery graft, IMAX exposure, and corresponding bypass provides educational value, as there are only a limited number of videos on this topic.

Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts.

We have successfully developed both spontaneous and inductive cardiomyocyte differentiation of iPS cells reprogrammed from human foreskin fibroblasts. The reprogrammed iPS cells morphologically resemble human cardiomyocytes which can beat. RT-PCR and immunostaining show that cardiac markers are expressed that are comparable to the differentiation pattern of authentic human embryonic stem cells, indicating the existence of both immature and mature differentiated cardiomyocytes. 5-Azacytidine greatly enhanced the efficiency of cardiomyocyte differentiation, whereas dimethylsulfoxide had no effect. Low serum and bone morphogenetic protein-2 marginally improved differentiation efficiency. iPS cell-derived cardiomyocytes changed their beat frequency in response to cardiac drugs, which included ion channel blockers and alpha/beta adrenergic stimulators. Derived cardiomyocytes look promising as an in vitro system for potential drug screen and/or toxicity, making this system closer to practical use in the near future.

Comparison of venous thromboembolism risk stratification models in a high risk otolaryngology patient cohort.

Our objective was to compare the venous thromboembolism outcomes in two of the most commonly utilised venous thromboembolism assessment tools, the Caprini system and the University of Michigan system, in a high risk head and neck surgery population. Currently, there is a lack of data reporting the validation of well known scoring systems in this patient population. Established risk factors for venous thromboembolism were included in the data collection process. We retrospectively evaluated all patients with the Caprini Risk Assessment and the University of Michigan Health System (UMHS) Scores. Out of all the risk factors, only length of surgery was found to be associated with venous thromboembolism. The mean Caprini scores in those with and without venous thromboembolism were 8.00 ± 3.00 and 6.86 ± 1.45, respectively. The mean UMHS scores in those with and without venous thromboembolism were 6.85 ± 1.28 and 6.54 ± 1.20, respectively. Both scoring systems were not found to be associated with venous thromboembolism.