Epstein-Barr virus directed screening for nasopharyngeal carcinoma in individuals with positive family history: A systematic review.

OBJECTIVES: Evidence to support Epstein-Barr virus (EBV)-directed population nasopharyngeal carcinoma (NPC) screening has been growing. Familial aggregation is a well-recognized phenomenon in endemic regions. This systematic review summarizes the role of EBV-directed screening in individuals with a positive family history (FH+) of NPC. METHODS: We searched four electronic databases from their inception to October 2021. We included studies on individuals with FH+ of NPC who had undergone EBV-directed investigations, with no restriction in the testing methods or analytic techniques. The primary and secondary outcomes were EBV positivity rates and NPC incidence rates, respectively. Meta-analyses were performed using the random-effect model. RESULTS: Ten cross-sectional studies (n = 7436) and three cohort studies (n = 4306) were included. The pooled relative risk (RR) of EBV positivity between individuals with and without FH+ of NPC were 2.79 (95 % CI 1.37-5.68, p = 0.005) for viral capsid antigen (VCA) IgA, 3.09 (95 % CI 0.65-14.83, p = 0.16) for Epstein-Barr nuclear antigen (EBNA1) IgA, and 1.76 (95 % CI 1.04-2.96, p = 0.03) for combined EBNA1/VCA IgA. In the three cohort studies, the NPC incidence rates ranged from 90.2 to 266 per 100 000 person-years with high proportions of early-stage diseases. FH+ individuals who were EBV-positive had a 2.5 to 30.7-fold risk of NPC development compared to their EBV-negative counterparts. CONCLUSION: Family members of NPC patients had significantly higher EBV positivity rates than the general population. FH+ individuals who are EBV-positive had high risks of developing NPC. Familial screening using EBV serology may facilitate early NPC detection in endemic areas.

Application of Artificial Intelligence for Nasopharyngeal Carcinoma Management - A Systematic Review.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC. METHODS: The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles. RESULTS: A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented. CONCLUSION: There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon.

The Relationships Between Radiation Dosage and Long-term Swallowing Kinematics and Timing in Nasopharyngeal Carcinoma Survivors.

This study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.

Improving Outcome of Superior Mediastinal Lymph Node Dissection During Esophagectomy: A Novel Approach Combining Continuous and Intermittent Recurrent Laryngeal Nerve Monitoring.

OBJECTIVE: This study aimed at demonstrating the effects and learning curve of utilizing combined intermittent and continuous recurrent laryngeal nerve (RLN) monitoring for lymphadenectomy during esophagectomy. BACKGROUND: RLN lymphadenectomy is oncologically important but is technically demanding. Vocal cord (VC) palsy as a result from RLN injury, carries significant morbidities. METHODS: This is a retrospective study of consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent transthoracic esophagectomy from 2010 to 2020. Combined nerve monitoring (CNM) included: CNM which involved a periodic stimulating left vagal electrode and intermittent nerve monitoring which utilized a stimulating probe to identify the RLNs. The integrity of the RLNs was assessed both intermittently and continuously. This technique was introduced in 2014. Patients were divided into "before CNM" and "CNM" groups. The primary outcome was the difference in number of RLN lymph nodes harvested and VC palsy rate. Learning curves were demonstrated by cumulative sum (CUSUM) analysis. RESULTS: Two hundred and fifty-five patients were included with 157 patients in "CNM" group. The mean number of RLN lymph nodes harvested was significantly higher (4.31 vs 0.45, P < 0.0001) for the "CNM" group. VC palsy rates were significantly lower (17.8% vs 32.7%, P = 0.007). There was an initial increase in VC palsy rate, peaked at around 46 cases. The increase in lymph nodes harvested above the mean plateaued at around 96 cases. CONCLUSIONS: CNM helped improve bilateral RLN lymphadenectomy. Lymph node harvesting was increased with reduction of VC palsy after a learning curve.

Contemporary management of the neck in nasopharyngeal carcinoma.

Up to 85% of the patients with nasopharyngeal carcinoma present with regional nodal metastasis. Although excellent nodal control is achieved with radiotherapy, a thorough understanding of the current TNM staging criteria and pattern of nodal spread is essential to optimize target delineation and minimize unnecessary irradiation to adjacent normal tissue. Selective nodal irradiation with sparing of the lower neck and submandibular region according to individual nodal risk is now emerging as the preferred treatment option. There has also been continual refinement in staging classification by incorporating relevant adverse nodal features. As for the uncommon occurrence of recurrent nodal metastasis after radiotherapy, surgery remains the standard of care.

There is no routine head and neck exam during the COVID-19 pandemic.

Head and neck examinations are commonly performed by all physicians. In the era of the COVID-19 pandemic caused by the SARS-CoV-2 virus, which has a high viral load in the upper airways, these examinations and procedures of the upper aerodigestive tract must be approached with caution. Based on experience and evidence from SARS-CoV-1 and early experience with SARS-CoV-2, we provide our perspective and guidance on mitigating transmission risk during head and neck examination, upper airway endoscopy, and head and neck mucosal surgery including tracheostomy.

Managing head and neck cancer patients with tracheostomy or laryngectomy during the COVID-19 pandemic.

Head and neck cancer patients with tracheostomies and laryngectomies, as well as their healthcare providers, face unique challenges in the context of the current COVID-19 pandemic. This document consolidates best available evidence to date and presents recommendations to minimize the risks of aerosolization and SARS-CoV-2 exposures in both the inpatient and outpatient settings. The cornerstones of these recommendations include the use of closed-circuit ventilation whenever possible, cuffed tracheostomy tubes, judicious use of heat moisture exchange units, appropriate personal protective equipment for providers and patients, meticulous hand hygiene, and minimal manipulation of tracheostomy tubes.

Augmented reality for image guidance in transoral robotic surgery.

With the advent of precision surgery, there have been attempts to integrate imaging with robotic systems to guide sound oncologic surgical resections while preserving critical structures. In the confined space of transoral robotic surgery (TORS), this offers great potential given the proximity of structures. In this cadaveric experiment, we describe the use of a 3D virtual model displayed in the surgeon's console with the surgical field in view, to facilitate image-guided surgery at the oropharynx where there is significant soft tissue deformation. We also utilized the 3D model that was registered to the maxillary dentition, allowing for real-time image overlay of the internal carotid artery system. This allowed for real-time visualization of the internal carotid artery system that was qualitatively accurate on cadaveric dissection. Overall, this shows that virtual models and image overlays can be useful in image-guided surgery while approaching different sites in head and neck surgery with TORS.

A Next-Generation Single-Port Robotic Surgical System for Transoral Robotic Surgery: Results From Prospective Nonrandomized Clinical Trials.

IMPORTANCE: Transoral endoscopic head and neck surgery now plays an important role in the multidisciplinary management of oropharyngeal carcinoma. Previous generations of robotic surgical systems used a multiport system with a rigid stereo-endoscope and 2 wristed instruments that facilitated transoral robotic surgery. OBJECTIVE: To evaluate a new single-port robotic surgical system in head and neck surgery prospectively through concurrent nonrandomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Two prospective clinical trials were conducted from December 16, 2016, to December 26, 2017, to assess the safety, feasibility, and performance of a flexible single-port robotic surgical system in 4 institutions, including 3 in the United States and 1 in Hong Kong. A total of 47 patients with tumors of the oropharynx were enrolled and underwent surgery. All patients were classified as having American Society of Anesthesiologists class I to III status and Eastern Cooperative Oncology Group status 0 to 1. An initial cohort of 7 patients underwent staging and endoscopic procedures for benign disease. The remaining 40 patients all had malignant tumors of the oropharynx. MAIN OUTCOMES AND MEASURES: Safety was measured by the incidence of device-related serious adverse events. Feasibility and performance were measured by the conversion rate from the use of the single-port robotic surgical system to either open surgery or the use of any other transoral technology required to complete the planned procedure. Secondary end points of swallowing function and surgical margins were also measured. RESULTS: All 47 patients (8 women and 39 men; mean [SD] age, 61 [8] years) safely underwent transoral resection with the single-port robotic surgical system without conversion to open surgery, laser surgery, or multiport robotic surgery. There were no intraoperative complications or device-related serious adverse events. Mean (SD) estimated intraoperative blood loss per procedure was 15.4 (23.9) mL; no patients received a transfusion. Two patients underwent a planned tracheotomy owing to medical comorbidity (previous chemoradiotherapy; obesity and severe sleep apnea). Two patients (4%) had grade III or IV postoperative hemorrhage, requiring a return to the operating room; however, both patients had medical comorbidities requiring the use of antithrombotic medication. The incidence of positive margins for patients with oropharyngeal malignancy was 3% (1 of 40). Within 30 days, 45 patients (96%) were eating by mouth and without the need for a percutaneous endoscopic gastrostomy tube. CONCLUSIONS AND RELEVANCE: This study describes the results of phase 2 clinical testing of a next-generation, robotic surgical system using a single-port architecture. The use of the device appears to be feasible, safe, and effective for transoral robotic surgery of oropharyngeal tumors. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03010813 and NCT03049280.

Continuous intraoperative vagus nerve stimulation for monitoring of recurrent laryngeal nerve during minimally invasive esophagectomy.

For squamous cell carcinoma of the esophagus, extended mediastinal lymphadenectomy especially around the bilateral recurrent laryngeal nerves (RLN) is associated with high risk of nerve injury. This does not only result in hoarseness of voice, increase the chance of pulmonary complications, but would also affect the quality of life of patients in the long term. Methods to improve safety of lymphadenectomy are desirable. Continuous intraoperative nerve monitoring (CIONM) based on a system using vagus nerve stimulation was tested. In thyroidectomy, this system has been shown to be useful. Our patient cohort was unselected, with the intent to perform bilateral RLN dissection undergoing video-assisted thoracoscopic (VATS) esophagectomy. Intermittent nerve stimulation for mapping and CIONM were employed to monitor left RLN nodal dissection, while only intermittent stimulation was used for the right RLN. CIONM has the potential to aid RLN dissection. The learning curves for the placement technique of CIONM, the threshold level and the interpretation of myographic amplitude and latency have been overcome. With the availability of nerve mapping and CIONM, more aggressive and thorough nodal dissection may be possible with less fear of RLN injury.

Evaluating the cost-effectiveness of laryngeal examination after elective total thyroidectomy.

BACKGROUND: Although routine laryngeal examination (RLE) after thyroidectomy may cost more than selective laryngeal examination (SLE), it permits earlier detection and treatment of vocal cord palsy (VCP) and so may be cost-saving in the longer term. We compared the 2-year cost-effectiveness between RLE and SLE with RLE performed at 2 weeks (SLE-2w), 1 month (SLE-1m), and 3 months (SLE-3m) after thyroidectomy in the institution's perspective. METHODS: Our case definition was a hypothetical 50-year-old woman who underwent an elective total thyroidectomy for a benign multinodular goiter. A decision-analytic model was constructed to compare the estimated cost-effectiveness between RLE, SLE-2w, SLE-1m, and SLE-3m after a 2-year period. Outcome probabilities, utilities, and costs were estimated from the literature. The threshold for cost-effectiveness was set at US$50,000/quality-adjusted life-year. Sensitivity and threshold analyses were used to examine model uncertainty. RESULTS: RLE was not cost-effective because its incremental cost-effectiveness ratio to SLE-2w, SLE-1m, and SLE-3m were US$302,755, US$227,883 and US$247,105, respectively. RLE was only cost-effective when the temporary VCP rate increased >42.7 % or when the cost of RLE equaled zero. Similarly, SLE-2w was only cost-effective to SLE-3m when dysphonia for temporary VCP at 3 months increased >39.13 %, dysphonia for permanent VCP at 3 months increased >50.29 %, or dysphonia without VCP at 3 months increased >42.69 %. However, none of these scenarios appeared clinically likely. CONCLUSIONS: In the institution's perspective, RLE was not cost-effective against the other three SLE strategies. Regarding to the optimal timing of SLE, SLE-3m appears to be a reasonable and acceptable strategy because of its relative low overall cost.

Review of salivary gland neoplasms.

Salivary gland tumours most often present as painless enlarging masses. Most are located in the parotid glands and most are benign. The principal hurdle in their management lies in the difficulty in distinguishing benign from malignant tumours. Investigations such as fine needle aspiration cytology and MRI scans provide some useful information, but most cases will require surgical excision as a means of coming to a definitive diagnosis. Benign tumours and early low-grade malignancies can be adequately treated with surgery alone, while more advanced and high-grade tumours with regional lymph node metastasis will require postoperative radiotherapy. The role of chemotherapy remains largely palliative. This paper highlights some of the more important aspects in the management of salivary gland tumours.

HER2 expression predicts improved survival in patients with cervical node-positive head and neck squamous cell carcinoma.

OBJECTIVE: To investigate the prognostic value of HER2 and p63 expression in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A case review of 186 HNSCCs from the oral tongue, palate, maxillary sinus, floor of mouth, oropharynx, hypopharynx, and larynx. SUBJECTS AND METHODS: All primary tumor specimens were evaluated by immunohistochemistry for HER2 and p63 expressions, which were correlated with clinical parameters including age, sex, grade, lymph node metastases, stage, and survival. RESULTS: One hundred forty-one patients had stage III-IV disease and 109 had lymph node metastases. For all cases, T and N stages were significant prognostic predictors for both overall and disease-free survivals. In the node-positive subgroup, T stage and HER2 expression were significant prognostic predictors for both overall and disease-free survivals. CONCLUSION: HER2 may be associated with longer survival in node-positive patients with HNSCC.

Nasopharyngectomy and surgical margin status: a survival analysis.

OBJECTIVE: To explore whether the margin status at surgical salvage nasopharyngectomy for local residual or recurrent nasopharyngeal carcinoma affects patient survival. DESIGN: Retrospective case series review. SETTING: Academic tertiary referral center. PATIENTS: Seventy-nine consecutive patients with operable local residual or recurrent nasopharyngeal carcinoma after failure of primary treatment with radiotherapy with or without chemotherapy underwent surgical salvage nasopharyngectomy with curative intent between November 28, 1987, and November 17, 2003. Sixty-one patients were men and 18 were women. Their mean age was 48 years (age range, 26-70 years). INTERVENTION: Surgical salvage nasopharyngectomy. MAIN OUTCOME MEASURES: The status of the closest margin at surgery was assessed as clear, close, or positive. Survival time was measured from the date of surgery to the date of the last follow-up, to the date of an event occurrence, or to the date of death. The Kaplan-Meier method was used to estimate the probability of local progression-free survival and overall survival at 5 years. Differences in survival rates between surgical margin statuses were assessed using the log-rank test. RESULTS: Five-year overall survival for patients with clear margins was 77%, for patients with close margins was 46% (P = .05), and for patients with positive margins was 23% (P < .001). CONCLUSION: Clear surgical margins at the time of surgical salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma positively affect patient survival.

Evaluation of Epstein-Barr virus antigen-based immunoassays for serological diagnosis of nasopharyngeal carcinoma.

BACKGROUND: Immunofluorescence (IF) assays based on Epstein-Barr virus (EBV)-encoded antigens have traditionally been the preferred approach for serological screening of nasopharyngeal carcinoma (NPC). OBJECTIVES: To compare the performance of two new commercial assays (indicated by COMM) using, respectively, the IF and enzyme-linked immunosorbent assay (ELISA) formats with an in-house IF assay (IFA). STUDY DESIGN: Sera from 163 patients with histologically confirmed NPC, and 98 healthy controls were tested with each of these assays and their results compared. RESULTS: The sensitivity, specificity, positive and negative predictive values, respectively, for the COMM VCA IgA ELISA were 92.6%, 94.9%, 96.8%, 88.6%; for the COMM VCA IgA IFA were 96.9%, 41.8%, 73.5%, 89.1%; for the in-house VCA IgA IFA were 98.2%, 72.4%, 85.6%, 95.9%; for the COMM EA IgA ELISA were 46.6%, 100%, 100%, 53.0%; for the COMM EA IgA IFA were 77.3%, 100%, 100%, 72.6%; and for the in-house EA IgA IFA were 77.9%, 99.0%, 99.2%, 72.9%. CONCLUSIONS: The receiver operating characteristic curves comparison showed a marginal superior accuracy for the COMM VCA IgA ELISA, suggesting this to be used as a high-throughput serological screening assay, with the more specific COMM EA IgA IFA as a follow-up confirmatory assay in this NPC-endemic area.

Strong immunohistochemical expression of vascular endothelial growth factor predicts overall survival in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has high morbidity and mortality, and its relationship with tumor angiogenesis as measured by microvessel density (MVD) or vascular endothelial growth factor (VEGF) expression has shown mixed results, with some, but not others, reporting correlation with outcome. METHODS: A retrospective study of 186 patients with HNSCC was performed. Patients were evaluated for MVD and VEGF and to correlate the levels with clinical parameters, including age at diagnosis, sex, site of tumor, stage, survival (disease free and overall), pathological tumor grade, and the presence of lymph node metastases. RESULTS: The 186 cancers included the following sites: oral tongue (n = 69), palate (n = 9), maxillary sinus (n = 8), floor of mouth (n = 13), oropharynx (n = 27), hypopharynx (n = 26) and larynx (n = 34). Over three-quarters of patients had advanced tumor (stage III/IV) and 58.6% had lymph node metastases. MVD and VEGF were assessed in 166 and 164 cases, respectively, but these were not correlated with site and grade. The 3-year overall and disease-free survival rates were 55.4% and 53.2%, respectively. Both univariate and multivariate survival analysis showed that advanced T stage, nodal metastasis, and strong VEGF intensity were independent adverse predictors for overall and disease-free survival. In stage IV disease, strong VEGF immunoreactivity was found to be the single adverse factor affecting the overall survival and a contributory factor for disease-free survival. CONCLUSIONS: VEGF immunoreactivity is a strong predictor of adverse outcome, particularly in locoregionally advanced disease.

Treatment of profuse epistaxis in patients irradiated for nasopharyngeal carcinoma.

BACKGROUND: Profuse epistaxis in patients with nasopharyngeal carcinoma (NPC) previously treated with radiotherapy (RT) can be life threatening. Surgical means to prevent rebleeding may at times be difficult and unsuccessful. We aim to investigate the characteristics of this group of patients and our experience of endovascular embolization technique in the management of epistaxis in this group of patients. METHODS: A retrospective review of all nasopharyngeal carcinoma patients presented with profuse epistaxis during follow up after radiotherapy was carried out in a regional neurosurgical centre in Hong Kong. Seventeen patients were included for the analysis within the recent 6-year period. The age of patients was 55.5 +/- 8.358 years (mean +/- standard deviation). The sex ratio was 5:1 (M : F). Diagnostic catheter angiography was carried out in all 17 patients. Endovascular embolization was carried out in 11 patients with the joint decision of the otolaryngologist and neurointerventionist in charge . RESULTS: Four patients underwent main trunk occlusion for internal carotid pseudoaneurysm. Seven patients underwent embolization of branches of external carotid artery. One patient required another session of external carotid artery embolization 1 month later. There was one inpatient death because of pneumonia and hepatic encephalopathy. With our protocol, there were only two patients (11.7%) with delayed rebleed at 2 and 5 months, respectively. Both patients had advanced diseases and died. CONCLUSION: In irradiated patients with nasopharyngeal carcinoma presenting with profuse epistaxis, angiography had a high yield of pseudoaneurysm or hypervascularity and these lesions could be safely managed through endovascular embolization.

Laryngeal carcinoma: five-year survival and patterns of failure in 202 consecutive patients treated with primary or post-operative radiotherapy in Hong Kong.

OBJECTIVES: We aimed to conduct a retrospective analysis of patients treated with radiotherapy for laryngeal carcinoma at a single institution. METHODS: We analysed data from 202 consecutive patients treated with primary or post-operative radiotherapy for laryngeal carcinoma over a 10-year period. RESULTS: Sixty-nine patients had a T1, 65 a T2, 39 a T3 and 29 a T4 lesion. Forty-one patients were node-positive. The clinical stage was I in 67 patients, II in 53, III in 36 and IV in 46. Primary radiotherapy was given to 152 patients. The median follow up was 60 months. The five-year overall local control rate was 86 per cent, the ultimate local control rate was 93 per cent, the five-year regional control rate was 96 per cent, the five-year relapse-free survival rate was 82 per cent and the five-year overall survival rate was 69 per cent. CONCLUSIONS: Patients with laryngeal carcinoma treated with primary or post-operative radiotherapy had a five-year overall survival rate of 69 per cent.