Assessment of endpoint definitions in recurrent and metastatic mucosal head and neck squamous cell carcinoma trials: Head and Neck Cancer International Group consensus recommendations.

Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.

Long-term results of robotic-assisted nasopharyngectomy for recurrent nasopharyngeal carcinoma.

BACKGROUND: We have previously reported our early experience in robotic-assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic-assisted nasopharyngectomy. METHODS: Prospective series of patients who underwent robotic-assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019. RESULTS: Thirty-one patients underwent robotic-assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55 years (29-85). Twenty-five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227 min and median blood loss was 200 ml. The median follow-up period for all patients were 38 months. Four patients had local recurrence. Five-year local control rate, overall survival, and disease-free survival are 85.1%, 55.7%, and 69.1%, respectively. CONCLUSION: Robotic-assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery.

Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract.

BACKGROUND: The Omicron BA.2 sublineage has replaced BA.1 worldwide and has comparable levels of immune evasion to BA.1. These observations suggest that the increased transmissibility of BA.2 cannot be explained by the antibody evasion. METHODS: Here, we characterized the replication competence and respiratory tissue tropism of three Omicron variants (BA.1, BA.1.1, BA.2), and compared these with the wild-type virus and Delta variant, in human nasal, bronchial and lung tissues cultured ex vivo. FINDINGS: BA.2 replicated more efficiently in nasal and bronchial tissues at 33°C than wild-type, Delta and BA.1. Both BA.2 and BA.1 had higher replication competence than wild-type and Delta viruses in bronchial tissues at 37°C. BA.1, BA.1.1 and BA.2 replicated at a lower level in lung parenchymal tissues compared to wild-type and Delta viruses. INTERPRETATION: Higher replication competence of Omicron BA.2 in the human upper airway at 33°C than BA.1 may be one of the reasons to explain the current advantage of BA.2 over BA.1. A lower replication level of the tested Omicron variants in human lung tissues is in line with the clinical manifestations of decreased disease severity of patients infected with the Omicron strains compared with other ancestral strains. FUNDING: This work was supported by US National Institute of Allergy and Infectious Diseases and the Theme-Based Research Scheme under University Grants Committee of Hong Kong Special Administrative Region, China.

Surgical repair of a large intrathoracic meningocele associated with neurofibromatosis type 1 after failed cystoperitoneal shunts: illustrative case.

BACKGROUND: Surgical treatment of intrathoracic meningoceles, commonly associated with neurofibromatosis type 1 (NF1), aims to reduce sac size for symptomatic relief. The procedures can be divided into cerebrospinal fluid diversion and definitive repair. The authors describe the management of an intrathoracic meningocele in a 56-year-old female with preexisting NF1. OBSERVATIONS: The patient presented with progressive dyspnea. Magnetic resonance imaging revealed a left hemithoracic meningocele arising from the thecal sac at C7-T2. Two attempts at diversion by cystoperitoneal shunts resulted in recurrence. For definitive repair, T2-3 costotransversectomy was performed, and intradural closure of the meningocele opening was performed utilizing spinal dura and autologous fascia lata graft. Trapezius muscle regional flap was turned for reinforcement. Persistent leak warranted reoperation 7 days later. A transthoracic approach was undertaken using video-assisted thoracoscopic resection of the sac at aortic arch level, with reinforcement by latissimus dorsi flap and synthetic materials. Mechanical pleurodesis was performed. Intradural repair of the meningocele opening was revised. LESSONS: Inherent dural abnormality makes repair difficult for meningoceles associated with NF1. A combined intradural and thoracoscopic approach with regional muscle flap and synthetic material reinforcement is a unique method for definitive treatment. Some essential points of perioperative management are highlighted.

Transcervical Transtracheal Resection of Cervical Esophageal Smooth Muscle Tumor.

Cervical esophageal smooth muscle tumors are traditionally resected via lateral transcervical with or without video-assisted thoracoscopic approaches. Exposure is frequently limited, however, with risks of recurrent laryngeal nerve and posterior tracheal wall injury and jeopardization of cervical tracheal and cervical esophageal blood supply. We herein describe an anterior transcervical transtracheal approach to counter some of the aforementioned problems and avoid morbidities associated with thoracoscopic surgery when resecting smooth muscle tumors arising from the cervical esophagus.

Swallowing disorders following free jejunal flap reconstruction of circumferential pharyngeal defect: Does Botox help?

OBJECTIVES: Free jejunal flap for circumferential pharyngeal reconstruction is associated with late-onset dysphagia, regurgitation and prolonged transit time. This study aims to assess the feasibility and efficacy of Botulinum toxin A (Botox) in alleviating such swallowing dysfunction. MATERIALS AND METHODS: Twenty-six consecutive patients underwent free jejunal flap for circumferential pharyngeal reconstruction between January 2012 and December 2018. Outcomes were compared at 6, 12 and 24 months. RESULTS: In the non-Botox group (n = 13), video-fluoroscopic and manometry studies demonstrated asynchronous contractions and retrograde propulsion. All patients complained of nasal regurgitation on thin fluids at 6, 12 and 24 months. Bolus residue accumulation along jejunal mucosal folds resulted in prolonged transit time. In the Botox group (n = 13), amplitude of asynchronous contractions were lower: 25.4 mmHg vs. 52.1 mmHg (p = 0.037) for thin fluids at 12 months. Three patients complained of nasal regurgitation on thin fluids at 6 months. All 3 were asymptomatic at 12 months. Transit time was shortened overall. Functional Oral Intake Scale was higher. MD Anderson Dysphagia Inventory global (72.5% vs 45.7%, p = 0.003) and functional (62.0% vs 40.6%, p = 0.012) subscales were significantly improved at 24 months. CONCLUSION: Botox safely and effectively alleviates swallowing dysfunction associated with free jejunal flap for circumferential pharyngeal reconstruction.

Esophagogastric Preservation in the Surgical Management of Proximal Esophageal Cancer.

BACKGROUND: Definitive chemoradiotherapy is offered for most patients with isolated cervical esophageal tumor. Surgery is reserved for locally advanced diseases and salvage for failed chemoradiotherapy. Traditionally, surgery comprises total pharyngolaryngeal esophagectomy and gastric pull-up, which is associated with high morbidity and mortality rates. We hereby propose pharyngo-laryngo-cervico-esophagectomy by a transcervical approach, allowing preservation of the esophagus and stomach below, reducing operative morbidity and mortality. METHODS: A retrospective review of 31 patients who underwent curative pharyngo-laryngo-cervico-esophagectomy for isolated cervical esophageal tumor at the Department of Surgery, The University of Hong Kong, Queen Mary Hospital, between January 1, 2005, and June 30, 2018, was performed. RESULTS: There were 26 male and 5 female patients. Median age was 64.8 years. Seventeen patients underwent definitive surgery. Fourteen patients underwent salvage surgery for failed chemoradiotherapy. Most patients presented with stage III and IV diseases (90.3%). Median length of pharyngoesophageal defect was 14.0 cm (range, 8.0-21.0 cm). Free jejunal flap was used for pharyngoesophageal reconstruction in 77.4%. Eight complications developed in 7 patients (22.6%). There was no in-hospital mortality. Clear radial and longitudinal resection margins were achieved in 96.8%. Median follow-up was 21.5 months. Locoregional recurrence rate was 32.3%. Nine patients died of disease progression (29.0%). Seven died of other causes (22.6%). Median survival was 21.5 months. Overall 2-year survival rate was 36.7%. CONCLUSIONS: Transcervical pharyngo-laryngo-cervico-esophagectomy should be considered in patients with isolated cervical esophageal tumors. Pharyngo-laryngo-cervico-esophagectomy allows adequate tumor resection while preserving the esophagus and stomach below. Operative morbidity and mortality outcomes were improved without compromising oncologic control.

Salvage surgery for recurrent carcinoma of the cervical esophagus postesophagectomy.

BACKGROUND: Management of cervical esophageal tumor postesophagectomy is mainly palliative because of inadequate exposure of tumor in the cervicothoracic region. In this study, we propose a means of cure for these patients. METHODS: Between January 2003 and June 2013, 6 patients underwent curative pharyngolaryngectomy and completion cervical esophagectomy via manubrial resection. Operative outcomes were analyzed and compared with a historical cohort who received palliative therapy. RESULTS: One patient required prolonged hospital stay for pneumonia, resulting in a median hospital stay of 30 days (range, 21-55 days). All patients resumed oral feeding at a mean of 15.2 days (range, 14-19 days). Tracheostoma stenosis was noted in 2 patients. One patient developed nodal recurrence, another with distant metastasis, resulting in a median disease-free survival of 13 months (range, 4-20 months). Median overall survival was significantly longer than the cohort group (19.0 vs 3.0 months; p = .013). CONCLUSION: Salvage surgery in patients with carcinoma of the cervical esophagus postesophagectomy is feasible with significantly prolonged survival.