The role of Epstein-Barr virus-encoded microRNA BART7 status of resection margins in the prediction of local recurrence after salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma.

BACKGROUND: Local recurrence is the major cause of treatment failure in patients who undergo surgical salvage of recurrent nasopharyngeal carcinoma (NPC) after radiotherapy. The authors investigated the role of Epstein-Barr virus (EBV)-encoded Bam HI-A rightward transcript 7 microRNA (BART7) status in resection margins in the identification of a subgroup of patients who may benefit from adjuvant reradiation after surgery. METHODS: One hundred two consecutive patients who had histologically clear resection margins after undergoing nasopharyngectomy for recurrent NPC were studied. The status of EBV microRNA BART7 in resection margins was investigated and correlated with the pattern of subsequent disease recurrence. RESULTS: After a median follow-up of 64 months, 20 patients (19.6%) developed local recurrence after surgery despite histologically uninvolved margins. The risk of local recurrence in patients with histologically close (<5 mm) and clear (≥5 mm) margins was 31.6% and 12.5%, respectively. In patients with clear histologic margins, those with margins that were positive for EBV microRNA BART7 has a significantly higher chance of developing local tumor recurrence (P = .016) than those with negative molecular margins. The difference was not significant when the histologic clearance at the resection margins was <5 mm. CONCLUSIONS: Tissue EBV microRNA BART7 is useful for identifying a subgroup of patients with histologically clear margins who are at increased risk of subsequent local tumor recurrence. Postoperative adjuvant treatment is warranted for these patients.

Long non-coding RNA expression profiles predict clinical phenotypes in glioma.

Glioma is the commonest form of primary brain tumor in adults with varying malignancy grades and histological subtypes. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been shown to play important roles in cancer development. To discover novel tumor-related lncRNAs and determine their associations with glioma subtypes, we first applied a lncRNA classification pipeline to identify 1970 lncRNAs that were represented on Affymetrix HG-U133 Plus 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published glioma gene expression profiles of 268 clinical specimens, and identified sets of lncRNAs that were unique to different histological subtypes (astrocytic versus oligodendroglial tumors) and malignancy grades. These lncRNAs signatures were then subject to validation in another non-overlapping, independent data set that contained 157 glioma samples. This is the first reported study that correlates lncRNA expression profiles with malignancy grade and histological differentiation in human gliomas. Our findings indicate the potential roles of lncRNAs in the biogenesis, development and differentiation of gliomas, and provide an important platform for future studies.

Novel approach to reduce SARS-CoV-2 transmission during trans-oral robotic surgery.

This study describes a novel approach in the reduction of SARS-CoV-2 transmission during trans-oral robotic surgery (TORS). Eight patients underwent TORS between 01 February 2020 and 07 September 2020. A sterile plastic sheet draped over sterile supports with water-tight seal around each cannula was used to create a sterile working space within which the robotic arms could freely move during operation. This set-up acts as an additional physical barrier against droplet and aerosol transmission. Operative diagnosis; droplet count and distribution on plastic sheet and face shields of console and assistant surgeons, and scrub nurse were documented. TORS tumour excision was performed for patients with suspected tonsillar tumour (n = 3) and tongue base tumour (n = 2). TORS tonsillectomy and tongue base mucosectomy was performed for cervical nodal metastatic carcinoma of unknown origin (n = 3). Droplet contamination was noted on all plastic drapes (n = 8). Droplet contamination was most severe over the central surface at 97.2% (91.7-100.0%), with the highest droplet count along the centre-most column where it overlies the site of operation in the oral cavity 33.3% (n = 31). Droplet count decreased towards the periphery. Contamination rate was 2.8% (0.0-8.3%) over the right lateral surface. There was no droplet contamination over the vertex and left lateral surface of plastic drapes. No droplet contamination was noted on face shields of all parties. The use of sterile plastic drapes with water-tight seal around each robotic cannula can help reduce viral transmission to healthcare providers during TORS.

Recommendations for surgical management of recurrent nasopharyngeal carcinoma during COVID-19 pandemic.

Nasopharyngeal carcinoma is endemic in southern parts of China including Hong Kong. Primary treatment entails radiotherapy ± chemotherapy depending on disease stage at presentation. Surgery is offered as a means of salvage for persistent and recurrent disease. Comprehensive preoperative work-up, careful patient selection, attention to details perioperation and multidisciplinary approach is essential in ensuring optimal outcomes after salvage surgery for recurrent nasopharyngeal carcinoma patients. Since the COVID-19 outbreak, we are faced with unprecedented challenges with priorities of care and resources being shifted to combat the virus. These include patient selection and timing of treatment, while preventing disease transmission to heath care providers. Practices and recommendations made in this document are intended to support safe clinical practice and efficient use of resources during this challenging time.

Conservation of personal protective equipment for head and neck cancer surgery during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has led to a global shortage of personal protective equipment (PPE). This study aims to stratify face shield needs when performing head and neck cancer surgery. METHODS: Fifteen patients underwent surgery between March 1, 2020 and April 9, 2020. Operative diagnosis and procedure; droplet count and distribution on face shields were documented. RESULTS: Forty-five surgical procedures were performed for neck nodal metastatic carcinoma of unknown origin (n = 3); carcinoma of tonsil (n = 2), tongue (n = 2), nasopharynx (n = 3), maxilla (n = 1), and laryngopharynx (n = 4). Droplet contamination was 57.8%, 59.5%, 8.0%, and 0% for operating, first and second assistant surgeons, and scrub nurse respectively. Droplet count was highest and most widespread during osteotomies. No droplet splash was noted for transoral robotic surgery. CONCLUSION: Face shield is not a mandatory adjunctive PPE for all head and neck surgical procedures and health care providers. Judicious use helps to conserve resources during such difficult times.

Tracheostomy during COVID-19 pandemic-Novel approach.

BACKGROUND: This study describes a novel approach in reducing SARS-CoV-2 transmission during tracheostomy. METHODS: Five patients underwent tracheostomy between April 1, 2020 and April 17, 2020. A clear and sterile plastic drape was used as an additional physical barrier against droplets and aerosols. Operative diagnosis; droplet count and distribution on plastic sheet and face shields were documented. RESULTS: Tracheostomy was performed for patients with carcinoma of tonsil (n = 2) and nasopharynx (n = 1), and aspiration pneumonia (n = 2). Droplet contamination was noted on all plastic sheets (n = 5). Droplet contamination was most severe over the central surface at 91.5% (86.7%-100.0%) followed by the left and right lateral surfaces at 5.2% (6.7%-10.0%) and 3.3% (6.7%-10.0%), respectively. No droplet contamination was noted on all face shields. CONCLUSION: Plastic drapes can help reduce viral transmission to health care providers during tracheostomy. Face shields may be spared which in turn helps to conserve resources during the novel coronavirus disease 2019 pandemic.

Surgical salvage of recurrent T3 nasopharyngeal carcinoma: Prognostic significance of clivus, maxillary, temporal and sphenoid bone invasion.

BACKGROUND: To study the efficacy of surgery for recurrent T3 nasopharyngeal carcinoma (NPC) and to determine the prognostic significance of various skull base bone invasion. METHOD: Retrospective view of the surgical outcome for recurrent T3 NPC. Kaplan Meier and log rank tests were used to determine the 5-year overall and disease specific survival. Multivariate analysis was used to identify significant independent prognostic factors that affect the surgical outcome. RESULTS: Between 1990 and 2017, 208 patients with recurrent T3 NPC were recruited. Salvage surgery was performed via the endoscopic endonasal approach (n = 22, 10.6%), endoscopic transpterygoid approach (n = 63, 30.3%) and the maxillary swing approach (n = 123, 59.1%). Thirty-eight (18.3%) patients required vascular bypass. The skull base bone involved by the tumours included: maxillary sinus (n = 13), clivus (n = 36), pterygoid process (n = 61), sphenoid sinus (n = 30), petrous part of the temporal bone (n = 42) and a combination of the above (n = 26). The mean follow-up duration was 41.7 months. Multivariate analysis identified tumours involving with both cortexes of the clivus and the lateral wall of the sphenoid sinus, as well as positive bone resection margins as the significant independent prognostic factors for surgical outcome. CONCLUSION: Outcome of surgical salvage is significantly worse for tumours that involve multiple bones at the skull base, particularly when both cortexes of the clivus and the lateral wall of the sphenoid sinus are invaded. Indication of aggressive surgery in such circumstances is controversial.

Real time indocyanin green near infrared lymphangiography for the reduction of drainage volume after neck dissection.

BACKGROUND: To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of drainage after neck dissection. METHODS: Patients with oral cavity squamous cell carcinoma were randomized into Group A (study group) and Group B (control). In the study group, upon the completion of neck dissection, a total of 2.5 mg of ICG was injected submucosally at the four quadrants around the tumour. Another 2.5 mg of ICG was injected subdermally in the groin bilaterally. The neck was screened using Near Infrared fluorescence. The presence of lymphatic leakage was noted and plicated with silk stitches. The total drainage volume of post-operative day 1, day 2 and the total accumulated volume until drain removal was measured. RESULTS: Twenty-two patients (Group A, n = 12; Group B, n = 10) were recruited. All patients in Group A had at least one site of lymphatic leakage identified. One patient in Group B developed chylous fistula and was excluded from analysis. The mean total drain output for day 1 and 2 after surgery, as well as the mean total output before drain removal, were significantly lower in Group A (22.4 ml vs. 86.2 ml [p = .02]; 14.2 ml vs. 72.8 ml [p = .02]; and 58.4 ml vs. 392 ml [p = .01], respectively), allowing earlier drain removal (2.2 days vs. 7.2 days, p = .02). CONCLUSIONS: Intra-operative ICG lymphangiography is useful in the reduction of drainage volume after neck dissection for caners in the head and neck region.

Role of surgery in the treatment of osteoradionecrosis and its complications after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to review the efficacy of surgery for patients with osteoradionecrosis (ORN) after radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: Between 2000 and 2016, we identified 162 patients with skull base ORN, among which 58 patients required surgery. A retrospective medical chart review was performed and the indications and results of surgical interventions were recorded. RESULTS: All surgeries were performed for the treatment of secondary complications of ORN, including central nervous system (CNS) infection (48.4%), blowout bleeding (24.1%), and severe pain (17.2%). Endoscopic debridement was done in 12 patients, whereas the rest required either maxillary swing or mandibulotomy, depending on the location of the necrosis. The majority of the patients required free vastus lateralis flap (72.5%) for reconstruction. Surgery was effective in the control of infection, bleeding, and pain. Multivariate analysis identified reirradiation and bone exposure on MRI as the significant independent risk factors predicting the future need of surgery. CONCLUSION: Surgery is effective in the treatment of secondary complications of skull base ORN after previous radiotherapy for NPC.

Stage II recurrent nasopharyngeal carcinoma: Prognostic significance of retropharyngeal nodal metastasis, parapharyngeal invasion, and carotid encasement.

BACKGROUND: The purpose of this study was to assess the predictability of the American Joint Committee on Cancer (AJCC) staging system on patients with stage II recurrent nasopharyngeal carcinoma (NPC). METHOD: We conducted a retrospective review of the surgical outcome for patients with recurrent NPC and retropharyngeal lymph node (RLN) metastasis (group I), recurrent NPC and parapharyngeal space (PPS) invasion (group II), and recurrent NPC and internal carotid artery (ICA) encasement (group III). RESULTS: Between 1990 and 2013, 145 patients received an operation for stage II recurrent NPC (group I, n = 62; group II, n = 65; and group III, n = 18). The rate of local tumor recurrence was significantly higher in groups II and III. The rate of systemic metastasis was significantly higher in group III (16.7%). Accordingly, the 5-year overall survival was significantly worse for patients in group III (group I: 81.2%; group II: 68.4%; and group III: 48.5%). CONCLUSION: The significantly worse prognosis of recurrent NPC encasing the ICA warrants an upstage to the T3 classification in the current AJCC staging system.

Transoral robotic total laryngopharyngectomy and free jejunal flap reconstruction for hypopharyngeal cancer.

BACKGROUND: To report on the feasibility of total laryngopharyngectomy and free jejunal flap transfer for patient with hypopharyngeal cancer via the transoral robotic surgery (TORS) approach. MATERIAL AND METHODS: A patient with hypopharyngeal cancer involving the post-cricoid region is used for demonstration of the TORS total laryngopharyngectomy and free jejunal flap reconstruction. RESULTS: The procedure starts with a cruciate incision for terminal tracheostomy. The trachea and cervical esophagus is exposed and transected, making sure that the resection margins are adequate. This is followed by the transoral dissection using the robotic surgical system. The laryngopharyngectomy specimen is delivered and the free jejunal flap is replaced transorally. Jejuno-oesophageal suturing and the microvascular anastomosis are performed through the tracheostomy wound. The remaining pharyngo-jejunal anastomosis is performed transorally via the TORS approach. CONCLUSION: TORS total laryngopharyngectomy and free jejunal flap reconstruction is feasible and provides and alternative option to the traditional transcervical approach.

Extracranial/intracranial vascular bypass and craniofacial resection: New hope for patients with locally advanced recurrent nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the oncologic outcome and quality of life after surgical treatment of locally advanced (rT3-rT4) recurrent nasopharyngeal carcinoma (NPC) using the staged extracranial/intracranial vascular bypass and combined craniofacial approach. METHODS: We conducted a prospective study. RESULTS: Between 1998 and 2013, 28 patients with rT3 to rT4 tumors were treated with the proposed surgical protocol. Clear resection margin was achieved in 46.4%. The median follow-up was 42.6 months. The rate of local recurrence was 17.8%. The 5-year overall survival was 52%. There was no change in the mean global health system score after the extensive surgery, although the physical functioning scores deteriorated significantly. The most common symptoms experienced by patients were speech and swallowing problems. CONCLUSION: The proposed surgical treatment for locally advanced recurrent NPC was associated with satisfactory local tumor control and survival. Quality of life after surgery was reasonable, although multidisciplinary training was required to maximize the postoperative speech and swallowing function. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1404-E1412, 2016.

Implantable Doppler Probes for Postoperatively Monitoring Free Flaps: Efficacy. A Systematic Review and Meta-analysis.

BACKGROUND: Although clinical assessment remains the gold standard for monitoring the circulation of free flaps, several adjunct techniques promote timely salvage by detecting circulation compromise early. The objective of this systematic review was to evaluate the efficacy of an implantable Doppler probe for postoperatively monitoring free flaps. MATERIALS AND METHODS: English-language articles evaluating the efficacy of implantable Doppler probes compared with clinical assessment for postoperatively monitoring free flaps were analyzed. The outcome measures were total flap failure rates, salvage rates, sensitivity, false-positive rates, and positive likelihood ratios. RESULTS: Of the 504 citations identified, 6 comparative studies were included for meta-analysis. An implantable Doppler probe significantly lowered the flap failure rate (risk ratio: 0.40; 95% confidence interval: 0.21-0.75) and raised the successful salvage rate (risk ratio: 1.73; 95% confidence interval: 1.16-2.59). Pooled sensitivity was higher (1.00 vs 0.98), the positive likelihood ratio was lower (72.16 vs 220.48), and the false-positive rate was higher (0.01 vs 0) in the implantable Doppler probe group than in the clinical assessment group. CONCLUSION: An implantable Doppler probe is significantly more efficacious than clinical assessment for postoperatively monitoring free flaps.

Shoulder Dysfunction after Selective Neck Dissection in Recurrent Nasopharyngeal Carcinoma.

OBJECTIVE: To investigate the incidence of occult nodal metastasis and severity of shoulder dysfunction after selective neck dissection (SND) for recurrent nasopharyngeal carcinoma (NPC) with N0 status. STUDY DESIGN: Prospective, single-group, pre/post test design. SETTING: Academic medical center. SUBJECTS AND METHODS: Between 1998 and 2012, 46 patients who had recurrent NPC and N0 status were recruited. They subsequently received salvage nasopharyngectomy and SND, removing ipsilateral level I to III and V lymphatics. The incidence of occult nodal metastasis was noted. All patients underwent standardized physiotherapy after surgery. Postoperative shoulder function was measured using the Disability of Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: The incidence of microscopic nodal metastasis was 15.2%. For first year posttreatment, the mean DASH score was 44.2. With time, there was no improvement in shoulder function despite targeted physiotherapy (P = .09), and the second postoperative year mean DASH score was 46.3. The degree of daily activity affected was rated as moderate to very limited, and 30% of the patients had at least moderate shoulder pain at rest. CONCLUSION: Shoulder dysfunction after SND for recurrent NPC is significant and persistent. Given the low incidence of microscopic nodal metastasis in such circumstances, routine SND is not recommended.

Indocyanine green fluorescence mapping of sentinel lymph node in patients with recurrent nasopharyngeal carcinoma after previous radiotherapy.

BACKGROUND: The purpose of this study was to present the feasibility of indocyanine green (ICG) mapping of sentinel lymph node in recurrent nasopharyngeal carcinoma (NPC). M1ETHODS: Peritumoral injection of 5-mg ICG solution and real-time mapping of the sentinel lymph nodes in the neck was performed during surgery. The sentinel lymph node identified was excised and sent separately for laboratory analysis. Selective neck dissection was then performed. The number and level of the sentinel lymph nodes, their signal-to-background ratio, and the histopathology of the sentinel lymph nodes and the neck dissection specimens were studied. RESULTS: A total of 5 patients were recruited into this study, of which 9 sentinel lymph nodes were identified. The majority of them were located in level II. The mean detection time after ICG injection was 288 seconds. The sentinel lymph nodes in 3 patients tested positive for malignancy. None of the selective neck dissection specimens harbored microscopic tumor deposits. CONCLUSION: ICG mapping of sentinel lymph nodes in locally recurrent NPC is potentially feasible. It offers a better nodal staging in patients with clinically N0 disease status.

Co-expression of Cytoskeletal Protein Adducin 3 and CD133 in Neurospheres and a Temozolomide-resistant Subclone of Glioblastoma.

BACKGROUND: Glioma stem cells are associated for temozolomide-resistance in glioblastoma. Adducin 3 (ADD3) is a cytoskeletal protein associated with chemoresistance but its role in glioblastoma has not been investigated. MATERIALS AND METHODS: Using an in vitro model of glioblastoma cells with acquired temozolomide resistance (D54-MG-R), the expressions of ADD3 and cancer stem cell markers were compared to those in temozolomide-sensitive glioblastoma cells (D54-MG-S). Immunofluorescence staining was used to investigate the expression patterns of ADD3 and cancer stem cell markers in temozolomide resistance and neurospheres of glioblastoma. RESULTS: Chemoresistant cells were found to have up-regulation of ADD3 and CD133 expression. A sub-population of D54-MG-R cells and glioma neurospheres exhibited coexpression of ADD3 with CD133. CONCLUSION: To our knowledge, this is the first report of a possible link between cytoskeletal protein expression, cancer stem cell phenotype and temozolomide resistance in human glioblastoma. This report lays the foundation for further investigation for ADD3 as a potential biomarker and therapeutic target in temozolomide-resistant glioma cells.

The role of plasma Epstein-Barr virus DNA in the management of recurrent nasopharyngeal carcinoma.

OBJECTIVES/HYPOTHESIS: To study the role of plasma Epstein-Barr virus (EBV) DNA in patients with recurrent nasopharyngeal carcinoma (NPC) after previous chemoradiation. STUDY DESIGN: Prospective. METHODS: Sixty patients with recurrent NPC were recruited, and their plasma EBV DNA was checked preoperatively, 1 week postoperatively, and 6 months thereafter. In a pilot group of 30 patients, further testing was performed at 60 minutes after tumor resection. The plasma EBV DNA level was correlated with tumor T classification, resection margin status, and subsequent relapse. RESULTS: The mean preoperative plasma EBV DNA reflected the tumor load (T1: 48 copies/mL, T2: 316 copies/mL, T3: 890 copies/mL, P = .03). It was significantly higher in patients with positive margins at the time of surgery (722 vs. 126 copies/mL, P = .02) and in those with subsequent systemic metastasis (668 vs. 92 copies/mL, P = .01). However, it failed to predict local recurrence after surgery. Postoperative plasma EBV DNA was undetectable in all patients with positive resection margins. Serial measurements were able to identify 87.5% of local recurrences and 100% of distance metastases. CONCLUSIONS: In patients with recurrent NPC requiring salvage nasopharyngectomy, preoperative plasma EBV DNA identifies patients at high-risk of subsequent distant failure after surgery. Serial measurements of plasma EBV DNA after surgery, especially for those with high preoperative levels, is crucial to allow early detection of local of distant failure.

Radiation-induced squamous cell carcinoma of the nasopharynx after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the treatment outcome of radiation-induced squamous cell carcinoma (SCC) of the nasopharynx after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). METHODS: We conducted a retrospective review of patients who underwent radiation therapy for NPC, which resulted in radiation-induced SCC of the nasopharynx. RESULTS: Between 1998 and 2011, 24 patients had radiation-induced SCC of the nasopharynx. The median age of diagnosis was 68.2 years. The majority of patients (66.7%) presented with early-stage NPC initially, and they were treated with RT alone (n = 18) or concurrent chemoradiation (n = 6). The mean latency period for the second malignancy was 10.5 years. All the patients were treated with maxillary-swing nasopharyngectomy. Clear resection margin was achieved in 66.7%, and 75% of those with involved margin received adjuvant RT. The mean follow-up duration was 48.2 months. The overall 5-year actuarial local tumor control was 56% and the overall 5-year disease-free survival was 38%. CONCLUSION: Radiation-induced SCC of the nasopharynx is rare after RT for NPC. The prognosis remained poor despite aggressive surgery and adjuvant RT.

Multivariate analysis of prognostic factors for salvage nasopharyngectomy via the maxillary swing approach.

BACKGROUND: The purpose of this study was to investigate the prognostic factors for salvage nasopharyngectomy. METHODS: A retrospective review was conducted on maxillary swing nasopharyngectomy performed between 1998 and 2010. Univariate and multivariate analyses identified prognostic factors affecting actuarial local tumor control and overall survival. RESULTS: The median follow-up duration was 52 months. Among the 268 patients, 79.1% had clear resection margins. The 5-year actuarial local tumor control and overall survival was 74% and 62.1%, respectively. On multivariate analysis, tumor size, resection margin status, and gross tumor in the sphenoid sinus were independent prognostic factors for local tumor control. For overall survival, resection margin status, synchronous cervical nodal recurrence, and cavernous sinus invasion had a negative influence on overall survival after surgery. CONCLUSION: Extent of nasopharyngectomy should be tailored to the individual tumor to achieve clear resection margins. Cavernous sinus invasion is associated with poor survival outcome, and detailed counseling and meticulous surgical planning is crucial in such circumstances.

MicroRNA-21 inhibition enhances in vitro chemosensitivity of temozolomide-resistant glioblastoma cells.

BACKGROUND: Glioblastoma multiforme (GBM) is a form of highly malignant brain tumour. Temozolomide (TMZ) is the standard agent for GBM, but TMZ-resistance is common and accounts for many treatment failures. MicroRNA-21 (miR-21) is a non-coding RNA that plays critical roles in many biological processes in cancer, including chemoresistance. We investigated miR-21 expression and the effect of miR-21 inhibition in GBM with acquired TMZ resistance. MATERIALS AND METHODS: Human GBM cell line D54MG was treated with TMZ chronically to develop a chemoresistant subclone. MiR-21 inhibition was achieved by transfection with anti-mir-21 oligonucleotide. RESULTS: Chronic TMZ exposure resulted in acquired TMZ-resistance and elevated miR-21 expression. Concomitant treatment with miR-21 inhibitor and TMZ resulted in a significantly higher apoptotic rate than TMZ treatment alone. CONCLUSION: MiR-21 may have a potential for use as a biomarker of acquired TMZ resistance. MiR-21 inhibition can be further explored as a potential chemotherapy adjunct in the treatment of TMZ-resistant GBM.