Head and Neck 2024-03-01

Differential modulation of PI3K/Akt/mTOR activity by EGFR inhibitors: A rationale for co‐targeting EGFR and PI3K in cisplatin‐resistant HNSCC

Jipei Liao, Zejia Yang, Shirin Abarzarzin, Kevin J. Cullen, Hancai Dan

Publication date 01-03-2024


Abstract Purpose To find a new strategy to treat cisplatin-resistant head and neck squamous cell carcinoma (HNSCC), we investigated the effects of EGFR inhibitors on the PI3K/Akt/mTOR pathway and determined the efficacy of EGFR inhibitors in combination with PI3K inhibitors to suppress cell proliferation in cisplatin-resistant-HNSCC.
Methods The cisplatin-resistant HNSCC cell lines were treated with four FDA approved EGFR inhibitors, which included Gefitinb or Erlotinib alone, or in combination with the pan-PI3K inhibitor, BKM120. Phosphorylation and total protein levels of cells were assessed by Western blot analysis. Cell proliferation was examined by MTS assay. Apoptosis was analyzed by flow cytometry.
Results Cisplatin-resistant HNSCC cells were also resistant to EGFR inhibitors. However, a combination of EGFR inhibitors with PI3K inhibitor BKM120 dramatically improved the efficacy of EGFR inhibitors to inhibit cell proliferation and induce apoptosis. Furthermore, treatment with EGFR inhibitors differentially affected the phosphorylation of Akt and mTOR, which included partial inhibition, no inhibition, and induction. A combination of EGFR inhibitors and BKM120 completely blocked phosphorylation of EGFR, Akt, and S6K (an mTOR target).
Conclusion Our data provided a rationale for EGFR inhibitors in combination with PI3K inhibitors to treat cisplatin-resistant HNSCC.

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The effect of carbon nanoparticles vs. immune colloidal gold technique test strips on parathyroid protection in total thyroidectomy: A randomized clinical trial study

Bochun Wang, Yiyuan Zhu, Shiguo Zhou, Cheng Lu, Aobo Zhang, Jun Tian, Wanxin Li, Shuling Ren, Yanbo Dong, Liangfa Liu

Publication date 01-03-2024


Abstract Background The long-term effect of intraoperative usage of carbon nanoparticles (CN) and parathyroid hormone (PTH) test strip using immune colloidal gold technique (ICGT) is unclear. This study aims to compare the effect of intraoperative usage of CN and ICGT test strips on PG function.
Methods This randomized clinical study involved adult patients who underwent total thyroidectomy. They were randomly allocated into three groups (control, CN, and ICGT group). Clinical data were analyzed.
Results Each group involved 98 patients. Serum calcium and PTH concentrations at 24 h postoperatively (PTH24h) were higher in CN group. The parathyroid function recovered quicker in CN group. Use of CN increased in situ PG preservation and PTH24h. Mediation analysis indicated that 23.05% of the total effect of CN on PTH24h was attributed to PGRIS.
ConclusionCN holds promise to improve in situ PG preservation and protect PG vasculature, thereby reducing the incidence of early hypoparathyroidism. The value of ICGT test strips for PG protection is dubious.

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Various arrangements of pharyngeal flap in soft palate reconstruction after cancer treatment

Hiroshi Matsumoto, Tomoyuki Ota, Motoi Kato, Takuma Makino, Seiichiro Makihara, Mizuo Ando, Yoshihiro Kimata

Publication date 01-03-2024


Abstract Background The pharyngeal flap (PF) is useful for reconstruction of soft palate defects, but effective arrangements of PF for various types of soft palate defects are controversial. Here, we classify three types of soft palate defects and discuss the arrangements of PF and their functional prognosis.
Methods Reconstruction was performed based on the classification of the defects. Clinical details were collected, and postoperative function was analyzed.
Results Eight patients were included in the study. The defect sizes ranged from 25 (width) × 40 (depth) to 40 × 60 mm. Six patients underwent pharyngeal flap reconstruction with free-flap reconstruction, and two underwent pharyngeal flap reconstruction. The pharyngeal flap was harvested at the maximum width of the posterior pharyngeal wall, ranging from 25 to 40 mm in length. Eating and speaking functions were maintained in all patients.
Conclusions Good postoperative function can be maintained by narrowing the velopharyngeal space with a pharyngeal flap.

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Reliability and outcomes of lymph nodes biopsy in cT1–cT2 N0 supraglottic laryngeal squamous cell carcinoma

Maryline Hoste, Sébastien Van der Vorst, Georges Lawson, Marie‐Cécile Nollevaux, Anne‐Sophie Pirson, Vincent Bachy, Olivier Desgain, Samantha Hassid, Gilles Delahaut

Publication date 29-02-2024


Abstract Background In oral and oropharyngeal squamous cell carcinoma (SCC), sentinel node biopsy (SNB) was described as a reliable and reproductive alternative to elective neck dissection for the staging of clinical N0 T1–T2 patients. The SNB technique in supraglottic laryngeal SCC was successfully described in small series. The aim of this study is to analyze retrospectively the results of SNB technique in supraglottic SCC in CHU Godinne, to determine if the technique is reliable and may be proposed in a future multicentral prospective trial.
Methods The study involved a retrospective analysis of 39 patients who underwent surgery between 2003 and 2019 at CHU Godinne. All patients presented with clinical N0 neck status. The SNB procedure included general anesthesia, 99-technetium colloid peritumoral injection, and lymphoscintigraphy. The hand-held gamma probe was utilized for SNB after tumoral resection during the same operating session. Out of 39 patients, 36 underwent SNB as the sole staging tool, while 3 patients received SNB in combination with elective neck dissection.
Primary outcome was the 2-years neck recurrence-free survival (RFS). Secondary outcomes were the 2- and 5-years disease-specific survival (DSS). Additionally, sensitivity and negative predictive value (NPV) of the SNB technique were analyzed.
Results Sentinel nodes were successfully identified in all 39 patients. An average of 4 nodes excised per patient. Positives SN were detected in 23% (9 in 39) cases, leading to subsequent selective neck dissection. Two cases of neck recurrence were observed, both considered as false negatives, occurring after an average of 3.5 months. Th median follow-up period was 48 months with a 2-year RFS of 95%. Sensitivity and NPV of the SNB technique were found to be 82% and 94%, respectively. Two and five years DSS were 84% and 71.7%, respectively.
Conclusions The results suggest that SNB in T1–T2 supraglottic SCC is a feasible and reliable technique for managing the neck in N0 early-stage patients. However, to establish its oncological equivalence with selective node dissection, further prospective and comparative studies are warranted. The findings of this study underscore the importance of ongoing research in refining and validating the role of SNB in the management of supraglottic SCC, potentially paving the way for more widespread adoption in clinical practice.

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Free flap jaw reconstruction with dental implantation: A single‐institution experience

Benjamin T. Ostrander, Leo Meller, Matthew Harmon, Katya Archambault, Thanos Kristallis, Daniel Hammer, Ryan K. Orosco

Publication date 29-02-2024


Abstract Background We sought to review our institutions experience with dental implant placement in free flap jaw reconstruction to determine factors impacting restoration of dental occlusion.
Methods Exactly 48 patients underwent free flap jaw reconstruction with or without dental restoration from 2017 to 2022. Primary outcome was achievement of restored dental occlusion after jaw free flap reconstruction.
ResultsA total of 48 patients with a mean age of 59.8 ± 16.4 years underwent jaw reconstruction from 2017 to 2022. Ten patients (20.8%) received osteointegrated dental implants. Two patients received a temporary dental prosthesis, 12 ± 4 months after initial reconstruction. Three patients received a final prosthesis, with a mean time to final prosthesis of 17.7 ± 12.4 months. Five patients did not receive any prosthesis despite placement of implants.
ConclusionA minority of patients received dental implant placement with free flap jaw reconstruction and only a small subset of these received a definitive dental prosthesis.

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Post‐surgical readmission risk factors in otolaryngology/head and neck surgery

Jane Kwon, Douglas Farquhar, Jason Tasoulas, Trevor G. Hackman

Publication date 28-02-2024


Abstract Background Otolaryngology patients are a high-readmission-risk group due to the complexity of surgeries, significant alterations to speech and swallowing functions, and high postoperative complications risk.
MethodsA retrospective review was performed on patients who underwent otolaryngologic surgery at a single-academic-institution between March 2019 and February 2020.
Results Among 365 discharges, 21 patients had unplanned readmissions within 30 days. On univariable analysis, acute myocardial infarction, number of total comorbidities, prior chemotherapy/radiation, active smoking, airway surgery, and enteral feeding, and on multivariable analysis, prior chemotherapy/radiation and active smoking were identified as significant readmission risk factors. Readmission risk increased from 2.43% to 7.48% and 41.67% with the addition of each risk factor.
Conclusion Nearly 75% of the readmissions were due to potentially preventable reasons. By identifying and proactively intervening on “at risk” patients during the perioperative timeframe, complications and readmission can be reduced, thereby improving the overall quality of care delivered.

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Airway protection and outcomes after staged versus concurrent bilateral neck dissections with transoral base of tongue cancer resection

Jake J. Lee, Nicholas A. Rapoport, Patrik Pipkorn, Sidharth V. Puram, Ryan S. Jackson

Publication date 27-02-2024


Abstract Objectives To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND).
MethodsA retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded.
Results Of 126 patients (46 37% staged and 80 63% concurrent BND), there were no significant differences in rates of postoperative intubation, tracheostomy, intensive care admission, operative takebacks, gastrostomy, and 30-day readmission. Total operative time (median difference 1.4 95% CI 0.9–1.8 hours), length of stay (1.0 1.0–1.0 day), and time between primary surgery and adjuvant therapy initiation (4.0 0.0–8.0 days) were lower in the concurrent BND cohort.
Conclusion Concurrent BND alongside transoral BOT resection is safe with similar airway outcomes and lower total operative time, length of stay, and time to adjuvant therapy initiation compared to staged BND.

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Early feeding after free flap reconstruction of the oral cavity: A systematic review and meta‐analysis

Joshua Barlow, Zara Sragi, Nina Rodriguez, Mathilda Alsen, Catharine Kappauf, Rocco Ferrandino, Susmita Chennareddy, Tamar Kotz, Diana N. Kirke, Marita S. Teng, Eric M. Genden, Mohemmed N. Khan, Scott A. Roof

Publication date 27-02-2024


Abstract Background Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6–14 days post-operatively due to concern for orocutaneous fistula development.
Methods Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed- and random-effects meta-analyses were used.
Results One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = −0.02, p = 0.06) or free flap failure (RD = −0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference days = −2.43, p < 0.01).
Conclusions While further prospective trials are necessary, initiation of oral intake before post-operative day 5 may be appropriate in properly selected patients following oral reconstruction.

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Prognostic risk factors of buccal squamous cell carcinoma: A case–control study

Jacquelyn K. Callander, Spenser S. Souza, Yasmin Eltawil, Ivan H. El‐Sayed, Jonathan R. George, Patrick Ha, William R. Ryan, Mary Jue Xu, Chase M. Heaton

Publication date 27-02-2024


Abstract Objectives To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival.
Methods This is a retrospective case–control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review.
Results Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14–61). Median age was 67 years (IQR 57–75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors.
Conclusions Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

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Salvage skull base surgery after proton beam therapy for recurrent sinonasal malignancies: A retrospective study

Shinichi Okada, Takashi Mukaigawa, Seiya Goto, Yohei Hiiragi, Fuyuki Sato, Shoichi Deguchi, Hirofumi Ogawa, Tsuyoshi Onoe, Shigeyuki Murayama, Yoshichika Yasunaga, Nakamasa Hayashi

Publication date 26-02-2024


Abstract Background This study aimed to examine treatment outcomes and postoperative complications associated with salvage skull base surgery following radical proton beam therapy (PBT).
Methods Nine patients who underwent salvage skull base surgery following curative PBT as the initial treatment at our institution between September 2002 and May 2023 were retrospectively reviewed.
Results The cohort comprised four males and five females with a mean age of 48.1 years. The average proton dose administered during initial therapy was 68.5 Gy (relative biological effectiveness). Among the salvage surgeries, eight were anterior skull base surgeries, and one was an anterior middle skull base surgery. No local recurrences or perioperative deaths were observed. Postoperative complications occurred in three patients (33.3%), all experiencing surgical site infections, with one also having cerebrospinal fluid leakage.
Conclusion The study demonstrates that salvage skull base surgery after PBT effectively achieves local control and safety in patients with recurrent sinonasal malignancies.

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Postoperative pain management using an intravenous combination of ibuprofen and acetaminophen compared with acetaminophen alone after thyroidectomy: A prospective randomized controlled trial

Jaesik Park, Do Kyung Lee, Ji Eun Kim, Ja Seong Bae, Jeong‐Soo Kim, Yung Eun Moon

Publication date 25-02-2024


Abstract Background Multiple medications are more effective than single agents for postoperative pain management. We investigated the analgesic effects of an intravenous combination of acetaminophen and ibuprofen immediately after thyroidectomy.
Methods In this double-blind clinical trial, 62 patients who underwent thyroidectomies were randomized to either the treatment (1000 mg acetaminophen, 300 mg ibuprofen) or control (1000 mg acetaminophen) group. Postoperative pain intensity was assessed using the visual analog scale (VAS) 0, 15, and 30 min after recovery room admission. Opioid rescue consumption was also recorded.
Results The VAS scores were significantly lower in the treatment than in the control group 15 3 (2–4.3) vs. 5 (3–6); p = 0.015 and 30 3 (2–4.3) vs. 4 (3–5); p = 0.018 min after recovery room admission, as were the opioid rescue dose requirements (p = 0.033).
Conclusions Combined intravenous acetaminophen and ibuprofen may be better than acetaminophen alone for immediately acute postoperative pain after thyroidectomy.

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Latissimus dorsi myocutaneous free flap for the laryngopharyngectomy defect

Corin M. Kinkhabwala, Julian Amin, Tyler Rist, Vilija J. Vaitaitis, Judith M. Skoner

Publication date 23-02-2024


Abstract Background Partial or total laryngopharyngectomy defects have traditionally been reconstructed using the radial forearm, anterolateral thigh, or jejunal free flaps. The latissimus dorsi myocutaneous free flap (LDMFF) is an option for high-risk patients with complex laryngopharyngeal ± cutaneous neck defects.
Methods Retrospective single-surgeon case series from 2017 to 2022. Outcomes were assessed at both the back donor site and head and neck.
Results Twenty-four patients were identified. Flap survival was 100%. There was 1 (4.2%) pharyngocutaneous fistula and 2 (8.3%) tracheo-esophageal peristomal fistulas. At last follow-up, 17 (71%) were sustaining weight on oral intake, and 7 (29%) were G-tube dependent with 4 of these able to do some type of oral intake. Seven (29.2%) had post-operative stricture/stenosis requiring dilation. There were only minor donor site complications, all managed conservatively.
Conclusions The LDMFF can be a robust reconstructive option, particularly for radiated high-risk patients with complex pharyngeal defects, including skin.

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Oncocytic carcinoma of the thyroid: Conclusions from a 20‐year patient cohort

Nelson R. Gruszczynski, Shahzeb S. Hasan, Ana G. Brennan, Julian De La Chapa, Adithya S. Reddy, David N. Martin, Prem P. Batchala, Edward B. Stelow, Eric M. Dowling, Katherine L. Fedder, Jonathan C. Garneau, David C. Shonka Jr

Publication date 23-02-2024


Abstract Background Oncocytic carcinoma (OCA) was recently reclassified as a distinct differentiated thyroid carcinoma (DTC). Given its rarity, OCA studies are limited. This study describes the characteristics of OCA in a 20-year cohort.
Methods Retrospective analysis of patients with OCA at a single tertiary care hospital from 2000 to 2021.
Results Fifty-one OCA patients (22M:29F) were identified. The mean age at diagnosis was 60.3 years; 90% presented as palpable mass; 24% had a family history of thyroid cancer. None had vocal fold paresis. On ultrasound, most tumors were solid and hypoechoic. FNA (n = 14) showed Bethesda-4 lesions in 93%. All were treated surgically. Histologically, 63% demonstrated angioinvasion, 35% had lymphovascular invasion, and 15% had extrathyroidal extension. Radioactive iodine was used as adjunct therapy in 77%.
ConclusionOCA has distinct features that distinguish it from other DTCs, and additional focused studies will help clarify the aggressive nature, treatment options, and prognosis of the disease.

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Immunotherapy targeting tumor‐associated antigen in a mouse model of head and neck cancer

Michihisa Kono, Risa Wakisaka, Hiroki Komatsuda, Ryusuke Hayashi, Takumi Kumai, Hidekiyo Yamaki, Ryosuke Sato, Toshihiro Nagato, Takayuki Ohkuri, Akemi Kosaka, Kenzo Ohara, Kan Kishibe, Hiroya Kobayashi, Tatsuya Hayashi, Miki Takahara

Publication date 23-02-2024


Abstract Background The identification of epitope peptides from tumor-associated antigens (TAAs) is informative for developing tumor-specific immunotherapy. However, only a few epitopes have been detected in mouse TAAs of head and neck cancer (HNSCC).
Methods Novel mouse c-Met-derived T-cell epitopes were predicted by computer-based algorithms. Mouse HNSCC cell line-bearing mice were treated with a c-Met peptide vaccine. The effects of CD8 and/or CD4 T-cell depletion, and vaccine combination with immune checkpoint inhibitors (ICIs) were evaluated. Tumor re-inoculation was performed to assess T-cell memory.
Results We identified c-Met-derived short and long epitopes that elicited c-Met-reactive antitumor CD8 and/or CD4 T-cell responses. Vaccination using these peptides showed remarkable antitumor responses via T cells in which ICIs were not required. The c-Met peptide-vaccinated mice rejected the re-inoculated tumors.
Conclusions We demonstrated that novel c-Met peptide vaccines can induce antitumor T-cell response, and could be a potent immunotherapy in a syngeneic mouse HNSCC model.

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Clinical outcomes of cetuximab‐based treatment for distant metastatic head and neck squamous cell carcinoma: A real‐world study using Taiwan Head Neck Society registry database

Hsueh‐Ju Lu, Meng‐Che Hsieh, Hung‐Ming Wang, Jason Chia‐Hsun Hsieh, Chia‐Jui Yen, Shang‐Yin Wu, Huai‐Cheng Huang, Hui‐Ching Wang, Pen‐Yuan Chu, Tien‐Hua Chen, Chih‐Yen Chien, Tai‐Lin Huang, Yi‐Fang Chang, Chun‐Hung Hua, Ming‐Yu Lien, Jo‐Pai Chen, Wei‐Chen Lu, Jin‐Ching Lin, Chen‐Chi Wang, Yi‐Chun Liu, Muh‐Hwa Yang, Pei‐Jen Lou

Publication date 22-02-2024


Abstract Background For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear.
Methods From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis.
Results Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen.
ConclusionDM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.

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Development of a head and neck lymphoedema specific quality of life tool: The Comprehensive Assessment of Lymphoedema Impact in the Head and Neck

Heather M. Starmer, Joanne Patterson, Bridget Young, Jason Fleming, Mary Gemma Cherry

Publication date 21-02-2024


Abstract Purpose To develop a head and neck lymphoedema (HNL) specific quality of life (QoL) instrument to assess physical, functional, and social/emotional impacts of HNL.
Methods Instrument candidate items were reviewed by patients with HNL and clinicians and rated for importance, clarity, and invasiveness. The Content Validity Ratio was applied for item reduction. Three-step cognitive interviews were conducted with HNL patients to validate the items, survey format, and instructions.
Results Initially, 130 candidate questions were developed. Following item reduction, 52 items progressed to three-step cognitive interviews. Following cognitive interviews, the Comprehensive Assessment of Lymphoedema Impact in Head and Neck (CALI-HaN) included 33 items; 1 global, 10 physical, 7 functional, and 15 emotional.
Conclusions Physical, functional, and socioemotional effects need to be considered when measuring QoL in patients with HNL. This study describes initial development of the CALI-HaN, an instrument that shows promise for clinical and research applications following future validation.

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Tumor microenvironment in thyroid cancer: Immune cells, patterns, and novel treatments

Beatriz Febrero, Juan José Ruiz‐Manzanera, Inmaculada Ros‐Madrid, Antonio Miguel Hernández, Esteban Orenes‐Piñero, José Manuel Rodríguez

Publication date 21-02-2024


Abstract The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. Published data from this review were identified by search and selection database of Pubmed, Elsevier, and Science Direct. Searching was made in two steps using different keywords. In thyroid pathology, the inflammatory response is very important, and might have a key role finding new diagnostic and therapeutic methods, particularly in thyroid cancer. Different immune cells may be more or less present in different types of thyroid cancer and may even have different functions, hence the importance of knowing their presence in different thyroid tumor pathologies. Cancer-related inflammation could be a useful target for new diagnostic and therapeutic strategies by analyzing peritumoral and intratumoral immune cells in different types of thyroid tumors. Moreover, novel strategies for thyroid cancer treatments, such as monoclonal antibodies targeting checkpoint inhibitors, are emerging as promising alternatives.

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Development of a novel senescence‐related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma

An Wang, Na Xiao, Hong Wang, Qin Yao, Jin Li, Yaping Wu, Han Ge, Pengfei Diao

Publication date 21-02-2024


Abstract Background Cellular senescence significantly associates with tumor initiation, progression, and therapeutic response across multiple cancers. Here, we sought to develop a novel senescence-related genes (SRGs)-derived signature for oral squamous cell carcinoma (OSCC) prognostication and therapeutic response prediction.
MethodsOSCC-specific SRG prognostic signature was established with univariate Cox regression, Kaplan–Meier survival, and LASSO-penalized multivariate Cox regression analyses. A SRG nomogram integrating this signature and selected clinicopathological parameters were constructed by multivariate Cox regression. SiRNA-mediated gene knockdown was exploited to validate its function in vitro. The utilities of SRG signature in predicting immune status and chemotherapeutic sensitivities were analyzed.
Results The prognostic performance of SRG signature/nomogram was satisfactory in multiple independent cohorts. CDK1 knockdown induced senescence phenotype in vitro. Moreover, SRG signature scores negatively correlated with tumor-infiltrating immune cells and associated with multiple chemotherapeutic drug sensitivities.
Conclusions Our results established SRG-derived signature/nomogram as powerful predictors for prognosis and chemotherapeutic response for OSCC.

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Monoamine oxidase B inhibits epithelial‐mesenchymal transition and trigger apoptosis via targeting ERK1/2 signaling pathway in head and neck squamous cell carcinoma

Yibo Qi, Weihua Shao, Jing Gao, Nan Ni, Feifei Xue, Tianxiao Wang, Yuli Wang, Yi Fan, Hua Yuan

Publication date 20-02-2024


Abstract Background Monoamine oxidase B (MAOB), a flavin monoamine oxidase, regulates biogenic and xenobiotic amine oxidative deaminization. We demonstrate MAOB expression in head and neck epithelium and its biological importance in head and neck squamous cell carcinoma (HNSCC) development.
Methods First, we found a possible MAOB downregulation in HNSCC using bioinformatic analysis. Second, we validated MAOB expression changes in vitro and assessed its tumorigenicity in HNSCC. Finally, preclinical xenograft models further confirmed our findings.
Results Results proved that MAOB was significantly reduced in HNSCC tissues and cell lines. By comparing MAOB localization in patient specimens, we found that epithelial basal cells express MAOB and that it changes throughout HNSCC development. We observed that MAOB overexpression inhibited HNSCC cell malignancy via lentiviral transfection. We additionally discovered that selegiline partly counter-regulated MAOB overexpression-induced phenotypes in HNSCC cells.
Conclusions We found that MAOB is a potent biomarker and a unique and essential indication of HNSCC carcinogenesis.

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Retropharyngeal abscess due to Fusobacterium necrophorum complicated by progressive internal carotid artery stenosis and multiple cranial nerve palsies

Sohta Matsumura, Takeo Sato, Satoshi Matsushima, Tatsushi Kokubu, Tadashi Umehara, Teppei Komatsu, Kenichiro Sakai, Hidetaka Mitsumura, Yasuyuki Iguchi

Publication date 20-02-2024


Abstract BackgroundA case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported.
MethodsA 36-year-old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space.
Results These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum.
Conclusions This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation.

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Effect of waiting time for radiotherapy after last induction chemotherapy on prognosis of locally advanced nasopharyngeal carcinoma

Kui‐Xuan Zhu, Ting Ding, Yi‐Min E, Hong‐Wei Yang, Rui‐Ping Wu, Run‐Jia Liu, Ling‐Li Zhou, Wen‐Jie Fu, Mei‐Ping Jiang, Xiao‐Li Wang

Publication date 17-02-2024


Abstract Background The effect of radiotherapy waiting time after last induction chemotherapy (IC-RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion.
Methods Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study.
Results The IC-RT was a risk factor for the post-treatment progression of LANPC (OR = 1.017 95%CI: 1.003–1.031), For patients with LANPC, the IC-RT > 40 days significantly reduced 5-year PFS (70% vs. 55%; p = 0.0012), 5-year OS (84% vs. 73%; p = 0.028), 5-year DMFS (80% vs. 66%; p = 0.003), 5-year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC-RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57–4.6), OS (HR = 2.55; 95%CI: 1.29–5.03), DMFS (HR = 3.07; 95%CI: 1.64–5.76) and LRFS (HR = 2.26; 95%CI: 1.21–4.21).
Conclusion The prognosis of patients will be adversely affected if the IC-RT exceeds 40 days, especially for stage IVa patients.

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Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III‐IVa nasopharyngeal carcinoma: A real‐world study based on medical comorbidities

Ya‐Nan Jin, Zhi‐Wen Xiao, Wei Yao, Jing Yu, Wang‐Jian Zhang, Tia Marks, Hong‐Yu Zhang, Ji‐Jin Yao, Liang‐Ping Xia

Publication date 17-02-2024


Abstract Purpose To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa).
Methods and Materials Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/− NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein–Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS).
Results Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences.
Conclusions The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.

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Surgery for nonlocalizing hyperparathyroidism in high volume center

Austin B. Miller, Ethan Frank, Alfred A. Simental Jr, Max Feng

Publication date 16-02-2024


Abstract Background Patients with nonlocalizing hyperparathyroidism pose a significant challenge to surgeons when undergoing neck exploration for parathyroidectomy.
Methods We evaluated 536 patients that had parathyroidectomy for primary hyperparathyroidism (PHPT) from 2005 to 2018 at a single tertiary academic center, and 155 (29%) had standard nonlocalizing preoperative imaging (negative ultrasound and sestamibi scans).
Results There were a total of 102 (66%) non-ectopic single adenomas in the nonlocalizing group and 325 (85%) single adenomas in the localizing group. There was no significant difference (p = 0.09) in adenoma quadrant between localizing and nonlocalizing single adenomas, but the most common location in both groups was right inferior. Patients with nonlocalizing scans were more likely to have double adenomas (21% vs. 9%, p < 0.001), ectopic glands (10% vs. 5%, p = 0.052), and multi-gland disease (13% vs. 8%, p = 0.002).
Conclusion Nonlocalizing PHPT patients experienced similar cure and complication rates as localizing PHPT, but required more bilateral explorations and increased operative time.

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Next‐generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal‐type sinonasal adenocarcinoma

Cristina Riobello, Paula Sánchez‐Fernández, María Camila Cubides Córdoba, Maripaz González‐Gutiérrez, Blanca Vivanco, Virginia N. Cabal, Laura Suárez Fernández, Rocío García‐Marín, Helena Codina‐Martínez, Sara Lucila Lorenzo‐Guerra, Fernando López, Mario A. Hermsen, José Luis Llorente

Publication date 16-02-2024


Abstract Background Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC.
Methods Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing.
Results Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence.
Conclusions We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.

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Predicting reoperation and readmission for head and neck free flap patients using machine learning

Stephanie Y. Wang, Louis‐Xavier Barrette, Jinggang J. Ng, Neel R. Sangal, Steven B. Cannady, Robert M. Brody, Andrés M. Bur, Jason A. Brant

Publication date 15-02-2024


Abstract Background To develop machine learning (ML) models predicting unplanned readmission and reoperation among patients undergoing free flap reconstruction for head and neck (HN) surgery.
Methods Data were extracted from the 2012–2019 NSQIP database. e Xtreme Gradient Boosting (XGBoost) was used to develop ML models predicting 30-day readmission and reoperation based on demographic and perioperative factors. Models were validated using 2019 data and evaluated.
Results Four-hundred and sixty-six (10.7%) of 4333 included patients were readmitted within 30 days of initial surgery. The ML model demonstrated 82% accuracy, 63% sensitivity, 85% specificity, and AUC of 0.78. Nine-hundred and four (18.3%) of 4931 patients underwent reoperation within 30 days of index surgery. The ML model demonstrated 62% accuracy, 51% sensitivity, 64% specificity, and AUC of 0.58.
ConclusionXGBoost was used to predict 30-day readmission and reoperation for HN free flap patients. Findings may be used to assist clinicians and patients in shared decision-making and improve data collection in future database iterations.

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Patient‐reported outcome measures for dysphagia in head and neck cancer: A systematic review and appraisal of content validity and internal structure

Beatrice Manduchi, Zhiyao Che, Jolie G. Ringash, Margaret I. Fitch, Doris Howell, Rosemary Martino

Publication date 15-02-2024


Abstract Dysphagia is a major head and neck cancer (HNC) issue. Dysphagia-related patient-reported outcome measures (PROMs) are critical for patient-centred assessment and intervention tailoring. This systematic review aimed to derive a comprehensive inventory of HNC dysphagia PROMs and appraise their content validity and internal structure. Six electronic databases were searched to February 2023 for studies detailing PROM content validity or internal structure. Eligible PROMs were those developed or validated for HNC, with ≥20% of items related to swallowing. Two independent raters screened citations and full-text articles. Critical appraisal followed COSMIN guidelines. Overall, 114 studies were included, yielding 39 PROMs (17 dysphagia-specific and 22 generic). Of included studies, 33 addressed PROM content validity and 78 internal structure. Of all PROMs, only the SOAL met COSMIN standards for both sufficient content validity and internal structure. Notably, the development of 18 PROMs predated the publication of COSMIN standards. In conclusion, this review identified 39 PROMs addressing dysphagia in HNC, of which only one met COSMIN quality criteria. Given that half of PROMs were developed prior to COSMIN guidelines, future application of current standards is needed to establish their psychometric quality.

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Quality of life following surgery for head and neck cancer: Evidence from ACRIN 6685

Christopher S. Hollenbeak, Fenghai Duan, Rathan M. Subramaniam, Alexander Taurone, JoRean Sicks, Val J. Lowe, Brendan C. Stack Jr

Publication date 14-02-2024


Abstract Background This study examined the trajectory of health-related quality of life (HRQoL) for patients with clinical stage N0 HNSCC enrolled in ACRIN 6685 who underwent elective neck dissection(s).
MethodsHRQoL of 230 patients in the ACRIN 6685 trial was measured prospectively up to 2 years following surgery using the University of Washington Quality of Life instrument.
Results General Health Within the Last 7 Days did not differ significantly from baseline at any follow-up. General Health Relative to Before Cancer fell significantly by 5.8 points following surgery (p = 0.048), and then returned to 3.0 points above baseline at 1 year (p = 0.65). For Overall Quality of Life, HRQoL fell significantly by 4.3 points following surgery (p = 0.031) and then returned to levels not significantly different from baseline.
Conclusions Patients with stage N0 HNSCC experience significant declines in HRQoL immediately following surgery, including neck dissection, which recovers to near or better than baseline within 1–2 years.

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Electromyography findings in radiation‐induced unilateral tongue immobility

Randall J. Harley, Jonas T. Johnson, Marci L. Nilsen, Michael C. Munin

Publication date 14-02-2024


Abstract Background We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility.
Methods Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve.
Results The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2–25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function.
Discussion These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction.

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Sarcopenia predicts short‐term treatment‐related toxicity in patients undergoing curative‐intent therapy for head and neck cancer: A systematic review and meta‐analysis

Marco A. Mascarella, Jannatul Ferdus, Varun Vendra, Shaum Sridharan, Khalil Sultanem, Christina Tsien, George Shenouda, Nathaniel Bouganim, Khashayar Esfahani, Keith Richardson, Alex Mlynarek, Nader Sadeghi, Michael Hier, Marie‐Jeanne Kergoat

Publication date 14-02-2024


Abstract Sarcopenia is an increasingly recognized biomarker associated with poorer outcomes. The objective of this study was to ascertain the effect of sarcopenia on treatment tolerance and short-term toxicity in head and neck cancer (HNC). A systematic review was performed using multiple databases. An inverse-variation, random-effects model was used to perform the meta-analysis to evaluate the effect of sarcopenia on severe treatment toxicity and poor treatment tolerance. Sixteen observational studies, including 3187 patients with HNC, were analyzed. The combined odds ratio (OR) for severe treatment toxicity and tolerance was 2.22 (95%CI 1.50–3.29) and 1.40 (95%CI 0.84–2.32), respectively. The effect of sarcopenia on short-term severe treatment toxicity was similar with upfront surgery (OR 2.03, 95%CI 1.22–3.37) and definitive radiotherapy (OR 2.24, 95%CI 1.18–4.27) Patients with sarcopenia are more than twice as likely to suffer a short-term treatment-related toxicity when undergoing curative-intent HNC treatment.

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Intraoperative AI‐assisted early prediction of parathyroid and ischemia alert in endoscopic thyroid surgery

Bo Wang, Jia‐Fan Yu, Si‐Ying Lin, Yi‐Jian Li, Wen‐Yu Huang, Shou‐Yi Yan, Si‐Si Wang, Li‐Yong Zhang, Shao‐Jun Cai, Si‐Bin Wu, Meng‐Yao Li, Ting‐Yi Wang, Amr H. Abdelhamid Ahmed, Gregory W. Randolph, Fei Chen, Wen‐Xin Zhao

Publication date 13-02-2024


Abstract Background The preservation of parathyroid glands is crucial in endoscopic thyroid surgery to prevent hypocalcemia and related complications. However, current methods for identifying and protecting these glands have limitations. We propose a novel technique that has the potential to improve the safety and efficacy of endoscopic thyroid surgery.
Purpose Our study aims to develop a deep learning model called PTAIR 2.0 (Parathyroid gland Artificial Intelligence Recognition) to enhance parathyroid gland recognition during endoscopic thyroidectomy. We compare its performance against traditional surgeon-based identification methods.
Materials and methods Parathyroid tissues were annotated in 32 428 images extracted from 838 endoscopic thyroidectomy videos, forming the internal training cohort. An external validation cohort comprised 54 full-length videos. Six candidate algorithms were evaluated to select the optimal one. We assessed the models performance in terms of initial recognition time, identification duration, and recognition rate and compared it with the performance of surgeons.
Results Utilizing the YOLOX algorithm, we developed PTAIR 2.0, which demonstrated superior performance with an AP50 score of 92.1%. The YOLOX algorithm achieved a frame rate of 25.14 Hz, meeting real-time requirements. In the internal training cohort, PTAIR 2.0 achieved AP50 values of 94.1%, 98.9%, and 92.1% for parathyroid gland early prediction, identification, and ischemia alert, respectively. Additionally, in the external validation cohort, PTAIR outperformed both junior and senior surgeons in identifying and tracking parathyroid glands (p < 0.001).
Conclusion The AI-driven PTAIR 2.0 model significantly outperforms both senior and junior surgeons in parathyroid gland identification and ischemia alert during endoscopic thyroid surgery, offering potential for enhanced surgical precision and patient outcomes.

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Neutrophil‐to‐lymphocyte ratio associates with nutritional parameters, intratumoral immune profiles, and clinical outcomes of pembrolizumab in head and neck squamous cell carcinoma

Hiroki Morimoto, Takahiro Tsujikawa, Aya Miyagawa‐Hayashino, Alisa Kimura, Sumiyo Saburi, Nanako Murakami, Kayo Kitamoto, Shigeyuki Mukudai, Hikaru Nagao, Shibata Saya, Hiroshi Ogi, Eiichi Konishi, Kyoko Itoh, Shigeru Hirano

Publication date 12-02-2024


Abstract Background The relationship between the tumor-immune microenvironment and systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), is unclear.
Methods We examined the characteristics of systemic inflammatory markers and tumor immune microenvironments in relation to treatment outcomes in 29 consecutive patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who received pembrolizumab, using 14-marker multiplex immunohistochemistry and image cytometry.
ResultsNLR ≥4.5 (high NLR) at pretreatment status significantly correlated with short overall survival (OS) and progression-free survival-2 (PFS2) and malnutrition status. High NLR in peripheral blood was significantly correlated with low lymphoid cell and high tumor-associated macrophage counts in tissues, especially myeloid-to-lymphoid cell ratios, suggesting an association between circulating and intratumoral immune complexity profiles.
Conclusions This study suggests a link between NLR in circulating blood, systemic nutritional status, and immune composition within the tumor.

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Prognostic significances of systemic inflammatory response markers in patients with synchronous esophageal and head and neck cancers

Chih‐Chun Wang, Ming‐Hung Hsu, Ching‐Tai Lee, Chi‐Jen Chen, Tzer‐Zen Hwang, Hsiu‐Po Wang, Jaw‐Town Lin, Wen‐Lun Wang

Publication date 12-02-2024


Abstract Background Patients with head and neck squamous cell carcinoma (HNSCC) frequently develop synchronous esophageal cancer (ESCC), but there is a lack of clinical predictors. The neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR), and lymphocyte to monocyte ratios (LMRs), reflect the balance between pro-cancer inflammation and anti-cancer immune responses, but their role in HNSCC and synchronous cancer remain uncertain.
Method The study consecutively enrolled a total of 717 patients with newly diagnosed HNSCC who received pre-treatment esophageal endoscopic screening. The pretreatment NLR, LMR and PLRs were calculated and analyzed in comparison with the clinical factors.
ResultsA total of 103 patients (14.4%) were found to have synchronous ESCCs, and were associated with a significantly lower absolute lymphocyte count (p < 0.001), higher NLRs (p = 0.044) and lower LMRs (p = 0.001), but not PLRs (p = 0.49). The ROC curve for the presence of synchronous ESCC verified the optimal cutoff value as 2.5 for NLRs and 4.0 for LMRs. Multivariable logistic regression revealed that a LMR <4 (OR 2.22; 95% CI 1.27–3.88, p = 0.005), alcohol consumption (OR 4.19; 95% CI 1.47–11.91, p = 0.007), tumor location over the pharynx (OR 1.68; 95% CI 1.07–2.64, p = 0.025), and low body mass index (OR 0.94; 95% CI 0.88–0.99, p = 0.039) were risk factors for developing synchronous ESCC. A low-LMR was significantly associated with decreases in overall survival (p < 0.0001), in both synchronous and non-synchronous groups. Multivariate analysis demonstrated that LMR <4 (HR 1.97; 95% CI 1.38–2.81, p < 0.001), a low-BMI (HR 0.96; 95% CI 0.93–0.99, p = 0.044) and presence of synchronous ESCC (HR 1.56; 95% CI 1.10–2.22, p = 0.013) were independent prognostic factors for HNSCC patients.
Conclusion Incorporation of LMR into other identified risk factors, such as alcohol consumption, tumor location over pharynx, and low-BMI, may establish a more efficient screening program for esophageal exploration in HNSCC patients. The significances of LMR also suggest that anti-cancer immunity may play a role in the filed cancerization to initiate multiple cancers, and the immunotherapy may have potentials for prevention or as an adjuvant treatment for synchronous SCC in the future.

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A supervised machine learning model for identifying predictive factors for recommending head and neck cancer surgery

Max L. Jiam, Kevin Z. Xin, Patrick K. Ha, Nicole T. Jiam

Publication date 12-02-2024


Abstract Background New patient referrals are often processed by practice coordinators with little-to-no medical background. Treatment delays due to incorrect referral processing, however, have detrimental consequences. Identifying variables that are associated with a higher likelihood of surgical oncological resection may improve patient referral processing and expedite the time to treatment. The study objective is to develop a supervised machine learning (ML) platform that identifies relevant variables associated with head and neck surgical resection.
MethodsA retrospective cohort study was conducted on 64 222 patient datapoints from the SEER database.
Results The random forest ML model correctly classified patients who were offered head and neck surgery with an 81% accuracy rate. The sensitivity and specificity rates were 86% and 71%. The positive and negative predictive values were 85% and 73%.
ConclusionsML modeling accurately predicts head and neck cancer surgery recommendations based on patient and cancer information from a large population-based dataset. ML adjuncts for referral processing may decrease the time to treatment for patients with cancer.

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The methodological and reporting quality of randomized controlled trials of tyrosine kinase inhibitors for advanced differentiated thyroid cancer: Meta‐research study

Rogério Aparecido Dedivitis, Mario Augusto Ferrari de Castro, Alice Matos Dal Boni, Ana Carolina Beltrão Alvares, Ana Júlia Piazentin Tresso, Andrea Davedovicz de Oliveira, Amanda Gonçalves da Silva Dourado Vieira, Fernanda Assaf Mendes, Giovana de Oliveira Rossi, Giullia Neworal Fava, Isabela Santos Pouza, Izabelle Pimenta Santana, Julia Gibran Laino, Letícia Barbosa de Lima, Ana Luiza Cabrera Martimbianco

Publication date 12-02-2024


Abstract Introduction Clinical trials on tyrosine kinase inhibitors (TKI) treatment have shown an improvement in overall and progression-free survival in patients with advanced differentiated thyroid cancer. However, it is necessary to evaluate these studies to assess methodological biases and inconsistencies that may impact the effects.
Objective To map and assess the methodological quality of randomized clinical trials (RCTs) regarding randomization, allocation concealment, blinding, and selective reporting bias.
MethodsRCTs assessing the efficacy and safety of TKI for the treatment of advanced differentiated thyroid cancer were included. The search was performed in the MEDLINE database. The included RCTs were assessed for the adequacy of the methodological steps, as recommended by the Cochrane Risk of Bias tool.
Results Nine studies were analyzed, of which 77.7% were classified as low risk of bias regarding selective reporting and 33.3% as high risk of reporting bias. The mean time between protocol registration and study publication was approximately 5.11 years. Moreover, 66.7% were classified as low risk of bias for randomization and allocation concealment, and 33.3% did not specify the randomization process and allocation concealment in a way that would allow the identification of occurrences of bias. Concerning blinding of participants and outcome assessors, 77.8% of the RCTs reported adequate blinding and were classified as having a low risk of bias, 11.1% had a high risk of bias, and 11.1% had insufficient information and were classified as having unclear risk of bias. Regarding the blinding of the outcome assessors, 33.3% did the blinding correctly, 11.1% did not blind, and 55.6% did not provide enough information.
Conclusion Overall, the assessed RCTs were predominantly at low risk of bias. The critical evaluation of these studies is essential to have confidence in the treatment estimated effect that will support clinical decision-making and provide information to preclude future clinical study flaws.

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Lymph node yield: Impact on oncologic outcomes in oral cavity cancer

Carlos Khalil, Mark Khoury, Kevin Higgins, Danny Enepekides, Irene Karam, Zain Ali Husain, Andrew Bayley, Ian Poon, Tra Truong, Kelvin K. W. Chan, Martin Smoragiewicz, Rui Fu, Antoine Eskander

Publication date 12-02-2024


Abstract Background Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery.
Methods This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome.
Results Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR aHR: 0.73, 95% CI: 0.54–0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49–0.95), and regional failure (aHR: 0.61, 95% CI: 0.39–0.93).
Conclusions Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.

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High‐grade intraductal carcinoma of the parotid gland harboring CTNNA1::ALK rearrangement: Changes in genetic status using genetic testing during treatment with an ALK inhibitor

Takane Watanabe, Yoshitaka Honma, Kan Yonemori, Kuniko Sunami, Seiichi Yoshimoto, Taisuke Mori

Publication date 12-02-2024


Abstract Background Salivary gland carcinomas harboring anaplastic lymphoma kinase (ALK) rearrangements are rare. Here, we present the pathological characteristics, clinical course, and changes in the genetic status of a salivary gland carcinoma harboring a catenin alpha 1 (CTNNA1)::ALK rearrangement during treatment with an ALK tyrosine kinase inhibitor (TKI).
MethodsA 59-year-old man with a parotid tumor and cervical lymph node metastases underwent total parotidectomy and radical neck dissection. One month after completion of postoperative radiotherapy, the patient experienced multiple recurrences.
Results Subsequent treatment with the ALK-TKI alectinib was initially effective against the intraductal carcinoma harboring CTNNA1::ALK rearrangement and TP53 mutation. However, 10 months later the patients condition deteriorated, and an additional phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation was detected. The patient ultimately succumbed to multiple organ failure.
Conclusion The clinical course suggested the concurrent emergence of TP53 and PIK3CA mutations and ALK-TKI drug-selective growth of non-ALK rearrangement gene tumor cells.

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SMARCB1 (INI1)‐deficient sinonasal carcinoma manifesting as oral lesions: A report of two cases

Jessie Fuoco, Michelle Huang, Najmeh Esfandiari, Christina MacMillan, Aiman Ali, Kanan Dave, Marshall Freilich, Marco Magalhaes

Publication date 12-02-2024


Abstract Background Sinonasal carcinomas represent a rare group of malignancies, accounting for less than 5% of all head and neck cancers and a worldwide incidence of less than 1 case per 100 000 inhabitants annually. Despite the restricted anatomical location, sinonasal carcinomas harbor some of the most histologically and molecularly diverse groups of tumors. SMARCB1 (INI1)-deficient sinonasal carcinomas are locally aggressive tumors commonly detected late, leading to devastating morbidity and mortality.
Case Report We present two cases of SMARCB1-deficient sinonasal carcinoma involving the oral cavity and presenting as progressive radiolucent lesions with local swelling associated with maxillary dentition and alveolar bone. Both cases were initially considered odontogenic in origin and involved the destruction of the left anterior maxilla.
Conclusion Given the rarity and the variable presentation of these tumors, they pose a challenge for head and neck surgeons, dentists, and pathologists due to the potential overlapping features with odontogenic and non-odontogenic inflammatory and neoplastic lesions. These cases highlight the importance of a multidisciplinary team and include SMARCB1-deficient sinonasal carcinomas in the differential diagnosis of destructive lesions of the maxilla.

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Issue Information

Publication date 12-02-2024


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Front Cover

Nathan J. Hansen, Karin Woodman, Sheila Buoy, Shitong Mao, Carly E. A. Barbon, Stephen Y. Lai, C. David Fuller, Katherine A. Hutcheson, Benjamin Sanchez

Publication date 12-02-2024


The cover image is based on the Original Article Tongue electrical impedance myography correlates with functional, neurophysiologic, and clinical outcome measures in long-term oropharyngeal cancer survivors with and without hypoglossal neuropathy: An exploratory study by Nathan J. Hansen BSc et al., https://doi.org/10.1002/hed.27618.

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Tumor budding to investigate local invasion, metastasis, and prognosis of head and neck carcinoma: A systematic review

Elisabetta Zanoletti, Antonio Daloiso, Lorenzo Nicolè, Diego Cazzador, Tiziana Mondello, Leonardo Franz, Laura Astolfi, Gino Marioni

Publication date 12-02-2024


Abstract The aim of this systematic review is to shed light on the role of tumor budding (TB) in the biology, behavior, and prognosis of head and neck squamous cell carcinoma (HNSCC). A search was run in Pub Med, Scopus, and Embase databases following PRISMA guidelines. After full-text screening and application of inclusion/exclusion criteria, 36 articles were included. Several investigations support the prognostic role of TB, which might play a role in selecting rational treatment strategies. To achieve this goal, further research is needed for greater standardization in TB quantification. Although TB is not included as a negative prognostic factor in the current management guidelines, it might be reasonable to consider a closer follow-up for HNSCC cases with high histopathological evidence of TB.

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Malignant carotid body tumors: What we know, what we do, and what we need to achieve. A systematic review of the literature

Cesare Piazza, Davide Lancini, Michele Tomasoni, Mark Zafereo, Vincent Vander Poorten, Ehab Hanna, Antti A. Mäkitie, Veronica Fernandez‐Alvarez, Luiz P. Kowalski, Carlos Chiesa‐Estomba, Alfio Ferlito

Publication date 12-02-2024


Abstract Malignant carotid body tumors (MCBT) are rare and diagnosed after detection of nodal or distant metastases. This systematic review (SR) focuses on MCBT initially approached by surgery. Preferred Reporting Items for SR and Meta-Analysis (MA) guided the articles search from 2000 to 2023 on Pub Med, Scopus, and Web of Science. Among 3548 papers, 132 (337 patients) were considered for SR; of these, 20 (158 patients) for MA. Malignancy rate was 7.3%, succinate dehydrogenase (SDH) mutation 17%, age at diagnosis between 4th and 6th decades, with a higher prevalence of females. MCBTs were mostly Shamblin III, with nodal and distant metastasis in 79.7% and 44.7%, respectively. Malignancy should be suspected if CBT >4 cm, Shamblin III, painful or otherwise symptomatic, at the extremes of age, bilateral, with multifocal disease, and SDHx mutations. Levels II–III clearance should be performed to exclude nodal metastases and adjuvant treatments considered on a case-by-case basis.

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Comparison of surgical outcomes of transoral robotic and endoscopic thyroidectomy: A systematic review and network meta‐analysis

Van Cuong Nguyen, Chang Myeon Song, Yong Bae Ji, Sukjoong Oh, Jin Hyeok Jeong, Kyung Tae

Publication date 12-02-2024


Abstract This study aimed to compare surgical outcomes of transoral robotic thyroidectomy (TORT) and transoral endoscopic thyroidectomy vestibular approach (TOETVA), concurrently compared with conventional transcervical thyroidectomy (CTT). A network meta-analysis, comprising 23 studies, was performed in this study. The operative time of the CTT group was significantly shorter than that of the TOETVA and TORT groups. The hospital stay of the TOETVA group was significantly longer than that of the CTT group. Rates of transient recurrent laryngeal nerve palsy and total complications were higher in association with TOETVA than with TORT. No significant differences were found between the three groups in intraoperative blood loss, retrieved lymph nodes, postoperative pain, and other complications. Cosmetic satisfaction was significantly superior with TORT and TOETVA than with CTT. Compared with CTT, TOETVA and TORT showed superior cosmesis but no significant difference in surgical outcomes except for operative time and hospital stay.

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Extended orbital exenteration, epithetic restoration, and patient supply: A cross‐sectional study of a historic cohort

Lucas M. Ritschl, Matthias Schwarz, Franziska Klinger, Klaus‐Dietrich Wolff, Minli Niu, Jochen Weitz

Publication date 12-02-2024


Abstract Background The aim of this study was to investigate the clinical course and to redefine an optimized algorithm for OE cases until epithetic restoration.
Methods Indication, defect type according to Kesting, reconstructive technique, incidence of postoperative complications and peri-implantitis, patients quality of life, timing of periorbital implant insertion, incidence of and interval to implant loss, and time until epithetic restoration were analyzed in 43 patients.
ResultsA significant correlation was detected between wound dehiscence and defect type. Out of 24 patients, 7 were implanted secondarily with a median time interval of 399 days (270–2015) after OE. Eleven out of 83 placed implants were lost in 8 patients with a median time interval of 586 days (264–4485) after insertion. The majority of epithesis carriers had no or few restrictions in their quality of life.
Conclusions We recommend our modified treatment algorithm to further improve and shorten the clinical course.

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Heterogeneous parathyroid near‐infrared autofluorescence patterns are associated with single adenomas in primary hyperparathyroidism

Sang Min Lee, Priya H. Dedhia, John E. Phay

Publication date 12-02-2024


Abstract Background Primary adenoma (PA) and multi-gland hyperplasia (MGH) account for 85% and 15% of primary hyperparathyroidism (PHPT) cases, respectively. Near-infrared autofluorescence (NIRAF) enhances intraoperative parathyroid identification. We hypothesized that PA would display a more heterogeneous NIRAF pattern compared to MGH.
Methods Patients undergoing surgery for sporadic PHPT were categorized based on the presence of PA or MGH. To quantify heterogeneity, we utilized ratios of (1) mean parathyroid gland (PG) NIRAF over background NIRAF (mean ratio), (2) minimum and (3) maximum PG NIRAF over mean PG NIRAF (minimum and maximum ratios). Additionally, a heterogeneity score was quantified using mean ratio (mean PG NIRAF over background NIRAF), and overall NIRAF (mean NIRAF of eight random 15 × 15 pixel areas). A point was assigned to ratios <0.8 or >1.2. Images were quantified by ImageJ software. Mann–Whitney test was performed for all comparisons.
Results Of 78 patients, 63 had a single PA and 15 had MGH, totaling 102 PGs. There was no difference between their mean ratios. PA had a lower minimum ratio compared to that of MGH (0.86 ± 0.01 vs. 0.93 ± 0.01, p = 0.001) and a brighter maximum ratio (1.21 ± 0.02 vs. 1.12 ± 0.01, p = 0.0008). PA also scored higher on their heterogeneity scores compared to MGH (1.27 ± 0.23 vs. 0.33 ± 0.15, p = 0.001).
Conclusion Single parathyroid adenomas display a more heterogeneous autofluorescence pattern compared to that of multi-gland hyperplasia. Intraoperative characterization of PGs by real-time NIR imaging patterns may be a beneficial adjunct during parathyroid surgery.

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Clinical validation of NerveTrend versus conventional i‐IONM mode of NIM Vital in prevention of recurrent laryngeal nerve events during bilateral thyroid surgery: A randomized controlled trial

Marcin Barczyński, Aleksander Konturek

Publication date 12-02-2024


Abstract Background The aim of this study was to test the hypothesis that use of Nerve Trend™ mode of intermittent neuromonitoring (i-IONM) during thyroidectomy may identify and prevent impending recurrent laryngeal nerve (RLN) injury.
MethodsA randomized clinical trial. The primary outcome was prevalence of RLN injury on postoperative day 1. In Nerve Trend™ group the i-IONM stimulator was used for trending of amplitude and latency changes from initial vagal electromyographic baseline to tailor surgical strategy.
Results Some 264 patients were randomized into the intervention versus the control group, 132 patients each. RLN injury was found on postoperative day 1 in 5/264 (1.89%) nerves at risk (NAR) versus 12/258 (4.65%) NAR whereas staged thyroidectomy was used in 0/132 (0.00%) versus 6/132 (4.54%) patients (p = 0.067 and p = 0.029, respectively).
Conclusion The use of Nerve Trend™ mode resulted in tendency towards reduced RLN injury on postoperative day 1 and significant decrease of need for a staged thyroidectomy.

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Differences in geometric patterns of failure in human papillomavirus (HPV)‐associated and HPV‐non‐associated oropharyngeal cancer after definitive radiotherapy

"Trada Yuvnik, Low Chia, O Connor Laura, Tieu Thi Tieu, Kumar Mahesh, Beeksma Bradley, Cope Daron, Wratten Chris"

Publication date 12-02-2024


Abstract Introduction The aim of this study was to evaluate and compare the spatial pattern of locoregional recurrences in patients diagnosed with HPV-associated and HPV-non-associated oropharyngeal SCC (OPSCC) treated with definitive radiotherapy.
Methods and materials Patients who had locoregional recurrence following definitive intensity-modulated radiation therapy were identified at a single tertiary institution. Target volumes were delineated according to the latest consensus international guidelines. Recurrences were classified into five categories based on radiotherapy dose distribution and target volume, using a previously validated methodology; type A (central high dose), type B (peripheral high dose), type C (central elective dose), type D (peripheral elective dose), and type E (extraneous dose). The types of failure were compared between p16-positive and p16-negative tumors using the Pearson chi-square test.
Results Fifty-eight locoregional recurrences were observed in 36 patients. The majority of recurrences were in nodal locations (66%, 38/58). Among these, 34 (59%) were classified as type A, 6 (10%) as type B, 9 (15%) as type C, 5 (9%) as type D, and 4 (7%) as type E failure. A significant difference was found in the types of failure between p16-positive and p16-negative tumors (X2 9.52, p = 0.044). p16-negative tumors were more likely to have recurrences in a peripheral location compared to p16-positive tumors (32% vs. 7%). p16-positive tumor were more likely to have extraneous recurrences (17% vs. 0%).
Conclusion Our study results identified a significant difference in patterns of locoregional failure among patients diagnosed with oropharyngeal cancer following consensus-based tumor delineation and modern radiotherapy. Further confirmatory pattern of failure studies are required to enable greater individualization of radiotherapy for patients diagnosed with oropharyngeal malignancy in the future.

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Implementing flexible endoscopic evaluation of swallow screening within annual cancer surveillance appointments to monitor for late‐stage radiation‐induced dysphagia: A feasibility study

Emma J. Stradling, Molly K. Barnhart, Rachelle A. Robinson, Penny J. Mogg, Elizabeth C. Ward, Robert I. Smee

Publication date 12-02-2024


Abstract Background Late-stage progressive decline of swallowing function after radiotherapy for head and neck cancer (HNC) is often difficult to monitor. This study examined the feasibility and clinical outcomes of speech-language pathology implementing flexible endoscopic evaluation of swallow (FEES) screening during annual cancer surveillance visits to monitor late-stage swallowing function.
Methods Patients >2 years post treatment who attended routine oncological visits underwent FEES screening. Feasibility (service data, stakeholder survey) and swallowing outcomes (oral intake, secretions, internal lymphedema, penetration–aspiration, and residue) were collected.
Results Screening was completed with 70% (50/71) of eligible patients. Medical staff and speech-language pathologists indicated the protocol was worthwhile and achievable to incorporate into practice. Almost all patients were willing to complete the protocol annually. FEES outcomes identified 84% with dysphagia versus only 26% self-reported dysphagia.
Conclusion Findings indicate FEES screening incorporated into annual oncological reviews is feasible and effective at monitoring late-stage swallowing function following HNC.

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A comparison of timing and patterns of treatment failure, and survival outcomes after progression between HPV+ and HPV− patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas

Francisco Laxague, Peter Y. F. Zeng, Dorsa Zabihi, Naif Fnais, Mohammed Alshahrani, Kevin Fung, Danielle MacNeil, Adrian Mendez, John Yoo, Joseph S. Mymryk, John W. Barrett, David A. Palma, Anthony C. Nichols

Publication date 12-02-2024


Abstract Background We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV-positive (HPV+) and HPV-negative (HPV−) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC).
MethodsA retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected. Kaplan–Meier estimates for overall survival (OS), and time to recurrence/metastases (TTR) were compared using the log-rank test, with Cox regression used for multivariable modeling comparing HPV+ and HPV− patients.
ResultsHPV− patients developed recurrence or metastases at earlier time points than HPV+ patients (8.8 vs. 15.2 months, p < 0.05), due to earlier local/locoregional recurrence and distant metastases, but not isolated regional recurrences. HPV− distant metastases exclusively occurred in a single organ, most commonly the lungs or bone, while HPV+ metastases frequently had multi-organ involvement in a wide variety of locations (p < 0.05). Once progression (recurrence/metastases) was diagnosed, HPV+ patients experienced superior survival to HPV− patients on univariate and multivariate analysis, largely due to improved outcomes after treatment of local/locoregional recurrences (p < 0.05). There were no differences in survival after isolated regional recurrences or distant metastases.
ConclusionHPV+ OPSCC patients relapse later compared to HPV− patients in local/locoregional and distant sites. HPV+ patients with local/locoregional recurrence experience superior survival after recurrence, which does not hold true for isolated regional recurrences or distant metastases. These data can be useful to inform prognosis and guide treatment decisions in patients with recurrent OPSCC.

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Endoscopic endonasal combined transoral medial approach to the nasopharynx, parapharyngeal space, and jugular foramen

Song Mao, Ru Tang, Yuelong Gu, Bin Chen, Weitian Zhang

Publication date 12-02-2024


Abstract Objective This study aimed to validate the feasibility of an endoscopic endonasal combined transoral medial approach for treating lesions in the nasopharynx, parapharyngeal space (PPS), and jugular foramen.
Methods Anatomical and imaging information of six patients who underwent surgery via this approach were reviewed and analyzed.
Results The feasibility and advantages of the endoscopic endonasal combined transoral medial approach, which uses an inside-to-outside medial surgical corridor, were identified. Total resection was achieved in 3 cases with benign tumors. Safe resection margins were obtained in 2 cases with recurrent nasopharyngeal carcinoma (NPC). Pathological biopsy of NPC lesion between the Eustachian tube and arterial sheath was achieved. The internal carotid artery (ICA) was accurately located and protected in all cases and no complications occurred.
Conclusion Lesions in the nasopharynx, PPS, and jugular foramen can be directly assessed via this approach. The ICA can be well identified during the surgery.

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Unveiling the role of MGMT and DAPK hypermethylation in response to anti‐EGFR agents: Molecular insights for advancing HNSCC treatment

Lidia Maria Rebolho Batista Arantes, Renato José Silva‐Oliveira, Ana Carolina de Carvalho, Matias Eliseo Melendez, Bruna Pereira Sorroche, Renan de Jesus Teixeira, Katiane Tostes, Edenir Inez Palmero, Rui Manuel Reis, André Lopes Carvalho

Publication date 12-02-2024


Abstract Background Epidermal growth factor receptor (EGFR) is frequently activated in head and neck squamous cell carcinoma (HNSCC) and serves as a valuable target for therapy. Despite the availability of the EGFR inhibitors Cetuximab, Afatinib, and Allitinib, there are limited predictive markers for their response. Understanding molecular aberrations in HNSCC could facilitate the identification of new strategies for patient clinical and biological classification, offering novel therapeutic avenues.
Methods We assessed CCNA1, DCC, MGMT, CDKN2A/p16, and DAPK methylation status in HNSCC cell lines and their association with anti-EGFR treatment response.
ResultsMGMT methylation status displayed high sensitivity and specificity in distinguishing sensitive and resistant HNSCC cell lines to Afatinib (AUC = 0.955) and Allitinib (AUC = 0.935). Moreover, DAPK methylation status predicted response to Allitinib with high accuracy (AUC = 0.852), indicating their putative predictive biomarker roles.
Conclusion These findings hold promise for the development of more personalized and effective treatment approaches for HNSCC patients.

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Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population

Qunxing Li, Genhai Zhu, Lizao Zhang, Binghui Zeng, Tingting Cai, Jiaying Wu, Bin Wei, Zhijun Xie, Lile He, Wenbing Tang, Xinyu Lin, Huaiwu Lu, Fan Wu, Jintao Huang, Huijun Hu, Niu Liu, Song Fan

Publication date 12-02-2024


Abstract Background We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort).
Methods Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the Yuan SuTM450 gene panel (Origi Med, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts.
Results Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A).
Conclusion In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.

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Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors

Cielito C. Reyes‐Gibby, Aiham Qdaisat, Renata Ferrarotto, Anecita Fadol, Jason J. Bischof, Christopher J. Coyne, Demis N. Lipe, Ehab Y. Hanna, Sanjay Shete, Jun‐Ichi Abe, Sai‐Ching J. Yeung

Publication date 12-02-2024


Abstract Background Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant.
Methods We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016–December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification of Disease-version10 (ICD-10) codes. We recorded receipt of care at the ED as one of the outcome variables.
ResultsA total of 610 HNC patients with a median follow-up time of 12.3 months (median, interquartile range = 5–30 months) comprised our study cohort. Overall, 25.7% of patients had pre-existing CVD prior to ICI treatment. Of the remaining 453 patients without pre-existing CVD, 31.5% (n = 143) had at least one CVD-related diagnosis after ICI initiation. Tachyarrhythmias (91 new events) was the most frequent CVD-related diagnosis after ICI. The time to diagnosis of myocarditis from initiation of ICI occurred the earliest (median 2.5 months, 1.5–6.8 months), followed by myocardial infarction (3.7, 0.5–9), cardiomyopathy (4.5, 1.6–7.3), and tachyarrhythmias (4.9, 1.2–11.4). Patients with myocarditis and tachyarrhythmias mainly presented to the ED for care.
Conclusion The use of ICI in HNC is still expanding and the spectrum of delayed manifestation of ICI-induced cardiovascular toxicities is yet to be fully defined in HNC survivors.

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The application of radiomics machine learning models based on multimodal MRI with different sequence combinations in predicting cervical lymph node metastasis in oral tongue squamous cell carcinoma patients

Sheng Liu, Aihua Zhang, Jianjun Xiong, Xingzhou Su, Yuhang Zhou, Yang Li, Zheng Zhang, Zhenning Li, Fayu Liu

Publication date 12-02-2024


Abstract Background The purpose of this study was to explore preliminary the performance of radiomics machine learning models based on multimodal MRI to predict the risk of cervical lymph node metastasis (CLNM) for oral tongue squamous cell carcinoma (OTSCC) patients.
MethodsA total of 400 patients were enrolled in this study and divided into six groups according to the different combinations of MRI sequences. Group I consisted of patients with T1-weighted images (T1WI) and FS-T2WI (fat-suppressed T2-weighted images), group II consisted of patients with T1WI, FS-T2WI, and contrast enhanced MRI (CE-MRI), group III consisted of patients with T1WI, FS-T2WI, and T2-weighted images (T2WI), group IV consisted of patients with T1WI, FS-T2WI, CE-MRI, and T2WI, group V consisted of patients with T1WI, FS-T2WI, T2WI, and apparent diffusion coefficient map (ADC), and group VI consisted of patients with T1WI, FS-T2WI, CE-MRI, T2WI, and ADC. Machine learning models were constructed. The performance of the models was compared in each group.
Results The machine learning model in group IV including T1WI, FS-T2WI, T2WI, and CE-MRI presented best prediction performance, with AUCs of 0.881 and 0.868 in the two sets. The models with CE-MRI performed better than the models without CE-MRI(I vs. II, III vs. IV, V vs. VI).
Conclusions The radiomics machine learning models based on CE-MRI showed great accuracy and stability in predicting the risk of CLNM for OTSCC patients.

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Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative

Nauman H. Malik, Rui Fu, Nicolin Hainc, Christopher W. Noel, John R. de Almeida, Ali Hosni, Shao Hui Huang, Eugene Yu, Agnieszka Dzioba, Andrew Leung, Arvindpaul Mangat, Danielle MacNeil, Anthony C. Nichols, Shivaprakash B. Hiremath, Santanu Chakraborty, Alborz Jooya, Marc Gaudet, Stephanie Johnson‐Obaseki, Jonathan Whelan, Reza Forghani, Michael P. Hier, Grégoire Morand, Khalil Sultanem, Joseph Dort, John Lysack, Wayne Matthews, Steven Nakoneshny, Gia Gill, Adam Globerman, Paul Kerr, Pejman Maralani, Irene Karam, Antoine Eskander

Publication date 12-02-2024


Abstract Purpose To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT).
Methods This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan–Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS.
Results Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3. With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%–78.9%) and DFS was 53.6% (47.4%–60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00–1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00–1.02, p = 0.02).
Conclusions Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

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Long‐term outcomes of patients with oral cavity cancer receiving postoperative radiotherapy after salvage neck dissection for cervical lymph node recurrence

Takeshi Fujisawa, Atsushi Motegi, Hidenari Hirata, Sadamoto Zenda, Hidehiro Hojo, Masaki Nakamura, Hidekazu Oyoshi, Kento Tomizawa, Yuzheng Zhou, Keiko Fukushi, Shun‐Ichiro Kageyama, Tomohiro Enokida, Susumu Okano, Makoto Tahara, Takeshi Shinozaki, Ryuichi Hayashi, Kazuto Matsuura, Tetsuo Akimoto

Publication date 12-02-2024


Abstract Backgrounds We aimed to clarify the outcomes of postoperative radiotherapy (PORT) after salvage neck dissection for cervical lymph node (LN) recurrence in oral cavity cancer.
Methods We retrospectively evaluated overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and adverse events of 51 patients with high-risk features receiving PORT after salvage neck dissection between 2009 and 2019.
Results After a median follow-up of 7.4 years from PORT initiation, the 7-year OS and RFS rates were 66.3% (95% CI: 54.0–81.3) and 54.6% (95% CI: 42.1–70.9), respectively. Age <70 years and isolated LN recurrence were significantly associated with longer OS and RFS. Among the 22 patients who experienced recurrence, 14 experienced recurrence within the radiation field. PORT-related grade 3 acute mucositis (35%) and late adverse events (osteoradionecrosis 4% and laryngeal stenosis 2%) were observed.
ConclusionsPORT after salvage neck dissection for cervical LN recurrence achieved good survival with acceptable toxicity.

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Quality of life and swallowing outcomes following major glossectomy: A prospective single‐center experience

Sandipta Mitra, Smriti Panda, Alok Thakar, Vimmi Gautam, Kaustav M. Talukdar, Suresh Mani, Chirom Amit Singh, Kapil Sikka, Rajeev Kumar, Sumit Kumar Das, Anup Singh

Publication date 12-02-2024


Abstract Background There exists a lacuna in the structured reporting of swallowing dysfunction and quality of life (QoL) outcome following major glossectomy.
Methods Prospective cohort study to assess the swallowing dysfunction and QoL following STG (subtotal glossectomy) or NTG (near total glossectomy) over a 6-month period using FEES and PAS scale, MDADI, and FACT-HN.
Results Twenty-four patients were available for analysis. The pre- and post-adjuvant evaluation revealed a statistically significant improvement in the composite MDADI and FACT-HN scores. Subscale analysis of FACT-HN scores revealed maximum deficit in the head and neck cancer-specific score domain followed by functional domain and social well-being domain, with serial improvement noted in the post-adjuvant setting.
Conclusion This study showed serial improvement in terms of swallowing dysfunction although social and functional well-being domains related to QoL continued to reveal major deficits. Better outcomes were seen with preservation of bilateral base of tongue and mandible.

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Development of a nomogram for predicting pharyngocutaneous fistula based on skeletal muscle mass and systemic inflammation indices

Ce Wu, Xudong Yan, Feng Xie, Xiaolong Lai, Lin Wang, Yan Jiang

Publication date 12-02-2024


Abstract Background Laryngeal and hypopharyngeal cancers often require surgical treatment, which can lead to the development of pharyngocutaneous fistula (PCF). Our research aimed to assess the predictive value of skeletal muscle mass (SMM) and systemic inflammation indices for PCF and construct a clinically effective nomogram.
MethodsA nested case–control study of 244 patients matched from 1171 patients with laryngeal or hypopharyngeal cancer was conducted. SMM was measured at the third cervical level based on CT scans. A PCF nomogram was developed based on the univariate and multivariate analyses.
Results Glucose, white blood cell count, platelet-to-lymphocyte ratio, and skeletal muscle index were independent risk factors for PCF. The area under the curve for the PCF nomogram was 0.841 (95% CI 0.786–0.897). The calibration and decision curves indicated that the nomogram was well-calibrated with good clinical utility.
Conclusions The nomogram we constructed may help clinicians predict PCF risk early in the postoperative period, pending external validation.

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"Increasing health care providers knowledge of tracheostomy and laryngectomy"

John J. Sykes IV, Kaitlyn Edwards, Deepa Danan

Publication date 12-02-2024


Abstract Background The differences between tracheostomy and total laryngectomy are frequently misunderstood by healthcare professionals. Insufficient knowledge can potentially result in life-threatening consequences in the event of an emergent airway situation.
MethodsA seven-question assessment of providers anatomical knowledge and airway management was completed prior to and following a standardized one-hour didactic lecture.
Results Forty-six participants completed the pre- and post-assessment. There were 20 (43.5%) ENT ICU/IMC Staff (EBU), 20 (43.5%) Florida Surgical Center Staff (FSC), and 6 (13%) Anesthesia providers (Anes). Pre-lecture score average was 44.7% across all providers, significantly improving to 83.8% post-lecture (p < 0.001). Nursing staff from the Otolaryngology ICU, and OR staff, had significant improvement in knowledge base (p < 0.001). Anesthesia providers showed improvement, but the difference was not statistically significant (p = 0.052).
Conclusions Didactic lectures are a simple and low-cost option with significant potential in improving provider knowledge on these critical topics and improve patient care by non-otolaryngology providers.

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Tongue electrical impedance myography correlates with functional, neurophysiologic, and clinical outcome measures in long‐term oropharyngeal cancer survivors with and without hypoglossal neuropathy: An exploratory study

Nathan J. Hansen, Karin Woodman, Sheila Buoy, Shitong Mao, Carly E. A. Barbon, Stephen Y. Lai, C. David Fuller, Katherine A. Hutcheson, Benjamin Sanchez

Publication date 12-02-2024


Abstract Background This pilot study analyzed correlations between tongue electrical impedance myography (EIM), standard tongue electromyography (EMG), and tongue functional measures in N = 4 long-term oropharyngeal cancer (OPC) survivors.
Methods Patients were screened for a supportive care trial (NCT04151082). Hypoglossal nerve function was evaluated with genioglossus needle EMG, functional measures with the Iowa oral performance instrument (IOPI), and multi-frequency tissue composition with tongue EIM.
Results Tongue EIM conductivity was higher for patients with EMG-confirmed cranial nerve XII neuropathy than those without (p = 0.005) and in patients with mild versus normal EMG reinnervation ratings (16 k Hz EIM: p = 0.051). Tongue EIM correlated with IOPI strength measurements (e.g., anterior maximum isometric lingual strength: r2 = 0.62, p = 0.020).
Conclusions Tongue EIM measures related to tongue strength and the presence of XII neuropathy. Noninvasive tongue EIM may be a convenient adjunctive biomarker to assess tongue health in OPC survivors.

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Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system

Tatsuo Ogawa, Kisho Ono, Shoji Ryumon, Hotaka Kawai, Tomoya Nakamura, Koki Umemori, Kunihiro Yoshida, Hideka Kanemoto, Kyoichi Obata, Norie Yoshioka, Tatsuo Okui, Kuniaki Okamoto, Hitoshi Nagatsuka, Soichiro Ibaragi

Publication date 12-02-2024


Abstract Background Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC.
Methods We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression.
Results The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDPs cell-killing effect.
ConclusionsEVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC.

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The art of specimen orientation: Two‐dimensional maps for oropharynx squamous cell carcinoma

Prashanthi Divakar, Stephanie S. Kim, Darcy A. Kerr, Jason R. Pettus, Joseph A. Paydarfar

Publication date 12-02-2024


Abstract The goal of surgical treatment for oropharynx squamous cell carcinoma (SCCa) is resection to negative margins. Current methods of orienting resection specimens often do not give a comprehensive view, especially in oropharynx SCCa where specimens can lack anatomic landmarks. We created standardized two-dimensional maps of oropharynx anatomy drawn to scale to improve communication between surgeons and pathologists. Notes regarding surgery including anatomic landmarks, areas of concern, additional margins, and relevant clinical information were added to the map. The maps guided pathology work-up, and the pathologist could communicate details back to the surgeon on how the specimen was sectioned or locations of microscopic foci to direct future treatment and clinical monitoring. The use of two-dimensional maps for oropharynx SCCa specimens offers a standardized solution to address the challenges of anatomic orientation. These maps summarized key pathological information, preserved clinical details from the specimens, and guided multidisciplinary conferences when planning adjuvant treatment.

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Operative technique: Pectoralis major flap with rib

Randy W. Lesh, Ryan N. Hellums, Priscilla Pichardo, Madison Gladfelter, Nicholas C. Purdy

Publication date 12-02-2024


Abstract The osteomyocutaneous pectoralis major flap was first described in 1980 and provides a single stage reconstructive option for poor free flap or pectoralis major flap with reconstruction plate candidates requiring bony reconstruction. The flap provides good functional and cosmetic outcomes in appropriately selected patients. We describe the indications and operative techinique for harvesting this flap in written and video format.

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Transoral robotic vertical partial laryngectomy (hemilaryngectomy) extended to the hypopharynx

Piero Giuseppe Meliante, Ludovica Battilocchi, Andrea Costantino, Kyuin Lee, Seo Jin Moon, Massimo Ralli, Antonio Minni, Pasquale Capaccio, Lorenzo Pignataro, Marco de Vincentiis, Se‐Heon Kim

Publication date 12-02-2024


Abstract Locally advanced laryngeal cancers treatment often involves total laryngectomy, which some patients are unwilling to undergo, even if this choice reduces their survival probability. Therefore, the objective of laryngeal oncologic surgery is not only to remove the tumor, but also to preserve the organ and its functions. To overcome these concerns, several partial laryngectomy techniques have been developed. This article describes the surgical technique and a case study of a 64-year-old male patient with locally advanced laryngeal squamous cell carcinoma who underwent vertical partial laryngectomy extending to the subglottis and hypopharynx using transoral robotic surgery (TORS) with a da Vinci Single Port surgical robot. The video and article provide a detailed description of the surgical technique, which resulted in successful tumor removal with excellent oncological and functional outcomes.

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Imaging manifestations of head and neck lymphatic malformations: A single‐center experience of 170 surgical cases

Wei Chen, Hongming Xu, Lina Zhang, Rong Xu, Xiaoyan Li, Guangbin Sun

Publication date 09-02-2024


Abstract Objectives To discuss the imaging manifestations and the utility of preoperative ultrasonography (US), contrast-enhanced computed tomography (CE-CT) and contrast enhanced magnetic resonance imaging (CE-MRI) in diagnosing the pediatric head and neck lymphatic malformations (HNLMs).
Methods We performed a retrospective review of 170 children who were referred to our hospital in the past 9 years for the treatment of HNLMs.
Results The diagnostic rates of US, CE-CT and CE-MRI were 93.0% (146/157), 94.7% (143/151) and 100% (45/45), respectively. As in multilocular cases, intracystic septa detection rate was 91.5% (130/142), 50.4% (68/135) and 88.1% (37/42), and which had a statistical difference (χ2 = 25.8131, p < 0.05). US showed capsule contents anechoic in 51.0% (80/157) cases, hypoechoic or mixed echoic in 49.0% (77/157) cases, and flocculent or dotted echo floating in 36.9% (58/157) cases. CT showed low density of the capsule contents without enhancement in 69.5% (105/151) cases and mixed density with enhancement in 30.4% (46/151) cases. Liquid–liquid levers were seen in 8.6% (13/151) cases. MRI showed T1WI high signal and T2WI low signal of the capsule contents without enhancement in 28.9% (13/45) cases and mixed density in 71.1% (32/45) cases. Liquid–liquid levers were seen in 46.7% (21/45) cases. There were statistically significant differences between pure HNLMs and intracystic hemorrhage in capsule content (echo, density, signal), enhancement, and liquid–liquid lever (all p < 0.05). Among US, CE-CT and CE-MRI, intracystic hemorrhage diagnostic accuracy had a statistical difference (χ2 = 25.4152, p < 0.05).
Conclusions For clinical diagnosis and evaluation of HNLMs, we suggest that US combined with CE-CT for acute cases, and for stable cases, US combined with CE-MRI.

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Neck management in cutaneous squamous cell carcinoma with parotid metastasis

Qigen Fang, Junhui Yuan, Xu Zhang, Liyuan Dai, Ruihua Luo, Chunmiao Xu

Publication date 09-02-2024


Abstract Objective Our objective is to assess the oncologic outcomes of observation, elective neck dissection (END), and elective neck irradiation (ENI) in the neck management of head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis (P+) and to evaluate the quality of life (QoL) of patients who received END or ENI.
Methods Patients with P+ HNcSCC were retrospectively enrolled. The impact of observation, END, and ENI on regional control (RC) and overall survival (OS) was analyzed using Cox proportional hazards model with presentation via hazard ratio (HR) with a 95% confidence interval (CI). QoL was evaluated using the University of Washington Quality of Life questionnaire.
ResultsA total of 134 patients were included in our analysis. In the Cox model for RC, both END and ENI had decreased HRs of 0.27 (95% CI: 0.15–0.69) and 0.34 (95% CI: 0.18–0.86), respectively, in comparison with observation. In the Cox model for OS, both END (p = 0.001, HR: 0.22, 95% CI: 0.10–0.72) and ENI (p = 0.006, HR: 0.30, 95% CI: 0.17–0.83) were superior to observation. In patients with three or more positive parotid lymph nodes, END resulted in significantly better RC (p < 0.001) and OS (p = 0.001) compared with ENI. The two groups were found to be comparable in all 12 domains of the University of Washington Quality of Life questionnaire.
Conclusion In the neck management of P+ HNcSCC, observation is not recommended. END is the preferred option, but ENI is an alternative method without compromise to survival or QoL, except in cases with three or more metastatic parotid lymph nodes.

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Vascular events in patients with head and neck cancer: A systematic review and meta‐analysis

Neil P. Monaghan, Kelsey A. Duckett, Shaun A. Nguyen, Jason G. Newman, W. Greer Albergotti, Alexandra E. Kejner

Publication date 09-02-2024


Abstract Objective To assess the incidence of vascular events in patients with head and neck cancer.
Review Methods Primary studies identified through April 2023. Meta-analysis was performed.
Results There were 146 studies included in the systematic review. Rates of events were collected in the overall group, those with chemoprophylaxis, and those that underwent surgery, radiation, or chemotherapy. Of 1 184 160 patients, 4.3% had a vascular event. Radiation therapy had highest risk of overall events and stroke when compared to surgery and chemotherapy. Chemotherapy had a higher risk of stroke and overall events when compared to surgery.
Conclusions Vascular events occur in 4%–5% of patients with head and neck cancer. Our data does not support the use of routine anticoagulation. Patients undergoing radiation therapy had the highest frequency of events.

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Intraoperative hybrid technique for excision of temporal bone paraganglioma: A case report

Roee Noy, Ido Livneh, Yaniv Zohar, Eitan Abergel, Yona Vaisbuch

Publication date 09-02-2024


Abstract Background Temporal bone paragangliomas are vascularized neoplasms. Although preoperative angioembolization serves as a valuable approach to reduce intraoperative blood loss, it comes with an elevated risk of cranial neuropathies, offers no assurance of complete hemostasis, and precludes real-time adjustments during surgery.
MethodsA 74-year-old patient presented with recurrent episodes of ear bleeding. On examination, a vascular lesion obstructed her external auditory canal. It had the clinical and radiological characteristics of a paraganglioma. Angiography revealed that it had three feeding vessels.
Results The patient was successfully scheduled for hybrid, intraoperative angiography and temporary balloon occlusion of the feeding vessels supplying the lesion instead of preoperative angioembolization.
Conclusions Utilizing hybrid intraoperative angiography with temporary balloon occlusion during the surgical removal of temporal bone paragangliomas represents an innovative technique that reduces the risk of permanent cranial neuropathies while providing the capacity for real-time adjustments and improved hemostasis.

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The use of customized 3D‐printed mandibular prostheses with pressure‐reducing device: A clinical trial

Chun‐Feng Chen, Chun‐Ming Chen, Wei‐Chin Huang, Sung‐Ho Liu, Ling‐Lin Wang, Pei‐Feng Liu, Ping‐Ho Chen

Publication date 08-02-2024


Abstract Background Segmental bone defects of the mandible result in the complete loss of the affected region. We had incorporated the pressure-reducing device (PRD) designs into the customized mandible prostheses (CMP) and conducted a clinical trial to evaluate this approach.
Methods Seven patients were enrolled in this study. We examined the association among the history of radiotherapy, the number of CMP regions, the number of chin regions involved, and CMP exposure.
Results We included five men and two women with an average age of 55 years. We excised tumors with an average weight of 147.8 g and the average weight of the CMP was 68.5 g. No significant difference between the two weights was noted (p = 0.3882). Three patients received temporary dentures and the CMP remained stable in all patients.
Conclusion The use of PRD in CMP may address the previous challenges associated with CMP, but further research is necessary.

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Loco‐regional radiotherapy in de novo metastatic nasopharyngeal carcinoma with chemotherapy and immunotherapy: A real‐world retrospective study from two cancer centers

Li Ma, Fengming Lan, Peng Chen, Ling Lei, Teng Zou, Fangmeng Fu, Runye Wu, Jing Jin, Jianghu Zhang

Publication date 05-02-2024


Abstract Background Immunochemotherapy has become the first-line treatment for initial diagnosed metastatic nasopharyngeal carcinoma (mNPC). Loco-regional radiotherapy combined with systemic chemotherapy significantly improves the survival. However, the safety and efficacy of loco-regional radiotherapy combined with immunochemotherapy remained unknown.
Methods Patients with de novo mNPC who received immunochemotherapy followed by loco-regional radiotherapy were included from two cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan–Meier method.
Results From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median follow-up was 28 months (range 14–47 months). No one died. One-year, 2-year, and 3-year PFS rate was 93.8%, 58.4% and 50.1%, respectively. Radiotherapy-related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%).
Conclusions Loco-regional radiotherapy provided a promising efficacy with modest toxicity for patients with mNPC who received immunochemotherapy.

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Malignancy risk of indeterminate lymph node at the central compartment in patients with thyroid cancer and concomitant sonographic thyroiditis

Jung Hyo Rhim, Ji Ye Lee, Sun‐Won Park, Younghen Lee, So Lyung Jung, Tae Jin Yun, Eun Ju Ha, Jung Hwan Baek, Jinna Kim, Dong Gyu Na, Ji‐hoon Kim

Publication date 02-02-2024


Abstract Background To evaluate the malignancy risk of sonographic (US) indeterminate lymph node (LN)s at the central compartment in thyroid cancer patients with US-thyroiditis (ST).
Methods Among the central compartments of suspicious, indeterminate, and probably benign LN US categories, the malignancy rates were compared between ST and non-US-thyroiditis (non-ST) groups. Those of indeterminate category were compared with suspicious and probably benign categories.
Results At 531 central compartments from 349 patients, the malignancy rate was lower in ST group (34.4% 44/128) than non-ST group (43.4% 175/403), although statistically not significant (p = 0.08). The malignancy rate of indeterminate category in ST group (35.7% 5/14) was lower than non-ST group (71.9% 23/32) (p = 0.047). Within ST group, the malignancy rate of indeterminate category (35.7% 5/14) did not differ from probably benign category (29.1% 30/103) (p = 0.756), but was lower than suspicious category (81.8% 9/11) (p = 0.042).
Conclusions The malignancy risk of US indeterminate LNs at the central compartment in thyroid cancer patients with US thyroiditis was lower than that in patients without US thyroiditis.

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Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma

Ester Benaiges, Victòria Ceperuelo‐Mallafré, Sandra Guaita, Elsa Maymó‐Masip, Ana Madeira, David Gómez, Victor Hernández, Isabel Vilaseca, Carla Merma, Xavier León, Ximena Terra, Joan Vendrell, Francesc Xavier Avilés‐Jurado, Sonia Fernández‐Veledo

Publication date 02-02-2024


Abstract Background Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies.
Methods We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response.
Results Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells.
Conclusions Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

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Discrimination of vocal folds lesions by multiclass classification using autofluorescence spectroscopy: An ex vivo study

Olivier Gaiffe, Joackim Mahdjoub, Emmanuel Ramasso, Olivier Mauvais, Thomas Lihoreau, Lionel Pazart, Bruno Wacogne, Laurent Tavernier

Publication date 01-02-2024


Abstract Background Autofluorescence spectroscopy is effective for noninvasive detection but underutilized in tissue with various pathology analyses. This study evaluates whether AFS can be used to discriminate between different types of laryngeal lesions in view of assisting in vocal fold surgery and preoperative investigations.
MethodsA total of 1308 spectra were recorded from 29 vocal fold samples obtained from 23 patients. Multiclass analysis was performed on the spectral data, categorizing lesions into normal, benign, dysplastic, or carcinoma.
Results Through an appropriate selection of spectral components and a cascading classification approach based on artificial neural networks, a classification rate of 97% was achieved for each lesion class, compared to 52% using autofluorescence intensity.
Conclusions The ex vivo study demonstrates the effectiveness of AFS combined with multivariate analysis for accurate classification of vocal fold lesions. Comprehensive analysis of spectral data significantly improves classification accuracy, such as distinguishing malignant from precancerous or benign lesions.

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Fasciocutaneous and jejunal free flaps for circumferential hypopharyngeal defect reconstruction: A 22‐year multicenter cohort study

Anthony M. Tonsbeek, Caroline A. Hundepool, Merel M. Smit, Pieter S. Verduijn, Liron S. Duraku, Aniel Sewnaik, Bas P. L. Wijnhoven, Marc A. M. Mureau

Publication date 31-01-2024


Abstract Background It remains unclear whether a tubed fasciocutaneous or jejunal free flap (FCFF and JFF) is preferable for reconstruction of circumferential pharyngolaryngoesophageal defects.
Methods All consecutive patients with circumferential pharyngolaryngoesophageal defects reconstructed with an FCFF or JFF between 2000 and 2022 were included. Outcomes of interest were rates of fistulas, strictures, and donor-site complications.
Results In total, 112 patients were included (35 FCFFs and 77 JFFs). Fistula and stricture rates were significantly lower following JFF compared to FCFF reconstructions, with 12% versus 34% (p = 0.008) and 29% versus 49% (p = 0.04), respectively. Severe donor-site complications leading to surgical intervention or ICU admittance only occurred after JFF reconstructions (18%, p = 0.007).
Conclusions The high fistula and stricture rates in FCFF reconstructions and the rate of severe abdominal complications in JFF reconstructions illustrate inherent procedure-specific advantages and disadvantages. Relative pros and cons should be carefully weighed when tailoring treatments to the individual needs of patients.

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Microvascular reconstruction of medication related osteonecrosis of the head and neck

Larissa Sweeny, Sallie M. Long, Patrik Pipkorn, Mark K. Wax, Carissa M. Thomas, Joseph M. Curry, Sara Yang, Daniel Lander, Farshad Chowdhury, Dev Amin, Anne C. Kane, Brett A. Miles, Andrew Salama, Steven B. Cannady, Kendall Tasche, Derek Mann, Ryan Jackson

Publication date 31-01-2024


Abstract Background Medication related osteonecrosis of the jaw (MRONJ) requiring free flap (FF) reconstruction is uncommon with limited reported findings.
Methods Multicenter, retrospective case series of 49 consecutive adult patients presenting with advanced MRONJ requiring FF reconstruction from 2010 to 2022. Perioperative complications and outcomes were analyzed.
Results Eighty-two percent (n = 40) of cases were of the mandible and 18% (n = 9) were of the maxilla. The mean follow-up was 15 months (±19.6). The majority of FF survived (96%, n = 47). FF reconstructions of the maxilla were more likely to require postoperative debridement (56%, 95% CI 27, 81% vs. 15%, 95% CI 7, 25%, p = 0.008) or develop intraoral bone exposure (56%, 95% CI 27, 81% vs. 18%, 95% CI 9, 27%, p = 0.02). Most patients (71%, n = 35) received preoperative antibiotics which was associated with a higher rate of FF survival (100% vs. 86%, 95% CI 60, 96%, p = 0.02) and fewer complications.
Conclusions Patients undergoing FF reconstruction for MRONJ do well with high rates of FF success. MRONJ of the maxilla have a higher rate of some complications. Preoperative antibiotics correlated with higher FF survival and fewer postoperative complications.

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Noninvasive monitoring of the vagus nerve during thyroid surgery using cutaneous adhesive and needle electrodes: What is the optimal configuration?

Amanda Silver Karcioglu, Lily N. Trinh, Dioan Mcllroy, Okenwa C. Okose, Bo Wang, Ian J. Behr, Anthony Y. Cheung, Adithya Srikanthan, Marika D. Russell, Dipti Kamani, Amr H. Abdelhamid Ahmed, Gregory W. Randolph

Publication date 31-01-2024


Abstract Objective Endotracheal tube (ETT) surface electrodes are used to monitor the vagus nerve (VN), recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) during thyroid and parathyroid surgery. Alternative nerve monitoring methods are desirable when intubation under general anesthesia is not desirable or possible. In this pilot study, we compared the performance of standard ETT electrodes to four different noninvasive cutaneous recording electrode types (two adhesive electrodes and two needle electrodes) in three different orientations.
Methods The VN was stimulated directly during thyroid and parathyroid surgery using a Prass stimulator probe. Electromyographic (EMG) responses for each patient were recorded using an ETT plus one of the following four cutaneous electrode types: large-foot adhesive, small-foot adhesive, long-needle and short-needle.
Each of the four electrode types was placed in three orientations: (1) bilateral, (2) ipsilateral mediolateral, and (3) ipsilateral craniocaudal.
Results Four surgical cases were utilized for data collection with the repetitive measures obtained in each subject. Bilateral electrode orientation was superior to ipsilateral craniocaudal and ipsilateral mediolateral orientations. Regardless of electrodes type, all amplitudes in the bilateral orientation were >100 μV. When placed bilaterally, the small-foot adhesive and the long-needle electrodes obtained the highest EMG amplitudes as a percentage of ETT amplitudes.
Conclusion Cutaneous electrodes could potentially be used to monitor the VN during thyroid and parathyroid procedures. Different electrode types vary in their ability to record amplitudes and latencies. Bilateral orientation improves EMG responses in all electrode types. Additional validation of cutaneous electrodes as an alternative noninvasive method to monitor the VN is needed.

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Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study

Koji Ushiro, Yoshiki Watanabe, Yo Kishimoto, Yoshitaka Kawai, Shintaro Fujimura, Ryo Asato, Takashi Tsujimura, Ryusuke Hori, Yohei Kumabe, Kaori Yasuda, Hisanobu Tamaki, Takehiro Iki, Yoshiharu Kitani, Keisuke Kurata, Tsuyoshi Kojima, Kuniaki Takata, Shinpei Kada, Shinji Takebayashi, Shogo Shinohara, Kiyomi Hamaguchi, Masakazu Miyazaki, Tadashi Ikenaga, Toshiki Maetani, Hiroyuki Harada, Tomoyuki Haji, Koichi Omori

Publication date 31-01-2024


Abstract Background Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery.
Methods We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021.
Results Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035).
Conclusions In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

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Correction to “Endoscopic‐assisted total maxillectomy with precise surgical margins”

Publication date 30-01-2024


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Correction to “Transcriptional subtypes of glottic cancer characterized by differential activation of canonical oncogenic programming”

Publication date 30-01-2024


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Genetic and environmental contributions for the relationship between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma

Adriana M. da Silva, Michelle M. L. Falcão, Valéria S. Freitas, Alexandre R. Vieira

Publication date 30-01-2024


Abstract Background To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants.
Methods Case–control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single-nucleotides polymorphisms were tested for individuals with and without missing teeth.
Results Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively).
Conclusions Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma.

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Effectiveness and risk of second primary malignancies after radiotherapy in major salivary gland carcinomas: A retrospective study using SEER database

Yuan Feng, Kai Qian, Kai Guo, Yuan Shi, Jiaqing Zhou, Zhuoying Wang

Publication date 29-01-2024


Abstract Objective To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients.
Methods Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs.
Results Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower.
Conclusion Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.

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Early outcomes of osteofascial versus osteocutaneous fibula free flap mandibular reconstruction

Shahaf Shilo, Nidal Muhanna, Dan M. Fliss, Gilad Horowitz, Anton Warshavsky, Jobran Mansour, Clariel Ianculovici, Ehud Fliss, Yoav Barnea, Arik Zaretski, Ravit Yanko

Publication date 26-01-2024


Abstract Background This study compares early outcomes of osteofascial fibula free flap (OF-FFF) with donor-site primary closure and osteocutaneous (OC) FFF with donor-site skin grafting in segmental mandibular reconstruction.
MethodsA retrospective chart review of FFF mandibular reconstruction patients (2006–2022) divided into OF-FFF and OC-FFF groups. Clinical data, operative parameters, and early postoperative outcomes (≤ 90 days) were analyzed.
Results The study included 67 patients (39 OF-FFF, 28 OC-FFF). OF-FFF had significantly lower donor-site complications (12.8% vs. 53.6%, p < 0.001) and revision surgeries (7.7% vs. 35.7%, p = 0.004) compared to OC-FFF. Recipient-site (28.2% vs. 25%, p = 0.77) and flap (15.4% vs. 17.9%, p > 0.99) complications were comparable.
ConclusionsOF-FFF mandibular reconstruction with donor-site primary closure is a safe and reliable technique associated with superior donor-site and comparable flap and recipient-site outcomes to OC-FFF, thus may be considered as a viable alternative to OC-FFF for selected patients.

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Perforator‐based chimeric ulnar forearm microvascular free tissue transfer reconstruction of post‐radiated tracheoesophageal puncture fistulae

Ray Wang, Victoria Manon, Andrew T. Huang

Publication date 26-01-2024


Abstract Tracheoesophageal puncture (TEP) performed during total laryngectomy in the primary treatment of laryngeal cancer is the standard method for voice restoration. Following adjuvant radiotherapy, the TEP site can experience complications resulting in a tracheoesophageal fistula (TEF) with chronic leakage making oral alimentation unsafe due to aspiration. Here, we describe a technique using chimeric ulnar artery perforator forearm free flaps (UAPFF) in the reconstruction of these complex deformities. Four patients underwent chimeric UAPFF reconstruction of TEP site TEFs following primary TL with TEP and adjuvant radiotherapy. No flap failures or surgical complications occurred. Average time from end of radiotherapy to persistent TEF was 66 months (range 4–190 months). All patients had resolution in their TEF with average time to total oral diet achievement of 22 days (14–42 days). Chimeric UAPFF reconstruction is a safe and effective method to reconstruct recalcitrant TEP site TEFs.

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Pedicled flaps reconstruction of hypopharynx and laryngeal defects: Successful preservation of laryngeal function in patients with advanced hypopharyngeal cancer

Leyu Li, Lixiao Fan, Zheng Jiang, Xin Yang, Dejuan Wang, Fei Chen, Deying Gu, Jun Liu

Publication date 26-01-2024


Abstract Background Preserving laryngeal function and reconstructing the hypopharynx in advanced hypopharyngeal cancer pose significant challenges for head and neck surgeons.
MethodsA 48-year-old male patient was diagnosed with advanced hypopharyngeal cancer originating from the left pyriform sinus. The tumor extended into the hypopharynx, left vocal cord, ventricular fold, partial aryepiglottic fold, and a segment of the cervical esophagus. A curative tumor resection was performed, and a well-thought-out strategy was employed for hypopharyngeal repair and laryngeal reconstruction.
Results Following the surgery, the patient demonstrated exceptional flap survival, and the tracheostomy tube was removed at the 6-month mark. No surgery-related complications were observed, and both swallowing and vocal functions exhibited a robust recovery.
Conclusion Our reconstruction strategy proves effective in preserving laryngeal function among patients with advanced hypopharyngeal cancer.

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"Succinate dehydrogenase mutations in head and neck paragangliomas: A systematic review and meta‐analysis of individual patients data"

Elizabeth S. Koh, Anas Dabsha, Mohamed Rahouma, Kyle Zappi, Yashes Srinivasan, Andy Hickner, David I. Kutler

Publication date 25-01-2024


Abstract Background Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs.
Methods Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochrans Q test and I2 test assessed heterogeneity. Funnel plot and Eggers regression test assessed publication bias.
Results Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations.
Conclusion Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.

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Cutaneous fistula formation after thyroid nodule rupture: A rare complication after radiofrequency ablation

Amanda J. Bastien, Luv Amin, Jeffrey Moses, Wendy Sacks, Allen S. Ho

Publication date 25-01-2024


Abstract Background With innovative treatment options such as radiofrequency ablation (RFA) for thyroid nodules, new complications are being identified. It is important to define and delineate complications in order to counsel patients appropriately about treatment options and their associated risks and benefits.
MethodsA 46-year-old male presented with a left thyroid nodule (6.5 cm). Fine needle aspiration results were benign. He started to develop intermittent dyspnea and underwent one RFA procedure. Approximately 6 days post-RFA, the neck area was raised and red with blister. The skin overlying the blister underwent eventual dehiscence with fluid spillage. Several months later, MRI imaging showed substernal extension with tracheal deviation.
ResultsA left thyroid lobectomy was performed with cutaneous excision and successful closure of a fistula.
Conclusions This is the first reported case of a thyroid nodule rupture following RFA which manifested into a thyro-cutaneous fistula and required surgical intervention.

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Complications related to thyroidectomy among patients with hyperthyroidism: Exploring the potential for ambulatory surgery

Faye G. Zhang, Thomas J. Ow, Juan Lin, Richard V. Smith, Bradley A. Schiff, Carolyn A. DeBiase, John C. McAuliffe, Noah Bloomgarden, Vikas Mehta

Publication date 25-01-2024


Abstract Background Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied.
Methods This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions.
Results Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted.
Conclusion Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.

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Impact of pretreatment body mass index on the survival of head and neck cancer patients

Zheng Yang, Jobran Mansour, Peng Sun, Peng Wei, Kristina R. Dahlstrom, Mark Zafereo, Guojun Li, Neil D. Gross

Publication date 25-01-2024


Abstract Background Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite.
Methods Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival.
ResultsBMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors.
Conclusions This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.

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Safety and outcome of three‐dimensional transoral videolaryngoscopic surgery

Koji Ebisumoto, Akihiro Sakai, Hiroaki Iijima, Daisuke Maki, Mayu Yamauchi, Kosuke Saito, Shoji Kaneda, Takanobu Teramura, Takane Watanabe, Toshihide Inagi, Ryoko Yanagiya, Aritomo Yamazaki, Hiroshi Ashida, Yoshiyuki Ota, Yurina Sato, Ai Yamamoto, Naoya Kobayashi, Kenji Okami

Publication date 24-01-2024


Abstract Background Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS).
Methods This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed.
Results One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively.
Conclusions Three-dimensional endoscopy can be safely applied to TOVS.

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