Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

Chronic heart failure in patients undergoing major head and neck surgery: A hospital-based study.

OBJECTIVE: To investigate the effects of chronic heart failure on various post-operative outcomes in head and neck cancer patients undergoing major cancer surgery. STUDY DESIGN: For this retrospective cohort study of patients undergoing major head and neck cancer surgery, a sample of 10,002 patients between 2017 and 2019 were identified through the Nationwide Inpatient Sample. SETTING: Patients were selected as undergoing major head and neck cancer surgery, defined as laryngectomy, pharyngectomy, glossectomy, neck dissection, mandibulectomy, and maxillectomy, then separated based on pre-surgical diagnosis of chronic heart failure. METHODS: The effects of pre-operative chronic heart failure on post-surgical outcomes in these patients were investigated by univariable and multivariable logistic regression using ICD-10 codes and SPSS. RESULTS: A diagnosis of chronic heart failure was observed in 265 patients (2.6 %). Patients with chronic heart failure had more preexisting comorbidities when compared to patients without chronic heart failure (mean ± SD; 4 ± 1 vs. 2 ± 1). Multivariable logistic regression showed that chronic heart failure patients had significantly greater odds of dying during hospitalization (OR 2.86, 95 % CI 1.38-5.91) and experiencing non-routine discharge from admission (OR 1.89, 95 % CI 1.41-2.54) after undergoing major head and neck cancer surgery. CONCLUSION: Chronic heart failure is associated with greater length of stay and hospital charges among head and neck cancer patients undergoing major head and neck cancer surgeries. Chronic heart failure patients have significantly greater rates of unfavorable post-operative outcomes, including death during hospitalization and non-routine discharge from admission.

Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

Rapalogs induce non-apoptotic, autophagy-dependent cell death in HPV-negative TP53 mutant head and neck squamous cell carcinoma.

TP53 is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis, necessitating additional agents for treatment. Since mutant p53 causes sustained activation of the PI3K/AKT/mTOR signaling pathway, we investigated the effect of rapalogs RAD001 and CCI-779 on HPV-negative mutTP53 HNSCC cell lines and xenografts. Rapalogs significantly reduced cell viability and colony formation. Interestingly, rapalogs-induced autophagy with no effect on apoptosis. Pretreatment with autophagy inhibitors, 3-methyladenine (3-MA) and ULK-101 rescued the cell viability by inhibiting rapalog-induced autophagy, suggesting that both RAD001 and CCI-779 induce non-apoptotic autophagy-dependent cell death (ADCD). Moreover, rapalogs upregulated the levels of ULK1 and pULK1 S555 with concomitant downregulation of the mTORC1 pathway. However, pretreatment of cells with rapalogs prevented the ULK-101-mediated inhibition of ULK1 to sustained autophagy, suggesting that rapalogs induce ADCD through the activation of ULK1. To further translate our in vitro studies, we investigated the effect of RAD001 in HPV-negative mutTP53 (HN31 and FaDu) tumor cell xenograft model in nude mice. Mice treated with RAD001 exhibited a significant tumor volume reduction without induction of apoptosis, and with a concomitant increase in autophagy. Further, treatment with RAD001 was associated with a considerable increase in pULK1 S555 and ULK1 levels through the inhibition of mTORC1. 3-MA reversed the effect of RAD001 on FaDu tumor growth suggesting that RAD001 promotes ACDC in HPV-negative mutTP53 xenograft. This is the first report demonstrating that rapalogs promote non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. Further studies are required to establish the promising role of rapalogs in preventing the regrowth of HPV-negative mutTP53 HNSCC.

TP53 mutations in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Fibroblast growth factor receptor promotes progression of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived invasive and metastatic tumor of the skin. It is the second-most commonly diagnosed form of skin cancer striking 200 000 Americans annually. Further, in organ transplant patients, there is a 65- to 100-fold increased incidence of cSCC compared to the general population. Excision of cSCC of the head and neck results in significant facial disfigurement. Therefore, increased understanding of the mechanisms involved in the pathogeneses of cSCC could identify means to prevent, inhibit, and reverse this process. In our previous studies, inhibition of fibroblast growth factor receptor (FGFR) significantly decreased ultraviolet B-induced epidermal hyperplasia and hyperproliferation in SKH-1 mice, suggesting an important role for FGFR signaling in skin cancer development. However, the role of FGFR signaling in the progression of cSCC is not yet elucidated. Analysis of the expression of FGFR in cSCC cells and normal epidermal keratinocytes revealed protein overexpression and increased FGFR2 activation in cSCC cells compared to normal keratinocytes. Further, tumor cell-specific overexpression of FGFR2 was detected in human cSCCs, whereas the expression of FGFR2 was low in premalignant lesions and normal skin. Pretreatment with the pan-FGFR inhibitor; AZD4547 significantly decreased cSCC cell-cycle traverse, proliferation, migration, and motility. Interestingly, AZD4547 also significantly downregulated mammalian target of rapamycin complex 1 and AKT activation in cSCC cells, suggesting an important role of these signaling pathways in FGFR-mediated effects. To further bolster the in vitro studies, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice with SCC12A tumor xenografts treated with AZD4547 (15 mg/kg/bw, twice weekly oral gavage) exhibited significantly decreased tumor volume compared to the vehicle-only treatment group. The current studies provide mechanistic evidence for the role of FGFR and selectively FGFR2 in the early progression of cSCC and identifies FGFR as a putative therapeutic target in the treatment of skin cancer.

SKLB188 inhibits the growth of head and neck squamous cell carcinoma by suppressing EGFR signalling.

BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) occurs in approximately 90% of head and neck squamous cell carcinoma (HNSCC), and is correlated with poor prognosis. Thus, targeting EGFR is a promising strategy for treatment of HNSCC. Several small molecule EGFR inhibitors have been tested in clinical trials for treatment of HNSCC, but none of them are more effective than the current chemotherapeutic drugs. Thus, it is urgently needed to develop novel EGFR inhibitors for HNSCC treatment. METHODS: By screening an in-house focused library containing approximately 650 000 known kinase inhibitors and kinase inhibitor-like compounds containing common kinase inhibitor core scaffolds, we identified SKLB188 as a lead compound for inhibition of EGFR. The anticancer effects of SKLB188 on HNSCC cells were investigated by in vitro cell growth, cell cycle and apoptosis assays, as well as in vivo FaDu xenograft mouse model. Molecular docking, in vitro kinase profiling and western blotting were performed to characterise EGFR as the molecular target. RESULTS: SKLB188 inhibited HNSCC cell proliferation by inducing G1 cell cycle arrest, which was associated with downregulating the expression of Cdc25A, cyclins D1/A and cyclin-dependent kinases (CDK2/4), and upregulating the expression of cyclin-dependent kinase (CDK) inhibitors (p21Cip1 and p27Kip1), leading to decreased phosphorylation of Rb. SKLB188 also induced caspase-dependent apoptosis of HNSCC cells by downregulating the expression of Mcl-1 and survivin. Molecular docking revealed that SKLB188 could bind to the kinase domain of EGFR through hydrogen bonds and hydrophobic interactions. In vitro kinase assay showed that SKLB188 inhibited the activity of a recombinant human EGFR very potently (IC50=5 nM). Western blot analysis demonstrated that SKLB188 inhibited the phosphorylation of EGFR and its downstream targets, extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) and Akt in the cells. In addition, SKLB188 dose-dependently inhibited FaDu xenograft growth in nude mice, and concurrently inhibited the phosphorylation of Erk1/2 and Akt in the tumours. CONCLUSIONS: SKLB188 potently inhibits the growth of HNSCC cells in vitro and in vivo by targeting EGFR signalling. The results provide a basis for further clinical investigation of SKLB188 as a targeted therapy for HNSCC. Our findings may open a new avenue for development of novel EGFR inhibitors for treatment of HNSCC and other cancers.

Association between human papilloma virus/Epstein-Barr virus coinfection and oral carcinogenesis.

BACKGROUND: The recent epidemic of head and neck squamous cell carcinomas associated with human papilloma virus (HPV) has not addressed its association with lymphoid tissue in the oropharynx or the potential role of Epstein-Barr virus (EBV)/HPV coinfection. METHODS: The prevalence of HPV and EBV infection/coinfection and CD21 mRNA expression were determined in normal and cancerous tissues from the oropharynx using in situ hybridization (ISH), p16, and quantitative reverse transcriptase PCR (qRT-PCR). The effects of coinfection on tumorigenicity were evaluated using proliferation and invasion assays. RESULTS: Normal oropharynx, tonsil, non-cancer base of tongue (BOT), and BOT from sleep apnea patients demonstrated EBV positivity ranging from 7% to 36% depending on the site and methods of detection used (qRT-PCR or ISH). Among non-malignant BOT samples, HPV positivity was noted only in 20%. The percent of tonsil and BOT cancers positive for HPV (up to 63% and 80%, respectively) or coinfected with HPV/EBV (up to 25% and 70%, respectively) were both significantly associated with cancer status. Notably, HPV/EBV coinfection was observed only in malignant tissue originating in lymphoid-rich oropharynx sites (tonsil, BOT). CD21 mRNA (the major EBV attachment receptor) was detected in tonsil and BOT epithelium, but not in soft-palate epithelium. Coinfected cell lines showed a significant increase in invasiveness (P < 0.01). CONCLUSIONS: There is a high prevalence of HPV/EBV infection and coinfection in BOT and tonsil cancers, possibly reflecting their origins in lymphoid-rich tissue. In vitro, cells modeling coinfection have an increased invasive potential.

Inducible Keratinocyte Specific FGFR2 Deficiency Inhibits UVB-Induced Signaling, Proliferation, Inflammation, and Skin Carcinogenesis.

A potential role for fibroblast growth factor receptor 2 (FGFR2) in cutaneous squamous cell carcinoma (cSCC) has been reported. To demonstrate the specific role of FGFR2 in UVB-induced skin carcinogenesis and development of cSCC, we generated a keratinocyte specific, tamoxifen inducible mouse model of FGFR2 deficiency. In this mouse model, topical application of 4-hydroxy tamoxifen led to the induction of Cre recombinase to delete FGFR2 in epidermal keratinocytes of both male and female transgenic mice. Analysis of epidermal protein lysates isolated from FGFR2 deficient mice exposed to UVB showed significant reductions of phospho-FGFR (pFGFR; Y653/654) and phospho-fibroblast growth factor receptor substrate 2α as well as downstream effectors of mTORC1 signaling. Phosphorylation of signal transducer and activators of transcription 1/3 was significantly reduced as well as levels of IRF-1, DUSP6, early growth response 1, and PD-L1 compared to the control groups. Keratinocyte-specific ablation of FGFR2 also significantly inhibited epidermal hyperproliferation, hyperplasia, and inflammation after exposure to UVB. Finally, keratinocyte-specific deletion of FGFR2 significantly inhibited UVB-induced cSCC formation. Collectively, the current data demonstrate an important role of FGFR2 in UVB-induced oncogenic signaling as well as development of cSCC. In addition, the current preclinical findings suggest that inhibition of FGFR2 signaling may provide a previously unreported strategy to prevent and/or treat UVB-induced cSCC.

Established Adult Tracheostomy Tube Exchange: How Often is Enough?

Currently, there is no clinical consensus on how often adults with long-term tracheostomies should have their tubes exchanged. For high-functioning patients who are able to provide diligent tracheostomy care tubes can be exchanged every 6 months. Patients who have a difficult time with tracheostomy care should have them exchanged every 1-3 months.

Impact of Dementia on the Postoperative Outcomes in Patients Undergoing Surgery for Head and Neck Cancers: A National Study.

BACKGROUND: Dementia, a growing concern among the elderly, has an increased poor postoperative outcome that goes unrecognized by many. Our study aims to establish if dementia plays a role in the outcomes of head and neck cancer patients that undergo resections. METHODS: We queried the National Inpatient Sample (NIS) database from 2016 to 2019 with a primary diagnosis of head and neck cancer who underwent surgical resection. Outcomes analyzed include postoperative delirium, ICU stay, complications, length of stay, and non-routine discharge. RESULTS: A total of 77095 patients were included, of which 1140 patients had dementia. The mean age of the patients with dementia was 77.5 years (±9.1) versus 63.2 years (±12.1) with no dementia. Dementia patients had a higher non-home discharge rate (77.2% vs 46.8%, p = <0.001), extended length of stay (10.9 days ±14.7 vs 7.9 days ±8.8), postoperative delirium (15.4% vs 1.5%, p = <0.001), and longer ICU stay (8.3% vs 5.8%) as compared with patients with no dementia. A higher number of patients with Dementia were placed in long-term facilities (53.5% vs 14.6%) postoperatively. More dementia patients (7.9% vs 0.9%) were transferred in from another health care facility for surgery. Dementia was associated with higher odds of delirium (OR, 6.36; 95% CI, 5.2-7.77), non-routine discharge (OR, 2.05; 95% CI, 1.76-2.3), ventilation (OR, 0.8; 95% CI, 0.6-1.05), and length of stay (estimate 3.01, 95% CI, 1.84-4.184). CONCLUSION: Preoperative dementia significantly impacts postoperative delirium, non-home discharge, and extended length of stay in head and neck cancer patients undergoing surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1258-1264, 2024.

Survival Outcomes of Transoral Microsurgery in T3/T4a Laryngeal Tumors: Systematic Review and Meta-Analysis.

OBJECTIVE: To critically evaluate oncological and functional outcomes following transoral laser microsurgery (TLM) in patients with T3/T4a glottic and supraglottic squamous cell carcinoma (SCC). DATA SOURCES: A comprehensive search of five major databases-PubMed, Embase, Scopus, ScienceDirect, and Web of Science-was conducted using a combination of relevant keywords and MeSH terms. REVIEW METHODS: Systematic review and meta-analysis of odds ratio (OR), hazards ratio (HR), and proportion, focusing on oncological and functional outcomes of TLM in advanced T3/T4a glottic and supraglottic tumors. A random-effects meta-analysis model was employed. RESULTS: The review incorporated 29 cohort studies, representing a total of 1,897 patients undergoing TLM for T3/T4a glottic and supraglottic SCC. The cumulative 5-year disease-free survival (DFS) rate for T3 glottic and supraglottic tumors was 44.4% (95% CI: 47-66%) and 62.8% (95% CI: 63-81%), while the 5-year DFS for T4 glottic and supraglottic tumors was 41.1% (95% CI: 33.4-49.2%) and 32.9% (95% CI: 19.3-50.1%), respectively. T3 glottic tumors exhibited a 2.5-fold significantly higher odds of local recurrence post-TLM compared to their T3 supraglottic tumors (95% CI: 1.6-3.9, p < 0.0001). Laryngeal preservation rates for T3glottic and supraglottic tumors were 68.9% (95% CI: 48.7-83.8%) and 88.4% (95% CI: 79.4-93.8%), respectively. Both groups showed comparable rates of tracheostomy (p = 0.48) and gastrostomy performed (p = 0.17). CONCLUSIONS: This meta-analysis suggests that TLM is a viable larynx preservation approach in select patients with T3/T4a glottic and supraglottic tumors. However, glottic tumors may have less favorable outcomes after TLM compared to those with advanced supraglottic tumors. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024 Laryngoscope, 2024.

Vocal Cord Function Return After Larynx Preservation is Associated With Recurrence-Free Probability.

OBJECTIVES: Vocal cord fixation is one of the main upstaging features of laryngeal cancer. In our previously conducted retrospective study, vocal cord (VC) mobility restoration after chemoradiotherapy was a favorable prognostic variable. In this prospective study, we examined the significance of VC mobility restoration after definitive treatment as a prognostic variable. METHODS: In this prospective cohort study, we enrolled 30 patients with squamous cell carcinoma of the larynx with VC impairment/fixation (T2/3, T4a) who underwent definitive chemoradiotherapy with complete response. Video laryngoscopy before and at 3 months after treatment was used to evaluate VC mobility. The primary endpoint of the study was the local recurrence-free probability. Secondary endpoints included recurrence-free probability, disease-specific survival (DSS), and overall survival (OS). RESULTS: The median age of patients was 62 years (IQR 54-67). The primary subsites were the glottis (n = 13) and supraglottis (n = 14). After treatment, 18 (60%) patients had a full recovery of VC mobility, and 12 (40%) patients' VCs were fixed or impaired. Five-year local recurrence-free probability was worse in the VC-impaired group compared to a group with restored VC mobility (46% vs. 85%, p = 0.012). Recurrence-free probability, OS, and DSS differences were not statistically significant in both groups. VC mobility restoration predicted local recurrence-free probability on univariable analysis (HR 6.15, 95% CI 1.23-30.6). CONCLUSION: In this prospective study, we show that the absence of VC mobility restoration is associated with worse local recurrence-free probability after definitive laryngeal preservation treatment. Patients with persistent vocal cord immobility warrant closer follow-up to detect recurrence early. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

ctDNA as an Adjunct to Posttreatment PET for Head and Neck Cancer Recurrence Risk Assessment.

OBJECTIVE: Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence. STUDY DESIGN: Retrospective Single Institutional Study. SETTING: University Hospital Setting. METHODS: Twenty-nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment. A personalized, tumor-informed, multiplex polymerase chain reaction (PCR) next-generation sequencing (NGS) assay was used to detect the ctDNA levels. The primary outcome was recurrence-free probability (RFP), and the secondary outcomes were overall survival (OS), sensitivity, specificity, and the test's negative (NPV) and positive predictive values (PPV). RESULTS: The median age of patients was 65 years (interquartile range: 56-69), with majority being males (n = 22, 76%). The primary sites were larynx (n = 12), oropharynx (n = 10), and oral cavity (n = 6). Posttreatment ctDNA was detected in 7 patients, all of whom had disease recurrence. ctDNA detection after definitive treatment was associated with a higher risk of disease recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56-63.3, P = .015). ctDNA identified recurrence with 100% specificity and 78% sensitivity. The NPV and PPV were 91% and 100%. PET had 78% sensitivity but only 68% specificity with 86% NPV, and 54% PPV. CONCLUSION: Based on our data, ctDNA can be an excellent adjunct test for posttreatment PET and can help guide physicians in cases where PET results are inconclusive and difficult to interpret.

Sexual history of patients with human papillomavirus positive and negative oropharyngeal cancer: A systematic review and meta-analysis.

BACKGROUND: Increased sexual activity is associated with higher human papillomavirus (HPV) rates; however, there is a lack of analysis comparing the sexual history of patients with HPV positive and HPV negative oropharyngeal cancer (OPC). METHODS: In this meta-analysis, PubMed, Scopus, and CINAHL were searched for articles that included patients with OPC and reported information regarding HPV status and either history of oral sex, number of sexual partners, or sexually transmitted infections (STI). RESULTS: A total of 11 studies were included with 3296 patients with OPC. Patients with HPV positive OPC were more likely than patients with HPV negative OPC to report a history of oral sex (92%, 95% CI: 87.0-97.0 vs. 74.5%, 95% CI: 50.6-98.4, p < 0.0001), higher mean number of sexual partners (18.4 partners, 95% CI: 1.5-35.4 vs. 7.2 partners, 95% CI: 1.0-13.4, p < 0.0001), and more frequent history of STI (23.7%, 95% CI: 18.4-29.0 vs. 8.8%, 95% CI: 4.7-12.8, p = 0.0001). CONCLUSIONS: Compared to patients with HPV negative OPC, our analysis shows a larger proportion of patients with HPV positive OPC had participated in oral sex, had a higher number of sexual partners, and had a higher proportion of STI history.

Outcomes of internal mammary artery perforator flap in head and neck reconstruction: A systematic review.

This study aims to evaluate the functional and prognostic outcomes associated with the internal mammary artery perforator (IMAP) flap in various head and neck defect repairs, given the current lack of clarity on its effectiveness. We performed a systematic review of various databases: PubMed, Embase, Scopus, Web of Science, and ScienceDirect using keywords such as "Internal mammary artery perforator flap" and "IMAP." Screening and data extractions were performed by two individual reviewers. Articles were considered eligible if they included sufficient information on IMAP flap features, their applications in the head and neck, and outcomes. From 264 articles analyzed, 24 studies were included for qualitative analysis. Out of which, 125 patients who received internal mammary artery perforator flaps were included. Most of the patients, 103 (88%), received pedicled IMAP flaps, and 22 (12%) received IMAP free flaps. The second internal mammary artery (IMA) was favored as the single perforator (81.5%), with the combination of the first and second IMA being the primary choice for dual perforators (92.5%). IMAP flaps were predominantly single perforator flaps (65%), with 35% being dual perforator flaps. Among various applications, IMAP flaps are commonly employed in the reconstruction of neck defects (25.5%), pharyngocutaneous fistula repair (20.8%), and burn scar contracture restoration (8%). Only seven (5.6%) patients had flap complications, including venous congestion (1.6%), partial necrosis (1.6%), complete necrosis (1.6%), and incision dehiscence (0.8%). Donor sites were predominantly closed by the primary closure (92%). 3.2% of donor sites had minor complications. The average follow-up was 12.6 (IQR: 6-18) months. This systematic review highlights the effectiveness and safety of IMAP flaps in head and neck reconstruction, with positive outcomes and minimal complications.

Efficacy and safety of proton therapy versus intensity-modulated radiation therapy in the treatment of head and neck tumors: A systematic review and meta-analysis.

To comprehensively evaluate the therapeutic efficacy and safety when utilizing proton therapy (PT) versus intensity-modulated radiation therapy (IMRT) in head and neck cancer patients. Pubmed, ScienceDirect, Embase, Scopus, and Web of Science were systematically searched for studies on comparative PT and IMRT outcomes. We performed a random effect model meta-analysis to estimate the hazard ratio (HR) and odds ratio (OR) for efficacy and safety outcome variables between PT and IMRT. From 641 identified articles, 11 studies met the inclusion criteria, comprising 3087 patients (606 treated with PT and 2481 with IMRT). On toxicity analysis, PT is associated with decreased acute grade 1 nausea (OR = 0.34, 95% CI: 0.13-0.84, p = 0.02) compared to IMRT. In grade 2 toxicity, PT showed significant advantages over IMRT in mucositis (OR = 0.44, p < 0.0001), dysgeusia (OR = 0.35, p = 0.02), dysphagia (OR = 0.36, p < 0.0001), fatigue (OR = 0.29, p = 0.001), pain (OR = 0.34, p = 0.01), and weight loss (OR = 0.54, p = 0.02). Proton therapy also exhibited increased safety in grade 3 dysphagia incidence (OR = 0.44, p < 0.0001) compared to IMRT. PT demonstrated improved overall survival (OS) compared to IMRT across multiple time points: 1-year OS (HR = 0.43, p = 0.02), 2-year OS (HR = 0.44, p < 0.0001), and 5-year OS (HR = 0.78, p = 0.004). In terms of disease-free survival (DFS), PT also showed improved outcomes at 2-year DFS (HR = 0.65, p = 0.03) and 5-year DFS (HR = 0.81, p = 0.03). Proton therapy demonstrated superior overall survival (OS), disease-free survival (DFS), and better local control rate (LCR) compared to IMRT. The data also showed better safety outcomes in PT patients, particularly when involving grade 2 acute toxicity events.

Risk Factors for Complications in Patients Undergoing Temporal Bone Resection and Neck Dissection: Insights From a National Database.

BACKGROUND: Temporal bone resection (TBR) with or without neck dissection (ND) is performed for otologic malignancies with occult or clinical cervical lymph node metastases. To date, characterization of post-operative complications in single institution case series may be non-representative of real-world outcomes. Here, we used data from the National Inpatient Sample (NIS) to comprehensively assess the complications encountered, their frequencies, and to identify underlying risk factors to improve future outcomes. METHODS: The population was patients undergoing TBR and ND derived from the NIS between the years of 2017 and 2019. We utilized ICD-10 diagnosis codes to identify patients with post-operative complications, those discharged to non-home facilities (DNHF), and those with increased length of stay (LOS). Multivariable regression was performed to identify significant variables related to the above outcomes. RESULTS: Ninety of 277 patients that underwent LTBR with ND had postoperative complications. Wound complications were the most frequent complication, occurring in 11 (4%) of patients, followed by CSF leak (n = 6; 2.2%), with acute respiratory failure being the most common medical complication (n = 4; 1.4%). Sixteen percent (45/277) were discharged to a facility besides home. Dementia (OR = 7.96; CI95 3.62-17.48), anemia (OR = 2.39; CI95 1.15-4.99), congestive heart failure (OR = 5.31; CI95 1.82-15.45), COPD (OR = 3.70; CI95 1.35-10.16), and history of prior stroke (OR = 8.50; CI95 1.55-46.68) increased the odds of DNHF. When evaluating LOS (median = 5 days, IQR = 1, 9), anemia (OR = 5.49; CI95 2.86-10.52), and Medicaid insurance (OR = 3.07; CI95 1.06-10.52) were found to increase the LOS. CONCLUSIONS: The vast majority of patients undergoing LTBR with ND have no complications and are discharged within a week. Liver disease is a risk factor for medical complications and increased charges. Patients with dementia or a prior stroke are at risk for DNHF, and those with prior anemia are at risk for a wound complication. LAY SUMMARY: This study identified factors related to worse post-operative outcomes in patients undergoing temporal bone resection and neck dissection. Although safe for most patients, an existing diagnosis of liver disease, stroke, dementia, and anemia specifically are at risk for developing negative outcomes. LEVEL OF EVIDENCE: 3.

Radiotherapy vs Surgery for Survival and Locoregional Control of Head and Neck Extramedullary Plasmacytoma: A Systematic Review and Meta-Analysis.

Importance: There are significant gaps in the literature pertaining to the locoregional control and survival rates of extramedullary plasmacytoma (EMP) with respect to various treatment approaches. Objective: To systematically evaluate the differences in radiotherapy and surgical outcomes in EMP. Data Sources: Databases including PubMed, Scopus, Web of Science, Embase, and ScienceDirect were systematically searched from their inception up to November 2023. Study Selection: Articles reporting radiotherapy and surgical outcomes of head and neck EMP were included. Data Extraction and Synthesis: A random-effects model for meta-analysis was used to obtain pooled estimates and calculate hazard ratios for survival and odds ratios for recurrence and progression of EMP. Main Outcomes and Measures: Survival, tumor control, and progression rates to multiple myeloma (MM) between radiation therapy and surgery for EMP of the head and neck. Results: Of 742 included patients from 12 studies, 527 (71.0%) were male, and the median (IQR) age was 59.1 (53-62) years. A total of 505 patients (68.1%) received radiotherapy only, while 237 (31.9%) underwent surgery-only treatment for EMP. All included patients had an initial diagnosis of EMP without MM. Comparable trends were observed in overall survival and disease-free survival (DFS) rates at 2, 3, 5, and 10 years between patients with EMP treated with radiotherapy only and surgery only. Notably, there were no significant differences in recurrence rate (odds ratio, 0.65; 95% CI, 0.20-2.06) between radiotherapy-only and surgery-only treatment. However, radiotherapy-only treatment of EMP was associated with decreased odds of progression to MM compared with surgery (odds ratio, 0.4; 95% CI, 0.1-0.9). Sensitivity analysis revealed that the radiotherapy-only population had significantly better 5-year DFS (hazard ratio, 0.55; 95% CI, 0.31-0.96) compared with surgery-only treatment. Conclusions and Relevance: This systematic review and meta-analysis provides evidence that patients with EMP receiving radiotherapy had significantly lower chances of progression to MM compared with surgery-only therapy. Additionally, radiotherapy had better 5-year DFS outcomes compared with surgery. Comparable outcomes in terms of overall survival rates, recurrence, and mortality rates were noted between radiotherapy-only and surgery-only EMP treatment groups.