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.

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.

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.

Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

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.

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.

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.

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.

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.

Enhanced recovery after surgery, current, and future considerations in head and neck cancer.

Objectives: Review of the current and relevant literature to develop a list of evidence-based recommendations that can be implemented in head and neck surgical practices. To provide rationale for the multiple aspects of comprehensive care for head and neck surgical patients. To improve postsurgical outcomes for head and neck surgical patients. Methods: Extensive review of the medical literature was performed and relevant studies in both the head and neck surgery and other surgical specialties were considered for inclusion. Results: A total of 18 aspects of perioperative care were included in this review. The literature search included 276 publications considered to be the most relevant and up to date evidence. Each topic is concluded with recommendation grade and quality of evidence for the recommendation. Conclusion: Since it's conception, enhanced recovery after surgery (ERAS) protocols have continued to push for comprehensive and evidence based postsurgical care to improve patient outcomes. Head and neck oncology is one of the newest fields to develop a protocol. Due to the complexity of this patient population and their postsurgical needs, a multidisciplinary approach is needed to facilitate recovery while minimizing complications. Current and future advances in head and neck cancer research will serve to strengthen and add new principles to a comprehensive ERAS protocol. Level of Evidence: 2a.

Editorial: Special Issue on the Epidemiology of Human Papilloma Virus-Associated Oropharyngeal Squamous Cell Carcinoma.

In this Special Issue of Cancers, the role of oncogenic human papilloma virus (HPV) with oropharyngeal squamous cell carcinoma is explored […].

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.

Regional pedicled flap salvage options for large head and neck defects: The old, the new, and the forgotten.

Objectives: The objective of this article is to review options for regional pedicled reconstruction for large head and neck defects in a salvage setting. Methods: Relevant regional pedicled flaps were identified and reviewed. Expert opinion and supporting literature were used to summarize and describe the available options. Results: Specific regional pedicled flap options are presented including the pectoralis major flap, deltopectoral flap, supraclavicular flap, submental flap, latissimus flap, and trapezius flap. Conclusions: Regional pedicled flaps are useful options in a salvage setting even for large defects and should be in the armamentarium of any reconstructive head and neck surgeon. Each flap option carries specific characteristics and considerations.

Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC).

TP53 mutant head and neck squamous cell carcinoma (HNSCC) patients exhibit poor clinical outcomes with 50-60% recurrence rates in advanced stage patients. In a recent phase II clinical trial, adjuvant therapy with everolimus (mTOR inhibitor) significantly increased 2-year progression-free survival in p53 mutated patients. TP53-driven mTOR activation in solid malignancies causes upregulation of HIF-1α and its target, downstream effector VEGF, by activating STAT3 cell signaling pathway. Here, we investigated the effects of everolimus on the STAT3/HIF-1α/VEGF pathway in TP53 mutant cell lines and xenograft models. Treatment with everolimus significantly inhibited cell growth in vitro and effectively reduced the growth of TP53 mutant xenografts in a minimal residual disease (MRD) model in nude mice. Everolimus treatment was associated with significant downregulation of STAT3/HIF-1α/VEGF pathway in both models. Further, treatment with everolimus was associated with attenuation in tumor angiogenesis and lymphangiogenesis as indicated by decreased microvessel density of vascular and lymphatic vessels in HN31 and FaDu xenografts. Everolimus downregulated the STAT3/HIF-1α/VEGF pathway to inhibit growth and in vitro tube formation of HMEC-1 (endothelial) and HMEC-1A (lymphatic endothelial) cell lines. Our studies demonstrated that everolimus inhibits the growth of TP53 mutant tumors by inhibiting angiogenesis and lymphangiogenesis through the downregulation of STAT3/HIF-1α/VEGF signaling.

Intraoperative Imaging Techniques to Improve Surgical Resection Margins of Oropharyngeal Squamous Cell Cancer: A Comprehensive Review of Current Literature.

Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC.

Circulating Human Papillomavirus DNA in Head and Neck Squamous Cell Carcinoma: Possible Applications and Future Directions.

There has been a rising trend in HPV-induced head and neck cancers in the last several decades. This subgroup of squamous cell carcinoma is mostly located in the oropharynx and comprises a subset of patients who are typically younger and without the usual risk factors of smoking and alcohol use. As the prognosis of HPV-induced OPC is more favorable, there is a desire to properly select these patients for de-intensification protocols while identifying individuals who may suffer treatment failure. Here, we describe recent developments in circulating tumor HPV DNA as a marker of HPV-positive oropharyngeal cancer that can potentially be used as a diagnostic tool to stratify patients for de-escalation strategies and to survey for recurrence.

Assessment of Facial Injury by "Slock" in Incarcerated Patients.

A "slock" is a padlock in a sock used as a weapon in correctional facilities to induce trauma. This assessment examined the prevalence, pattern, and degree of slock- and padlock-induced facial fractures. This quality assessment initiative was performed through retrospective analysis of 435 incarcerated patients treated surgically for facial fractures at an academic medical center from 2011 to 2019. Fifty-seven patients (16%) described injury from a padlock, of whom 23 (6%) specified a slock. The prevalence of padlock-induced facial fractures doubled from 2012 to 2017. Padlock-induced facial fractures were determined to be more complex than those by a fist (p < .001). These findings support reducing the facial trauma in Louisiana correctional facilities by removing access to padlocks.