Salvage surgery for recurrent or residual hypopharyngeal squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review aggregates the data of studies that include site-specific analyses of patients undergoing salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma. METHODS: The primary outcomes are disease-free, disease-specific, and overall survival (DFS, DSS, and OS, respectively). Secondary outcomes include complications and postoperative feeding requirements. RESULTS: Fifteen studies met the inclusion criteria with a total of 442 patients. Two-year DFS is reported from 30.0 to 50.0% and 5-year DFS ranges from 15.0 to 57.1%. Five-year DSS ranges from 28.0 to 57.1%. Two-year OS ranges from 38.8 to 52.0% and 5-year OS ranges from 15.5 to 57.1%. Complications include pharyngocutaneous fistula (0.0-71.4%), carotid artery rupture (2.9-13.3%), and stomal stenosis (4.2-20.0%). Complete oral feeding achieved following surgery ranges from 61.9 to 100.0%, while complete gastrostomy tube dependence ranges from 0.0 to 28.6%. CONCLUSIONS: Salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma has a relatively high complication rate and should be offered to patients with the understanding of a guarded prognosis.

Neck scar perception after neck dissection in HPV-associated oropharyngeal squamous cell carcinoma.

IMPORTANCE: While there has been an increased understanding of the impact of visible neck scars in some patients with certain diseases, this has not yet been explored in the HPV+ OPSCC population. OBJECTIVE: To understand patients' perception of their scar and the impact on their quality of life (QOL) at least 6 months after neck dissection (ND) for HPV+ oropharyngeal squamous cell carcinoma (OPSCC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case-control study, patients who underwent primary transoral robotic surgery (TORS) and ND for HPV+ OPSCC between 2016 and 2021 at a single tertiary care center were identified. Data analysis was performed in January 2022. MAIN OUTCOMES AND MEASURES: Dermatology Life Quality Index was modified (mDLQI) to assess patients' perceptions of their scars. The primary outcome was the mean mDLQI survey score with higher scores corresponding to worse perceptions. Three questions adapted from the Self-Consciousness Scale (SCS) were also included to assess awareness of appearance. All questions were scaled on a 0-3 Likert Scale. Tweedie generalized linear model was used to understand the relationship between mDLQI score and patient- and procedure-specific factors (including the three SCS survey questions). An additional exploratory logistic regression was performed to understand the risk factors for clinically significant mDLQI score change. RESULTS: A total of 67 patients (response rate 57 %) completed the survey with a mean mDLQI survey score of 0.84 (max 30). Although there was a statistically significant negative association between private insurance and mDLQI survey score (95 % Confidence Interval [CI]: -2.72 - -0.38), and a positive association between the SCS score and mDLQI survey score (95 % CI: 0.23-0.81) (p < 0.05), these variables were not found to be risk factors for a clinically significant difference in mDLQI on multivariable analysis. CONCLUSION: The majority of patients felt their neck scars did not interfere with their daily lives. Patient perceptions of neck scars were consistent despite differing patient characteristics and treatment regimens.

Predictors of multiple dilations and functional outcomes after total laryngectomy and laryngopharyngectomy.

BACKGROUND: Following total laryngectomy (TL) or laryngopharyngectomy (TLP), patients may develop strictures that require multiple dilations to treat. However, the risk factors associated with dysphagia refractory to a single dilation are unknown. METHODS: Single-institution retrospective review of patients who underwent at least one stricture dilation after TL/TLP between March 2013 and March 2022. RESULTS: A total of 49 patients underwent stricture dilation after TL/TLP. Thirty-five (71%) underwent multiple dilations. Pharyngocutaneous fistula, primary chemoradiation therapy, and a shorter time interval from TL/TLP to first dilation were independently associated with dysphagia requiring multiple dilations. Patients in the multiple dilations group had a higher rate of limited diet and G-tube dependence compared to patients in the single dilation group. CONCLUSIONS: Shorter time interval to stricture formation is a prognostic indicator of the need for multiple dilations following TL/TLP. Patients requiring multiple dilations are at increased risk of persistent dysphagia long-term.

Early Weight-Bearing After Fibula Free Flap Surgery.

Importance: Despite the widespread use of fibula free flap (FFF) surgery for head and neck reconstruction, there are no studies assessing if early weight-bearing (EWB) affects postoperative recovery, and the timing of weight-bearing initiation following FFF surgery varies considerably across institutions. Therefore, it is important to understand the effect of EWB in these patients and whether it could improve postoperative recovery. Objective: To assess the association of EWB after FFF surgery with donor-site complications, length of stay, and discharge to home status. Design, Setting, and Participants: This retrospective cohort study took place at Massachusetts Eye and Ear, a single tertiary care institution in Boston, Massachusetts. A total of 152 patients who received head and neck reconstruction with a fibula osteocutaneous free flap between January 11, 2010, and August 11, 2022, were included. Exposure: EWB on postoperative day 1 vs non-EWB on postoperative day 2 or later. Main Outcomes and Measures: Patient characteristics, including demographic characteristics and comorbidities, surgical characteristics, donor-site complications, length of stay, and discharge disposition, were recorded. Descriptive statistics and multivariate logistic regressions were used to compute effect sizes and 95% CIs to compare postoperative outcomes in EWB and non-EWB groups. Results: A total of 152 patients (median [IQR] age, 63 [55-70] years; 89 [58.6%] male) were included. The median (IQR) time to postoperative weight-bearing was 3 (1-5) days. Among all patients, 14 (9.2%) had donor-site complications. EWB on postoperative day 1 was associated with shorter length of stay (adjusted odds ratio [AOR], 0.10; 95% CI, 0.02-0.60), increased rate of discharge to home (AOR, 7.43; 95% CI, 2.23-24.80), and decreased donor-site complications (AOR, 0.11; 95% CI, 0.01-0.94). Conversely, weight-bearing 3 or more days postoperatively was associated with an increased risk of pneumonia (AOR, 6.82; 95% CI, 1.33-34.99). Conclusions and Relevance: In this cohort study, EWB after FFF surgery was associated with shorter length of stay, increased rate of discharge to home, and decreased donor-site complications. These findings support the role of early mobilization to optimize postoperative recovery after FFF surgery.

Sacral metastases in a patient with BRAF V600E+ papillary thyroid carcinoma.

Lack of consensus exists on an algorithm to screen for synchronous distant metastases in patients presenting with papillary thyroid carcinoma (PTC). A 68-year-old male presented with a 3 cm supraclavicular neck mass. Computed tomography (CT) scan revealed a 1.3 cm left thyroid lobe nodule and 3 cm left level 3 and 4 lymphadenopathy. Ultrasound-guided fine needle aspiration was positive for PTC. Patient underwent total thyroidectomy and lymph node dissection with molecular testing confirming BRAF V600E+ PTC. Six weeks post-operatively, he developed left hip pain and numbness. Magnetic resonance imaging (MRI) revealed a large sacral mass and multiple bony lesions confirmed to be osseous metastases. Given the relatively rapid report of hip pain after surgery, metastases were likely synchronous at presentation and may have been detected with earlier suspicion. Further investigation is necessary to systematically stratify risk of synchronous distant metastases in patients with metastatic PTC.

Depth of resection predicts loss of tongue tip sensation after partial glossectomy in oral tongue cancer: A pilot study.

OBJECTIVE(S): To characterize the change in sensory function following partial glossectomy for oral tongue cancer (OTC) and to identify predictors of loss of tongue-tip sensation (LoTTS). MATERIALS AND METHODS: Patients with at least three months follow-up after partial glossectomy for primary OTC were included. All patients underwent a qualitative tongue sensation assessment and an objective tongue sensory exam of the native tongue tip. Additional details regarding the oncologic resection, surgical reconstruction, and pathological stage were collected. Multiple linear and logistic regressions were used for statistical analysis. RESULTS: Sixty-four patients were enrolled, including 34 (53%) men with a median age of 65 at enrollment. Ten (15%) patients reported LoTTS. Increased depth of resection (DOR) was an independent predictor of LoTTS on multivariate analysis, with an increased risk at a threshold of 1.3 cm. LoTTS was also associated with worse subjective quality of life and perceptive speech performance in our qualitative tongue assessment. CONCLUSIONS: In this pilot study, we found that DOR is a critical prognostic factor in predicting post treatment function. Patients with an increased DOR, particularly above 1.3 cm, are at greatest risk of LoTTS and associated morbidity. These findings may be used to predict post-operative sensory deficits, manage patients' expectations, and optimize the reconstructive approach. Future studies are needed to validate and replicate our results.

CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers.

Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs and disease outcome, we focused on tumor-to-tumor variation to examine 52 head and neck squamous cell carcinomas. We found that macrophage polarity-defined by CXCL9 and SPP1 (CS) expression but not by conventional M1 and M2 markers-had a noticeably strong prognostic association. CS macrophage polarity also identified a highly coordinated network of either pro- or antitumor variables, which involved each tumor-associated cell type and was spatially organized. We extended these findings to other cancer indications. Overall, these results suggest that, despite their complexity, TMEs coordinate coherent responses that control human cancers and for which CS macrophage polarity is a relevant yet simple variable.

Comparison of patient-reported upper extremity disability following free flaps in head and neck reconstruction: A systematic review and meta-analysis.

BACKGROUND: Comparisons of patient-reported donor site morbidity based on the Disabilities in Arm, Shoulder, and Hand (DASH) instrument across upper trunk free flaps in head and neck surgery, including radial forearm (RFFF), osteocutaneous radial forearm (OCRFF), scapular tip (STFF), and serratus anterior (SAFF) free flaps, may help inform donor tissue selection. METHODS: In this meta-analysis, 12 studies were included and the primary outcome was average DASH score. RESULTS: The pooled DASH scores were 12.14 (95% CI: 7.40-16.88) for RFFF (5 studies), 17.99 (11.87-24.12) for OCRFF (2 studies), 12.19 (8.74-15.64) for STFF (3 studies), and 16.49 (5.92-27.05) for SAFF (2 studies) and were not significantly different. CONCLUSIONS: Results suggest that patients generally function well, with minimal to mild donor site morbidity, when assessed at an average of 20 months after flap harvest. These results are based on few effects from primarily retrospective studies of fair quality, and further research is needed.

Protocol for tumor dissociation and fluorescence-activated cell sorting of human head and neck cancers.

Tumors originating from the head and neck represent diverse histologies and are comprised of several cell types, including malignant cells, cancer-associated fibroblasts, endothelial cells, and immune cells. In this protocol, we describe a step-by-step approach for the dissociation of fresh human head and neck tumor specimens, followed by isolation of viable single cells using fluorescence-activated cell sorting. Our protocol facilitates the effective downstream use of techniques, including single-cell RNA sequencing and generation of three-dimensional patient-derived organoids. For complete details on the use and execution of this protocol, please refer to Puram et al. (2017)1 and Parikh et al. (2022).2.

Inferring early genetic progression in cancers with unobtainable premalignant disease.

Analysis of premalignant tissue has identified the typical order of somatic events leading to invasive tumors in several cancer types. For other cancers, premalignant tissue is unobtainable, leaving genetic progression unknown. Here, we demonstrate how to infer progression from exome sequencing of primary tumors. Our computational method, PhylogicNDT, recapitulated the previous experimentally determined genetic progression of human papillomavirus-negative (HPV-) head and neck squamous cell carcinoma (HNSCC). We then evaluated HPV+ HNSCC, which lacks premalignant tissue, and uncovered its previously unknown progression, identifying early drivers. We converted relative timing estimates of driver mutations and HPV integration to years before diagnosis based on a clock-like mutational signature. We associated the timing of transitions to aneuploidy with increased intratumor genetic heterogeneity and shorter overall survival. Our approach can establish previously unknown early genetic progression of cancers with unobtainable premalignant tissue, supporting development of experimental models and methods for early detection, interception and prognostication.

Comparison of Preoperative DOI Estimation in Oral Tongue Cancer With cN0 Disease.

OBJECTIVE: To understand the accuracy of pre- and intraoperative estimation of tumor depth of invasion (DOI). STUDY DESIGN: A retrospective case-control study. SETTING: Patients who presented at 1 institution with oral tongue squamous cell carcinoma that underwent oncologic resection between 2017 and 2019 were identified. METHODS: Patients that met the inclusion criteria were included. Patients with nodal, distant, or recurrent disease, prior history of head and neck cancer, or preoperative tumor assessment and/or final histopathology that did not include DOI were excluded. Preoperative DOI estimation and technique and pathology reports were obtained. Our primary outcome was the sensitivity and specificity of DOI estimation modalities including full-thickness biopsy (FTB), manual palpation (MP), punch biopsy (PB), and intraoperative ultrasound (IOUS). RESULTS: Tumor DOI was assessed quantitatively preoperatively in 40 patients by FTB (n = 19, 48%), MP (n = 17, 42%), or PB (n = 4, 10%). Additionally, 19 patients underwent IOUS to assess DOI. The sensitivities of FTB, MP, and IOUS for DOI ≥ 4 mm were 83% (confidence interval [CI]: 44%-97%), 83% (CI: 55%-95%), and 90% (CI: 60%-98%), respectively, and the specificities were 85% (CI: 58%-96%), 60% (CI: 23%-88%), and 78% (CI: 45%-94%). CONCLUSION: Our study demonstrated that DOI assessment tools measured had similar sensitivity and specificity in stratifying patients with DOI ≥4 mm, with no statistically superior diagnostic test. Our results support the need for additional research into nodal disease prediction and continued refinement of ND decisions with respect to DOI.

Surgical factors affecting regionally metastatic cutaneous squamous cell carcinoma to the parotid gland.

BACKGROUND: Understanding the impact of surgical treatment on regionally metastatic cutaneous squamous cell carcinoma (cSCC). METHODS: Retrospective series of 145 patients undergoing parotidectomy and neck dissection for regionally metastatic cSCC to the parotid. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analyzed over 3 years. Multivariate analysis was completed using Cox proportional hazard models. RESULTS: OS was 74.5%, DSS was 85.5% and DFS was 64.8%. On multivariate analysis, immune status (HR = 3.225[OS], 5.119[DSS], 2.071[DFS]) and lymphovascular invasion (HR = 2.380[OS], 5.237[DSS], 2.595[DFS]) were predictive for OS, DSS, and DFS. Margin status (HR = 2.296[OS], 2.499[DSS]) and ≥18 resected nodes (HR = 0.242[OS], 0.255[DSS]) were predictive of OS and DSS, while adjuvant therapy was predictive of DSS (p = 0.018). CONCLUSIONS: Immunosuppression and lymphovascular invasion portended worse outcomes in patients with metastatic cSCC to the parotid. Microscopically positive margins and <18 nodes resected are associated with worse OS and DSS, while patients receiving adjuvant therapy had improved DSS.

Molecular Evidence for Olfactory Neuroblastoma as a Tumor of Malignant Globose Basal Cells.

Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor misclassification throughout the literature. Despite its name, connections between the cancer and normal cells of the olfactory epithelium have not been systematically explored and markers of olfactory epithelial cell types are not deployed in clinical practice. Here, we utilize an integrated human-mouse single-cell atlas of the nasal mucosa, including the olfactory epithelium, to identify transcriptomic programs that link ONB to a specific population of stem/progenitor cells known as olfactory epithelial globose basal cells (GBCs). Expression of a GBC transcription factor NEUROD1 distinguishes both low- and high-grade ONB from sinonasal undifferentiated carcinoma, a potential histologic mimic with a distinctly unfavorable prognosis. Furthermore, we identify a reproducible subpopulation of highly proliferative ONB cells expressing the GBC stemness marker EZH2, suggesting that EZH2 inhibition may play a role in the targeted treatment of ONB. Finally, we study the cellular states comprising ONB parenchyma using single-cell transcriptomics and identify evidence of a conserved GBC transcriptional regulatory circuit that governs divergent neuronal-versus-sustentacular differentiation. These results link ONB to a specific cell type for the first time and identify conserved developmental pathways within ONB that inform diagnostic, prognostic, and mechanistic investigation.

Assessment of Blue Light Phototherapy for Grover Disease: A Nonrandomized Controlled Trial.

This nonrandomized clinical trial assesses treatment of patients diagnosed with Grover disease with blue light phytotherapy for several weeks.

Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing.

Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatiotemporal resolution of current methods. Since the imbalance of cortical excitation/inhibition (E:I) ratios are associated with a variety of neurological disorders, accurate monitoring of excitatory and inhibitory neurotransmitter levels is crucial for investigating the underlying neural mechanisms of these conditions. Specifically, levels of the excitatory neurotransmitter L-glutamate, and the inhibitory neurotransmitter GABA, are assumed to play critical roles in the E:I balance. Therefore, in this work, a flexible electrochemical microsensor is developed for real-time simultaneous detection of L-glutamate and GABA. The flexible polyimide substrate was used for easier handling during implantation and measurement, along with less brain damage. Further, by electrochemically depositing Pt-black nanostructures on the sensor's surface, the active surface area was enhanced for higher sensitivity. This dual neurotransmitter sensor probe was validated under various settings for its performance, including in vitro, ex vivo tests with glutamatergic neuronal cells and in vivo test with anesthetized rats. Additionally, the sensor's performance has been further investigated in terms of longevity and biocompatibility. Overall, our dual L-glutamate:GABA sensor microprobe has its unique features to enable accurate, real-time, and long-term monitoring of the E:I balance in vivo. Thus, this new tool should aid investigations of neural mechanisms of normal brain function and various neurological disorders.

Cross-legged modification for medial sural artery perforator flap harvest.

When thin and pliable free tissue is needed, the medial sural artery perforator (MSAP) flap provides an excellent option with minimal donor site morbidity. However, among its pitfalls include difficult patient positioning and surgeon ergonomics throughout the harvest. We describe a novel positioning technique that may significantly improve surgeon ergonomics and ease of MSAP flap harvest. A cross-legged modification may eliminate many of the issues associated with the classic frog-leg position. While the patient is cross-legged, the surgeon is afforded a normal field of view that is closer to their body, while simultaneously providing support to the lateral side of the gastrocnemius muscle. This pictorial essay describes this positioning technique and subsequent harvest. By incorporating a more ergonomic cross-legged position during flap elevation, many of thedrawbacks of the MSAP flap could be eliminated.

Rate of atypical nodal metastases in surgically treated HPV-associated oropharyngeal squamous cell carcinoma.

BACKGROUND: Understanding of nodal metastasis in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is warranted. METHODS: Patients with HPV+ OPSCC who underwent neck dissection (ND) between 2016 and 2021 were reviewed. Pathology reports were reviewed for lymph node (LN) metastases. Noncontiguous metastases were defined as pathologic evidence of level II disease with another involved LN in a noncontiguous neck level. Skip metastases were defined as pathologic lymph node(s) in the neck without disease in level II. RESULTS: One hundred and thirty-one patients underwent levels II-IV ND with a mean (SD) LN yield of 33.3 (±13.5). The rate of atypical metastases in both the therapeutic and elective ND cohort was 5%. The noncontiguous and skip metastases were in level IV (n = 2) and level III (n = 4), respectively. CONCLUSIONS: Skip and noncontiguous metastases were rare in patients with HPV+ OPSCC undergoing surgical treatment. Surgeons may consider a selective ND omitting Level IV in select patients with HPV+ OPSCC undergoing surgery.

Wireless, Soft Sensors of Skin Hydration with Designs Optimized for Rapid, Accurate Diagnostics of Dermatological Health.

Accurate measurements of skin hydration are of great interest to dermatological science and clinical practice. This parameter serves as a relevant surrogate of skin barrier function, a key representative benchmark for overall skin health. The skin hydration sensor (SHS) is a soft, skin-interfaced wireless system that exploits a thermal measurement method, as an alternative to conventional impedance-based hand-held probes. This study presents multiple strategies for maximizing the sensitivity and reliability of this previously reported SHS platform. An in-depth analysis of the thermal physics of the measurement process serves as the basis for structural optimizations of the electronics and the interface to the skin. Additional engineering advances eliminate variabilities associated with manual use of the device and with protocols for the measurement. The cumulative effect is an improvement in sensitivity by 135% and in repeatability by 36% over previously reported results. Pilot trials on more than 200 patients in a dermatology clinic validate the practical utility of the sensor for fast, reliable measurements.

Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma.

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We validate this selective expression in three published cohorts of patients with ACC. Our data provide a potential explanation for the biphasic nature of low- and intermediate-grade ACC and may help direct new therapeutic strategies against these tumors.