An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications. METHODS: A 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary-CUP) was admitted with a right-sided epi-/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction. RESULTS: Due to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient's airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief. CONCLUSIONS: The present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Survival Outcome in True Carcinoma of Unknown Primary (tCUP) with p16 + Cervical Metastasis.

Introduction Age and lymph node ratio have been attributed as independent predictors for survival and recurrence in carcinoma of unknown primary (CUP). Objective The purpose of this study was to analyze the prognostic value of p16 overexpression for CUP in the absence of true primary (TP). Methods The study involved 43 patients who underwent therapeutic lymph node dissection (LND) from 2000 to 2015 after all the diagnostic work up for CUP. Immunohistochemistry for p16 overexpression was performed. Cox proportional hazard regression analysis was used to analyze the prognostic impact on 5-year overall survival (OS) and recurrence-free survival (RFS). Results The male-to-female ratio was 5.1:1, with a median age of 62 years. The clinicopathological data, except for p16 overexpression, did not differ significantly in terms of 5-year OS and RFS. The Cox regression analysis proposed p16 positivity to be an independent prognosticator of regional recurrence-free survival (RRFS) (hazard ratio [HR] 6.180, p = 0.21). The median time to recurrence and death were 10 and 25 months, respectively. Conclusion Cervical metastasis with p16 overexpression is a significant prognostic factor of improved RFS after surgery in CUP. The prognostic significance of lymph node p16 positivity should be further studied.

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

BACKGROUND: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. METHODS: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. RESULTS: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. CONCLUSIONS: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

Long-Term Care and Follow-Up in Laryngeal Cancer Patients: A Multicenter Retrospective Analysis.

PURPOSE: We conducted an outcome analysis on surgically treated laryngeal squamous cell carcinoma (LSCC) patients. METHODS: A multicenter retrospective study with 352 patients was analyzed. A new nomogram that incorporates age, T- and N-classification, and treatment was created. RESULTS: Recurrence was observed in 65 (18.5%) patients after a mean time of 16.5 months. After 60 months, 91 (25.9%) of patients developed secondary primary tumors (SPT), most commonly in the lungs (n = 29; 8.2%) followed by other head and neck cancers (n = 21; 6.0%). Notably, the mean time to occurrence of secondary head and neck cancers was twice that of lung cancer (101.1 vs. 47.5 months). CONCLUSION: Recurrent disease is less common in LSCC patients and appears much earlier than SPT. Because one in every four laryngeal cancer patients develops SPTs within 5-10 years, long-term care and follow-up, including imaging studies, are highly recommended. The nomogram was useful for estimating survival.

Influence of Grading on Management and Outcome in Mucoepidermoid Carcinoma of the Parotid-A Multi-institutional Analysis.

OBJECTIVE: To evaluate clinical outcome of low (G1), intermediate (G2), and high-(G3) grade mucoepidermoid carcinomas (MEC) of the parotid gland. STUDY DESIGN: Retrospective chart review including 212 patients. Clinicopathological data was statistically analyzed regarding grading, overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: 105 (49.5%) G1, 73 (34.5%) G2, and 34 (16%) G3 MEC were included and 56 (26.4%) patients presented with neck node metastases. The risk of occult nodal metastases was significantly associated with grading and increased from 9.2% in G1 to 26.7% and 27.8% in G2 and G3 tumors, respectively (p = 0.008). Elective periparotid and cervical lymph node dissection was performed in 170 (80.2%) and 70 (33%) patients, respectively. All patients with positive periparotid nodes when subjected to an additional neck dissection had associated cervical neck node involvement (p < 0.001). Grading was an independent significant prognostic factor for OS (HR 4.05; 95%CI: 1.15-14.35; p = 0.030) and DSS (HR 17.35; 95%CI: 1.10-273.53; p = 0.043). In a subgroup analysis, elective neck dissection (END) was also significantly associated with a better DFS (p = 0.041) in neck node-negative G1 MECs. CONCLUSION: The risk of occult nodal metastasis in intermediate-grade MEC is as high as in high-grade MEC and that END in G1 tumors is associated with a prolonged DFS. Additionally, periparotid node involvement seems to be a predictor for positive neck node involvement. This study presents some preliminary data to consider END in clinically neck node negative patients with parotid MEC; however, larger series are needed. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:124-132, 2023.

Using the serratus anterior free flap for dynamic facial reanimation: Systematic review.

It was the purpose of this study to evaluate the role of the serratus anterior free flap (SAFF) with its long thoracic nerve (LTN) as composite flap for dynamic facial reanimation. A total of 10 studies, published between 2004 and 2021, met inclusion criteria. Clinical data of 48 patients were used for the systematic review and analysis. One to three slips were used, mainly as one-stage procedures (n = 39; 81.3%), to create different force vectors. Single or double innervated muscle transfers were utilized in 32 (66.7%) and 16 (33.3%) cases with additionally harvested skin paddles in 4 (8.3%) patients. The LTN was mostly anastomosed to the ipsilateral masseteric nerve (45.8%; n = 22) or to remaining facial nerve branches (37.5%; n = 18), while cross-facial-nerve-grafting was rarely used (16.7%; n = 8). The SAFF as composite flap with different force vectors proved to be a good candidate for immediate dynamic facial reanimation after any midface defects.

Chemosensory Functions After Glossectomy-A Cross-Sectional Pilot Study.

OBJECTIVE: To evaluate potential interactions and compensatory mechanisms of subjectively impaired taste function with ortho- and retronasal olfaction after glossectomy. STUDY DESIGN: In this cross-sectional pilot study, chemosensory functions were assessed in 25 patients with tongue carcinomas after glossectomy. The orthonasal-, retronasal-, and gustatory functions were tested with a mean time of 25 months after surgery with the Sniffin' Sticks odor identification test kit (ISST), the Candy Smell-27 test (CST-27) and the Taste strip test (TST). Visual analog scales (VAS) were additionally used for self-assessment of taste, flavor perception, and odor ranging from 0 (no perception) to 10 (excellent perception) and further correlated with our psychophysical evaluated outcome measures. RESULTS: The TST, ISST, and CST-27 tests revealed that only eight (32%) and 13 (52%) glossectomy patients had normal taste and orthonasal function, e 21 (84%) patients showed normal retronasal function. Importantly, neither extent of resection and reconstruction nor prior radiotherapy affected chemosensory functions. Contrary, 20 (80%) patients rated their taste and flavor perception as acceptable (VAS >5). Results of the TST, ISST, and CST-27 tests did not correlate with the equivalent self-assessments of taste (p = 0.260, r = 0.234), odor (p = 0.588, r = -0.114), and flavor (p = 0.728, r = 0.073) perception. CONCLUSION: There was a significant discrepancy between self-perception of taste and flavor and assessed gustatory function after glossectomy. A contribution of the intact retronasal olfactory system could be a possible explanation of our results. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:375-382, 2023.

A new nomogram to predict oncological outcome in laryngeal and hypopharyngeal carcinoma patients after laryngopharyngectomy.

BACKGROUND: To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy. MATERIALS: 239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS). RESULTS: HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%. CONCLUSIONS: The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation.

Survival Outcome in True Carcinoma of Unknown Primary (tCUP) with p16 + Cervical Metastasis

Abstract Introduction Age and lymph node ratio have been attributed as independent predictors for survival and recurrence in carcinoma of unknown primary (CUP). Objective The purpose of this study was to analyze the prognostic value of p16 overexpression for CUP in the absence of true primary (TP). Methods The study involved 43 patients who underwent therapeutic lymph node dissection (LND) from 2000 to 2015 after all the diagnostic work up for CUP. Immunohistochemistry for p16 overexpression was performed. Cox proportional hazard regression analysis was used to analyze the prognostic impact on 5-year overall survival (OS) and recurrence-free survival (RFS). Results The male-to-female ratio was 5.1:1, with a median age of 62 years. The clinicopathological data, except for p16 overexpression, did not differ significantly in terms of 5-year OS and RFS. The Cox regression analysis proposed p16 positivity to be an independent prognosticator of regional recurrence-free survival (RRFS) (hazard ratio [HR] 6.180, p = 0.21). The median time to recurrence and death were 10 and 25 months, respectively. Conclusion Cervical metastasis with p16 overexpression is a significant prognostic factor of improved RFS after surgery in CUP. The prognostic significance of lymph node p16 positivity should be further studied.

Long-Term Swallowing Outcome and Dysphagia in Advanced Staged Head and Neck Squamous Cell Carcinomas after Radiotherapy.

Objective: To evaluate the impact of radiotherapy (RT) on dysphagia and long-term swallowing outcome in patients with stage III and IV head and neck squamous cell carcinomas (HNSCCs). Material and Methods: Between 2005 and 2008, 189 patients with HNSCCs underwent primary or adjuvant RT in a curative setting. Long-term swallowing outcome was evaluated in 50 patients. Among them, 26 were further eligible for prospective analysis of long-term swallowing and dysphagia outcome. Medical charts were retrospectively reviewed regarding pre- and post-treatment dysphagia (3 months after last irradiation setting) as well as persisting long-term dysphagia (2019−2021). Results: Pre-treatment dysphagia was observed in 24 (48%) of 50 patients, particularly in oropharyngeal or hypopharyngeal stage III−IV tumors (OR 9.3; p = 0.003). Conversely, 46 patients (92%) complained about post-treatment dysphagic symptoms, which were more commonly seen in patients with positive neck nodes (OR 10.5; p = 0.037). The post-treatment dysphagia rate dropped from 92% to 24% (p < 0.001) during surveillance, which was significantly linked to xerostomia (OR 5.77; p = 0.019), dysgeusia (OR 9.9; p = 0.036) and free flap reconstruction (OR 6.1; p = 0.022). Conclusion: Pretreatment dysphagia is common in advanced stage HNSCCs and almost all patients complain about dysphagia at the end of RT. Importantly, applied RT protocols did not affect long-term dysphagia, which improves significantly in the majority of patients over time. Meeting Information: Preliminary results have been presented at the 65th Annual Meeting of the Austrian Society of Otorhinolaryngology, 22−26 September 2021, Austria.

Using the DASH Questionnaire to Evaluate Donor Site Morbidity of the Serratus Anterior Free Flap in Head and Neck Reconstruction: A Multicenter Study.

Objective: To evaluate donor site morbidity of the serratus anterior free flap (SAFF) in head and neck reconstruction. Methods: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (0 no disability to 100 most severe disability) was applied to 20 patients (M: 16; F: 4) who underwent ablative surgery and reconstruction of the head and neck using a SAFF. Applications, as well as the donor site, recipient site and flap-related complications, were evaluated. Results: SAFF was mainly used for tongue (n = 11; 55.0%) and pharyngeal reconstruction after a laryngopharyngectomy (n = 4; 20.0%). The majority of patients presented with stage IV disease (n = 12; 60%) and had undergone previous radiotherapy (n = 14; 70%). Our free flap survival rate was 88.9% and the pectoralis major muscle flap (PMMF) was used in 5 patients as a salvage option to reconstruct pharyngeal defects. The mean/median DASH score was 21.6/19.9 (healthy norm 10.1), indicating only mild to moderate disability. However, free flap failure and the additional harvest of PMMF multiplies donor site morbidity since it was associated with a 3- and 2.6-times higher DASH score (46.0 vs. 15.5; p = 0.039 and 39.9 vs. 15.47; p = 0.081). Conclusions: The SAFF represents a versatile flap for head and neck reconstruction with low donor site morbidity.

Carcinoma of Unknown Primary (CUP) versus CUP Turned to Primary Carcinoma of the Head and Neck-An Analysis of Diagnostic Methods and the Impact of Primary Tumor on Clinical Outcome.

BACKGROUND: The purpose of this study was to analyze the value of different diagnostic methods in detecting the primary site and the impact of primary tumors on the clinical outcome of carcinoma of unknown primary (CUP). METHODS: In this multicenter, retrospective study, 124 patients with true CUP (n = 94) and CUP turned to primary carcinoma (n = 30) were included. Patients with evidence of primary site during the clinical examination were excluded a priori. The diagnostic procedure was comprised of imaging and invasive methods (fine-needle-aspiration, tonsillectomy and panendoscopy). All patients were treated with curative intent. RESULTS: Despite extensive diagnostic workup, the primary site remained unknown in 75.8%. Invasive diagnostic methods showed higher primary detection rates than imaging modalities (15.1% vs. 7.8%). Tonsillectomy and panendoscopy revealed the primary tumor in 14.9% and 15.2% of patients, whereas the detection rates of CT, MRI and FDG-PET-CT were 10.1%, 4.8% and 6.5%, respectively. The occurrence of primary tumors led to a significantly deteriorating 5-year overall survival (p = 0.002) and emerged as survival prognosticator (HR = 2.764, p = 0.003). CONCLUSION: Clinical examination in combination with tonsillectomy and panendoscopy was superior to imaging alone in detecting the primary tumor. When the CUP of patients turned to a primary tumor, clinical outcome was significantly worse than in CUP patients.

Temporal fluctuations of post-tonsillectomy haemorrhage.

PURPOSE: Although haemorrhage is a common and in some cases life-threatening complication after tonsillectomy, surprisingly little is known about the temporal fluctuations of the onset of bleeding. The purpose of this study was to assess circadian and seasonal rhythms of post-tonsillectomy haemorrhage (PTH) and potential ramifications to educate patients and health care staff. METHODS: This retrospective study carried out at a tertiary referral hospital included paediatric and adult patients requiring emergency surgery due to severe PTH between 1993 and 2019. Medical records were reviewed and patient demographics, details regarding the initial procedure, postoperative day of haemorrhage, and start time of emergency surgery were extracted. Descriptive statistics, Kruskal-Wallis test, Mann-Whitney U test, and Chi-square goodness of fit tests were used to detect potential differences. RESULTS: A total of 300 patients with severe PTH and subsequent emergency surgery were identified. The median postoperative duration until PTH was 6 (range: < 1-19) days. 64.7% (n = 194) of all emergency surgeries had to be performed during evening and night hours (6 pm-6 am) (p < 0.0001). Compared to diurnal incidents, the risk of a nocturnal PTH event increased, the longer ago the initial surgery was (p < 0.0001). No seasonal variations were identified. Age, sex, and details of the initial procedure had no significant influence on the start time according to the surgical protocol. CONCLUSION: The discovered temporal fluctuations of PTH are of relevance for patient awareness and preoperative education. Due to possible life-threatening complications, management of severe PTH requires specific resources and trained medical staff on call.

A novel electrosurgical divider: performance in a self-controlled tonsillectomy study.

PURPOSE: Tonsillectomies are among the most common surgeries in otorhinolaryngology. A novel electrosurgical temperature-controlled instrument (device) promises rapid tonsillectomies and might reduce postoperative pain, but comparative studies to assess performance are warranted. METHODS: This randomized self-controlled clinical trial was conducted from October 2019 to October 2020 at the Department of Otorhinolaryngology, Head and Neck Surgery of the Medical University of Vienna. Forty-eight patients underwent a tonsillectomy with the device on one side and using cold-steel with localized bipolar cauterization on the other side (control). Main outcomes were the time for tonsil removal (per side) and the time to stop bleeding (per side). Secondary measurements were postoperative pain, assessed once on day 0 and five times on days 1, 3, 5, 7, and 10. Postoperative bleeding episodes and consequences were recorded. RESULTS: Device tonsillectomies were performed significantly faster than controls; the mean surgical time difference was 209 s (p < 0.001, 95% CI 129; 288). Intraoperative blood loss was significantly lower on the device side (all p < 0.05). Postoperative measurements of pain and bleeding were similar for both sides. Two return-to-theatre secondary bleeding events were recorded for the control side. CONCLUSION: The novel electrosurgical temperature-controlled divider reduced the tonsillectomy surgical time and intraoperative blood loss, with no apparent negative effects on postoperative pain or bleeding, compared to a cold-steel tonsillectomy with localized bipolar cauterization. In time-restricted settings, the device could be beneficial, particularly after familiarization with device handling. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03793816.

Prognostic factors in mammary analogue secretory carcinomas of the parotid gland: Systematic review and meta-analysis.

Mammary analogue secretory carcinomas (MASCs) of the parotid gland are considered as low-grade malignancies with good clinical outcome but lacking data regarding prognostic factors. We performed meta-analysis assessing prognostic factors for disease-free survival (DFS) and overall survival (OS) in 256 patients with MASCs of the parotid gland. A total of 73 studies have met the inclusion criteria and 76.3% of patients were seen with T1 and T2 tumors and negative neck nodes. Lymph node metastasis (57.4%) and distant recurrences (46.2%) were particularly found in T4 tumors (p < 0.001). DFS at 5 and 10 years was 77.9% and 47.2% compared to 88.1% and 77.2% for OS at the same time points. Male sex, T3-T4 tumors, and recurrent disease represented independent worse prognosticators for survival outcome. Altogether, parotid gland MASCs show good long-term outcome, but T4 tumors behave significantly more aggressive and require extended treatment strategies along with close follow-ups.

Do Salivary Bypass Tubes Reduce the Risk of Pharyngocutaneous Fistula after Laryngopharyngectomy-A Systematic Review and Meta-Analysis.

To evaluate the effect of salivary bypass tube (SBT) usage on the occurrence of pharyngocutaneous fistula (PCF) in patients after a laryngopharyngectomy, a total of 20 studies, published between 1988 and 2021, were identified including 2946 patients. We performed a meta-analysis assessing the risk of PCF occurrence in patients after SBT application compared to those without. PCF occurred in 26.8% of cases (669/2496) and SBT was applied in 33.0% of patients (820/2483). There was an overall trend towards lower PCF rates when using SBTs (22.2% vs. 35.3%; p = 0.057). We further selected five studies, comprising 580 patients who underwent laryngopharyngectomies, for meta-analysis showing that application of SBT reduced the risk of PCF formation (OR 0.46; 95% CI 0.18-1.18; p = 0.11). The meta-analysis demonstrates a beneficial effect of SBT insertion on PCF formation in patients after laryngopharyngectomy.

Impact of Previous Irradiation on Wound Healing after Negative Pressure Wound Therapy in Head and Neck Cancer Patients-A Systematic Review.

(1) Background: Negative pressure wound therapy (NPWT) has been effectively used for wound management in comparison to traditional dressings. The purpose of this study was to provide an evidence-based review of NPWT in head and neck cancer patients, as well as the impact of previous irradiation and other risk factors on wound healing. (2) Material and Methods: We conducted a comprehensive search in PubMed, Medline, Embase, Web of Science, and Cochrane Library databases for relevant literature. (3) Results: 15 studies fulfilled the inclusion criteria. The most common etiologies requiring NPWT were defects post tumor resection and flap reconstruction and oro/pharyngo-cutaneous fistulas. The neck was found to be the most common site of involvement (47.3%). The overall wound healing response rate was 87.5%. The median negative pressure recorded was 125 mm of Hg, with a median dressing change time of three days. Previous irradiation (p = 0.01; OR = 4.07) and diabetes mellitus (DM) (p = 0.001; OR = 5.62) were found to be significantly associated with delayed wound healing after NPWT. (4) Conclusion: NPWT treats complex wounds in head and neck cancer patients and should represent a significant armamentarium in head and neck cancers. Previous irradiation and DM have detrimental effects on wound healing after NPWT.

A New Classification System to Predict Functional Outcome after Laryngectomy and Laryngopharyngectomy.

(1) Objective: To evaluate long-term functional outcome in patients who underwent primary or salvage total laryngectomy (TL), TL with partial (TLPP), or total pharyngectomy (TLTP), and to establish a new scoring system to predict complication rate and long-term functional outcome; (2) Material and Methods: Between 1993 and 2019, 258 patients underwent TL (n = 85), TLPP (n = 101), or TLTP (n = 72). Based on the extent of tumor resection, all patients were stratified to (i) localization I: TL; II: TLPP; III: TLTP and (ii) surgical treatment (A: primary resection; B: salvage surgery). Type and rate of complication and functional outcome, including oral nutrition, G-tube dependence, pharyngeal stenosis, and voice rehabilitation were evaluated in 163 patients with a follow-up ≥ 12 months and absence of recurrent disease; (3) Results: We found 61 IA, 24 IB, 63 IIA, 38 IIB, 37 IIIA, and 35 IIIA patients. Complications and subsequently revision surgeries occurred most frequently in IIIB cases but rarely in IA patients (57.1% vs. 18%; p = 0.001 and 51.4% vs. 14.8%; p = 0.002), respectively. Pharyngocutaneous fistula (PCF) was the most common complication (33%), although it did not significantly differ among cohorts (p = 0.345). Pharyngeal stenosis was found in 27% of cases, with the highest incidence in IIIA (45.5%) and IIIB (72.7%) patients (p < 0.001). Most (91.1%) IA patients achieved complete oral nutrition compared to only 41.7% in class IIIB patients (p < 0.001). Absence of PCF (odds ratio (OR) 3.29; p = 0.003), presence of complications (OR 3.47; p = 0.004), and no need for pharyngeal reconstruction (OR 4.44; p = 0.042) represented independent favorable factors for oral nutrition. Verbal communication was achieved in 69.3% of patients and was accomplished by the insertion of voice prosthesis in 37.4%. Acquisition of esophageal speech was reached in 31.9% of cases. Based on these data, we stratified patients regarding the extent of surgery and previous treatment into subgroups reflecting risk profiles and expectable functional outcome; (4) Conclusions: The extent of resection accompanied by the need for reconstruction and salvage surgery both carry a higher risk of complications and subsequently worse functional outcome. Both factors are reflected in our classification system that can be helpful to better predict patients' functional outcome.

PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis.

Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan-Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.