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.

Preoperative diagnostic of parotid gland neoplasms: fine-needle aspiration cytology or core needle biopsy?

A preoperative cytologic or histologic diagnosis of parotid gland neoplasms is mandatory to decide which surgical procedure would be appropriate. Open biopsies are contraindicated because of the risk of recurrence secondary to tumour cell seeding; furthermore a subsequent curative parotid surgery can be complicated by a previous open biopsy. While fine-needle aspiration cytology (FNAC) was the only preoperative diagnostic procedure to distinguish benign versus malignant neoplasms over the past decades, core needle biopsy (CNB) has been increasingly used over the last few years. This created a debate as to whether FNAC or CNB should be the preoperative procedure of choice. The focus of this editorial is to analyse the advantages and disadvantages of FNAC and CNB, and to discuss which procedure is more appropriate in the preoperative work-up of parotid neoplasms.

Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Tracheal Autotransplantation for Functional Reconstruction of Extended Hemilaryngectomy Defects: A Single-Center Experience in 30 Patients.

BACKGROUND: Tracheal autotransplantation is a reconstructive technique that allows for organ-sparing treatment of selected patients with advanced cricoid cartilage chondrosarcoma and T2 or T3 laryngeal squamous cell carcinoma (SCC) (unilateral T2 with impaired vocal fold mobility; T3 with subglottic extension and/or arytenoid cartilage fixation). This study evaluated the functional and oncologic outcomes of an optimized autotransplant technique that the authors have been using since 2003. METHODS: The study retrospectively reviewed the charts of all patients who underwent tracheal autotransplantation at the authors' center between 2003 and 2015. RESULTS: The cohort included 30 patients: 7 with cricoid chondrosarcoma and 23 with laryngeal SCC. The median age of the patients was 60.5 years. The median follow-up period was 78 months. The 3- and 5-year overall survival rates were respectively 92 and 80 %, and the cause-specific survival rates were respectively 100 and 96 %. Only one patient experienced tumor recurrence. The temporary tracheostomy was closed in 22 patients (73 %). The laryngeal preservation rate was 90 %, with 25 patients (83 %) obtaining a functional voice and 25 patients (83 %) resuming normal oral feeding. The univariate analysis showed advanced age (>65 years) as a negative prognostic factor for functional outcome but exhibited no statistical influence of gender, tumor type or stage, or previous radiotherapy. Strikingly, all chondrosarcoma patients experienced optimal functional outcomes. CONCLUSION: For this particular group of patients, the authors' tracheal autotransplantation technique provides excellent functional results for respiration, speech, and swallowing without compromising the oncologic outcome. This is particularly true for patients younger than 65 years and for those with cricoid chondrosarcoma.

Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study.

BACKGROUND: Diagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine-needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures. METHODS: Cytological specimens (n = 106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated. RESULTS: Of n = 63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential. CONCLUSION: Molecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine-needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.

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

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

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities.

Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.

Maxillomandibular Reconstruction Using Insourced Virtual Surgical Planning and Homemade CAD/CAM: A Single-Center Evolution in 75 Patients.

BACKGROUND: Virtual surgical planning (VSP) and computer-aided design and manufacturing (CAD/CAM) of surgical guides and jigs have dramatically changed the predictability of bony reconstruction of the jaw. VSP craftsmanship can lead to precision and enables the surgeon to complement the donor bone osteotomies with bony resection of the jaw. In recent years, immediate dental rehabilitation has become an integral part of VSP. However, outsourced CAD/CAM technology is expensive and may not be an option for many institutions worldwide. METHODS: The authors present here a consecutive series of 75 maxillofacial reconstructions from 2015 to 2020. We established an insourced "in-house" protocol for VSP and "home-made" CAD/CAM for the reconstruction of maxilla-mandibular defects with fibula, iliac crest, and scapular angle flaps. All patient files were analyzed retrospectively, and relevant parameters influencing the reconstructive outcome were determined. RESULTS: The authors went from a fibula-based protocol toward the selection of optimal vascularized bone for immediate placement of osteointegrated implants. Bone flap survival was 94.7% after 4 months. The 3-year patient survival is 77.6%. The authors show the multiple steps required for the routine use of in-house CAD/CAM and report the related financial balance. CONCLUSIONS: Insourced VSP and CAD/CAM has evolved into a valuable strategy in maxillomandibular reconstruction that promotes accuracy and precision and allows for occlusion-based planning with quality-of-life and aesthetic outcomes as essential parts of the reconstruction even in high-level oral cancers. Further reductions in the hardware and software acquisition costs may lead to widespread implementation of this innovative technology. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Atypical findings in three patients with Pai syndrome and literature review.

Pai syndrome is a rare disorder characterized by congenital nasal or facial polyp, midline cleft lip, pericallosal lipoma, ocular anomalies, and normal neuropsychological development. Here, we report on three patients with Pai syndrome and atypical findings: temporal triangular alopecia, posterior lenticonus, bilateral palatal pits, bifid uvula, hypospadias, sacral dimple, true tracheal bronchus, and epilepsy. Thirty-three cases of Pai syndrome have been described so far. We present a review of the previously reported cases and suggest modified diagnostic criteria for Pai syndrome.

Cervical squamous cell carcinoma of unknown primary: Oncological outcomes and prognostic factors.

Background/Objectives: Cervical squamous cell carcinoma of unknown primary (SCCUP) is a rare entity within head and neck cancer and both treatment regimens as well as identified potential predictors for oncological outcomes vary between published series. In this study, we evaluated oncological outcomes and identified potential prognostic factors for outcome. Patients and methods: This retrospective monocentric cohort study includes 82 SCCUP patients diagnosed and treated between January 2000 and June 2021. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) were evaluated. The Cox proportional hazards model was used to analyze the prognostic effect of patient and tumor characteristics on oncological outcomes. Results: Five year OS, DSS, DFS and LRFS were respectively 53.9%, 72.2%, 68.9% and 67.3%. The p16 status was evaluated in 55 patients with 40% being p16 positive. On univariable analysis, p16 negative SCCUPs had significantly worse survival and recurrence rates in the presence of clinical extranodal extension (cENE) (OS: p=0.0013, DSS: p=0.0099, DFS: p=0.0164, LRFS: p=0.0099) and radiological extranodal extension (rENE) (OS: p=0.0034, DSS: p=0.0137, DFS: p=0.0167, LRFS: p=0.0100). In p16 positive SCCUP patients, rENE had a significantly negative prognostic effect on DFS (p=0.0345) and LRFS (p=0.0367). Total group multivariate analysis identified rENE as an independent negative predictor for all oncological outcomes. The "number of positive lymph nodes" was a second independent predictor for DSS (p=0.0257) and DFS (p=0.0435). Conclusions: We report favorable oncological outcomes, comparable to previously published results. Although the presence of rENE seems associated with poor oncological outcomes, the differential effect of clinical, radiological and pathological ENE in both p16 positive and negative subgroups remain to be elucidated by further prospective research.

Voice Outcome After Carbon Dioxide Transoral Laser Microsurgery for Glottic Cancer According to the European Laryngological Society Classification of Cordectomy Types - A Systematic Review.

BACKGROUND: Voice outcome after carbon dioxide transoral laser microsurgery (CO2TOLMS) for glottic cancer is of prime importance. However, a comprehensive overview according to the European Laryngological Society (ELS) classification of cordectomies is still lacking. The aim of this systematic review is to summarize data on voice outcome associated with individual types of ELS glottic cordectomy after CO2TOLMS. MATERIALS AND METHODS: A systematic review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The initial search identified 936 records of which 25 publications were then included. Voice outcome data (Voice Handicap Index [VHI] version 30, grade of dysphonia [G] and maximum phonation time [MPT]) were extracted per resection type. Weighted averages were calculated. RESULTS: Data show a gradual increase in the VHI scores although they were still similar for all cordectomy types (range 14.2 to 21.5). The grade of dysphonia showed a gradual increase with increasing resection depth (range 1.0 to 1.9). There was a gradual decrease in the MPT (range 15.2 to 7.2). CONCLUSION: Voice outcome is related to cordectomy type with mild dysphonia characterizing ELS type I, II and III cordectomies, while more extended cordectomies (ELS type IV, V and VI) result in moderate dysphonia and shortness of breath during phonation. The voice handicap experienced by patients is limited even in the more extended cordectomies.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

A Solitary Melanoma Metastasis Confined to the Submandibular Gland.

Malignant melanoma is a type of cancer that most commonly originates from the skin, less frequently from mucosal surfaces, the eye, or meninges [Annu Rev Pathol. 2014;9(1):239-71]. In 2019, this type of malignancy was the third most frequent cancer to be diagnosed in males and the fifth most in females according to the American Cancer Society and the National Cancer Institute [CA Cancer J Clin. 2019;69(5):363-85]. The majority of the malignant melanomas in the head and neck region (85-90%) are cutaneous lesions, most often arising in the skin of the face [Head Neck. 2016;38:147-155]. In sharp contrast are the histological findings of metastatic melanoma with an unknown primary site: they are much more scarce and histologically difficult to diagnose. The literature is limited to case studies or small cohorts. In 2-6% of all patients suffering from metastatic melanoma, after clinical examination of the skin and mucosa, imaging, and other diagnostic examination, a primary tumor cannot be found [Eur J Cancer. 2004;40(9):1454-5]. A very small subgroup (0.5%) presents with a single focus of melanoma within the dermis or subcutaneous tissues [Arch Dermatol. 2000;136(11):1397-9]. We hereby report a case in this subgroup of a solitary melanoma metastasis found in the submandibular gland in a 59-year-old male. The tumor was discovered incidentally after surgical excision of this gland because of nodular enlargement.

Spontaneous cervical swelling syndrome as a rare cause of neck edema: case series and literature review.

Spontaneous cervical swelling syndrome (SCSS) is a rare disorder characterized by unprovoked, self-limiting and often unilateral cervical edema. SCSS is a recurrent disorder that predominantly affects adult women and is not associated with laboratory abnormalities. We report on eight female patients with a mean age of 56 (38-82) years at the time of the first presentation. The episodes were characterized by an acute onset in all patients and had a mean duration of 3.8 (1-7) days. Biochemical analysis did not reveal any related abnormalities. Imaging of the neck and chest demonstrated diffuse edema in the supraclavicular fossa and left infrahyoid region in all patients. At the time of the acute event, lymphatic scintigraphy revealed tracer accumulation in the left supraclavicular region in three patients and could not demonstrate any abnormalities in the in-between episodes in two patients.

Frozen section in thyroid gland follicular neoplasms: It's high time to abandon it!

Thyroid nodules are a very common clinical condition. The 2015 American Thyroid Association (ATA) guidelines recommend surgical excision for Bethesda IV nodules. The use of intraoperative frozen section (FS) has been recommended as a strategy to tailor the extent of the initial surgery. We critically evaluated the literature that discusses the utility and cost-effectiveness of FS to make an intraoperative decision in patients with thyroid nodules classified as follicular neoplasm. FS should not be recommended as a routine intraoperative test to assess for malignancy in thyroid follicular patterned lesions due to its low performance; the high number of deferred results; the inability to adequately assess histologically defining features; the improvements in risk stratification guiding total thyroidectomy; and the low cost-effectiveness of FS.

De-escalation studies in HPV-positive oropharyngeal cancer: How should we proceed?

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com).

Laryngeal Manifestations of Inflammatory Bowel Disease.

BACKGROUND: Laryngeal involvement in inflammatory bowel disease is rare. Only 12 cases of laryngeal involvement in Crohn disease have been reported until now. Moreover, only one case of laryngeal manifestations in ulcerative colitis has been reported so far. MATERIALS AND METHODS: In this article, we present a patient with ulcerative colitis, who consulted our ear, nose, and throat (ENT) clinic with laryngeal complaints. Furthermore, a review of current literature was performed. RESULTS: A concise overview of this rare extraintestinal manifestation and other ENT manifestations of inflammatory bowel diseases is provided. CONCLUSIONS: Laryngeal manifestations in inflammatory bowel disease are very rare, but these manifestations should be known by the otorhinolaryngologist.

Organ Preservation and Late Functional Outcome in Oropharyngeal Carcinoma: Rationale of EORTC 1420, the "Best of" Trial.

Dysphagia represents one of the most serious adverse events after curative-intent treatments with a tremendous impact on quality of life in patients with head and neck cancers. Novel surgical and radiation therapy techniques have been developed to better preserve swallowing function, while not negatively influencing local control and/or overall survival. This review focuses on the current literature of swallowing outcomes after curative treatment strategies. Available results from recent studies relevant to this topic are presented, demonstrating the potential role of new treatment modalities for early- and intermediate-stage oropharyngeal cancers. Based on this, we present the rationale and design of the currently active EORTC 1420 "Best of" trial, and highlight the potential of this study to help prioritizing either surgery- or radiation-based treatment modalities for the treatment of oropharyngeal cancer in the future.

An evidence-based analysis of the management of N0 neck in patients with cancer of the parotid gland.

Introduction: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.

Organ preservation surgery for advanced unilateral glottic and subglottic cancer.

OBJECTIVES: Functional surgery of unilateral T(2b) to T3 glottic cancer and cricoid chondrosarcoma is possible using the technique of tracheal autotransplantation. The objective of this paper is to report the functional and oncologic outcome of 24 consecutive patients treated with this technique between 2001 and 2007. METHODS: Seventeen patients, of whom nine were previously irradiated, had unilateral glottic cancer with impaired mobility of the vocal fold. Clinical staging was T(2b) to (3)N(0). Seven patients had a chondrosarcoma of the cricoid cartilage. In a first operation, an extended hemilaryngectomy was performed, and a radial forearm flap, comprising a distal fascial and a proximal skin component, was transferred to the neck. The fascial paddle was wrapped around the upper 4-cm segment of cervical trachea, and the skin paddle was used for temporary closure of the extended hemilaryngectomy defect. The definitive reconstruction was performed after 2 to 3 months and consisted of removal of the skin paddle from the laryngeal defect and a transplantation of a patch of revascularized cervical trachea to reconstruct the laryngeal defect. RESULTS: Swallowing and speech were restored after the first operation. The glottic and subglottic airway lumen was restored during the second operation. The tracheostomy could be closed in 20 patients. After a median follow-up period of 33 (range, 1-66) months or almost 3 years, 23 patients remained free of tumor recurrence. CONCLUSIONS: Tracheal autotransplantation can be recommended as a functional treatment for selected T(2b) to T(3) glottic cancers and for unilateral chondrosarcomas of the cricoid cartilage. The technique is oncologically robust while resulting in good postoperative function.