European Laryngological Society position paper on laryngeal dysplasia Part I: aetiology and pathological classification.

PURPOSE OF REVIEW: To give an overview of the current knowledge regarding the aetiology, epidemiology, and classification of laryngeal dysplasia (LD) and to highlight the contributions of recent literature. As most cases of dysplasia occur at the glottic level and data on diagnosis and management are almost exclusively from this location, laryngeal dysplasia in this position paper is taken to be synonymous with dysplasia of the vocal folds. LD has long been recognized as a precursor lesion to laryngeal squamous cell carcinoma (SCC). Tobacco and alcohol consumption are the two single most important etiological factors for the development of LD. There is currently insufficient evidence to support a role of reflux. Although varying levels of human papillomavirus have been identified in LD, its causal role is still uncertain, and there are data suggesting that it may be limited. Dysplasia has a varying presentation including leukoplakia, erythroleukoplakia, mucosal reddening or thickening with exophytic, "tumor-like" alterations. About 50% of leukoplakic lesions will contain some form of dysplasia. It has become clear that the traditionally accepted molecular pathways to cancer, involving accumulated mutations in a specific order, do not apply to LD. Although the molecular nature of the progression of LD to SCC is still unclear, it can be concluded that the risk of malignant transformation does rise with increasing grade of dysplasia, but not predictably so. Consequently, grading systems are inherently troubled by the weak correlation between the degree of the dysplasia and the risk of malignant transformation. The best data on LD grading and outcomes come from the Ljubljana group, forming the basis for the World Health Organization classification published in 2017.

European Laryngological Society position paper on laryngeal dysplasia Part II: diagnosis, treatment, and follow-up.

PURPOSE OF REVIEW: To give an overview of the current knowledge regarding the diagnosis, treatment, and follow-up of laryngeal dysplasia (LD) and to highlight the contributions of recent literature. The diagnosis of LD largely relies on endoscopic procedures and on histopathology. Diagnostic efficiency of endoscopy may be improved using videolaryngostroboscopy (VLS) and bioendoscopic tools such as Narrow Band Imaging (NBI) or Storz Professional Image Enhancement System (SPIES). Current histological classifications are not powerful enough to clearly predict the risk to carcinoma evolution and technical issues such as sampling error, variation in epithelial thickness and inflammation hamper pathological examination. Almost all dysplasia grading systems are effective in different ways. The 2017 World Health Organization (WHO) system should prove to be an improvement as it is slightly more reproducible and easier for the non-specialist pathologist to apply. To optimize treatment decisions, surgeons should know how their pathologist grades samples and preferably audit their transformation rates locally. Whether carcinoma in situ should be used as part of such classification remains contentious and pathologists should agree with their clinicians whether they find this additional grade useful in treatment decisions. Recently, different studies have defined the possible utility of different biomarkers in risk classification. The main treatment modality for LD is represented by transoral laser microsurgery. Radiotherapy may be indicated in specific circumstances such as multiple recurrence or wide-field lesions. Medical treatment currently does not have a significant role in the management of LD. Follow-up for patients treated with LD is a fundamental part of their care and investigations may be supported by the same techniques used during diagnosis (VLS and NBI/SPIES).

Modifications of the midline mandibulotomy for access to the parapharyngeal space.

When considering a mandibular osteotomy for access to resect a parapharyngeal neoplasm, the following goals should be considered: preservation of the facial nerve, complete removal of the neoplasm without tumor rupture, maintenance of the preoperative teeth occlusion, acceptable temporomandibular joint function, functional preservation of the inferior alveolar nerve sensation, and satisfying aesthetic results. We propose a modified median osteotomy technique, which combines the advantages of sufficient exposition of the tumor with very good functional and aesthetic results. A case series of nine patients suffering from extended pleomorphic adenomas of the inner lobe of the parotid gland is presented.

Second-look microlaryngoscopy to detect residual carcinoma in patients after laser surgery for T1 and T2 laryngeal cancer.

CONCLUSIONS: The presented concept of second-look microlaryngoscopy in patients treated with transoral laser surgery (TLS) for early glottic carcinoma is promising and warrants further studies to evaluate its benefits. OBJECTIVES: Clear surgical margins at the primary site influence the course of the disease in patients with laryngeal carcinoma who undergo TLS. Several factors may lead to a reduced sensitivity in detecting tumor remnants at the time of the initial procedure. We therefore developed the concept of second-look microlaryngoscopies to enable a microscopic and histologic reassessment at the primary tumor site to exclude residual carcinoma. PATIENTS AND METHODS: Patients were scheduled for two second-look microlaryngoscopies under general anesthesia at 8-10 weeks and 16-20 weeks after the initial TLS procedure. We analyzed the histopathologic findings of biopsies taken in the second-look microlaryngoscopies and the survival parameters of 181 patients treated with TLS for early laryngeal carcinoma. RESULTS: Carcinoma at the primary site was found in 5.1% of all patients within the first and in 11.5% of all patients within the second second-look microlaryngoscopy, although the preoperative indirect laryngoscopy was inconspicuous in most cases. The survival analysis showed a 5-year and 10-year disease-free survival of 96.3% and 92.7%, respectively. The disease-free survival was significantly decreased when carcinoma was found in the second-look microlaryngoscopy (p=0.004).

Surgery of adult bilateral vocal fold paralysis in adduction: history and trends.

Bilateral vocal fold paralysis (BVFP) in adduction is characterised by inspiratory dyspnea, due to the paramedian position of the vocal folds with narrowing of the airway at the glottic level. The condition is often life threatening and therefore requires surgical intervention to prevent acute asphyxiation or pulmonary consequences of chronic airway obstruction. Aside from corticosteroid administration and intubation, which are only temporary measures, the standard approach for improving respiration is to perform a tracheotomy. Over the past century, a vast majority of surgical interventions have been developed and applied to restore the patency of the airway and achieve decannulation. Surgeons can generally choose for every individual patient from various well-established treatment options, which have a predictable outcome. An overview of the surgical techniques for laryngeal airway enlargement in BVFP is presented. Included are operative techniques, which have found application in clinical practice, and only to a small extent in purely anatomic or animal studies. The focus is on two major groups of interventions--for temporary and for definitive glottic enlargement. The major types of interventions include the following: (1) resection of anatomical structures; (2) retailoring and displacing the existing structures, with minimal tissue removal; (3) displacing existing structures, without tissue resection; (4) restoration or substitution of the missing innervation of the laryngeal musculature. The single interventions of these four major types have always followed the development of the medical equipment and anaesthesia. At the beginning of the twentieth century, when medicine was unable to counteract surgical infection, endoscopic or extramucosal surgical techniques were dominant. In the 1950s, the microscopic endoscopic laryngeal surgery boomed. At the end of the twentieth century many of the classical endoscopic operations were performed either with the help of surgical lasers alone, or in combination with other interventions.

Fiberoptic endoscopic evaluation of swallowing in intensive care unit patients.

Aspiration in critically ill patients frequently causes severe co-morbidity. We evaluated a diagnostic protocol using routine FEES in critically ill patients at risk to develop aspiration following extubation. We instructed intensive care unit physicians on specific risk factors for and clinical signs of aspiration following extubation in critically ill patients and offered bedside FEES for such patients. Over a 45-month period, we were called to perform 913 endoscopic examinations in 553 patients. Silent aspiration or aspiration with acute symptoms (cough or gag reflex as the bolus passed into the trachea) was detected in 69.3% of all patients. Prolonged non-oral feeding via a naso-gastric tube was initiated in 49.7% of all patients. In 13.2% of patients, a percutaneous endoscopic gastrostomy was initiated as a result of FEES findings, and in 6.3% an additional tracheotomy to prevent aspiration had to be initiated. In 59 out of 258 patients (22.9%), tracheotomies were closed, and 30.7% of all 553 patients could be managed with the immediate onset of an oral diet and compensatory treatment procedures. Additional radiological examinations were not required. FEES in critically ill patients allows for a rapid evaluation of deglutition and for the immediate initiation of symptom-related rehabilitation or for an early resumption of oral feeding.

Mapping of Ki-67 protein distribution on whole organ serial sections of the larynx.

CONCLUSIONS: Immunostaining of whole organ serial sections of the larynx is feasible and will allow analysis of cellular alterations in the undisturbed anatomical context of whole organ serial sections of the larynx. OBJECTIVES: Whole organ serial sections of the larynx have to date been used for conventional macroscopic evaluation of laryngeal tissues. The aim of this study was to establish a protocol for immunohistochemistry of whole organ sections of the larynx. MATERIALS AND METHODS: Five laryngectomy specimens were obtained during surgery for advanced laryngeal carcinoma. Using a novel method for paraffin embedding, we chose the proliferation marker Ki-67 antigen as a model target for immunoreactivity on serial sections. RESULTS: We were able to produce whole organ serial sections that could then be immunostained for Ki-67. A complete mapping of proliferating cells throughout the tumour, at the tumour front and in skip lesions was subsequently obtained.

Long-term results of surgical treatment for recurrent respiratory papillomatosis.

CONCLUSIONS: The presented results add further support to the observation that laser microsurgery is the preferential surgical treatment for recurrent respiratory papillomatosis (RRP). A meticulous follow-up for early recognition of local recurrence and malignant transformation is recommended. OBJECTIVES: Endoscopic microsurgery continues to be the treatment of choice for RRP. The aim of this study was to evaluate the outcome of patients treated surgically. We focused on demographic data, recurrence rates, and treatment-related complications. PATIENTS AND METHODS: The charts of 194 patients treated at our institution between 1963 and 1993 were analyzed retrospectively. RESULTS: In all, 64 patients (33%) underwent a total of 137 operations using the CO2 laser; 130 patients (67%) underwent a total of 565 microlaryngeal operations by surgery with cold instruments. Five percent of the patients treated with conventional microlaryngeal surgery and none of the patients treated with laser surgery required tracheostomy (p<0.05). Postoperative glottic webs and scar formations were found in 6% of all patients after laser surgery and 20% after conventional surgery (p<0.05). The different methods of treatment did not affect the rate of recurrence (p=0.61) Malignant transformation or secondary airway carcinoma were observed in 4% of all patients.

Immunohistochemistry of whole-organ sections of advanced human laryngeal cancer.

Whole-mount sections have been in the interest of laryngologists for long time. The aim of this study was to demonstrate the technical aspects of processing horizontal whole-mount sections of advanced laryngeal cancer specimens after total laryngectomy. Those sections may provide new insights in the biology of laryngeal cancer. Six excised human larynges were block-embedded in paraffine. Serial sections were obtained as thin as 9 mum. Sections were stained by Giemsa and standard immunohistochemistry protocols with commercial antibodies against Cytokeratine5/6, Ki-67, Topoisomerase IIalpha, and p53. Four high-power fields were selected randomly in each section of a surface grid and the percentage of positive tumor cells was noted for each antibody in the respective field. Morphometric surface maps of protein expression were generated for each parameter. The tissues remained intact without major artifacts. Specific characteristics of the tumors were identified after evaluation of the whole-mount sections. Staining of cytokeratine was homogenous, whereas nuclear markers showed a distinct heterogeneity in the respective staining patterns. By analyzation of color-coded fusion images the spatial expression of the respective antibodies could be visualized.

Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer.

PURPOSE: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. PATIENTS AND METHODS: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. RESULTS: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. CONCLUSIONS: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

Successful adjuvant tamoxifen therapy for estrogen receptor-positive metastasizing sweat gland adenocarcinoma: need for a clinical trial?

We report on successful adjuvant tamoxifen therapy for a metastasizing sweat gland adenocarcinoma of the scalp in a 64-year-old woman. Before the antihormonal therapy, the patient had undergone repeated surgery for ipsilateral intraparotid, soft tissue, and lymph node metastases and had had disease-free intervals of less than 5 months. As the immunohistochemical analysis of the tumor tissue revealed a 100% nuclear reactivity to estrogen and progesterone receptors, we started empirical tamoxifen citrate therapy, which dramatically changed the course of the disease. The patient has been in complete remission for 3 years. This is the third report in the literature of substantial therapeutic benefit of antiestrogen therapy in metastasizing eccrine gland adenocarcinoma with positive hormone receptor immunohistochemistry. We suggest examining the hormone receptor expression in these neoplasms regularly. A prospective study should be commenced to assess the benefit of adjuvant antihormonal therapy in eccrine gland adenocarcinomas.

High incidence of lymph node metastasis in major salivary gland cancer.

OBJECTIVE: To analyze the incidence and risk factors for clinically apparent and occult lymph node metastases in patients with major salivary gland cancers. DESIGN: Cohort of patients with a median follow-up of 46 months (range, 1-174 months). SETTING: University-based referral center. PATIENTS: A total of 160 consecutive patients with complete clinical and pathologic data. INTERVENTION: Neck dissection was performed in all cases. Patients were treated with surgery alone (55%); surgery and radiation therapy (43%); or a combination of surgery, radiation, and chemotherapy (2%). MAIN OUTCOME MEASURE: Incidence of apparent and occult lymph node metastases. Univariate and multivariate analyses were used to evaluate the significance of clinical and pathologic data. RESULTS: Histologically confirmed positive neck was found in 53% of all cases. Histologic diagnosis was significantly related to the incidence of lymph node metastasis: 89% (16/18) for undifferentiated carcinomas. However, so-called low-risk tumors had incidence rates of 22% to 47%. Twenty-one patients (13%) presented with clinically apparent cervical lymph node metastasis. Of the 139 patients with clinical N0 neck, 45% had occult neck metastasis. Neck metastasis was found in 29% (10/34) of T1, 54% (38/70) of T2, 65% (20/31) of T3, and 54% (16/25) of T4 tumors. Assessment of survival according to nodal status revealed significant correlations for overall (P<.001) and disease-free survival (P<.001). CONCLUSIONS: We found a high incidence of lymph node metastasis from major salivary gland cancers. Neck dissections should be considered as an integral part of the surgical approach in patients with major salivary gland cancer, especially if no postoperative radiation therapy is planned.

Management of bilateral arytenoid cartilage fixation versus recurrent laryngeal nerve paralysis.

Bilateral arytenoid cartilage fixation (ACF) closely resembles vocal cord immobility due to recurrent laryngeal nerve paralysis (RLNP). This study sought to determine the etiologic differences between these two entities and to derive conclusions about treatment. The charts of 218 consecutive adult patients with immobility of both vocal cords requiring surgery for airway restoration were reviewed. The results of laryngeal electromyography and laryngotracheoscopy were used to distinguish ACF from RLNP. In 186 patients (85.3%), RLNP was identified. Of these, 154 paralyses (82.8%) were caused by surgical interventions, 5 (2.7%) were caused by previous intubation, 16 (8.6%) were caused by various malignancies, and 7 (3.8%) were neurogenic. In 4 patients (2.2%), the cause remained unclear. We identified ACF in 32 patients. The etiologic factors included previous long-term intubation in 22 patients (68.8%), short-term intubation in 3 patients (9.4%), Wegener's granulomatosis in 3 patients (9.4%), rheumatoid arthritis in 2 patients (6.3%), previous laryngeal surgery in 1 patient (3.1%), and caustic ingestion in 1 patient (3.1%). Additional second-site airway stenosis was found in 10 of the RLNP patients (5.4%) and in 15 of the ACF patients (46.9%). All RLNP patients had endoscopic surgery without temporary tracheotomy. Eighteen ACF patients required open surgery, and 4 were managed endoscopically but required temporary tracheotomy. The etiologic factors were significantly different for the two entities under study. Additional sites of stenosis were more frequent in ACF patients. Stenosis due to RLNP could be managed endoscopically without preliminary tracheotomy, while ACF frequently required open surgery and temporary tracheotomy.

Suspension laryngoscopy for endotracheal stenting.

OBJECTIVES/HYPOTHESIS: Airway stents have recently been used to establish and maintain patent airways in patients with malignant central airway obstruction, but insertion modalities remain controversial to date. The study seeks to determine the role of suspension laryngoscopy in interdisciplinary airway stenting. STUDY DESIGN: Retrospective, single-institution analysis of a case series treated by a multidisciplinary airway team. METHODS: Ninety-three consecutive patients with malignant obstruction of the trachea and/or tracheobronchial bifurcation underwent endotracheal stenting through a suspension laryngoscopy approach for the relief of impending respiratory distress. Feasibility, mortality, survival, and complications were analyzed as main outcome measures. RESULTS: Stenting through a suspension laryngoscopy approach was feasible 91 of 93 patients (97.8%). Fifteen patients needed repeated stenting, and in all, 121 stents were implanted during the observation period. This approach allowed for the repeated insertion of rigid bronchoscopes of graded sizes to establish an airway and for precise stent positioning. Optical instruments and stent introducer systems could easily be used while adequate ventilation was continuously maintained. Silicone stents of maximal size were inserted without injury of the vocal cords during intubation. Median survival for all patients was 8 months. No intraoperative airway complications were observed, and no patient died secondary to stenting. CONCLUSIONS: Suspension laryngoscopy and jet ventilation provide an ideal setting for the precise placement of tracheal and bifurcation airway stents. Laryngologists should actively participate in interdisciplinary airway stenting programs.

Complications of suspension laryngoscopy.

Although suspension laryngoscopy (SL) is routinely used in operative laryngology, no prospectively gathered data on the complications of this procedure have so far been available. We prospectively analyzed 339 consecutive procedures for intervention-related complications. The survey included preoperative dental status and assessment of postoperative dental, mucosal, and nerve injuries. Minor mucosal lesions were found in 75% of all patients. All healed spontaneously within a few days. Dental injuries occurred in 6.5% of all patients. These were more frequent in therapeutic laryngoscopy than in diagnostic procedures (6.8% versus 6.0%). Highly significant correlations were found between dental injury rate and preoperative dental disease (p < .04) and grade of periodontitis (p <.001). Temporary nerve lesions were observed in 13 patients (9 of the lingual nerve and 4 of the hypoglossal nerve). Although minor complications frequently occur during SL, it is a relatively safe procedure with a low risk of significant morbidity.

Surgical voice rehabilitation after laser surgery for glottic carcinoma.

Transoral laser surgery today is the mainstay of treatment for T1 and T2 glottic carcinoma. The vocal ability remains sufficient in the majority of patients. However, in some cases, a significant glottic gap may persist, leading to poor voice quality. We report a special technique of medialization thyroplasty using autologous cartilage specifically adapted for vocal rehabilitation after laser resection. Six patients with a significant glottic gap following laser surgery were treated. For vocal rehabilitation, a special medialization technique was performed. The superior rim of the thyroid cartilage of the resected side was exposed. A 1 x 2-cm piece of cartilage was harvested and reimplanted into a subperichondrial pouch created on the inner side of the thyroid cartilage. When phonation was optimal, this cartilaginous strut was sutured and/or glued in place. In all 6 cases, the vocal function improved significantly. The dysphonia index (0 = normal, 3 = aphonia), which includes objective parameters as well as expert voice ratings and the patient's perception, increased by 1.1 on average (range, 0.4 to 1.6). The results have been lasting. The established medialization techniques are of limited value in a larynx scarred by laser surgery. Injection augmentation is often futile because the tight scar tissue does not lend itself to augmentation. Implantation of nonorganic material may cause problems if revision surgery for tumor recurrence should become necessary or if the implant protrudes into the scarred endolarynx. The technique reported avoids these pitfalls and leads to voice quality improvement comparable to that of established medialization procedures.