Finding balance between minimally invasive surgery and laryngotracheal resection in the management of adult laryngotracheal stenosis.

Management of adult laryngotracheal stenosis is complex and several treatment options are known. The present study focuses on finding the right balance between minimally invasive surgery and laryngotracheal resection by reviewing a single institution's experiences. Retrospective analysis was performed of all adult and adolescent patients with laryngotracheal stenosis who underwent treatment in a tertiary referral center, between 1990 and 2012. Age, gender, etiology, treatment, recurrence, pre- and post-operative peak flow (PF), and pre- and post-treatment subjective complain scores (SCS) were registered. 87 patients with 267 interventions were analyzed. There were 238 dilatation tracheoscopies, 22 open surgeries and various other endoscopic procedures registered. Idiopathic stenoses required the most dilatation tracheoscopies, while post-tracheotomy stenoses required the least. Patients in the post-intubation and post-tracheotomy groups were significantly more often treated with open surgery compared to those in the granulomatosis with polyangiitis (GPA) and idiopathic groups. The gain in PF flow after dilatation tracheoscopy was significantly higher in the idiopathic group compared to the other groups. The median SCS of dyspnoea decreased in the whole population, while other SCS did not change remarkably. Repeated endoscopic procedures are recommended in patients with severe systemic disease which do not allow open surgery or when other comorbidities contraindicate open surgery. Open surgery very often offers the definitive solution in the treatment of laryngotracheal stenosis and cannot be avoided when the laryngeal or the tracheal framework is damaged. Patients' personal preferences have to be considered in the pre-operative assessment process.

Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were retrospectively analyzed. Clinical data were subtracted from patients' files. Pretreatment biopsy material was tested for the presence of HPV6, 11, 16, and 18 using a PCR-based detection method. Immunohistochemical staining was performed for Ki-67, p16(INK4A), and p53 expression. All cases were negative for the low-risk HPV types HPV6 and HPV11 that are associated with laryngeal papillomatosis. High-risk HPV was detected in two cases; an atypical carcinoid was positive for HPV16 and a large-cell neuroendocrine carcinoma for HPV18. Both HPV-positive tumors had a high Ki-67 labeling index. Two of the four cases with a good response to therapy were hrHPV-positive (both HPV DNA positive) compared with none of the five poor responders. Our findings show that HPV may play a role in the pathogenesis of LNEC. The relationship between HPV, improved prognosis and good response to therapy for squamous cell carcinoma of the head and neck may also be true for a subset of LNEC.

The importance of multimodality therapy in the treatment of sinonasal neuroendocrine carcinoma.

Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors known for their aggressive behavior and poor response to treatment. The data in the literature are sparse and cover a wide range of therapeutic approaches over a protracted timeline. Therefore, it is important that institutions report on their experience with these rare neoplasms. Clinical data, such as age at diagnosis, gender, tumor subtype and stage, treatment intention and modality, recurrence, salvage treatment, and survival of patients with a SCND, diagnosed at our department between 1980 and 2010, were retrospectively analyzed. Fifteen patients were available for analysis; eight with sinonasal undifferentiated carcinoma (SNUC), five with sinonasal neuroendocrine carcinoma (SNEC), and two with small cell neuroendocrine carcinoma (SmCC). The median age at the time of diagnosis was 68 years (range 28-87). Treatment consisted of surgery (2), radiotherapy (4), a combination of these modalities (6) and palliation (3). The estimated 5-year overall survival was 60 % for SNEC, 44 % for SNUC and 0 % for SmCC. According to our institutional experience an aggressive multi-modality approach incorporating (neoadjuvant) chemoradiotherapy, radical surgery and elective treatment of the neck is the best treatment strategy for SCND. The high propensity for distant metastasis and poor prognosis of SmCC warrants consideration of the impact of treatment on the remaining quality of life in these patients.

Meta-analysis of 701 published cases of sinonasal neuroendocrine carcinoma: The importance of differentiation grade in determining treatment strategy.

The aim of this meta-analysis was to provide treatment guidelines for sinonasal neuroendocrine carcinoma (SNC) by combining all available data in the literature. A literature search for all studies concerning SNC was performed against the MEDLINE and EMBASE databases. Available clinical data was normalized, pooled, and statistically analyzed. A total of 701 cases of SNC were available for analysis, comprising 127 well or moderately differentiated sinonasal neuroendocrine carcinomas (SNEC), 459 sinonasal undifferentiated carcinoma (SNUC) and 115 sinonasal small cell carcinoma (SmCC). Tumor type was the most important predictor of survival, with a 5-year disease-specific survival (DSS) of 70.2% for SNEC, 35.9% for SNUC and 46.1% for SmCC. Tumor stage on presentation was of limited value in predicting survival or response to treatment. Overall, the application of surgery yielded significantly better results (5-year DSS 52.2% versus 30.1%, p<0.001). In SNUC, radiotherapy was a beneficial supplement to surgery (5-year DSS 54.7% versus 15.7%, p=0.027), while radiotherapy as monotherapy performed poorly (5-year DSS 17.9%). Chemotherapy did not appear to contribute to survival. Based on these findings, we can conclude that the most important predictors of survival in SNC are differentiation grade and the associated choice of treatment modality. In contrast to other head and neck cancers, tumor staging appears of limited value in predicting survival or deciding on a treatment strategy. Surgery should be the cornerstone of treatment, supplemented by radiotherapy in poorly differentiated subtypes (SNUC, SmCC). Chemotherapy does not appear to contribute to survival.

Clinical recommendations on the treatment of neuroendocrine carcinoma of the larynx: A meta-analysis of 436 reported cases.

BACKGROUND: Current recommendations on the treatment of neuroendocrine carcinoma of the larynx (NCL) are based on anecdotal evidence. With this meta-analysis, our purpose was to provide clinicians with more substantiated guidelines in order to improve the treatment outcome of the patients affected with NCL. METHODS: A structured literature search for all research concerning NCL was performed against the MEDLINE and EMBASE databases. Available data was normalized, pooled, and statistically analyzed. RESULTS: Four hundred thirty-six cases of NCL were extracted from 182 studies, of which 23 were typical carcinoid, 163 were atypical carcinoid, 183 were small-cell neuroendocrine carcinoma, 29 were large-cell neuroendocrine carcinoma, and 38 were unspecified carcinoid tumors. The 5-year disease-specific survival (DSS) was 100% for typical carcinoid, 53% for atypical carcinoid, 19% for small-cell neuroendocrine carcinoma, and 15% for large-cell neuroendocrine carcinoma (p < .001). Patients with an atypical carcinoid treated with surgery had better DSS than those treated with radiotherapy (60% vs 54%; p = .035). Postoperative radiotherapy did not result in better DSS in atypical carcinoid. Patients with an atypical carcinoid, not undergoing surgical treatment of the neck, developed isolated regional recurrence in 30% of cases (p = .001). Radiochemotherapy yielded the best DSS for small-cell neuroendocrine carcinoma compared to other modalities (31% vs 13%; p = .001). CONCLUSION: Typical carcinoid can be treated by local excision alone. Atypical carcinoids do not seem to respond well to radiotherapy and are best managed through radical surgical excision in combination with elective neck dissection. Patients with small-cell neuroendocrine carcinoma or large-cell neuroendocrine carcinoma seem to benefit most from chemoradiotherapy.