Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma.

In this study, we analyzed the expression profile of four genes (CCNA2, CCNB1, CCNB2, and CDK1) in laryngeal squamous cell carcinoma (LSCC) cell lines and tumor samples. With the application of microarray platform, we have shown the overexpression of these genes in all analyzed LSCC samples in comparison to non-cancer controls from head and neck region. We have selected CDK1 for further analysis, due to its leading role in cell cycle regulation. It is a member of the Ser/Thr protein kinase family of proven oncogenic properties. The results obtained for CDK1 were further confirmed with the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique, Western blot, and immunohistochemistry (IHC). The observed upregulation of CDK1 in laryngeal squamous cell carcinoma has encouraged us to analyze for genetic mechanisms that can be responsible this phenomenon. Therefore, with the application of array-CGH, sequencing analysis and two methods for epigenetic regulation analysis (DNA methylation and miRNA expression), we tried to identify such potential mechanisms. Our attempts to identify the molecular mechanisms responsible for observed changes failed as we did not observe significant alterations neither in the DNA sequence nor in the gene copy number that could underline CDK1 upregulation. Similarly, the pyrosequencing and miRNA expression analyses did not reveal any differences in methylation level and miRNA expression, respectively; thus, these mechanisms probably do not contribute to elevation of CDK1 expression in LSCC. However, our results suggest that alteration of CDK1 expression on both mRNA and protein level probably appears on the very early step of carcinogenesis.

Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

OBJECTIVE: Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. DESIGN: Cross-sectional distribution analysis. PARTICIPANTS: Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. MAIN OUTCOME MEASURES: A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. RESULTS: Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. CONCLUSIONS: Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64.

Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients.

Intralesional use of cidofovir (Vistide(®)) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.

Author Correction: Evaluation of narrow band imaging in the assessment of laryngeal granuloma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of narrow band imaging in the assessment of laryngeal granuloma.

Laryngeal granulomas belong to common complications following trans-oral laser microsurgery (TLM). The aim of this study was to evaluate NBI in the differentiation between granuloma-like lesions and local tumor recurrence. 154 consecutive patients after TLM due to early laryngeal cancer were enrolled. In the group, a monthly follow-up including NBI endoscopy was performed. Moderate and severe dysplasia, carcinoma in situ and invasive cancer were defined as positive histology, laryngeal granuloma and other benign laryngeal lesions as negative histology and premalignant lesions as suspicious histology. In 47/154 (31%) cases, granuloma-like lesion (GLL) was found. Patients with GLL were divided into two groups based on the NBI classification. In all patients, the microvascular pattern in NBI was compared with the final histology. In group A, with suspicious, perpendicular vessels, 13/13 (100%) samples were positive. In group B, with normal vascular pattern 3/34 (9%) samples were positive and 31/34 (91%) samples were negative. There was a significant correlation between the positive NBI vascular pattern and the final histology (p = 0.00001). Sensitivity, specificity, accuracy of NBI were as follows: 81%, 100%, 94%, respectively.Based on our results, NBI can reliably differentiate between postoperative laryngeal granuloma and local tumor recurrence. In such a manner, this method is very helpful in the follow-up of tumor patients.

The usefulness of narrow band imaging in the assessment of laryngeal papillomatosis.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus 6 and 11. The characteristic feature of this disease are wart-like lesions covering the respiratory epithelium with a predilection for the larynx. There is no curative treatment for the disease. The goal of the treatment is a total surgical removal of the papillomatous lesions in order to reduce the number of relapses. Therefore, a good visualization method of papillomas is crucial during surgery. The aim of the study was to compare the accuracy of narrow band imaging (NBI) to the use of white light alone in detecting RRP. METHODS: The study was carried out between April 2013 and November 2015 at Poznan University of Medical Sciences, Department of Otolaryngology, Poland. Rigid endoscopy with conventional white light (WL) and NBI (CV-260SL processor and CLV- 260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan) was performed in all patients during direct laryngoscopy. All anatomical sites of the larynx and trachea were assessed using the Dikkers scale and Derkay total site scoring system with WL and NBI. The consensus was reached as to the number of lesions seen in WL compared to NBI. RESULTS: During 36 microlaryngoscopies, the number of papillomas detected in the larynx (by Derkay total site score) differed significantly between white light endoscopy and NBI (Wilcoxon test p = 0.000655). In endoscopy with NBI, a mean of 1.3 more papillomas in Derkay total site score was detected in comparison to white light endoscopy NBI showed additional areas of diseased tissue in 15/36 (41.67%) patients. CONCLUSIONS: NBI as an additional tool during microlaryngoscopy can improve the detection of papillomatous lesions.

[Tinnitus as the first symptom of Arnold-Chiari-Syndrome]. / Szumy uszne jako objaw zespolu Arnolda-Chiariego.

The Arnold-Chiari malformation is very rare hindbrain abnormalities characterized by herniation of the hindbrain through the foramen magnum. It usually does not present until adulthood, and then its symptoms may be varied and subtle. Patient 49 years was diagnosed in Foniatrics and Audiology Clinic because of tinnitus in left ear lasting 3 months. She underwent audiological diagnostic, that did not reveal any abnormalities, except for electrogustometry and hyporeflexia of stapedial reflex and labyrinth on the left side. In MRI scan we have noticed hindbrain abnormalities characteristic for Chiari type I malformation. Treatment consisted of immediate supportive care as needed but without surgical decompression, which was found unnecessary.

Narrow-band imaging (NBI) for improving the assessment of vocal fold leukoplakia and overcoming the umbrella effect.

BACKGROUND: It is crucial to find a balance between functional and oncological outcome when choosing an adequate method for the management of vocal fold leukoplakia. Therefore, a detailed examination is a milestone in the decision-making process. AIM: To examine whether narrow-band imaging (NBI) can be helpful in vocal fold assessment in the case of leukoplakia and how to overcome the "umbrella effect"- understood as the submucosal vascular pattern hidden under the plaque. MATERIAL AND METHODS: Prospective cohort of 41 consecutive patients. Inclusion criteria: vocal fold leukoplakia, no previous procedures (surgery, radiotherapy), and preoperative endoscopy with an optical filter for NBI. Two groups: "suspicious" and "normal", according to the submucosal microvascular pattern of peripheral regions of the mucosa surrounding the plaque, were distinguished. Patients were qualified for a full-thickness or partial-thickness biopsy, respectively. Criteria defining suspected characters were well-demarcated brownish areas with scattered brown spots corresponding to type IV, Va, Vb, and Vc NI classifications. RESULTS: In 22/41 (53.7%) patients with "suspected" microvascular pattern, full-thickness biopsy was performed. Moderate and severe dysplasia was revealed in 15 type IV and 7 type Va NI patients. In 19/41 (46.3%) patients with proper NBI vessel pattern treated by partial-thickness biopsy, hyperkeratosis was diagnosed. There was a strong correlation between the NBI pattern and final histology: Chi2 (2) = 41.0 (p = 0.0000). CONCLUSION: The results demonstrate that NBI endoscopic assessment of the submucosal microvascular pattern of mucosa surrounding the plaque can be an effective method to categorise the risk in vocal fold leukoplakia prior to treatment.