Is nasal airflow disrupted after endoscopic skull base surgery? A short review.

Even the most delicate endonasal surgery for skull base lesion causes changes in the nasal cavity, some of them permanent. Morphological changes in the nasal cavity and their consequences (changes in nasal airflow) are often studied by advanced numerical analysis called computational fluid dynamics. This review summarizes current knowledge of endoscopic transsphenoidal skull base surgery effects on nasal airflow. Several studies have shown that endoscopic skull base surgery changes nasal anatomy to the extent that nasal airflow changes significantly postoperatively. Removing any intranasal structure increases the cross-sectional area of the respective nasal meatus, leading to increased nasal airflow in this area while airflow in the narrower periphery decreases. Middle turbinate resection increases airflow in the middle meatus and reduces airflow in the superior and inferior meatus. Small posterior septectomy does not cause a significant change in nasal airflow. Nasal septum deviation is an important factor in airflow changes. Current studies describe nasal changes after rather extensive procedures (e.g., middle turbinectomy, ethmoidectomy) that are unnecessary in routine pituitary adenoma surgery. No studies have compared changes using pre- and postoperative scans of the same patients after actual surgery.

Morbidity and mortality associated with thyroid surgery - retrospective analysis 19912010.

INTRODUCTION: The incidence of thyroid disorders has been rising worldwide. Unlike the incidence, mortality associated with malignant thyroid cancer shows only a modest increase. Between 1979 and 2009, mortality in Czech women increased from 1.21 to 1.31 and in Czech men from 0.54 to 0.74 cases per 100,000 individuals.  Methods: A retrospective statistical analysis was performed in patients undergoing thyroid surgery at the Department of Otorhinolaryngology and Head and Neck Surgery of the 1st Faculty of Medicine, Charles University and University Hospital Motol, and at the Department of Otorhinolaryngology of the Institute for Postgraduate Medical Education in Prague from 1991 to 2010 (twenty years). In this period, 11,005 procedures were done for thyroid disease. The study analysed the incidence, morbidity, mortality, surgical complications and lethality. RESULTS: The study group included surgeries in 1588 male and 9417 female patients. The male/female ratio was 1:5.93. Benign thyroid tumours - mean patient age is 54.7 years; recurrent nerve morbidity is 1.37% (calculated from exposed nerves). Hypocalcaemia incidence is low, 5.4% of permanent hypocalcaemia or hypoparathyroidism, respectively, based on decreased serum parathyroid hormone (PTH) levels. Temporary hypocalcaemia is much more frequent, occurring in almost 15% cases depending on age, season of the year, and nutritional status. Hypoparathyroidism was demonstrated based on laboratory serum PTH levels only in 0.3% patients. In total, 442 patients were operated for the mechanic syndrome (a large goitre). The mean thyroid volume was 493 ml±136 ml; however, the maximum volume was 980 ml and weight 1115 g. The incidence of recurrent nerve injury occurs in 4.5%, i.e. the morbidity is 2 times higher compared to surgeries for other diagnoses. The incidence of hypoparathyroidism is not higher compared to other surgeries. Revision surgeries were indicated more commonly in malignant thyroid diseases, particularly in papillary and follicular carcinomas. Cervical lymph nodes procedures comprise another large segment in tumour treatment. Our analysis supports selective neck dissections while preserving non-lymphatic structures. As a rule, mortality associated with thyroid surgery is divided as mortality in the perioperative period (within 24 hours after the procedure) and early postoperative mortality (within 120 hours after the procedure). Surgery-related mortality was never classified as perioperative or within 24 hours after the procedure. Despite that, we believe that perioperative mortality within 120 hours after the procedure, which occurred in 7 cases, is very important. Mortality of the group was 0.007%. CONCLUSIONS: Each surgery procedure is associated with complications, morbidity and mortality. Experience of endocrine surgeons of all disciplines leads to a very low incidence of recurrent nerve and parathyroid gland injuries while at the same time achieving sufficient radicality. This, in cooperation with other medical fields such as endocrinologists, nuclear medicine specialists and oncologists, supports a safe and effective management of all thyroid disorders, including a good prognosis of patients with most types of cancer. Key word: thyroid surgery - complications recurrent nerve - hypoparathyroidism lethality.

[The Tear Osmolarity of PATIENTS with Lagophthalmos]. / Osmolarita slz u pacientu s lagoftalmem.

INTRODUCTION: Lagophthalmos can be characterized as the dysfunction of the eye aperture and in some cases even by the disruption of tear production. Dry eye syndrome can consequently develop. Instability of the tear film, hyperosmolarity and inflammatory reaction are considered as the key mechanisms of dry eye syndrome. In our report we monitored the tear osmolarity of patients with postsurgical unilateral lagophthalmos. Results were compared with tear osmolarity of the non-lagophthalmic eyes. METHODS: We examined 10 patients (6 women, 4 men) with postsurgical facial nerve palsy and lagophthalmos complicating management of either cerebellopontine (8 patients) or salivary gland tumors (2 patients). Only patients without severe corneal defects enrolled the study. The tear osmolarity was measured in lower tear meniscus by TearLab Osmolarity System device. The lagophthalmic eye was always examined first. The results are presented as mean plus/minus the standard deviation. The paired t-test was used for statistical data processing. The p-value 0,05 was considered as statistically significant. RESULTS: The mean tear osmolarity of the lagophthalmic eyes was 296 ± 15,0 mosmol/l (275-315 mosmol/l). In case of healthy eyes the mean osmolarity was 310 ± 12 mosmol/l (292-336 mosmol/l). The tear osmolarity in case of lagophthalmos was significantly lower than in the healthy eyes (p = 0,05). CONCLUSION: In contrary to the studies demonstrating higher tear osmolarity under the scenario of dry eye syndrome, we found lower tear osmolarity in the lagophthalmic eyes than in the healthy eyes. The possible reason could be the changes in tear dynamics of the lagophthalmic eye due to disturbance of eye lid function. Our results also stress the need of evaluation of the actual tear osmolarity in the view of complex clinical eye findings. The place of tear collection should also be considered.Key words: lagophthalmos, dry eye syndrom, tear osmolarity.

A 3-bp Deletion VK600-1E in the BRAF Gene Detected in a Young Woman with Papillary Thyroid Carcinoma.

Papillary thyroid cancer (PTC) derived from follicular cells is a frequent thyroid tumor. The incidence of this type of malignancy is still growing worldwide. Several major genetic causes are recognized to cause PTC-mutations in the BRAF and RAS genes or rearrangements with the RET proto-oncogene. The most common genetic change found in PTC is a V600E mutation in the BRAF gene presented in 36-69 % of all PTC cases. For routine purposes, several methods were developed to selectively detect only this mutation. However, these methods miss other mutations in the BRAF gene located elsewhere. We focused on the analysis of the exon 15 of the BRAF gene by next-generation sequencing. Here we report a three nucleotide deletion VK600-1E in one patient and present this finding in the context of 13 previously described PTC cases with this deletion. Our patient is the second youngest one among the reported cases. Clinical features of PTC patients with VK600-1E are summarized. For the future, it is important to evaluate genotype-phenotype characteristics of patients with rare BRAF mutations and to follow up them for years.

Revision operations after previous stapes surgery for persisting hearing loss.

OBJECTIVES: The aim of the study was to find out the reasons of the recurrent or persisting hearing loss after previous stapes surgery indicated for otosclerosis. BACKGROUND: Revision stapes surgery is a relatively safe surgical method. Recurrent or persisting conductive hearing loss is commonly caused by prosthesis dislocation and adhesions in the oval window. Hearing loss is directly proportional to the number of previous operations. METHOD: Retrospective analysis of 48 patients after revision stapes surgery was done over a period of 4 years (2005-2008). Improvement of the hearing and the reasons of a previous surgery failure were studied. RESULTS: RESULTS were compared to the other studies. The main reason of the failed surgery was adhesions and dislocation of the prosthesis. The mean postoperative air-bone gap was 12.0 dB. A mean postoperative air-bone gap closure within 10 dB occurred in 24 cases (55.8 %), between 11-20 dB occurred in 11 cases (25.6 %) and above 20 dB in 8 cases (18.6 %). The original prosthesis was replaced with a new one in 41 (95.3 %) cases. In 2 cases (4.7 %), previous prostheses were left in place and fixed by a ionomer glass cement to the long process of incus. CONCLUSION: Revision stapes surgery is a relatively safe surgical procedure allowing to improve hearing. The number of previous stapes surgery deteriorates hearing (p < 0.05) (Tab. 4, Ref. 20).

Towards dissecting molecular routes of intercellular communication in the tumour microenvironment: phenotypic plasticity of stem cell-associated markers in co-culture (carcinoma cell/fibroblast) systems.

Increasing evidence attributes tumour fates to a small population of cells (cancer stem cells) capable of surviving therapeutic interventions. Investigation of their characteristics, especially in cross-talk with other cell types of the tumour microenvironment, can pave the way to innovative therapeutic concepts. The central issue of this study was to evaluate the impact of stroma on tumour cells with stem cell-like features in a squamous cell carcinoma model (FaDu). Six different types of experimental conditions were tested using distinct compositions of the culture system, and both morphologic and molecular features of the tumour cells were analysed. In detail, FaDu cells alone were used as a control, compared to tumour cells from co-culture, with squamous cell cancer-derived stromal fibroblasts or normal skin human fibroblasts, both in the direct and indirect (insert) systems, adding analysis of side population cells of FaDu culture. Measurements were taken on days 2, 7 and 9 of culture and immediately after preparation in the case of the side population. A panel of antibodies against keratins 8, 10, 19, stem cell markers CD29, CD44, CD133, as well as biotinylated adhesion/growth-regulatory galectin 1 served as a toolbox for phenotypic characterization. Co-culture with fibroblasts prepared from tumour stroma and with dermal fibroblasts affected marker presentation, maintaining an undifferentiated stage phenotypically related to stem cells. Side-population cells showed close relationship to cancer stem cells in these characteristics. In conclusion, normal and tumour stromal fibroblasts are capable of shifting the marker expression profile of FaDu cells to a stem cell-like phenotypic pattern in co-culture.

[Current treatment strategies for papillary thyroid microcarcinoma]. / Aktuelle Behandlungskonzepte des papillären Schilddrüsenmikrokarzinoms.

The increase in the incidence of thyroid cancer is accompanied by a mortality rate that is stable or perhaps even slightly decreasing. This phenomenon is due to the increased frequency of papillary microcarcinomas (thyroid tumors with a diameter of less than 1 cm), which is presumably attributable to the improved diagnosis enabled by high resolution ultrasound and fine needle aspiration cytology. The American and European Thyroid Associations have recently published new guidelines for the diagnosis and therapy of differentiated thyroid tumors. These guidelines are aimed at minimizing the diagnostic and therapeutic procedures without reducing their effectiveness. This goal is particularly important for papillary thyroid microcarcinoma patients, who have an excellent prognosis and almost normal life expectancy. This article summarizes the history of thyroid surgery and introduces papillary thyroid microcarcinoma--an important topic in modern thyroid oncology. Current methods for diagnosis, treatment and follow-up care of this disease are discussed.

Immediate revision in patients with bilateral recurrent laryngeal nerve palsy after thyroid and parathyroid surgery. How worthy is it?

The aim of the present study was to determine whether immediate revision surgery has benefits for patients with iatrogenic bilateral recurrent laryngeal nerve (RLN) palsy. From January 1, 2004 to January 30, 2011, 29 consecutive patients underwent immediate revision after total thyroidectomy. The cohort comprised 29 patients, 2 males and 27 females, aged 23 to 76 years (median 52 years). Identification of the type and extent of injury of each branch was reported in the protocol, and reconstruction was performed whenever possible. A complete transection of the nerve or one of its branches was found in 14 and 5 nerves, respectively. In three patients, the nerve was completely or partially transected on both sides. Seven anatomically intact nerves were injured by loaded ligature, in one case there was a sign of thermal damage and four nerves showed signs of excessive manipulation (thinning of the nerve trunk). Primary end-to-end anastomosis was performed in seven completely transected RLN and four transected anterior branches of RLN. None of the reconstructed nerve trunks or its branches regained function, although good muscle tone was observed. 23 of 38 intact nerves (61%) regained function, and normal vocalcord mobility on both sides was restored in only four patients. In all cases with regained vocal-cord mobility, functional recovery occurred within 3 months after primary surgery. In conclusion, immediate revision after thyroidectomy may help to indicate the type of RLN damage, which is a predictor of functional recovery and one of major factors influencing future therapeutic management.

Early stages of trachea healing process: (immuno/lectin) histochemical monitoring of selected markers and adhesion/growth-regulatory endogenous lectins.

Tracheotomy may be associated with numerous acute and chronic complications including extensive formation of granulation tissue. The emerging functional versatility of the adhesion/growth-regulatory galectins prompted us to perform a histochemical study of wound healing using rat trachea as model. By using non-cross-reactive antibodies and the labelled tissue lectins we addressed the issue of the presence and regulation of galectin reactivity during trachea wound healing. Beside localization of high-molecular-weight keratin, wide-spectrum cytokeratin, keratins 10 and 14, α-smooth muscle actin, vimentin, fibronectin, and Sox-2, galectins -1, -2, and -3 and their reactivity profiles were measured in frozen sections of wounded and control trachea specimens 7, 14, and 28 days after trauma. A clear trend for decreased galectin-1 presence and increased reactivity for galectin-1 was revealed from day 7 to day 28. Sox-2-positive cells were present after seven days and found in the wound bed. Interestingly, several similarities were observed in comparison to skin wound healing including regulation of galectin-1 parameters.

Comparison of Helicobacter pylori genotypes obtained from the oropharynx and stomach of the same individuals - a pilot study.

Helicobacter pylori has been recently detected in the oral cavity and oropharynx. However, the role it plays in oral and oropharyngeal pathogenesis remains unclear. The virulence of H. pylori strains can be distinguished according to the virulence factors genes carried. Our research has been focused on realtime PCR analysis of cagA and vacA genes of H. pylori strains in tonsils and tonsillar squamous cell cancer and their comparison with H. pylori strains obtained from the gastric mucosa of the same patients. Urea breath test (UBT) test was used to detect a gastric H. pylori infection in 20 patients with previously proven H. pylori in the oropharynx. Genotyping of H. pylori in gastric biopsies was performed in patients with positive gastric infection. Out of 20 patients positive for oropharyngeal H. pylori, 8 were positive for concurrent gastric H. pylori infection. In 6 of them gastric biopsies were obtained. Comparison of oropharyngeal and stomach H. pylori genotypes showed important differences. Four of 6 patients had different H. pylori strains in the oropharynx and stomach. The differences were found in cagA gene as well as in vacA gene. The finding of oral presence of H. pylori without concurrent stomach infection was confirmed using UBT. The results show that more than one H. pylori strain can be present in oropharynx and stomach in the same patient. The oropharyngeal infection seems to be independent to the gastric infection.

Subcutaneous calcification in the pectoralis major flap: a late complication of radiotherapy.

Heterotopic calcification following radiotherapy is a very rare event. Here, we report a case of a patient who underwent surgical intervention including pectoralis major flap reconstruction for locally advanced pharyngolaryngeal squamous cell carcinoma with skin invasion. He was followed up post-operatively with adjuvant radiotherapy. 13 years after the treatment, suspect resistance in the myocutaneous flap region appeared and was diagnosed as a calcification. To date, the occurrence of subcutaneous calcification in the myocutaneous flap in the neck has not been described as a late complication of neck irradiation.

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323).

BACKGROUND: The EORTC 24971/TAX 323, a phase III study of 358 patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck, showed an improved progression-free and overall survival (OS) with less toxicity when docetaxel (T) was added to cisplatin and 5-fluorouracil (PF) for induction and given before radiotherapy (RT). The impact of the addition of docetaxel on patients' health-related quality of life (HRQOL) and symptoms was investigated. METHODS: HRQOL was assessed at baseline, at end of cycle 2, and 4, 6, and 9 months after completion of RT using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (EORTC QLQ-H&N35). The primary HRQOL scale was global HRQOL per protocol. RESULTS: Compliance to HRQOL assessments was 97% at baseline, but dropped to 54% by 6 months. Data were analysed up to 6 months. There was a trend towards improved global HRQOL during the treatment period. At 6 months after the end of RT, global HRQOL was higher in the TPF arm than in the PF arm, but the low compliance does not allow to draw definitive conclusions. Swallowing and coughing problems decreased more in the TPF arm than in the PF arm at the end of cycle 2, but to a limited extent. CONCLUSION: Induction chemotherapy with TPF before RT not only improves survival and reduces toxicity compared with PF but also seems to improve global HRQOL in a more sustainable manner.

BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic.

BACKGROUND: Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. AIM: Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters. SUBJECTS AND METHODS: DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. RESULTS: BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). CONCLUSIONS: Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.

Galectin-7: will the lectin's activity establish clinical correlations in head and neck squamous cell and basal cell carcinomas?

The human lectin galectin-7 (Gal-7; p53-induced gene-1) has anti- and pro-malignant features in different in vitro models. We tried to clarify relation of its expression to cellular and clinical parameters in head and neck squamous and basal cell carcinomas. Using a non-cross-reactive antibody, immunohistochemical staining in squamous cell epithelia (epidermis, epithelium of oropharynx and larynx) (n = 57), squamous cell carcinomas (n = 47) and lymph node metastases (n = 25), as well as basal cell carcinomas (n = 10) were studied. This monitoring was flanked by processing to assess the level of differentiation (cytokeratins 10 and 14), proliferation (Ki67) and basal lamina formation (collagen IV). The results were correlated with clinical and pathological findings (grading, TNM-staging, extracapsular spread, angio- and lymphangioinvasion, perineural invasion, recurrence and survival). Gal-7 resides in all layers of epithelia with cytoplasmic and nuclear localization in normal specimens. Basal cell carcinomas were devoid of the Gal-7 respective signal. Squamous cell carcinomas were positive, presenting different staining profiles. Intense staining was predominantly found in squamous cell cancers with high degrees of differentiation and keratinization. Fittingly, poor level of differentiation (P = 0.0009), absence of keratinization (P = 0.0105) and significant discontinuity or absence of collagen IV expression in the peritumoral basal lamina (P = 0.0024) was found in Gal-7-negative tumors. Gal-7 presence was not related to gender, primary tumor site, T-stage, N-stage, clinical stage, extracapsular spread, angio- and lymphangioinvasion, perineural spread or treatment outcome at a statistically significant level. Immunohistochemical analysis revealed a positive correlation for differentiation and keratinization to Gal-7 presence in squamous cell carcinomas. Absence of Gal-7 expression was detected in basal cell carcinomas. These clinical data delineate Gal-7 influence on differentiation in vivo, without evidence for a role in dissemination reported for lymphoma.

Human Papilloma Virus (HPV) in head and neck region: review of literature.

The evidence that human papillomavirus infection is related to head and neck squamous cell carcinoma is supported by molecular and epidemiological data. The definition of a distinct subset of head and neck squamous cell carcinoma, independent of the traditional risk factors and with different clinical presentation and outcome, has led to increasing interest in human papillomavirus infection. This review summarizes current knowledge regarding human papillomavirus biology, oncogenic mechanisms, risk factors for transmission, clinical significance and prophylactic strategies.

Occult thyroid carcinoma.

Some medical definitions remain the same for many years, others change due to the progress in the diagnostic tools, which are able to distinguish markers and symptoms until then undetectable. Occult thyroid carcinoma is a general term indicating clinically different situations, whereas the incidentally detected papillary thyroid microcarcinoma is the most important from the clinical point of view. It is fundamental, for therapeutic management, to determine biological parameters which would define a small group of papillary thyroid microcarcinomas with aggressive biological behaviour. The most promising genetic and molecular markers for papillary thyroid carcinoma risk stratification are discussed in this review. Preoperative evaluation of these markers, obtained through analysis of ultrasonography-guided fine needle biopsy specimens of papillary thyroid microcarcinoma, could be very valuable in guiding treatment of this type of cancer.

[Galectins in squamous cell carcinomas of the head and neck cancers]. / Galektiny v dlazdicových karcinomech hlavy a krku.

Cancers of head and neck represents about 5% of all tumors. 80 to 90% of these tumors are constituted of squamous cell carcinomas. Despite a rapid progress in diagnostics and therapy the overall 5-year survival of this type of cancer is among the lowest of the major cancer types. This unfavourable situation needs the extensive research to found new markers to better characterize biological behavior of tumors as a rational background for more sophisticated therapeutic modalities. Among the most promising markers are endogenous lectins called galectins and their ligands. Especially galectin-1, -3 and -7 play a key role in pathology of squamous cell carcinomas.

Helicobacter pylori in tonsillar and adenoid tissue and its possible role in oropharyngeal carcinogenesis.

Helicobacter pylori is a well-known gastric pathogen. It plays a major role in the pathogenesis of chronic gastritis, duodenal and gastric ulcers, adenocarcinoma and gastric lymphoma. HP infection is one of the most common bacterial infections worldwide. Recently, the oral cavity was proposed as an extragastric reservoir of HP infection. HP was detected by culture and PCR in both dental plaque and saliva. It is supposed that HP infection can cause the same immunological changes in the oropharyngeal mucosa as in gastric mucosa and can also contribute to the progression of oropharyngeal diseases. HP can induce production of different cytokines and regulatory molecules, which are suggested to play a role in carcinogenesis of the oropharynx. Only a few studies have explored the presence of HP in tonsillar and adenoid tissue, where MALT is present similar to the gastric mucosa. The results of these studies were inconsistent. The question of persistence of HP in tonsillar and adenoid tissue and its role in the pathogenesis of oropharyngeal diseases still remains unclear. In this review, recent findings about oral HP are considered. Possibilities of diagnostics of HP in oral specimens are discussed.

Early detection of cancer: ideas for a debate.

Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.

Complicated decisionmaking in indications for auditory brainstem implant (ABI) in a patient with neurofibromatosis 2.

A case of an accidental finding of neurofibromatosis 2 in a practically asymptomatic patient is described. Various therapeutic modalities, including restoration of hearing after vestibular schwannoma surgery with an auditory brainstem implant (ABI), are considered.