Jaroslav Betka

Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck

Regulatory T cells (Treg) are important regulators of anti‐cancer immune responses, and an increase in Treg frequency was observed in the blood of cancer patients. Blood samples from 112 patients with head and neck squamous cell carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and lymphocyte subpopulations (CD3+; CD3−CD16+CD56+; CD4+; CD8+; CD19+; CD4+CD45RA+) with emphasis on Treg counts (CD3+CD4+CD25+), complete blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; α‐1‐antitrypsin [AAT]; Cyfra 21–1; C‐reactive protein [CRP]) were analysed. The data were grouped according to TNM classification, and their significance for the course of the disease at an interval of 1 year after the end of the therapy was determined. The percentage of CD8+ cells increased and the CD/D8 ratio decreased with tumour grade. The ratio of B lymphocytes decreased in patients with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4+ cells (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21–1 and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 × 1012/l versus 4.45 × 1012/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl) decreased, while Treg counts (8.91%versus 15.70%) increased in patients with early recurrence. Our results show that examination of these parameters could be helpful for prognostication in HNSCC patients and aid improvement of treatment strategy.

The Role of NBI HDTV Magnifying Endoscopy in the Prehistologic Diagnosis of Laryngeal Papillomatosis and Spinocellular Cancer

Narrow band imaging (NBI) HDTV (high definition television) magnifying endoscopy is considered to be superior for the accurate display of the microvascular patterns of superficial mucosal lesions. Observation of changes in intraepithelial papillary capillary loops (IPCL) can help distinguish benign from malignant lesions as part of an “optical biopsy.” However, IPCL changes in papillomas may be mistaken for spinocellular cancer (SCC). The aim of the study was to determine whether observing microvascular changes alone is sufficient for discriminating between laryngeal SCC and papillomatosis. An additional aim was to identify associated characteristics that could clarify the diagnosis. The study included 109 patients with a suspected laryngeal tumor or papilloma. HDTV NBI magnifying endoscopy was performed during direct laryngoscopy. It was possible to visualize IPCL changes in 82 out of 109 patients (75.2%). In 71 (86.6%) patients, the diagnosis was correctly determined. In 4 (4.9%) cases, the diagnosis of SCC was expressed on the basis of finding pathologic IPCL, but histology did not demonstrate malignancy. To achieve a correct diagnosis using HDTV NBI magnifying endoscopy, it is important not only to observe changes in the shape of IPCL but also to note possible papillary structures with central-axis capillaries typical of papillomatosis.

Combined bipolar radiofrequency surgery of the tongue base and uvulopalatopharyngoplasty for obstructive sleep apnea.

Introduction The aim of the study was to investigate the effectiveness of combined bipolar radiofrequency surgery of the tongue base (RFBT) and uvulopalatopharyngoplasty (UPPP) in a single session for obstructive sleep apnea and whether this combination is safe and well tolerated. Material and methods Seventy-nine patients with obstructive sleep apnea and both palatal and retroglossal obstruction underwent UPPP with bipolar RFBT. The control group consisted of 35 patients treated by UPPP alone. Results The apnea-hypopnea index significantly decreased from 28.7 to 14.1. The oxygen desaturation index decreased from 15.1 to 10.3. Mean oxygen saturation was unchanged. Subjectively, the Epworth Sleepiness Scale was significantly improved from 10.6 to 7.3, and the snoring level decreased from 8.4 to 6.0. The overall treatment success rate increased from 41.9% for UPPP alone to 51.7% for UPPP + RFBT. No serious adverse events occurred. Two patients had postoperative bleeding from the tonsillar bed after UPPP. Four patients had ulceration of the base of the tongue after RFBT with spontaneous cure. One patient had a taste change in half of the tongue that resolved within two months. Conclusions Combined bipolar RFBT and UPPP in a single session is well tolerated and safe surgery in the treatment of obstructive sleep apnea. It is effective in reducing respiratory parameters and subjective symptoms of obstructive sleep apnea. Further advantages are a single session, simple feasibility, bipolar technique and short time of the procedure.

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan–Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow‐up time of 4.6 years, nearly 50% (n = 586) of patients died. Five‐year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09–2.38 (LH) and HR = 2.12, 95% CI 1.35–3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40–5.08 (LH) and HR = 2.16, 95% CI 1.32–3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78–3.79 (LH) and HR = 3.17, 95% CI 2.05–4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Fine needle aspiration biopsy proves increased T-lymphocyte proliferation in tumor and decreased metastatic infiltration after treatment with doxorubicin bound to PHPMA copolymer carrier

Abstract Introduction: Fine needle aspiration biopsy (FNAB) is an easy method with an option of repetitive withdrawal of cell material. Methods: First, mice were inoculated with mouse T-lymphoma, after 10 d the samples from tumor, lymph nodes and spleen gained by FNAB and excision were analyzed by flow cytometry. Tumor progression was compared to the control group simultaneously. Then, 10 d after tumor cell inoculation free doxorubicin (DOX) or different PHPMA DOX conjugates were injected. Cell material was analyzed to detect subpopulations of lymphocyte infiltrate, and levels of cytokines in correlation with progression or regression of the disease. Results: FNAB has no influence on the tumor’s growth or survival of experimental animals. After treatment with PHPMA conjugates there was a significant increase of T-lymphocyte subpopulations in tumor microenvironment compared to controls or free DOX, but only in mice with confirmed macroscopic regression of tumor within two weeks. Mice treated with conjugates showed significantly lower cancer infiltration of lymph nodes and spleen. Conclusion: FNAB provides a great benefit to in vivo monitoring of cell changes directly in the tumor after treatment. The number of infiltrating T-lymphocytes increases in correlation with consecutive tumor eradication after treatment with PHPMA. This proves that not only direct cytotoxic but also imunostimulating effect are necessary for successful treatment.

Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study

Although previous studies on tobacco and alcohol and the risk of upper‐aerodigestive‐tract (UADT) cancers have clearly shown dose‐response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case–control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56–5.73 for score of 3–7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.

Lasers in otorhinolaryngology (ORL) and head and neck surgery

Abstract: The CO2 laser was first used for surgery of the larynx in the 1970s. The introduction of lasers in otorhinolaryngology and head and neck surgery offers patients new ways of disease management. It improves traditional surgical techniques, and expands their scope. Outcomes of laser surgery have improved in association with advances in laser technology and improvements in delivery systems. Nowadays we use several laser systems in many other areas of head and neck surgery. This chapter represents a state-of-the-art update on the use of lasers in otology, in rhinology and for benign and malignant lesions of the larynx and hypopharynx.

Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study: Smoking addiction and upper-aerodigestive-tract cancer

Although previous studies on tobacco and alcohol and the risk of upper‐aerodigestive‐tract (UADT) cancers have clearly shown dose‐response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case–control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56–5.73 for score of 3–7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.

Impact of Regulatory T Cells in Oropharyngeal Cancer

Objective: Oropharyngeal cancer is the most frequent type of malignancy in the head and neck area. Regulatory T cells (Treg, CD4+CD25+Foxp3+) and Th17 cells were described as critical factors for regulation or inhibition of effective anti-cancer immune response and, consequently, prognosis and survival. Method: We examined Treg and Th17 from periphery blood and tumor samples of patients with oropharyngeal cancer before the start of anti-tumor therapy. We particularly focused on lymphocytes subpopulations (CD3+, CD3-CD16+CD56+, CD4+, CD8+, CD19+, CD4+CD45RA+, CD3+CD4+CD25+, CD161+CD4+ a CD161+CD8+) and tumor markers (SCC, CEA, AAT, Cyfra 21-1). Results: In comparison with control group (nononcologic surgery), the Treg population in the peripheral blood of the patients with oropharyngeal cancer was 1.6-fold higher. Infiltration of Treg in specimens from primary tumors and metastatic neck lymph nodes was higher (8.7% and 9.6%) in comparison with oropharyngeal tissue and neck lymph nodes without tumor or metastatic extension (3.12% and 3.3%, both p+CD161+cells and 12.8% CD8+CD161+ cells, and in tumor tissue, 1.66% CD4+CD161+ cells and 3.9% CD8+CD161+ cells. Level of tumor marker CEA correlated with higher T stadium (T3+4, t-test, P < .005). Conclusion: We can conclude that regulatory T cells and Th17 generally represent a highly important factor in the progression of many types of malignancies and our data indicated their particular importance for oropharyngeal cancer.