СHARACTERISTICS OF CYCLIN D1-MEDIATED REGULATION OF CELL CYCLE OF PERIPHERAL BLOOD LIMPHOCYTES OF CHORNOBYL CLEAN-UP WORKERS AND PERSONS WITH MALIGNANT NEOPLASMS OF THE ORAL CAVITY, OROPHARYNX AND LARYNGOPHARYNX. / KhARAKTERYSTYKA TsYKLIN D1-OPOSEREDKOVANOÏ REGULIaTsIÏ KLITYNNOGO TsYKLU LIMFOTsYTIV PERYFERYChNOÏ KROVI UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES TA OSIB, KhVORYKh NA ZLOIaKISNI NOVOUTVORENNIa POROZhNYNY ROTA, ROTOVOÏ TA GORTANNOÏ ChASTYN GLOTKY.

OBJECTIVE: to explore proliferative potential of peripheral blood lymphocytes of Chornobyl clean-up workers and persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx by level of expression of cyclin D1 and quantitative parameters of cell cycle. MATERIALS AND METHODS: A total of 294 men aged (58.47 ± 7.32) were surveyed, 215 of them were Chornobyl clean"up workers (1986-1987), exposed at the dose range 10.43-3623.31 mSv; 49 persons of the control group and 30persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx at III, IVА and IVВ stages ofthe disease. The analysis of parameters of cell cycle and proliferative activity of peripheral blood (PB) lymphocyteswas performed using the flow cytometry. The evaluation of distribution of cells by G0/G1, S, G2/M cell cycle phaseswas done in vivo and in in vitro. Proliferative potential was analyzed by level of expression of cytoplasmic protein ofcyclin D1. RESULTS: Proliferative potential of PB lymphocytes of Chornobyl clean"up workers and persons with malignant neo"plasms of the oral cavity, oropharynx and laryngopharynx was assessed. An increase in the level of spontaneousсyclin D1 expression and disturbance of сyclin D1-dependent regulation of cell cycle of PB lymphocytes after mito"gen activation were determined in the Chornobyl clean-up workers. An increase in pool of cells in the S" and G2/M"phases of cell cycle was detected, which characterizes high proliferative potential of PB lymphocytes. These changesare most pronounced in the subgroup of persons with a radiation dose of D > 500 mSv, and in persons with oncolo"gical pathology. CONCLUSIONS: A positive linear dependence has been established between the radiation dose and the number of cellsin the S"phase of cell cycle in the subgroup of Chornobyl clean"up workers with a radiation dose of D > 500 mSv. The detected changes of cyclin D1-dependent regulation of cell cycle and proliferative status of lymphocytes depend on the radiation dose, can be a manifestation of genome instability and be a cause for risks of oncogenesis, in a remote period after radiation exposure.

Swallowing functional outcomes and nutritional status in head and neck cancer radiotherapy: longitudinal study.

OBJECTIVE: To explore the relationships between swallowing functional outcomes and nutritional status in patients with head and neck cancer undergoing radiotherapy (RT). METHODS: This longitudinal study included 122 patients. Data were collected at three time points: baseline (T1), the third week of RT (T2) and the completion of RT (T3). The Common Terminology Criteria for Adverse Events was used to assess the symptom of dysphagia and other toxicities; the MD Anderson Dysphagia Inventory (MDADI) was used to assess the patient-perceived swallowing functional outcomes; the nutritional status was evaluated by the weight ratio and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalised estimating equation (GEE) was used to measure the correlation of MDADI with the weight ratio or PG-SGA and also to analyse the influential factors of swallowing functional outcomes. RESULTS: The participants' acute dysphagia rates were 5.7% at T1, 69.7% at T2 and 77.9% at T3. The swallowing functional outcomes worsen over RT (p<0.001) and were associated with weight ratio (ß=0.032, p=0.008) and PG-SGA (ß=-0.115, p<0.001). GEE models showed that patients with cancer of the pharynx region, advanced stage, chemoradiotherapy and high RT dose perceived worse swallowing functional outcomes. Oral mucositis, pharynx mucositis and salivary gland inflammation were positively correlated with swallowing functional outcomes, and the pharynx mucositis presented the highest absolute value of ß. CONCLUSION: The swallowing functional outcomes were negatively correlated with nutritional status. Healthcare professionals should identify early on the population at higher risk and focus on multiple toxicities, especially the management of pharynx mucositis, to improve nutritional status.

Differences in incidence and survival of oral cavity and pharyngeal cancers between Germany and the United States depend on the HPV-association of the cancer site.

INTRODUCTION: The epidemiology of squamous cell oral cavity and pharyngeal cancers (OCPC) has changed rapidly during the last years, possibly due to an increase of human papilloma virus (HPV) positive tumors and successes in tobacco prevention. Here, we compare incidence and survival of OCPC by HPV-relation of the site in Germany and the United States (US). MATERIALS AND METHODS: Age-standardized and age-specific incidence and 5-year relative survival was estimated using data from population-based cancer registries in Germany and the US Surveillance Epidemiology and End Results (SEER) 13 database. Incidence was estimated for each year between 1999 and 2013. Relative survival for 2002-2005, 2006-2009, and 2010-2013 was estimated using period analysis. RESULTS: The datasets included 52,787 and 48,861 cases with OCPC diagnosis between 1997 and 2013 in Germany and the US. Incidence was much higher in Germany compared to the US for HPV-unrelated OCPC and more recently also for HPV-related OCPC in women. Five-year relative survival differences between Germany and the US were small for HPV-unrelated OCPC. For HPV-related OCPC, men had higher survival in the US (62.1%) than in Germany (45.4%) in 2010-2013. These differences increased over time and were largest in younger patients and stage IV disease without metastasis. In contrast, women had comparable survival for HPV-related OCPC in both countries. CONCLUSIONS: Strong survival differences between Germany and the US were observed for HPV-related OCPC in men, which might be explained by differences in HPV-attributable proportions. Close monitoring of the epidemiology of OCPC in each country is needed.

Survival patterns in squamous cell carcinoma of the head and neck: pain as an independent prognostic factor for survival.

UNLABELLED: Survival outcomes in patients with squamous cell carcinoma of the head and neck (HNSCC) vary by extent of disease, behavioral factors, and socioeconomic factors. We assessed the extent to which pretreatment pain influences survival in 2,340 newly diagnosed patients with HNSCC, adjusting for disease stage, symptoms, pain medications, comorbidities, smoking, alcohol consumption, age, sex, and race/ethnicity. Patients rated their pain at presentation to the cancer center (0 = "no pain" and 10 = "pain as bad as you can imagine"). Survival time was calculated from the date of diagnosis to the date of death of any cause or last follow-up. Five-year overall survival was calculated for all the variables assessed in the study. Severe pain (≥7) was most prevalent among those with oral cancer (20.4%; pharynx = 18.8%; larynx = 16.1%) and significantly varied by tumor stage, fatigue severity, smoking status, comorbid lung disease, and race (all P < .05) across cancer diagnoses. Overall 5-year survival varied by pain for oral (severe pain = 31% vs nonsevere pain = 52%; P < .001) and pharyngeal cancer (severe pain = 33% vs nonsevere pain = 53%; P < .001). Multivariable analyses showed that pain persisted as an independent prognostic factor for survival. Pain reported prior to treatment should be considered in understanding survival outcomes in HNSCC patients. PERSPECTIVE: Pretreatment pain was an independent predictor of survival in a large sample of HNSCC patients even after accounting for tumor node metastasis stage, fatigue, age, race/ethnicity, smoking, and alcohol intake. Therefore, symptoms at presentation and before cancer treatment are important factors to be considered in understanding survival outcomes in HNSCC patients.

Reversing effect of sorcin in the drug resistance of human nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx, and chemoresistance is an essential aspect of NPC chemotherapy failure. Sorcin has been implicated in multidrug resistance (MDR) of many types of human tumor. However, the effect and mechanism of Sorcin in MDR of human NPC is not fully clear. In this report, we silenced Sorcin in human NPC CNE2/DDP cells, and explored the role of Sorcin in MDR reversal. The results showed an increased cytotoxicity of cisplatin and intracellular accumulation of Rhodamine-123 and glutathione depletion in Sorcin silencing CNE2/DDP cells. We also found a decreased messenger RNA and protein expression of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase-π (GST-n), RhoE, Bcl-2, and Survivin in Sorcin silencing CNE2/DDP cells. The increased expression of PTEN and decreased expression of p-Akt and NF-κB suggested that the key cellular signaling pathways were triggered by Sorcin silencing. We concluded that Sorcin silencing would contribute to establish a potent target point for MDR reversal.

Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers: use it or lose it.

IMPORTANCE: Data support proactive swallowing therapy during radiotherapy (RT) or chemoradiotherapy (CRT) for pharyngeal cancers. The benefits of adherence to a regimen of swallowing exercises and maintaining oral intake throughout treatment are reported, but independent effects are unclear. OBJECTIVE: To evaluate the independent effects of maintaining oral intake throughout radiotherapy and adherence to preventive swallowing exercise. DESIGN: Retrospective observational study. SETTING: The University of Texas MD Anderson Cancer Center, Houston. PATIENTS: The study included 497 patients treated with definitive RT or CRT for pharyngeal cancer (458 oropharynx, 39 hypopharynx) between 2002 and 2008. MAIN OUTCOMES AND MEASURES: Swallowing-related end points were final diet after RT or CRT and duration of gastrostomy dependence. Primary independent variables included oral intake status at the end of RT or CRT (no oral intake, partial oral intake, or full oral intake) and adherence to a swallowing exercise regimen. Multiple linear regression and ordered logistic regression models were analyzed. RESULTS: At the conclusion of RT or CRT, 131 patients (26%) had no oral intake and 74% maintained oral intake (167 partial [34%], 199 full [40%]). Fifty-eight percent (286 of 497) reported adherence to swallowing exercises. Maintenance of oral intake during RT or CRT and swallowing exercise adherence were independently associated with better long-term diet after RT or CRT (P = .045 and P < .001, respectively) and shorter duration of gastrostomy dependence (P < .001 and P = .007, respectively) in models adjusted for tumor and treatment burden. CONCLUSIONS AND RELEVANCE: The data indicate independent, positive associations of maintenance of oral intake throughout RT or CRT and swallowing exercise adherence with long-term swallowing outcomes. Patients who either eat or exercise fare better than those who do neither. Patients who both eat and exercise have the highest rate of return to a regular diet and shortest duration of gastrostomy dependence.

Increase of phosphatase and tensin homolog by silymarin to inhibit human pharynx squamous cancer.

Silymarin is an active principle from the seeds of the milk thistle plant and is widely used as a hepatoprotective gent due to its antioxidant-like activity. In the present study, we evaluated the potential efficacy of silymarin against oral cancer and investigated its possible mechanism of action. Cell viability assay and western blotting analyses were used to identify silymarin-induced apoptotic cell death in human pharynx squamous cell carcinoma (FaDu) cells. The short interfering RNA (siRNA) is used to confirm the role of phosphatase and tensin homolog (PTEN) in silymarin-induced apoptosis. Treatment of FaDu cells with silymarin resulted in a significant decrease in cell viability (up to 70%). Silymarin inhibited the phosphorylation of Akt (over 10-fold) with an increase in expression of PTEN (five to sixfold). Consequently, the level of Bcl-2 expression was decreased five to sixfold and caspase 3 activated to induce apoptosis. Treatment with siRNA specific to PTEN gene diminished the action of silymarin. The results suggest that silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members. Also, we demonstrated the inhibitory activity of silymarin for oral cancer is related to cell survival. These mechanisms may in part explain the actions of silymarin and provide a rationale for the development of silymarin as an anticancer agent.

Oral and pharyngeal cancer in women.

Although in the United States the incidence of oral and pharyngeal cancer (OPC) has been significantly higher in men than in women, the identification of human papilloma virus as a risk factor for OPC has focused new scrutiny on who may develop OPC. One surprising element is that non-Hispanic white women have a higher incidence of OPC than of cervical cancer. OPC is thus a woman's disease, and diligence is needed to ensure that the occurrence of OPC in women does not go undetected by their oral health care providers.

Neurofibromatosis and velopharyngeal insufficiency: is there an association?

OBJECTIVE: Velopharyngeal insufficiency (VPI) is an often underrecognized disorder of palatal and nasopharyngeal closure that leads to the production of hypernasal speech. However, the potential clinical association between VPI and neurofibromatosis type 1 (NF1) remains undefined in the literature. The purpose of this study sought to identify and describe the potential clinical association of VPI in NF1 patients. DESIGN: A combined retrospective and prospective study. SETTING: Tertiary referral centre. METHODS: The NF1 database from 1998 to 2007 from the Medical Genetics Unit of our institution was used for this project. All NF1 patients seen during this period were sent a letter soliciting their participation in the study, which was designed to screen for the presence of VPI. MAIN OUTCOME MEASURES: Perceptual testing was undertaken using the American Cleft Palate-Craniofacial Association (ACPA) clinical database form and acoustic measurement of nasal flow, including standard nasometry and nasalance scores. A comprehensive chart review was also performed. RESULTS: One hundred forty-nine NF1 patients were identified from the database; 18 patients responded to our request for participation, with 3 additional participants recruited from recent clinical visits. Eleven of these 21 patients exhibited VPI based on perceptual evaluation and nasometry screening. CONCLUSIONS: This preliminary study attempted to identify a potential association between NF1 and VPI. Although this sample of NF1 patients was small, the finding of 11 of 21 patients being positively identified with some degree of VPI is of clinical interest, and further research is warranted.

Characterization of Yemeni patients treated for oral and pharyngeal cancers in Saudi Arabia.

OBJECTIVE: To determine the relative frequency and rank of oral cancer (OC) and pharyngeal cancer (PC) among Yemeni cancer patients who were treated and registered in the Kingdom of Saudi Arabia (KSA) over 14 years, and to characterize these patients by different grouping factors. METHODS: In this retrospective study, the Saudi Cancer Registry, Riyadh, KSA officially provided the data regarding all Yemeni patients registered between 1994 and 2007. These data were reclassified and analyzed to present the cancer distribution by the main sites adopted by Globocan 2008. The OC and PC patients were statistically described and analyzed according to the demographic data and tumor details. This study was conducted at the Oral Medicine, Medically Compromised and Research Clinic, Department of Dentistry, Riyadh Military Hospital, Saudi Arabia between January and April 2011. RESULTS: There were 5862 Yemenis registered with malignancies. The OC ranked the eighth most common malignancy (215, 3.7%) with 1.65:1 male to female ratio, whereas PC ranked the seventh (245, 4.2%) with 2.06:1 male to female ratio. The most affected oral sub-site was the tongue (91, 42.3%) while the nasopharynx accounted for 79% (194) of PC. The PC patients were significantly younger than those with OC (45.88+/-16.72 versus 55.6+/-15.75). The squamous cell carcinoma was the most frequent morphological type (289, 63.5%) but significantly more frequent in OC. Approximately 56% (255 patients) were diagnosed at advanced stage, however, significantly more frequent in PC (155, 64.6%). CONCLUSION: The relative frequencies of oral and pharyngeal cancers in Yemen are quite high. The demographic and tumor characteristics of these cancers are obviously different.

Pyriform sinus haemangioma: an unusual presentation of an unusual condition.

OBJECTIVE: We present a rare case of an unusual presentation of a pyriform sinus haemangioma in a normally healthy, Caucasian woman, including our management and a review of the literature. CASE REPORT: A 44-year-old woman presented complaining of bringing up fresh blood whilst brushing her teeth, dysphonia, food sticking in her throat, and epigastric pain for the preceding 12 months, accompanied by a 17.5 kg weight loss. She underwent pre-operative computed tomography and subsequent complete excision of a pyriform sinus haemangioma using CO2 laser. DISCUSSION: Haemangiomas are congenital vascular malformations and can affect any part of the body. They are not prevalent in adults and are rarely found in the pyriform sinus. Their common presenting symptoms and management have been previously documented; however, the presented case is unusual in both its presentation and management.

[Endolaryngeal laser-assisted microsurgery of benign pharyngeal neoplasms: objective evaluation of functional outcome].

A new technique for endolaryngeal microsurgery is proposed. It based on the irradiation of benign laryngeal tumours using Ho:YAG and potassium-titanyl-phosphate (KTP) lasers. A total of 198 patients of either sex aged from 2 to 77 years with a variety of benign laryngeal neoplasms were treated by this method between 2004 and 2007. Its application allowed the results of the treatment to be optimized as confirmed by the statistically significant improvement of the external respiration function, acoustic characteristics of the voice, and positive dynamics of laryngeal endoscopic imaging data.

First-bite syndrome: a review of 29 patients with parapharyngeal space tumor.

OBJECTIVE: The aim of this study is to clarify the etiology of first-bite syndrome. METHODS: A total of 29 consecutive patients treated with a surgical resection for parapharyngeal space tumor between April 1999 and April 2005 were retrospectively reviewed. RESULTS: Nine cases of first-bite syndrome were developed. Eight of those patients had undergone surgical ablation of the cervical sympathetic chain and/or external carotid artery. In two patients who underwent ablation of the sympathetic chain but in whom first-bite syndrome did not develop, the superior cervical ganglion was probably preserved. CONCLUSION: The present findings strongly indicate that loss of sympathetic innervation to the parotid gland from the superior cervical ganglion causes first-bite syndrome. They also suggest that some residual or autonomous activity of the superior cervical ganglion could prevent development of first-bite syndrome even if the lower sympathetic trunk was ablated.

Functional outcomes following total laryngopharyngectomy.

BACKGROUND: Despite increasing use of laryngeal preserving protocols, laryngopharyngectomy remains the gold standard treatment for locally advanced hypopharyngeal and upper oesophageal tumours and for salvage following failed chemoradiotherapy. Nevertheless, improved perioperative medical care and experience in reconstruction have reduced mortality and improved functional outcomes. METHODS: All patients undergoing total laryngopharyngectomy between July 2001 and July 2006 were prospectively recorded in a head and neck database. Demographics and functional outcomes were recorded. RESULTS: Eighteen patients underwent laryngopharyngectomies with 5 having failed chemoradiotherapy and 13 presented with locally advanced tumours. Patients were reconstructed using free jejunal interposition if the lower anastomosis was in the neck (50%). They developed early fistulas (33%), late strictures (33%) and 44% spoke with a tracheo-oesophageal puncture, the rest with an electrolarynx. If the lower anastomosis was below the manubrium, patients required a gastric pull-up (38.9%). Gastric pull-up patients had fewer fistulas but more number of chest complications. More gastric pull-up patients tolerated solid diet and 43% managed oesophageal speech, the remainder using an electrolarynx. Overall, 88.9% of jejunums and 100% of gastric pull-ups tolerated oral alimentation and 100% used verbal communication. During a mean follow up of 34 months, 7 patients (38.9%) died; four patients died of local recurrence, two of distant metastases and one of unrelated causes. CONCLUSION: Surgical treatment of neoplasms of the hypopharynx and cervical oesophagus is technically demanding and involves careful postoperative care to manage complications. Despite having a poor tumour-related prognosis, laryngopharyngectomy may be carried out in selected patients with low mortality and acceptable functional and survival results.

Nutritional status in head and neck cancer patients.

OBJECTIVE: Patients suffering from cancer of head and neck are at risk of nutritional depletion. The aim of our study was to investigate the role of type, location and stage of tumors in nutritional status. PATIENTS AND METHODS: A population of 230 consecutive patients with head and neck cancer was enrolled. A nutritional evaluation was realized. RESULTS: The distribution of tumour sites was: oral cavity (77 patients), pharynx (30 patients) and larynx (123 patients). Subjective Global Assessment (SGA) test showed significant differences. Midly malnourished frequency is higher in larynx site than others. Severely malnourished is higher in larynx and oral cavity than pharynx. In pharynx, larynx and oral cavity tumours is more frequent to be well nourished than severely malnourished. In pharynx and larynx tumours is more frequent to be mildly malnourished than severely malnourished. In stages II, III and IV are more frequent to be well nourished than severely malnourished and in stages II and III is more frequent to be mildly malnourished than severely malnourished. CONCLUSIONS: SGA test shows a good nutritional status in patients with head and neck tumours. However, SGA test shows statistical differences in some categories of tumours stages or sites.