Cigarette smoke, saliva, the translocator protein 18 kDa (TSPO), and oral cancer.

Oral squamous cell carcinoma (OSCC) incidence is induced primarily by cigarette smoke (CS). The 5-year survival rate for advanced OSCC stands at only 20%. Studies exploring underlying mechanisms of OSCC development have suggested free radicals such as reactive oxygen species generated by CS as contributing to OSCC, with effects enhanced by transition metal ions iron and copper contained in the saliva. Located on the outer mitochondrial membrane of various cell types, the 18-kDa translocator protein (TSPO) is up-regulated under pathological conditions such as cancer and inflammation. We focused on studying the interaction between TSPO, CS, salivary effects, and OSCC. Increased TSPO expression in OSCC tumors correlates significantly with reduced patient survival rate, indicating the possible role of TSPO in OSCC pathogenesis. We speculate that TSPO in OSCC is dysfunctional or mutated, rendering it ineffective in promoting apoptosis and blocking malignant transformation. Basal, precancer lower function of TSPO may diminish the TSPO capacity for pro-apoptotic and anti-cancer activity, resulting in development of OSCC. In order to overcome this, TSPO over-expression is induced, unfortunately with no benefit, as it is a malfunctioning TSPO, similar to cases where over-expression of a mutated form of the p53 gene in tumors is associated with carcinogenesis.

Two populations of TSPO binding sites in oral cancer SCC-15 cells.

Oral cancer mortality and morbidity rates remain high. The main inducer of oral cancer is cigarette smoke (CS). Translocator protein 18kDa (TSPO) was shown to play a role in carcinogenesis. We characterized TSPO binding sites in human oral cancer cell line SCC-15 and examined effect of CS on TSPO binding. We exposed SCC-15 human squamous cells to cigarette smoke. [3H]PK 11195 binding results were assessed in cells confluent for one day. To characterize the number of population sites, a custom written Matlab program compared Pearson linear correlation coefficients between all points in the Scatchard plot. Using [3H]PK 11195 as a radio ligand, we found that TSPO binding sites are not uniform, but separated into two sub-populations, one with high affinity (respective Kd and Bmax values of 1.40±0.08nM and 1586±48 fmol/mg protein), another with lower affinity (respective Kd and Bmax values of 61±5nM and 26260±1050 fmol/mg protein). We demonstrate rapid decrease in TSPO binding to the high affinity site induced by exposure to CS; specifically, significant 36% decrease in binding after 30min CS exposure (p<0.05), and 69% decrease after 2h CS exposure (p<0.05). Association between TSPO and CS exposure may contribute to understanding the underlying mechanism of oral carcinogenesis.

Transarterial Embolization in Maxillofacial Intractable Potentially Life-Threatening Hemorrhage.

PURPOSE: Although transarterial embolization (TAE) of vascular lesions with embolizing agents through angiographic catheters has been used for more than 45 years, reports of life-threatening maxillofacial bleeding are relatively rare and have not been updated. The authors review treatment modalities, present their experience of the past 21 years, and suggest a comprehensive algorithm and guidelines for the use of TAE in the treatment of intractable life-threatening maxillofacial hemorrhage. MATERIALS AND METHODS: This article describes 28 patients treated with TAE for severe bleeding that did not respond to conservative therapies. Of these, 13 had uncontrolled epistaxis, 9 were oncologic patients, 4 were postsurgical patients, and 2 were trauma patients. RESULTS: Details of patients' medical history, failed conservative therapy administered before TAE, imaging results, and blood vessels involved are presented, as are the TAE procedures and materials used, outcome, and complications. All these are discussed in relation to the available updated literature. All 9 oncologic patients (100%) had been treated with chemotherapy before the uncontrolled bleeding, and 7 also had radiotherapy administered to the maxillofacial region. Continuous anticoagulant therapy also seemed to predict such bleeding episodes. TAE resolved the bleeding in all 28 cases and rapidly in 90% of cases. Only in 3 oncologic cases did continued bleeding require 3 to 4 consecutive TAE sessions and combinations of embolizing agents. CONCLUSIONS: The reported high rate of success could be the result of careful techniques, appropriate preoperative imaging, highly professional personnel, and intraoperative and perioperative treatments.

The Effect of Cigarette Smoke on the Translocator Protein (TSPO) in Cultured Lung Cancer Cells.

Lung cancer is prevalent in cigarette smokers. The mitochondrial membrane translocator protein (TSPO), is thought to protect cells from free radical damage. We examined the effect of cigarette smoke (CS) (containing free radicals) alone and in the presence of saliva (containing redox active free iron), on survival of H1299 lung cancer cells and on their mitochondrial characteristics, and whether TSPO binding was influenced by CS and by saliva. We exposed H1299 cells to CS in the presence/absence of saliva and also characterized TSPO binding in the cells using [3H]PK 11195 as a radioligand. CS induced a significant drop in mitochondrial potential (ΔΨm), while addition of saliva did not lead to further loss of ΔΨm (42.5% vs. 39.85%). Scatchard analysis of the saturation curve of [3H]PK 11195 binding (0.2-6 nM final concentration) yielded a straight-line plot (R = 0.9). Average Bmax value was 3274 ± 787 fmol/mg of protein, and average Kd value was 9.2 ± 1.3 nM. Benzodiazepine diazepam partially prevented decrease in cell survival following exposure to CS and redox active iron containing media (saliva) while benzodiazepine clonazepam did not, indicating that this effect is TSPO-specific. Exposure of cells to CS resulted in alternation of biomolecules expressed by CLs peroxidation, reduction of TSPO binding, and depletion of the mitochondrial potential. This irreversible damage was enhanced in the presence of saliva. All these modulations may result in cellular death increase following CS exposure, enhanced in the presence of saliva.

Bypassing the emergency room to reduce door-to-balloon time and improve outcomes of ST elevation myocardial infarction patients: analysis of data from 2004-2010 ACSIS registry.

OBJECTIVES: Our objective was to assess whether bypassing the emergency room (ER) is associated with meaningful reduction in Major Adverse Cardiac and Cerebrovascular Event (MACCE) or mortality in a large cohort of ST Elevation Myocardial Infarction (STEMI) patients. BACKGROUND: Prior studies suggest that bypassing the emergency room reduces door-to-balloon time (DBT). However, it is not clear whether this translates into reduced mortality. METHODS: We analyzed data of 1,552 consecutive patients with STEMI treated by primary percutaneous coronary intervention (PCI) and enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) registry. Thirty percent of patients (n = 459) arrived directly to the Intensive Cardiac Care Unit or catheterization laboratory and 70% (n = 1093) were assessed first in the ER. Our primary end points were DBT, 30-day MACCE, and 30-day and 1-year mortality. Our secondary end points were pre-discharge ejection fraction less than 40%, in-hospital pulmonary edema, in-hospital cardiogenic shock, ST resolution, and duration of hospitalization. RESULTS: Bypassing the ER was associated with signficantly shorter DBT (59 vs. 97 minutes, P = 0.001). There was no difference in 30-day MACCE and 30-day or 1-year mortality between the 2 study groups. The findings were consistent in multiple subgroups, including women, anterior STEMI, off hours PCI, and patients with pain-to-door (PDT) time of less than 120 minutes. CONCLUSION: Bypassing the ER is associated with significant shortening of DBT. This reduction, however, is not associated with any change in 30-day MACCE and 30-day or 1-year mortality.

Oral cancer, cigarette smoke and mitochondrial 18kDa translocator protein (TSPO) - In vitro, in vivo, salivary analysis.

Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Deltapsi(m)), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p<0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133+/-643 fmol/mg protein and 6956+/-549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p<0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p<0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p<0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p<0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer.

Horizontal alveolar ridge distraction in an edentulous patient.

PURPOSE: Full fixed dental rehabilitation, including attachment based over denture (to dental implants) is the optimal solution for edentulous patients, although the insertion of implants will be impossible when the alveolar ridge has been horizontally and severely absorbed. A full arch narrow ("knife-edge") alveolar crest creates a "borderline" condition. Dental implants cannot be inserted into a narrow ridge, which is also at risk of rapid absorption, especially under the pressure of a full denture. Current clinical solutions have been limited. In bone augmentation, the bone absorption rate has been approximately 50%, requiring 6-month therapy prolongation for the grafted bone to consolidate. MATERIALS AND METHODS: We have described an edentulous patient whose "knife-edge" maxillary alveolar crest was widened with crest expanders (horizontal distractors). RESULTS: Only 6 weeks after initiation of the distraction, a wide enough ridge had been created, allowing bilateral insertion of implants, followed by attachment-based full dental rehabilitation. Bone augmentation was avoided, and the implants were placed in the correct lateral position, with sufficient attached gingiva obtained. CONCLUSIONS: Horizontal crest expanding in narrow-alveolar edentulous patients can significantly reduce both morbidity and the therapeutic period and substantially increase the therapeutic success rate, based on both soft tissue and bone distraction. With this technique, our patient was without the denture for only 6 weeks.

The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung Cancer Cells.

TSPO is involved in cigarette smoke (CS)-induced cellular toxicity, which may result in oral and pulmonary diseases and lung cancer. H1299 lung cancer cells were exposed directly to CS. The H1299 cells were pretreated with our TSPO ligands MGV-1 and 2-Cl-MGV-1 (Ki = 825 nM for both) at a concentration of 25 µM 24 h prior to CS exposure. Cell death and apoptotic markers were measured, in addition to TSPO expression levels, ATP synthase activity, generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), cAMP and LDH levels. Pretreatment with MGV-1 and 2-Cl-MGV-1 (25 µM), 24 h prior to CS exposure, differentially attenuated the CS-induced cellular insult as well as cell death in H1299 lung cancer cells. These protective effects included prevention of ATP synthase reversal, ROS generation, depolarization of the mitochondrial membrane and elevation in LDH. The preventive efficacy of 2-Cl-MGV-1 was superior to that achieved by MGV-1. Both ligands did not prevent the elevation in cAMP. These findings may indicate a mild protective effect of these TSPO ligands in CS-related pulmonary and keratinocyte cellular pathology.

Salivary antioxidants and metalloproteinases in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common autoimmune inflammatory disease in children; joint inflammation is the hallmark of the disease. Thirty-five children with JIA were studied, of whom 26 had active disease and 14 were receiving anti-TNF therapy (5 with Infliximab, 9 with Etanercept). Sixteen healthy controls also were studied. Saliva samples were obtained for analysis of anti-oxidant status, metalloproteinases (MMPs) and sialochemistry. The total antioxidant status was significantly higher in the saliva of all JIA patients, whether treated (P = 0.014) or not treated (P = 0.038) with anti-TNF agents. The increase in antioxidant status (TAS) in the saliva of the active patients was nearly two times higher than that of non-active patients (P = 0.01). MMP levels were significantly lower in JIA patients than in controls. MMP-9, MMP-3 and MMP-2 were lower in JIA patients without anti-TNF treatment by 36.7% (P = 0.01), 30.0% (P = 0.0001) and 10.7% (P = 0.0001), respectively. A greater reduction in MMP levels was observed in the group of patients treated with anti-TNF drugs: MMP-9, MMP-3 and MMP-2 were lower than in controls by 51.1% (P = 0.0001), 61.5% (P = 0.0001) and 55.4% (P = 0.0001), respectively. Children with JIA exhibited a significantly higher salivary antioxidant activity and significantly lower MMP levels. Anti-TNF treatment was associated with a further decrease in MMP levels in the saliva of JIA patients while an active state of JIA was associated with a further increase in the salivary antioxidant activity. Anti-TNF treatment may modulate the degradation process during the course of arthritis by inhibition of the activity of MMP.

Salivary monitoring related to major surgery.

BACKGROUND: Prolonged surgical procedures involving stress, extended general anaesthesia and a long pre-surgical fasting period may have systemic effects such as alterations in saliva flow rate and composition. These may compromise the patient's electrolytes and fluid balance and cause dehydration, systemic stress and oxidative changes. PATIENTS AND METHODS: Saliva was collected prior and following surgery from 20 patients and 20 control subjects. The saliva samples were analysed for flow rates and levels of the following: calcium (Ca), magnesium (Mg), total protein, albumin and lactate dehydrogenase (LDH), total antioxidant status (TAS), uric acid (UA), superoxide dismutase (SOD), carbonyls, matrix metalloproteinases (MMPs) -2, -3 and -9 and heat shock proteins (HSPs) 70 and 90. RESULTS: Salivary levels of Ca, Mg, protein, albumin and LDH were higher in post-surgical patients by 70% (P = 0·002), 88% (P = 0·0001), 120% (P = 0·13), 111% (P = 0·039) and 492% (P = 0·006) respectively than that in healthy controls. Salivary antioxidants in the surgical patients were higher while salivary carbonyls remained unchanged. Salivary TAS levels in pre- and post-surgical patients were higher by 63% (P = 0·001) and 85% (P = 0·0001) respectively, UA concentrations by 92% (P = 0·014) and 81% (P = 0·036) respectively and SOD values by 47% (P = 0·61) and 112% (P = 0·049) respectively. Salivary concentrations of MMP3 were higher in pre- and post-surgical patients by 23% (P = 0·067) and 30% (P = 0·044) respectively. CONCLUSIONS: Local salivary, oral and systemic-induced alterations should be prevented. Moreover, salivary collection and analysis may be a new, efficient tool in the monitoring of patients undergoing major surgery. Further related research is necessary.

Penicillamine as a potent protector against injurious effects of cigarette smoke in aerodigestive tract cancer.

BACKGROUND: Cigarette smoke (CS) is the major risk factor for aerodigestive tract cancers such as lung and oral cancers. METHODS: In in vitro models of lung and oral cancers, we found D-penicillamine (PenA) to be a most potent protector against CS, both in the absence and presence of saliva (a highly pro-oxidative condition). RESULTS: The survival rate of lung cancer cells and oral cancer cells was reduced by CS in the absence of saliva by 39-45% (p < 0.01) and by 55-60% (p < 0.01) in the presence of saliva. The addition of 5 mM PenA to cell medium prior to CS exposure limited cell loss to 22-25% only (p < 0.01). Similarly, the iron chelator desferal protected the cells only in the presence of saliva. PenA also protected against a CS-induced increase in carbonyls (oxidized proteins) and decrease in p53 levels (in the presence of saliva) and mitochondrial membrane potential (a hallmark of CS-induced apoptotic cell death). Malfunctioning p53 often characterizes carcinogenesis of CS-induced cancers. CONCLUSIONS: Redox-active iron and copper in pleural fluid and saliva, upon encounter with CS, may be responsible for this carcinogenesis, mediated via alteration of p53 function. Chelation of redox-active metals may be an efficient tool for prevention of CS-induced lung and oral cancers. The superiority of PenA results from its copper-chelating action as well as its antialdehyde and anti-inflammatory capabilities.

18-kDa Translocator Protein Ligands Protect H9C2 Cardiomyocytes from Cigarette Smoke-induced Cell Death: In Vitro Study.

BACKGROUND: Cigarette smoke (CS) can induce cellular damage via alterations in 18 kDa translocator protein (TSPO)-related functions, leading to cardiovascular diseases. The current study focused on the possible protective effect of TSPO ligands against CS-induced damage to cardiac cells. MATERIALS AND METHODS: H9C2 Cardiomyocyte cell line of rat origin was pre-treated with TSPO ligands. Cell death, TSPO binding, and TSPO protein expression levels were assessed following 30-min CS exposure with/without TSPO ligands. RESULTS: CS exposure of H9C2 cells significantly incensed cell death (by 26%, p<0.001). Pre-treatment with TSPO ligands at two concentrations prevented cell death. Neither CS nor ligands affected TSPO protein expression in H9C2 cells. CS led to increased cell death and reduced TSPO binding. CONCLUSION: Reduced TSPO binding may have a role in CS-induced cell death, and TSPO ligand MGV-1 can prevent suppression of TSPO binding and corresponding cell death. These results may be relevant to treatment of cardiovascular diseases associated with CS.

p27 and salivary cancer.

This study examined p27 expression in a cohort of salivary malignancies (n = 74) for a prolonged period (20 years). Reduction of p27 expression was found to be a most powerful predictor for poor survival and more so when the tumor concurrently expressed high levels of p53, TUNEL and heparanase markers, dramatically dropping the patient survival probability to 0! While no patient whose tumor-staining profile included: p27 > 50%, p53 = 0, TUNEL = 0 and heparanase = 0, died of the disease during the 20-year follow up, the median of survival of the group with p27 0, TUNEL > 0 and heparanase > 0 was only 39 months. The survival probabilities of these two groups at 5 years were 100 and 50%, respectively, and at 20 years they were 100 and 0%, respectively (P = 0.05). Significant p27 reduction also resulted in significantly larger tumor size (T value), higher spread of neck metastasis and extra capsular spread and in more advanced disease (higher stage). Significant correlation rates were found between age and poor survival, age and reduced p27 expression, and reduced p27 expression and other general co-existing malignancies, indicating p27 reduction as part of a general phenomenon-age related mutagenesis. Significantly more extensive therapy applied to patients with salivary reduced-p27 tumors could not prevent the rise in mortality rate, questioning the justification for extensive therapy which is naturally accompanied by higher morbidity. Additional therapeutic tools for fighting salivary cancer, possibly based on the new understanding of the p27, p53, TUNEL and heparanase carcinogenic network, are necessary.

The expression and prognostic significance of Cks1 in salivary cancer.

Cks1 is an essential factor in facilitating Skp2-dependent degradation of p27, but its role in salivary malignancies is unknown. Expression of cyclin-dependent kinase subunit 1 (Cks1) was examined in 64 salivary malignancies, compared with p27, S-phase kinase protein 2 (Skp2), Ki-67, p53, and TDT-mediated dutp-biotin nick end labeling (TUNEL) expression, and with THE patient's clinical and pathological parameters. Cks1 expression was markedly increased in 30 patients (47%) and strongly correlated with increased expression of Skp2, Ki-67, p53, and TUNEL, but inversely with p27 levels. High expression of Cks1 WAS strongly associated with lymph node metastases and poor prognosis and survival. Cks1 alterations may have a significant biological role in the pathogenesis of salivary cancer.

A novel technique for vertical bone augmentation in the premaxillary region.

A severely absorbed alveolar ridge in an edentulous premaxillary region is often augmented vertically with various methods to allow for dental implant insertion. Such a severely absorbed ridge most often results from loss of bone due to periodontitis or trauma or after dental extraction; and if socket preservation is not performed immediately after extraction, the alveolus narrows and its vertical dimension may often be reduced by 4 to 5 mm. We introduce a new technique for bone augmentation in the premaxillary region, in which vertical bone augmentation can be performed simultaneously with the insertion of dental implants. The dental implants fix the bone transferred to the maxilla, and particulate bovine bone is placed in the gap between the 2 segments. This method involves a single operation only, requires minimal chair time, and reduces postoperative pain and swelling and involved gingival trauma. In addition, the period required before prosthodontic rehabilitation is shortened.

Foreign body granulomas after injection of Bio-alcamid for lip augmentation.

Bio-alcamid is one of the newest agents on the market for soft tissue augmentation. Seven studies were documented in the medical literature that examined the safety of Bio-alcamid (Polymekon, Brindisy, Italy); all reported no cases of tissue migration, foreign body granulomas, allergenicity, or interference with the control of cell proliferation. On 2 separate occasions, a woman who had recently undergone lip augmentation presented at our hospital with submucosal nodules of the lip. Histologic examination revealed multiple foreign body-type granulomas composed of giant cells, epithelioid cells, and chronic inflammation of the lip. Efforts to produce a cosmetic material that fulfills all the criteria as an "ideal" agent has not yet been found because all injectable foreign agents have the potential to induce adverse reactions. Caution must be exercised in all cases and the risks explained to the patient before its use.

Non-primary salivary malignancies: A 22-year retrospective study.

PURPOSE: Most salivary gland malignancies are primary tumors, but in our medical center one of six is non-primary. The relative scarcity of such reports justifies studying them. SUBJECTS & METHODS: We studied patients' demographic and clinical parameters, salivary tumors/metastasis, diagnosis and treatment, and survival rates. RESULTS: Of all our salivary malignancy patients over the last 22 years, 15% (18/119) had non-primary malignant tumors, all located in the parotid glands. Of these, nine had skin cancer (SCC), 3 malignant solid tumors and 6 hematological systemic malignancies. Four had concomitant second malignancy. Mean age was 70.2 ± 13.8 years, 66.7% of the patients were males, 27.8% were smokers, none reported alcohol use. The most prevalent diagnostic tools used were CT (16 patients), FNA (13) and PET-CT (12). Eleven of 18 patients died from the disease despite receiving therapy: 6 SCC patients, 2 CLL patients and all 3 with solid tumors. All four lymphoma patients survived as did another three SCC patients. CONCLUSIONS: Chemotherapy and radiotherapy for systemic disease prolonged life rather than surgery. Patients with poor prognosis non-primary salivary tumors should be treated conservatively; surgery should be for those without widespread metastases or systemic disease. Sometimes a palliative patient may benefit from tumor debulking.

Effects of Cigarette Smoke on TSPO-related Mitochondrial Processes.

The 18 kDa translocator protein (TSPO) is an initiator of the mitochondrial apoptosis cascade. Cigarette smoke (CS) exposure provokes alterations in TSPO expression as well as upregulation of its related functions such as mitochondrial membrane potential (ΔψM) and reactive oxygen species generation, which are associated with cell death. In the current study, H1299 lung cancer cell line exposed to CS for various time periods (30 mins, 60 mins and 120 mins) and TSPO expression and cell death processes were studied. CS exposure for 30 mins resulted in a non-significant increase in TSPO expression by 24% (p > 0.05 vs. control). CS exposure for 60 mins and 120 mins resulted in a significant increase by 43% (p < 0.05 vs. control) and by 47% (p < 0.01 vs. control), respectively. Furthermore, TSPO-related mitochondrial functions were upregulated at the 120 mins time point following CS exposure. TSPO expression is upregulated by CS, suggesting that TSPO plays a role in cell death processes induced by CS exposure. Alterations in TSPO-related cell death processes suggest that TSPO may be involved in the tissue damage caused by CS.

Survival Probabilities Related to Histology, Grade and Stage in Patients With Salivary Gland Tumors.

BACKGROUND: The diversity of malignant salivary gland tumors challenges the study of survival rates. The current study evaluated patient survival rates using Kaplan-Meier analysis and examined the relative effects of histology, grade and stage on survival. MATERIALS AND METHODS: Using the Kaplan-Meier model, cancer-specific (CSS) and disease-free (DFS) survival probabilities were calculated as a function of time. RESULTS: Of 101 patients, 79 survived and 22 died of their disease. The probability of CSS was 0.83, 0.73 and 0.61 at 5, 10 and 15 years, respectively; corresponding probability of DFS was 0.69, 0.59 and 0.54, respectively. CONCLUSION: CSS and the DFS probabilities in patients with salivary malignancies were quite high at 5 years, although these rates dropped over the long-term; the lethal effect of the malignancy is often delayed and prolonged. Tumor histology, grade and stage are well established factors in predicting prognosis. Although the subgroups of patients with MECA and SCC were too small to allow adequate statistical analysis, clear tendencies for devastating effects of poor differentiation in SCC and higher grade in MECA were shown. That is, 2/4 patients with high-grade MECA died from their disease, while only 1/15 with low-intermediate grade MECA died from their disease. Similarly, 2/4 patients with poorly differentiated SCC died from their disease, while only 1/5 with well-to-moderately-differentiated SCC died from their disease. Factors such as molecular markers should be further studied in an effort to improve prognosis prediction.

Salivary malignancies- medical, demographic and diagnostic analysis.

We examined systemic medical and demographic characteristics of patients diagnosed with salivary malignant tumors in order to better understand the pathogenesis of the disease. Of 101 patients who received definitive treatment for malignant salivary gland tumors in our medical center, 22 died with disease (DwD) and were compared with the remaining 79 patients (Other). Mean ages were 66.7 years (median 68.0) in DwD group and 58.7 years (median 59.0) in the Others. The difference is significant (p = 0.037). Mucoepidermoid carcinoma was the diagnosis in 27.3% of DwDs and 27.8% of the others, Adenoidcystic carcinoma in 36.4% vs 21.5%, SCC and Acinic cell carcinoma were diagnosed in 18.3% vs 7.6% and 4.6% vs 7.6%, respectively. Alcohol consumption, concomitant malignancies, and chronic illnesses other than hypertension, were similar in the two groups, but hypertension (63.6%) in the DwD group was significantly higher than in the Other group (26.6%), (p = 0.0010). Smoking was also significantly different between the two groups: 50% of the DwD vs. 27.9% of the Others group smoked cigarettes. Similar distribution of the various malignant tumors in both groups emphasizes the relative importance of systemic factors such as smoking, aging and hypertension, in the salivary carcinogenesis process.