THE ROLE OF SALIVARY AND SERUM CA125 AND ROUTINE BLOOD TESTS IN PATIENTS WITH OVARIAN MALIGNANCIES.

The use of routine blood tests has recently been shown to be promising in determining disease-free and overall survival in patients with various malignancies, and also in gynecologic malignancies. The aim of this study was to evaluate whether salivary and serum CA125 levels correlate and whether salivary and serum CA125, C-reactive protein and routine blood tests might serve as a prognostic factor in malignant ovarian tumors, and whether they might differentiate between benign and malignant ovarian tumors. A total of 98 women were included (48 with benign ovarian tumors and 50 with malignant ovarian tumors), in whom routine blood tests were made and salivary and serum CA125 levels were determined by use of ELISA. Increase in serum CA125 and amylase decreased overall survival, whereas increase in salivary CA125, potassium levels and hemoglobin increased overall survival. Significant correlation of serum CA125 and C-reactive protein was found in the group with malignant tumors. In conclusion, significant increase in the levels of serum CA125 and amylase correlated with decreased survival, whereas increased salivary CA125, hemoglobin and potassium levels significantly correlated with increased survival.

Environmental and behavioural head and neck cancer risk factors.

OBJECTIVES: The high incidence of head and neck cancer (HNC), significantly associated with living environment and behaviour, can be prevented more efficiently. The aim of this study was to evaluate the environmental and behavioural risk factors for HNC. METHODS: Using a detailed questionnaire on social status, education, living and occupational environment exposures, family cancer and lifestyle, HNC patients (103 cases, 76.7% of men) were compared with control subjects (244 subjects, 73% of men) balanced by age: mean (standard deviation) 63.8 (9.3) and 63.8 (9.0) for cases and controls, respectively. RESULTS: The results of this study showed that smoking and low education were significant risk factors for HNC regardless of sex. Family HNC and breast cancer were significant predictors of HNC risk. CONCLUSION: The study confirmed previous results that smoking and low education are significantly associated with HNC. Additionally, results pointed to significant HNC and breast cancer risk in HNC patient's families that may have originated from passive smoking or a smoking habit stemming from social environments that support it. Better dissemination programmes regarding smoking risks for children and adults are needed, targeting not only individuals but also families.

GINGIVAL ULCERATIONS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA: A case report and literature review.

A 40-year-old female patient was admitted to the Department of Oral Medicine due to oral ulcerations. Oral ulcerations were present on vestibular mucosa above teeth 21, 22, 25 and 26 and were 1 cm in diameter, and also around teeth 45 and 46. The patient had prolonged neutropenia due to therapy-related myelodysplastic syndrome that progressed to therapy-related acute myeloid leukemia. Initially, the patient was successfully treated with polychemotherapy for non-Hodgkin lymphoma. Unfortunately, many toxic complications ensued, such as peripheral neuropathy, dilated cardiomyopathy and therapy-related myelodysplastic syndrome/therapy-related acute myeloid leukemia. The onset of therapy-related myelodysplastic syndrome was less than six months after initiation of chemotherapy treatment, which was rather early, but cytogenetic changes (monosomy 5 and 7) were consistent with the diagnosis. Upon admission to our Department, microbiological swabs were obtained and were all negative, while x-ray finding showed that ulcerations did not have dental cause. Biopsy was not obtained as the patient had severe neutropenia and thrombocytopenia. While viral and fungal swabs were negative, Stenotrophomonas maltophilia was cultured from the oral cavity. Thus, differential diagnoses are listed in this report. Neutropenic ulcerations did not heal albeit extensive medicamentous oral and systemic treatments were applied and the patient died.

EVALUATION OF INNOVATIVE DIGITALLY CONTROLLED ER:YAG LASER IN SURGICAL TREATMENT OF ORAL LEUKOPLAKIA - A PRELIMINARY STUDY.

The use of lasers for treatment of oral leukoplakia has gained a lot of interest in the past years, however, data on the use of Er:YAG laser are scarce. The aim of this study was to compare the efficacy of Er:YAG laser and 1% topical isotretinoin in the treatment of 27 oral leukoplakia patients. Er:YAG laser (LightWalker AT, Fotona, Slovenia) was used in 27 patients with 27 leukoplakia lesions. Postoperative pain was assessed by use of visual analog scale (VAS), and the impact of laser treatment on the quality of life was assessed by the OHIP-14 questionnaire (Croatian version). Control group consisted of the same 27 patients previously treated with 1% topical isotretionin three times a day during the period of one year. No improvement in the size of leukoplakia lesions was observed after treatment with topical isotretinoin. There were significant differences between men and women according to leukoplakia localization, number of laser sessions and VAS (p<0.05). At follow-up after six months and one year, there was no recurrence of lesions. Er:YAG laser is a successful treatment for oral leukoplakia. Topical isotretionin treatment is unsuccessful in patients with oral leukoplakia.

THE ROLE OF COMPLETE BLOOD COUNT PARAMETERS IN PATIENTS WITH COLORECTAL CANCER.

- Chronic inflammation has been linked with many cancers. It seems that easily available and usual blood inflammatory markers might serve as a prognostic factor for overall survival and disease-free survival in patients with various cancers. Preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as hemoglobinemia, thrombocytosis, elevated C-reactive protein values, neutropenia and leukocytosis have been shown to affect overall survival and disease-free survival in patients with colorectal cancer (CRC), however, with controversial results. Complete blood count, NLR and PLR were determined in 71 patients with CRC (stages 3 and 4) after neoadjuvant chemo-radiotherapy and before surgery, treated at Hospital for Tumors in Zagreb. Statistical analysis included Mann-Whitney U test, Student's t-test, univariate and multivariate analysis. The results of Mann-Whitney U test and Student's t-test showed that neutrophil count (p=0.024), NLR (p=0.003) and PLR (p=0.007) correlated significantly with overall survival. However, there was no significant correlation of age, leukocyte, lymphocyte and platelet counts and hemoglobin values with overall survival of patients. Furthermore, the same tests showed that leukocyte (p=0.04), neutrophil (p=0.0014) and platelet (p=0.006) counts, NLR (p=0.0006) and PLR (p=0.0015), as well as hemoglobin values (p=0.028) correlated significantly with disease-free survival. The results of univariate analysis showed that unlike PLR, NLR correlated with overall survival and disease-free survival (p=0.0002), although the correlation of PLR and disease-free survival almost reached significance (p=0.059). Furthermore, the results of univariate analysis showed significant correlation of advanced pathological TNM stage with overall survival. There was no correlation of patient age and gender, tumor stage and neoadjuvant chemo-radiotherapy with overall survival and disease-free survival. The results of multivariate analysis showed that NLR (cut-off value 3.27) and advanced pathological TNM stage significantly correlated with disease-free survival but not with overall survival. It seems that NLR might be an accurate marker for overall survival and disease-free survival in CRC patients after neoadjuvant chemo-radiotherapy and before surgery.

Comparison between three different saliva substitutes in patients with hyposalivation.

OBJECTIVE: The aim of the present study was to compare the efficiency of oral spray based on thermal spring water (Buccotherm®) versus commercial saliva substitute (Xeros®) and marshmallow root on the quality of life in patients with hyposalivation. MATERIALS AND METHODS: A total of 60 patients with unstimulated salivary flow rate <0.2 ml/min were randomized into three groups. In the first group, 30 patients were using Buccotherm®; in the second group, 15 patients were using Xeros®; and in the third group, 15 patients were using marshmallow root. Therapy lasted for 2 weeks; everyday, patients used one of the products four times a day. Quality of life was measured by the Croatian version of Oral Health Impact Profile 14 questionnaire, and visual analog scale was used to determine the intensity of dry mouth before and after therapy. Statistical analysis was performed by Wilcoxon signed-rank test and Kruskal-Wallis test. Standardized effect size was calculated for OHIP following treatment. RESULTS: Buccotherm® has shown the biggest effect on quality of life in patients with hyposalivation. Intensity of dry mouth was lower after the applied therapy whatever substitute patients used. CONCLUSIONS: We recommend the use of all three saliva substitutes for decreasing the intensity of dry mouth symptoms as well as improvement in the quality of life. CLINICAL RELEVANCE: Although all tested agents showed beneficial effect in alleviating hyposalivation symptoms, it seems that Buccotherm® was superior to Xeros® and marshmallow root.

Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all cancers with predominant occurrence in middle aged and elderly males. Tumour recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) have been suggested to play a certain role in variety of tumours. The aim of this study was to investigate the relationship of pretreatment serum IL-6 and TNF-α levels on tumour recurrence in patients with OSCC in order to identify potential biomarkers for the early detection of disease recurrence. MATERIAL AND METHODS: The patients with newly diagnosed OSCC were treated and followed from the first visit from November 2006 until January 2008. Serum IL-6 and TNF-α concentrations were measured. The records of the patients were re-examined in July 2012 and data were recorded about cancer characteristics and tumour recurrence. Disease free survival was analyzed by Kaplan-Meier survival curves, log rank test and Cox proportional hazards regression. RESULTS: Serum IL-6 was shown as an independent risk factor for tumour recurrence. CONCLUSIONS: Pretreatment serum IL-6 concentration may be a useful biomarker for identification of OSCC patients with increased risk of the disease recurrence.

Oral lichen planus - retrospective study of 563 Croatian patients.

OBJECTIVES: To investigate the epidemiological and clinical characteristics of oral lichen planus (OLP) in a group of Croatian patients seen between 2006 and 2012. STUDY DESIGN: A group of 563 patients with a diagnosis of OLP was retrospectively reviewed in our clinic. Data regarding age, gender, medical history, drugs, smoking, alcohol, chief complaint, clinical type, localization, histology, treatment and malignant transformation were registered. RESULTS: Of the 563 patients, 414 were females and 149 were males. The average age at the diagnosis was 58 (range 11-94). The most common site was buccal mucosa (82.4%). Most of our patients did not smoke (72.5%) or consume alcohol (69.6%). Patients reported oral soreness (43.3%), mucosal roughness (7%), xerostomia (3%), gingival bleeding (2%) and altered taste (0.5%) as the chief complaint, while almost half of them were asymptomatic (44.2%). The most common types of OLP were reticular (64.8%) and erosive (22.9%). Plaque-like (5.7%) atrophic/erythemtous (4.3%) and bullous (2.3%) type were also observed. Malignant transformation rate of 0.7% was recorded. CONCLUSIONS: OLP mostly affects non-smoking middle-aged women. Buccal mucosa is the most commonly affected site. In almost half of the cases patients are asymptomatic. In spite of the small risk for malignant transformation all patients should be regularly monitored.

Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer.

OBJECTIVES: The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls. STUDY DESIGN: Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay. RESULTS: Salivary IL-1ß and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (p<0.05). No differences in concentrations of salivary TNF-α between either of the groups were observed. Serum concentrations of IL-1ß were below level of detection in all but two participants. No significant differences between the groups were observed in serum concentrations of IL-6. Serum TNF-α was significantly higher in control subjects than in oral cancer patients. CONCLUSIONS: Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies.

Topical NAVS naphthalan for the treatment of oral lichen planus and recurrent aphthous stomatitis: A double blind, randomized, parallel group study.

AIM: To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS. METHODS: The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14). RESULTS: No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found. CONCLUSION: No evidence of differences between the two compared interventions was found. REGISTRATION: Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4.

Salivary Cortisol Levels and Burning Symptoms in Patients with Burning Mouth Syndrome before and after Low Level Laser Therapy: a Double Blind Controlled Randomized Clinical Trial.

OBJECTIVES: Burning mouth syndrome (BMS) is a disorder which is described as burning sensation of the oral mucosa without pathological changes. Most of the patients have some underlying stressful conditions. Stress induces an increase in secretion of different endocrine glands resulting in higher levels of glucocorticoids. One of the options for treatment of BMS includes low level laser therapy (LLLT). The aim of this research was to determine salivary cortisol levels and intensity of burning symptoms in BMS patients before and after LLLT. MATERIALS AND METHODS: Twenty-three participants were allocated by randomization in two groups: 12 patients in the study group and 11 patients in the placebo group. Cortisol levels in all patients were analyzed from the sample of saliva collected without stimulation. In both groups, the LLLT was performed once a day for ten consecutive days (excluding weekend) with Ga-Al-As light-emitting diode type of laser, with a wavelength of 685nm. In the control group, LLLT was done with inactive laser probe which was only emitting audio signal. The intensity of burning symptoms was measured by a visual analogue scale (VAS). The VAS and unstimulated saliva were measured at baseline and on the last day of the LLLT. A quantitative analysis of saliva was performed using competitive commercial ELISA-kit. RESULTS: VAS scores and salivary cortisol levels were significantly lower in both groups after LLLT. CONCLUSIONS: LLLT can be useful in patients with BMS for reducing burning symptoms and salivary cortisol level. Future studies on a larger number of patients should clarify whether the positive results are an outcome of laser effectiveness or of placebo effect.

Idiopathic Exposed Bone Lesions of the Jaw.

INTRODUCTION: Osteonecrosis of the jaw is defined as exposed bone in the oral cavity that does not heal longer than eight weeks after identification. The two most common predisposing factors for osteonecrosis of the jaw are medication-related and radiotherapy. Rarely, exposed bone in the maxillofacial region can occur due to other causes and represents a clinical and therapeutic challenge for the dentist because there is no universally accepted treatment protocol. CASE PRESENTATION: We report a case of a patient with two idiopathic lesions of exposed bone which have healed after systemic antibiotic therapy, seven weeks after the first examination. CONCLUSION: Exposed bone lesions of the jaw are a rare entity and are poorly documented in the literature. It is necessary to exclude possible local or systemic contributing factors. Surgical and conservative therapy (antibiotics) are the treatment of choice.

Salivary Cortisol Levels in Patients with Oral Lichen Planus-A Pilot Case-Control Study.

It is known that cortisol level increases in stress situations. The aim of the study was to measure the levels of salivary cortisol in patients with oral lichen planus (OLP) and healthy controls. This was a case-control pilot study which included seven patients with reticular (non-symptomatic) OLP, eight patients with atrophic/erosive (symptomatic) OLP, and nine healthy controls. We hypothesized that patients with an atrophic/erosive type of OLP have higher levels of cortisol compared to patients with the reticular type of OLP and healthy controls. In each participant, unstimulated saliva was collected in order to determine cortisol levels by using commercially available ELISA kit. Our results have shown no differences between levels of salivary cortisol in OLP patients and healthy controls. We can conclude that further research with a larger number of OLP patients is needed to determine the correlation between OLP and stress.

Case of Unrecognised of Maxillary Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma is a less commonly diagnosed cancer that may affect the major or minor salivary glands. We present a 70 year old male patient who was admitted to the Department of Oral Medicine, School of Dental Medicine in Zagreb, Croatia due to pain in the right maxilla. In this case we report a case of the patient with unilateral pain in the maxilla & eye which lead to the diagnosis of adenoid cystic cancer without any visible oral lesions.

Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC. PATIENTS AND METHODS: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry. RESULTS: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients. CONCLUSION: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.

Oral Mucormycosis and Aspergillosis in the Patient with Acute Leukemia.

A 54-year-old male patient with acute lymphoblastic leukemia was referred to the Department of Oral Medicine. He had a primary refractory disease and was treated according to HOVON71 and HAM protocol. Sixteen days after the start of the HAM protocol the patient developed palatal dark red/brownish lesion and maxillary vestibular exophytic lesion. Biopsy specimens from oral lesions were taken and microbiologic evaluation confirmed the presence of Aspergillus fumigatus and Rhizopus genus. The treatment of the patient consisted of the inferior maxillectomy and intravenous posaconazole and amphotericine B for the following 28 days. Since the coinfection with Aspergillus and Rhizopus is extremely rarely seen in the oral cavity, a diagnostic and therapeutic dilemma easily presents itself.

Oral and Vulvar Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin (1). Simultaneous involvement of the oral mucosa is extremely rare, but it may be the only affected area (2). A 55-year-old woman was referred to the Department of Oral Medicine, School of Dental Medicine University of Zagreb due to whitish lesions on the right ventrolateral part of the tongue and buccal mucosa with desquamative gingivitis (Figure 1, a-c). The lesions were asymptomatic but indurated on palpation. Histology was conclusive for oral lichen sclerosus (OLS). The lesions on gingiva were successfully treated with betamethasone ointment, three times a day for two weeks. One year earlier, she had been referred to the Department of Dermatology and Venereology with progressive pruritus and dyspareunia, white patches, obliteration of the labia minora, and stenosis of the introitus (Figure 2). Histology was conclusive for vulvar LS (Figure 3, a and b). She was successfully treated for 5 months with clobetasol propionate 0.05% ointment. The patient was taking levothyroxine to treat hypothyroidism associated with Hashimoto's thyroiditis and was otherwise healthy. Oral LS is clinically characterized by the appearance of white macules, papules, or plaques mostly appearing on labial mucosa but also on buccal, palate mucosa and on the lower lip (2,3). On the genitals, it typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring (1). While vulvar LS is often associated with pruritus, dyspareunia, and dysuria, OLS is often asymptomatic, although pain, soreness, pruritus, and tightness when opening the mouth can be present (1,2). Oral manifestations of LS, as well as association of anogenital and oral LS, are rarely reported in the literature (4-6). Tomo et al. searched the Medline database for papers reporting oral LS cases with histological diagnosis confirmation from 1957 to 2016 and found only 34 cases of oral LS with histopathologic confirmation of the diagnosis (4). Kakko et al. reported 39 histologically proven cases of OLS (2). Attilli et al. (5) reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement. They reported that LS was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in only 7 cases (5). Some believe that many cases of clinically diagnosed lichen planus may actually be LS and that isolated oral mucosal LS may not be as rare as is generally thought (2). While vulvar LS can occur at any age with increasing incidence with age, the median age of patients with OLS was 34 years and most of the patients were female (1,2,5). Due to the small number of patients in the literature, treatment recommendations for OLS are not available. In case of symptomatic oral lesions, topical or intralesional corticosteroids are considered to be the first-line treatment (2). First-line treatment for anogenital LS is a potent to very potent topical corticosteroid ointment, and second-line therapies include topical calcineurin inhibitors 1% pimecrolimus and 0.1% and 0.03% tacrolimus (1). For treatment-resistant genital LS, oral retinoids, methotrexate, and possibly local steroid injections for single lesions are mainly applicable for women (1). There is limited evidence for systemic treatments for both conditions. If it is not treated, genital LS is associated with a greater degree of scarring and an elevated risk of progression to squamous cell cancer; however, malignant transformation of OLS has not been reported (1-6). Due to the very rare presentation in the oral cavity, it is important to notice these lesions during a dental exam.

The Efficacy of Low-Level Laser Therapy in Burning Mouth Syndrome - A Pilot Study.

The aim of this clinical study was to compare low-level laser therapy (LLLT) switched on and switched off in the treatment of burning mouth syndrome (BMS). BMS is a debilitating condition for patients and highly demanding for physicians, characterized by burning symptoms in the oral cavity. Despite extensive research, so far only cognitive behavioral therapy and clonazepam have been proven successful for its treatment in randomized controlled trials. Forty-four patients with BMS were randomly assigned to the study laser group (LLLT) or the sham laser group. LLLT was performed with the GaAlAs laser (830 nm) used in non-contact mode on the site in the mouth where burning symptoms were present; study patients received 10 sessions (10 days). Each participant filled out the visual analog scale (VAS) and oral health impact on the quality of life scale (OHIP-CRO 14) before and after either therapy protocol. There were no significant differences between the groups before and after LLLT (switched on and off) in the quality of life (OHIP CRO 14 scores) (p>0.05). There was significant decrease in pain symptoms (VAS) in both LLLT switched on and LLLT switched off groups (p <0.05). Both LLLT switched on and switched off decreased pain symptoms (VAS) in patients with BMS; however, neither LLLT switched off or switched on im-proved the OHIP-CRO 14 scores.

Significance of stroma in biology of oral squamous cell carcinoma.

The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is an aggressive cancer that metastasizes rapidly. Despite the development of new therapies in the treatment of OSCC, no significant increase in 5-year survival has been recorded in the past decades. The latest research suggests focus should be put on examining tumor stroma activation within OSCC, as the stroma may contain cells that can produce signal molecules and a microenvironment crucial for the development of metastases. The aim of this review is to provide an insight into the factors that activate OSCC stroma and hence faciliate neoplastic progression. It is based on the currently available data on the role and interaction between metalloproteinases, cytokines, growth factors, hypoxia factor and extracellular adhesion proteins in the stroma of OSCC and neoplastic cells. Their interplay is additionally presented using the Systems Biology Graphical Notation in order to sublimate the collected knowledge and enable the more efficient recognition of possible new biomarkers in the diagnostics and follow-up of OSCC or in finding new therapeutic targets.

Oral aphthous-like ulceration due to tiotropium bromide.

Unwanted side-effects of a drug therapy are well known to oral medicine specialists and other colleagues. Usually they manifest itself as dry mouth, taste disturbances, various allergic or toxic reactions on the lips and/or in the oral cavity. However, the list of the drugs which might induce unwanted reactions is everyday becoming longer as more and more drugs are introduced on the market. Certain problems when diagnosing and reporting unwanted side effects of the drugs exist as only accurate method of diagnosis is repeated drug use in controlled clinical setting where fatal consequences due to the anaphilactic shock could be avoided. We report a side effect reaction to tiotropium bromide (Spiriva) cap used with HandiHaler manifesting itself as an oral ulceration in a 65 yrs old male. On the third day of drug intake the patient developed oral ulceration two times in a period of few months. Other medications he has been using for several years. To our knowledge this is a first report as an oral side-effect of this drug used for treatment of chronic obstructive pulmonary disease (COPD).