Defining health-related quality of life in localized and advanced stages of breast cancer - the first step towards hereditary cancer genetic counseling.

The important goal in breast cancer treatment is to improve patient quality of life. Due to the huge economic burden, it is necessary to estimate the health state utility values for different breast cancer stages accurately. A group of 114 women filled out the EuroQol-5D-3L questionnaire at two time points. The participants were divided into three groups, as follows: group 1 including healthy high-risk individuals; group 2 including patients with localized stage breast cancer; and group 3 including patients with advanced stage breast cancer. Results were expressed either as summary health state utility score or summary visual-analog score. The EuroQol utility index score and EuroQol visual-analog score were statistically significantly higher in the group of healthy high-risk individuals. The EuroQol visual-analog score was mostly correlated with the anxiety/depression and pain/discomfort quality of life dimensions. Health state utility values for different breast cancer stages are a necessary tool to perform economic analyses in breast cancer management decision making, due to its huge economic burden. Special attention should be paid to assessment of the psychosocial aspects of the disease, as well as pain management.

Corrigendum to "Oral Adverse Reactions Caused by Over-the-Counter Oral Agents".

[This corrects the article DOI: 10.1155/2015/196292.].

Spontaneous Rupture of Venae Gastricae Breves in Pregnancy: Case Report.

INTRODUCTION: Hemiperitoneum caused by venous bleeding from the hilum of the spleen is a rare cause of acute abdomen in the last trimester of pregnancy. MATERIAL AND METHODS: We are presenting a case of a twenty-nine-year-old primipara with the clinical picture of acute abdomen. CASE REPORT: Primipara in the 36th week of pregnancy presented with the clinical picture of acute abdomen with the ultrasound finding of free fluid in the abdominal cavity and foetal bradycardia. Considering the clinical picture of the mother and the risks for the foetus, it was decided to complete the pregnancy with an emergency caesarean section. During the procedure, exploration of the abdominal cavity found the bleeding site from the venae gastricae breves, and a surgeon stopped active bleeding. CONCLUSION: Non-obstetric bleedings are not common in pregnancy, but they are life-threatening both to the mother and the foetus. The exact cause is usually found during the surgical procedure. If a pregnant woman presents with a clinical picture of abdominal pain, and the signs of foetal distress or clinical instability of the mother are also present, an emergency surgical procedure is indicated. In this case, the indication was foetal bradycardia, and the child was born alive by a caesarean section, while an extended surgical procedure saved the mother's life.

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.

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.

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.

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.

[CANCER PATIENTS FOLLOW-UP ­ CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES Part IV: planocellular head and neck cancer, oesophageal cancer, gastric cancer, colorectal cancer].

Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert's opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures' algorithm in follow­up of oncological patients after primary treatment, in patients with planocellular head and neck cancer, oesophageal cancer, gastric cancer and colorectal cancer.

The Effectiveness of Low-Level Laser Therapy in Patients with Drug-Induced Hyposalivation: A Pilot Study.

OBJECTIVE: The aim of this study was to compare switched on and switched off (sham) low-level laser therapy (LLLT) in the treatment of drug-induced hyposalivation. BACKGROUND DATA: Hyposalivation is decreased salivary flow rate most frequently present in patients who take a lot of medication, suffer from Sjögren's syndrome, or were irradiated. Available therapies provide only short-term relief. MATERIALS AND METHODS: Forty-three participants (40 females and 3 males, average age 72.3 ± 8.9) participated in the study. Before therapy or after therapy, every participant fulfilled quality-of-life assessment scale (OHIP-CRO14). Unstimulated and stimulated salivary flow rates were measured before and after treatment. The LLLT was performed by the use of gallium-aluminum-arsenide (GaAlAs) laser (830 nm) on parotid, submandibular, and sublingual glands every day except during weekends for 14 days. RESULTS: Significant difference in unstimulated salivary flow rate after the treatment was found in the study group (p = 0.002) compared with the sham group. No significant difference in stimulated salivary flow rate after treatment was found in the laser group (p = 0.626) nor in the sham laser group (p = 0.233). No significant difference in patient's quality-of-life score was found after both treatments. CONCLUSIONS: The results of this study showed that the LLLT increased unstimulated salivary flow rate significantly. However, stimulated salivary flow rate did not increase significantly after the LLLT. In patients who underwent sham laser therapy, neither unstimulated nor stimulated salivary flow rate increased significantly.

IMMUNOHISTOCHEMICAL DIFFERENTIATION OF TRIPLE NEGATIVE BREAST CANCER.

Based on immunohistochemical staining for the basal markers cytokeratin 5/6 (CK 5/6), cytokeratin 14 (CK 14) and P-cadherin, triple negative tumors (TNT) are divided into two groups: 1) basal-like (BL) positive for one or all three markers; and 2) non basal-like (NBL) negative for all three markers. Even though the different origin of the cells of these two types of tumors implies different biological properties, they had been treated as one entity until recently. This paper analyzes TNT collected from 150 patients and distributed into two groups according to the results of immunohistochemical analysis, i.e. BL 116 (77.3%) and NBL 34 (22.67%). In this study, CK 5/6, CK 14 and P-cadherin were used as markers for identifying BL tumors. The immunohistochemical reaction was positive for CK 5/6 in 37%, for CK 14 in 50.86% and for P-cadherin in 68.34% of cases. The subclassification of triple negative breast cancer using the basal markers CK 5/6, CK 14 and P-cadherin has enabled identification of BL and NBL breast cancers in a proportion that is in line with the only accurate analysis of TNT gene expression. Using the mentioned combination of markers in daily practice is easy to perform and economically affordable.

Case report of nodular melanoma within congenital melanocytic nevus- primary closure challenge.

INTRODUCTION: Congenital melanocytic nevi (CMN) are present in 1-2% of newborn infants. The size of CMN defines the risk of developing melanoma which is estimated from 5-10%, especially in lesions that are located across the spine. PRESENTATION OF CASE: Herein we report a case where nodular melanoma was discovered on the periphery of medium sized CMN in a high risk patient. After complete excision, the defect was reconstructed with random pattern, triple rhomboid flap. DISCUSSION: Melanoma that arose within medium sized CMN would leave a complex posterior lower trunk defect. We used a triple Limberg flap which was proven to be straightforward and simple method when large defects are to be covered with vital tissue. We have also showed that this type of reconstruction is suitable for high risk patients that could not withstand any complex procedures. CONCLUSION: In our case, the method we choose to reconstruct the defect proved to be simple, safe and easy, especially when surgery is performed in a high risk patient.

MESONEPHRIC ADENOCARCINOMA OF ENDOCERVIX WITH LOBULAR MESONEPHRIC HYPERPLASIA: CASE REPORT.

Mesonephric adenocarcinoma is a rare variant of cervical adenocarcinoma. We present a case of mesonephric adenocarcinoma of endocervix with cervical and vaginal lobular mesonephric hyperplasia in a 57-year-old woman. Vaginal bleeding persisting for 12 months was the only symptom. Histopathologic findings and characteristic immunophenotype are crucial for the diagnosis. The tumor was composed of papillary formation with a central fi brovascular stroma, villoglandular and densely compact tubular structures containing intraluminal eosinophilic secretion, and coated with one or more rows of cylindrical atypical epithelial cells. There were 30 pathologic mitotic shapes found per 10 HPF. The tumor invaded nearly full-thickness of cervical stroma with positive lymphovascular space invasion and clear margins. The case demonstrated characteristic cytokeratin 7, vimentin and epithelial membrane antigen positivity and high Ki-67 proliferation index (60%). Estrogen receptors, progesterone receptors and carcinoembryonic antigen were negative. Intratubular lumen secretion was periodic acid-Schiff positive with periodic acid-Schiff negative carcinoma cells. Diff erential diagnoses include adenoma malignum, well-diff erentiated villoglandular adenocarcinoma, endometrioid adenocarcinoma, serous adenocarcinoma, mesonephric adenocarcinoma with a sarcomatous component, clear-cell carcinoma and mesonephric hyperplasia. Radical hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy was performed. Three years after the surgery, the patient remains well. There has not been any evidence of local or distant recurrence. There are no specific recommendations for the treatment of this rare disease. It remains uncertain whether surgical approach is sufficient or the treatment should include additional radio/chemotherapy.

[CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER--CROATIAN ONCOLOGY SOCIETY]. / KLINICKE UPUTE HRVATSKOGA ONKOLOSKOG DRUSTVA ZA DIJAGNOZU, LIJECENJE I PRACENJE BOLESNICA/KA OBOLJELIH OD INVAZIVNOG RAKA DOJKE.

Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia.

ADVERSE DRUG REACTIONS IN THE ORAL CAVITY.

Every medication may lead to adverse effects, even when used in standard doses and mode of application. In the oral cavity, adverse effects may affect every part of oral mucosa and are the result of medications taken either locally or systemically. Oral adverse reactions to drugs are not typical and therefore sometimes not easy to recognize. On diagnosing adverse side effects in the oral cavity, experienced clinician will usually diagnose the condition on the basis of detailed medical history and clinical finding. However, the only objective evidence for the offending drug is 're-challenge', i.e. exposure to the drug after its discontinuation. It carries a huge risk of anaphylactic reaction; therefore it has to be performed in a controlled hospital setting. Therapy is based on immediate exclusion of the offending drug and, if lesions are present in the oral cavity, topical or systemic corticosteroid therapy is prescribed. This article gives a review of patients with oral adverse drug reactions referred to the Department of Oral Medicine in Zagreb.

Dental infection and dermatological diseases: analysis of ninety-two patients and review of the literature.

Dental disease has long been proposed as a potential causative agent in certain dermatological diseases. However, literature data on this association are scarce. The aim of this retrospective study was to evaluate dental status in 92 patients with various dermatological diseases who were referred to our Department for elimination of dental disease and to assess the relationship between dental infection and dermatological diseases. Dermatological conditions due to which patients were referred were alopecia, urticaria, eczematoid dermatitis, psoriasis, edema, etc. Out of 92 patients, 42 (45.7%) patients were referred for further dental treatment, while the remaining 50 (54.3%) patients had no observable dental pathology. None of the patients reported improvement following dental treatment. Based on the results of this study, we might conclude that dental infection does not play any role in the development of dermatological disease.

Oral Adverse Reactions Caused by Over-the-Counter Oral Agents.

Over-the-counter products rarely cause unwanted reactions in the oral cavity. Oral reactions to these agents are not specific and might present with various clinical oral findings. Detailed medical history is a key to the proper diagnosis of these lesions and fortunately other diagnostic procedures are rarely needed. Lesions are usually managed with elimination of the offending agent and with topical steroids. In more severe cases systemic steroids should be applied.

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.