Uticaj indeksa proliferacije KI-67 ćelijskih morfometrijskih paremetara na efekat hemioterapije cisplatinom kod pacijentkinja obolelih od karcinoma grlića materice

Cervical cancer is the third most common malignant tumor in the world. Cisplatin is the most commonly used chemotherapeutic agent in the treatment of cervical cancer and is now considered a medication of choice for locally advanced, metastatic and recurrent cervical cancers. To determine the therapeutic protocol in some cancers, it is necessary to determine the Ki-67 proliferation index (Ki-67 PI), while in the treatment of cervical cancer it is still novel. This prospective study included 59 subjects treated at the Clinical Center Niš, with locally advanced cervical cancer, in order to determine the relationship between the therapeutic response to cisplatin and Ki-67 PI, as well as the cell morphometric parameters of the cancer tissue. Survival time in cervical cancer patients is rising with an increase in Ki-67 PI values. The cut off value of Ki-67 PI was determined at 60%, which influenced the statistically significant survival of patients with cervical cancer and represented the sensitivity value of this cancer to chemotherapy with cisplatin. Of the examined cell morphometric parameters, the cell area, perimeter, circularity, Feret diameter, integrated optical density, whose values statistically significantly influenced the length of survival of the subjects, were singled out. Their common use achieves a more reliable prediction of the therapeutic response to cisplatin chemotherapy in patients with cervical cancer, which is the basis of individualization of therapy in these oncology patients

Ascitic Fluid in Ovarian Carcinoma – From Pathophysiology to the Treatment

Due to low symptomatology, a lack of screening, and relatively complicated diagnostic procedures of ovarian carcinoma, more and more women are believed to visit their doctors in advanced stage of the disease, complicated with ascitic fluid. There is an increasing evidence that peritoneal cytology is a subjective assessment with certain percentage of false-positive and false-negative results that may cause application of unnecessary chemotherapy or nonapplication of necessary chemotherapy. Maximal cytoreductive surgery followed by intraperitoneal or systemic chemotherapy remains to be the gold standard in preventing ascites. Ascites is not only a symptom of a disease, but a specific microenvironment for formation and mediation of protumorigenic signals that control ovarian cancer progression, proliferation, invasion, anti-apoptosis, chemoresistance and tumor heterogeneity. Acellular cytokines and immunological factors influence ovarian cancer progression and its ability to prevent immune responses of the body and tumor reaction to chemotherapy. Ascites contributes to disease dissemination, changing its course and final outcomes. Management of patients with ascites and ovarian carcinoma is complex and often the goal of the treatment is to target palliative procedures. Multidisciplinary approach is necessary in the management of these patients. Further investigations of new drugs and immunomodulators are needed aiming at prolonged periods between relapses

ATYPICAL, CHOLESTATIC FORM OF HEPATITIS A WITH AN EXTRAHEPATIC, CUTANEOUS MANIFESTATION – A CASE REPORT

Hepatitis A sometimes can present through atypical forms and merged extrahepatic manifestations. Most atypical forms include relapsing hepatitis and cholestatic hepatitis. Extrahepatic manifestations of HAV are rare, and include evanescent skin rash and transient arthralgias. A 25-year-old male, previously healthy, developed acute hepatitis. Hepatitis A virus was serologically confirmed. No skin efflorescences were seen at the beginning. Over the course of the illness which extended up to fifteen weeks, bilirubin and aminotransferase levels were continuously highly elevated. Nine weeks after the initial presentation he developed a painless, non-pruritic, purpura-like maculopapular erythematous rash over both lower extremities. Five weeks later, the rash had completely disappeared and the patient’s clinical status much improved. This case demonstrates two unusual and unrelated manifestations: prolonged cholestatic form of hepatitis and cutaneous vasculitis. Possible unusual manifestations of this disease should be a reminder of a brief diagnostic examination, which is usually not done in hepatitis A

Drugs with the highest drug expenditure in the Republic of Serbia

Introduction: The policy concerning drugs represents a concentrated effort to achieve better health outcomes for all, with a particular focus on people's access to and rational use of medications. On the basis of pharmacoeconomic analyses, it is possible to modify established prescribing habits, it is possible to influence the creation of guidelines, development strategy and long-term health care planning. Aim: The aim of the work was to determine drugs with the highest expenditure in the Republic of Serbia, and to compare the results obtained in three consecutive years 2016, 2017 and 2018. Also, to analyze which are the most expensive medications listed in the National Register of Medications and what is the trend of changing them. Material and methods: The drug expenditure was monitored using the ATC/DDD methodology. It implies the classification of medications according to the internationally accepted ATC classification of drugs, while DDD, i.e. defined daily dose, is used as a statistical unit for consumption monitoring. The number of DDD/1,000 inhabitants per day provides an insight into how many inhabitants (out of 1,000 of them) used the observed medication and were exposed to its effects during one day. Results: The trend of expenditure of these medications was growing exponentially from 2016 to 2018. The most expensive medications per box are from group J - anti-infective drugs for systemic use and L - antineoplastics and immunomodulators, but their expenditure in the Republic of Serbia is very low. The drugs with the highest price per 1 DDD are: enzymes imiglucerase, laronidase and the biological medication basiliximab in all three years, but considering the indications and rare prescribing, the total cost for these drugs is not high. The largest funds in the Republic of Serbia for the mentioned period were spent on drugs such as: acetylsalicylic acid, paracetamol in combinations, trastuzumab, pantoprazole, amlodipine and rosuvastatin. Comparing the spending on L group of drugs in 2017 compared to 2016, there was a significant increase. Conclusion: The medications with the highest expenditure in the Republic of Serbia are used very little compared to countries with good pharmacotherapy practice. The most expensive drugs are those that are used for special and rare indications, and large amounts of money are not allocated for them as for some cheaper, but more frequently prescribed drugs

VAGINAL CANDIDIASIS – GYNECOLOGICAL ASPECT OF THE PROBLEM

Vaginal candidiasis (VC) is one of the most common reasons for consultations with a gynecologist, with an increasing trend in occurrence in female patients. It is estimated that 75% of all women experience an episode of vulvovaginal candidiasis in their lifetime, 50% of them experience at least a second episode, and 5% have recurrent candidiasis. Cervical and vaginal secretions act as the last line of defense from ascendant infection pathway spreading. Factors that may disturb vaginal ecosystem are: endogenous factors, way of life, infectious factors and iatrogenic factors. The most common cause of VC in 85-90% of cases is C. albicans, but other Candida species tend to be more likely to cause VVC (Candida tropicalis , Candida glabrata , C particulary, C crusei and so on). These non-albicans species have been found to be fluconazole and antimycotics resistant in more than 70% of cases. This is especially true for C. glabrata. There are several predisposing factors that have been associated with VC recurrence and resistance, such as Candida genotypes, resistance and virulence, immunodeficiency, unregulated hyperglycemia, use of oral contraceptives, long-term use of antibiotics. Therapy approach should be individual, including local and oral antimycotics until the symptoms disappear. The maintenance dose can be continuous or intermittent. Due to hormone concentration increase, increase in local glycogen, alternations of vaginal flora, VC incidence in pregnancy is two times higher in comparison to other female population. The problem of vaginal candidiasis requires individual approach, taking into account all the risk factors and accompanying physiological conditions or diseases in female patients

THROMBOPHILIA IN PREGNANCY – CURRENT ISSUE OF MODERN PERINATOLOGY

Pregnancy is a condition of increased affinity to blood clotting. The most important changes of coagulation system in pregnancy involve the increase of the following coagulation factors: fibrinogen production, level of numerous blood coagulation factors- FII, FVII, FVIII, FX, FXII, acquired activated protein C resistance, and the decrease of: fibrinolysis due to the increase of a large number of fibrinolytic activator inhibitors PAI-1 and PAI-2, thrombin activatable fibrinolysis inhibitor TAFI, and levels of proteins S and C. This disease is not a disease on its own, but a group of inherited and acquired coagulation disorders that increase the predisposition to thrombosis. The treatment of choice in pregnancy are low-molecular-weight heparins (LMWHs) which are derived from standard heparin by controlled hydrolysis, thus obtaining heparins of a lower molecular mass. The most commonly used LMWHs are: dalteparin sodium, enoxaparin, nadroparin-calcium, reviparin. LMWH is given in prophylactic doses – low and medium doses in therapeutic doses. Thromboprophylaxis in pregnancy is implemented as: intrapartal, intra- and postpartum according to the official recommendations of the American Association of Obstetricians and Gynecologists (ACOG). Specific recommendations of ACOG refer to the treatment of hereditary thrombophilia in pregnancy

BILATERAL OSSIFICATION OF THE STYLOHYOID LIGAMENT

The stylohyoid ligament extends from the styloid process of the temporal bone to the lesser horn of the styloid bone. Various forms of ossification of this anatomical structure have been described in the literature. In our case, there was bilateral ossification of the stylohyoid ligament, a very rare occurrence. Ossification was partial on the right, and complete on the left side. The right stylohyoid ligament was only loosely attached to the styloid process, followed by a larger, ossified part of the attachment, finally attaching to the lesser horn of the hyoid bone in the form of a connective tissue bond. On the left, styloid process was present with its base and completely ossified stylohyoid ligament all the way to the lesser horn of the hyoid bone