Association of axillary node status with clinicopathological characteristics and expression of EZH2 and CD44 in primary breast ductal carcinoma.

OBJECTIVE: In order to enhance the prognostic benefit of new molecular markers, the aim of this study was to identify possible association of axillary lymph node (ALN) status and pN with clinicopathological characteristics and expression of EZH2 and CD44 in invasive ductal carcinoma (IDC) of the breast. METHODS: The investigation included 106 patients with IDC who had undergone radical mastectomy at the Clinic of Endocrine Surgery in Nis. Clinicopathologic parameters and immunohistochemical expression of EZH2 and CD44 in primary IDC were investigated in relation to ALN status and pN. RESULTS: Our univariate analysis established that T3-T4 stage, high EZH2, and high EZH2 with ER- were associated with ALN metastasis (p=0.014; 0.003; 0.013). Decreased probability for ALN involvement was found with T1 stage, and low EZH2 with ER+ (p=0.032; 0.022). Multivariant analysis established that high EZH2 in cancer cells was associated with high risk for ALN metastases (p=0.004); T1 tumors were associated with low risk (p=0.037). Higher pN was associated with high EZH2, high EZH2 with ER-, as well as an advanced clinical and disease stage (p=0.006; 0.001; p=0.002, 0.001). Lower pN was associated with ER+, and ER+ with low EZH2 (p= 0.004; 0.012). CD44 was not associated with ALN involvement, nor with pN. CONCLUSIONS: This study revealed association of EZH2 with ALN metastases, where disease stage and expression profiles of EZH2 and ER may have affected regional pN.

Comparison of recurrence patterns of colorectal cancer in laparoscopic and open surgery groups of patients: A meta-analysis.

PURPOSE: The purpose of this meta-analysis was to evaluate differences between laparoscopic and open surgery and also the development of local and distant colorectal cancer (CRC) recurrences in treated patients. METHODS: 2,058 cases treated with laparoscopic surgery and 2,365 cases with open surgery from 20 included studies were analyzed, using the random-effects model. The mean difference and odds ratio (OR) with 95% confidence interval (95%CI) were calculated. An overall and a subgroup analysis was performed according to the type of cancer - colon or rectal, and we registered the operating time, number of dissected lymph nodes and need for intraoperative blood transfusion in the laparoscopic and open surgery group of patients. RESULTS: The operating time in the laparoscopic surgery group was significantly longer than in the open surgery group (mean difference 38.23 min). There was no significant differences in the number of dissected lymph nodes between the two groups when we pooled data for treatment of CRC (p=0.16). The OR of overall and local recurrences was significantly decreased in patients in the laparoscopic surgery group compared to those in the open surgery group (OR 0.83; 95%CI 0.70-0.98; p=0.03) and (OR 0.70; 95%CI 0.50-0.97; p=0.03), respectively. No significant differences were found between patients who underwent laparoscopic surgery and those that had open surgery for distant recurrences after CRC treatment. CONCLUSIONS: There was statistically significant difference between laparoscopic or open surgery and development of local and overall CRC recurrences.

Ten years of using adjuvant trastuzumab in breast cancer in Serbia - Single institution experience.

PURPOSE: The purpose of this study was to determinate disease-free interval (DFI) and overall survival (OS) in HER2-positive breast cancer patients who received adjuvant trastuzumab at the University Clinic of Nis, Serbia, and to investigate the influence of clinicopathological and biological characteristics of the tumor on prognosis. The second aim was to determinate the most frequent cause for the treatment discontinuation, recurrence rate, as well as the site of most common localization of the first recurrence of disease. METHODS: This research was conducted as a retrospective study at the University Oncology Clinic, Clinical Centre in Nis. The study included 238 patients who were operated and treated for HER2-positive breast cancer between January 1st, 2007 to September 30th, 2012 and followed up until December 31st, 2016. Trastuzumab was administered concurrently with taxanes, if administered, or after the completed anthracycline-based chemotherapy. RESULTS: After a median follow up of 69 months the 5-year DFI was 65.9% and 5-year OS was 81.8% and, as expected, significantly longer in the group of patients with smaller tumors, a smaller number of positive axillary lymph nodes, as well as a lower stage of disease (p<0.0001). Patients older than 65 years had a longer DFI compared to the 45-65 and under 45 age groups of patients (p=0.01). No statistical significance was found in the length of DFI in relation to the histological tumor subtype, tumor grade, or the status of hormone receptors. Unlike DFI, a longer OS was recorded in the group of patients with lower tumor grade (p=0.03) and there was no statistically significant difference in survival regarding the age of patients (p=0.07). Recurrence occurred in approximately one third of the patients (38.23%), mostly in the form of local recurrence. Adjuvant therapy with trastuzumab was not completely carried out in 18.49% of the patients, the most common reason being the progression of disease. CONCLUSIONS: A long median follow up period of 69 months indicated that anti-HER2 monoclonal antibody trastuzumab, after anthracycline-based chemotherapy or concurrently with taxanes, is efficient and safe in treating early breast cancer.

Serbian consensus of neoadjuvant therapy for breast cancer: NeoPULSE.

Even though surgery is the primary treatment of operable breast cancer, it has been known for decades that the administration of postoperative adjuvant or preoperative neoadjuvant therapy is extremely important. Indications for neodjuvant therapy administration have been expanded over the years, and nowadays this kind of treatment represents an inevitable option in early breast cancer treatment. The NeoPULSE project, which gathered a group of experts in the field of breast cancer from five Serbian university centres, was formed with the aim to define optimal breast cancer diagnosis, indications for neoadjuvant therapy, therapeutic combinations in relation to molecular/biological parameters of breast cancer, as well as the treatment after neoadjuvant therapy. During two separate expert meetings involving surgeons, medical oncologists, radiation oncologists, a pathologist, and a "Blueprint" workshop, the project participants answered questions over the indications for neoadjuvant therapy. The first part covered local practice and referred to the existence and work of a multidisciplinary team, as well as commonly applied therapeutic regimens in the neoadjuvant setting. Experts analysed personal views regarding indications for the administration and benefits of neoadjuvant therapy, their perception on the correlation between achieving a pathological complete response (pCR) and the outcome of treatment, as well as the attitude towards controversies about this type of treatment, primarily regarding a possible change in the receptor status after therapy and therapeutic options after a suboptimal response. The analysis of the answers pointed to problems and deviations from recommendations in everyday clinical practice, based on which appropriate solutions were proposed. The establishment of such a panel and consensus is an attempt to modernize multidisciplinary teams in Serbia, achieve reaching uniform decisions of all subjects dealing with breast cancer, and therefore, at least in one segment, improve breast cancer treatment in Serbia.

Acute Suppurative Thyroiditis with Thyroid Abscess and Bilateral Pneumonia: A Case Report.

Acute suppurative thyroiditis (AST) leading to thyroid abscess is a rare clinical entity. The aim of this article is to demonstrate a case of severe bilateral pneumonia which originated from a thyroid abscess. The authors report the case of a 57-year-old woman with severe bilateral pneumonia of thyroid origin. The patient had a painful throat and dysphagia for 2 or 3 days. She also had a history of mild fever and hard breathing with a discreet cough 7 days prior to hospital admission. In the past few months, the patient had frequent pneumonias. The patient was treated with a culture-appropriate antibiotic and total thyroidectomy. Primary recommendations for treatment of complicated infections of thyroid origin consider a multidisciplinary approach. Recurrent pneumonia in patients with thyroid nodules may be the result of thyroid inflammation, and, in such patients, neck ultrasound should be conducted as part of the diagnostic workup.

Characteristics and outcomes of patients with multifocal/multicentric and unifocal breast cancer.

PURPOSE: The clinical behavior and outcome of multifocal (MF) and multicentric (MC) breast tumors are not well characterized. The purpose of this study was to compare the prognosis of MF/MC tumors with unifocal (UF)tumors and its correlation with other pathological characteristics and patient outcomes. METHODS: Eighty-three patients with MC/MF breast cancer and 501 with UF breast cancer treated at the Surgical Clinic Nis were studied. We compared MC/MF and UF breast cancer patients with respect to demographics, tumor characteristics- adjuvant systemic therapy, local recurrence-free survival (LRFS) and overall survival (OS). RESULTS: There was no significant statistical difference between the two groups with respect to mean age at diagnosis, tumor grade, nodal status, estrogen receptor status, lymphovascular invasion (LVI) and adjuvant systemic therapy. The MC/MF group had more patients with modified radical mastectomy and the UF group had more patients with breast-conserving surgery. Cox multivariate regression analysis showed that the regional lymph node metastases and LVI were the most important predictors of 5-year OS rate. During this period, locoregional recurrence was registered in 29 (5.78%) patients in the UF group and in 5 (6.02%) patients in the MF/MC group (p=0.48). No statistically significant differences in the 5-year LRFS and OS between the two groups were noticed. CONCLUSION: The prognostic value of MF/MC disease is still not well known, although some studies have suggested that it is associated with a worse prognosis. This study showed no statistically significant difference in the 5-year LRFS and OS between UF and MF/MC groups.

Correlation between the season, temperature and atmospheric pressure with incidence and pathogenesis of acute appendicitis.

Introduction: There is very little literature data on the correlation between the seasons, temperature and atmospheric pressure, and pathogenesis of acute appendicitis (AA). Objective: The aim of this research is to investigate the association between the seasons, changes in atmospheric temperature and pressure, and patients' age and severity of the clinical form of AA in the city of Nis Methods: This study included 395 patients diagnosed with AA, who, during the two-year period, from July 1st 2011 to June 30th 2013, were hospitalized and operated on at the Department of General Surgery, Clinical Center in Nis, Serbia. Results: The increased average daily values of barometric pressure by 1 millibar on the day when the event took place was associated (p < 0.05) with the decrease of total risk of the occurrence of appendicitis by 2.2% (0.2­4.1%). In all observed patients, each increase of the mean daily temperature by 1°C three days before the event took place (Lag 3) was associated (p < 0.05) with the increase of total risk of the occurrence of appendicitis by 1.3% (0.1­2.5%). Conclusion: According to the results of this research, we can conclude that patients' sex, age and severity of the clinical form of AA are not in connection with the seasons, while there are certain connections between appendicitis occurrence and atmospheric temperature and pressure.

Total thyroidectomy as a method of choice in the treatment of Graves' disease - analysis of 1432 patients.

BACKGROUND: Graves' disease represents an autoimmune disease of the thyroid gland where surgery has an important role in its treatment. The aim of our paper was to analyze the results of surgical treatment, the frequency of microcarcinoma and carcinoma, as well as to compare surgical complications in relation to the various types of operations performed for Graves' disease. METHODS: We analysed 1432 patients (221 male and 1211 female) who underwent surgery for Graves' disease at the Centre for Endocrine Surgery in Belgrade during 15 years (1996-2010). Average age was 34.8 years. Frequency of surgical complications within the groups was analyzed with nonparametric Fisher's test. RESULTS: Total thyroidectomy (TT) was performed in 974 (68%) patients, and Dunhill operation (D) in 221 (15.4). Carcinoma of thyroid gland was found in 146 patients (10.2%), of which 129 (9%) were a microcarcinoma. Complication rates were higher in the TT group, where there were 31 (3.2%) patients with permanent hypoparathyroidism, 9 (0.9%) patients with unilateral recurrent nerve paralysis and 10 (1.0%) patients with postoperative bleeding. Combined complications, such as permanent hypoparathyroidism with bleeding were more common in the D group where there were 2 patients (0,9%), while unilateral recurrent nerve paralysis with bleeding was more common in the TT group where there were 3 cases (0,3%). CONCLUSIONS: Frequency of complications were not significantly statistically different in relation to the type of surgical procedure. Total thyroidectomy represents a safe and efficient method for treating patients with Graves' disease, and it is not followed by a greater frequency of complications in relation to less extensive procedures.

Incarcerated inguinal hernias surgical treatment specifics in elderly patients.

BACKGROUND/AIM: Incarcerated inguinal hernias surgical treatment represents one of the most frequent surgical treatments in elderly patients. The percentage of incarcerated inguinal hernias urgent surgical treatments is growing exponentially with the age in patients over 50. The aim of the study was to investigate some of the factors that may have impact on the incarcerated inguinal hernias surgical treatment outcome in elderly patients. METHODS: The study included 180 patients classified in two groups: the study group (> 65 years of age) and the control group (< or = 65), managed in the period from January 2005 till March 2009 at the General Surgery Clinic, Clinical Center Nis. RESULTS: Most of the patients had right inguinal hernia (52.6%, the study group; 59.1%, the control group). All the study group patients suffered from some of accompanying chronic diseases (100%), opposite to 39 (59%) patients of the control group. Synthetic material was implanted in 124 (68.90%) patients, while the tension technique was performed in 65 (31.1%) patients. The duration of incarceration more than 24 h (p = 0.015), previous abdominal surgery (p = 0.001), the American Society of Anesthesiologists physical status classification system (ASA classification) (p = 0.033) and the presence of chronic diseases (p = 0.01) appeared to be statistically significant risk factors for performing intestinal resection in the study group, while in the control group they represented risk factors, but not at the level of statistical significance (p < 0.05), except for the duration of incarceration (p = 0.007). A higher ASA stage (p = 0.001) and the presence of bowel resection (p <0.001) are the most important risk factors for lethal outcome in both groups of patients. CONCLUSION: Incarcerated inguinal hernia in elderly patients is a serious problem. A higher ASA score and the presence of bowel resection are the most important factors related to unfavorable outcome.

[Assessment of axillary lymph nodes involvement in patients with breast cancer depending on the tumor size and its histological and nuclear grades].

BACKGROUND/AIM: There are a lot of studies aiding to the opinion that the involvement degree of axilla lymph nodes grows depending on increase of breast tumor size, and its histological and nuclear grades. The aim of this study was to assess the risk of axillary lymph nodes involvement, as well as the relation between the tumor size, histological and nuclear grades in a group of female patients who underwent breast cancer surgery, including levels 1-3 axillary dissection. METHODS: Investigationcovered 900 patients operated on during 2005-2008 who underwent modified radical mastectomy including axillar dissection. We assessed a number of involved lymph nodes, depending on tumor macroscopic size (T), histological grade (HG) and nuclear grade (NG). RESULTS: A total number of examined lymph nodes was 9977. The incidence of involved lymph nodes was from 18.6% with T1 tumor size up to 60.2% with T4 tumor size. Concerning histological grade, the number of involved lymph nodes ranged from 14.2% (HGI) to 45.1% (HGIII); while in terms of nuclear grade, the number of involved lymph nodes ranged from 17.4% (NGI) to 54.5% (NGIV). By using chi2-test for trend and odds ratio (OR), the results showed that the axillary lymph nodes involvement degree was increased with the increase of the tumor size and its histological and nuclear grades. The risk of axillary lymphatic nodes involvement was 1.43 times higher in the group of T2 tumors size compared to the smaller tumors T1 size, and even up to 6.62 times higher in case of T4 tumor size. It was also increasied from 1.79 times for HGII to even 4.98 times for HGIII, and from 1.44 times for NGII to 5.71 times for NGIV. CONCLUSION: In breast cancer patients, there is a strong correlation between tumor size, its histological and nuclear grades and the risk of axillary lymph nodes involvement.

Diagnostic importance of pulse oximetry in the determination of the stage of chronic arterial insufficiency of lower extremities.

INTRODUCTION: Chronic arterial insufficiency (CAI) of lower extremities is important socio-economical and healthcare problem, due to its high incidence of morbidity, disability and mortality. OBJECTIVE: The aim of our work was to determine the diagnostic importance of pulse oximetry in the early detection of stage of lower extremities CAI based on peripheral arterial oxygen saturation of haemoglobin (SpO2). METHODS: Prospectively, we analyzed a group of 50 patients, admitted at the Vascular Department of Surgical Clinic in Nis during the period from September 2006 to October 2007, with evident symptoms and signs of different stages of lower extremities CAI verified by ultrasonography. In patients with lower extremity disorder of tissue arterial capillaries, SpO2 was determined by pulse oximetry. RESULTS: Using pulse oximetry, depending on the of stage of lower extremities CAI, we revealed a considerable difference in the stages of functional ischemia SpO2: Fontaine I - 95.33 +/- 1.41%, Fontaine IIa - 92.14 +/- 2.27% and Fontaine IIb - 79.67 +/- 2.73%; in stage critical ischemia SpO2: Fontaine III - 62.54 +/- 4.39% and Fontaine IV - 47.67 +/- 6.16%. In 3 patients with gangrenous foot and fingers SpO2 was immeasurable and progressive decrease in SpO2 of arterial capillaries (p < 0.01 between stages). CONCLUSION: Due to the reliability and simplicity of pulse oximetry it can be a routinely used diagnostic device for patients with early determined stage of lower extremities CAI.

Serum anti-Helicobacter pylori IgA and IgG antibodies in asymptomatic children in Serbia.

The aim of this study was to determine the seroprevalence of Helicobacter pylori and the distribution of anti-H.pylori IgA and IgG antibodies in asymptomatic children aged between 7 and 18 y. We studied the serum samples of 283 children using the commercial ELISA test for the detection of anti-H. pylori IgA and IgG antibodies. The overall prevalence of anti-H. pylori antibodies was 36.4%. The seroprevalence was 35%, 28.3%, 37.5%, and 42.2% for the ages of 7, 10, 14 and 18 y, respectively. Serum IgG antibodies alone were detected in 88.3%, IgA alone in 4.9%, and both IgA and IgG antibodies were detected in 6.8% of samples. The mean levels of IgG antibodies to H. pylori increased with age. We concluded that the prevalence of H. pylori antibodies in Serbian children was high (36.4%), ranging from 35% to 42.2%. The detection of IgG antibodies is useful for the determination of seroprevalence in asymptomatic children.

Hepatitis C virus genotypes and the development of hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to investigate the prevalence of hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC) in our geographic area, and to determine if there is a correlation between HCV genotypes and the development of HCC. METHODS: Thirty-six patients with HCV-related HCC and 35 controls with HCV-associated cirrhosis without HCC were studied. The diagnosis of HCV infection was performed by the enzyme-linked immunosorbent assay test for the detection of anti-HCV antibodies and by reverse transcription-polymerase chain reaction for the detection of HCV-RNA. HCV genotyping was performed by line probe assay-Inno-LIPA HCV II. The diagnosis of underlying disease in the patients with HCC was performed on the basis of clinical, biochemical or histological evidence. RESULTS: Genotype 1b was found in 28 (77.77%) patients with HCC, and in 16 (45.71%) controls. There was significant difference in the prevalence of genotype 1b between the patients with HCC and those with cirrhosis without HCC (P<0.05). Having analyzed the diagnosis of underlying diseases, underlying cirrhosis in 29 (80.55%) and chronic active hepatitis in 7 (19.44%) patients with HCC was found. CONCLUSION: Results of the present study suggest that there is a correlation between HCV genotype 1b and the development of HCC. Our findings also add support to the hypothesis that cirrhosis is a major step in liver carcinogenesis associated with HCV, which suggests an indirect role of HCV in the pathogenesis of HCC.

[Systemic inflammatory response syndrome in surgical patients with sepsis]. / Sindrom sistemskog zapaljenjskog odgovora kod hirurskih bolesnika sa sepsom.

Systemic inflammatory response syndrome and sepsis are common in surgically treated patients. Systemic inflammatory response syndrome represents a major factor of morbidity and mortality in these patients. The pathogenesis of these syndromes has been increasingly clarified. The objective of this review is to present an overview of our current understanding of the physiology underlying these conditions.

Breast cancer in elderly women.

Although the number of elderly patients with breast cancer is increasing, knowledge about possible differences in the biology and clinical outcomes of breast cancer according to age is limited. Retrospectively were followed: diagnosis, surgical treatment, stage of disease, histology, and survival of breast cancer treated women at the Surgical and Oncological Clinic in Nis between 1985 and 1990. Patients were divided in two groups: study (=65 years) and control (<65 years). The study involved 2196 women (862 study group; 1334 control group). Ductal carcinoma was the most frequently observed histological type (70.3% versus 61.92%). The majority of our patients presented with early-stage disease (69.02% versus 60.20%). Estrogen receptor positive tumors occurred in 67.88% of elderly patients versus 28.42% of young cases, and negative axillary lymph nodes were observed in 45.78 and 34.40% of patients in the elderly and young group, respectively. Modified radical mastectomy was selected by a large proportion of patients in both groups. Adjuvant radiation and chemotherapy were more frequently performed in the younger group (P < 1 x 10(-8)). There is no significant difference in disease-specific survival by age. In our population the presentation, surgical treatment, and survival from breast cancer is similar in older and younger women.

[Coagulation status in patients with deep venous thrombosis of the lower extremities]. / Koagulacioni status kod bolesnika sa trombozom dubokih vena donjih ekstremiteta.

PURPOSE: Venous thromboembolism is a relevant social and health care problem for its high incidence, pulmonary embolism-related mortality and long-term sequelae which may be disabling (post-thrombotic syndrome and ulceration). PROCEDURES: The aim of our work was to establish the presence of coagulation disorders (hypercoagulable states) in the patients with deep vein thrombosis (DVT) of the leg. Prospectively we have analyzed a group of 30 patients with echosonographicaly verified DVT of the leg who were admitted to the department of vascular surgery from August 1st 2000 to July 31st 2001. The following parameters were monitored: prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (Fib), alpha 2 anti-plasmin (A-2 AP), D-dimer (DD), antithrombin III (AT III) and factor VII. FINDINGS: Activation of the coagulation process was registered. The values of monitored coagulation parameters are shown in table 1. Plasma levels of monitored parameters in the patients with DVT of the leg were significantly higher than in the control subjects. CONCLUSION: In patients with a DVT a hypercoagulable state is common finding. Some parameters of coagulation activity such as D-dimer might be of great interest in the diagnostic strategy of DVT.