Incidence of brain metastases in early stage HER2 3+ breast cancer patients; is there a role for brain CT in asymptomatic patients?

PURPOSE: Human epidermal growth factor receptor 2 overexpression (HER2 3+) is reported in retrospective studies as a factor that contributes to higher incidence of brain metastases (BM) in patients with metastatic breast carcinoma. Although there are some reports suggesting higher incidence of BM in adjuvant trastuzumab trials, the true incidence, as well as the time of occurrence of BM in early-stage high risk breast carcinoma patients, has not been widely prospectively explored. The main objective of this study was to prospectively explore the incidence of BM during and after adjuvant trastuzumab administration in HER2 3+ early-breast carcinoma patients. METHODS: Two hundred and fifty-eight patients with early, HER2 3+ breast carcinoma have been included in this analysis. Brain computed tomography (CT) scan was scheduled once during adjuvant trastuzumab therapy and thereafter only if central nervous system (CNS) symptoms occurred. RESULTS: Eighty-five patients (33%) underwent brain CT in the absence of CNS symptoms. The median number of trastuzumab cycles at the time of brain CT was 9 (range 4-18). There were no BM detected by brain CT in these 85 asymptomatic patients. However, during a median follow up of 18 months 5/258 patients (1.93%) developed BM, but only 2 (0.77%) while still receiving adjuvant trastuzumab. The median time from breast cancer diagnosis to BM was 24 months (range 14-43). CONCLUSION: BM are a rare event during adjuvant trastuzumab treatment and brain CT screening is not justified in asymptomatic patients with early HER2 3+ breast carcinoma.

[Increase of newly--detected in situ cancers in non-palpable breast lesions].

Great importance in detecting cancer in the phase of in situ lays in the fact that the epithelial layer is deprived of blood and lymph vessels, so metastases may develop only when basal membrane has been broken. This paper includes 46 operated women in whom it preoperatively had been verified suspect non-palpable lesion. The preoperative diagnostics included use of high- resolution mammography, aimed mammography, palpatory examination, as well as fine-needle aspiration (FNA), biopsy and cytologic analysis of the sample. The methodology of this work implies the use of stereotaxic marking, specimen mammography and ex-tempore pathohistology analysis. Out of 46 investigated patients in clinical stage T0N0M0, in whom there were no signs of malignant disease, and according to suspect lesion of initial screening mammography, malignant lesions of breast tissue were diagnosed in 19 patients (41%) intraoperatively. Three of these lesions (15,8%) were histopathologically verified as in situ. Comparing our results with data of the Institute of oncology and radiology of Serbia hospital registry (IORS) for the year 2001, from 1173 patients registered with malignant lesions, only 16 ones (1,4%) had in situ cancer, operated on the basis of the suspect mammography of clinical stage T0N0M0. Statistically significant difference was found related to the number of detected cancers in this early phase of the breast malignant disease. This limits surgical intervention to tumorectomy, with preservation of the remaining breast tissue, what brings to healing, justifying in that way, screening examinations and routine application of the most contemporary diagnostic procedures.

[Preoperative procedures in diagnosis of central and peripheral lung cancer].

BACKGROUND: Actual problem in diagnostics and therapy of lung cancer is early diagnostic and choice of diagnostic procedure. The AIM of this work was to assess the sensitivity of various histocytologic methods in diagnosis of central and peripheral lung cancer lesions. MATERIAL AND METHODS: During 2003-2004, 348 patients with lung infiltrates suspect for malignancy were treated in University of Kragujevac Clinical Center. For the preoperative diagnostics, their sputum, bronchoaspirate, aspirate obtained by fine needle percutaneous biopsy and specimens obtained by forceps biopsy during fiber-bronchoscopy were analyzed using standard cytohistology methods. RESULTS: Lung cancer was diagnozed in 155 out of 348 patients. The malignant lesions were centrally located in 123 patients (79,4%), while peripheral localization was found in 32 patients (20,6%). In the former patients, forceps biopsy was positive in 89,4%, and when combined with bronchoaspirate analysis, positive results were obtained in 91,9% of patients. In patients with peripherally located lesions, fine needly biopsy was positive in 68,8%, while citological analysis of sputum and bronchoalveolar aspirate were positive in only three (9,4%) patients. When all three methods were combined, positive results were found in 25 (78,1%) patients. CONCLUSION: The central localization of tumors was four times greater than the peripheral one. In the patients with central tumour site, the best results were obtained when forceps biopsy specimens and sputum were analysed cytologically. The combination of transcutaneous fine-needle biopsy, bronchoscopy and sputum gave the best results in the group of patients whose lesions were located peripherally.

Synchronous and metachronous flat adenomas in colorectal cancer: single institution experience.

PURPOSE: To investigate the frequency of synchronous and metachronous flat adenomas in patients with colorectal cancer, aiming at achieving early detection and excision of such lesions. PATIENTS AND METHODS: From May 1999 to May 2001, 259 patients with colorectal cancer underwent initial colonoscopy for histological verification of the tumor and detection of any coexisting flat adenoma. Postoperative surveillance colonoscopy at regular intervals was carried out in all patients operated on (n=204) for detection of cancer relapse or the presence of any metachronous flat adenomas. RESULTS: No patient was found with synchronous flat adenoma at the time of diagnosis of colorectal cancer. Postoperatively 7 patients developed 9 flat adenomas. Eight adenomas displayed grade II and 1 grade I-II dysplasia. Of the 9 adenomas 7 had a diameter of

[Principles of lymph node surgery in differentiated thyroid carcinoma]. / Principi hirurgije limfnih nodusa kod diferentovanog tiroidnog karcinoma.

Surgery is the initial therapy in differentiated thyroid carcinoma (DTC). The surgery is performed on organ of tumor origin and regional lymphatic basins. The aim of surgery in DTC is to eradicate all tumor foci, cure the most number of patients, reduce recurrence and mortality rate, and provide good quality of life. There is no doubt between oncologists that the surgery for thyroid carcinoma has no alternative. The extent of surgery is matter of actual controversies. It should be performed by well trained surgeons. Dissection of central and biopsy of supraclavicular and lower third of jugulo-carotid chain of neck lymph nodes is the integral part of surgery in DTC, together with total thyroidectomy. If lymph node metastases are found in jugulo-carotid chain, modified radical neck dissection, unilateral or bilateral is indicated. Dissection of mediastinal lymph nodes should be performed too in cases of involvement. The extent of primary surgery should be dictated by stage of disease and prognostic factors. The quality of surgery and incidence of complications depends prognostic factors, as well as on surgeon's skill and experience. That is why the surgeon is factor of prognosis in treatment of patients with DTC.

[Identification of sentinel lymph nodes in thyroid carcinoma]. / Provera strazarskih limfnih nodusa kod tiroidnog karcinoma.

Sentinel lymph node (SLN) was defined as the first lymph node that the tumor would drain to, within that tumors regional lymphatic basin. In 1998, Kelemen and coworkers have published the first results on SLN lymphonodectomy in thyroid carcinomas. Different methods have been used in a goal of lymphatic mapping (application of vital blue dye and/or radiocolloid). In a period from 2001 to 2003 we have performed SLN biopsy in 64 patients with thyroid tumors. There were 12 cases of thyroid carcinoma. SLN identification rate was 73.44%. We found no false positive or negative results on definitive histopathology. The impact of lymph node metastases in differentiated thyroid carcinoma is still controversial. The management of cervical lymph nodes varies from berry picking to modified radical neck dissection. There is a significant disproportion in percentage of pre and intraoperatively enlarged lymph nodes (27-45%) and histologically confirmed lymph node metastases (80-90%) in papillary thyroid carcinoma. In the current literature the average rate of SLN identification is 91% (66-100%) and when identified, the SLN accurately predicts the disease status of the neck in most patients (80-100%). The SLN biopsy for thyroid carcinoma is good and feasible technique for estimating the cervical lymph node status.

Endothelium-dependent relaxation in perforating branch of human internal mammary artery.

The purpose of the present study was to examine the effect of acetylcholine on perforating branch of the human internal mammary artery (HIMA). Acetylcholine (10(-9)-10(-5)M) induced concentration- and endothelium-dependent relaxation (pEC(50)=7.54+/-0.03, maximal response was 98+/-1.3%) of the precontracted arterial segments. Indomethacin, 4-aminopyridine (10(-5)M) and precontraction with K(+)-rich Krebs-Ringer-bicarbonate solution had no effect on acethylcholine-induced relaxation. N(G)-monomethyl-L-arginine (L-NMMA) (10(-5)M) inhibited relaxation evoked by acetylcholine. Indomethacin applied together with L-NMMA lead to further inhibition of acethylcholine-induced relaxation. Even in the presence of both L-NMMA and indomethacin, 4-aminopyridine had no provoked further inhibition of acetylcholine-induced relaxation of perforating branch of HIMA. It was concluded that the acethylcholine-induced relaxation of isolated perforating branch of HIMA is probably mediated via endothelial production of nitric oxide. However, when NO-synthase is inhibited, acetylcholine-induced vasorelaxation may be, in part, mediated through activation of cyclooxygenase pathway and consequent production and release of prostacyclin or some other cyclooxygenase products.

[Immunologic reactivity in patients with breast carcinoma treated with interferon alpha]. / Imunoloska reaktivnost bolesnica od karcinoma dojke lecenih interferonom alfa.

We investigated the influence of the natural interferon alpha (IFN-alpha) on the nonspecific immune competence in the early stage of breast cancer. The IFN therapy, which started one month after surgery, lasted four months. Control group of patients received no therapy after surgical removal of the tumor. The immunological parameters (the number and function of T and B cells and mononuclear phagocytes) were monitored once a month during five months. In the course of IFN therapy the values of total and active T cells, as well as their proliferative response to PHA, were slightly decreased, while the number of mononuclear phagocytes and their activity was increased. These values returned into normal range at the end of monitoring. Only the phagocyting activity remained at high level. There was no significant difference between two groups of patients, indicating no effect of IFN therapy on the immunological parameters tested.