Safety and efficacy of addition of bevacizumab to oxaliplatin-based preoperative chemotherapy in colorectal cancer with liver metastasis- a single institution experience.

PURPOSE: To evaluate the safety and efficacy of the addition of bevacizumab to oxaliplatin-based preoperative chemotherapy in metastatic colorectal cancer (mCRC) patients. METHODS: Between August 2008 and December 2011, 51 patients with histologically documented CRC and liver metastases were treated with first-line oxaliplatin-based therapy plus bevacizumab: FOLFOX 4 (oxaliplatin, folinic acid and 5-FU) plus bevacizumab or OXFL mod.Mayo (folinic acid, oxaliplatin and 5-FU) plus bevacizumab. RESULTS: The mean patient age was 59.69+ 9.38 years (range 38-78) and 34 (66.67%) were male. Complete response (CR) was achieved in 7 (13.73%) patients, partial response (PR) in 29 (56. 86%) and stable disease (SD) in 6 (11.76%); progressive disease (PD) was registered in 9 (17.65%) patients. Disease control rate was 82.36% (42 patients). Liver resections were performed in 37 (72.55%) patients vs those without resection (p<0.01). The same regimen without bevacizumab was administered postoperatively to 18 (42. 86%) patients. The mean progression free survival (PFS) was 9.90±7.07 months (range 3-26) and was significantly longer in patients with postoperative therapy (p<0.001). Treatment-related toxicity appeared in 28 (54. 90%) patients vs those who did not (p<0.001) Independent of grade, nausea (19.61%), leucopenia (17.65%) and peripheral neuropathy (17.65%) were the most frequent toxicities. Chemotherapy was postponed in 9 (17.65%) patients due to grade 3-4 toxicities. The most frequent grade 3 or 4 toxicities were leucopenia (5.88%) and hypertension (3.92%). CONCLUSION: Bevacizumab plus oxaliplatin-based treatment is safe and efficient as preoperative treatment of mCRC with primarily unresectable liver metastases. Liver resection could offer a possibility for long-term survival in these patients.

Current and future anti-HER2 therapy in breast cancer.

The therapeutic strategy for breast cancer with the use of targeted drugs is, at present, mainly focused on coping with HER2. Currently, lapatinib and trastuzumab are in widespread use. Virtually all completed and in progress clinical trials have demonstrated a significant enhancement in the rate of pathologic complete response (pCR), the primary endpoint in these studies, in cases of patients with HER2-positive breast cancer that received trastuzumab in the neoadjuvant setting. Use of lapatinib in the neoadjuvant setting should be considered experimental. When a 12-month course of trastuzumab was added to adjuvant chemotherapy, the disease-free survival (DFS) was greater and the overall survival (OS) was also greater. Although trastuzumab is approved as single-agent therapy, most patients are treated with trastuzumab plus cytotoxic agents. Trastuzumab, administered as single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Dual targeting approach with a combination of trastuzumab and lapatinib improved progression-free survival (PFS) as compared with lapatinib alone in patients with metastatic breast cancer who have not had a response to trastuzumab. The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged PFS. Novel anti-HER2 targeted therapies are needed to utilise novel approaches to combat trastuzumab resistance.

The application of magnetic resonance imaging in preoperative evaluation of patients with endometrial carcinoma.

PURPOSE: The aim of this paper was to assess the usefulness of the preoperative application of magnetic resonance (MRI) imaging in patients with confirmed endometrial carcinoma. METHODS: This prospective study included 50 patients with endometrial cancer. MRI was used for preoperative disease staging and in planning the operative treatment. The parameters monitored by MRI were compared with the findings of curettage pathological examination. Estimated were the depth of myometrial invasion, the involvement of the cervix by the tumor, the presence of adnexal metastases and regional lymph nodes. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the MRI in relation to the aforementioned clinicopathological parameters were assessed. RESULTS: The presence of myometrial invasion was estimated with 100% specificity, 86% sensitivity, 100% PPV and 40% NPV. The estimation of the depth of myometrial invasion (>or<50%) was defined with 89% sensitivity, 54% specificity, 83% PPV and 60% NPV. MRI provided valuable data about cervical invasion (100% PPV for the presence of cervical invasion and 55% PPV for the depth of cervical invasion), thereby helping to decide on the kind of surgical intervention, the choice of approach (open or laparoscopic surgery) and the choice of the surgeon. CONCLUSION: MRI is useful and reliable in preoperative evaluation. The information obtained by MRI provides space and time for planning the treatment modality.

Breast cancer in women under 40 years of age.

PURPOSE: It is widely believed that breast cancer in young women is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinicopathological and biological characteristics in young patients with breast cancer. METHODS: The study enrolled 1029 consecutive female breast cancer patients who were admitted to the Clinical Centre Nis between July 2002 and December 2008. RESULTS: 91 (8.8%) patients were under and 938 (91.2%) were over 40 years. The mean age was 35.9 years for those under 40 years and 58.3 for those older than 40 years. In both patient groups, left breast was most commonly involved; the most common primary tumor site was the upper lateral quadrant; the most common histological type was ductal carcinoma; histological and nuclear grade 2 was most common. In the younger group of patients, the proportion of patients with T3 and T4 disease was higher (13.0 vs. 9.3% and 16.5 vs. 12.0%), the number of patients with histological and nuclear grade 3 disease was higher (27.5 vs. 24.7% and 37.4 vs. 33.2%), the proportion of patients with 4-9 and >10 positive lymph nodes was higher (22.6 vs. 18.3% and 7.1 vs. 4.0%), and the percentage of family history of breast cancer was higher (5.5 vs. 3.1%), without statistically significant differences between the two age groups. Patients in the younger age group exhibited higher estrogen (ER)/progesterone (PR) receptor negativity (32.6 vs. 24.4%) (p<0.05). CONCLUSION: Although uncommon, breast cancer in young women is worth special attention. The underlying causes of the disease must be investigated in large population- based studies in the future.

Concurrent chemoimmunotherapy: is it still the best option for the treatment of metastatic melanoma in patients with good performance status?

PURPOSE: To determine the efficacy, toxicity and survival of metastatic melanoma patients with Eastern Cooperative Oncology group good performance status (ECOG PS 0-1) receiving concurrent chemotherapy and immunotherapy. METHODS: From March 2003 to August 2008, 25 patients with metastatic melanoma were enrolled in the study. No patient had previously received chemotherapy or immunotherapy. Patients with ECOG PS 0-1 were treated with cisplatin+vinblastine+DTIC (CVD) and interferon-A2a (IFN-a). RESULTS: Response rate was 11/25 (44%): complete response (CR) 2, partial response (PR) 9, stable disease (SD) 11, progressive disease (PD) 3. Adverse effects were mild. The most common toxicities were nausea, vomiting and fever. Grade 3 and 4 toxicity was more common in hematologic parameters. No treatment-related deaths occurred. The median overall survival (OS) was 14 months and time to progression 8.0 months. CONCLUSION: Concomitant chemoimmunotherapy appeared to be a beneficial option for metastatic melanoma patients with good PS. Therapeutic approaches with less toxicity and regimens that could improve OS are still highly desired in the treatment of advanced malignant melanoma.

Therapy of stage IV B anaplastic thyroid carcinoma: single institution experience.

PURPOSE: To evaluate the efficacy of radiotherapy and chemotherapy in stage IV B anaplastic thyroid carcinoma (ATC). PATIENTS AND METHODS: From 1997 to 2007, 16 inoperable patients (12 females, 4 males, median age 60 years, range 27-71) with pathologically confirmed ATC without distant metastases (UICC stage IV B) were treated with radiotherapy and chemotherapy at our Institution. Five patients had Eastern Cooperative Oncology Group (ECOG) performance status 1, and 11 ECOG 2. All patients received the planned radiotherapy tumor dose of 60 Gy. Radiotherapy was followed by chemotherapy with doxorubicin 60 mg/m(2) and cisplatin 40 mg/m(2) every 3 weeks. The primary study endpoint was response rate (RR) and secondary endpoints were toxicity and overall survival (OS). RESULTS: Only one patient achieved complete response (CR: 6.25%, 95% CI: 0-35) and 3 patients (18.75%, 95% CI: 4-46) partial response (PR), for an overall response rate (ORR) of 25% (95% CI: 7-55). No toxic deaths occurred and no grade 4 adverse events were registered after radiotherapy. Grade 4 toxicity was seen in 3 patients (18.75%, 95% CI: 4- 46) after chemotherapy. Mean patient OS was 12.33 months (95% CI: 9.09-15.56) and median OS 11.0 months (95% CI: 8.56-13.44). CONCLUSION: Radiotherapy and chemotherapy of stage IV B anaplastic thyroid carcinoma are well tolerated. Although the clinical benefit was 50%, survival rates remain low with OS of no more than 2 years.

Chemotherapy in carcinomas of unknown primary site.

PURPOSE: Carcinomas of unknown primary site (CUPS) are highly malignant diseases with a usually ominous prognosis. We report on the efficacy of chemotherapy in the treatment and survival of patients with CUPS. PATIENTS AND METHODS: The study involved 63 patients with metastatic CUPS. Following routine light microscopy, the histological findings were classified into 3 groups: squamous cell carcinoma - 8 patients; adenocarcinoma - 33 patients; and undifferentiated carcinoma - 22 patients. Combination chemotherapy with doxorubicin 50 mg/m(2) (day 1), cisplatin 60 mg/m(2) (day 1), and etoposide 120 mg/m(2)/day (days 1-3) every 3 weeks was administered to 32 patients (20 females and 12 males), aged 29-70 years (median 54 years) who met the inclusion criteria. All patients with stable disease (SD), partial response (PR) or complete response (CR) received 6 cycles of chemotherapy. RESULTS: CR was achieved in 3 (9.4%), PR in 12 (37.5%), and SD in 10 (31.2%) patients. Seven (21.9%) patients had progressive disease (PD). The overall response rate (RR) was 46.9% (15/32) and the median response duration of CR+PR was 11 months (range 4-43(+) months). The overall survival (OS) of patients treated with chemotherapy (n=32; 50.8%) was better compared with the OS of those not receiving chemotherapy (n=31; 49.2%/; p <0.01). Also the 2-year survival of patients with chemotherapy (40%) and without chemotherapy (0%) implies potential curability in a specific subset of these patients. CONCLUSION: The usage of the aforementioned doses and chemotherapy scheme appears to improve the outcome of patients with carcinoma of unknown primary site.

Adjuvant chemotherapy of premenopausal breast cancer patients and patients under 35 years of age.

Micrometastases in patients with primary breast cancer are the rationale for adjuvant systemic treatment. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) sequential studies have shown that adjuvant systemic therapy decreases recurrence and prolongs survival. According to tumour and patient-related prognostic factors, the risk for relapse could be evaluated. If the risk for relapse is over 10% for 10 years, adjuvant systemic therapy is indicated. Adjuvant chemotherapy is associated with a greater 15-year absolute reduction in death in premenopausal than in postmenopausal patients. Anthracycline- based regimens have demonstrated superiority over classic cyclophoshamide, methotrexate and 5- fluorouracil (CMF) combination chemotherapy, and the role of taxanes is questionable. Timing and duration of adjuvant chemotherapy plays an important role in its individualization. The need for tailored treatments in premenopausal patients is most pronounced in women under 35 years of age at diagnosis.

Simultaneous or sequential chemotherapy for locally advanced breast cancer.

Chemotherapy of breast cancer is still an area of intensive research. Based on mathematical model of tumor cell growth kinetics, a novel concept of chemotherapy in breast cancer was launched which implies dose-densification of chemotherapy through the use of sequential non crossresistant single agents or regimens. The relative infrequency of locally advanced breast cancer (LABC) has limited the speed of clinical progress in this area. The introduction of primary (neoadjuvant) systemic chemotherapy (PSCT), however, improved the outcome of patients with LABC. The first data concerning neoadjuvant sequential chemotherapy were related to primary operable breast cancer. Many studies, using the two most active classes of cytotoxic drugs, anthracyclines and taxanes, in primary breast cancer, showed that sequential PSCT was superior to simultaneous combination chemotherapy in terms of enhancing the rates of patients rendering suitable for breast-conserving (BC) treatment. There are few trials dealing with sequential PSCT in LABC. In the majority of them sequential dose-dense PSCT was administered because the rapid delivery of the most active cytotoxic drugs (anthracyclines and taxanes) is necessary to achieve reduction of the size of the primary tumor, to increase the possibility of BC treatment and to eliminate occult distant micrometastases, contributing thus to possible prolongation of survival. This article summarises recent data concerning sequential PSCT in LABC in order to evaluate its possible use in clinical practice.

[Continuous ambulatory measurement of blood pressure in children--personal experience]. / Kontinuisano ambulatorno merenje krvnog pritiska kod dece--nasa iskustva.

UNLABELLED: Ambulatory blood pressure monitoring (ABPM) during normal daily activities and during night, when the patient is asleep, is a new method of measuring blood pressure (BP) in children, used for better diagnosis and treatment of hypertension. Compared to casual BP measurements, it documents normal daily BP variations, BP during sleep, the influence of emotional and physical stress on BP and is a better predictor of hypertension associated with end-organ damage. However, the experience in ABPM in children is still limited. In our country ABPM has been used since recently, and first results are referred to children with end-stage renal failure. SUBJECTS AND METHODS: ABPM was performed in two groups of children: group A consisted of 61 children, aged 14.3 +/- 2.9 (mean +/- SD) yrs in whom intermittent outpatient BP measurements (for at least 3 months) suggested the diagnosis of hypertension (according to the data of Second Task Force); group B consisted of 52 patients (pts), aged 12.8 +/- 4.6 yr with renal disease. Four pts from group A (6.6%) and 20 pts from group B (38.5%) received antihypertensive therapy (captopril, nifedipine, furosemide and propranolol ). All children from group A and half of the children from group B had normal renal function. Eighteen pts from group B were on chronic haemodialysis (34.6%). Blood pressure was recorded during a 24-hour period except in haemodialyzed pts (48 h) (Table 1). Results of BP measurements are presented as the mean values of BP during a 24-hour period, during normal daily activities and during sleep. We used the age- and gender-appropriate 95th percentile from the Task Force Study as the daytime upper-limit of normal and 10% lower for the upper-limit at night. According to BP load (the percentage of BPs exceeding the upper limits of normal for age), children were assumed to have mild-to-moderate hypertension (BP load between 20% and 40%) or severe hypertension (BP load more than 40%). The success of antihypertensive therapy was evaluated after 1-3 months in 11 pts (twice in 10 pts and three times in one pt). RESULTS: In group A 39.4% of pts were normotensive and 36.1% were without antihypertensive therapy, 58.4% of normotensive and 40.5% of hypertensive pts had blunted circadian BP rhythm (nocturnal BP reduction of less than 10% of diurnal values) (Graph. 1). In group B 38.5% of pts were normotensive and 27% were without antihypertensive therapy. In the group of normotensive pts alteration of circadian BP rhythm was found in 40% of pts with normal renal function, 80% of pts with chronic renal failure and in 100% of pts with terminal renal failure, while in the hypertensive group, altered circadian BP rhythm had 68%, 100% and 92% of pts, respectively (Graph 2). Mild-to-moderate hypertension had 54% of hypertensive pts from group A and 37.5% of hypertensive pts from group B. Severe hypertension was more frequent in group B (62.5%) comparing to group A (46%). The effectiveness of antihypertensive therapy was assessed in 11 pts. In 69.2% of pts BP became normal or was significantly decreased, in 23.1% of pts BP was not changed and 7.7% of pts had higher values of BP. DISCUSSION: ABPM is very useful for diagnosing white coat hypertension. Like other authors, we have pointed out that more than one third of pts who were hypertensive according to usual BP measurements had normal 24-hour BP and we classified them as white coat hypertensives. More than a half of the pts had blunted circadian BP rhythm, and as it is not certain whether they will become hypertensive in adulthood they should be periodically controlled. There are several proofs that results of ABPM have a better correlation with hypertensive end-organ damage; therefore ABPM is used for assessing the severity of hypertension. In our former work, we showed excellent correlation of BP with left ventricular mass index in children with end-stage renal failure. (ABSTRACT TRUNCATED)

[Continuous ambulatory blood pressure measurement--a new method for the detection of arterial hypertension in children]. / Kontinuisano ambulatorno merenje krvnog pritiska--nov metod u otkrivanju arterijske hipertenzije kod dece.

Blood pressure measurements obtained in a physicians office may not reflect the patients blood pressure during the whole day. Ambulatory blood pressure monitoring provides information about blood pressure during normal daily activities and night sleep. Further, the results of ambulatory blood pressure monitoring are in excellent correlation with end-organ damages. The paper discusses the chronobiology of blood pressure, the clinical use of ambulatory blood pressure monitoring, including the identified patterns of blood pressure, the correlation with end-organ damage and its use in clinical trials of antihypertensive medications.

[Serum osteocalcin in children with chronic renal insufficiency]. / Osteokalcin u serumu kod dece s hronicnom insuficijencijom bubrega.

UNLABELLED: The research of the bone metabolism has undergone a long evolution which began with the use of radioisotopes in calcium kinetic studies and went through the determination of several humoral parameters like alkaline phosphatase (ALP), hydroxyproline and intact immunoreactive parathyroid hormone (iPTH) and finally to the assay of a new serum and urinary parameters of bone metabolism, like osteocalcine (OC) and procollagen and collagen metabolites. The X-ray study of the skeleton, densitometric techniques, computerized tomography, scintigraphy and NMR are used for visualization of bone changes, but bone biopsy and histomorphometry provide the most precise evaluation [1]. Disorders of bone and mineral metabolism in children with chronic renal failure (CRF) are an almost regular occurrence; so early discovery and treatment of these changes are very important [2]. The aim of this study was to measure the serum OC level in children with CRF and terminal renal failure (TRF), treated with chronic haemodialysis, and to evaluate the significance of OC compared to other humoral parameters of renal osteodistrophy, such as ALP and iPTH. MATERIALS AND METHODS: We studied the fasting levels of OC in three different groups of children: group A consisted of 18 patients with TRF; group B consisted of 12 patients at different stages of CRF, and group C consisted of 32 healthy children, all of the approximately same age. Clinical characteristics of the examinded children are presented in Table 1. Of 30 patients, 26 were treated with calcium carbonate and 21 with vitamin D analogues. None were treated with aluminium hydroxide. Additional parameters included serum calcium, phosphate, ALP and body height, while serum concentrations of iPTH and ionized serum calcium were measured only in group A. Serum OC was measured by radioimmunoassay using OSTK PR RIA (CIS), while ELISA-PTH (CIS) radioimmunoassay was used to determine iPTH plasma levels. Statistical analyses were performed using Kolmogorov-Smirnov test to confirm normal distribution, the Pearson and Spearman rank sum test for correlation between variables of interest, while analysis of variance was used to compare the findings. RESULTS: Serum OC levels were significantly different in all groups (p < 0.01); they were three times higher in group A than in group C. Similar increase was noticed in plasma iPTH, assuming that "normal" uremic iPTH was raised up to threefold above normal range (between 10 and 60 pg/ml) [2]. However, the total serum ALP activity was not sensitive as OC and iPTH, since ALP increases were less as compared to them. OC was age related only in group A (p < 0.01), with a positive correlation between OC and duration of haemodialysis (p < 0.05), as well as between OC and serum phosphate (p < 0.05), but there was no correlation between OC and growth retardation (expressed by SDS), bone age and current therapy for renal osteodistrophy. A direct correlation between OC and ALP was found only in healthy children (p < 0.01), while in groups A and B it was remarkable, although not statistically significant (p = 0.08) (Graphs 1, 2, 3). In group A, ALP and iPTH were directly correlated (p < 0.001), but the correlation of OC with iPTH was less significant (p = 0.06). In patients with CRF no correlation was found between glomerular filtration rate and OC. DISCUSSION: OC is a bone-derived noncollagenous protein of low molecular weight (about 5800 D), containing residues of the vitamin K dependent amino acid gamma-carboxyglutamic acid and is synthesized by osteoblasts and odontoblasts. Calcitriol is a potent stimulator of OC synthesis, acting at the transcriptional level and increasing mRNA severalfold. OC is found mainly in bone, but nanomolar concentrations circulate in the blood. Its serum levels are an expression of the bone formation process and are age related (higher in the neonatal and adolescent period). ABSTRACT TRUNCATED.

[Cystic kidney disease--genetics, pathogenesis and clinical aspects in children]. / Cisticke bolesti bubrega--genetika, patogeneza i klinicka slika u decjem dobu.

This paper reviews recent studies producing insight into genetics and cellular abnormalities causing kidney cysts, their growth and development. Clinical features of various cystic kidney diseases in our patients are described. Special attention has been paid to those rarely reported in our literature. Important discovery concerns location of the gene for autosomal dominant polycystic kidney disease (ADPKD) 1 and 2 on the short arms of chromosome 16 and 4 respectively, as well as for autosomal recessive polycystic kidney disease (ARPKD) on chromosome 6 and for juvenile nephronophtisis on the short arm of chromosome 2. Two basic abnormalities necessary for cyst formation are increased: epithelial cell proliferation and altered fluid transport. Mitogenic action of epidermal growth factor (EGF) is significantly increased and EGF receptors have been demonstrated on apical as well as on basal surface of cyst lining epithelium. TGF-beta shows marked loos of inhibitory activity with regard to EGF. Cystic epithelium has altered polarity; Na-K-ATP-ase is located exclusively on the apical cell membrane. Tubular basement membrane shows alteration in structural components. Complex medullar cystic disease--nephronophtisis, complex as well as the hepatorenal complex of nephoronophtisis--congenital hepatic fibrosis are emphasized in this paper. The later has proved to be rather frequent in our population. We described a distinctive variant of hepato-renal disorder in 4 patients and reviewed 5 similar patients in the literature. The main characteristics are progressive tubulointerstitial nephritis and cholestatic liver disease. We strongly suggest that this variant represents a new syndrome (Popovic-Rolovic M, Kostic M, Sindic M. et al Progressive tubulointerstitialnephritis and chronic cholestatic liver disease.

[Urinary bladder dysfunction and vesicoureteral reflux in patients with enuresis]. / Disfunkcija mokracne besike i vezikoureterni refluks kod bolesnika s enurezom.

We present preliminary results of prospective study on 38 children (aged 4-15 y.) with enuresis. The aim of the study was to document the association between bladder disfunction and urinary tract abnormalities. Enuresis was more common in girls (71%). Twenty one children (44.7%) suffered from secondary, and 17 (55.3%) from primary enuresis. High incidence of enuresis (31.6%) or voiding dysfunction, renal lithiasis, constipation of other kidney disease (42%) were disclosed among family members of children with enuresis. Urodynamic studies revealed bladder dysfunction in 84.0% of children with enuresis mostly in the form of dyssingeric (45.5%) or unstable/hyperactive bladder (45.5%). In 9% of patients bladder dysfunction as in the form of inadequate bladder with small and poor detrusor contractions often associated with large residue. Ultrasonography revealed dilatation of pyelocaliceal system in 13.2%, and vesicoureteral reflux was confirmed in 10.5% of patients. We stress out high incidence of bladder dysfunction among children with enuresis as well as among their family members.

[Vesicoureteral reflux as a familial disease]. / Vezikoureterni refluks kao porodicna bolest.

Vesicoureteral reflux and reflux nephropathy are causes of end-stage renal failure in 43 percent of our patients on haemodialysis. Aiming at early discovering of vesicoureteral reflux and preventing reflux nephropathy, we started an investigation of the familial character or the primary vesicoureteral reflux in the families of 44 our patients with the diagnosed anomaly. Investigations which consist of urinalysis, urine culture and ultrasound of kidneys have so far been carried out for siblings of our patients in ten families. Complete investigations, including voiding cystourethrogram where indicated, have been carried out in five families. Familial vesicoureteral reflux ascertained in three families.

[Continuous blood pressure monitoring over a 24-hour period in children with terminal renal failure treated with hemodialysis]. / Kontinuisano pracenje krvnog pritiska u toku 24 sata kod dece s terminalnom insuficijencijom bubrega, lecenih hronicnim hemodijalizama.

Recent evidence suggests that circadian blood pressure changes are common in patients with impaired renal function and has excellent correlation with end-organ damage. The aim of this paper was to: 1) evaluate if children with end-stage renal failure have altered circadian blood pressure rhythm; 2) assess whether pre- or postdialytic blood pressure is representative for the average interdialytic blood pressure; 3) assess whether pre- or postdialytic blood pressure is representative for the average interdialytic blood pressure; 3) determine influence of pre-, post and interdialytic blood pressure. Ambulatory blood pressure monitoring was performed in two groups of patients: group A-13 children with end-stage renal failure, aged 15.15 +/- 5.58 years, on chronic haemodialysis from 2 to 156 (mean 45.3) months, 4 of whom were hypertensive and 9 normotensive; group B-19 children with chronic hypertension (essential or renal hypertension) aged 15.28 +/- 2.27 years. 84.62% of children from group A and 31.58% from group B (p = 0.0037) had blunted circadian blood pressure rhythm (a nocturnal reduction of blood pressure is less than 10% of daytime values). Pre- and postdialytic systolic, diastolic and mean arterial blood pressure did not differ significantly and were in correlation with interdialytic blood pressure (r = 0.9; p < 0.01). Pre-, post- and interdialytic blood pressures correlated well with left ventricular mass index (r = 0.6; p < 0.05), but were not in correlation with the degree of hypervolemia (p < 0.05).

[Management of hypertension in children]. / Savremni pristup u lecenju arterijske hipertenzije kod dece.

Treatment of hypertension depends on the cause and severity of hypertension, and wether it is acute or chronic hypertension. In hypertensive emergencies, antihypertensive therapy should be started immediately, even if the cause of the disease is unknown. If the hypertension is present for a short time, blood pressure could be normalized quickly, but if the hypertension is of long or unknown lasting, blood pressure should be normalized gradually, so in that way blood pressure is normalized in 2 to 4 days. In long-term antihypertensive therapy as little as possible drugs should be used, preferably in one or two daily doses. Depending on etiology and pathophysiology of hypertension, we use following drugs, alone or in combination: beta adrenergic blockers (atenolol, propranolol), vasodilators (hydralazine, minoxidil), ACE inhibitors (captopril, enalapril), calcium-channel blockers (nifedipine), diuretics (hydrochlorthiazide, frusemide) and alpha adrenergic blockers (prazosin, phenoxybenzamine). Recently, ACE inhibitors or calcium-channel blockers have been used as the first step in antihypertensive therapy. Surgical treatment includes elimination of tumors (Wilms tu, pheochromocytoma), coarctation of the aorta, revascularisation or percutaneous angioplasty (stenosis of renal artery) and parcial or unilateral nephrectomy in renal scarring. Nonpharmacological management: weight reduction, physical conditioning, dietary modifications etc. accompany pharmacological therapy in children with moderate-to-severe hypertension and are commonly recognized strategies to control mild elevations of blood pressure in children.