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1.
Eur Rev Med Pharmacol Sci ; 28(8): 3120-3134, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38708471

ABSTRACT

OBJECTIVE: Breast cancer, a prevalent global malignancy in women, necessitates a comprehensive treatment approach, with surgery playing a crucial role. Severe acute pain is common post-radical breast cancer surgery, emphasizing the significance of hemodynamic stability and postoperative pain control for optimal outcomes. This study evaluates the impact of ultrasound-guided erector spinae plane block (ESPB) on these parameters in ASA scores 1-2 patients undergoing modified radical breast cancer surgery with general anesthesia. PATIENTS AND METHODS: Forty-eight patients were divided into two groups: a general anesthesia group, with erector spinae plane block (GA+ESPB), and a control group receiving only general anesthesia (GA). Hemodynamic parameters were continuously monitored, and postoperative pain was assessed using the visual analog scale (VAS) at various time points. RESULTS: Ultrasound-guided ESPB effectively maintained hemodynamic stability and reduced postoperative pain in breast cancer surgery patients. Statistically significant differences were observed in heart rate, systolic and diastolic blood pressure, and mean arterial pressure between the GA and GA+ESPB groups at multiple time points (p < 0.05). VAS scores showed a significant interaction time*group (p < 0.001), with consistent differences between the groups at all time points (p ≤ 0.001). CONCLUSIONS: Ultrasound-guided ESPB application proved effective in preserving hemodynamic stability and managing postoperative pain in modified radical breast cancer surgery. The technique demonstrates promise in minimizing complications related to hemodynamic variations and postoperative pain, contributing to a comprehensive approach to breast cancer surgical treatment.


Subject(s)
Breast Neoplasms , Hemodynamics , Mastectomy, Modified Radical , Nerve Block , Pain, Postoperative , Ultrasonography, Interventional , Humans , Female , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Breast Neoplasms/surgery , Nerve Block/methods , Hemodynamics/drug effects , Middle Aged , Adult , Anesthesia, General , Aged
3.
Trials ; 20(1): 213, 2019 Apr 11.
Article in English | MEDLINE | ID: mdl-30975217

ABSTRACT

BACKGROUND: Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. METHODS: PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.


Subject(s)
One-Lung Ventilation/methods , Positive-Pressure Respiration/methods , Randomized Controlled Trials as Topic , Thoracic Surgical Procedures/methods , Humans , Intraoperative Complications/therapy , Research Design , Sample Size
4.
Eur J Gynaecol Oncol ; 38(1): 157-161, 2017.
Article in English | MEDLINE | ID: mdl-29767889

ABSTRACT

BACKGROUND: Adenocarcinoma, accounts for up to 14% of all vaginal cancer. In young patients, common histological feature is clear cell adenocarcinoma (CCA) while mesonephric adenocarcinoma (MA) is very rare. The authors report two patients in their early twenties with unilateral renal agenesis and vaginal adenocarcinoma not exposed to diethylstilbestrol (DES). CASES: Two patients with vaginal adenocarcinoma were treated, with external beam radiotherapy of pelvis combined with brachytherapy to a radical dose. In 2000, 25-year-old female, was admitted for radiotherapy after incomplete excision of the tumor localized in left vaginal apex and fornix. Histopathology confirmed CCA and classified as clinical Stage II. CT revealed left renal agenesis.The patient is alive and disease-free 15 years after therapy. Vaginal, urethral stenosis, and hydronephrosis occurred and ureteral stent was inserted. In the second patient, 22-year-old, in 2004, after biopsy of bulky tumor of vagina and histology, revealed MA in Stage III and CT scan also confirmed right renal agenesis. Radiotherapy was followed by chemotherapy. After 11 years, patient is disease-free with vaginal stenosis and incipient renal hydronephrosis. CONCLUSION: Radiotherapy is effective treatment in advance vaginal adenocarcinoma, however, with high morbidity. The authors advise rigorous gynecologic exams in young females with renal agenesis as there may be a risk of malignant changes in vagina.


Subject(s)
Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Solitary Kidney/complications , Vaginal Neoplasms/complications , Vaginal Neoplasms/diagnosis , Adenocarcinoma/therapy , Adult , Diethylstilbestrol , Estrogens, Non-Steroidal , Female , Humans , Vaginal Neoplasms/therapy , Young Adult
6.
Ann Anat ; 210: 25-31, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27777114

ABSTRACT

PURPOSE: Myocardial bridge is a congenital anomaly with a markedly variable reported incidence on autopsy (4.7%-86%), likely related to geographical regions. Our previous retrospective study showed a prevalence of 0.8%, which we doubted to be the true one in the examined sample of the Serbian population. To assess the importance of the phenomenon we conducted a 2-year prospective study at the same institution. METHODS: Ninety-six cadaver hearts from adult individuals of both genders (51 men, 45 women) who died from natural causes underwent special dissection. Tunneled coronary arteries and myocardium were examined using light microscopy. RESULTS: A total of 14 myocardial bridges were found in 13 (13.54%) hearts. This anomaly was insignificantly more common in men (13.72% vs. 13.33%, p>0.05). In one heart we noted two myocardial bridges (the left anterior interventricular artery and left marginal artery were overbridged). None of the myocardial bridges had been diagnosed during life. The most common causes of death were cardiac related. Myocardial bridges were located in the following areas: left anterior interventricular (50%), left circumflex artery (28.6%), left marginal artery (14.3%), and right coronary artery (7.1%). In 92.3% of cases, the right coronary artery was dominant. The only heart with a balanced-type had two bridges. Most of the myocardial bridges were long and deep. All tunneled coronary arteries, and although surrounded by "coronary cushion," were not protected from atherosclerosis. In 30.8% of hearts with myocardial bridges, we found additional coronary artery anomalies. CONCLUSION: Myocardial bridges were not rare in the examined sample of the Serbian population and were often associated with other coronary artery anomalies, rendering the carriers at higher risk.


Subject(s)
Heart Defects, Congenital/epidemiology , Heart Defects, Congenital/pathology , Myocardium/pathology , Adult , Aged , Aged, 80 and over , Atherosclerosis/epidemiology , Atherosclerosis/pathology , Autopsy , Cadaver , Cause of Death , Coronary Vessels/pathology , Dissection , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Serbia/epidemiology
7.
Acta Physiol Hung ; 101(4): 448-60, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25532956

ABSTRACT

The present study was undertaken in order to examine transduction mechanism involved in the single application of 100 µM homocysteine (Hcy) on isolated rat femoral artery (RFA) rings equilibrated on the basal tone; to establish if a single application of 100 µM Hcy alters contractile effect of phenylephrine (Phe), or oppositely the relaxant effect of acetylcholine (ACh) or bradykinin (BK) after 60-min-long incubation of 100 µM Hcy; and finally to identify morphological changes on the vascular wall after a 24-h-long incubation of 100 µM Hcy. Hcy produced contractile response of intact RFA, which was increased after endothelial denudation, while decreased by urapidil (an α1 receptor blocker), nifedipine (a voltage-gated L-type Ca++ channel blocker) or indomethacin (a cyclooxygenase inhibitor). The initial RFA contraction evoked by Phe was further increased by the single addition of Hcy, which was not the case when ouabain (an inhibitor of Na+/K+-ATPase) was preincubated. After 60-min-long incubation of Hcy relaxant actions of ACh and BK were unaltered, equieffective and equipotent. A 24-h-long incubation of RFA rings with Hcy produced an impairment of vascular endothelium, expressed as a minor or more pronounced interruption of endothelial cells.


Subject(s)
Femoral Artery/drug effects , Homocysteine/pharmacology , Signal Transduction/drug effects , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Animals , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Femoral Artery/metabolism , In Vitro Techniques , Male , Rats, Wistar , Time Factors , Vasodilator Agents/pharmacology
8.
J BUON ; 17(3): 575-80, 2012.
Article in English | MEDLINE | ID: mdl-23033302

ABSTRACT

PURPOSE: Mutations of KRAS and BRAF genes represent molecular biomarkers of response to targeted therapy in patients with metastatic colorectal cancer (mCRC). Since these mutations have been shown to exert different biological effects and impacts on patients' outcome, there is a need to determine reliably the frequency and types of KRAS mutations for diagnostic and individual therapeutic purposes. Despite having a wild type (wt) KRAS, some patients fail to respond to treatment. BRAF V600E mutation is an additional molecular determinant of response to the same therapy. In this study we described the KRAS and the BRAF V600E mutation spectra and frequencies in a group of Serbian mCRC specimens. METHODS: KRAS mutations were determined with DxS TheraScreen® K-RAS Mutation Kit and KRAS StripAssay(™), and for the BRAF V600E mutation we applied High Resolution Melting (HRM) analysis. RESULTS: KRAS mutations were present in 34.7% of 190 analyzed samples. The 7 most frequent mutation types observed were: G12D 43.9%, G12V 21.2%, G12A 10.6%, G12C 7.6%, G12S 4.5%, G12R 1.5%, G13D 10.6%. Among the wt KRAS patients, 17.8% carried the BRAF V600E mutation. CONCLUSIONS: We have shown that the spectrum and frequency distribution of the identified KRAS and BRAF mutations in Serbian study population are in good accordance with literature data. We believe that our results are significant concerning aspects related to tumor molecular biology as well as to patient selection in the diagnostic settings.


Subject(s)
Colorectal Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adult , Aged , Aged, 80 and over , Humans , Infant , Male , Middle Aged , Proto-Oncogene Proteins p21(ras) , Serbia
9.
J BUON ; 16(4): 701-7, 2011.
Article in English | MEDLINE | ID: mdl-22331725

ABSTRACT

PURPOSE: Lack of symptoms in early stages of disease and resistance to chemotherapy make epithelial ovarian carcinomas one of the most lethal neoplasms among gynaecological malignancies. The aim of this study was to analyse the impact of TP53 mutations, codon 72 polymorphism and human papillomavirus (HPV) infection on the response to platinum-taxane combination chemotherapy in patients with epithelial ovarian carcinomas. METHODS: The study was conducted on 26 ovarian carcinoma patients who received carboplatin plus paclitaxel combination chemotherapy. DNA was isolated by salting-out procedure. Mutations in exons 4-8 of TP53 gene were detected by PCR-SSCP and confirmed by automatic DNA sequencing. Codon 72 polymorphism was assessed by the RFLP method. HPV infection was detected through amplification of one part of L1 viral gene. Genotyping was performed by DNA sequencing. Fisher's exact and log-rank tests were used for statistical analysis. RESULTS: TP53 mutations were present in 5/26 (19.2%) ovarian carcinomas. The distribution of codon 72 TP53 genotypes was: Arg/Arg 38.5%, Arg/Pro 50.0%, Pro/Pro 11.5%. HPV was present in 4/26 (15.4%) ovarian carcinomas. All HPV-positive tumors were HPV16 type. Patients with mutations in TP53 gene, Arg/Arg genotype of codon 72 and absence of HPV infection experienced the highest tumor response rate to platinum-taxane chemotherapy. However, no significant correlation between progression free interval (PFI) and the examined biomarkers was observed. CONCLUSION: Our results indicate that, based on the TP53 gene status and the presence/absence of HPV infection, the subgroups of patients having better initial response to platinum-taxane therapy could be distinguished. This might contribute to more adequate treatment and individual therapeutic approach.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Genes, p53 , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Papillomaviridae/isolation & purification , Papillomavirus Infections/complications , Adult , Aged , Base Sequence , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Codon , DNA, Neoplasm/genetics , Disease-Free Survival , Female , Genotype , Humans , Middle Aged , Molecular Sequence Data , Mutation , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/virology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/virology , Paclitaxel/administration & dosage , Papillomaviridae/genetics , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Polymorphism, Single-Stranded Conformational
10.
J BUON ; 15(1): 101-6, 2010.
Article in English | MEDLINE | ID: mdl-20414935

ABSTRACT

PURPOSE: Ovarian cancer is the leading cause of death from gynecological malignancies. The early stages of this disease are asymptomatic and more than 75% of the cases are diagnosed with regional or distant metastases. p53 gene is frequently mutated in some histological subtypes of ovarian carcinomas. The role of p53 mutations and polymorphic variant of codon 72 in the prognosis of disease is still unclear. The aim of this study was to determine the frequency of p53 mutations and polymorphic variants of codon 72 among ovarian carcinoma patients and to correlate them with clinicopathological characteristics of disease. METHODS: 54 ovarian carcinoma patients were included in the study. DNA was isolated from tumor tissue by the salting- out method. p53 mutations in exons 4-8 were detected by PCR-SSCP (polymerase chain reaction - single-stranded conformational polymorphism) electrophoresis. Codon 72 polymorphism was assessed by RFLP (restriction fragment-length polymorphism) method. RESULTS: p53 mutations were present in 11 out of 54 patients (20.4%). Twenty-four patients (44.4%) exhibited Arg/ Arg, 24 patients (44.4%) Arg/Pro and 6 patients (11.2%) Pro/ Pro genotype of 72 codon polymorphism. Correlations between p53 mutations and various clinicopathological characteristics were not found. However, we observed that the frequency of Pro/Pro genotype was increasing with higher histological grade as well as in advanced compared to localized disease, but without statistical significance. Distribution of p53 gene mutations between Pro/Pro genotype and Arg/Pro plus Arg/Arg genotypes was not statistically significant. CONCLUSION: Our study suggests that Pro/Pro genotype of 72 codon polymorphism could be an independent prognostic marker in ovarian carcinomas.


Subject(s)
Carcinoma/genetics , Gene Expression Regulation, Neoplastic , Mutation , Ovarian Neoplasms/genetics , Polymorphism, Genetic , Tumor Suppressor Protein p53/genetics , Adult , Aged , Aged, 80 and over , Carcinoma/epidemiology , Carcinoma/pathology , Codon , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Phenotype , Prognosis , Risk Assessment , Risk Factors , Serbia/epidemiology
11.
J BUON ; 14 Suppl 1: S165-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19785060

ABSTRACT

Producing effective therapeutic vaccines has proved much more difficult and challenging than developing cancer preventive vaccines. Despite huge research in the area of cancer immunology, FDA/EMEA have not approved any type of cancer treatment vaccine so far. More than 99% of cervical cancers have detectable amounts of human papillomavirus (HPV) DNA. Integration of high-risk HPV into the host cell genome is followed by continual expression of HPV E6 and E7 oncoproteins, making them excellent targets for developing vaccines which could be used in high grade precancerous (CIN) lesions or invasive cancer or in the prevention of cancer recurrence. Therapeutic cervical cancer vaccines have been extensively studied. Strategies used were vaccination with HPV peptides or proteins, alone or in pulsed dendritic cells, DNA vaccines, virus-like particles or viral and bacterial vectors. Lovaxin-C is a recombinant live-attenuated Listeria monocytogenes (Lm) that secretes the antigen HPV-16 E7 fused to a non-hemolytic listeriolysin O protein. In a phase I study Lovaxin-C was administered to advanced cervical cancer patients refractory to existing therapies. The dose-limiting toxicity was hypotension and flue-like syndrome. There were no serious adverse events. Specific T-cell response was detected as well as clinical response to Lovaxin-C. Several other therapeutic HPV vaccines are in clinical development and in most of the studies specific immunological and clinical responses were seen. Efficacious therapeutic vaccine for the treatment of cervical cancer should be expected in the near future.


Subject(s)
Cancer Vaccines/toxicity , Uterine Cervical Neoplasms/immunology , Ampicillin/therapeutic use , Cancer Vaccines/therapeutic use , Dose-Response Relationship, Drug , Feasibility Studies , Female , Humans , Hypotension/chemically induced , Safety , Uterine Cervical Neoplasms/prevention & control
12.
J BUON ; 14 Suppl 1: S43-9, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19785069

ABSTRACT

In the process of RNA interference (RNAi), small RNAs pair with complementary messenger RNAs preventing their expression. The discovery of RNAi has revolutionized our understanding of gene regulation. Since cancer is a disease of altered genes, RNAi may have tremendous potential as a therapeutic strategy by downregulating altered genes. Just one decade after its discovery, this process is already being used in clinical trials and new technical achievements in delivering small RNAs to the cells are constantly improving the efficiency of this specific cancer treatment.


Subject(s)
Antineoplastic Agents/therapeutic use , MicroRNAs/therapeutic use , Neoplasms/drug therapy , RNA, Small Interfering/therapeutic use , Adenoma/drug therapy , Adenoma/genetics , Animals , Antineoplastic Agents/administration & dosage , Gene Silencing , Humans , Leukemia/drug therapy , Leukemia/genetics , MicroRNAs/administration & dosage , MicroRNAs/biosynthesis , Neoplasms/genetics , Prognosis , Protein Biosynthesis , RNA Interference , RNA, Double-Stranded/administration & dosage , RNA, Double-Stranded/genetics , RNA, Small Interfering/administration & dosage
13.
Int J Biol Markers ; 23(3): 147-53, 2008.
Article in English | MEDLINE | ID: mdl-18949740

ABSTRACT

PURPOSE: This study aimed to investigate the incidence of core domain TP53 mutations in Serbian breast cancer patients in view of their possible correlation with prognostic parameters, tumor characteristics and clinical disease course. METHODS: 145 breast cancer patients were included. Data on clinical disease course were available for 100 patients including 30 node-negative and 70 node-positive patients. After surgery, node-positive patients underwent adjuvant chemotherapy, mostly CMF. TP53 mutations were detected by PCR-SSCP. RESULTS: 31 mutations were found in 27/145 patients including 4/59 node-negative patients and 23/83 node-positive patients (4 double mutations). 26/31 TP53 mutations were found in patients with invasive ductal carcinoma and only 2 in patients with invasive lobular carcinoma. The presence of TP53 mutations was correlated with clinical disease course in premenopausal node-positive patients (n=70). 11/20 patients with TP53 mutations relapsed. Within the first 24 months of follow-up, significantly shorter disease-free intervals were observed in TP53-mutated patients. CONCLUSIONS: TP53 mutations correlated only with nodal status and ductal histology. The significance of the predominant distribution of TP53 mutations in tumors with a ductal histology for the aggressive behavior of these tumors has yet to be proved, since the favorable biological features of tumors with a lobular histology do not result in a better prognosis. Early relapse in mutated-TP53 carriers may support data on its predictive value with respect to adjuvant CMF.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Genes, p53 , Mutation , Tumor Suppressor Protein p53/genetics , Adult , Aged , Breast Neoplasms/ethnology , Case-Control Studies , Disease-Free Survival , Female , Humans , Middle Aged , Polymorphism, Single-Stranded Conformational , Receptors, Steroid/metabolism , Recurrence , Serbia
14.
Minerva Anestesiol ; 74(10): 521-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18854793

ABSTRACT

BACKGROUND: The inability to provide effective postoperative analgesia is one of the major disadvantages of intravenous regional anesthesia (IVRA). We designed a prospective, randomized, double blind study to evaluate the analgesic effectiveness of adding both ketorolac and dexamethasone to lidocaine for IVRA. METHODS: The study involved 45 patients undergoing ambulatory hand surgery. They were randomly allocated into three groups: Group L, Group LK and Group LDK. Group L received 3 mg x kg-1 lidocaine; Group LK received 3 mg x kg-1 lidocaine + 30 mg ketorolac; and Group LDK received 3 mg x kg-1 lidocaine for IVRA + 8 mg dexamethasone + 30 mg ketorolac for IVRA using a 40 mL solution. Sensory and motor block onset and recovery times were recorded. Tourniquet pain and pain at the operative site were assessed by a visual analog scale. In the first 24 h after surgery, opioid requirements and total analgesic consumption, including side effects, were noted. RESULTS: Sensory and motor block onset and recovery times were similar in all groups. Patients in Groups LK and LDK required less alfentanyl for control of intraoperative and early postoperative pain. Further, patients in Groups LK and LDK reported significantly lower pain scores compared to those in Group L (P<0.001). Patients in Groups LK and LDK required fewer postoperative ketorolac tablets (2.2+/-1.6 and 1.3+/-0.6 tablets, respectively) in the first 24 h after surgery and had significantly longer periods during which they required no analgesics (524 min and 566 min, respectively) compared to those in Group L (3.8+/-1.3 tablets; 122 min, P<0.001). CONCLUSION: IVRA with lidocaine and with the inclusion of ketorolac and dexamethasone provides effective perioperative analgesia for patients undergoing ambulatory hand surgery, when compared to the use of lidocaine alone or lidocaine with ketorolac IVRA.


Subject(s)
Ambulatory Surgical Procedures , Anesthesia, Conduction/methods , Anesthesia, Intravenous/methods , Anesthetics, Combined/administration & dosage , Anesthetics, Local/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Dexamethasone/administration & dosage , Hand/surgery , Ketorolac/administration & dosage , Lidocaine/administration & dosage , Adult , Double-Blind Method , Female , Humans , Male , Prospective Studies
15.
J BUON ; 13(4): 525-32, 2008.
Article in English | MEDLINE | ID: mdl-19145674

ABSTRACT

PURPOSE: The incidence rate (age-standardized) of cervical carcinoma in Serbia is the highest in Europe. p53 is mainly inactivated at protein level in carcinomas associated with human papillomavirus (HPV) infection, such as cervical carcinomas. These tumors show low rate of p53 mutations. It is not clear if p53 mutations confer additional impact on disease prognosis. The role of polymorphic variant at codon 72 of p53 gene on patient's prognosis is controversial. The aim of this study was to determine the frequency of p53 mutations and to assess polymorphic variants of codon 72 among cervical carcinoma patients. PATIENTS AND METHODS: 53 patients, mainly FIGO stage I (n=50), with squamous cell carcinoma (n=49) were included. 30/32 (94%) patients who received adjuvant radiotherapy were followed-up (median 15 months, range 4-39). DNA was isolated by the salting out method from tumor tissue (n=53) and blood (42/53). p53 mutations were detected by PCR-SSCP (polymerase chain reaction - single-stranded conformational polymorphism) electrophoresis. Codon 72 polymorphism was assessed by the restriction fragment-length polymorphism method. RESULTS: Six p53 mutations were detected in 5/53 (9%) patients with FIGO stage I squamous cell carcinoma (one patient had double mutations). 25/42 (60%) patients exhibited Arg/Arg genotype. HPV16 type was detected in 29/51 (57%) cervical carcinoma samples. Relapse of disease occurred in only 2 patients- both with Arg/Arg genotype and HPV16 positive. One of them exhibited p53 mutation. CONCLUSION: Our results showed low incidence of p53 mutations and prevalence of Arg/Arg genotype polymorphic variant of codon 72 of p53 gene in early stages of cervical carcinoma.


Subject(s)
Genes, p53 , Human papillomavirus 16/isolation & purification , Mutation , Uterine Cervical Neoplasms/genetics , Codon , Female , Humans , Neoplasm Staging , Polymorphism, Genetic , Radiation Tolerance , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/virology
16.
Minerva Anestesiol ; 73(4): 245-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17468737

ABSTRACT

The case of a patient who insisted on urgent surgical removal of a pheochromocytoma is presented. Rapid preparation started with continuous infusion of urapidil 3 days before surgery. On the evening before the operation, an additional infusion of magnesium sulphate was started. The target of preoperative optimization was to maintain blood pressure <140/90 mm Hg and heart rate <100 beats min(-l). Anesthesia was induced with fentanyl, propofol and rocuronium and maintained with sevoflurane in 100% oxygen and continuous infusion of fentanyl. Hypertensive events were treated by continuous infusions of urapidil and magnesium sulphate. Just before tumor resection, additional boluses of urapidil and MgSO4 were administered; both fentanyl infusion and end tidal concentration of sevoflurane were increased. Blood pressure was well maintained through the anesthesia; no transient periods of hypotension after tumor removal were observed. The patient's peroperative course was uneventful. He was discharged home without antihypertensive medication on the 5th postoperative day. This case demonstrates that with urapidil and magnesium sulphate administration rapid preparation for pheochromocytoma resection can be successfully achieved within 3 days.


Subject(s)
Adrenal Gland Neoplasms/surgery , Pheochromocytoma/surgery , Adrenergic alpha-Antagonists/therapeutic use , Adult , Blood Pressure/physiology , Catecholamines/urine , Heart Rate/physiology , Humans , Magnesium Sulfate/therapeutic use , Male , Piperazines/therapeutic use , Preoperative Care
17.
Surg Endosc ; 21(9): 1588-92, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17332962

ABSTRACT

BACKGROUND: Venous thromboembolism is a relevant social and health care problem because of its high incidence among patients who undergo surgery (20-30% after general surgical operations and 50-75% after orthopedic procedures), its pulmonary embolism-related mortality rate, and its long-term sequelae (postthrombotic syndrome and ulceration), which may be disabling. This study aimed to determine the coagulation status and the presence of postoperative deep vein thrombosis (DVT) in patients undergoing laparoscopic (LC) and open cholecystectomy (OC). METHODS: Prospectively, 114 patients were randomized into two groups. group 1 (58 patients undergoing LC) and group 2 (56 patients who are undergoing OC). The coagulation parameters (prothrombin time [PT], partial thromboplastin time [PTT], D-dimer, prothrombin F1 + 2, antithrombin III, and factor VII) were monitored preoperatively and during the operation, then 24 and 72 h after the operation. The patients in both groups underwent color duplex scan examination preoperatively, then 3 and 7 days after surgery to establish the presence of DVT. None of the patients in either group received thrombosis prophylaxis. RESULTS: In the LC group, postoperative DVT developed in four patients (6.9%; in the calf veins of 3 patients and in the popliteal vein of 1 patient). In the OC group, nine patients (16.07%) had postoperative DVT (in the calf veins of 7 patients and in the popliteal and femoral veins of 2 patients). The plasma levels of monitored parameters in the patients of both groups were altered, but the difference between the groups was not statistically significant. For the patients in both groups who experienced DVT, only the decrease of factor VII had statistical significance (p < 0.05). CONCLUSIONS: The incidence of postoperative DVT among the patients who underwent OC was higher than among the patients who underwent LC (p < 0.05). The decrease in factor VII among the patients who underwent surgery could be a potentially useful parameter indicating the patients at high risk for developing DVT.


Subject(s)
Blood Coagulation Factors/analysis , Blood Coagulation , Cholecystectomy, Laparoscopic/adverse effects , Postoperative Complications/blood , Venous Thrombosis/blood , Antithrombin III/analysis , Female , Humans , Male , Middle Aged , Partial Thromboplastin Time , Prothrombin/analysis , Venous Thrombosis/etiology
18.
J BUON ; 9(4): 347-54, 2004.
Article in English | MEDLINE | ID: mdl-17415838

ABSTRACT

Carcinogenesis represents a multistep process associated with accumulation of somatic mutations in the classes of genes that regulate cell proliferation, apoptosis as well as DNA repair. Oncogenes, positive regulators of cell proliferation are activated during carcinogenesis. On the contrary, tumor suppressor genes, negative regulators of cell proliferation have to be inactivated. Mutations in genes that function in the maintenance of genomic stability are manifested by increase in the mutation rate in cancer cells that drive tumor progression. In general, on the basis of malignant transformation lies the abrogation of the balance between cell proliferation and cell apoptosis. The genetic mechanisms included in the transformation of normally acting genes comprise a wide spectrum of events, such as gene mutation, gene and chromosome rearrangement and gene amplification. Besides the role of somatic gene alteration in the development of sporadic cancer, germline mutations are the basis of a substantial number of inherited cancer syndromes. The future decades will be marked with the expansion of data exploiting cancer genetics, epigenetics and genomics into clinical practice. Consequently, translational cancer research should provide the generating of new targeted therapies, since individual molecular profiling of a patient?s tumor should increase efficacy of conventional anticancer therapies such as chemotherapy and radiotherapy.

19.
Eur J Cancer Prev ; 12(1): 63-6, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12548112

ABSTRACT

A case-control study including 204 histologically verified female thyroid cancer patients and an equal number of hospital controls individually matched with cases by sex, age (+/- 2 years), place of residence and time of hospitalization was performed during the period 1996-2000. In the analysis of data, univariate and multivariate conditional logistic regression, methods were applied. According to multivariate analysis, out of hormonal, menstrual and reproductive characteristics, risk factors for thyroid cancer were spontaneous abortions (odds ratio: OR = 1.89, 95% confidence interval (CI) = 1.03-3.50), oral contraceptives use (OR = 2.34, 95% CI = 1.31-4.18) and thyroid enlargement during pregnancy (OR = 16.44, 95% CI = 3.81-70.80). However, none of these three factors remained independently related to thyroid cancer after adjustment for other factors, which were significantly associated with thyroid cancer in the present study (history of residence in endemic goitre area, history of goitre or thyroid nodule, history of other endocrine diseases, radioactive iodine therapy, occupational exposure to various chemicals, family history of thyroid gland diseases and malignant tumours as well as intake of cruciferous vegetables and other vegetables, and consumption of smoked meat and cheese).


Subject(s)
Menstruation , Thyroid Neoplasms/etiology , Adolescent , Adult , Aged , Case-Control Studies , Child , Contraceptives, Oral/adverse effects , Diet , Female , Humans , Middle Aged , Odds Ratio , Parity , Regression Analysis , Risk Factors , Thyroid Diseases/complications , Thyroid Neoplasms/epidemiology , Vegetables
20.
J Cancer Res Clin Oncol ; 128(1): 55-60, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11862473

ABSTRACT

PURPOSE: The usefulness of steroid receptor content in breast cancer metastases for metastatic disease therapy planning was examined in this study. METHODS: Steroid receptors in primary tumors and corresponding metastases in the same breast cancer patients ( n=23) were determined by five-point DCC assay. We carried out an analysis of the therapeutic response and comparison of the progression-free interval of patients treated with endocrine/chemo-endocrine therapy for metastatic disease according to the positive/negative progesterone receptor status of primary tumors, or of breast cancer metastases. RESULTS AND CONCLUSIONS: It seems that the lack of positive progesterone receptors in metastasis (0/8) and conversion from PR+ primary to PR- metastasis (5/8) may be important in describing the non-responder phenotype. We obtained a similar progression-free interval in patients with progesterone receptor-positive/negative primary tumors, but a longer progression-free interval in the patients with progesterone receptor-positive metastases ( n=9) than with negative ones ( n=14), indicating the possibility of using steroid receptor content from metastases for metastatic disease therapy planning.


Subject(s)
Breast Neoplasms/pathology , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Lymphatic Metastasis , Methotrexate/administration & dosage , Middle Aged , Neoplasm Metastasis , Tamoxifen/therapeutic use , Time Factors
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