BODY MASS INDEX AS A PROGNOSTIC FACTOR FOR DISEASE PROGRESSION IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH BEVACIZUMAB BASED SYSTEMIC THERAPY.

CONTEXT: Epidemiological data have shown that obesity increases the risk of developing colorectal cancer and also an increased body mass index (BMI) is associated with a worse prognosis. Bevacizumab based systemic therapy, an antiVEGF targeted therapy, is an important treatment option for metastatic colorectal cancer (mCRC) patients. Obesity is associated with high level of vascular endothelial growth factor (VEGF), that might provoke resistance to antiVEGF monoclonal antibody. OBJECTIVE: To evaluate the efficacy in terms of progression free survival (PFS) and overall survival (OS) of bevacizumab systemic therapy in patients with mCRC. DESIGN: Retrospective cohort, single center study. SUBJECTS AND METHODS: Between January 2007 and December 2012, 112 patients with mCRC, who followed bevacizumab based systemic therapy in the "Ion Chiricuta" Oncology Institute in Cluj-Napoca, were included in our analysis. RESULTS: Values of BMI ≥ or <27 kg/sqm was found that PFS is statistically significant superior in patients with BMI<27 kg/sqm (n=77) than in those with BMI ≥ 27 kg/sqm (n=35), 24 months versus 17.9 months (p = 0.04). Five years OS was not influenced by the BMI, 35% vs 30% (p=0.29). In patients with liver metastases with values of BMI ≥ 27 kg/sqm have PFS lower than patients with a BMI <27 kg/sqm, 17.5 months versus 24.5 months (p = 0.02). Five years OS was not influenced by the BMI, 39% (BMI <27 kg/sqm) vs. 22% (BMI ≥ 27 kg/sqm) (p = 0.09). CONCLUSIONS: This study demonstrated the negative influence of BMI on both PFS on the entire sample of patients and in patients with liver metastases only, BMI cut-off value proved to be 27 kg/square meter and shows that the BMI may be an important prognostic factor with a high clinical relevance in patients with mCRC.

Long-living periodic solutions of complex cubic-quintic Ginzburg-Landau equation in the presence of intrapulse Raman scattering: A bifurcation and numerical study.

We have found long-living periodic solutions of the complex cubic-quintic Ginzburg-Landau equation (CCQGLE) perturbed with intrapulse Raman scattering. To achieve this we have applied a model system of ordinary differential equations (SODE). A set of the fixed points of the system has been described. A complete phase portrait as well as phase portraits near the fixed points have been built for a proper choice of parameters. The behavior of the model system near the fixed points has been determined. We have presented a detailed description of the subcritical Poincaré-Andronov-Hopf bifurcation due to the intrapulse Raman scattering that appears at one of the fixed points. We have established that there appears an unstable limit cycle in the SODE. To check the validity of the obtained results from the model system we have compared them with the results of the numerical solution of the CCQGLE perturbed with intrapulse Raman scattering. There has been found a remarkable correspondence between the obtained numerical results for the amplitude and frequency of the soliton pulses and the results for these parameters of the bifurcation theory. We have observed that the numerical characteristics of the propagating solitonlike pulses-amplitude, frequency, width, and position-periodically change if we change the distance with a period determined by the bifurcation analysis.

Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

INTRODUCTION: Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. METHODS AND RESULTS: A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 µs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. CONCLUSIONS: AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF.

Left ventricular strain distribution in healthy dogs and in dogs with tachycardia-induced dilated cardiomyopathy.

BACKGROUND: Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. METHODS: Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. RESULTS: In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). CONCLUSION: TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This "reverse" distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology.

Can the epirubicin cardiotoxicity in cancer patients be prevented by angiotensin converting enzyme inhibitors?

PURPOSE: The aim of this study was to assess whether treatment with angiotensin converting enzyme inhibitors (ACEI) can prevent the alteration of left ventricular systolic and diastolic performance in cancer patients treated with different chemotherapy regimens containing epirubicin. METHODS: In this prospective study , 68 patients with different malignant tumors treated with epirubicin and perindopril in different chemotherapy protocols (study group), and a gender- and age-matched group of 68 patients with different malignant tumors treated with epirubicin without perindopril in different chemotherapy protocols (control group), were assessed by Doppler echocardiography. Left ventricular systolic function was assessed by measuring left ventricular ejection fraction (EF). Left ventricular diastolic function was assessed by Doppler ultrasound by evaluating the transmitral flow. We also assessed the QTc on the 12 lead electrocardiograms. RESULTS: At the end of chemotherapy the left ventricular systolic function was less altered in the study group compared to the control group and was superior in the study group (epirubicin+ACEI) compared to the control group (epirubicin alone). We documented a significantly deteriorated left ventricular diastolic function in both groups at the completion of chemotherapy. QTc time in both arms was also significantly prolonged. CONCLUSION: In the present echo-Doppler study we documented a preserved left ventricular systolic performance in patients with various malignancies treated with epirubicin plus perindopril. Although co-treatment with ACEI prevented the alteration of systolic performance, it failed to prevent the deterioration of the left ventricular diastolic performance impairment due to poor left ventricular compliance.

What is the significance of a microscopically positive resection margin in the curative-intent treatment of rectal adenocarcinoma? A retrospective study.

PURPOSE: The aim of this study was to analyze the characteristics of patients with rectal cancer operated with a microscopic positive margin (R1) and thus avoid these situations or adapt treatment in these particular cases. METHODS: We reviewed all the pathology data of resected specimens from patients with rectal or recto-sigmoid cancer operated with curative intent at the Institute of Oncology "Prof. Dr. Ion Chiricuta" between 2000-2011 (763 patients in 12 years) and the pathology files of patients from other institutions referred for adjuvant treatment to our hospital (318 patients). We included patients with anterior resection, Hartmann's procedure and abdomino-perineal resection, but we excluded patients with local excision and patients with R2/R1 at first, but R0 after re-resection (56 patients). We have identified 31 patients with R1, but had to exclude one case from analysis because this patient was lost to follow-up. RESULTS: With surgery alone the local relapse (LR) was unavoidable. In the neoadjuvant chemoradiation (CRT) group 85.7% of the patients did not develop LR despite of R1. In the adjuvant CRT cohort 50% of the patients were LR-free at 2 years after conventional radiotherapy (p<0.01). CONCLUSION: Based on these results it is concluded that a clear resection margin is extremely important for the local control of rectal cancer, because it cannot be always compensated by adjuvant CRT. In R1 cases neoadjuvant CRT seems to offer better prognosis than adjuvant CRT. To avoid R1 and its consequences a good quality control of total mesorectal excision (TME) is needed and CRT should be done before and not after surgery. R1 after primary surgery needs to be compensated by re-resection if possible, otherwise probably high dose radiotherapy with chemotherapy is needed.

COVID-19 vaccine acceptance among medical students in Romania.

Vaccination against COVID-19 is a highly debated subject that brings confusion due to contradictory information coming from the scientific community and the media. Our aim was to focus on a homogeneous group of students in the healthcare field to assess their intention to vaccinate and the drivers behind this decision. A cross-sectional study was performed in the spring of 2021 in a Medical University in Romania. 725 of the undergraduates that completed an online questionnaire regarding their intention to vaccinate against COVID-19 were included in the study. Univariable analysis and logistic regression were performed on several variables to analyze factors affecting the willingness to vaccinate against COVID-19. In our study sample, 93.1% of students presented a strong intention to vaccinate, out of which the highest proportion belonged to subjects studying general medicine (96%). On logistic regression, we identified the following predictor factors: previous infection with coronavirus, prior vaccination refusal, VAX score, scientifically oriented sources of information and preference for RNA-based technology. Medical students have an increased willingness towards vaccination. Even for them, a highly educated and informed group of subjects, the general attitude towards vaccinations has a strong impact on the choice of COVID-19 vaccination.

Outcomes of patients with cancer infected with SARS-CoV-2: results from the Ion Chiricuta Oncology Institute series.

BACKGROUND: The evolution of COVID-19 is a controversial topic in cancer patients. They have been designated by international organizations as a vulnerable population at greater risk for contracting SARS-CoV-2 and having a more severe clinical outcome. PATIENTS AND METHODS: Active screening at our institution became routine early in the pandemic. We have examined the clinical data of 341 cancer patients, with a positive RT-PCR SARS-CoV-2 test between April 2020 and February 2021, in the prevaccination era. RESULTS: During the infection, 40.5% remained asymptomatic, 27.6% developed a mild form, 20.5% had a moderate form, and 11.4% a severe/critical form of COVID-19 that led to death in 7.6% of cases. Treatment was adapted to disease severity according to national guidelines. In our series, the incidence of COVID-19 infection was lower in cancer patients compared with the general population (P < 0.001), however, the mortality rate was higher in cancer patients in comparison with the general population (7.6% versus 2.9%, P < 0.001). The prognostic factors were assessed by three distinct univariate and multivariate analyses: (i) evolution to a moderate or severe/critical clinical manifestation, (ii) clinical worsening (severe/critical form or death), and (iii) overall survival. In the multivariate analysis, the prognostic factors associated with the evolution to a moderate or severe/critical clinical manifestation were: performance status (PS) (P < 0.0001) and no active treatment in the previous 3 months (P = 0.031). Factors associated with clinical worsening were: PS (P < 0.0001), peripheral arterial disease (P = 0.03), and chronic liver disease (P = 0.04). Factors associated with impaired overall survival were PS (P < 0.0001), ischemic cardiac disease (P = 0.0126), chronic liver disease (P = 0.001), and radiotherapy (P = 0.0027). CONCLUSION: Our series confirms a more severe evolution for COVID-19 infection in cancer patients, with PS as the most prominent prognostic factor in all three multivariate analyses. By active screening, efforts should be in place to keep cancer units as coronavirus-free sanctuaries.

AV nodal dual pathway electrophysiology and Wenckebach periodicity.

INTRODUCTION: The precise mechanism(s) governing the phenomenon of AV nodal Wenckebach periodicity is not fully elucidated. Currently 2 hypotheses, the decremental conduction and the Rosenbluethian step-delay, are most frequently used. We have provided new evidence that, in addition, dual pathway (DPW) electrophysiology is directly involved in the manifestation of AV nodal Wenckebach phenomenon. METHODS AND RESULTS: AV nodal cellular action potentials (APs) were recorded from 6 rabbit AV node preparations during standard A1A2 and incremental pacing protocols. His electrogram alternans, a validated index of DPW electrophysiology, was used to monitor fast (FP) and slow (SP) pathway conduction. The data were collected in intact AV nodes, as well as after SP ablation. In all studied hearts the Wenckebach cycle started with FP propagation, followed by transition to SP until its ultimate block. During this process complex cellular APs were observed, with decremental foot formations reflecting the fading FP and second depolarizations produced by the SP. In addition, the AV node cells exhibited a progressive loss in maximal diastolic membrane potential (MDP) due to incomplete repolarization. The pause created with the blocked Wenckebach beat was associated with restoration of MDP and reinitiation of the conduction cycle via the FP wavefront. CONCLUSION: DPW electrophysiology is dynamically involved in the development of AV nodal Wenckebach periodicity. In the intact AV node, the cycle starts with FP that is progressively weakened and then replaced by SP propagation, until block occurs. AV nodal SP modification did not eliminate Wenckebach periodicity but strongly affected its paradigm.

Arrhythmias and vagus nerve stimulation.

Enhancing vagal tone by delivering electrical stimulation to the vagal nerves (VNS) is emerging as a promising novel therapy in heart failure. In addition, VNS is already an FDA-approved therapy for refractory epilepsy and depression. Besides its well-known negative chronotropic, inotropic, and dromotropic effects, VNS has profound effects on cardiac electrophysiology and arrhythmogenesis. This review summarizes current knowledge about the complex relationship between VNS and cardiac arrhythmias. Specifically, the focus is on VNS capability to become a therapeutic strategy along with important electrophysiological alterations that may constitute a potential arrhythmogenic substrate and become a clinical concern.

Higher-order correction terms to the nonlinear amplification or absorption, the nonlinear refractive index, and the intrapulse Raman scattering.

In this paper we have investigated through the numerical solution of the basic equation as well as through the dynamic model the influence of higher-order correction terms to the nonlinear amplification (absorption) and to the nonlinear refractive index on the self-frequency shift of Raman dissipative solitons. We have found a nonlinear dependence of the self-frequency shift of Raman dissipative solitons on the parameter describing intrapulse Raman scattering in the presence of the saturation of the nonlinear gain. With the increase of the absolute value of the saturation of the nonlinear gain, the maximum absolute value of the frequency shift decreases and its position moves to larger values of the parameter describing intrapulse Raman scattering. The increase in the value of the nonlinear gain leads to an increase in the maximum absolute value of the frequency shift, without changing its position. We have also observed the nonlinear dependence of the absolute value of the frequency shift on the parameter describing intrapulse Raman scattering in the presence of higher-order correction term to the nonlinear refractive index. The discovered nonlinear dependence of the self-frequency shift on the value of the saturation of the nonlinear gain as well as on the higher-order correction term to the nonlinear refractive index can be used for the better understanding and control of the spectral characteristics of Raman dissipative solitons. The dynamic model correctly describes all the features of the observed phenomena.

Oxaliplatin in patients with metastatic colorectal cancer: efficacy and pharmacokinetics parameters.

PURPOSE: The aim of this study was to investigate the efficiency of the FOLFOX-4 regimen and to evaluate the pharmacokinetics of oxaliplatin in untreated patients with metastatic colorectal cancer. METHODS: 43 patients were enrolled in the study. Patients received oxaliplatin 85 mg/m(2) as 2-h i.v. infusion, on day 1, and bolus 5-fluorouracil (5FU) 400 mg/m(2) plus leucovorin (LV) 200 mg/m(2) followed by 5FU 600 mg/m(2) as 22-h infusion on day 1 and 2, every 2 weeks. The pharmacokinetics of oxaliplatin evaluated in 4 patients was performed in blood, plasma and ultrafiltered plasma (UFT) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The overall response rate and the median time to progression (TTP) were 53.49% and 7.1 months, respectively. Grade 3-4 toxic effects were observed in 11 (25.5%) patients. Grade 3 neuropathy was observed in 13.95% of the cases. In univariate analysis only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was correlated with response. No correlation was found between grade 3-4 adverse events and the patient characteristics. The area under the time-concentration curve (AUC) in UFT was 4.8 + or - 0.72 standard deviation (SD) microg h/ml and the total clearance 30.17 + or - 7.75 l/min. The values for volume of distribution and the maximum concentration were 567 + or - 20 liters and 0.38 + or - 0.17 ug/ml, respectively. CONCLUSION: FOLFOX-4 was an effective regimen with good tolerability in previously untreated metastatic colorectal cancer patients. The pharmacokinetics of oxaliplatin was triphasic with a short initial distribution phase and a long terminal elimination phase.

Non-invasive assessment of left ventricular relaxation during atrial fibrillation using mitral flow propagation velocity.

AIMS: To elucidate the usefulness of the early diastolic mitral flow propagation velocity (V(p)) obtained from colour M-mode Doppler for non-invasively assessing left-ventricular (LV) relaxation during atrial fibrillation (AF). METHODS AND RESULTS: Ten healthy adult dogs were studied to correlate V(p) with the invasive minimum value of the first derivative of LV pressure decay (dP/dt(min)) and the time constant of isovolumic LV pressure decay (tau) at baseline, during rapid and slow AF, and during AF after inducing myocardial infarction. There were significant positive and negative curvilinear relationships between V(p) and dP/dt(min) and tau, respectively, during rapid AF. After slowing the ventricular rate, the average value of V(p) increased, while dP/dt(min) increased and tau decreased. After inducing myocardial infarction, the average value of V(p) decreased, while dP/dt(min) decreased and tau increased. CONCLUSION: The non-invasively obtained V(p) evaluates LV relaxation even during AF regardless of ventricular rhythm or the presence of pathological changes.

Capecitabine as salvage treatment in relapsed nasopharyngeal carcinoma: a phase II study.

PURPOSE: To evaluate the efficacy of capecitabine (Xeloda) as rescue treatment (2nd, 3rd and 4th line) in patients with relapsed nasopharyngeal carcinoma (NPC) in a phase II study. PATIENTS AND METHODS: Between 5/2002-11/2005, 23 relapsed NPC patients (17 locoregional relapse, 3 metastatic, 3 locoregional + metastatic) received capecitabine 2500 mg/m(2)/d, days 1-14 every 3 weeks, until progression or for a maximum of 6 cycles. PATIENT CHARACTERISTICS: 23 patients (14 men, 9 women) with median age 46 years (range 15-59); ECOG performance status 1 n=21, 2 n=2; histology: undifferentiated carcinoma (WHO type III) n=21, non-keratinizing epidermoid carcinoma (WHO type II), n=2. Capecitabine was given as 2nd--(13 patients), 3rd--(7 patients), and 4th--(3 patients) line chemotherapy. Previous chemotherapy regimes were epirubicin + cisplatin, paclitaxel + carboplatin, paclitaxel + 5-fluorouracil and leucovorin (5-FU/LV) or methotrexate. 104 cycles were given (median 5, range 2-6). Two (9%) patients achieved complete response (CR); 9 (39%) partial response (PR); 9 (39%) stable disease (SD) and 3 (13%) progressed (PD). Toxicity was mild without toxic deaths or grade 4 toxicities. The most frequent toxicities (grades 1-3) were anemia (38%), hand-foot syndrome (23%), leukopenia (13%) and diarrhea (7%). Median follow-up was 10 months (range 2-44). Median overall survival was not reached at 18 months and actuarial one-year survival was 62% (95% confidence interval/CI: 41-80). Median progression-free survival was 14 months. CONCLUSION: Capecitabine is active in relapsed NPC patients, achieving 48% objective responses, with mild toxicity. It is an attractive therapy to be administered in an outpatient setting.

Transitions of stationary to pulsating solutions in the complex cubic-quintic Ginzburg-Landau equation under the influence of nonlinear gain and higher-order effects.

In this paper we study the transitions of stationary to pulsating solutions in the complex cubic-quintic Ginzburg-Landau equation (CCQGLE) under the influence of nonlinear gain, its saturation, and higher-order effects: self-steepening, third-order of dispersion, and intrapulse Raman scattering in the anomalous dispersion region. The variation method and the method of moments are applied in order to obtain the dynamic models with finite degrees of freedom for the description of stationary and pulsating solutions. Having applied the first model and its bifurcation analysis we have discovered the existence of families of subcritical Poincaré-Andronov-Hopf bifurcations due to the intrapulse Raman scattering, as well as some small nonlinear gain and the saturation of the nonlinear gain. A phenomenon of nonlinear stability has been studied and it has been shown that long living pulsating solutions with relatively small fluctuations of amplitude and frequencies exist at the bifurcation point. The numerical analysis of the second model has revealed the existence of Poincaré-Andronov-Hopf bifurcations of Raman dissipative soliton under the influence of the self-steepening effect and large nonlinear gain. All our theoretical predictions have been confirmed by the direct numerical solution of the full perturbed CCQGLE. The detailed comparison between the results obtained by both dynamic models and the direct numerical solution of the perturbed CCQGLE has proved the applicability of the proposed models in the investigation of the solutions of the perturbed CCQGLE.

Quality of life and treatment related toxicity in 335 patients with locally advanced cervical carcinoma treated by two chemoradiation regimens.

PURPOSE: Concomitant chemoradiotherapy (CT/RT) is the gold standard for advanced cervical carcinoma, but with frequent debates over treatment schedules and toxicity. This study compared 2 concomitant CT/RT regimens in terms of quality of life (QoL) and acute toxicity. PATIENTS AND METHODS: Between March 2003 and March 2005, 335 patients with stage IIB-IIIB cervical carcinoma were evaluated in a randomized single-center phase III trial at the Oncology Institute Cluj-Napoca. Patients received concurrent CT/RT with cisplatin 20 mg/m(2), days 1-5, every 21 days (arm A, n=171) or 40 mg/m(2)/weekly (arm B, n=164). QoL was estimated using the EORTC QLQ-30, v.3.0 questionnaire and acute toxicity using the common toxicity criteria (CTC) v.2.0. RESULTS: Significant improvement of global health status (p <0.01) and a decrease in pain (p <0.01) was observed in arm A. In arm B fatigue increased (p=0.01) and role functioning diminished (p=0.05). In both arms depression, nausea, vomiting and diarrhea increased (p <0.05). Gastrointestinal toxicity was similar in both arms (76% vs. 77.5%). Hemoglobin drop was higher in arm B: 75% vs. 63% (p=0.02), while no differences were seen in leukocyte and platelet toxicity. CONCLUSION: Concomitant CT/RT with cisplatin 20 mg/m(2) x 5 days every 21 days has better impact on patients' QoL and lower toxicity compared with the weekly chemotherapy regimen.

Clinical results of medium dose rate brachytherapy combined with external beam radiotherapy in the treatment of advanced cervical carcinoma.

PURPOSE: To evaluate the overall and disease-free survival of patients with advanced cervical carcinoma (FIGO stages IIB-IIIB) treated with external beam radiotherapy (EBRT) and medium dose rate brachytherapy (MDR-BT) plus/minus surgery. PATIENTS AND METHODS: One hundred and seven patients received preoperative RT (group A) and 154 were treated with definitive RT (group B); 73 patients in both groups also received cisplatin as radiosensitizer. EBRT delivered as preoperative reached a total dose of 44-46 Gy/pelvis, whereas the definitive RT reached a total dose of 62-64 Gy with standard fractionation. MDR-BT was performed with a LDR/MDR Cs-137 Selectron machine; 10 Gy/point A were delivered in the preoperative group A and 14 Gy/point A/, 1-2 fractions in group B. Cisplatin as radiosensitizer was administered during EBRT at a dose of 20 mg/m(2)/day for 5 days with 21 days interval between cycles. RESULTS: With a median follow-up of 44.4 months (range 3.4-61.6) the overall survival at 3 years in group A was 92% vs. 68% for group B (p<0.01). According to FIGO stages 3-year overall survival was 88% in stage IIB, 79% in IIIA and 60% in IIIB (p<0.01). Three-year local control was 73.5% (192 patients). Thirty-three (13%) patients developed locoregional recurrences, and another 8 (3.07%) locoregional recurrences plus distant metastases. CONCLUSION: The association of EBRT with MDR-BT represents an effective treatment in advanced cervical carcinoma. A significant difference in 3-year overall survival was found, favoring preoperative RT, with a very good rate of local control.

Concurrent chemoradiotherapy with vinorelbine and a platinum compound followed by consolidation chemotherapy for unresectable stage III non-small cell lung cancer: preliminary results of a phase II study.

PURPOSE: To determine the efficacy, toxicity and survival of concurrent therapy with vinorelbine and a platinum compound with radiotherapy (RT), followed by consolidation chemotherapy with the same drugs, for locally advanced non small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-seven patients with stage III NSCLC were included in this phase II study: median age 56 years (range 44-71), males / females 49/8, ECOG performance status (PS) 1/2=27/30, stage IIIA/ IIIB 11/46, squamous cell carcinoma 44, adenocarcinoma 7, adenoid cystic carcinoma 1 and large cell carcinoma 5. Treatment consisted of 2 cycles of chemotherapy with vinorelbine and cisplatin or carboplatin, given concurrently with RT, followed by 2-4 more cycles of consolidation chemotherapy with the same drugs. Twenty-two patients received amifostine for radio- and chemoprotection. RESULTS: Grade 3 or 4 toxicities were neutropenia and esophagitis in 19% of the patients each, and gastrointestinal toxicity in 17% of the patients. Of the 55 patients evaluable for response, 23.64% achieved complete response (CR) and 40% partial response (PR) (overall response rate 63.64%). Progression-free survival curves showed 1- and 2-year values of 42% and 21%, respectively, and median time to progression 10.5 months. The 1- and 2- year disease-specific survival was 58% and 29%, and the median overall survival 15 months. CONCLUSION: Preliminary analysis indicates that concurrent vinorelbine and a platinum compound with RT followed by consolidation chemotherapy with the same drugs for advanced stage III NSCLC is well tolerated, has considerable activity and positive impact on survival.

Chronic atrioventricular nodal vagal stimulation: first evidence for long-term ventricular rate control in canine atrial fibrillation model.

BACKGROUND: We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs. METHODS AND RESULTS: In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 micros or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45+/-13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort. CONCLUSIONS: Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.

Novel robotic catheter remote control system: feasibility and safety of transseptal puncture and endocardial catheter navigation.

OBJECTIVES: The aims of this study were to demonstrate the safety and the feasibility of the robotic catheter remote control system (CCS) in endocardial navigation in all cardiac chambers, as well as facilitation of the transseptal puncture. BACKGROUND: CCS has been developed to facilitate control and precise positioning of catheters within the cardiovascular system. METHODS: CCS consists of a remote catheter manipulator, a set up joint, a physician workstation, and a steerable guide catheter (SGC) and sheath. A conventional 4-mm tip catheter was inserted through the SGC to perform mapping of five predefined targets in each cardiac chamber. Seven mongrel dogs were used in this study. Intracardiac echocardiography and three-dimensional (3-D) electroanatomical mapping were integrated with CCS to facilitate catheter manipulation and to guide transseptal puncture. The time to complete the transseptal puncture and the time to complete access to the predefined targets in each cardiac chamber were measured. Gross and microscopic examinations of the accessed and ablation sites were performed to evaluate safety. RESULTS: Transseptal puncture was performed successfully in all animals with a mean time of 7 +/- 3 minutes. Procedure times to access the five targets in the right atrium, right ventricle, left atrium, and left ventricle were 5.6 +/- 1.7, 4.6 +/- 1.5, 13.5 +/- 11.0, 7.0 +/- 2.9 minutes, respectively. There were no intracardiac damages associated with catheter manipulation noted in the excised hearts. CONCLUSIONS: Endocardial catheter navigation and mapping using the robotic catheter remote control is safe and feasible. Moreover, the CCS could be used to perform transseptal puncture and left atrial instrumentation.