Biljana Milicic

Hyperfractionated Radiation Therapy With or Without Concurrent Low-Dose Daily Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Prospective Randomized Trial

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence...

Role of Radiation Therapy in the Combined-Modality Treatment of Patients With Extensive Disease Small-Cell Lung Cancer: A Randomized Study

PURPOSE To investigate the efficacy and toxicity of cisplatin/etoposide (PE) chemotherapy (CHT) with or without accelerated hyperfractionated radiation therapy (ACC HFX RT) and concurrent daily carboplatin/etoposide (CE) in patients with extensive-disease small-cell lung cancer. PATIENTS AND METHODS A total of 210 patients were treated with three cycles of standard PE. Patients with a complete response (CR) at both the local and distant levels (CR/CR) or a partial response (PR) at the local level and CR at the distant level (PR/CR) received either thoracic ACC HFX RT with 54 Gy in 36 fractions over 18 treatment days in combination with CE followed by two cycles of PE (group 1, n = 55) or an additional four cycles of PE (group 2, n = 54). Patients who experienced less response were treated nonrandomly (groups 3, 4, and 5). All patients with a CR at the distant level received prophylactic cranial irradiation. RESULTS For 206 assessable patients, the median survival time (MST) was 9 months and the 5-year survival rate was 3.4%. Patients in group 1 had significantly better survival rates than those in group 2 (MST, 17 v 11 months; 5-year survival rate, 9.1% v 3.7%, respectively; P =.041). Local control was also better in group 1, but the difference was only marginally not significant (P =.062). There was no difference in distant metastasis-free survival between groups 1 and 2. Acute high-grade toxicity was higher in group 2 than in group 1. CONCLUSION The addition of ACC HFX RT to the treatment of the most favorable subset of patients led to improved survival over that obtained with CHT alone.

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Patients with Chronic Pancreatitis and Pancreatic Cancer

The purpose of this study was to determine the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and to investigate its role as a potential risk factor in patients with chronic pancreatitis and pancreatic cancer. Deletion polymorphism of the 287-bp fragment of intron 16 of the ACE gene results in higher levels of circulating enzyme and therefore may represent a risk factor for disease development. The study included 55 patients with chronic pancreatitis, 45 patients with pancreatic cancer and 128 healthy subjects. The presence of I and D variants in the ACE gene was analyzed by a polymerase chain reaction (PCR) method. Distribution of ACE ID genotypes was analyzed by means of logistic regression. When chronic pancreatitis and pancreatic cancer groups were compared in the univariate analysis, the following factors were identified as statistically significant predictors of pancreatic disease: age, gender, smoking, fat intake, ACE II genotype and ACE DD genotype. However, in the multivariate analysis, only age, gender and smoking were singled out as predictors for the occurrence of pancreatic disease. Our findings indicate that the ACE I/D polymorphism could play a role in the development of chronic pancreatitis and pancreatic cancer through interaction with other genetic and environmental factors.

Survivin gene promoter polymorphism ‐31G/C as a risk factor for keratocystic odontogenic tumor development

Several single nucleotide polymorphisms in survivin gene promoters, notably -31G/C, have been shown to modulate the expression and activity of the survivin protein. Consequently, the -31G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The aim of this study was to investigate a possible association between the -31G/C polymorphism and the risk for keratocystic odontogenic tumor (KCOT) development. DNA from 52 biopsy specimens of KCOTs and from 82 buccal swabs of healthy individuals was subjected to PCR restriction fragment length polymorphism analysis to identify individual genotypes. The distribution of genotypes in KCOT and control groups, respectively, was: GG: 30 (57.7%) vs. 26 (31.7%); CG: 17 (32.7%) vs. 45 (54.9%); and CC: 5 (9.6%) vs. 11 (13.4%), respectively. These differences were statistically significant. The G allele was more common in the KCOT group than in the control group: 76 (74%) vs. 96 (59%), respectively. Logistic regression analysis showed that GC heterozygotes had a considerably decreased susceptibility for KCOTs compared with GG homozygotes. The same was true for GC+CC vs. GG. The GG genotype of the -31G/C polymorphism might be a risk factor for KCOT development.

Immediately loaded mini dental implants as overdenture retainers: 1-Year cohort study of implant stability and peri-implant marginal bone level

AIM This 1-year cohort study investigated stability and peri-implant marginal bone level of immediately loaded mini dental implants used to retain overdentures. MATERIALS AND METHODS Each of 30 edentulous patients received 4 mini dental implants (1.8 mm × 13 mm) in the interforaminal mandibular region. The implants were immediately loaded with pre-made overdentures. Outcome measures included implant stability and bone resorption. Implant stability was measured using the Periotest Classic(®) device immediately after placement and on the 3rd and 6th weeks and the 4th, 6th and 12th months postoperatively. The peri-implant marginal bone level (PIBL) was evaluated at the implants mesial and distal sides from the polished platform to the marginal crest. Radiographs were taken using a tailored film holder to reproducibly position the X-ray tube at the 6th week, 4th and 12th months postoperatively. RESULTS The primary stability (Periotest value, PTV) measured -0.27 ± 3.41 on a scale of -8 to + 50 (lower PTV reflects higher stability). The secondary stability decreased significantly until week 6 (mean PTV = 7.61 ± 7.05) then increased significantly reaching (PTV = 6.17 ± 6.15) at 12 months. The mean PIBL measured -0.40 mm after 1 year of functional loading, with no statistically significant differences at the various follow-ups (p = 0.218). CONCLUSIONS Mini dental implants placed into the interforaminal region could achieve a favorable primary stability for immediate loading. The follow-up Periotest values fluctuated, apparently reflecting the dynamics of bone remodeling, with the implants remaining clinically stable (98.3%) after 1 year of function. The 1-year bone resorption around immediately loaded MDIs is within the clinically acceptable range for standard implants.

Risk factors for intraoperative hypotension during thyroid surgery

Background Hypotension is a common adverse effect of IV anaesthetics, especially during the induction of anaesthesia. The aim of our study was to determine the incidence and risk factors for intraoperative hypotension (IOH) in thyroid surgery, as well as to determine whether and to what extent IOH affects the occurrence of postoperative hypotension. Material/Methods The study included 1252 euthyroid patients, ASA 2 and ASA 3 status (American Society of Anesthesiologists physical status classification), who had thyroid surgery between 2007 and 2011. IOH was defined as a decrease in systolic blood pressure of >20% of baseline values. We studied the influence of demographic characteristics (sex, age, body mass index-BMI), comorbidity, type and duration of surgery, and anaesthesia on the occurrence of IOH. Univariate and multivariate logistic regression were used to determine predictors of occurrence of IOH. Results IOH was registered in 6.5% of patients. The most common operation was thyroidectomy. Patients with IOH were younger, had lower BMI, and significantly less often had hypertension as a coexisting disease. The multivariate regression model identified BMI and the absence of hypertension as a coexisting disease, and as independent predictors of occurrence of IOH. Significantly more patients with IOH had postoperative hypotension (9.9% vs. 2.4%, p=0.000). Conclusions IOH is common, even during operations of short duration and with minimal bleeding. It is necessary to pay special attention to these patients, given that many of these patients remained hypotensive during the postoperative period.

Clinical relevance of IL-6 gene polymorphism in severely injured patients

In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7 days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL- 6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism.

Training Induces Cognitive Bias: The Case of a Simulation-Based Emergency Airway Curriculum

Introduction Training-induced cognitive bias may affect performance. Using a simulation-based emergency airway curriculum, we tested the hypothesis that curriculum design would induce bias and affect decision making. Methods Twenty-three novice anesthesiology residents were randomized into 2 groups. The primary outcome measure was the initiation of supraglottic airway and cricothyroidotomy techniques in a simulated cannot-ventilate, cannot-intubate scenario during 3 evaluation sessions. Secondary outcomes were response times for device initiation. After a baseline evaluation and didactic lecture, residents received an initial practical training in either surgical cricothyroidotomy (CRIC group) or supraglottic airway (SGA group). After the midtest, the groups switched to receive the alternate training. Results From baseline to midtest, the SGA group increased initiation of supraglottic airway but not cricothyroidotomy. The CRIC group increased initiation of cricothyroidotomy but not supraglottic airway. After completion of training in both techniques, the SGA group increased initiation of both supraglottic airway and cricothyroidotomy. In contrast, the CRIC group increased initiation of cricothyroidotomy but failed to change practice in supraglottic airway. Final test response times showed that the CRIC group was slower to initiate supraglottic airway and faster to initiate cricothyroidotomy. Discussion Practical training in only 1 technique caused bias in both groups despite a preceding didactic lecture. The chief finding was an asymmetrical effect of training sequence even after training in both techniques. Initial training in cricothyroidotomy caused bias that did not correct despite subsequent supraglottic airway training. Educators must be alert to the risk of inducing cognitive bias when designing curricula.

Effect of myocardial revascularisation on left ventricular systolic function in patients with and without viable myocardium: should non-viable segments be revascularised?

Objective To assess the effect of surgical revascularisation on left ventricular (LV) systolic function in patients with viable and non-viable dysfunctional LV segments determined by low dose dobutamine stress echocardiography (DSE). Design Prospective observational cohort study. Setting Single tertiary care centre. Patients Consecutive patients referred to surgical revascularisation (n=115). Interventions DSE and surgical revascularisation. Main outcome measures Functional recovery defined as increase in ejection fraction ≥5% 1 year after revascularisation in patients with and without viable myocardium (viability defined as improvement of contractility in ≥4 LV segments on DSE). Results The mean age, ejection fraction and wall motion score index (WMSi) of patients were 59±9 years, 44±9% and 1.82±0.31, respectively. There was no difference between DSE positive and DSE negative patients for any of those parameters at baseline study (p>0.05 for all). After 12 months, the ejection fraction increased 11±1% in patients with viable myocardium vs 7±1% in patients without viable myocardium (p=0.002). Moreover, in patients with viable myocardium, the greatest increase of ejection fraction occurred 1 month after surgery (9±1%), whereas in those patients with negative DSE the ejection fraction increased more gradually (2±1% after 1 month, p=0.002 between groups for 1 month vs preoperative value), but still improved after 12 months follow-up (p<0.0001 in time for both groups). Conclusions It appears that patients with LV dysfunction, but without viable myocardium, may also benefit from myocardial revascularisation. Functional recovery continuously occurs throughout the first year after surgical treatment.

Occlusal stabilization splint for patients with temporomandibular disorders: Meta-analysis of short and long term effects

Background Psychological discomfort, physical disability and functional limitations of the orofacial system have a major impact on everyday life of patients with temporomandibular disorders (TMDs). In this study we sought to determine short and long term effects of stabilization splint (SS) in treatment of TMDs, and to identify factors influencing its efficacy. Methods MEDLINE, Web of Science and EMBASE were searched for randomized controlled trials (RCTs) comparing SS to: non-occluding splint, occlusal oral appliances, physiotherapy, behavioral therapy, counseling and no treatment. Random effects method was used to summarize outcomes. The effect estimates were expressed as odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval. Subgroup analyses were carried out according to the use of Research Diagnostic Criteria (RDC/TMD) and TMDs origin. Strength of evidence was assessed by GRADE. Meta-regression was applied. Results Thirty three eligible RCTs were included in meta-analysis. In short term, SS presented positive overall effect on pain reduction (OR 2.08; p = 0.01) and pain intensity (SMD -0.33; p = 0.02). Subgroup analyses confirmed SS effect in studies used RDC/TMD and revealed its effect in patients with TMDs of muscular origin. Important decrease of muscle tenderness (OR 1.97; p = 0.03) and improvement of mouth opening (SMD -0.30; p = 0.04) were found. SS in comparison to oral appliances showed no difference (OR 0.74; p = 0.24). Meta-regression identified continuous use of SS during the day as a factor influencing efficacy (p = 0.01). Long term results showed no difference in observed outcomes between groups. Low quality of evidence was found for primary outcomes. Conclusion SS presented short term benefit for patients with TMDs. In long term follow up, the effect is equalized with other therapeutic modalities. Further studies based on appropriate use of standardized criteria for patient recruitment and outcomes under assessment are needed to better define SS effect persistence in long term.