Quantitative Assessment of Rectal Cancer Response to Neoadjuvant Combined Chemotherapy and Radiation Therapy: Comparison of Three Methods of Positioning Region of Interest for ADC Measurements at Diffusion-weighted MR Imaging.

Purpose To determine the impact of three different methods of region of interest (ROI) positioning for apparent diffusion coefficient (ADC) measurements on the assessment of complete response (CR) to neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer. Materials and Methods Institutional review board approval was obtained for this study; all patients gave written informed consent. ADCs were measured by two radiologists using three circular ROIs (three-ROIs), single-section (SS), and whole-tumor volume (WTV) methods in 62 patients with locally advanced rectal cancer on pre- and post-CRT images. Interobserver variability was analyzed by calculating intraclass correlation coefficient (ICC). Descriptive statistics and areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate performance in determining CR from pre- and post-CRT ADCs and ADC change. Histopathologic tumor regression grade was the reference standard. Results SS and WTV methods yielded higher AUCs than did the three-ROIs method when determining CR from post-CRT ADC (0.874 [95% confidence interval {CI}: 0.778, 0.970] and 0.886 [95% CI: 0.781, 0.990] vs 0.731 [95% CI: 0.583, 0.878], respectively; P = .033 and P = .003) and numeric change (0.892 [95% CI: 0.812, 0.972] and 0.897 [95% CI: 0.801, 0.994] vs 0.740 [95% CI: 0.591, 0.890], respectively; P = .048 and P = .0021). Respective accuracies of SS, WTV, and three-ROIs methods were 79% (49 of 62), 77% (48 of 62), and 61% (38 of 62) for post-CRT, 79% (49 of 62), 86% (53 of 62), and 60% (37 of 62) for numeric ADC change, and 77% (48 of 62), 84% (52 of 62), and 57% (35 of 62) for percentage ADC change (ADC cut-offs: 1.21, 1.30, and 1.05 × 10-3 mm2/sec, 0.33, 0.45, and 0.27 × 10-3 mm2/sec increases, and 40%, 54%, and 27% increases, respectively). Post-CRT and ADC change measurements achieved negative predictive values of 96% (44 of 46) to 100% (39 of 39). Intraobserver agreement was highest for WTV-derived ADCs (ICC, 0.742 [95% CI: 0.316, 0.892] to 0.891 [95% CI: 0.615, 0.956]) and higher for all pretreatment than posttreatment measurements (ICC, 0.761 [95% CI: 0.209, 0.930] and 0.648 [95% CI: 0.164, 0.895] for three-ROIs method, 0.608 [95% CI: 0.287, 0.844] and 0.582 [95% CI: 0.176, 0.870] for SS method, 0.891 [95% CI: 0.615, 0.956] and 0.742 for WTV method [95% CI: 0.316, 0.892]). Conclusion Tumor ADCs are highly dependent on the ROI positioning method used. Larger area measurements yield greater accuracy in response assessment. Post-CRT ADCs and values of ADC changes accurately identify noncomplete responders. WTV measurement of percentage ADC change provides the best results. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on September 19, 2016.

In vitro evaluation of neurotoxicity potential and oxidative stress responses of diazinon and its degradation products in rat brain synaptosomes.

Although primary toxic action of organophosphorous insecticides is associated with acetylcholinesterase inhibition, later studies suggest that oxidative stress may be responsible for induced organophosphates toxicity. These studies mostly include thio forms, while the effects of their metabolites/degradation products have been less investigated. Therefore, this paper studies the toxic effects of diazinon degradation products, diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol, and compares them with the toxic potential of the parent compound. The toxicity induced by various concentrations of the investigated compounds was in vitro evaluated by the activities of acetylcholinesterase, ATPases, antioxidant defense enzymes and lactate dehydrogenase, and malondialdehyde level in rat brain synaptosomes. Diazinon inhibited acetylcholinesterase and Na(+)/K(+)-ATPase in dose-dependent manner, while the inhibition of ecto-ATPase activity was less than 15% at all investigated concentrations. It did not demonstrate noteworthy prooxidative properties causing increase (up to 10%) in antioxidant enzymes activity and malondialdehyde level, as a marker of lipid peroxidation. Diazinon oxidation product, diazoxon was found as the most toxic investigated compound. Beside the expected strong inhibitory effect on acetylcholinesterase, it induced dose-dependent and almost complete inhibition of Na(+)/K(+)-ATPase and ecto-ATPase at the highest investigated concentration (0.1mM). Increasing diazoxon concentrations activated catalase (up to 30%), superoxide dismutase (up to 50%), glutathione peroxidase (up to 30%), and significantly increased malondialdehyde level (up to 50%). The investigated hydrolysis product of diazinon, 2-isopropyl-6-methyl-4-pyrimidinol did not remarkably alter the activities of acetylcholinesterase, Na(+)/K(+)-ATPase, catalase, glutathione peroxidase and lipid peroxidation level (up to about 10%). Although this diazinon metabolite has been known as non toxic, it induced superoxide dismutase stimulation up to 30%. Finally, even high concentrations of both diazinon and its metabolites did noticeably affect lactate dehydrogenase activity as a marker of synaptosomal integrity. The changes in investigated biochemical parameters in rat brain synaptosomes could serve as indicators of toxicity due to the exposure to thio organophosphates and/or their break-down products.

Gallium-68 DOTATOC PET/CT in vivo characterization of somatostatin receptor expression in the prostate.

AIM: The aim was to investigate somatostatin receptor (sstr) expression in normal prostate by determining the maximum standardized uptake value (SUVmax) of (68)Ga-DOTATOC PET/CT in neuroendocrine tumor (NET) patients, without NET involvement of the prostate gland, for establishing the reference standard. METHODS: Sixty-four NET patients underwent (68)Ga-DOTATOC PET/CT. SUVmax of the prostate gland, normal liver, testes, and gluteus muscles were evaluated. The prostate gland size was measured. Statistical analysis was performed using dedicated software (SPSS13). RESULTS: Mean/median (68)Ga-DOTATOC SUVmax values were as follows: normal prostate 2.6 ± 0.0, slightly enlarged prostate 4.2 ± 1.6, prostatic hypertrophy 4.9 ± 1.6, prostatic hyperplasia 5.0 ± 1.5, prostate cancer 9.5 ± 2.1, normal liver 7.3 ± 1.8, testes 1.8 ± 0.5, and gluteus 1.0 ± 0.2. The normal prostate gland had three times less sstr expression than normal liver tissue. Strong correlation was found between patient age and sstr expression in prostate/prostate size. No significant difference existed in sstr expression between prostatic hypertrophy and hyperplasia. Much higher sstr expression was found in prostatic cancer compared with normal prostate. CONCLUSION: (68)Ga-DOTATOC PET/CT defines the baseline sstr uptake in prostate not affected by NET (significantly lower than in the liver). Higher values were established in prostatic hyperplasia and hypertrophy. Only concomitant prostate cancer was associated with higher SUVmax in comparison with non-neoplastic liver.

Activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in different stages of colorectal carcinoma.

BACKGROUND: Reactive oxygen species are involved in the pathogenesis of colorectal carcinoma. Clarification of oxidative/antioxidant specificities of different stages of colorectal carcinoma is of special importance. AIM: To determine oxidative/antioxidant status in plasma of patients with different stages of colorectal carcinoma using malondialdehyde concentration, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and distribution of superoxide dismutase isoforms. METHODS: Lipid peroxidation and antioxidant enzymes activity were estimated using spectrophotometric methods. Reverse zymography was applied for characterization of superoxide dismutase isoforms. RESULTS: Lipid peroxidation is increased in all groups compared to the control, but without differences between different stages of colorectal carcinoma. Total superoxide dismutase activity is lower in all colorectal carcinoma groups than in control, and there is a significant increase in tumor stage IV when compared with tumor stage II. Manganese superoxide dismutase isoform is dominant in all groups and its relative activities are significantly higher than activities of a copper/zinc isoform. Total peroxidase potential reflected in catalase and glutathione peroxidase activity is increased when compared to the control, but without any significant differences between colorectal carcinoma groups. Glutathione reductase activity is lower in all colorectal carcinoma groups than in control, and a significant decrease in glutathione reductase activity was obtained between patients in tumor stage II and III compared to tumor stage IV. CONCLUSIONS: Colorectal carcinoma is characterized by increased oxidative stress and antioxidant disbalance. Progression of disease is followed by an increase in redox disbalance.

Investigation of blood perfusion and metabolic activity of brain tumours in adults by using 99mTc-methoxyisobutylisonitrile.

OBJECTIVES: (i) To examine blood perfusion and metabolic activity of various brain tumours using radionuclide cerebral angiography (RCA) and single-photon emission tomography (SPET) after a single dose of Tc-methoxyisobutylisonitrile (MIBI). (ii) To examine if the inclusion of RCA can improve insight into the relative contribution of tumour perfusion to the uptake of MIBI shown by SPET, and to improve evaluation of tumour biology. (iii) To determine the value and the roles of MIBI in the management of brain tumour patients. METHODS: Fifty adult patients (38 male, 12 female) with a total of 56 intracranial space-occupying lesions have been included prospectively, 37 of which were newly diagnosed and the remaining with signs of recurrence/rest of earlier resected and irradiated brain tumours. The control group consisted of nine volunteers with no evidence of organic cerebral disease. Scintigraphic examination consisted of a dynamic first-pass study lasting 60 s (3 s/frame) and two SPET studies (60 projections each, 25 s/projection), starting 15 min and 2 h after intravenous injection of MIBI. Regions of interest of the tumour and normal brain tissue were drawn on RCA and both early and delayed SPET slices. The following tumour/brain activity ratios have been calculated: (i) tumour perfusion index (P); (ii) early uptake index (E); (iii) delayed uptake index (D); and(iv) retention index (R). Analogous indices have been calculated from the same examinations performed in controls, reflecting maximal physiologic regional variations of perfusion and uptake in brain tissue. RESULTS: Mean P of various brain tumours (low-grade gliomas 0.98, anaplastic gliomas 1.14, glioblastoma multiforme 1.20, metastases 1.09, lymphomas 1.08) differ little from each other and do not exceed maximal physiologic regional variations of cerebral perfusion (1.33), with the exception of meningioma (1.87, F=2.83, P=0.015). The receiver operating characteristics curve analysis of P showed that for the cut-off value of 1.45 the sensitivity for distinguishing meningioma from other tumours is 75%, specificity 87%, positive predictive value 33% and negative predictive value 97%. Mean E of malignant brain tumours (8.3, n=31, 23 primary, eight secondary), except anaplastic gliomas (3.5, n=5), differed significantly (P=0.02) from those of benign gliomas (3, n=9) but not from that of meningioma (11.9, n=4). The cut-off value for distinguishing malignant from benign lesions on the basis of E set at 4.8 resulted in sensitivity 67%, specificity 75%, accuracy 70%, positive predictive value 80% and negative predictive value 60%. D and R showed tendency of wash-out of MIBI from meningiomas, but otherwise did not improve the results substantially. CONCLUSION: Integrated results of RCA and SPET with Tc-MIBI indicate that blood perfusion, blood-tumour barrier permeability and metabolic activity of the tumour are all very important for the resultant uptake shown by SPET. If the perfusion index is less than 1.45, then meningioma can be ruled out. Early SPET is recommendable for distinguishing glioblastoma from low-grade gliomas, as a complement to standard magnetic resonance imaging and/or computed tomography.

Influence of chronic obstructive pulmonary disease on postoperative lung function and complications in patients undergoing operations for primary non-small cell lung cancer.

OBJECTIVES: Recent data have suggested that there is a flexibility of borderline values of lung function tests in allowing safe lung resection. The aim of this study was to assess the pattern of postoperative lung function change in patients with chronic obstructive pulmonary disease compared with that of patients with normal lung function, and to compare the operative morbidity and mortality between these groups. METHODS: The study included 35 patients with chronic obstructive pulmonary disease and a control group of 47 patients with normal lung function who underwent lung resection for non-small cell lung cancer. The percent changes of lung function parameters after lung resection and operative morbidity and mortality were compared between groups. RESULTS: The mean postoperative loss in forced expiratory volume in the 1st second was significantly less in patients with chronic obstructive pulmonary disease who underwent lobectomy compared with that of patients with normal lung function (11.88% vs 24.6%, P < .05); forced expiratory flows at low lung volumes (50% and 25%) improved in patients who underwent lobectomy. The lung function change after pneumonectomy followed the same trend as that after lobectomy. In patients with chronic obstructive pulmonary disease, forced expiratory volume in the 1st second and small airways function significantly improved after preoperative bronchodilator therapy. In the group with chronic obstructive pulmonary disease, operative mortality was 0 and operative morbidity was 51.43%. CONCLUSIONS: Because the pattern of lung function change is different in patients with chronic obstructive pulmonary disease compared with that of patients with normal lung function, surgery can be offered to carefully selected patients with lung cancer, even in the presence of severely limited lung function.

[Effects of nitrous oxide on middle ear pressure].

INTRODUCTION: Recent literature data suggest that permanent or reversible hearing loss may occur after general anesthesia. The etiology varies, while hearing loss following middle ear surgery is attributed to exposure to nitrous oxide (N,0). The objective of our study was to measure, using tympanometry, the middle air pressure change caused by nitrous oxide during general anesthesia and to establish its emetogenic effects during the postoperative period. MATERIAL AND METHODS: This academic (non-commercial) prospective study included two groups of patients (a total of 58), with ASA status I, II and III. The study group (n 30) consisted of patients undergoing unilateral ear surgery. In this group, the intratympanic pressure was measured in the unoperated (healthy) ear before and during the surgery. The control group (n 28) patients underwent nose, throat or neck surgical interventions. This group underwent measurement of bilateral intratympanic pressure in healthy ears, before and during the surgery. Both groups were operated under general balanced anesthesia. Pain, nausea and antiemetics were monitored during the first 24 postoperative hours. Statistical analysis was performed using the Mann-Whitney-Wilcoxon test. RESULTS: This perioperative study confirmed the following: highly significant (p < 0.001) increase in intratympanic pressure in nonoperated ears in the study group and significant (p < 0.05) in controls. However, there was no statistical significance (p > 0.05) between groups. Pain was more freguent in controls, and nausea in the study group, but without significant difference (p > 0.05). CONCLUSIONS: Postoperative audiometry findings showed no conductive or sensorineural hearing loss after interventions. Nitrous oxide can be used in general balanced anesthesia with discontinuation 15 to 45 minutes before insertion of the tvmpanic membrane and completion of middle ear surgery.

Antibiotic consumption monitoring at the Institute of Otorhinolaryngology and Maxillofacial Surgery--Clinical Center of Serbia in 2001-2003.

BACKGROUND: At the Clinical Center of Serbia (CCS), which includes 21 Institutes and 6 Centers, approximately 10% of the total annual budgetary funds is spent on the drugs. During the studied period, it was estimated that 0.5% of the above amount has been spent at the Institute for Otorhinolaryngology and Maxillofacial surgery (Institute for ORL and MFS), Clinical Center of Serbia. The aim of this study was to find out if these antibiotics had been used rationally by the monitoring of antibiotics in relation to the number of inpatients, and by the 5 most frequent diagnoses. METHODS: The authors monitored the three-year consumption of antibiotics for inhospital treated patients during the period 2001-2003. Data were obtained from the itemized quarterly report on the consumption by the Central Pharmacy of the CCS. RESULTS: The results were statistically analyzed and presented in percentages and Defined Daily Dosages (DDD) for each group of the antibiotics. The results were analyzed in accordance with the World Health Organization Recommendations and the Guidelines. CONCLUSION: The authors concluded that antibiotics were adequately used at the Institute for ORL and MFS-CCS. The most commonly used antibiotics for gram-positive infections were those from the penicillin and cephalosporin groups. According to the international trends and recommendations, the selected therapy was rational and the antibiotics consumption was cut down during the observed three-year period. It was a true confirmation that the recommendations for the rational antibiotics consumption had been fruitful (produced good results).