Comparison between low-dose and standard-dose multidetector CT in patients with suspected chronic sinusitis

OBJECTIVE: This study was designed to compare low- and standard-dose multidetector CT (MDCT) findings in patients with suspected chronic sinusitis. SUBJECTS AND METHODS. Fifty patients underwent MDCT at 10 and 150 effective mAs. The low-dose MDCT protocol delivered a radiation dose of 0.047 mSv in men and 0.051 mSv in women, whereas the standard-dose MDCT protocol delivered a radiation dose of 0.70 mSv in men and 0.76 mSv in women. Scans of the right and left sides of sinonasal cavities were reviewed by three radiologists, with each physician reviewing a scan twice over an interval of more than 2 weeks. The reviewers were asked to evaluate the scans for eight mucosal and two bone abnormalities. We calculated the number of discrepancies in observed abnormalities between pairs of reviewers, among all three reviewers, and between findings on scans acquired with the two radiation doses. RESULTS: The mean number of discrepancies in observed abnormalities on scans acquired with different radiation doses ranged from 0 to 5.2. Discrepancies between pairs of reviewers ranged from 1.0 to 12.8 for low-dose scans and from 1.0 to 13.0 for standard-dose scans. Discrepancies among all reviewers ranged from 1.0 to 10.3 for low-dose scans and from 1.0 to 8.7 for standard-dose scans. In analyzing cases of significant discrepancies in observations, we found greater variation between pairs of reviewers and among all three reviewers than between findings obtained with different dose levels. CONCLUSION: Dose reduction played a far less important role in discrepancies of detected abnormalities than did the human element of reviewer observation. Given this finding and the fact that low-dose MDCT delivers a radiation dose that is no higher than that delivered by a four-view radiographic examination, low-dose MDCT should be considered the imaging method of choice in patients with suspected chronic sinusitis.     

Patient-Physician Relationship and Service Utilization: Preliminary Findings

BACKGROUND: Difficult physician-patient encounters pose a challenge in all aspects of health care. Characteristics of both physicians and patients affect the office encounter and utilization of services. The objectives of this study were to explore the impact of patients' characteristics and the patient-physician relationship on service utilization. METHOD: A sample of 22 family practice patients and their physicians completed questionnaires prior to and/or after an office visit. Chart review yielded demographic information and history. The number of office visits and phone calls were obtained from billing records. RESULTS: The number of patient-reported physical problems was correlated with negative affect (r = 0.63, p <.002), the number of phone calls to the office (r = 0.52, p <.02), and the difficulty of the encounter as perceived by the physician (r = 0.58, p <.005). The number of phone calls also correlated with the number of life events (r = 0.43, p <.05) and the patient's perception of the physician's warmth (r = 0.48, p <.03) and understanding (r = 0.44, p <.04). CONCLUSION: Life stress, negative affect, physical complaints, and the patients' perception of their physician impact utilization. Armed with information about patient characteristics prior to the office visit, the physician can increase efficiency and facilitate a more productive encounter.     

Efficiency of [<Superscript>18</Superscript>F]FDG PET in characterising renal cancer and detecting distant metastases: a comparison with CT

The purpose of this study was to assess the efficiency of fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the characterisation and primary staging of suspicious renal masses, in comparison with computed tomography, the current standard imaging modality. Fifty-three FDG PET studies were performed within the framework of a prospective study: 35 for both characterisation and staging of a suspicious mass, and 18 for staging early after surgical removal of a renal cancer. In the characterisation of renal masses, a high rate of false negative results was observed, leading to a sensitivity, specificity and accuracy of 47%, 80% and 51% respectively, versus 97%, 0/5 and 83% respectively for CT. FDG PET detected all the sites of distant metastasis revealed by CT, as well as eight additional metastatic sites, leading to an accuracy of 94% versus 89% for CT. However, 36/53 patients (68%) did not have any distant metastasis on either CT or on PET. All but one of these patients had a low Fuhrman histological grade and a limited local stage (pT2). We conclude that FDG PET does not offer any advantage over CT for the characterisation of renal masses but that it appears to be an efficient tool for the detection of distant metastasis in renal cancer. However, our data suggest that a selection process could be implemented to determine which patients should undergo PET. FDG PET could be performed in the event of a solitary metastasis or doubtful images on CT. Selection could also be based on adverse histological findings from nephrectomy specimens in order to perform staging early after nephrectomy.     

Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma: comparison of LENT/SOMA,RTOG/EORTC,and NCI-CTC scoring systems

PURPOSE: To prospectively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales. METHODS AND MATERIALS: A total of 226 patients were entered in a Phase III multicenter, randomized trial comparing radiotherapy alone (70 Gy in 35 fractions: Arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen containing carboplatin and 5-fluorouracil: Arm B). Five living patients, free of local or distant recurrences, could not be evaluated for late toxicity. Forty-four patients were eligible for late toxicity with a median follow-up of 5 years. Late toxicity was evaluated by the radiation oncologist using a large questionnaire containing 120 mixed items of three scales (NCI-CTC, LENT/SOMA, and RTOG). The data were then transposed on separate scales using corresponding grades. RESULTS: The 5-year overall survival rate was 22% in Arm B and 16% in Arm A (p = 0.05). The 5-year locoregional control rate was 48% in Arm B and 25% in Arm A (p = 0.002). The spinal cord was not affected by the concomitant adjunct of chemotherapy, and no deaths were caused by late toxicity. Using the three late toxicity scales, 100% of the patients treated with the combined modality (Arm B) developed one or more late complications vs. 94% in the radiotherapy-alone arm (Arm A). The difference was not statistically significant. The most commonly damaged organs (all Grade 1-4) were the salivary glands (100% in Arm B vs. 82% in Arm A, p <0.05), skin (78% vs. 47%, p <0.05), teeth (67% vs. 18%, p <0.05), mucosa (59% vs. 63% p = not significant), and mandible (44% vs. 12%, p <0.05). One or more Grade 3-4 complications occurred in 82% of the patients in Arm B vs. 47% in Arm A (p = 0.02) but concerned only the teeth. The correlation between the RTOG and LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1-4 toxicity (near 30%). The transposability of a patient's symptoms was significantly greater using the LENT/SOMA or RTOG/EORTC scaling systems than using the NCI-CTC system. CONCLUSION: Concomitant radiochemotherapy increased overall survival and locoregional control rates. The difference between the two treatment groups for Grade 3-4 complications was only significant for the teeth. The late toxicity assessment of a treatment may depend on the toxicity scale used. The LENT/SOMA scale seems to be the most accurate scale, but most of the score results were not concordant with those obtained with other scales. The results of this study confirm the necessity of using a common late toxicity scale in clinical trials.     

Phase II Study of Lonidamine and Diazepam in the Treatment of Recurrent Glioblastoma Multiforme

Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavours, with low response rates and survival rarely exceeding 6 months. There are no standard chemotherapeutic regimens and new therapeutic approaches have to be found. We report an open-label, uncontrolled, multicentre phase II trial of lonidamine (LND) and diazepam in 16 patients with GBM at first relapse and a Karnofsky performance status 70. The treatment regimen consisted of LND 450mg/day and diazepam 15mg/day orally of every 28-day cycle until progression or unacceptable toxicity. Patients received a median of three cycles (range, 1–12). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was closed. Nevertheless, seven stabilizations (50%) were observed. Median time to progression was 8 weeks (range, 5–19 weeks). Median overall survival from recurrence was 15 weeks (range, 14–61 weeks). No grade 3–4 toxicity, except somnolence, was observed and there were no therapy-related deaths. Dose reduction for diazepam due to somnolence (grade III) was performed in 9 patients. The combination of LND and diazepam is well tolerated. LND and diazepam, acting on two distinct mitochondrial sites involved in cellular energy metabolism, may exert a cytostatic effect on tumour growth as shown by the high percentage of stable patients. The LND–diazepam at the used dosing schedule did not show a complete or partial response. LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index.     

Vaginal reconstruction after pelvic exenteration: when and which techniques?

Pelvic exenterations are commonly performed to treat locally advanced or recurrent tumours of the pelvic organs to achieve long-term survival. Those procedures may present complications. Reconstructive procedures have become an important part of radical pelvic surgery to improve quality of life. Various surgical procedure of vaginal reconstruction have been describe. Myocutaneous flaps are effective in the prevention of major morbidity with pelvic filling and physiological neovagina. Vertical rectus abdominis myocutaneous flap is the technique of choice with simple harvesting and large pelvic filling. Gracilis and gluteal thight flaps are particularly adapted in pelvectomy with perineal resection. Enteroclpoplasty and omental flap must be used in radical colpectomie or difficulty pelvic access.     

The choice of approach in the surgical management of endometrial carcinoma: a retrospective serie of 155 cases

SETTING: Retrospective study of patients consecutively managed surgically for apparent stage I endometrial carcinoma in a comprehensive cancer center, using a standardized protocol for the choice of surgical approach: laparoscopically assisted vaginal hysterectomy (LAVH) as standard procedure, vaginal surgery in apparent stage IA grade 1 or in patients in poor medical condition, laparotomy in the case of subserous myometrial involvement at imaging or in patients with enlarged uteri or in the presence of a contra-indication to laparoscopy. MATERIALS AND METHODS: Excluding 2 patients in whom laparoscopy was converted in laparotomy, and 1 patient who had a full laparoscopic hysterectomy, the records of 155 patients were reviewed. All patients had a preoperative sonogram, and 74% had a preoperative MRI. Preoperative data, preoperative staging, operative data, pathological staging, postoperative complications, recurrence and survival were recorded. RESULTS: 69 patients (43.6%) had a LAVH procedure (group LAVH), 58 patients (36.7%) were treated by laparotomy (group TAH), and 28 patients (18%) were treated by simple vaginal hysterectomy (group VH). Patients in the vaginal group were significantly heavier (VH 91.3 kg 33, range 53-175) than those of the other two groups (TAH 76.5 12.7, range 48-142; LAVH 71.1 18.5, range 47-102). The number of large (> 10 cm) uteri was significantly greater in the TAH group (46.5%) than the LAVH group (26.1%, p = 0.02) or the VH group (14.3%, p = 0.007). Myometrial invasion was suspected in 53.6% of the VH group, 72.6% of the LAVH group, and 71.4% of the TAH group. Deep myometrial invasion was suspected in no patient of the VH group, 14.5% of the LAVH group and 70.7% of the TAH group. The LAVH group had a significantly longer mean operative time than the TAH group or the VH group.The number of perioperative complications was significantly higher in the TAH group (22.4%) compared to the LAVH group (5.6%) and the VH group (0%). Blood loss was significantly elevated in the laparotomy group compared to the other two groups. The mean number of nodes removed was significantly higher in the LAVH group (15.8 7.8, range 4-37) compared to the TAH group (11 5.3, range 2-25, p = 0.002). Of 155 patients, 100 (64.5%) had correct preoperative staging. In 19 (12.3%), FIGO stage was overestimated preoperatively, and in 36 (23.2%) the FIGO stage was underestimated preoperatively. Survival curves were not found significantly different between groups.     

Alpha-methylacyl-CoA racemase as an androgen-independent growth modifier in prostate cancer

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in beta-oxidation of branched-chain fatty acids and bile acid intermediates. Recent work has identified AMACR as a new diagnostic marker for prostate cancer (PCa). The data from the present study suggest that AMACR is also functionally important for the growth of PCa cells. Overexpressed AMACR from both clinical tissues and PCa cell lines is wild type by sequence analysis and functionally active by enzymatic assay. Correspondingly, enzyme activity of AMACR increases approximately 4-fold in PCa in comparison with adjacent normal prostate. Small interference RNA (siRNA) against AMACR, but not the control inverted siRNA, reduced the expression of AMACR and significantly impaired proliferation of the androgen-responsive PCa cell line LAPC-4. No effect was observed in HeLaS3 cells, which express AMACR at a low level. Cell cycle analyses revealed a G(2)-M cell cycle arrest in LAPC-4 cells treated with siRNA compared with mock treatment or control inverted siRNA. Expression of a siRNA-resistant form of AMACR in LAPC-4 cells protects the cells from growth arrest after AMACR-specific siRNA treatment. Data from Western blotting and luciferase-based reporter assays suggest that the function and expression of AMACR are independent of androgen receptor-mediated signaling. Moreover, simultaneous inhibition of both the AMACR pathway by siRNA and androgen signaling by means of androgen withdrawal or antiandrogen suppressed the growth of LAPC-4 cells to a greater extent than either treatment alone. Taken together, these data suggest that AMACR is essential for optimal growth of PCa cells in vitro and that this enzyme has the potential to be a complementary target with androgen ablation in PCa treatment.     

The proline-rich acidic protein is epigenetically regulated and inhibits growth of cancer cell lines

The proline-rich acidic protein (PRAP) gene was found previously to be expressed in the epithelial cells of the mouse and rat gastrointestinal tracts, and pregnant mouse uterus. This article describes the isolation, distribution, and functional characterization of the human homologue. PRAP was abundantly expressed in the epithelial cells of the human liver, kidney, gastrointestinal tract, and cervix. PRAP expression was significantly down-regulated in hepatocellular carcinoma and right colon adenocarcinoma compared with the respective adjacent normal tissues. Treatment of the cells with butyrate, trichostatin A, and 5'-aza-2' deoxycytidine caused increases in PRAP gene expression of up to 30-fold, suggesting that the gene is suppressed through epigenetic mechanisms involving histone deacetylation and methylation. To determine the significance of PRAP expression in cancer cells, we cloned PRAP and its two major splice variants from human colon and liver, and overexpressed it in HeLa, HT29, and HepG2 cells. PRAP caused cell growth inhibition in the cancer cell lines in transient transfection assays, colony formation assays, and in the growth rates of stable clones. The data suggest that PRAP and its variants may play an important role in maintaining normal growth homeostasis in epithelial cells. The epigenetic suppression of PRAP expression in cancer may cause growth dysregulation, a hallmark of the carcinogenic process.     

Assessment of exposure to a flood disaster in a mental-health study

The lasting psychological consequences of disasters are an important public health issue, especially for determining the support needed by victims. One important question in evaluating psychological consequences remains the assessment of individual disaster-related experiences or stressors. This article proposes two approaches towards the construction of cumulative exposure indicators (CEIs) for a disaster and discusses their relevance for other disasters. In 1997, we carried out a cross-sectional study of the association between the severity of exposure to a 1992 flood in southeastern France and the prevalence of psychological symptoms 5 years later. We interviewed 500 randomly selected subjects residing in one of the most affected municipalities and constructed two CEIs: one based on relevant articles in the literature and the second based on the results of a principal component analysis (PCA) of all the items exploring exposure to the flood. We compared these CEIs with a map of flood damage and tested the association between these indicators and a score of post-traumatic stress symptoms. Most of the subjects (79.1%) had been exposed to at least one stressor besides physical presence. The two CEIs were significantly correlated with one another; comparisons with the map showed that both had good ability to discriminate between mild and severe exposure. Multiple regression analyses showed a significant exposure-effect relation, of the same level of magnitude and significance, between the post-traumatic stress disorder score and each CEI. Our results show the appropriateness of such indicators in assessing the effect of cumulative stress from natural disasters. Guidelines should be developed to improve the comparability of instruments and help standardize methods for evaluating cumulative stress from disasters insofar as possible. Further research is nonetheless necessary to assess the consistency and reproducibility of the data collected.