Conventionally prepared endobiliary brushings are moderately (42%) sensitive and highly (98%) specific in detecting malignancy. The performance and morphological features of brushings prepared by Thinprep®, a liquid‐based method are mostly unknown. All brushings were retrieved from the laboratory files. Disease was classified as benign or malignant by linkage with the provincial cancer registry and sensitivity, specificity, positive (PPV) and negative predictive values (NPV) calculated. True positives and negatives were reviewed and predictive morphological features analysed by regression tree analysis. Out of 149 brushings, 55 (37%) were positive and 94 (63%) negative. Malignancy was identified in 86 (58%) and benign disease in 63 (42%) of the cases. The sensitivity was 51%, specificity 83%, PPV 80% and NPV 55%. Absolute discriminants of positive and negative brushings were not found, but nuclear cytoplasmic ratio was a useful feature. The performance of Thinprep®‐prepared brushings from this anatomical site was comparable with conventional preparations.

5573 Background: Radical treatment of NPC consists of radiotherapy (RT) ± chemotherapy. The ideal chemotherapy regimen to be given with RT is unknown. We report our institute's experience with radical treatment of NPC. Methods: Seventy-nine NPC patients were treated radically at the Tom Baker Cancer Centre (TBCC) between 1992–2002. Their charts were reviewed for initial patient characteristics, treatment given, rate of grade 3–4 acute and late toxicities according to the Radiation Therapy Oncology Group (RTOG) scales, failure patterns and causes of death. Data was analyzed using Intercooled Stata 8 (Stata Corporation, College Station, TX). Kaplan Meier estimates of 3-year overall and disease-free survival (OS, DFS) were calculated. Results: The majority of patients (63.3%) had stage III-IVb disease. Mean RT dose to gross disease was 67.9 Gy and mean treatment time was 50.7 days. Patients were treated with one of three different regimens: RT alone (n=18), RT with concurrent carboplatin, 100 mg/m2 weekly X 5 doses (n=45) or RT with concurrent cisplatin, 20 mg/m2 weeks 1 & 5 of RT (n=16). 94.4%, 80.0%, and 81.2% of each group received all prescribed treatments, respectively. With a mean follow-up of 65 months, the 3-year estimate of DFS in each group was 54.4%, 64.4%, and 73.3%, respectively. With a mean follow-up of 88 months, the 3-year estimate of OS in each group was 49.9%, 67.9% and 70.2%, respectively. Maximal rates of RTOG acute grade 3–4 toxicities were 38.9%, 48.9% and 31.3% respectively. Five patients (6.3%) had late grade 3–4 toxicities. There were no treatment-related deaths. 25.3% of patients were hospitalized during treatment and 71.6% lost =< 9.9% of their pre-treatment weight. Most failures were locoregional (57.1%) with a significant proportion being distant (42.9%). The majority of deaths were NPC-related (90.3%). Conclusions: At the TBCC, concurrent chemoRT for NPC confers a trend for improved DFS and OS compared with RT alone. Toxicity rates in NPC patients receiving concurrent chemoRT were acceptable. No significant financial relationships to disclose.

This study examined the small area variation in motor vehicle crash fatality rates in the province of Alberta, Canada. Motor vehicle crash fatality rates per 100,000 population (1995–1997, inclusive) were determined for five geographic areas in the province. The rates showed substantial, statistically significant variation across areas, with fatality rates lowest in the urban areas of Calgary and Edmonton, and highest in the rural areas (south, central, and northern Alberta). Examination of area-level predictors—population density, impaired driving citation rates, education level, unemployment levels, and ethnicity—showed that population density and impaired driving rates were associated with motor vehicle crash fatality rates. There was a five-fold difference in annual motor vehicle crash fatality rates between rural (22.9/100,000) and urban areas (4.4/100,000), whereas annual impaired driving rates were around 1.8% in rural areas, compared with 0.6% in urban areas. Because of multicollinearity problems, it was not possible to estimate a multivariable Poisson regression model. In conclusion, rural areas in the province of Alberta demonstrate a significantly higher motor vehicle crash fatality rate, compared with urban areas.

Although controversial, diagnosis of luteal phase defect (LPD) includes the morphological assessment of endometrial development. This study was conducted to determine if refresher training in the histological criteria could improve the accuracy and interobserver reproducibility of endometrial dating. Seventy-eight endometrial biopsies were dated by a reference panel of two pathologists and then reviewed twice by a study panel of four pathologists. In the first review, usual practice was applied. Prior to the second review, they studied a standard document of histological criteria. Samples were dated as proliferative, secretory (post-ovulatory day, POD), menstrual, and undatable. Accuracy levels based on the reference dating and agreement levels using kappa values were calculated per review and compared. The kappa for overall dating was 0.683 in the first review and 0.696 in the second. The respective first and second review kappa values were 0.736 and 0.771 for proliferative, and 0.794 and 0.764 for secretory. Amongst those dated as secretory in the first and second reviews, respectively, 31 and 28% were assigned the same POD by any two panellists, 68 and 63% were dated to within 1 day, and 77 and 71% were dated to within 2 days. Accuracy levels per panellist for overall dating were very high in both reviews but were low for individual PODs. Accuracy and interobserver reproducibility were unaffected by refresher training, suggesting the limits of histological dating have been reached.

In this clinical and histopathological study, the frequency of long-term glioblastoma multiforme (GBM) survivors (LTGBMSs) was determined in a population-based study. The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in Alberta between January 1, 1975, and December 31, 1991. Patient charts were reviewed and histology reexamined. LTGBMSs were defined as GBM patients surviving 3 years after diagnosis. Each LTGBMS was compared with 3 age-, sex-, and year of diagnosis-matched controls, and patient/treatment or tumor characteristics that predicted long-term survival were determined. There were 689 GBMs diagnosed in the study period; 15 (2.2%) of these patients survived 3 years. LTGBMSs (average age, 43.5 +/- 3.3 years) were significantly younger when compared with all GBM patients (average age, 53.0 +/- 0.56 years). LTGBMSs had a higher Karnofsky Performance Status score at diagnosis compared with controls. LTGBMSs were much more likely to have had a gross total resection and adjuvant chemotherapy than control GBM patients. Tumors from LTGBMSs tended to have fewer mitoses and a significantly lower Ki-67 cellular proliferation index compared with controls. Radiation-induced dementia was common and disabling in LTG-BMSs. In conclusion, conventionally treated GBM patients in an unselected population have a very small chance of long-term survival. The use of aggressive surgical resection and adjuvant chemotherapy may make long-term survival more likely in GBM patients if their performance status is high at diagnosis.

We studied publication rates and determinants of publication in GI-research. In particular, our concern was the possibility of publication bias, i.e. publication based on the statistical significance of study results. Methods. A random sample (n=l,000, stratified by study type) of all abstracts submitted to the 1992 to 1995 AGA-meetings, was followed up by a computerized literature search (Medline), as well as by postal questionnaires to abstract authors. In addition, abstracts were evaluated for study design features, statistical significance of study results, sample size, and research topic. Abstract evaluation was blinded with respect to acceptance, authors and origin. A quality score was assigned to all abstracts, based on completeness of reporting and measures undertaken to improve internal validity. High impact journals were defined as scientific impact factors (IF) > 5. Differences in publication were tested using log rank tests and Cox regression analysis. Results. Information is available on research presented in 232 abstracts submitted to the 1992-1994 meetings. Within the follow-up period of 3-5 years, 121 research projects (52%) were published in full, 63% of the subgroup of controlled clinical trials (CCT), 57% of basic science studies (BSS). Thirty percent of all abstracts were published within one year of the meeting. The majority of publications (60%) were in GI&Hepatology journals (71% of CCT publications, most frequently Dig Dis Sci, Am J Gastroenterol and Gastroenterology), followed by basic science journals (51% of BSS, most frequently Am J Physiol). Only 2% of all projects presented as abstracts were subsequently published in general medical journals, 19% of all publications were in high IF-journals, 98% were in English. Log ranks tests showed significantly better outcomes, when abstracts had been accepted for AGApresentation (p=.01). Also, outcome was dependent on study type, with CCT and BSS being more likely to be published than epidemiological or other research on humans (p=.03). With respect to topics, research on IBD had the highest publication rates (86%), research on upper GI-problems the lowest (43%), but overall, the research area was not a significant predictor (p=.l). There was no difference in publication rates, or in the percentage of high IF publications between North-American, Australian, and European research. However, although not statistically significant, countries other than these had markedly less overall publications (30% as compared to 54%, p=0.07), and none in high IF-journals. Statistical significance of study results and sample size could not be shown to influence publication rates, nor was the formal quality of the respective AGA abstract predictive. Cox regression analysis retained abstract acceptance as the only significant predictor of subsequent full publication (HR 1,9, CI 1.2-3.0). Preliminary results from the postal survey found lack of time or loss of interest the most frequent reasons for non publication. In 43% of unpublished projects, a manuscript had not or not yet been prepared. Conclusions: Acceptance for abstract presentation was found to be the only significant predictor of full publication of research projects initially submitted as abstracts to DDW meetings. There is, in addition, some evidence, that the country of origin, research type and research topic may be of importance. Bias based on the statistical significance of the study findings (publication bias) does not seem to be an issue. *Fellow of the German Academic Exchange Service (DAAD). Research funded by the Calgary Regional Health Authority (CRHA).

We studied publication rates and determinants of publication in GI-research.In particular, our concern was the possibility of publication bias, i.e. publication based on the statistical significance of study results.Methods.A random sample (n=l,000, stratified by study type) of all abstracts submitted to the 1992 to 1995 AGA-meetings, was followed up by a computerized literature search (Medline), as well as by postal questionnaires to abstract authors.In addition, abstracts were evaluated for study design features, statistical significance of study results, sample size, and research topic.Abstract evaluation was blinded with respect to acceptance, authors and origin.A quality score was assigned to all abstracts, based on completeness of reporting and measures undertaken to improve internal validity.High impact journals were defined as scientific impact factors (IF) > 5. Differences in publication were tested using log rank tests and Cox regression analysis.Results.Information is available on research presented in 232 abstracts submitted to the 1992-1994 meetings.Within the follow-up period of 3-5 years, 121 research projects (52%) were published in full, 63% of the subgroup of controlled clinical trials (CCT), 57% of basic science studies (BSS).Thirty percent of all abstracts were published within one year of the meeting.The majority of publications (60%) were in GI&Hepatology journals (71% of CCT publications, most frequently Dig Dis Sci, Am J Gastroenterol and Gastroenterology), followed by basic science journals (51% of BSS, most frequently Am J Physiol).Only 2% of all projects presented as abstracts were subsequently published in general medical journals, 19% of all publications were in high IF-journals, 98% were in English.Log ranks tests showed significantly better outcomes, when abstracts had been accepted for AGApresentation (p=.01).Also, outcome was dependent on study type, with CCT and BSS being more likely to be published than epidemiological or other research on humans (p=.03).With respect to topics, research on IBD had the highest publication rates (86%), research on upper GI-problems the lowest (43%), but overall, the research area was not a significant predictor (p=.l).There was no difference in publication rates, or in the percentage of high IF publications between North-American, Australian, and European research.However, although not statistically significant, countries other than these had markedly less overall publications (30% as compared to 54%, p=0.07), and none in high IF-journals.Statistical significance of study results and sample size could not be shown to influence publication rates, nor was the formal quality of the respective AGA abstract predictive.Cox regression analysis retained abstract acceptance as the only significant predictor of subsequent full publication (HR 1,9, CI 1.2-3.0).Preliminary results from the postal survey found lack of time or loss of interest the most frequent reasons for non publication.

Purpose: Extra-neural metastases from glioblastoma multiforme (GBM) are rare. Because gelatinases-A and -B have been implicated in tumor invasion/metastasis in non-neural tumors, we compared the expression of gelatinase-A and -B in 2 patients (both had a prior craniotomy performed) with extraneural metastases from GBM to expression levels in 24 other gliomas; 15 non-metastatic GBMs, 9 other lower grade gliomas, and 7 normal brain tissues. Methods: The intracerebral tumor from both patients, patient # 1's extraneural metastases, 24 other gliomas, 1 sample of reactive astrocytes and 7 normal brain tissues were studied using gelatin zymography. The active form of gelatinases was confirmed by co-migration after activation with APMA. Results: Expression of the latent form of gelatinase-A correlated with glioma grade (r = 0.486; p=0.0053). Active gelatinase-A was found only in the 2 GBMs with extraneural metastases and patient # 1's cervical metastases. In contrast, latent gelatinase-B levels correlated more strongly with histologic grade (r=0.577; p=0.0009) (higher levels with higher grades). Very high levels of gelatinase-B were seen in both GBMs with extraneural metastases, a cervical extraneural metastases, and 2 GBMs without metastases. Conclusions: We observed that gelatinases-A and -B are present in most gliomas but we found active gelatinase-A only in the GBMs with extraneural metastases suggesting that the active form of this enzyme may determine the metastatic potential of GBMs. We propose that high levels of gelatinolytic activities are associated with intracerebral invasion and rarely, metastases of GBMs.

To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established asseous metastases and persistent bone pain were randomized to receive! either clodronate (600 mg or 1500 mg in 500 mt of normal saline) or 500 mt of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period Forty-six patients were evaluable (77%). A treatment X period interaction was identified in thc VAS and daily morphine equivalent dose (DMED) scores. First period analysis of thp VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively from baseline, but were not significantly different from changes following placebo. The average change in DMED was - 6.4 (SE = 2.9) following clodronate and was + 24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo and eight (17%) had no preference (p = 0.0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, a nd no difference was apparent in six (13%) (p < 0.0001). intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain. (C) U.S. Cancer Pain Relief Committee, 1997.

A paired-comparison study of manual and automated (PAPNET) screenings of cervico-vaginal smears (Pap tests) was conducted to determine whether primary PAPNET screening was a reliable alternative to manual screening. A series of 5,037 consecutive Pap tests was first screened by the manual method. Next they were scanned by the PAPNET system, the DAT tapes were reviewed, and using a nonspecific triage protocol, abnormal tests were identified for limited, manual rescreening. False-negative rates (FNR) for each method were calculated and analyzed for due cause. By manual and PAPNET screening, respectively, there were 436 (8.6%) and 250 (4.9%) abnormal results. Manual screening missed 18 abnormals (5 SIL) and PAPNET 202 (7 SIL). The primary, manual screenings relating to the PAPNET false-negative tests were reviewed and revised to normal in 30. Based on the changes in the other 172 tests, cellular features ostensibly missed by the PAPNET system were listed to form part of a specific triage protocol, and were used to scrutinize the companion 172 DAT tapes: 150 tapes were abnormal. The manual FNR for an abnormal (SIL) result was 4% and (8.8%), respectively. Equivalent FNR pre- and postreviews for the PAPNET system were 44.6% (10.6%) and 5.2% (1.3%), respectively. This study discovered that the evaluation of some cell features in monitor-based, video images was the most important factor limiting the application of the PAPNET system as a primary screener. When governed by a specific triage protocol incorporating these features, primary PAPNET screening has the potential to equal the laboratory threshold of manual screening and be a better detector of SIL.