bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXPRESSION OF CYCLOOXYGENASE‐2 PROTEIN IN SERRATED ADENOMAS OF THE LARGE INTESTINE
Authors: Takeuchi M , Kobayashi M , Suzuki Y , Honma T , Azumaya M , Shioji K , Narisawa R , Hayashi S , Ajioka Y , Asakura H 
Published: January 2004

Objectives  Recent studies suggest that cyclooxygenase‐2 (COX‐2) protein is involved in colorectal tumorigenesis, but its expression in serrated adenomas (SAs), a newly recognized category of colorectal neoplasia, has not been investigated in detail. The aim of this study was to evaluate the immunohistochemical expression of COX‐2 protein in SAs, especially compared with endoscopic features and with those in tubular adenomas and hyperplastic polyps.Materials and methods  A total of 79 SAs, 65 tubular adenomas, and 21 hyperplastic polyps, obtained by colonoscopic resection, was provided for the immunohistochemical staining using anti‐COX‐2 polyclonal antibody (PG27, 1:2500). The COX‐2 expression was scored in a semiquantitative evaluation according to the staining intensity and extent of positive neoplastic cells: score 0, no or faint chromagen deposition; 1, weak intensity or moderate intensity < 50%; 2, moderate intensity or strong intensity < 50%; 3, strong intensity.Results  Colonoscopically, SAs were divided into the following two patterns; cerebriform (n = 44), and hyperplastic (n = 35) pattern. The mean COX‐2 score in SAs with cerebriform pattern was significantly higher than that in SAs with hyperplastic pattern (1.61 vs. 0.97, P < 0.01). In contrast, the mean COX‐2 score in SAs with hyperplastic pattern was significantly higher than that in hyperplastic polyps (0.97 vs. 0.20, P < 0.01). In 26 SAs accompanied with hyperplastic glands, the COX‐2 expression in hyperplastic components was similar to that in traditional hyperplastic polyps, whereas its expression in serrated adenomatous components was similar to that in pure SAs.Conclusions  The colonoscopic feature of SAs correlated with the immunohistochemical expression of COX‐2 protein. The COX‐2 expression in SAs with cerebriform pattern was similar to that in traditional adenomas. On the other hand, SAs with hyperplastic pattern showed intermediate COX‐2 expression between hyperplastic polyps and tubular adenomas. The expression of COX‐2 protein may be involved in the progression from hyperplastic polyps to SAs with hyperplastic pattern, and to SAs with cerebriform pattern.
EXPRESSION OF THE INTESTINE SPECIFIC TRANSCRIPTION FACTOR CDX2 IN INTESTINAL METAPLASIA OF FURAN‐TREATED RAT LIVER
Authors: Yerkovich ST , De Boer B , Sirica AE , Yeoh GCT , James RJ , Ee HC 
Published: January 2004

Objectives  cdx2 is a homeodomain transcription factor exclusively expressed in intestinal epithelium and has been shown to regulate transcription of several intestine specific genes. The aim of this study was to investigate its expression in abnormal gastrointestinal differentiation, such as the development of intestinal metaplasia and subsequent ‘intestinal‐type’ adenocarcinoma in the liver of furan‐treated rats.Methods  Immunohistochemistry was performed on tissue sections from furan‐treated rat livers and transplanted ‘intestinal‐type’ hepatic adenocarcinoma by using a polyclonal antibody against cdx2.Results  Strong cdx2 immunoreactivity was seen in intestinal metaplastic foci, in which Alcian blue staining for mucin confirmed the presence of goblet cells. In contrast, regenerating ducts without intestinal features were negative for cdx2 immunoreactivity and Alcian blue staining. Transplanted tumours from furan‐derived hepatic adenocarcinomas were weakly positive for cdx2 and Alcian blue staining demonstrated scanty goblet cells.Conclusion  The strong association between cdx2 expression and intestinal morphology in furan‐treated rat liver suggests that cdx2 plays an important role in the differentiation towards an intestinal phenotype.
ALTERED BONE METABOLISM IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Onuk M Derya , Yassýkaya Bülent , Akarsu Ersin 
Published: January 2004

Patients with inflammatory bowel disease (IBD) are at risk of developing metabolic bone disease. We aimed to compare markers of bone metabolism and bone mineral density in patients with IBD and healthy subjects. Seventeen patients with ulcerative colitis (13 women, four men; median age 33.4; range 15–52), and eight patients with Crohn's disease (five women, three men; median age 30.2; range 21–44), and 20 healthy subjects (12 women, eight men; median age 32.5; range 17–52) were investigated.The diagnosis of IBD was based on endoscopical, radiological and histological examinations. Markers of bone metabolism (serum calcium, alkaline phosphatase (AP), osteocalcin, phosphate, parathyroid hormone (PTH), 25‐hydroxy‐vitamin D3 (25‐OH‐D3), and urine deoxyprydoline (DPD) were measured. Bone mineral density of lumbar L2–L4 vertebrae in the anterioposterior projection, femoral neck and Ward's triangle were determined by dual X‐ray absorbtiometry (DXA).While osteocalcine and AP levels (osteoblastic activity parameters) of patients did not differ from those of controls, urine DPD (osteoclastic activity parameter) was higher than that of controls (P < 0.05). Serum PTH and 25‐OH‐D3 levels were also higher in patients (P < 0.05). T scores of bone mineral density were statistically lower in patients than controls (P < 0.001).Osteopenia was observed in 12 patients with IBD (48%), osteoporosis was in five patients (20%). These were significantly higher than controls (14 and 8%, respectively). There was a high prevalence of reduced bone mineral density in patients with IBD which is independent of site, activity or type of disease.
ANTI‐HUMAN NEURONAL PROTEIN – A NEW TOOL FOR QUANTIFICATION OF NEURONES IN THE HUMAN ENTERIC NERVOUS SYSTEM
Authors: Murphy EM , Wattchow DA , Costa M , Brookes SJH 
Published: January 2004

Understanding how the enteric nervous system controls gastrointestinal function requires an account of the different classes of nerve cells present in the gut wall. Accurately quantifying immunohistochemically identified neurones, would make it possible to characterize changes underlying disorders such as slow transit constipation. Until now, quantification of classes of neurones has relied on antisera to Neuron Specific Enolase (NSE) or Protein Gene Product 9.5 (PGP9.5), however, both stain nerve fibres, making accurate counting of cell bodies unreliable. Anti‐Human Neuronal Protein Antibodies (Hu) were originally isolated from patients with paraneoplastic encephalomyelitis and paraneoplastic neuropathies and have been tested here as a marker for all neurons in the human myenteric plexus.Specimens of colon were obtained from the uninvolved margins of specimens from 10 patients undergoing elective surgery for carcinoma and were either fixed fresh, or maintained in organ culture for 3 days. Nerve cell bodies were identified using double labelling techniques to compare Hu (mouse monoclonal anti Hu, Chemicon, CA) and NSE antisera for quantification. In both fresh and cultured tissue, neuronal somata were readily identified using the Hu antibody but few axons or varicosities were labelled. In double‐stained preparations, Hu labelling consistently revealed more nerve cell bodies than NSE. In addition, counting was more reliable due to the lack of staining of nerve fibres which obscured some cell bodies in NSE or PGP9.5‐stained preparations.We used preparations triple labeled with antisera raised against nitric oxide synthase (NOS), choline acetyltransferase (ChAT) and Hu, to determine the size of these major populations. Approximately 47 + 1% (mean + SD, n= 4) of all myenteric nerve cell bodies were immunoreactive for NOS and 52 + 2% were immunoreactive for ChAT. In each preparation, approximately 8 + 2% of NOS cells also contained ChAT. In 5 + 1% of neurons, neither NOS nor ChAT was detectable. Anti‐Hu antiserum makes possible reliable labeling of all enteric neurons in the human colon, allowing accurate quantification of different populations of enteric neurones in normal and diseased tissue.
Including the quality‐of‐life effects in the evaluation of prostate cancer screening: expert opinions revisited?
Authors: Essink‐Bot M.L. , Korfage I.J. , De Koning H.J. 
Published: January 2004

OBJECTIVETo apply the general empirical framework for estimating utilities in cost‐utility analysis (CUA) of population‐based prostate cancer screening, including an assessment of empirical health status with a classifying measure (e.g. the EQ‐5D) and linking these descriptions to utility estimates using the standard preference‐based algorithm, combining them with the appropriate duration into quality‐adjusted life years, and sensitivity analysis.MATERIALS AND METHODSEmpirical studies to describe and value the health status effects of prostate cancer screening have been ongoing within the Rotterdam centre of the European Randomised Study on Screening for Prostate Cancer since 1995. The results of these studies, including the screening, the primary treatment phase and advanced disease, will be used in estimating utilities for cost‐utility analysis.RESULTSEstimation of cost‐utility of population‐based prostate cancer screening with the results of the three empirical health status studies yielded partly counterintuitive results, underestimating the unfavourable health status effects that are inevitably associated with prostate cancer screening. This may be caused by other than health effects of the screening itself (‘process effects’) and adaptive changes in perception of their situation in patients after curative primary treatment (‘response shift’), among other elements.CONCLUSIONThese results prompted us to reconsider the suitability of the general framework of CUA for screening programmes. Possible directions for solutions are indicated.
MISCAN: estimating lead‐time and over‐detection by simulation
Authors: Draisma G. , De Koning H.J. 
Published: January 2004

OBJECTIVETo estimate the mean lead‐time and rate of over‐detection associated with screening for prostate cancer with prostate‐specific antigen.METHODSSimulation models, fitted to the results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, were used to predict the mean lead‐time and over‐detection rate in population‐based screening programmes.RESULTSThe mean lead‐time is estimated to be 11–12 years and over‐detection to occur in half the cases found by population screening. The estimates are compared with published estimates.CONCLUSIONThe effect of lead‐time and over‐detection on the balance of positive and negative consequences of screening cannot be neglected.
The Spanish contribution to the European Randomized Study of Screening for Prostate Cancer
Authors: Berenguer A. , Luján M. , Páez A. , Santonja C. , Pascual T. 
Published: January 2004

OBJECTIVETo summarize the experience of the Spanish participation in the European Randomized Study of Screening for Prostate Cancer (ERSPC)METHODSIn this study men aged 45–70 years were randomized (1 : 1) and allocated to one of two arms: screening, with an indication for transrectal ultrasonography (TRUS) and sextant prostate biopsy when the serum prostate‐specific antigen (PSA) level was > 4 ng/mL (until May 1998) and from then when the PSA was > 2.9 ng/mL; and a control group (no diagnostic tests). The findings from a digital rectal examination were not considered as a criterion for biopsy. When the serum PSA was above the threshold levels, biopsy‐negative men were invited again after a year (‘early recall’). The next (second) screening round was programmed for the rest of participants after a 4‐year interval. Cancer‐specific mortality was recorded and compared in both groups.RESULTSIn all, 4278 men were recruited (2416 in the screening group and 1862 in the control group). The recruitment phase was closed in June 1999. During the first screening round 40 cancers were detected; the detection rate was then 1.7% and 4.15 biopsies were needed to detect each cancer. The clinical stage was localized in 88.6% and regional or metastatic in 11.4%. Within the first round, 17 more cancers were detected at early recall attendance. During the second screening round 14 cancers were found, giving a detection rate of 1.9%; 17 more cancers were also diagnosed outside the screening programme (contamination), seven in the screening group and 10 in the control group. Until February 2003, 85 participants had died (53 screened and 32 control) but none from prostate cancer.CONCLUSIONSCancer detection rates can be increased with further early recalls; the clinical stage was localized in an important proportion of cancers detected.
Features and preliminary results of prostate cancer screening in Canton Aargau, Switzerland
Authors: Kwiatkowski M. , Huber A. , Stamm B. , Lehmann K. , Wernli M. , Häfeli A. , Recker F. 
Published: January 2004

OBJECTIVETo report the results from Switzerland's participation in the ERSPC from 1998; importantly, epidemiological data showed that Switzerland has one of the highest rates of morbidity and mortality from prostate cancer in the world. The local study protocol was accepted by the ethical committee and after the successful pilot study phase, the centre joined the ERSPC.SUBJECTS AND METHODSFrom September 1998 to June 2003 10 300 men accepted an invitation for the study and were then randomized 1 : 1 into an active screening arm (assessed by testing prostate‐specific antigen, PSA) or a control group (no intervention). The re‐screening interval is 4 years and is ongoing (beginning in September 2002). The study protocol includes offering a prostate biopsy when the total PSA is > 3.0 ng/mL (the main study protocol in agreement with ERSPC requirements) or when the total PSA is 1–3 ng/mL and the free‐to‐total PSA ratio < 20% (side study protocol).RESULTSDuring the first 3 years of screening 3562 men aged 55–70 years were screened; 395 (11.1%) of all participants had a total PSA of > 3 ng/mL and 251 (7.4%) were eligible for the side‐study. In all, 599 (17.2%) of 3562 accepted a prostate biopsy (93% of 646); 120 cases of prostate cancer were detected (3.4% detection rate). The incidence was 2.5% in main study group (positive predictive value, PPV, 24%) and 0.9% in side study group (PPV 13.6%). In radical prostatectomy specimens the cancers were mostly ‘significant’ (92% in main study group and 87% in side‐study group).CONCLUSIONSA randomized screening study for prostate cancer is feasible in Switzerland. A longer follow‐up is needed to address within the ERSPC the primary hypothesis (that there will be a reduction in mortality in the active screening arm) and to determine the level of over/under‐diagnosis and over/under‐treatment in the active screening and control arms, respectively.
Population‐based screening for prostate cancer by measuring free and total serum prostate‐specific antigen in Sweden
Authors: Hugosson J. , Aus G. , Bergdahl S. , Fernlund P. , Frösing R. , Lodding P. , Pihl C.‐G. , Lilja H. 
Published: January 2004

OBJECTIVESTo report the initial results from Sweden of a large population‐based randomized study of screening using prostate‐specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven.METHODSFrom the population registry men aged 50–66 years were randomized to screening (9973) and to future controls (9973). Men randomized to screening were invited to have their serum measured for free PSA (fPSA) and total PSA (tPSA) in serum using the Prostatus® f/tPSA assay (Perkin‐Elmer, Turku, Finland). Men with a tPSA of < 3.0 ng/mL were not further investigated, while those with a tPSA of ≥ 3.0 ng/mL were investigated with a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and sextant biopsies.RESULTSOf those invited, 60% accepted PSA testing and 11.3% had a tPSA of ≥ 3.0 ng/mL. Altogether 145 cancers were detected (positive predictive value, PPV, 24%); none were stage M1, two were stage N+ and 10 stage T3–4. Most (59%) cancers were impalpable and 39% were both impalpable and invisible on TRUS. At biopsy, 7% were Gleason score 2–4, 71% 5–6, 19% 7 and 2% Gleason score 8–10. A threshold tPSA of ≥ 4.0 ng/mL would have detected 109 cancers in 366 biopsied men (PPV 30%) while cancer detection would have been 14% higher with a PPV of 36% using a threshold tPSA of ≥ 3.0 ng/mL combined with a f/tPSA threshold of ≤ 18%.CONCLUSIONPSA screening detects early‐stage low‐grade prostate cancer. Both the sensitivity and specificity can be increased by incorporating f/tPSA with a tPSA threshold of < 4 ng/mL.
Quality assessment for prostate‐specific antigen (PSA) in relation to ERSPC: report of the PSA Committee
Authors: Blijenberg B.G. , Lilja H. , Neels H. , Stenman U.‐H. 
Published: January 2004

OBJECTIVETo assess the application of a quality control scheme for total prostate‐specific antigen (PSA) as used for participants of the European Randomized Study for Screening of Prostate Cancer (ERSPC) during 1996–2002.METHODSFrom 1996, the first complete year being 1997, an external scheme was organized by the Dutch Quality Assessment Foundation especially for the ERSPC. This scheme consists of one control round every 2 months with two different human serum samples and is only meant to compare the recovery of methods. From 1998 an internal scheme was also applied by adding two distinct samples to every round.RESULTSInitially there was a wide variation (coefficient of variation of ±15% at threshold PSA of 4.0 ng/mL) among all ERSPC participants who were all using the Tandem assay (Hybritech Inc, USA). After introducing the internal scheme the performance of some intra‐ERSPC group comparisons for PSA and the introduction of the completely automated Beckman‐Access analyser in 2001 there was state‐of‐the‐art precision for PSA of ± 5% in the 2002 surveys.CONCLUSIONThe ERSPC group measurements of PSA have considerably improved since 1996 because of the application of a quality‐assessment scheme and with the introduction of complete automation of the PSA assay. Both findings are in line with earlier developments in clinical chemistry.
Four‐year prostate‐specific antigen progression in the non‐cancer population of the European Randomized Study of Screening for Prostate Cancer
Authors: Páez A. , Luján M. , Raaijmakers R. , Berenguer A. ,   ERSPC
Published: January 2004

OBJECTIVETo determine the rate of conversion of prostate‐specific antigen (PSA) to values of > 4 ng/mL in a normal male population.PATIENTS AND METHODSIn men with an initial PSA level of < 4 ng/mL the probability of having a PSA of ≥ 4 ng/mL and its relationship with the age at first PSA test, baseline PSA level and time to the determination was evaluated. Statistical methods were used to correct for the within‐subject variability across many PSA determinations.RESULTSIn all, 45 433 PSA tests in 21 169 men with an initial PSA of < 4 ng/mL were available. Overall, in 960 men (4.5%) the PSA level changed to ≥ 4 ng/mL. The lowest chance was for men aged < 55 years with an initial PSA of < 1 ng/mL and a new PSA determination during the first 18 months (0.952 conversions per 1000 men) while the highest was for men aged < 55 years with an initial PSA level of > 2.5 ng/mL (395 conversions per 1000 men). There was a significant and independent relationship between conversion and the interval between determinations, with conversion being 3.33 times more frequent during 18–42 months than with the reference category (<18 months) and 5.23 times more frequent during > 42 months. The probability of conversion independently increased by 3 λ for every additional year of age. Every unit of basal PSA multiplied by 6.48 the probability of conversion.CONCLUSIONThe risk for conversion to a PSA of ≥ 4 ng/mL can be anticipated from the patient's age and initial PSA level. Re‐screening before 4 years after the first round can be useless for men with an initial PSA of < 1 ng/mL. Four‐year intervals could be inadequate for men with an initial PSA of > 2.5 ng/mL if conversion to > 4 ng/mL is to be avoided.
Consistency of prostate cancer grading results in screened populations across Europe
Authors: Van der Kwast T.H. , Roobol M.J. , Wildhagen M.F. , Martikainen P.M. , Määtänen L. , Pihl C.‐G. , Santonja C. , Bubendorf L. , Neetens I. , Di Lollo S. , Hoedemaeker R.F. 
Published: January 2004

OBJECTIVETo assess the consistency of grading outcome among seven of eight participating centres of the European Randomised Screening Program of Prostate Cancer (ERSPC), a multicentre randomized trial intended to detect a difference in prostate cancer‐related mortality between screened participants and a control group. Currently, tumour stage and grade in prostatectomy specimens represent the most predictive variables for biological behaviour. In prostate needle biopsies the tumour grade is a strong factor for deciding therapy.PATIENTS AND METHODSWithin the ERSPC all prostate cancers detected in needle biopsies were graded according to the Gleason score system. Gleason scores were compressed in three categories of ≤ 6, 7 and 8–10. Data for grading outcome were obtained from the databases from seven individual centres; in one centre the slide sets with cancer were separately reviewed.RESULTSCombining the data of seven ERSPC centres 66% of cancers detected in the screening arm were Gleason score ≤ 6 and 92% were ≤7. Gleason score 8–10 cancers varied from 2 to 11%. This variation in Gleason scores may be attributed to differences in the population characteristics and biopsy indications.CONCLUSIONThese data indicate that in the seven ERSPC centres most screen‐detected cancers have favourable characteristics on biopsy. Men with these cancers are amenable for treatment with curative intent. The observed differences in Gleason score distribution in different centres may partly be attributed to geographical differences and differences in the age range of the screened populations.
The clinical significance of a small focus of well‐differentiated carcinoma at prostate biopsy
Authors: Hoedemaeker R.F. , Van Der Kwast T.H. , Schröder F.H. 
Published: January 2004

OBJECTIVETo compare a series of 121 sextant needle biopsy sets with their corresponding radical prostatectomy specimens in screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC), investigating the effect of screening for prostate cancer on disease‐specific mortality and quality of life, as the clinical significance of a small focus of well‐differentiated prostate cancer on biopsy is unclear.PATIENTS AND METHODSThe expected clinical significance of the discovered tumours was estimated using an arbitrary model combining volume, grade, and stage characteristics.RESULTSOf 34 patients who had a small focus (<3 mm on a single biopsy core) of well‐differentiated carcinoma on biopsy, only 18 (53%) were found to have minimal carcinoma (a small focus of well‐differentiated carcinoma) at radical prostatectomy, while 16 (47%) had moderately advanced or advanced carcinoma at radical prostatectomy. The preoperative prediction of minimal carcinoma improved when the amount of cancer in the sextant biopsy set was combined with the preoperative serum prostate specific antigen (PSA) level. Of 12 patients with a small focus of well‐differentiated carcinoma on biopsy and a serum PSA of < 4 ng/mL, 11 had minimal carcinoma at radical prostatectomy, while there was minimal carcinoma in only seven of 22 (32%) patients with a small focus of well‐differentiated carcinoma on biopsy and a serum PSA of ≥ 4 ng/mL.CONCLUSIONThe predictive value of a small focus of well‐differentiated cancer on systematic sextant biopsy for a small well‐differentiated tumour in the prostate is limited. The predictive value improves when serum PSA levels are considered concurrently, but is still considered insufficient to support a base for selecting therapy for the individual patient.