[Preoperative chemotherapy in the surgical treatment of colorectal liver metastases]. / Preoperatív kemoterápia a colorectalis májáttétes betegek sebészi kezelésében.

INTRODUCTION: The only curative treatment of colorectal liver metastases (CRLM) is surgical resection. Preoperative/neoadjuvant chemotherapy can be used for resectable, for borderline resectable or even for irresectable CRLM patients. PATIENTS: Data of CRLM patients treated with surgical resection at the Uzsoki Hospital were analysed. Patients were classified into two groups, (A) who received preoperative chemotherapy before hepatic resection, and (B) who received no chemotherapy before resection. RESULTS: Between 01.01.2007. and 31.12.2010. 128 CRLM patients were treated with hepatic resection. 68 patients (53%) received chemotherapy before hepatic resection, 60 patients (47%) were resected without neoadjuvant chemotherapy. There was no significant difference in the complications between the groups (p = 0.39). Median overall survival was 41 months. The progression free survival (PFS) at 3 and 5 years were 25%, the 3 and 5 year overall survival (OS) were 55% and 31%. Both PFS and OS were significantly worse in the chemotherapy group (p = 0.014, p = 0.015). The subgroup of patients receiving bevacizumab containing preoperative chemotherapy has significanly better PFS than patients receiving only cytotoxic chemotherapy (p = 0.004). CONCLUSION: Surgical resection of CRLM patients results good survival data even in non-selected patients, although the very long survival results reported in the literature couldn't have been reproduced in this patient population. When preoperative chemotherapy was combined with bevacizumab, survival was similar to the upfront resected patients.

Short-term in-vitro expansion improves monitoring and allows affordable generation of virus-specific T-cells against several viruses for a broad clinical application.

Adenoviral infections are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. Adoptive transfer of donor-derived human adenovirus (HAdV)-specific T-cells represents a promising treatment option. However, the difficulty in identifying and selecting rare HAdV-specific T-cells, and the short time span between patients at high risk for invasive infection and viremia are major limitations. We therefore developed an IL-15-driven 6 to 12 day short-term protocol for in vitro detection of HAdV-specific T cells, as revealed by known MHC class I multimers and a newly identified adenoviral CD8 T-cell epitope derived from the E1A protein for the frequent HLA-type A*02∶01 and IFN-γ. Using this novel and improved diagnostic approach we observed a correlation between adenoviral load and reconstitution of CD8(+) and CD4(+) HAdV-specific T-cells including central memory cells in HSCT-patients. Adaption of the 12-day protocol to good manufacturing practice conditions resulted in a 2.6-log (mean) expansion of HAdV-specific T-cells displaying high cytolytic activity (4-fold) compared to controls and low or absent alloreactivity. Similar protocols successfully identified and rapidly expanded CMV-, EBV-, and BKV-specific T-cells. Our approach provides a powerful clinical-grade convertible tool for rapid and cost-effective detection and enrichment of multiple virus-specific T-cells that may facilitate broad clinical application.

[Role of pulse oximetric monitoring during gastrointestinal endoscopy. Prospective multicenter study of the Gastroenterology Working Group of the Veszprém Regional Committee of the Hungarian Academy of Sciences (VEAB)]. / Az endoszkópos vizsgálatok pulzoximetriás monitorozásának jelentosége. Az MTA VEAB Gasztroenterológiai Munkabizottságának prospektív multicentrikus vizsgálata.

INTRODUCTION: Recent guidelines recommend routine pulse oximetric monitoring during endoscopy, however, this has not been the common practice yet in the majority of the local endoscopic units. AIMS: To draw attention to the importance of the routine use of pulse oximetric recording during endoscopy. METHOD: A prospective multicenter study was performed with the participation of 11 gastrointestinal endoscopic units. Data of pulse oximetric monitoring of 1249 endoscopic investigations were evaluated, of which 1183 were carried out with and 66 without sedation. RESULTS: Oxygen saturation less than 90% was observed in 239 cases corresponding to 19.1% of all cases. It occurred most often during endoscopic retrograde cholangiopancreatography (31.2%) and proximal enteroscopy (20%). Procedure-related risk factors proved to be the long duration of the investigation, premedication with pethidine (31.3%), and combined sedoanalgesia with pethidine and midazolam (34.38%). The age over 60 years, obesity, consumption of hypnotics or sedatives, severe cardiopulmonary state, and risk factor scores III and IV of the American Society of Anestwere found as patient-related risk factors. CONCLUSION: To increase the safety of patients undergoing endoscopic investigation, pulse oximeter and oxygen supplementation should be the standard requirement in all of the endoscopic investigation rooms. Pulse oximetric monitoring is advised routinely during endoscopy with special regard to the risk factors of hypoxemia.

Evolution of disease phenotype in adult and pediatric onset Crohn's disease in a population-based cohort.

AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn's disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long-term evolution of disease behavior was not different in pediatric- and adult-onset CD patients in this population-based cohort but was associated to location, perianal disease and smoking status.

Is current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort.

BACKGROUND: Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. RESULTS: Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). CONCLUSIONS: Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

Mass spectrometry reveals changes in MHC I antigen presentation after lentivector expression of a gene regulation system.

The rapamycin-inducible gene regulation system was designed to minimize immune reactions in man and may thus be suited for gene therapy. We assessed whether this system indeed induces no immune responses. The protein components of the regulation system were produced in the human cell lines HEK 293T, D407, and HER 911 following lentiviral transfer of the corresponding genes. Stable cell lines were established, and the peptides presented by major histocompatibility complex class I (MHC I) molecules on transduced and wild-type (wt) cells were compared by differential mass spectrometry. In all cell lines examined, expression of the transgenes resulted in prominent changes in the repertoire of MHC I-presented self-peptides. No MHC I ligands originating from the transgenic proteins were detected. In vitro analysis of immunogenicity revealed that transduced D407 cells displayed slightly higher capacity than wt controls to promote proliferation of cytotoxic T cells. These results indicate that therapeutic manipulations within the genome of target cells may affect pathways involved in the processing of peptide antigens and their presentation by MHC I. This makes the genomic modifications visible to the immune system which may recognize these events and respond. Ultimately, the findings call attention to a possible immune risk.Molecular Therapy - Nucleic Acids (2013) 2, e75; doi:10.1038/mtna.2013.3; published online 12 February 2013.

The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: results from a population-based cohort in Eastern Europe.

BACKGROUND AND AIMS: Prior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in- and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD. RESULTS: Of the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval [CI]: 0.44-4.26). No cases have been exposed to either azathioprine or biologicals. CONCLUSIONS: The overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found.

[The effect of early immunosuppressive therapy on the rate of resections performed in patients with Chron's disease, in Veszprém county, Hungary, a population-based cohort study]. / A korai immunszuppresszív kezelés hatása a reszekciós mutétek arányára Crohn-betegekben, Veszprém megyében, populációs alapú kohorszvizsgálat alapján.

UNLABELLED: Medical therapy for Crohn's disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn's disease over the past decades is scarce. AIMS: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. METHODS: Data of 506 Crohn's disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn's disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26-0.67). CONCLUSIONS: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

OBJECTIVES: Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). CONCLUSIONS: This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.

BACKGROUND: Recent trends indicate a change in the epidemiology of inflammatory bowel diseases (IBD), with previously low incidence areas now reporting a progressive rise in the incidence. Our aim was to analyze the incidence and disease phenotype at diagnosis in IBD in the population-based Veszprem Province database, which included incident patients diagnosed between January 1, 2002 and December 31, 2006. METHODS: Data of 393 incident patients were analyzed (ulcerative colitis [UC]: 220, age-at-diagnosis: 40.5 years; Crohn's disease [CD]: 163, age-at-diagnosis: 32.5 years; and indeterminate colitis [IC]: 10). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: Adjusted mean incidence rates were 8.9/10(5) person-years for CD and 11.9/10(5) person-years in UC. Peak onset age in both CD and UC patients was 21-30 years old. Location at diagnosis in UC was proctitis in 26.8%, left-sided colitis in 50.9%, and pancolitis in 22.3%. The probability of proximal extension and colectomy after 5 years was 12.7% and 2.8%. The disease location in CD was ileal in 20.2%, colonic in 35.6%, ileocolonic in 44.2%, and upper gastrointestinal in four patients. Behavior at diagnosis was stenosing/penetrating in 35.6% and perianal in 11.1%. Patients with colonic disease were older at diagnosis compared to patients with ileal or ileocolonic disease. In a Kaplan-Meier analysis, probability of surgical resection was 9.8%, 18.5%, and 21.3% after 1, 3, and 5 years of disease duration, respectively. CONCLUSIONS: The incidence of IBD in Veszprem Province in the last decade was high, equal to that in high-incidence areas in Western European countries. Early disease course is milder compared to data reported in the literature.

Risk of colorectal cancer and small bowel adenocarcinoma in Crohn's disease: a population-based study from western Hungary 1977-2008.

BACKGROUND AND AIMS: Limited data are available on the incidence and predictors of colorectal (CRC) and small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) from population-based cohorts. Since data are completely missing from Eastern Europe, our aim was to analyze the incidence and risk factors of CD associated CRC and SBA in the population-based, Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. METHODS: The data of 506 incident CD patients were analyzed (age-at-diagnosis: 31.5, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: CRC was diagnosed in five patients (5/5758 person-year-duration) during follow-up, while no patients developed SBA in this cohort. Standardized incidence ratio (SIR) of CRC was not increased overall with five cases observed vs. 5.02 expected (SIR: 0.99, 95% CI: 0.41-2.39); however, there was a tendency for increased incidence in males (five cases observed vs. 2.56 expected; SIR: 1.95, 95% CI: 0.81-4.70). Age at onset of CD (p<0.001), male gender (p=0.022) and stenosing disease behavior at diagnosis (p<0.001) but not disease location were identified as risk factors for developing CRC in univariate analysis and Kaplan-Meier analysis. The cumulative risk for developing CRC after a disease duration of 20 years was 1.1% (95% CI: 0.6-1.7%). CONCLUSIONS: The incidence of CRC and SBA was not increased in this population-based CD cohort. Age at onset of CD, male gender and stenosing disease behavior at diagnosis were identified as risk factors of CRC.

Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands.

Short peptides derived from intracellular proteins and presented on MHC class I molecules on the cell surface serve as a showcase for the immune system to detect pathogenic or malignant alterations inside the cell, and the sequencing and analysis of the presented peptide pool has received considerable attention over the last two decades. In this review, we give a comprehensive presentation of the methods employed for the large-scale qualitative and quantitative analysis of the MHC class I ligandome. Furthermore, we focus on insights gained into the underlying processing pathway, especially involving the roles of the proteasome, the TAP complex, and the peptide specificities and motifs of MHC molecules. The identification of post-translational modifications in MHC ligands and their implications for processing are also considered. Finally, we review the correlations of the ligandome to the proteome and the transcriptome.

IBD in the elderly population: results from a population-based study in Western Hungary, 1977-2008.

BACKGROUND AND AIMS: Limited data are available on the incidence and disease course of IBD in the elderly population. Our aim was to analyze the incidence and disease course of IBD according to the age at diagnosis in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. METHODS: Data of 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 SD 15.9 years; CD: 506, age at diagnosis: 31.5 SD 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: 106 (11.6%) of UC patients and 21 (4.2%) of CD patients were diagnosed with >60 years of age. In UC, the incidence increased from 1.09 to 10.8/10(5) in the elderly, while CD increased to 3.04/10(5) in 2002-2007. In CD, colonic location (elderly: 61.9% vs. pediatric: 24.3%, p=0.001, and adults: 36.8%, p=0.02) and stenosing disease (elderly: 42.9% vs. pediatric: 14.9%, p=0.005, and adults: 19.5%, p=0.01) were more frequent in the elderly. A change in disease behavior was absent in the elderly, while in pediatric and adult CD population it was 20.3% (p=0.037), 19.8% (p=0.036) after 5 years. In UC, extensive disease was more frequent in pediatric patients compared to the elderly (p=0.003, OR: 2.73, 95%CI: 1.38-5.41). In addition, pediatric (57.3%, p<0.001, OR: 6.58; 95%CI: 3.22-12.9) and adult (39.8%, p<0.001, OR: 3.24; 95%CI: 1.91-5.49) patients required more often systemic steroids during follow-up compared to the elderly (17%). Proximal extension at 10 years was 11.6%, but time to extension was not different according to the age at onset. CONCLUSIONS: Elderly patients represent an increasing proportion of the IBD population. Stenosing and colon-only disease were characteristic for elderly CD patients, while the disease course in UC was milder.

Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA-B44 supertype.

Human leukocyte antigens (HLA) have long been grouped into supertypes to facilitate peptide-based immunotherapy. Analysis of several hundreds of peptides presented by all nine antigens of the HLA-B44 supertype (HLA-B*18, B*37, B*40, B*41, B*44, B*45, B*47, B*49 and B*50) revealed unique peptide motifs for each of them. Taking all supertype members into consideration only 25 out of 670 natural ligands were found on more than one HLA molecule. Further direct comparisons by two mass spectrometric methods--isotope labeling as well as a label-free approach--consistently demonstrated only minute overlaps of below 3% between the ligandomes of different HLA antigens. In addition, T cell reactions of healthy donors against immunodominant HLA-B*44 and HLA-B*40 epitopes from EBV lacked promiscuous T-cell recognition within the HLA-B44 supertype. Taken together, these results challenge the common paradigm of broadly presented epitopes within this supertype.

Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a population-based study.

BACKGROUND: There is an increased risk of colorectal cancer (CRC) in ulcerative colitis (UC). The prevalence of UC-associated CRC is different in various geographic regions. The risk depends primarily on the duration and extent of disease. The aim of this study was to identify the risk factors for and the epidemiology of CRC in Hungarian patients with UC. METHODS: We retrospectively evaluated the relevant epidemiological and clinical data of all patients with UC in Veszprem province in our 30-year IBD database (723 patients with UC; male/female, 380/343; non-CRC related colectomies, 3.7%). RESULTS: CRC was diagnosed in 13 patients (13/8564 person-year duration) during follow-up. Age at diagnosis of CRC was at a median of 51 (range 27-70) years. Eight patients are still alive, 4 died of CRC, and 1 died of an unrelated cause. Longer disease duration, extensive colitis, primary sclerosing cholangitis, and dysplasia found in the biopsy specimen were identified as risk factors for developing CRC. The cumulative risk of developing CRC after a disease duration of 10 years was 0.6% (95% confidence interval [CI] 0.2%-1.0%); 20 years, 5.4% (95% CI 3.7%-7.1%); and 30 years, 7.5% (95% CI 4.8%-10.2%). CRC diagnosed at surveillance colonoscopy was associated with a tendency for longer survival (P = 0.08). CONCLUSIONS: The cumulative risk of CRC was high in our patients with UC; however, it was lower compared with that reported in Western European and North American studies. CRC developed approximately 15 years earlier compared with sporadic CRC patients in Hungary. Longer disease duration, extensive colitis, dysplasia, and primary sclerosing cholangitis were identified as important risk factors for developing CRC.

[Risk factors for ulcerative colitis associated colorectal cancers in a Hungarian cohort of ulcerative colitis patients]. / A colorectális rák rizikófaktorai colitis ulcerosás betegekben populációs alapú vizsgálat eredményei alapján.

BACKGROUND: There is an increased risk of colorectal cancer (CRC) in ulcerative colitis (UC). The prevalence of UC associated CRC is different in various geographical regions. The risk depends primarily on the duration and extent of disease. AIM: The aim of the study was to identify risk factors for and epidemiology of CRC in UC patients in Veszprem province. PATIENTS AND METHODS: From our thirty-year IBD database we retrospectively studied the relevant epidemiological and clinical data of all UC patients in Veszprem province. The data of 723 UC patients (m/f: 380/343) were evaluated. The rate of familial disease was 5.2%, the rate of non-CRC related colectomies was 3.7% in our UC patients. RESULTS: CRC was diagnosed in 13 patients (m/f: 6/7, 13/8564 person year duration) during follow-up. The onset of UC in the 13 patients with UC-CRC was 34.5 (13-61) years, 4.1 years younger compared to UC patients without CRC. Mean age of UC-CRC patients at diagnosis of CRC was 50.9 (27-70) years (duration of UC: 16.5 +/- 8.2 years), almost 15 years younger than the average in sporadic CRC population in Hungary. Eight patients are still alive (survival: 67.9 (10-163) months), four patients died because of CRC (survival: 8.0 months), one died due to unrelated cause after 10 years of the diagnosis of CRC. Longer disease duration, chronic continuous disease, more extensive colitis, the presence of iron deficiency or chronic anaemia, primary sclerosing cholangitis (PSC) and dysplasia in the biopsy were identified as risk factors for developing CRC. In a logistic regression model longer disease duration, extensive colitis, PSC and dysplasia were still associated with increased risk. The cumulative risk for developing CRC after a disease duration of 10 years was 0.6% (95% CI: 0.2-1.0%), at 20 years 5.4 % (95% CI: 3.7-7.1%) and at 32 years 12.6% (95% CI: 7.0-18.2%). CRC diagnosed at surveillance colonoscopy was associated with longer survival (p = 0.04). CONCLUSION: The cumulative risk of CRC was high in our UC patients, however it was lower compared to that reported in Western European and North American studies. CRC developed approximately fifteen years earlier compared to the sporadic CRC cases. Long disease duration, extensive colitis, the presence of iron deficiency or chronic anaemia, dysplasia and primary sclerosing cholangitis (PSC) seem to be important risk factor for developing CRC in UC patients.

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones: results of a retrospective, single center study between 1996-2002.

AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing preoperative ERCP (< or =90 d before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1st of January 1996 to the 31st of December 2002. The indications for ERCP were elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (> or =8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and the combination of factors were compared to the result of ERCP. RESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%, for three 72.5%, for four or more 91.4%. CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients). Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (e.g. skill of the endoscopist, other diagnostic tools).

[Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy. Results of a 7-year, retrospective, single center study]. / A praeoperatív endoszkópos retrográd cholangiopancreatographia (ERCP) szelekciós kritériumai laparoszkópos cholecystectomia elott egy centrum hétéves adatainak retrospektív elemzése alapján.

UNLABELLED: The optimal treatment for bile duct stones (in terms of accuracy, complications and cost) is unclear. The aim of our study was to determine the predictive factors for preoperative ERCP. PATIENTS AND METHODS: Patients who underwent preoperative ERCP (= 90 days before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1st January 1996 to the 31st December 2002. The indication for ERCP was elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (> or = 8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and combination of factors were compared to the results of the ERCP. RESULTS: 206 preoperative ERCP-s were performed during the observed period, 200 were successful (97.1%). Bile duct stone was detected in 81 patients (39.3%), it was successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones: the positive predictive value for one prognostic factor was 1.2%, for two 43%, for three 72.5%, for four or more 91.4%. CONCLUSIONS: The practical conclusion of this study is that preoperative ERCP is highly recommended in patients with three or more positive factors. In contrast, ERCP is not indicated in patients with zero or one factor. Preoperative ERCP should be offered to patients with two positive factors, however the practice should be based also on the local conditions (e.g. skill of the endoscopist, other diagnostic tools).

Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001.

AIM: An investigation into inflammatory bowel disease and colorectal cancer in Veszprem Province was conducted from 1977 to 2001. METHODS: Both hospital and outpatient records were collected and reviewed comprehensively. The majority of patients were followed up regularly. RESULTS: The population of the province was decreased from 386,000 to 376,000 during the period. Five hundred sixty new cases of ulcerative colitis (UC), 212 of Crohn's disease (CD), and 40 of indeterminate colitis (IC) were diagnosed. The incidence rates increased from 1.66 to 11.01 cases per 100,000 persons for UC, from 0.41 to 4.68 for CD and from 0.26 to 0.74 for IC. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9 cases per 100,000 persons for CD. The peak onset age in UC patients was between 30 and 40 years, in CD between 20 and 30 years. A family history of IBD was present in 3.4 % in UC and 9.9 % in CD patients. Smoking increased the risk for CD (OR=1.98) while it decreased the risk for UC (OR=0.25). Twelve colorectal carcinomas were observed in this cohort, the cumulative colorectal cancer risk after 10 years in UC was 2%, after 20 years 8.8%, after 30 years 13.3%. CONCLUSION: The incidence and prevalence rates of IBD have increased steadily in Veszprem Province, now equivalent to that in Western European countries. Rapid increase in incidence rates supports a probable role for environmental factors. The rate of colorectal cancers in IBD is similar to that observed in Western countries.

[Epidemiology of inflammatory bowel diseases in Veszprém county of Western Hungary between 1977 and 2001]. / A gyulladásos bélbetegségek epidemiológiája Veszprém megyében--25 éves felmérés eredményei (1977-2001).

INTRODUCTION: An epidemiological study of inflammatory bowel disease (IBD) in Veszprém county (located in western part of Hungary) was carried out from 1977 to 2001. METHODS: Both hospital and outpatient records of IBD patients were collected reviewed carefully. Most patients have been followed up regularly. RESULTS: The number of population has decreased during the observed period from 386,000 to 376,000. The county has both industrial and agrarian parts. 560 new ulcerative colitis (UC) cases, 212 Crohn's disease (CD), and 40 indeterminate colitides (IC) were diagnosed in the investigated period. Incidence rate increased from 1.66 (1977-1981) to 11.01 (1997-2001) in UC, and from 0.41 to 4.68 in CD, respectively. The incidence rate in IC rose from 0.26 to 0.74. The M/F ratio in UC was 1.06, in CD: 1.03, respectively, 41 UD patients and 13 CD patients died, the cause of death was disease related in 6 UC and in 6 CD patients. The average age at death in UC was not different from that observed in general population (66.4 years) but in CD (50.1 years) it was much earlier. The disease related mortality was low, 0.06/100,000 both in UC and CD. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9/100,000 inhabitants for CD. Mean age at onset in UC was 38.9 +/- 15.5 years, in CD 31.7 +/- 12.8 years. We observed only one peak onset of the diseases, in UC it was between 30 and 40 years, in CD between 20 and 30 years. People living in towns were more liable to acquire the disease (ORUC = 1.27, ORCD = 1.13). The rate of smokers at the onset was 14.3% (OR = 0.25) in UC and 50.5% (OR = 1.98) in CD. Ex-smokers were 18.4% and 6.4%. Family history of IBD was present in 3.4% in UC and 9.9% in CD. The location of UC (according to the known largest extent) was proctitis in 112 cases, proctosigmoiditis in 162 cases, left sided colitis in 117 and subtotal or pancolitis in 169 cases. The location of CD was only ileal in 68 cases, ileocolonic in 87 cases, colonic in 57 cases. The behaviour of CD was non-stricturing-non-penetrating in 63 cases, stricturing in 54 cases, penetrating in 95 cases. 59.4% of the CD patients had at least one operation, 6.1% had more than 3 operations. CONCLUSION: The incidence and prevalence rates have increased steadily in Veszprém County, now it reaches that of most western European countries. There were no gender differences either in UC or CD. Smoking seemed to be a risk factor for CD, but it was preventive for UC. The rapid increase in incidence supports a role for environmental (e.g. diet, lifestyle changes) risk factors.