Bariatric Nutritional Intervention in Obese Patients with Compensated Liver Cirrhosis: A Four-Year Prospective Study.

BACKGROUND: Obesity and liver cirrhosis represent significant health challenges, often leading to various complications. AIMS: This prospective study aimed to investigate the impact of a four-year bariatric intervention, focusing on adherence to the Mediterranean Diet, on anthropometric, hematologic, and biochemical parameters in obese patients with compensated liver cirrhosis. Additionally, the study evaluated the concurrent contribution of weight loss to these health indicators. METHODS: The study involved 62 patients with compensated liver cirrhosis (mean age 65.87 ± 6 years) and 44 healthy controls (mean age 59.11 ± 8 years), all with a BMI > 30 kg/m2. Both groups underwent a weight loss intervention based on the Mediterranean diet, with a four-year follow-up. Anthropometric, biochemical and hematologic parameters were evaluated at several time points during the study and their statistical significance was assessed. RESULTS: Anthropometric parameters, including weight, BMI, waist and hip circumference, percentage of fat mass, and handgrip strength, exhibited significant improvements (p < 0.05), particularly within the first year of the intervention. Liver function tests and lipid profiles of the patients also showed significant enhancements (p < 0.05). Hematological and biochemical indices, such as hematocrit and ferritin, experienced discreet improvements in the patient cohort (p < 0.05). CONCLUSIONS: This study highlights the potential of a structured bariatric intervention rooted in the Mediterranean diet to positively influence the health of obese patients with compensated liver cirrhosis. The observed improvements in anthropometric, biochemical, and hematologic parameters, particularly within the first year of the intervention, suggest the importance of dietary modifications in managing the health of this patient population.

Aberrant function of myeloid-derived suppressor cells (MDSCs) in experimental colitis and in inflammatory bowel disease (IBD) immune responses.

BACKGROUND AND AIMS: Myeloid-derived suppressor cells (MDSCs) encompass a novel population of suppressor cells and a potential candidate for cell-based therapies in inflammatory diseases. Herein, we investigated their immunomodulatory properties in experimental inflammatory colitis and T cell-mediated immune responses in inflammatory bowel disease (IBD) patients. METHODS: MDSCs (defined as CD14-HLA-DR-/lowCD33+CD15+) numbers were determined in peripheral blood (PB) from IBD patients. PB MDSC function was assessed in vitro. Experimental colitis was induced upon 2,4,6-trinitrobenzene sulfonic acid (TNBS) treatment and MDSCs were characterized by flow cytometry. The in vivo suppressive potential of bone marrow (BM)-derived MDSCs (BM-MDSCs) was tested by using both depleting and adoptive transfer strategies. RESULTS: MDSCs were enriched in the periphery of IBD patients during active disease. TNBS colitis induced amplification of MDSCs, particularly of the granulocytic (Ly6G+) subset during the effector phase of disease. Of interest, BM-MDSCs potently suppressed CD4+ T cell responses under steady state but failed to control colitis-associated immune responses in vivo. Mechanistically, under the colonic inflammatory milieu MDSCs switched phenotype (decreased proportion of Gr1high and increased numbers of Gr1low) and downregulated CCAAT/enhancer-binding protein beta (CEBPß) expression, a critical transcription factor for the suppressive function of MDSCs. In accordance with the murine data, human CD33 + CD15+ MDSCs from peripheral blood of IBD patients not only failed to suppress autologous T cell responses but instead enhanced T cell proliferation in vitro. CONCLUSIONS: Our findings demonstrate an aberrant function of MDSCs in experimental inflammatory colitis and in IBD-associated immune responses in vitro. Delineation of the mechanisms that underlie the loss of MDSCs function in IBD may provide novel therapeutic targets.

Recurrent episodes of acute pancreatitis due to duodenal gangliocytic paraganglioma: report of a case.

CONTEXT: Gangliocytic paraganglioma is a rare tumor, almost always located in the second portion of the duodenum, and manifested with upper gastrointestinal bleeding and abdominal pain. To date, only one case of duodenal gangliocytic paraganglioma presented with recurrent acute pancreatitis has been reported in the literature. CASE REPORT: We present a 72-year-old woman admitted to the hospital due to recurrent episodes of acute pancreatitis. Paraclinical examinations showed a polypoid mass in the second portion of duodenum which was removed surgically by local excision. The preoperative differential diagnosis was suggestive with gastrointestinal stromal tumor or adenoma. The histopathology examination revealed a duodenal gangliocytic paraganglioma. After a follow up period of seventeen months the patient remained without clinical evidence of tumor recurrence. CONCLUSION: Our case report draws attention to the need for including in our differential diagnosis of recurrent acute pancreatitis the mechanical obstruction of the pancreatic duct due to this tumor.

Ciprofloxacin decreases survival in HT-29 cells via the induction of TGF-beta1 secretion and enhances the anti-proliferative effect of 5-fluorouracil.

BACKGROUND AND PURPOSE: Fluoroquinolones are potent anti-microbial agents with multiple effects on host cells and tissues. Previous studies have highlighted their pro-apoptotic effect on human cancer cells and an immunoregulatory role in animal models of inflammatory bowel disease. We examined the effect of ciprofloxacin on proliferation, cell cycle and apoptosis of HT-29 cells, a human colonic epithelial cell line sensitive to transforming growth factor (TGF)-beta1-mediated growth inhibition and its role in TGF-beta1 production. We also examined the effect of ciprofloxacin on proliferation of HT-29 cells in combination with 5-fluorouracil (5-FU), a well-established pro-apoptotic agent. EXPERIMENTAL APPROACH: Using subconfluent cultures of HT-29 and Caco-2 cells, we studied the effect of ciprofloxacin, TGF-beta1 and 5-FU on proliferation, apoptosis, necrosis and cell cycle. The effect of ciprofloxacin on TGF-beta1 mRNA expression and production was studied in RNA extracts and cell culture supernatants respectively, using confluent cultures. KEY RESULTS: Ciprofloxacin decreased proliferation of HT-29 cells in a concentration- and time-dependent manner. This was mediated by accumulation of HT-29 cells into the S-phase but without any effect on apoptosis or necrosis. Additionally, ciprofloxacin enhanced the antiproliferative effect of 5-FU. Interestingly, ciprofloxacin was found to up-regulate TGF-beta1 production by HT-29 cells and its anti-proliferative effect was abolished when TGF-beta1 was blocked. Confirming this mechanism further, ciprofloxacin had no effect on Caco-2, a human colonic epithelial cell line that lacks functional TGF-beta1 receptors. CONCLUSIONS AND IMPLICATIONS: We demonstrate a novel anti-proliferative and immunoregulatory effect of ciprofloxacin on human intestinal epithelial cells mediated via TGF-beta1.

Therapeutic ERCP and pregnancy: is the radiation risk for the conceptus trivial?

BACKGROUND: Symptomatic choledocholithiasis can be treated during pregnancy. Conceptus doses ranged from 0.1 mGy to 3 mGy in previous studies. OBJECTIVE: The objectives of the current study were to investigate whether the conceptus dose may exceed the threshold of 10 mGy in the case of a pregnant patient undergoing ERCP, and to provide data for the accurate assessment of a conceptus dose. DESIGN: Monte Carlo methodology and mathematical anthropomorphic phantoms were used to determine normalized conceptus dose data. Phantoms simulated pregnant patients of different body sizes and gestational stages. Monte Carlo simulations were performed to estimate the efficiency of external shielding. SETTING: University hospital. PATIENTS: Twenty-four consecutive patients. INTERVENTIONS: All patients underwent therapeutic ERCP. Exposure parameters and dose-area product were recorded during the procedures. MAIN OUTCOME MEASUREMENTS: The total dose-area product recorded during ERCP procedures ranged between 62 x 10(3) and 491 x 10(3) mGy . cm(2). RESULTS: Monte Carlo normalized conceptus dose data are presented as a function of kV(p), total filtration, gestational stage, and body mass index. The conceptus dose may exceed 10 mGy when the total dose-area product surpasses 130 mGy . cm(2). LIMITATIONS: Variations of conceptus location and size from the average. CONCLUSIONS: Conceptus dose from ERCP may occasionally exceed 10 mGy, the dose above which the analytical dose calculation is recommended. The use of external shielding is unnecessary because the associated dose reduction is negligible. The normalized dose data may be used for the accurate estimation of conceptus dose from an ERCP procedure performed on a pregnant patient, regardless of body size, gestational stage, operating parameters, and equipment used.

Patients' perceptions as an indicator of quality of care, in Greek patients with inflammatory bowel disease.

AIM AND METHOD: The chronic nature of inflammatory bowel disease (IBD) and its frequent relapses result to a considerable utilization of healthcare resources. Current approaches for the assessment of quality of care are based on the perception of the healthcare provider, which may be different from that of the healthcare user. The purpose of this study was to assess IBD patients' satisfaction, as an indicator of healthcare quality, with the use of a validated instrument (QUOTE-IBD). Ninety-five patients with IBD completed the GR-QUOTE-IBD questionnaire, for the assessment of patient's perception, regarding the quality of the perceived care. RESULTS: According to this evaluation suboptimal care was observed in the dimensions of accommodation, accessibility and information (mean values: 8.92, 8.94 and 8.95, respectively). In the subgroup analysis significant differences were observed in relation to patient's age groups and educational level. Differences were also noted in relation to the disease duration (longer and shorter than 5 years). CONCLUSIONS: The assessment of the quality of health care, based on patients' perception, revealed quality problems in the dimensions of accommodation, accessibility and information. According to subgroup analysis, disease type, educational status, age and disease duration play an important role in the formation of patients' expectations from the healthcare system.

Exploring the agreement between diagnostic criteria for IBS in primary care in Greece.

BACKGROUND: Irritable Bowel Syndrome (IBS) is frequently diagnosed in primary care. Its diagnosis is based on diagnostic criteria but their use is limited in primary care.We aimed to assess the diagnostic agreement between the older (Manning's and Rome II) and the new (Rome III) criteria for the diagnosis of IBS in primary care in Greece. METHODS: Medical records of 5 Health Centers in rural Crete, Greece, were reviewed for a four-year period and patients with the diagnosis of IBS were invited to a structured interview. Kappa agreement of the Rome III criteria with the criteria of Manning and Rome II was estimated. One hundred and twenty three patients were eligible for interview and 67 (54.5%) participated. Forty-six (69%) fulfilled the Manning, 32(48%) the Rome II, and 16(24%) the Rome III criteria. Twenty-seven (40%) patients were identified as IBS according to the questionnaire for the identification of functional gastrointestinal diseases (FGIDs). The agreement of Rome III with Manning criteria was poor (kappa = 0.25). The agreement between the FGIDs questionnaire and the Manning, Rome II and Rome III criteria was: kappa = 0.30, 0.31 and 0.24 respectively. Moderate agreement was found between the Rome II and III criteria (kappa = 0.51). CONCLUSION: Questionnaires and criteria deriving from expert's consensus meetings or tertiary hospitals are not easy to apply in rural primary care where symptoms are often underestimated by patients and complicated questions can be confusing.

Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course.

OBJECTIVE: Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. MATERIAL AND METHODS: A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. RESULTS: Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. CONCLUSIONS: In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients.

BACKGROUND AND AIM: The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort. METHODS: Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. RESULTS: Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. CONCLUSION: The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Bile leakage presenting as acute abdomen due to a stone created around a migrated surgical clip.

BACKGROUND: Surgical clips may migrate into the common bile duct after surgery for cholecystolithiasis leading to usually early or middle-term complications. CASE REPORT: A 31-year-old woman, 6 years after laparoscopic cholecystectomy, developed acute abdomen and choloperitoneum after rupture of a secondary bile duct and bile leakage. This complication was due to a solitary common bile duct stone. The stone was formed around a surgical clip that had migrated from the cystic duct remnant to the common bile duct. The patient underwent investigative laparotomy and, subsequently, an ERCP with stone extraction and clearance of the common bile duct. She was perfectly well at the follow-up after 14 months. CONCLUSIONS: Rupture of a bile duct and biliary peritonitis may be a delayed complication of laparoscopic cholecystectomy due to surgical clip migration and formation of a stone. Definitive treatment of the condition may be achieved through ERCP. Surgeons, gastroenterologists and radiologists should be aware of this late complication of laparoscopic cholecystectomy in cases of acute abdomen.

Nitric oxide and pro-inflammatory cytokines in acute hepatitis B.

Background: Experimental studies demonstrate that hepatitis B virus may induce nitric oxide (NO) production in infected hepatocytes. Its presence in acute hepatitis B patients has not been studied. Methods: Serum levels of nitric oxide and its regulatory pro-inflammatory cytokines were detected in 15 patients with uncomplicated acute hepatitis B, 19 blood donors and 15 chronic hepatitis B patients. Cytokines were determined with an immunoassay. Nitric oxide was measured as the serum metabolic products of nitrates and nitrites using a modification of the Griess reaction. Results: All detected cytokines were increased in acute hepatitis B patients compared to healthy controls (p<0.001 for TNF-alpha, p<0.05 for IL-6, p<0.001 for IL1-beta and p<0.001 for IFN-gamma). High serum levels of nitric oxide were found in acute hepatitis B patients (156.96+/-9.76 micromol/l) compared to healthy controls (51+/-6.2 micromol/l, p<0.001) and chronic hepatitis B patients (63.97+/-3.78 micromol/l, p<0.001). No significant correlations were found between NO, cytokine levels and transaminases. Conclusions: High levels of nitric oxide and its regulatory cytokines were found in a group of patients with uncomplicated acute hepatitis B. The exact role of NO in the disease pathogenesis and outcome needs to be studied further.

Binge drinking and nitric oxide metabolites in chronic liver disease.

AIMS: The effect of binge drinking in the production of nitric oxide metabolites has not been studied in patients with chronic viral liver disease. METHODS: We therefore studied serum levels of nitrites and nitrates (NOx) in 13 patients with chronic viral hepatitis and nine patients with compensated viral cirrhosis, after administration of 80 g alcohol. 15 patients with compensated alcoholic cirrhosis and seven healthy individuals were used as controls. Serum NOx levels were measured by a modification of the Griess reaction before and at 2, 12 and 24 h after alcohol consumption. RESULTS: An increase of serum NOx levels, that was statistically significant at 12 h, was found in healthy controls (P < 0.05). A similar pattern of NOx levels was observed in patients with chronic hepatitis. By contrast, in patients with cirrhosis, either viral or alcoholic, no significant increase was found after alcohol administration. However, basal levels in cirrhotics were significantly elevated (82.2 +/- 13.8 vs. 43.1 +/- 7.2 micro mol/l, P < 0.01) compared to healthy controls. CONCLUSIONS: Binge drinking causes a significant increase of serum NOx evident after 12 h with a return after 24 h at pre-drinking levels in healthy controls and patients with chronic viral hepatitis. In cirrhosis, such an increase is not observed serum levels being constantly elevated throughout the study period.

Validation of a reliable instrument (QUOTE-IBD) for assessing the quality of health care in Greek patients with inflammatory bowel disease.

Given the early onset, the chronic and recurrent nature of their disease and their normal life expectancy, patients with inflammatory bowel disease (IBD) may need considerable health care. The purpose of this study is to validate the Greek translation of the QUOTE-IBD questionnaire (GR-QUOTE-IBD). For that purpose we assessed its construct validity, and reliability. Fifty patients (33 ulcerative colitis, 17 Crohn's disease) completed the GR-QUOTE-IBD and visual-analogue scales (VAS) for the patients' evaluation of the quality of separate care dimensions, and of the total care. A subgroup of 33 patients (64%) completed the GR-QUOTE-IBD for a second time. Quality of life was assessed by the short version of the IBDQ. Clinical activity was assessed by Harvey-Bradshaw index and Colitis Activity Index. Correlations among all care dimensions and VAS were positive and highly significant (p<0.001). The total care and all eight dimensional care scores (quality impact and importance) had no significant differences between the baseline and the follow-up visit. Similarly, the correlation coefficients between the scores of the two occasions were all positive (close to one) and highly significant (p<0.001). The GR-QUOTE-IBD proved to be a valid and reliable instrument, applicable in international clinical studies.

Improved validation of the Inflammatory Bowel Disease Questionnaire and development of a short form in Greek patients.

OBJECTIVES: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease-specific questionnaire for assessing health-related quality of life. The main objective of this study is to assess three main areas of the validation of the Greek IBDQ: internal validity, designating items to dimensions, and selecting items for a short form. An additional aim is to present alternative validation methods for improved and robust results. METHODS: A total of 134 patients with IBD, including 74 with ulcerative colitis (UC) and 60 with Crohn's disease (CD), completed the Greek IBDQ. Internal validity was assessed by using standard methods and multiple correlation analysis. Factor analysis of the 32 items of the questionnaire was carried out to identify the underlying dimensions, using principal factor analysis and maximal likelihood. For selecting items for a short form, three methods of linear regression analysis were used. RESULTS: All items had adequate convergent validity (except item 11 in the CD group) and acceptable discriminant validity (except item 11 for both groups). Factor analysis yielded five factors (emotional function, social function, systemic symptoms, bowel symptoms, and abdominal symptoms). The combination of three regression techniques and their internal validity yielded two similar but distinct short forms, one for UC and one for CD. Both forms had high correlation with the total IBDQ score (R(2) = 0.949 and 0.977, respectively). CONCLUSIONS: The Greek IBDQ had good internal validity. The original designation in four dimensions and the original short form could be improved with only slight modifications.

Validation and results of a questionnaire for functional bowel disease in out-patients.

BACKGROUND: The aim was to evaluate and validate a bowel disease questionnaire in patients attending an out-patient gastroenterology clinic in Greece. METHODS: This was a prospective study. Diagnosis was based on detailed clinical and laboratory evaluation. The questionnaire was tested on a pilot group of patients. Interviewer-administration technique was used. One-hundred-and-forty consecutive patients attending the out-patient clinic for the first time and fifty healthy controls selected randomly participated in the study. Reliability (kappa statistics) and validity of the questionnaire were tested. We used logistic regression models and binary recursive partitioning for assessing distinguishing ability among irritable bowel syndrome (IBS), functional dyspepsia and organic disease patients. RESULTS: Mean time for questionnaire completion was 18 min. In test-retest procedure a good agreement was obtained (kappa statistics 0.82). There were 55 patients diagnosed as having IBS, 18 with functional dyspepsia (Rome I criteria), 38 with organic disease. Location of pain was a significant distinguishing factor, patients with functional dyspepsia having no lower abdominal pain (p < 0.001). Significant factors distinguishing between IBS and functional dyspepsia were relief of pain by either antacids or defecation (19% vs 71% and 66% vs 0% respectively). Awakening from pain at night was also a factor distinguishing between IBS and organic disease groups (26% vs 61%, p < 0.01). CONCLUSIONS: This questionnaire for functional bowel disease is a valid and reliable instrument that can distinguish satisfactorily between organic and functional disease in an out-patient setting.

Is endosonography an effective method for detection and local staging of the ampullary carcinoma? A prospective study.

BACKGROUND: The relatively rare carcinoma of the ampulla of Vater is a neoplasia with a good prognosis compared to pancreatic cancer. Preoperative staging is important in planning the most suitable surgical intervention. AIM: To prospectively evaluate the diagnostic accuracy of Endoscopic Ultrasonography (EUS) in comparison with conventional US and CT scan, in staging of patients with ampullary carcinoma. PATIENTS AND METHODS: 20 patients (7 women and 13 men) with histologically proven carcinoma of the ampulla of Vater were assessed by EUS, CT scan and US. Results were compared to surgical findings. RESULTS: Endoscopic biopsies were diagnostic in 76% of the patients. Detection of ampullary cancer with US and CT scan was 15% and 20% respectively. Only indirect signs of the disease were identified in the majority of cases using these methods. Overall accuracy of EUS in detection of ampullary tumours was 100%. The EUS was significantly (p < 0.001) superior than US and CT scan in ampullary carcinoma detection. Tumour size, tumour extension and the existence of metastatic lymph nodes were also identified and EUS proved to be very useful for the preoperative classification both for the T and the N components of the TNM staging of this neoplasia. The diagnostic accuracy for tumour extension (T) was 82% and for detection of metastatic lymph nodes (N) was 71%. CONCLUSION: EUS is more accurate in detecting ampullary cancer than US and CT scan. Tumor extension and locally metastatic lymph nodes are more accurately assessed by means of EUS than with other imaging methods.

Assessing health-related quality of life in patients with inflammatory bowel disease, in Crete, Greece.

BACKGROUND: Health Related Quality of Life (HRQoL) is an important outcome measure in Inflammatory Bowel Disease (IBD). The aim of our study was to assess HRQoL in a population of 135 Greek patients with IBD. METHODS: A cohort of 135 patients with IBD, 81 with ulcerative colitis (UC) and 54 with Crohn's disease (CD) were enrolled in our study. Demographic and disease-related data were recorded. HRQoL was assessed by a disease-specific and a generic questionnaire, IBDQ and SF-36, respectively. Disease activity was assessed by Harvey-Bradshaw Index and the Colitis Activity Index for CD and UC patients, respectively. RESULTS: Among all variables recorded in our study, only disease activity had a significant effect on HRQoL. Patients with active disease scored significantly lower on both IBDQ and SF-36 when compared to those in remission. Only two among the four IBDQ dimensions, bowel and systemic, had significant ability in distinguishing best patients in remission from those with active disease. CONCLUSIONS: IBD has a negative impact on HRQoL. Patients with active disease are more impaired than patients in remission. In our population of patients bowel and systemic dimensions had a predominant value in patients' perception of quality of life. Patients in our study using the same instrument scored higher than previously reported.

Increasing incidence of cholangiocarcinoma in Crete 1992-2000.

BACKGROUND: There have been recent reports of an increased incidence of cholangiocarcinoma. PATIENTS AND METHODS: Patients with cholangiocarcinoma, resident on the island of Crete, diagnosed between 1992 and 2000, were studied. Case ascertainment was enhanced by collaboration of the pathology departments and all gastroenterologists of Crete in providing relevant data. A specially designed patient protocol was used. Crude incidence rates are presented. RESULTS: During the 9-year period 7 patients were diagnosed with cholangiocarcinoma of the intrahepatic ducts, 17 with Klatskin and 16 patients with extrahepatic ducts carcinoma. A steady incidence increase of cholangiocarcinoma, irrespective of location, was shown. The estimated incidence rate per three-year period progressively increased from 0.998 to 2.329 and 3.327 per 100,000 for the periods 92-94, 95-97 and 98-2000, respectively. Median survival time was 8.5 months. No significant difference was seen between survival according to the location of cholangiocarcinoma. CONCLUSION: A steady incidence increase of cholangiocarcinoma cases in Crete during the time-period 1992-2000 was shown.