C. Verslype

Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) can lead to the development of cholangiocarcinoma (CCA). The tumor may present as an intrahepatic focal cholangiocellular carcinoma but more often as a ductal infiltrating desmoplastic lesion. CCA is found synchronously with the diagnosis of PSC in 20–30% and within 1 year in 50%. During later follow-up, the yearly developmental rate of CCA is 0.5–1.5%. Most patients with PSC and CCA do not yet have cirrhosis but present with a severe stenosis at the hilum of the liver. This type of tumor is difficult to diagnose by imaging techniques.18F-FDG-PET scanning and CEA or CA 19-9 are not early diagnostic tools. Regular MRI, multislice CT, and repeated endoscopically obtained brush cytology of stenotic lesions are recommended. The recent use of more extensive surgical resection techniques in patients with CCA results in 5-year survival rates of ≥50%. If tumors are small or incidental findings, liver transplantation leads to a 3- to 5-year survival rate of 35%. Pretransplant radiotherapy with 5-FU chemosensitization followed by endoscopic brachytherapy with iridium-192 seems to greatly improve the outcome of transplantation. Treatment with ursodeoxycholic acid may prevent development of CCA.

Congenital veno-venous malformations of the liver: widely variable clinical presentations.

Background and Aim:  Congenital portosystemic veno‐venous malformations are rare abnomalities that often remain undiagnosed. Typically they are classified by their anatomical characteristics according to Morgan (extrahepatic, Abernethy malformations type Ia,b and II) and Park (intrahepatic, types 1–4). However, their clinical presentation is less dependent on the anatomical type.

Tolerance of Liver Transplant Patients to Strenuous Physical Activity in High-Altitude

Physical functioning is improved after liver transplantation but studies comparing liver transplant recipients with normal healthy people are lacking. How liver (and other organ) transplant recipients tolerate strenuous physical activities is unknown. There are no data on the tolerance of transplant patients at high altitude. Six liver transplant subjects were selected to participate in a trek up Mount Kilimanjaro 5895m, Tanzania. Physical performance and susceptibility to acute mountain sickness were prospectively compared with fifteen control subjects with similar profiles and matched for age and body mass index. The Borg‐scale (a rating of perceived exertion) and cardiopulmonary parameters at rest were prospectively compared with six control subjects also matched for gender and VO2max. Immunosuppression in transplant subjects was based on tacrolimus. No difference was seen in physical performance, Borg‐scales and acute mountain sickness scores between transplant and control subjects. Eight‐three percent of transplant subjects and 84.6% of control subjects reached the summit (p = 0.7). Oxygen saturation decreased whereas arterial blood pressure and heart rate increased with altitude in both groups. The only difference was the development of arterial hypertension in transplant subjects at 3950 m (p = 0.036). Selected and well‐prepared liver transplant recipients can perform strenuous physical activities and tolerate exposure to high altitude similar to normal healthy people.

Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder

BackgroundThe probability that a patient has common bile duct stones (CBDS) is a key factor in determining diagnostic and treatment strategies. This prospective cohort study evaluated the accuracy of clinical models in predicting CBDS for patients who will undergo cholecystectomy for lithiasis.MethodsFrom October 2005 until September 2006, 335 consecutive patients with symptoms of gallstone disease underwent cholecystectomy. Statistical analysis was performed on prospective patient data obtained at the time of first presentation to the hospital. Demonstrable CBDS at the time of endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography (IOC) was considered the gold standard for the presence of CBDS.ResultsCommon bile duct stones were demonstrated in 53 patients. For 35 patients, ERCP was performed, with successful stone clearance in 24 of 30 patients who had proven CBDS. In 29 patients, IOC showed CBDS, which were managed successfully via laparoscopic common bile duct exploration, with stone extraction at the time of cholecystectomy. Prospective validation of the existing model for CBDS resulted in a predictive accuracy rate of 73%. The new model showed a predictive accuracy rate of 79%.ConclusionClinical models are inaccurate in predicting CBDS in patients with cholelithiasis. Management strategies should be based on the local availability of therapeutic expertise.

MALIGNANT INVOLVEMENT OF THE KNEE SYNOVIUM IN A PATIENT WITH METASTASTIC OESOPHAGEAL ADENOCARCINOMA

Abstract We describe the case of a malignant arthritis of the knee. This is the first description with an oesophageal adenocarcinoma being the primary site of the malignancy. Diagnosis of this rare condition can be made by cytological examination of joint fluid or by synovial biopsy. X-ray of the joint can, as in our case, be negative. There is no standard therapy and the prognosis seems to be poor. Although rare, malignant synovitis represents an important differential diagnosis in patients with an unexplaned monoarthritis, as it can be the first sign of malignancy or the only site of metastic disease.

Dynamic 68Ga-DOTATOC PET/CT and static image in NET patients

Purpose: To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs). Patients, methods: 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio). Results: SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001). Conclusions: As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.PURPOSE To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs). PATIENTS, METHODS 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio). RESULTS SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001). CONCLUSIONS As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.

Dynamische und statische 68Ga-DOTATOC-PET/CT bei Patienten mit NET

Purpose: To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs). Patients, methods: 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio). Results: SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001). Conclusions: As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.PURPOSE To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs). PATIENTS, METHODS 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio). RESULTS SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001). CONCLUSIONS As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.

654 A NEW CLASSIFICATION OF PRIMARY LIVER CARCINOMAS BASED ON THEIR POSSIBLE CELLULAR ORIGIN

universal sustained virological response (SVR), it is eagerly hoped that morbidity and mortality from hepatitis C virus (HCV) will soon disappear. At present, cirrhosis, the predominant risk factor for hepatocellular carcinoma (HCC), is increasing among patients with HCV as they become older and the duration of infection longer. We estimate the impact of DAAs with high SVR rates on the incidence of HCC in the population. Methods: Since the extent to which the risk of HCC decreases in patients with established cirrhosis achieving SVR remains poorly defined, we conducted a simulation experiment in which a cohort of 50 year-old subjects (n = 1,000) with compensated HCV cirrhosis (MELD=6) is followed for 20 years. In a viremic subject, the MELD score, HCC and mortality from end stage liver disease (ESLD) would increase progressively. Once SVR is achieved, MELD would stop increasing and the proportion at risk of HCC decrease over time. Results: The Table summarizes 20-year outcomes in the 50 year-old cohort based on SVR eliminating HCC risk in 3%/year.

682 APPARENT DIFFUSION COEFFICIENT DETERMINED TARGET RESPONSE AT DIFFUSION-WEIGHTED MRI IS AN INDEPENDENT PREDICTOR OF OUTCOME IN HEPATOCELLULAR CANCER PATIENTS TREATED WITH TRANSARTERIAL CHEMOEMBOLIZATION

Patients and Methods: Two hundred pairs of patients with cirrhosis and HCC and unrelated patients with cirrhosis alone were enrolled. Polymorphisms of TNFa −238, TNFa −308, and lymphotoxin (LT)a +252 were genotyped by the polymerase chain reaction with direct sequencing or restriction fragmented length polymorphism. TNF haplotypes were also analyzed. From routine laboratory data, the following surrogate markers associated with hepatic fibrosis were measured: platelet count, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase/platelet ratio index, Pohl score, and cirrhosis discriminant score. These fibrosis surrogate markers were analyzed with polymorphisms and haplotypes of TNF locus. Results: The frequencies of the variant genotypes and alleles of LTa +252 and TNFa −308 in patients with HCC were significantly higher than those in patients with cirrhosis alone. There was no such a difference in the TNFa −238 polymorphisms. Univariate analysis indicated that LTa +252 G/G genotype (odds ratio (OR) = 2.31) and TNFa −308 G/A genotype (OR=2.31) were significantly associated with HCC. Multivariate analysis indicated that LTa +252 G/G (OR=2.05, 95% confidence interval (CI), 1.20– 3.51), TNFa −308 G/A (OR=1.77, 95%CI, 1.02–3.07), and TNF haplotypes (AGA, OR=5.69; 95%CI, 1.90–17.10; GGA, OR=2.07; 95%CI, 1.18–3.63; and GGG, OR=1.51, 95%CI, 1.11–2.04) were independent risk factors for HCC. Among patients with cirrhosis and HCC, significant hepatic fibrosis was found between 71.4% and 93.5% of patients with variant TNF genotypes and between 54.4% and 86.8% of patients harboring TNF haplotypes (AGA, GAG and GGG). Multivariate analysis showed that factors associated with variant genotypes included cirrhosis with Child–Pugh C (OR=8.85; 95%CI, 3.08–35.64), serum a-fetoprotein >100ng/ml (OR=2.50; 95%CI, 1.23–5.06), and thrombocytopenia (OR=3.26; 95%CI, 1.14– 9.30). Conclusions: Patients with cirrhosis who carry the TNF genetic variants were correlated with advanced fibrosis and severe liver damage, which may contribute to a higher risk to HCC.

178 A PROSPECTIVE STUDY COMPARING THE DIFFERENT INDIRECT METHODS TO MEASURE PORTAL PRESSURE

[Maleux, G; Willems, E; Heye, S; Vaninbroukx, J] Katholieke Univ Leuven Hosp, Dept Radiol, B-3000 Louvain, Belgium. [Laleman, W; Cassiman, D; Verslype, C; Nevens, F] Katholieke Univ Leuven Hosp, Dept Hepatol, B-3000 Louvain, Belgium. [Fieuws, S] Katholieke Univ Leuven, Interuniv Inst Biostat & Stat Bioinformat, Louvain, Belgium. Univ Hasselt, Louvain, Belgium. geert.maleux@uzleuven.be