Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy.

PURPOSE: To define the maximum tolerated dose (MTD) of hepatic intraarterial chemotherapy with gemcitabine, administered with and without starch microspheres, in patients with inoperable intrahepatic cholangiocarcinomas and liver metastases of pancreatic carcinomas. METHODS: Gemcitabine was administered on days 1 and 8 with intervals of 2 weeks between the cycles. In group A the initial gemcitabine dose of 1,000 mg/m(2) (without microspheres) was increased in 200-mg/m(2) steps up to a maximum dose of 2,000 mg/m(2). In group B the MTD with microspheres was assessed by giving an additional microsphere dose according to tumor extent and body weight, increasing gemcitabine starting from a dose-step below the MTD with microspheres. The MTD was evaluated via clinical and laboratory findings. RESULTS: Twenty-four patients were enrolled (12 males, 12 females, mean age 59.17 years; intrahepatic cholangiocarcinoma: n = 17, liver metastases of pancreatic carcinoma: n = 7). The MTD of gemcitabine without microspheres was reached at 1,400 mg/m(2), and of gemcitabine with microspheres at 1,800 mg/m(2). The comparative evaluation revealed statistically significant better data for the time to progression (p < 0.01) and survival for the group with microspheres (6.8 and 20.2 months) in comparison to the group without microspheres (4.2 and 13.5 months). CONCLUSION: This clinical study indicates that the intraarterial application of gemcitabine with doses higher than the recommended 1,000 mg/m(2) is well tolerated if combined with microspheres, and yields respectable results in patients who do not respond to systemic chemotherapy.

Does secretin-stimulated MRCP predict exocrine pancreatic insufficiency?: A comparison with noninvasive exocrine pancreatic function tests.

BACKGROUND: Data on magnetic resonance cholangiopancreatography with secretin stimulation (S-MRCP) for the assessment of exocrine pancreatic insufficiency (EPI) are limited. We compared pancreatic function tests with the findings of S-MRCP in patients with chronic pancreatitis (CP) and disease controls. METHODS: S-MRCP was performed in 23 patients (18 CP, 5 disease controls). MRCP images were analyzed for secretin-induced duodenal liquid filling (0=no filling; 1=duodenal bulb; 2=up to lower flexure; 3=beyond lower flexure). EPI was evaluated by fecal elastase, fecal fat concentration, and a 13C mixed chain triglyceride breath test. Clinically relevant EPI was stated if 2 of 3 tests were pathologic. RESULTS: EPI was diagnosed in 10 of 18 patients with CP. Patients without EPI showed either grade 2 (n=4) or grade 3 (n=9) duodenal filling, whereas only 1/10 patients with EPI showed grade 3 duodenal filling. Sensitivity and specificity of S-MRCP for the diagnosis of EPI were 69% and 90%, respectively. CONCLUSIONS: Assessment of duodenal filling should be performed in patients who undergo S-MRCP for the evaluation of pancreatic morphology. However, minor degrees of duodenal filling are equivocal and require further diagnostic evaluation.

Staging of Klatskin tumours (hilar cholangiocarcinomas): comparison of MR cholangiography, MR imaging, and endoscopic retrograde cholangiography.

The aim of the study was to compare prospectively magnetic resonance cholangiography (MRC) and magnetic resonance imaging (MRI) with endoscopic retrograde cholangiography (ERC) in the diagnosis and staging of Klatskin tumours of the biliary tree (hilar cholangiocarcinomas). Forty-six patients with suspected Klatskin tumours of the biliary tract underwent MRI and heavily T2-weighted, non-breathhold, respiratory-triggered fast spin-echo MRC. Forty-two patients underwent ERC within 24 h; in four patients, ERC was not feasible, and percutaneous trans-hepatic cholangiography (PTC) was carried out instead. Two independent investigators evaluated imaging results for the presence of tumour, bile duct dilatation, and stenosis. Clinical and histopathological correlation revealed Klatskin tumours in 33 patients. MRI revealed a slightly hyperintense signal of infiltrated bile ducts in T2-weighted fast spin-echo sequences. The malignant lesion was regularly visualized as a hypointense area in T1-weighted gradient-echo sequences with substantial contrast enhancement along the involved bile duct walls. MRC revealed the location and extension of the tumour in 31 of 33 cases correctly (sensitivity 94%, specificity 100%, diagnostic accuracy 95%). In 27 of 31 cases, ERC enabled accurate staging and diagnosis of Klatskin tumours with a sensitivity of 87%. ERC and PTC combined yielded a sensitivity of 84% and a specificity of 97%. Tumours were grouped according to the Bismuth classification, with MRC allowing correct identification of type I tumour in seven patients, type II tumour in four patients, type III tumour in 12 patients, and type IV tumour in ten patients. MRC provided superior visualization of completely obstructed peripheral systems. MRC in combination with MRI is a reliable non-invasive diagnostic method for the pre-therapeutic staging of Klatskin tumours.