A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion.

PURPOSE: This study was performed to assess the toxicities, the maximum-tolerated dose (MTD), the pharmacokinetics and the anti-tumour activity of gemcitabine given by 24-h hepatic arterial infusion (HAI). PATIENTS AND METHODS: Patients with liver malignancies received gemcitabine by 24-h HAI, weekly x 3, every 4 weeks. On day 1 or day 8 of the first cycle, patients received one administration by 24-h intravenous infusion for pharmacokinetic comparison and to determine hepatic extraction. RESULTS: Thirteen patients received gemcitabine at the dose levels of 75, 135 and 180 mg/m(2). The MTD was 180 mg/m(2) with thrombocytopaenia as the dose-limiting toxicity. Pharmacokinetic analysis showed a significantly lower maximum gemcitabine plasma concentration (C(max): HAI, 26, 80 and 128 nM, respectively; IV, 229, 264 and 293 nM, respectively) and area under the plasma-concentration-versus-time curve (AUC(0-24h): HAI, 386, 1247 and 2033 nmol x h/L, respectively; IV, 3526, 4818 and 5363 nmol x h/L, respectively) during HAI, compared with intravenous infusion (both P<0.001). Additionally, the mean hepatic extraction ratios of gemcitabine at the 75, 135 and 180 mg/m(2) dose level were 0.89, 0.75 and 0.55, respectively. Hepatic extraction decreased linearly with increasing dose. The C(max) and AUC(0-24h) of 2',2'-difluoro-2'-deoxyuridine, the deaminated product of gemcitabine, were similar for HAI and intravenous infusion. Seven patients had stable disease for a median duration of 9 months (range: 2-11 months). CONCLUSIONS: Gemcitabine given by 24-h HAI was well tolerated and resulted in significantly lower systemic gemcitabine plasma concentrations than intravenous infusion due to a relatively high hepatic extraction.

Acute necrotizing pancreatitis following inadvertent extensive splenic artery embolisation for trauma.

We present a case of splenic artery embolisation (SAE) after traumatic splenic injury that was complicated by acute necrotizing pancreatitis, caused by inadvertently extensive embolisation of the splenic artery. Although SAE is increasingly used for splenic preservation in trauma, there is insufficient knowledge on its efficacy and pitfalls. This report aims to draw attention to a rare but potentially serious complication of SAE.

Increased pulmonary capillary permeability and extravascular lung water after major vascular surgery: effect on radiography and ventilatory variables.

INTRODUCTION: We decided to investigate the pathogenesis of pulmonary ventilatory and radiographic abnormalities in patients after major vascular surgery. PATIENTS AND METHODS: Sixteen mechanically ventilated patients without heart failure were studied, within 3 h after major abdominal surgery. We measured extravascular lung water, intrathoracic, global end-diastolic and pulmonary blood volumes, (67)Ga-transferrin pulmonary leak index and ventilatory and radiographic variables. The latter allowed computation of the lung injury score as a measure of lung injury. RESULTS: The extravascular lung water was elevated (>7 mL kg(-1)) in 5 of 16 patients, while the pulmonary leak index was elevated in 11 patients and a supranormal extravascular lung water was associated with a high pulmonary leak index and higher extravascular lung water relative to intrathoracic blood volume or pulmonary blood volume. Patients were arbitrarily divided into those with a lung injury score >1 and < or =1, and only differed in the factors composing the score as well as in extravascular lung water divided by pulmonary blood volume. A lung injury score >1 was associated with a longer duration of mechanical ventilation. CONCLUSION: Our data suggest that mild, subclinical, pulmonary oedema is relatively common after major vascular surgery, mainly caused by increased pulmonary capillary permeability in the absence of overt heart failure. However, permeability oedema only partially contributes to postoperative lung injury score and need for mechanical ventilation, suggesting a major contribution by atelectasis.

Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema.

BACKGROUND: Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate. METHODS: A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal-dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer. RESULTS: The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 x 10(-3)/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end-expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without. CONCLUSIONS: After cardiac surgery, mild pulmonary oedema is relatively common, even in the absence of high filling pressures, and is mainly attributable to a low COP, irrespective of increased permeability in about one-half of patients. It may prolong mechanical ventilation at EVLW > 10 ml/kg. However, pulmonary radiographic and ventilatory abnormalities may result, at least in part, from atelectasis rather than increased permeability oedema.

Anomaly of the inferior vena cava causing recurrent deep vein thrombosis in a young male.

Anomaly of the inferior vena cava (IVC) as a cause of (recurrent) deep vein thrombosis (DVT) is uncommon. We report on a 33-year-old patient suffering from this unusual cause of DVT without the presence of known predisposing factors (immobilization, trauma, surgery, or underlying thrombophilia). Thus, in young patients with recurrent DVT, anomaly of the IVC should be regarded as an independent risk factor.

Treatment of haemangiopericytoma-associated hypoglycaemia with embolisation.

A 48-year-old woman with a known history of metastatic haemangiopericytoma presented with intractable hypoglycaemia. Hypoglycaemia was accompanied by undetectable serum insulin levels with high levels of proforms of insulin-like growth factor-II ('big' IGF-II). Reduction of tumour load with embolisation resulted in a normal pattern of serum glucose levels throughout the day.

The role of type III collagen in family members of patients with abdominal aortic aneurysms.

OBJECTIVES: type III collagen is responsible for the tensile strength of the aorta-wall. To determine if genetic defect in the type III collagen production is associated with familial clustering of AAA. METHODS: fifty-six patients with AAA and 82 first-degree family members participated. The medical and family histories were obtained. All these relatives were screened by ultrasound for AAA. In 58 relatives of 20 families, skin biopsies were taken for protein analysis to measure type III collagen production in cultured fibroblasts. RESULTS: only one new AAA was detected in a brother of a patient. Four other relatives were already known with AAA. Three AAA patients had a type III collagen deficiency, but type III collagen was normal in all family members. CONCLUSION: type III collagen deficiency does not appear to be an aetiological factor in the development of AAA.

Retroperitoneal endoscopic ligation of lumbar and inferior mesenteric arteries as a treatment of persistent endoleak after endoluminal aortic aneurysm repair.

A 74-year-old man receiving long-term anticoagulation therapy for intermittent atrial fibrillation had a type II endoleak after endovascular abdominal aortic aneurysm repair. During an 8-month follow-up, the endoleak persisted, and the aneurysm failed to decrease in diameter. By means of a left flank retroperitoneal endoscopic surgical approach, the aneurysm was dissected free, and the lumbar arteries emanating from the aneurysm, as well as the inferior mesenteric artery, were ligated with titanium clips. A postoperative spiral computed tomography scan depicted one pair of unclipped lumbar arteries just proximal to the aortic bifurcation. After immediate reoperation with the same approach, complete thrombosis of the aneurysm sac was radiographically confirmed.

Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: single-centre experience in 145 patients.

BACKGROUND: Hepatic arterial chemotherapy for liver metastases of colorectal cancer is still under discussion. Mainly because of the technical complications of this mode of treatment and the lack of a survival benefit in randomized studies. We performed an analysis of hepatic arterial 5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at a single institution. PATIENTS AND METHODS: One hundred forty-five patients with inoperable liver metastases from colorectal cancer were included. 5-FU, 1000 mg/m2/day continuous infusion for five days every three weeks, was delivered in the hepatic artery by percutaneous catheter or arterial access device. RESULTS: The response rate was 34% for all patients, 40% in patients with extrahepatic disease, and 15% in patients with i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and 14.3 months, respectively. In patients with extrahepatic disease or i.v. 5-FU-based pretreatment, OS was significantly shorter compared to patients without extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 months and 10.1 vs. 17.4 months, respectively), forty-seven percent of patients stopped treatment because of a complication. Complications most often seen in patients with arterial ports were hepatic artery thrombosis (48%) and dislocation of the catheter (22%). CONCLUSIONS: The results of our analysis are in line with previous phase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment were prognostic for reduced OS. The complication rate of hepatic arterial delivery was worrisome. although, no negative impact on survival could be established. There is a strong need for improvement of hepatic arterial delivery methods before further evaluation of hepatic arterial

Intravascular ultrasound predictors of restenosis after balloon angioplasty of the femoropopliteal artery.

OBJECTIVES: To determine intravascular ultrasound parameters related to restenosis following percutaneous transluminal balloon angioplasty (PTA) of the femoropopliteal artery. DESIGN: Prospective study. MATERIALS AND METHODS: Patients were studies with intravascular ultrasound before and after angiographic successful PTA (n = 114). Intravascular ultrasound cross-sections obtained with 1 cm interval in the dilated segment were analysed. A distinction was made between anatomic (duplex scanning) and clinical (Rutherford criteria) restenosis assessed within 1 month and at 6 months after PTA. RESULTS: Intravascular ultrasound predictors of 1 month anatomic outcome were lumen area stenosis after PTA, lumen area increase, plaque area decrease, and area stenosis decrease; predictor of 6 months anatomic outcome was area stenosis after PTA. Multivariate analysis revealed that area stenosis after PTA was the only independent predictor of both 1 and 6 months anatomic outcome. Intravascular ultrasound predictors of 1 month clinical outcome were the presence of hard lesion and the mean arc of hard lesion. Multivariate analysis revealed that the mean arc of hard lesion was the only independent predictor of 1 month clinical outcome. No predictors for 6 months clinical outcome were found. CONCLUSIONS: Intravascular ultrasound can elucidate parameters predictive of restonosis after PTA. The strongest intravascular ultrasound parameter predictive of anatomic restenosis was a large area stenosis after PTA.

Intravascular ultrasound predictors of outcome after peripheral balloon angioplasty.

OBJECTIVE: This study investigates the potential role of intravascular ultrasound (IVUS) in the outcome in patients undergoing percutaneous transluminal angioplasty (PTA) of the superficial femoral artery. MATERIALS: Angiographic and the qualitative and quantitative IVUS data obtained at the narrowest site derived from 39 patients before and after PTA were analysed. RESULTS: Angiographically the diameter of the remaining stenosis seen after PTA was classified as < 50% in 31 patients (success); in eight patients a failure was encountered. Evaluating at 6 months the functional and anatomic results of the PTA in 31 patients, the intervention was a success in 14 patients (Group I) and a failure in 17 patients (Group II). The remaining eight patients defined as angiographic failure following PTA comprised Group III. Neither qualitative nor quantitative IVUS data obtained before PTA could predict outcome. Conversely, after PTA, the extent of dissection was significantly more severe in Groups II and III than in Group I. Similarly, significant differences were found between Groups I and II for mean free lumen area (13.2 vs. 9.7 mm2, respectively) and mean free lumen diameter (4.1 vs. 3.5 mm, respectively). Quantitative data obtained in Group II were similar to those in Group III. CONCLUSION: This preliminary study demonstrates that following PTA the extent of dissection, free lumen area and diameter seen with IVUS are predictive factors of patency. Future studies with more patients are mandatory to further highlight the sensitivity of these observations.

Remodeling of De Novo atherosclerotic lesions in femoral arteries: impact on mechanism of balloon angioplasty.

OBJECTIVES: Using 30-MHz intravascular ultrasound in the human femoral artery, we related the mode of arterial remodeling to the immediate result and the mechanism of balloon angioplasty. BACKGROUND: The atherosclerotic femoral artery may undergo three modes of remodeling in response to plaque formation: compensatory enlargement, failure of compensatory enlargement and paradoxic shrinkage. METHODS: In 83 patients an ultrasound catheter pullback maneuver was performed before and after balloon angioplasty. For each lesion (n = 121), the cross section with the narrowest lumen was selected for further analysis. For each cross section, the lumen area stenosis was expressed as percent of the lumen area at an adjacent reference site. Similarly, the media-bounded area was expressed as percent of the media-bounded area at the reference site. Cross sections were classified into one of three groups based on percent relative media-bounded area: 1) > 105% (group A, compensatory enlargement, n = 24); 2) 95% to 105% (group B, failure of compensatory enlargement, n = 26); and 3) < 95% (group C, arterial wall shrinkage, n = 71). The power of the present study was 99.3% to demonstrate a difference in lumen gain of 2.5 mm2 among groups. RESULTS: The gain in lumen area induced by balloon angioplasty did not differ significantly among the three groups (group A, 7.0 +/- 4.0 mm2 [mean +/- SD]; group B, 8.6 +/- 4.8 mm2; group C, 8.9 +/- 4.9 mm2). Stretch of the media-bounded area was observed in all three groups, but it was significantly larger in group C (7.5 +/- 5.2 mm2) than in the other two groups (group A, 3.9 +/- 5.1 mm2; group B, 5.1 +/- 4.1 mm2). A significantly positive correlation between balloon/media-bounded area ratio and elastic recoil was observed for cross sections in groups A and B (r = 0.71 and r = 0.69, respectively). However, no correlation was observed between balloon/media-bounded area ratio and elastic recoil for cross sections in group C (r = 0.17). CONCLUSIONS: We conclude that lumen gain by balloon angioplasty is not related to the mode of atherosclerotic arterial remodeling. However, the mode of arterial remodeling affects the dilation mechanism.

[Synchronous and metachronous bilateral hypernephroid renal carcinomas]. / Synchrone und metachrone bilaterale hypernephroide Nierenkarzinome.

In 1.4-3.9% Grawitz tumours occur bilaterally, either synchronously or metachronously. Three patients with a bilateral Grawitz tumour are described, two with a synchronous and one with a metachronous one. Epidemiology, pathology, clinical symptoms, radiodiagnostics, therapy and prognosis of the bilateral Grawitz tumours are discussed.

[Simultaneous bilateral Wilms' tumors]. / Simultane bilaterale Wilms-Tumoren.

Wilms' tumors occur in 4-14% bilaterally, partially simultaneously, partially metachronously. Therefore in every case with Wilms' tumor the contralateral kidney has to be examined thoroughly too. 5 children of a series of 52 patients with Wilms' tumor showed simultaneous bilateral occurrence (9,6%). The radiological procedures and their importance in diagnosis of bilateral Wilms' tumor are discussed. The prognosis of simultaneous bilateral Wilms' tumors is much better than that of metachronous ones and almost the same as that of unilateral ones.

Comparison of pain and heat sensation of contrast media in aortofemoral angiography: meglumine-amidotrizoate (Angiografin) mixed with lidocaine versus sodium-meglumine-ioxaglate (Hexabrix).

A total of 116 translumbar aortofemoral angiograms were performed in 92 patients. At random, 58 contrast injections were done with Hexabrix and 58 with Angiografin mixed with lidocaine. Pain and heat sensation was evaluated by a verbal rating system. Most patients in both groups had no or mild pain sensation. There was, however, a slight but statistically significant difference (p less than 0.05) in favor of Hexabrix. No difference was found in heat sensation in either of the groups.