Introducing the clusterin gene into human renal cell carcinoma cells enhances their metastatic potential

PURPOSE: We recently reported a protective role of clusterin expression against apoptosis induced by a wide variety of stimuli in several human cancer models. In the current study we tested the hypothesis that clusterin over expression confers a benefit for the metastasis of renal cell carcinoma through the inhibition of apoptosis induced by the various obstacles the cancer cells may confront after detachment from their primary origin. MATERIALS AND METHODS: We introduced clusterin complementary DNA into human renal cell carcinoma ACHN cells, which do not express detectable level of clusterin expression, and generated the clusterin over expressing cell line ACHN/CL and the control vector only transfected cell line ACHN/C. In vitro anti-cell death activity under anchorage independent conditions among ACHN sublines was examined by limiting dilution assay and cell survival assay in suspension. To investigate the in vivo effects of clusterin over expression on metastatic potentials each cell line was injected into the tail vein or renal subcapsule of nonobese diabetic, severe combined immunodeficient mice and the metastatic features in all abdominal and thoracic organs were evaluated. RESULTS: ACHN/CL showed significantly enhanced growth in limiting dilution cultures compared with ACHN/C. The analysis of cell survival in the floating assay also revealed that ACHN/CL had a powerful survival advantage in suspension compared with ACHN/C. Furthermore, ACHN/CL formed more than 5-fold as many metastatic nodules in the lung after intravenous injection than ACHN/C. Similarly more marked lung metastasis was observed after implanting ACHN/CL cells into the renal subcapsule than after implanting ACHN/C cells. In contrast, there were no significant differences among ACHN sublines in the growth rates in vitro and in vivo, cell motility or invasive ability. CONCLUSIONS: These findings suggest that, if clusterin is over expressed, it prolongs cell survival under unfavorable conditions in the metastatic process, resulting in the enhanced metastatic potential of renal cell carcinoma.     

Blunt renal trauma in children: experience with conservative management at a pediatric trauma center

BACKGROUND: The authors reviewed the outcome for children with blunt renal injury managed with a nonoperative protocol at their pediatric trauma center. METHODS: Fifty-five consecutive children aged 0.5 to 17 years with blunt renal injury managed over a 14-year period were reviewed. All patients were evaluated with computed tomographic scanning. Injuries were graded according to the American Association for the Surgery of Trauma Organ Injury Scale. RESULTS: Forty-eight of 55 children (87%) were successfully managed nonoperatively. Overall, there were 5 grade I, 13 grade II, 18 grade III, 14 grade IV, and 5 grade V injuries. All children with grades I and III injuries were successfully managed nonoperatively. Two (6%) of these children required transfusion. Only four (29%) children with grade IV and three (60%) with grade V injuries required surgical interventions (one nephrostomy, six nephrectomies). Excluding patients with continuing hemorrhage, only 2 (14%) of 14 with high-grade injuries required surgical intervention (1 nephrostomy, 1 nephrectomy). Clearance of gross hematuria correlated with severity of injury and was prolonged in grade IV and V compared with grade I to III injuries (6.8 +/- 2.7 vs. 3.2 +/- 2.1 days, respectively; p < 0.05). Fifty-one children (93%) available for follow-up were normotensive with normal renal function. CONCLUSION: These data support the use of conservative management for all grades in stable children with blunt renal injury. Transfusion requirements, operative rates, and outcome are consistent with other pediatric solid organ injuries.     

Occlusion versus shunting during MIDCAB: effects on left ventricular function and quality of anastomosis

BACKGROUND: Minimally invasive direct coronary artery bypass is an established clinical procedure for revascularization of the left anterior descending coronary artery. Mechanical stabilization and temporary occlusion is currently used to perform the anastomosis of the internal thoracic artery to the left anterior descending coronary artery. However, critical reduction of cardiac function can occur as a result of temporary ischemia. The purpose of this study was to evaluate whether ischemic sequelae can be avoided by using temporary intraluminal shunts and whether this alters early outcome. METHODS: Thirty-five patients underwent minimally invasive direct coronary artery bypass revascularization using a mechanical stabilizer. In group A (n = 20), the anastomotic site was temporarily occluded by tourniquets. In group B (n = 15), temporary intraluminal shunts were inserted into the anastomotic site without any occlusion of the left anterior descending coronary artery. Anastomosis of the internal thoracic artery to the left anterior descending coronary artery was performed in an identical fashion. A Swan-Ganz catheter was inserted, and transesophageal echocardiographic measurements were obtained for analysis of left ventricular (LV) function. Regional wall motion, cardiac index, stroke volume index, systolic and diastolic LV diameters, and fractional area change were measured during four periods: at the start of the operation (baseline), placement of the stabilizer (stabilization), left anterior descending coronary artery occlusion (occlusion) or insertion of temporary intraluminal shunts (shunt), and 30 minutes after reperfusion (reperfusion). Angiograms were obtained 4 to 6 days postoperatively. RESULTS: In group A, LV performance, cardiac index, stroke volume index, and fractional area change decreased during occlusion whereas systolic diameters increased. Almost two myocardial segments per patient developed severe hypokinesia in the perfusion area. These changes disappeared after 30 minutes of reperfusion, with increased LV function. In group B, LV function remained stable whereas hypokinetic wall motion was only detected in 2 patients. Early angiograms revealed 90% of the grafts were patent in group A versus 100% in group B. The need for percutaneous intervention during the first 6 months was 20% in group A versus 6.7% in group B. CONCLUSIONS: The use of temporary intraluminal shunts resulted in reduced acute ischemia and revealed wall motion abnormalities and maintained LV function. Furthermore, this technique suggests an improvement of early graft patency and a lower reintervention rate within the first 6 postoperative months. Thus, use of temporary intraluminal shunts appears to be superior to the occlusion technique early after minimally invasive direct coronary artery bypass procedures.     

Evaluation of superficial papillary ablation by endoscopic lasers in an ex vivo kidney model

BACKGROUND AND PURPOSE: Endoscopic examinations of stone-forming kidneys show a coincidence of plaques and microliths on the surface of and within papillary epithelial tissue. These calcifications are thought to be precursors of calcium oxalate urolithiasis. We hypothesized that minimally invasive endoscopic laser ablation of microliths and necrotic cell layers enables epithelial regeneration and prevents recurrent urolithiasis. The aim of this study was to determine the most suitable laser type and dose intensity for selective superficial cell ablation. MATERIALS AND METHODS: Conventional Nd:YAG (1-40 W) or Ho:YAG (0.5-3 J/single impulse) lasers were used endoscopically on an ex vivo blood-perfused porcine kidney model. Defined doses were applied to the papillary surface in the contact and noncontact modes for 10 to 30 seconds. Papillae were excised after treatment and histopathologically analyzed in continuous sections. Lesions were microscopically assessed with the aid of a Leica Quantimed computer program. RESULTS: Depending on the time and dose, vaporization by the Nd:YAG laser caused large tissue defects and coagulation necrosis at energy levels over 5 W (contact and noncontact mode). Lower energy levels with tissue contact produced only superficial cell defects (<20 cell layers) but more extensive coagulation necrosis, whereas no histologic effects were observed at the same energy level without contact. In contrast, independent of delivered energy but dependent on time, Ho:YAG laser application caused pure tissue loss without relevant coagulation necrosis. The generation of small lesions (6-10 cell layers) without tissue contact was possible at energy levels under 2 J. CONCLUSIONS: Selective superficial papillary cell ablation is possible. Low-energy Nd:YAG treatment in the contact mode and Ho:YAG treatment in the noncontact mode led to superficial vaporization with no (Ho:YAG) or minimum (Nd:YAG) coagulation defects.     

Reproducibility of constant-load treadmill testing with various treadmill protocols and predictability of treadmill test results in patients with intermittent claudication

BACKGROUND: Most trials on the reliability of constant-load treadmill testing use one pair of treadmill settings (speed, grade) only. The question of whether the results can be applied to tests with different settings is left open. Also, claudication distances measured with differing settings are not comparable, rendering the comparison of the results from different trials difficult. This study evaluates the reliability of constant-load testing with various workloads and compares them with claudication distances achieved with walking at normal speed on level ground but also evaluates whether metabolic equivalent (MET) normalization can be used to translate the results of different treadmill tests into each other. METHODS: Fifteen patients with claudication underwent repeated treadmill testing with different treadmill settings, including speeds of 2.0, 3.2, and 4.0 km/h (1.25, 2.0, and 2.5 mph, respectively) and grades of 0% and 12%. The walking capacity was also tested on level ground with a speed chosen by the individual patient. Results of virtual treadmill tests with all possible combinations of the speeds and the grades used were predicted from real tests, with MET normalization. The relationship between real and predicted claudication distances was tested with regression modeling. RESULTS: Reliability coefficients (RCs) for the absolute claudication distance (ACD) were superior to RCs for the initial claudication distance. RCs for ACD ranged between 0.61 and 0.95, with increasing values found with increasing workloads. The best coefficients for the regression of measured on predicted claudication distances were achieved with a model on the basis of a power function (r = 0.963). The model was only appropriate for the prediction of group mean results from clinical trials but cannot be applied to single patient data. For proof of concept, the model was tested with six published studies in which the claudication distances of a patient sample were double treadmill tested with different workloads. The result of the second test was predicted from the first test, and estimated and measured claudication distances were compared. The mean difference (all trials) was 7.9%, whereas the maximum difference amounted to 16.5%. CONCLUSION: For an optimal treadmill test reliability, higher workloads should be used and ACD should be preferred over initial claudication distance. MET normalization provides the basis for the comparability of treadmill test results achieved with different test conditions.     

Management of Vascular Complications following Femoral Artery Catheterization with and without Percutaneous Arterial Closure Devices

Percutaneous arterial closure devices allow earlier mobilization and discharge of patients after arterial catheterization than with manual compression for puncture site hemostasis. We reviewed our recent experience managing the complications of femoral artery catheterization with and without these devices on the vascular surgery service at a tertiary hospital. Thirty-one patients presenting over an 18-month period with complications after femoral artery catheterization with manual compression (n = 21) or percutaneous arterial closure devices (n = 10) were retrospectively reviewed.     

Fractures of the lateral humeral condyle: role of the cartilage hinge in fracture stability.

This study investigates the hypothesis that the integrity of the cartilage hinge at the distal humeral epiphysis determines the stability of fractures of the lateral humeral condyle. Sixteen patients with lateral humeral condyle fractures were studied with radiographs and magnetic resonance imaging (MRI). The clinical course of each patient was compared using these imaging studies to determine whether initial fracture displacement and the integrity of the cartilage hinge correlated with fracture stability. Radiographically, 4 fractures were considered unstable (with initial fracture displacement >3 mm) and 12 were stable (initial displacement < or =3 mm). On MRI, 6 fractures were complete (with disruption of the lateral cartilage hinge) and 10 were incomplete. All unstable fractures had complete fractures on MRI. Ten of the 12 patients with radiographically stable injuries had incomplete fractures on MRI. None of these displaced during treatment. Two patients had radiographically stable fractures and complete fractures on MRI. One of these fractures displaced, confirming the hypothesis that the stability of lateral humeral condyle fractures is related to the integrity of the cartilage hinge.     

Living-related liver transplantation and vena cava reconstruction after total hepatectomy including the vena cava for hepatoblastoma.

BACKGROUND: In most cases of total hepatectomy (TH) required for hepatoblastoma (HB), the retrohepatic inferior vena cava (IVC) has to be removed with the native liver for complete tumor excision. Because the liver graft procured by living donation has no IVC, a reconstruction of the recipient IVC is needed. We report our experience with living-related liver transplantation (LRLT) and IVC replacement in such cases. METHODS: Between May 1998 and December 1999, four children underwent TH, including IVC and LRLT with IVC replacement for otherwise irresectable HB after chemotherapy (SIOPEL 2 and 3 protocols). IVC reconstruction used an allogenic iliac vein procured from a cadaveric donor (bank graft) in two cases and an internal jugular vein procured from the donor parent in two cases. Median age and weight at surgery were 17 months (range 10-60) and 9.6 kg (range 8.3-17.9). RESULTS: In the living donors, there were two complications of the procurement: one intra-abdominal biliary collection and one subcutaneous abscess. In all four children, complete excision of the tumor could be achieved without any intra-operative complication. One patient died 5 months after LRLT due to lung metastases. Three patients were alive and well with no evidence of tumor recurrence 13-24 months after surgery. Reconstructed IVC was patent in two patients, and asymptomatic thrombosis occurred 2 years after operation in one patient. CONCLUSION: Total hepatectomy including the retrohepatic IVC is not a technical obstacle to LRLT. Therefore, scheduled surgery, at the best time after chemotherapy, can be considered in all patients with otherwise irresectable HBs.