Tyrosine kinase expression in pulmonary metastases and paired primary tumors.

Tyrosine kinase inhibitors against the receptors of vascular endothelial growth factor (VEGFR), epidermal growth factor (EGFR) and the platelet derived growth factor (PDGFR) are increasingly used in the treatment of progressive cancers. However, the expression of these receptors especially in lung metastases has not been examined. Tissue specimen from 35 lung metastases of 33 patients with renal cell carcinoma (n=8), sarcoma (n=10), colorectal carcinoma (n=6), otolaryngologic carcinoma (OLC, n=4), testicular and endometrial cancer (n=1 each), malignant melanoma (n=1), adrenal cancer (n=2), malignant fibrous histiocytoma and malignant peripheral nerve sheath tumor (n=1 each) have been immunohistochemically tested for the expression of PDGFR alpha/beta, VEGFR and EGFR. None of the patients had been pretreated with angiogenic inhibitors prior to metastasectomy. PDGFRalpha was expressed in all metastases; 31% stained negative for PDGFRbeta, 86% negative for VEGFR and 45% negative for EGFR. Primary tumors revealed positive staining for PDGFRalpha in 88%, for PDGFRbeta in 59%, for VEGFR in 0% and for EGFR in 18%. Our investigation of a pilot character represents a 'biomarker-based' analysis of pulmonary metastases of different primary tumors; we conclude that an immediate 'tumor profiling' at initial diagnosis should be considered in order to guide tumor therapy individually.

Elective infrarenal abdominal aortic aneurysm repair--transperitoneal, retroperitoneal, endovascular?

We retrospectively analyzed the peri-operative outcome of 210 consecutive patients undergoing elective infrarenal abdominal aortic aneurysm (AAA) repair according to the surgical approach: transperitoneal (TP; 63 patients), retroperitoneal (RP; 81 patients) and endovascular (EV; 66 patients) repair. Concerning gender, AAA diameter and classification of the American Society of Anesthesiologists (ASA score) all groups were comparable; the median age in the EV group was significantly higher (78 years vs. 68 years and 67 years, respectively, P=0.001). Mortality rates were 0% for TP, 1.2% for RP and 3% for EV repair (n.s.). Morbidity rates did not significantly differ between the groups. In specialized centres mortality rates of elective infrarenal aneurysm repair are low - regardless of the surgical approach. In such centres the best treatment options for each patient as to the surgical approach as well as peri-operative management can be provided individually.

A prospective randomized trial comparing traditional and fast-track patient care in elective open infrarenal aneurysm repair.

BACKGROUND: Fast-track recovery programs have led to reduced patient morbidity and mortality after major surgery. In terms of elective open infrarenal aneurysm repair, no evidence is available about such programs. To address this issue, we have conducted a randomized prospective pilot study. METHODS: The study involved prospective randomization of 101 patients with the indication for elective open aneurysm repair in a traditional and a fast-track treatment arm. The basic fast-track elements were no bowel preparation, reduced preoperative fasting, patient-controlled epidural analgesia (PCEA), enhanced postoperative feeding, and postoperative mobilization. Morbidity and mortality, need for postoperative mechanical ventilation, length of stay (LOS) in the intensive care unit (ICU) and total length of postoperative hospital stay were analyzed in terms of an intention to treat. RESULTS: Demographic data for the two groups were similar. In the fast-track group the need for postoperative ventilation was significantly lower (6.1% versus 32%; p = 0.002), the median LOS on ICU did not significantly differ (20 h versus 32 h; p = 0.183), full enteral feeding was achieved significantly earlier (5 versus 7 days; p < 0.0001), and the rate of postoperative medical complications-gastrointestinal, cardiac, pulmonary, renal, and infective-was significantly lower (16% versus 36%; p = 0.039). The postoperative hospital stay was significantly shorter in the fast-track group (10 days versus 11 days; p = 0.016); the mortality rate in both groups was 0%. CONCLUSIONS: An optimized patient care program in open infrarenal aortic aneurysm repair shows favorable results concerning need for postoperative assisted mechanical ventilation, time to full enteral feeding, and incidence of medical complications. Further ranomized multicentric trials are necessary to justify broad implementation (clinical trials. gov identifier NCT 00615888).

The retroperitoneal approach combined with epidural anesthesia reduces morbidity in elective infrarenal aortic aneurysm repair.

In elective open infrarenal aortic aneurysm repair the surgical approach and the use of epidural anesthesia (EDA) may determine patients' outcome. Hence we analyzed our results after elective open aneurysm repair in the light of the surgical approach and the use of EDA. Retrospective analysis of a prospective data base. From December 2005 to April 2008, 125 patients with infrarenal aortic aneurysm underwent elective open repair. Patients were divided into four groups: retro- and transperitoneal approach with and without epidural anesthesia (RP+/-EDA and TP+/-EDA). In terms of age, sex, aneurysm diameter, ASA score and clamping time all groups were comparable. In the retroperitoneal groups significantly more tube grafts were implanted (63 vs. 27; P=0.001). The rate of surgical complications did not differ between the groups. The RP+EDA group had the lowest rate of postoperative assisted mechanical ventilation (5.1% vs. 35.7%; P=0.002) and medical complications (17.9% vs. 42.8%; P=0.032). Concerning frequency of surgical complications, the retroperitoneal incision was comparable to the transperitoneal approach in infrarenal aortic reconstruction. Supplementation with EDA resulted in a decreased rate of postoperative assisted mechanical ventilation and in lower morbidity rates.

Reduction of postoperative pulmonary complications after lung surgery using a fast track clinical pathway.

BACKGROUND: Fast track programs, multimodal therapy strategies, have been introduced in many surgical fields to minimize postoperative morbidity and mortality. In terms of lung resections no randomized controlled trials exist to evaluate such patient care programs. METHODS: In a prospective, randomized controlled pilot study a conservative and fast track treatment regimen in patients undergoing lung resections was compared. Main differences between the two groups consisted in preoperative fasting (6h vs 2h) and analgesia (patient controlled analgesia vs patient controlled epidural analgesia). Study endpoints were pulmonary complications (pneumonia, atelectasis, prolonged air leak), overall morbidity and mortality. Analysis was performed in an intention to treat. RESULTS: Both study groups were similar in terms of age, sex, preoperative forced expiratory volume in one second (FEV(1)), American Society of Anesthesiologists score and operations performed. The rate of postoperative pulmonary complications was 35% in the conservative and 6.6% in the fast track group (p=0.009). A subgroup of patients with reduced preoperative FEV(1) (<75% of predicted value) experienced less pulmonary complications in the fast track group (55% vs 7%, p=0.023). Overall morbidity was not significantly different (46% vs 26%, p=0.172), mortality was comparable in both groups (4% vs 3%). CONCLUSION: We evaluated an optimized patient care program for patients undergoing lung resections in a prospective randomized pilot study. Using this fast track clinical pathway the rate of pulmonary complications could be significantly decreased as compared to a conservative treatment regimen; our results support the implementation of an optimized perioperative treatment in lung surgery in order to reduce pulmonary complications after major lung surgery.

Prospective randomized controlled trial to evaluate "fast-track" elective open infrarenal aneurysm repair.

BACKGROUND AND AIMS: Fast-track programs have been introduced in many surgical fields to minimize postoperative morbidity and mortality. Morbidity after elective open infrarenal aneurysm repair is as high as 30%; mortality ranges up to 10%. In terms of open infrarenal aneurysm repair, no randomized controlled trials exist to introduce and evaluate such patient care programs. MATERIALS AND METHODS: This study involved prospective randomization of 82 patients in a "traditional" and a "fast-track" treatment arm. Main differences consisted in preoperative bowel washout (none vs. 3 l cleaning solution) and analgesia (patient controlled analgesia vs. patient controlled epidural analgesia). Study endpoints were morbidity and mortality, need for postoperative mechanical ventilation, and length of stay (LOS) on intensive care unit (ICU). RESULTS: The need for assisted postoperative ventilation was significantly higher in the traditional group (33.3% vs. 5.4%; p = 0.011). Median LOS on ICU was shorter in the fast-track group, 41 vs. 20 h. The rate of postoperative medical complications was significantly lower in the fast-track group, 16.2% vs. 35.7% (p = 0.045). CONCLUSION: We introduced and evaluated an optimized patient care program for patients undergoing open infrarenal aortic aneurysm repair which showed a significant advantage for "fast-track" patients in terms of postoperative morbidity.

Performance of integrated FDG-PET/CT for differentiating benign and malignant lung lesions--results from a large prospective clinical trial.

PURPOSE: The purpose of the study was to evaluate prospectively whether integrated 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is more accurate for determination of malignancy in newly diagnosed pulmonary lesions compared to separate interpretation of CT and FDG-PET. PROCEDURES: Two hundred and seventy-six patients with newly diagnosed lung lesions underwent FDG-PET/CT. Helical CT, FDG-PET, and FDG-PET/CT were interpreted separately to determine the performance of each imaging modality. Histopathology served as reference in all patients, and in further 60 patients, a benign lesion was verified at follow-up (mean follow-up of 1,040 days). RESULTS: Histology revealed malignant lung tumors in 216 of 276 patients. With PET and PET/CT, a significantly lower number of lesions were classified as equivocal compared to CT alone (p < 0.001). Assuming that equivocal lesions are benign, performance of diagnostic tests was as follows: sensitivity, specificity, and accuracy for CT was 94, 75, and 90%, for PET 97, 83, and 94% (p = 0.021), and for PET/CT 96, 87, and 94% (p = 0.010). Assuming that equivocal lesions are malignant, sensitivity, specificity, and accuracy for CT was 99, 37, and 86%, for PET 99, 77, and 94% (p < 0.001), and for PET/CT 98, 68, and 92% (p = 0.002). PET and PET/CT showed the highest concordance (K = 0.912; confidence interval 0.866-0.958). In lesions less than or equal to 3 cm, there was a significant difference in the performance of PET alone and multidetector row CT as well as PET/CT and multidetector row CT (p = 0.007), irrespective if equivocal findings were judged as malignant or benign. CONCLUSION: For differentiation of benign from malignant lung lesions, integrated FDG-PET/CT imaging was significantly more accurate than CT but not FDG-PET. The addition of metabolic imaging (FDG-PET) to morphological imaging (CT) leads to an increase in specificity and significantly reduced equivocal findings and is therefore recommended to further specify newly diagnosed lung lesions.

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm.

BACKGROUND AND AIMS: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL). METHODS: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter. RESULTS: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter. CONCLUSION: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurysmal disease remains to be elucidated.

Effect of rosiglitazone treatment on plaque inflammation and collagen content in nondiabetic patients: data from a randomized placebo-controlled trial.

BACKGROUND: Therapeutic strategies to stabilize advanced arteriosclerotic lesions may prevent plaque rupture and reduce the incidence of acute coronary syndromes. Thiazolidinediones (TZDs), like rosiglitazone, are oral antidiabetic drugs with additional antiinflammatory and potential antiatherogenic properties. In a randomized, placebo-controlled, single-blind trial, we examined the effect of 4 weeks of rosiglitazone therapy on histomorphological characteristics of plaque stability in artery specimen of nondiabetic patients scheduled for elective carotid endarterectomy. METHODS AND RESULTS: A total of 24 nondiabetic patients with symptomatic carotid artery stenosis were randomly assigned to rosiglitazone (4 mg BID) or placebo in addition to standard therapy. In this population of nondiabetic patients, rosiglitazone treatment did not significantly change fasting blood glucose, fasting insulin, or lipid parameters. In contrast, rosiglitazone significantly reduced CD4-lymphocyte content as well as macrophage HLA-DR expression in the shoulder region, reflecting less inflammatory activation of these cells by lymphocyte interferon-gamma. Moreover, rosiglitazone significantly increased plaque collagen content (7.7+/-1.6% versus 3.7+/-0.7% of plaque area; P=0.036) compared with placebo, suggesting that TZD treatment may stabilize arteriosclerotic lesions. In addition, rosiglitazone reduced serum levels of 2 inflammatory arteriosclerosis markers: C-reactive protein and serum amyloid A. CONCLUSIONS: Four weeks of treatment with rosiglitazone significantly reduces vascular inflammation in nondiabetic patients, leading to a more stable type of arteriosclerotic lesion.

Thoracic surgery in children.

OBJECTIVE: Children rarely undergo thoracic surgery. When they do, the procedures fall into five main groups: oncologic indications, immune defects, malformations, infections and trauma. In addition to considerations associated with the underlying indication, the different proportions of the anatomical structures in children require special modifications in both diagnostics and surgical technique compared to corresponding procedures in adults. METHODS: Of a total 2137 thoracic surgical procedures performed between 1992 and 2001, 49 were performed in children (n = 37; age: 3 months-15 years; median age: 8 years). Indications for surgery included underlying oncologic disease (n = 20), immunodeficiency (n = 5), thoracic or pulmonary malformation (n = 6) and trauma (n = 3). Patients' postoperative clinical course was analyzed retrospectively for all 49 procedures. Pre- and postoperative pulmonary function test results are available for 16 children. Data regarding quality of life were documented in 24 children. RESULTS: The following procedures were performed: 27 atypical resections, seven lobectomies, one pneumonectomy, three decortications, four mediastinotomies or mediastinoscopies and seven other procedures. Six procedures represented second or third procedures in the same patient. Two of six patients with immune defects died during the perioperative period. Eleven of 20 oncologic patients (55%) have remained free of recurrent disease. Quality of life, as assessed by the Karnowski index in 24 children, was at least 80%. CONCLUSIONS: Thoracic surgical procedures in children with underlying benign disease are associated with a good prognosis and high quality of life scores. Surgical treatment of pulmonary metastases is a feasible component of the overall oncologic therapy concept and can offer the only opportunity for curation for a selected group of patients. Because of high postoperative mortality, however, the indication for diagnostic thoracotomies in children with immunodeficiencies and poor general health should be weighed critically.

Complications after endovascular treatment of thoracic aortic aneurysms.

PURPOSE: To retrospectively determine the value of stent-graft repair of descending thoracic aortic aneurysms by analyzing the results and complications. METHODS: From May 1997 to July 2002, 45 patients (33 men; mean age 69 years, range 31-88) received endovascular treatment for thoracic aortic aneurysms. In 11 patients, emergency treatment was necessary for a contained rupture. The medical records of these patients were reviewed to gather data on the procedures, immediate results, complications, mortality, and survival in follow-up. RESULTS: In all cases, the stent-grafts were successfully implanted. In 15 (33%) cases, the subclavian artery was covered by the stent-graft without complications. There was no paraparesis/paraplegia; 2 (4.4%) patients suffered a stroke intraoperatively. The in-hospital mortality was 2.2% (n=1); 3 (6.7%) patients died within 30 days. Primary endoleaks occurred in 8 (17.8%) cases. Procedural success (technical success without endoleak or death) was 80% (93.3% after primary endoleak repair). During follow-up, 2 (4.4%) secondary endoleaks developed. All endoleaks were treated successfully or sealed spontaneously (n=2). At a mean 24-month follow-up (range 1-62), 84% of patients were alive. CONCLUSIONS: The endovascular treatment of thoracic aortic aneurysms appears to be safe and effective, with lower morbidity and mortality than in conventional open operations. For these reasons, endovascular treatment should be administered whenever possible.

Endovascular stent-graft repair of ruptured aortic aneurysms.

PURPOSE: To demonstrate the endovascular approach to the management of ruptured abdominal aortic aneurysms (AAA). METHODS: From 1995 to 2001, 24 patients (21 men; mean age 69 years, range 26-92) underwent emergency endovascular treatment for ruptured AAA. The average interval between onset of symptoms and admission to the hospital was 8.0 hours; the mean time between admission and the operation was 2.3 hours. No suprarenal occluding catheter was used. The stent-graft configurations were 19 bifurcated, 4 tube, and 1 aortomonoiliac. RESULTS: Stent-graft placement was successful in 23 (96%) cases. Failed limb extension deployment prompted conversion to open surgery in the remaining patient. One case was converted to open surgery. Mean duration of treatment was 122 minutes. Three (12.5%) patients died in-hospital. The median hospital stay was 12 days. The rate of endoleaks (all type I) was 16.7%. The overall technical success rate was 77%. The 3-year actuarial survival rate was 75%. CONCLUSIONS: Our experience shows excellent results in emergency patients with ruptured AAAs treated with endovascular surgery. In order to verify these promising results, a broader-scale clinical study must be conducted.

Endovascular repair of traumatic descending aortic transection.

PURPOSE: To present the results of endovascular repair of acute traumatic descending aortic transection. METHODS: Among 66 thoracic stent-graft repairs performed between 1995 and 2001, 11 patients (9 men; mean age 34 years, range 12-73) underwent emergent endovascular repair of acute traumatic descending aortic transection following traffic accidents. Immediate treatment of aortic rupture was indicated in all patients because of a marked fresh hematoma with hemothorax; the spiral computed tomographic (CT) scans showed circular or semicircular descending thoracic aortic injuries. The devices used included 11 thoracic Excluders and 1 Talent stent-graft. RESULTS: No patient required conversion to an open transthoracic operation. No patient developed temporary or permanent neurological deficit after endovascular treatment. Two type I endoleaks required periprocedural treatment: a second stent-graft was deployed in one and the existing stent-graft was balloon dilated in the other. Two patients underwent secondary procedures (iliac access complication and revascularization of the left subclavian artery). One patient died 22 days postoperatively secondary to injuries unrelated to the aortic repair. Over a mean 14-month follow-up (range 1-26), the surveillance CT scans have shown the stent-graft to be correctly positioned in all patients. CONCLUSIONS: The treatment of acute traumatic descending aortic transection with an endovascular approach is feasible and safe and may offer the best means of therapy. Mortality and the risk of neurological deficit are low compared with open operations.

Initial experience with intentional stent-graft coverage of the subclavian artery during endovascular thoracic aortic repairs.

PURPOSE: To investigate the extent to which clinical status is affected by covering the left subclavian artery (LSA) with stent-grafts in the thoracic aorta. METHODS: Stent-graft reconstruction of the thoracic aorta was performed in 23 patients (20 men; mean age 50.8 years, range 17-77) for management of rupture (n = 11), type B dissection (n = 9), or aneurysm (n = 3). All patients had bilaterally equal systolic and diastolic blood pressures (141.3+/-19.8 and 78.9+/-11.0 mmHg, respectively). Twenty Gore TAG and 1 Talent thoracic endografts were used; 2 cases required a combination of prostheses. In all patients, the stent-graft was intentionally placed to cover the LSA. Follow-up included clinical examination with blood pressure measurements and computed tomography during the first postoperative week and at 3-month intervals thereafter. RESULTS: After coverage of the LSA by the stent-graft, systolic pressure fell by a mean 48.3+/-23.4 mmHg. In 4 cases of proximal endoleak, however, systolic pressure fell by only 25.0+/-15.0 mmHg. Twenty (78.5%) patients reported no complaints during a mean follow-up of 12.1+/-7.3 months. Postinterventional complaints reported by 3 patients included exercise-dependent paresthesias; nonexercise-dependent, intermittent, and completely reversible dizziness; and a temperature difference between the upper extremities with no decrease in strength. CONCLUSIONS: Covering the LSA is generally well tolerated by patients and increases the landing zone for the placement of thoracic stent-grafts. Long-term studies, however, must investigate the hemodynamic effects of this procedure on the vertebrobasilar circulation.

Thromboembolic complications after endovascular aortic aneurysm repair.

PURPOSE: To evaluate the frequency and significance of thromboembolic complications following endovascular treatment of aortic aneurysms. METHODS: One hundred seventy-four patients (153 men; mean 71.4 years, range 26-90) underwent endovascular repair of aneurysms of the thoracic (n = 38) or abdominal (n = 136) aorta using a variety of endografts. All patients were examined preprocedurally using 3-phase helical computed tomography (CT) to determine appropriate endograft size. To exclude the occurrence of infarction in parenchymal organs, the first postprocedural CT scan was compared with preoperative findings. Newly recognized perfusion deficits were taken as evidence of procedure-related infarction. RESULTS: Infarctions were detected in 16 (9.2%) patients: 13 in the kidneys, 2 in the spleen, with 1 in the mesentery; only the mesenteric infarction was clinically symptomatic. Both splenic infarctions were associated with deployment of stent-grafts in the thoracic aorta (5.3% of the 38 patients), while the mesenteric and 13 renal infarctions were seen in patients with infrarenal abdominal aortic aneurysms (0.7% and 9.6%, respectively, of 136 patients). One patient experienced complete thromboembolic occlusion of a renal artery, which was partially recanalized with intraoperative lysis. CONCLUSIONS: Thromboembolic complications of endovascular aortic aneurysm repairs are not uncommon, and although usually asymptomatic, these sequelae have the potential to be life threatening. Perfusion abnormalities may respond to immediate lytic therapy with complete dissolution of the thrombus in certain isolated cases.

Renal infarction following endovascular aortic aneurysm repair: incidence and clinical consequences.

PURPOSE: To investigate the incidence of renal infarction following endovascular abdominal aortic aneurysm (AAA) repair, with particular emphasis on a comparison of suprarenal versus infrarenal endograft placement. METHODS: Ninety-nine patients (92 men; average age 68 years) who had undergone endovascular AAA repair between July 1995 and July 1999 and who had at least 12 months' follow-up were studied with spiral computed tomographic scans to identify suprarenal endograft deployment and renal infarction. RESULTS: Among the 193 renal arteries available for study, partial or complete transrenal endograft placement was found in 69 (36%). Sixteen (8.3%) renal infarctions were identified by the postoperative imaging studies. Perfusion of these kidneys was supplied by 6 (8.7%) of the 69 overstented renal arteries and 7 (5.6%) of the 124 uncovered arteries (p > 0.05). In the 3 other cases, intentional accessory renal artery occlusion by the stent-graft fabric led to frank segmental renal infarctions, which were visualized as territorial-perfusion defects affecting up to 27% of the renal volume. In the other 13 infarcted kidneys, the punctate deficits involved <10% of the parenchymal volume. Renal retention values were unaffected in 15 (94%) of 16 patients. CONCLUSIONS: Documented renal infarctions following endovascular aortic stent-graft placement are not common and do not appear to be associated with suprarenal endograft fixation.

Complications after endovascular repair of type B aortic dissection.

PURPOSE: To outline the complications encountered after endoluminal treatment in patients with type B aortic dissection. METHODS: Between 1999 and 2001, 14 patients (12 men; mean age 60.3 years, range 39-79) with isolated type B aortic dissection (13 chronic, 1 acute) underwent aortic stent-grafting. Three patients with chronic dissection presented an acute clinical picture and were managed emergently. The left subclavian artery was intentionally covered by the prosthesis in 9 patients. Follow-up studies were performed at 6-month intervals. RESULTS: Stent-graft implantation was technically successful in all patients, but incomplete sealing (endoleak) of the entry site required additional proximal stent-graft implantation in 4. The left subclavian artery remained patent in 5 patients. Secondary conversion was required in 3 patients: 2 for acute type A dissection resulting from injury to the aortic arch by Talent endografts and a sustained hemorrhage (left hemothorax). In another patient, a secondary intramural hematoma subsided spontaneously. Anterior spinal artery syndrome in 1 patient persisted at 1 month. No bypass was necessary for the 9 patients with the covered left subclavian arteries. Mean follow-up was 14 months (range 1-23). CONCLUSIONS: Stent-grafting is feasible in patients with type B aortic dissection, although it is associated with a considerable rate of complications. Frank reporting of these sequelae for a variety of stent-grafts is of paramount importance to clarifying the limitations of the method.