Oncological short-term effects and adverse events of MRI-guided selective neoadjuvant radiochemotherapy for rectal cancer.

AIM: To investigate the oncological short-term effects and acute side-effects of magnetic resonance imaging (MRI)-guided selective neoadjuvant radiochemotherapy (nRCT) for rectal cancer. PATIENTS AND METHODS: In a prospective multicenter cohort study of 230 patients with rectal cancer stage II or III, nRCT was applied in the following situations (n=96) only: cT4 tumors, cT3 tumors of the distal rectum or tumors leaving a circumferential resection margin (CRM) of ≤1 mm between the tumor and the mesorectal fascia (mrCRM+). Pre-therapeutical tumor stage and involvement of mesorectal fascia were assessed by MRI and were compared with the pathological findings of the rectal specimens. Furthermore, tumor regression grades, acute side-effects, and surgical complications were analysed. RESULTS: Using selective nRCT, 62 out of 72 patients (86%) with mrCRM+ had tumor-negative pathological CRM. Reduction of T category was observed in 62% and of N category in 88% of patients. Lymph node metastasis was found by pathology in only 21% of all irradiated patients. Histologically complete tumor regression (ypT0ypN0) was observed in 15% and intermediate regression (more than 25%, but not complete) in 67% of patients. Fifteen percent of patients suffered from grade 3 toxicity, but no grade 4 toxicity occurred. nRCT did not adversely influence surgical morbidity. CONCLUSION: Despite the negative selection of locally advanced rectal cancer cases for nRCT, impressive rates of tumor down-staging and eradication of tumor from the mesorectal fascia were achieved. The rate of complete regression is comparable to that in the literature. Moreover, the selective use of nRCT spared a considerable percentage of patients with stage II/III rectal cancer severe irradiation toxicity.

Pulmonary vein thrombosis after lower lobectomy of the left lung.

Pulmonary vein thrombosis is a known complication after lung transplantation but has rarely been reported after lobectomy or bilobectomy. We report the case of a left upper pulmonary vein thrombosis following an uneventful left lower lobectomy for bronchial carcinoma. Postoperative arterial blood gas values and chest radiographs were normal. On postoperative day 5, the patient became progressively dyspneic, developed hemoptysis and showed total opacification of the left lung without mediastinal shift on chest radiography. The patient remained dyspneic despite intravenous antibiotic therapy for suspected pneumonia and absence of obstruction at bronchoscopy. Diagnosis of left upper pulmonary vein thrombosis was finally made by contrast-enhanced multislice computed tomography followed by pulmonary angiography. Further clinical deterioration under conservative treatment forced us to remove the remnant left upper lobe that already showed gangrenous alterations. Pulmonary vein thrombosis following lobectomy or bilobectomy is very rare. Only 7 cases have been reported in the literature so far. Conservative treatment with antibiotics and anticoagulants may be successful but in case of clinical deterioration the affected lobe has to be resected. The mechanism of thrombosis remains unclear although intraoperative torsion and injury of vessels seem to be most likely since pulmonary vein thrombosis occurred in the operated hemithorax only.

PPS-PEG surface coating to reduce thrombogenicity of small diameter ePTFE vascular grafts.

AIMS: Patency failure of small vascular synthetic grafts is still a major problem for coronary and peripheral revascularization. Thus, three new surface coatings of small synthetic grafts were tested in an acute pig model to evaluate their thrombogenicity (extracorporeal arterio-venous shunt) and in a chronic rat model to evaluate the tissue reaction they induced (subcutaneous implantation). METHODS: In five domestic pigs (25-30 kg) an extracorporeal femoro-femoral arterio-venous shunt model was used. The study protocol included first a non-heparinized perfusion sequence followed by graft perfusion after 10,000 UI iv heparin. Grafts were perfused for 3 and 9 minutes. The following coatings were tested on ePTFE grafts: poly-propylene sulphide (PPS)--poly-ethylene glycol (PEG) (wet and dry applications) as well as carbon. Two sets of control were used, one dry and one wet (vehicle only). After perfusion grafts were examined by scanning electron microscopy for semi-quantitative assessment (score 0-3) of cellular and microthrombi deposition. To assess tissue compatibility, pieces of each material were implanted subcutaneously in 16 Wistar rats. At 2, 4, 8, 12 weeks four animals each were sacrificed for semi-quantitative (score 0-3) histologic evaluation of tissue reaction. RESULTS: In the pig model, cellular deposition and microthrombi formation increased over time. In non- heparinized animals, the coatings did not improve the surface characteristics, since they did not prevent microthrombi formation and cellular deposition. In heparinized animals, thrombogenicity was lowest in coated grafts,especially in PPS -PEG dry (p<0.05), and highest in controls. Cell deposition was lowest in PPS-PEG dry, but this difference was not statistically significant vs.controls. In the rat model,no significant differences of the tissue reaction could be shown between materials. CONCLUSION: While all coatings failed to add any benefit for lowering tissue reaction, surface coating with PPS -PEG (dry application) reduced thrombogenicity significantly (in heparinized animals) and thus appears to be promising for improving graft patency of small synthetic vascular prostheses.

Clinical experience with autologous endothelial cell-seeded polytetrafluoroethylene coronary artery bypass grafts.

OBJECTIVE: Autologous endothelial cell seeding was used to improve the patency of 4-mm polytetrafluoroethylene vascular prostheses. METHODS: Since 1995, 14 patients with coronary artery disease received 21 autologous endothelial cell-seeded polytetrafluoroethylene vascular bypass grafts for coronary artery revascularization. The polytetrafluoroethylene grafts were seeded with the endothelial cells in a multiple step procedure, including cell culture techniques before coronary bypass operation. With the use of extracorporal circulation and cardioplegic arrest, a bypass operation was performed by means of conventional surgical techniques. RESULTS: After a mean postoperative follow-up of 27.7 months (range, 7.5-48 months), the graft patency rate is 90.5%. Follow-up angiograms of the aorta-coronary polytetrafluoroethylene bypass grafts showed patent bypasses in all cases except two. Angiograms of all 19 patent endothelial cell-seeded polytetrafluoroethylene bypass grafts showed a smooth luminal borderline without stenotic regions. The percutaneous transluminal angioscopic evaluation showed a glossy white and smooth endoluminal graft surface without any fibrin, platelet, or erythrocyte deposits. Intravascular ultrasonographic examinations confirmed the results. CONCLUSION: Patency of autologous endothelial cell-seeded 4-mm polytetrafluoroethylene vascular prostheses as coronary artery bypass grafts was much better than that of unseeded polytetrafluoroethylene grafts. Further evaluations and a larger population of patients will prove whether the encouraging patency will last.

Iron- and ascorbic acid-induced lipid peroxidation in renal microsomes isolated from rats treated with platinum compounds.

Renal microsomes isolated on day 3 from cisplatin (CDDP, single i.p. injection, 4 or 6 mg/kg)-treated rats were monitored for their susceptibility to lipid peroxidation as compared with microsomes from rats treated with carboplatin (CBDCA, 30 mg/kg), transplatin (TDDP, 6 mg/kg) or CDDP hydrolysis products (4 or 6 mg/kg) or from control animals. Cephaloridine (1 g/kg daily for 4 days, i.p. injection) was used as a positive control. The effect of CDDP on renal microsomal glucose-6-phosphatase activity was investigated in vivo and in vitro. Following treatment with CDDP and CDDP hydrolysis products vs CBDCA and TDDP treatment, microsomes revealed an enhanced susceptibility to lipid peroxidation in a Fe2+ and/or ascorbic acid stimulation system. Increased lipid peroxidation, expressed as an increase in malondialdehyde (MDA) generation, paralleled the alterations in body and kidney weight and the elevations of plasma creatinine and blood urea nitrogen concentrations. Injection of the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD, 0.5 g/kg, i.p.) at 24 h prior to CDDP treatment abolished the increased vulnerability of renal microsomes to lipid peroxidation. In vivo, only CDDP hydrolysis products exhibited a significant inhibitory effect on renal glucose-6-phosphatase activity. In vitro, rat renal and hepatic microsomal glucose-6-phosphatase activity was decreased by CDDP both time- and concentration-dependently. Nephrotoxicity induced by CDDP and CDDP hydrolysis products might be attributable to iron-dependent lipid peroxidation and microsomes might represent target organelles on a subcellular level.