Prevention of postoperative paraplegia during thoracoabdominal aortic surgery

BACKGROUND: We present data showing the impact of sequential multisegmental aortic clamping accompanied by reimplantation of as many segmental arteries as possible on the prevention of postoperative paraplegia or paraparesis during thoracoabdominal aortic graft replacement. METHODS: Since 1987 we have performed graft replacements in 51 individuals undergoing thoracoabdominal aortic surgery using the technique of normothermic partial bypass with sequential multisegmental aortic clamping. The procedure was performed emergently in 10 patients and electively in 41 patients. The patients ranged in age from 22 to 82 years (mean, 57.6 +/- 13.8 years). Indications for surgery included dissecting thoracoabdominal aortic aneurysm (n = 19) and nondissecting thoracoabdominal aortic aneurysm (n = 32). The extent of aneurysm was Crawford type I in 19 patients, type II in 7 patients, type III in 12 patients, and type IV in 13 patients. Along the entire extent of aneurysm to be replaced, we reimplanted as many of the patent segmental arteries as feasible. RESULTS: Five patients died during hospitalization, for an in-hospital mortality rate of 9.8%. The number of aortic clampings per patient ranged from one to five (median, three). A total of 124 segmental arteries were reimplanted in 44 (86.3%) of 51 patients. Of the 124 arteries, 90 (72.6%) were distributed between T9 and L2. Postoperative paraplegia or paraparesis did not develop in any of the patients. CONCLUSIONS: Our results demonstrate that extensive reimplantation of segmental arteries using sequential multisegmental aortic clamping, accompanied by adequate intraoperative distal aortic perfusion, is effective in preventing spinal cord ischemia.     

Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells

PURPOSE: The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGEs), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death. METHODS: First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGEs were added to the culture media of the cultured CECs, and the uptake of AGEs, the generation of reactive oxygen species, and the induction of apoptosis were investigated. RESULTS: Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGEs, the generation of reactive oxygen and the number of apoptotic cells also increased. CONCLUSIONS: These results show that the accumulation of AGEs in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGEs in the CECs of elderly patients may be involved in the loss of CECs during the aging process.     

Thalidomide is anti-angiogenic in a xenograft model of neuroblastoma

Thalidomide has previously been shown to have anti-angiogenic properties. More recently, clinical efficacy of this agent has been demonstrated in multiple myeloma and prostate cancer. Neuroblastoma is the most frequent solid tumor of the abdomen of childhood, yet children with this disease frequently have metastases at presentation. Such patients have a very poor prognosis with current therapies. Thus, new approaches are needed. We have previously shown that VEGF antagonists can inhibit neoangiogenesis and tumor growth in experimental neuroblastoma. In this study, we investigated the anti-angiogenic and anti-tumor properties of thalidomide in a xenograft model of human neuroblastoma. Tumors were induced in athymic mice using the human neuroblastoma cell line NGP. Intraperitoneal thalidomide (100 mg/kg/dose) or vehicle was administered beginning one week after implantation, and animals euthanized at six weeks. Thalidomide treatment did not significantly alter tumor growth as compared with controls. However, thalidomide suppressed angiogenesis, as demonstrated both by fluorescein angiography and immunohistochemical staining, and induced apoptosis of endothelial cells in neuroblastoma xenografts. Quantification of microvessel density demonstrated a significant reduction of vasculature in treated tumors (p<0.004). Thalidomide induced co-option of host vasculature, an effect noted previously after VEGF blockade. This study demonstrates that thalidomide has anti-angiogenic properties in experimental neuroblastoma.     

Metastatic breast cancer of HER2 scored 2+ by IHC and HER2 gene amplification assayed by FISH has a good response to single agent therapy with trastuzumab: A case report

We report that single agent therapy with trastuzumab had a significant effect on metastatic breast cancer, which was confirmed to be HER2 positive by Herceptest showing 2+staining, and gene amplification positively detected by FISH analysis. A 48-year-old woman underwent extended radical mastectomy (T2N0M0 stage II). Three years after the operation supraclavicular lymph node metastasis was noted. Bone scintigraphy showed metastases to the left ribs 5 years after operation. She was treated with chemo-endocrine therapy, but nonetheless could not bear the back pain caused by the bone metastases. Another chemotherapy course could not be permitted because of leukopenia. Immunohistochemistry (IHC) analysis with Herceptest showed 2+staining for HER2 and FISH analysis showed gene amplification of HER2. We started single agent therapy with trastuzumab and she subsequently had remarkably improved back pain. Physical examination and ultrasonography showed disappearance of the previous palpable supraclaviclar lymph nodes. Serum tumor markers were also reduced after the first administration of trastuzumab. The patient is currently alive, with no further progression of the lymph node or bone metastases.     

Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers

Chemoresistance is a major problem in the chemotherapy of non-small cell lung cancers (NSCLCs). Several mechanisms are thought to be involved in drug resistance, including those associated with apoptosis, drug transport and detoxification. Here, we investigated the predictive value of P53, Bcl-2 and lung resistance-related protein (LRP) expression for response to platinum-based chemotherapy, using transbronchial biopsy (TBB) specimens from patients with NSCLC. We evaluated TBB specimens from 57 patients with NSCLC who had not previously been treated with either chemotherapy or radiotherapy before TBB, and who were treated with systemic platinum-based chemotherapy. The specimens included 33 adenocarcinomas, 22 squamous cell carcinomas and two large cell carcinomas. One to 6 courses of chemotherapy were administered. Expression of P53, Bcl-2 and LRP was analyzed by immunohistochemistry using TBB specimens. Positive expression of P53, Bcl-2 and LRP was observed in 28 (49%), 41 (71%) and 42 (73%) of the 57 NSCLCs, respectively. P53 expression correlated significantly with response to chemotherapy in nonsquamous cell carcinomas, including adenocarcinomas and large cell carcinomas (response rates, 38% and 6% for patients with P53-positive and P53-negative tumors, respectively, P =0.03). LRP expression significantly correlated inversely with response to chemotherapy in squamous cell carcinomas (response rates, 33% and 100% for patients with LRP-positive and LRP-negative tumors, respectively, P=0.02). Bcl-2 expression did not correlate with response to chemotherapy. These findings indicate that im-munostaining for P53 and LRP using TBB specimens may be useful for dividing patients with NSCLC into chemoresponsive and chemoresistant groups. (Cancer Sci 2003; 94: 394–399)     

Antenatal three-dimensional sonographic features of Pierre-Robin syndrome. Case report

A case of Pierre-Robin syndrome with polyhydramnios is described. Three-dimensional sonography clearly showed fetal micrognathia and hypoplastic ear antenatally. The benefits and advantages of the use of three-dimensional sonography to diagnose Pierre-Robin syndrome in utero are discussed.     

Ventricular tachycardia with congenital left ventricular aneurysm in an adult

A 60-year-old woman without any risk factors for coronary artery disease presented with symptomatic, recurrent, non-sustained ventricular tachycardia. She was found to have a postero-lateral left ventricular aneurysm. Coronary angiography revealed normal coronary arteries. The 12-lead electrocardiogram showed sinus rhythm with frequent premature ventricular contraction. Her non-sustained ventricular tachycardia was reproduced by programmed electrical stimulation and was unresponsive to procainamide, mexiletine, and disopyramide. Aneurysmal resection and cryoablative surgery was performed. After surgery, ventricular programmed stimulation was negative, and premature ventricular contraction was disappeared. The patient discharged on no antiarrhythmic therapy.     

VEGF blocking therapy in the treatment of cancer

It is widely accepted that tumour growth beyond a few cubic millimetres cannot occur without the induction of a new vascular supply. Inhibiting the development of new blood vessels (antiangiogenesis) is a potential approach to cancer therapy that has attracted interest in recent years. In theory, this approach should be relatively selective for tumour cells. The endothelial cells which form new vascular networks in tumours are responding to angiogenic stimuli produced by the tumour, but are themselves genetically normal. Endothelium in normal tissue, by contrast, is usually quiescent. Vascular endothelial growth factor (VEGF) is the best-characterised pro-angiogenic factor. It is virtually ubiquitous in human tumours, and higher levels have been correlated with more aggressive disease. Effective blockade of the VEGF pathway has been demonstrated with multiple agents: neutralising antibody, receptor tyrosine kinase inhibitors, and ribozyme or antisense molecules targeting expression. Promising preclinical data document the potential of these agents for tumour growth inhibition and even tumour regression, yet translation of novel therapeutics targeting the VEGF pathway to the clinic has proved a substantial challenge in itself. While showing clear evidence of antitumour activity over a broad spectrum of experimental tumours, the proper selection, dose, timing and sequence of anti-VEGF treatment in human cancer is not at all obvious. Classic Phase I dose escalation trial design may need to be modified, as higher doses may not be optimal in all patients or for all tumours. In addition, alternate or secondary biological end points (e.g., non-progression) may be needed for early phase studies to document true activity, so as not to abandon effective agents. Recent studies of the neutralising antibody bevacizumab, and small molecule tyrosine kinase inhibitor SU5416, demonstrate that, while unlikely to be effective as monotherapy, incorporation of VEGF blockade into cytotoxic regimens may increase overall response rates. However, incorporation may also produce new toxicities, including thromboembolic complications and bleeding. Newer oral agents, such as SU6668, SU11248, PTK787/ZK222584 and ZD6474, are particularly interesting for their potential for chronic therapy. Future clinical trials are likely to build on past experience with stricter entry criteria, supportive care guidelines and the use of surrogate markers.