Analysis of nidus obliteration rates after gamma knife surgery for arteriovenous malformations based on long-term follow-up data: the University of Tokyo experience

OBJECT: A large number of clinical studies have been made on treatment outcomes of radiosurgery for arteriovenous malformations (AVMs), but the reported obliteration rates following this treatment vary significantly, perhaps reflecting the different methods and timings of the imaging studies used. METHODS: The authors retrospectively analyzed their experience with gamma knife surgery in 400 patients with AVMs (follow-up period 1-135 months, median 65 months), with special reference to the imaging modality used in each case. The calculated obliteration rates varied from 68.2 to 92%, depending on imaging modality and timing of evaluation. When only unquestionable imaging data such as demonstrations of a residual nidus on computerized tomography (CT) or magnetic resonance (MR) images or findings on angiograms were used in the calculation, the obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as determined in a multivariate analysis. Factors leading to an earlier obliteration of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039), smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p = 0.0201). CONCLUSIONS: After the introduction of CT and MR images into dose planning, the conformity and selectivity of dosimetry improved remarkably, although the latency intervals until obliteration were prolonged. Imaging outcomes for AVMs should be evaluated using data provided by longer follow-up periods. The timing of additional treatments for residual AVMs should be decided cautiously, considering the size of the AVM, the patient age and sex, and the history of hemorrhage before radiosurgery.     

Multiple myxoma in the left ventricle and the left atrium

Left ventricular myxoma is particulary rare. Our case is a 77-year-old female. Transesophageal echocardiography showed a giant tumor in the left atrium. An urgent operation was performed. A giant mass was excised en bloc via a transinteratrial septal approach. Histopathologically it was myxoma. As a transthoracic echocardiography at 1-year postoperation showed a tumor in the left ventricle. A mass was excised en bloc via a vertical approach. Histopathologically it was diagnosed again as myxoma. We looked at the earliest transesophageal echocardiogram again, and found the small tumor on the same area under the posterior mitral leaflet. At the diagnose of cardiac tumor, possibility of multiple formation should be always considered.     

Osteogenic differentiation of human bone marrow-derived mesenchymal cells cultured on alumina ceramics

Alumina ceramics have excellent mechanical and biocompatible properties, but are bioinert and hence have no bone-bonding properties. We took a tissue-engineering approach in an attempt to modify the ceramic surface and so provide an osteogenic/osteoconductive milieu. We obtained human bone marrow mesenchymal cells from four donors and then cultured the cells for two weeks on alumina ceramic in the presence of beta-glycerophosphate, ascorbic acid and dexamethasone. The cells showed extensive alkaline phosphatase staining and mineralization, as evidenced by Alizarin Red S staining and calcein uptake. Biochemical analyses revealed high levels of alkaline phosphatase activity, osteocalcin expression and calcium content. This data indicates the appearance of active osteoblasts that are concomitant with bone matrix formation, i.e., in vitro cultured bone. The cultured bone/alumina composites should prevent the aseptic loosening of all-alumina ceramic joints or the detachment of implanted alumina ceramics, and thus could have clinical significance in orthopedic reconstructive surgery.     

Restricted cytokine production from mouse peritoneal macrophages in culture in spite of extensive uptake of plasmid DNA

The production of inflammatory cytokines from macrophages (Mphi), upon stimulation with plasmid DNA (pDNA) containing CpG motifs, is a critical process for DNA-based therapies such as DNA vaccination and gene therapy. We compared Mphi activation, following stimulation with naked pDNA, based on the production of cytokines from cell lines (RAW264.7 and J774A1) and peritoneal Mphis in primary culture. The Mphi cell lines RAW264.7 and J774A1 produced a significant amount of tumour necrosis factor-alpha (TNF-alpha) upon stimulation with naked pDNA and this response required endosomal acidification. On the other hand, peritoneal Mphis (both resident and elicited) in primary culture did not secrete TNF-alpha or interleukin-6, although they contain the mRNA of toll-like receptor-9 (TLR-9) and are able to respond to CpG oligodeoxynucleotides. This unresponsiveness was not a result of impaired cellular uptake of pDNA because the primary cultured Mphis showed a higher uptake of pDNA than the RAW264.7 and J774A1 cell lines. These findings have important implications for Mphi activation by naked pDNA as it has been generally assumed that pDNA that contains CpG motifs is a potent agent for inducing inflammatory cytokines in vivo, based on evidence from in vitro studies using Mphi cell lines.     

Tissue engineered ceramic artificial joint--ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis

Total joint arthroplasty is the common treatment of severe cases of osteoarthritis. However, complications involving failure of the bone-prosthesis interface are significant, especially in ankle arthroplasty. To prevent this complication, we attempted a tissue engineering approach using the mesenchymal cells of the patient. We collected a small amount of fresh bone marrow cells from the patient's iliac crest and expanded the number of mesenchymal cells. We then applied the mesenchymal cells to a ceramic ankle prosthesis and cultured them to form an osteoblasts/bone matrix on the prosthesis. We used tissue engineered prostheses on three patients suffering from ankle arthritis and followed their progress for at least 2 years. Follow-up X-ray examinations revealed early radiodense appearance (bone formation) around the cell-seeded areas of the prostheses about 2 months after the operation after which a stable host bone-prosthesis interface was established. All patients showed high clinical scores after the operation and did not exhibit inflammatory reactions. These preliminary results indicate that the tissue engineering approach using autologous cultured marrow mesenchymal cells might prevent aseptic loosening of the total ankle arthroplasty.     

Hemodynamic evaluation of 19-mm Carpentier-Edwards pericardial bioprosthesis in aortic position

BACKGROUND: The aortic Carpentier-Edwards pericardial bioprosthesis offers good long-term clinical outcomes with a low rate of structural deterioration. However, little in vivo hemodynamic data is available for this bioprosthesis. METHODS: To determine the hemodynamic performance of the 19-mm Carpentier-Edwards pericardial valve, both cardiac catheterization and dobutamine stress echocardiography were electively performed in 10 patients. The mean age at the study was 71.6 +/- 4.4 years and the mean body surface area was 1.39 +/- 0.11 m2. The peak-to-peak gradient, instantaneous peak gradient, mean gradient, and valve orifice area were measured by standard cardiac catheterization. The Doppler-derived gradients and valve orifice area were also measured both at rest and during dobutamine infusion. RESULTS: The average peak-to-peak gradient, instantaneous peak gradient, mean gradient, and valve orifice area measured by catheterization were 13.0 +/- 5.4 mmHg, 28.5 +/- 7.7 mmHg, 12.0 +/- 4.9 mmHg, and 1.55 +/- 0.45 cm2, respectively. The peak and mean Doppler gradients, and valve orifice area by resting echocardiography were 27.7 +/- 9.5 mmHg, 12.3 +/- 4.8 mmHg, and 1.39 +/- 0.26 cm2, respectively. At a dosage of 10 microg/kg/min of dobutamine, the mean Doppler gradient rose mildly to 22.2 +/- 4.8 mmHg, while the cardiac output increased from 4.49 +/- 0.44 to 6.64 +/- 0.87 L/min. The valve orifice area during the 10 microg/kg/min dobutamine infusion (1.55 +/- 0.25 cm2) was significantly larger than its value at rest (p < 0.05). CONCLUSIONS: With acceptable hemodynamic performance, use of the aortic 19-mm Carpentier-Edwards pericardial valve is a reliable option for elderly patients with a small annulus.     

A case of cardiac cancer for which radiation therapy was effective in improving stenosis of the esophagogastric junction

The patient was a seventy-seven-year old woman, who was diagnosed with advanced gastric cancer with stenosis of the esophagocardiac junction. Her cancer was diagnosed as Stage IV (T3N3H0P3M0). As there was no indication for surgery, radiation therapy (Linac electron beam, 1.8 Gy/day, total 50.4 Gy) was selected to improve the stenosis, after which she was able to eat food. Subjective complaints such as nausea and vomiting were also decreased, promoting her QOL. We conclude that radiation therapy treatment can be a treatment option for far advanced cardiac cancer.     

Extracorporeal ventriculoatrial shunt with the use of one-way ball valve

We developed a simple system of an "extracorporeal" ventriculoatrial (VA) shunt using a one-way ball valve (Acty valve II, Kaneka Medix) to release the patient from postoperative constraint during the ventricular drainage. The system is constructed in such a way that the ventricular drainage tube is connected to the central venous catheter via a one-way valve. The CSF is regulated by using the valve and is diverted into the systemic circulation as in the conventional ventriculoatrial shunt. After 2 or 3 weeks of CSF diversion through the extracorporeal VA shunt, a ventriculoperitoneal shunt is placed if hydrocephalus is apparent by temporary occlusion of the system. We applied this system to 4 patients with hydrocephalus, and we found it useful and free from adverse effects. The patient was freed from physical constraint involved in conventional ventricular drainage and an effective program of early rehabilitation was able to be started.