Prognostic nomogram for predicting the 5-year probability of developing metastasis after neo-adjuvant chemotherapy and definitive surgery for AJCC stage II extremity osteosarcoma.

BACKGROUND: In this retrospective study, we developed and internally validate a nomogram for predicting 5-year metastasis probability for nonmetastatic extremity osteosarcoma. PATIENTS AND METHODS: We reviewed 365 osteosarcoma patients treated at our institute from 1990 to 2003. Clinicopathologic variables were recorded. Multivariate analysis using Cox proportional hazards regression was done and this Cox model was used as the basis for the nomogram. RESULTS: By American Joint Committee on Cancer (AJCC) staging system, 141 patients (38.6%) were stage IIA and 224 (61.4%) were stage IIB. Multivariate Cox model identified patient age at diagnosis, tumor size, humeral location, and tumor necrosis rate after chemotherapy as correlated with metastasis-free survival. The degree of contribution of each covariate to the total point was tumor location, tumor necrosis rate, maximal tumor diameter, and age in decreasing order. The concordance index for the model was 0.78. Nomogram discrimination was superior to that of AJCC stage (concordance index 0.78 versus 0.68; P = 0.02) and histologic response grouping (concordance index 0.78 versus 0.69; P = 0.0004). CONCLUSIONS: We devised a nomogram for nonmetastatic osteosarcoma that proposes improved estimates of metastasis over AJCC staging system or tumor necrosis rate. We suggest that this nomogram allows individualized risk assessments and could be used as the basis for risk-adapted therapy.

An ion optics study for KSTAR neutral beam injector development.

Ion optics of three accelerator geometries was studied in terms of an analytic linear optics analysis, a numerical simulation using the IGUN program, an optical multichannel measurement of Doppler-shifted H(alpha) lines, and a water-flow calorimetry on the beam absorbing target. In general, there was a reasonable agreement observed between the four analysis methods and thus the theoretical analyses can be utilized with confidence for design iteration.

Osteosarcoma in pre-adolescent patients.

The medical records of 38 pre-adolescent (aged < or = 10 years) and 43 adolescent (aged 11 - 15 years) patients with primary osteosarcoma treated using the same protocol were reviewed in order to determine whether the clinical features and prognosis differed between these two groups. Gender, tumour location, tumour size, serum levels of alkaline phosphatase and lactic dehydrogenase before treatment, and chemotherapy-induced tumour necrosis were recorded, together with survival data. These parameters were compared in the two groups, and their prognostic significance was evaluated in the pre-adolescent patients. There were no statistically significant differences in the clinical parameters between pre-adolescent and adolescent patients. Only a poor level of chemotherapy-induced tumour necrosis was significantly associated with a poor prognosis in pre-adolescent patients. This study indicates that osteosarcoma behaviour is similar in pre-adolescent and adolescent patients, and there appears to be little justification for adopting different therapies in these two groups.

Isovolemic hemodilution normalizes the prolonged passage of red cells and plasma through cerebral microvessels in the partially ischemic forebrain of rats.

The objective of this study was to determine whether hemodilution could normalize the mean transit times of red blood cells (Tr) and plasma (Tp) through cerebral microvessels in a partially ischemic brain. Wistar-Kyoto (WKY) rats, aged 30-40 weeks, were divided randomly into three groups. The first group was the nonocclusion, nonhemodilution (NN) normal control group. The second group was the occlusion, nonhemodilution (ON) group, in which animals were treated with bilateral carotid artery ligation. The third group was the occlusion-hemodilution (OH) group, in which animals were treated with bilateral common carotid artery ligation and, then, isovolemic hemodilution by replacing blood with the same volume of 3% modified fluid gelatin. Local cerebral blood flow (lCBF) and microvascular volumes of red blood cells (Vr) and plasma (Vp) in 14 brain structures were measured using 14C-iodoantipyrine, iron-55 labeled red blood cells, and 14C-inulin, respectively. The amount of oxygen delivered to local brain structures (OD), cerebral microvascular blood volume (Vb), mean transit time of blood (Tb), Tr, and Tp through cerebral microvessels were calculated from the data. Two hours after carotid artery ligation, lCBF decreased by approximately 38% in forebrain structures, 22% in rostral hindbrain areas, and 8% in the caudal hindbrain (29% for all 14 structures). The decreases in ODs were parallel with those of lCBFs, at 33, 17, and 2% in the three regions, respectively (24% for all structures). In contrast, Vb increased by 68, 37, and 16% in the three regions, respectively (48% for all structures). Tr and Tp were markedly prolonged (180% for Tr and 154% for Tp) in the forebrain regions, moderately (91% for Tr and 73% for Tp) in the rostral hindbrain, and mildly (60% for Tr and 13% for Tp) in the caudal hindbrain, with a mean increase of 136% for Tr and 111% for Tp in all structures. When data in the OH and NN groups were compared, lCBF values tended to be slightly higher and Vb values were significantly higher (p < 0.05) in the OH group. ODs in the eight forebrain structures were all significantly less (p < 0.05) in the OH group than the NN group. Tr and Tp values in the forebrain were similar between the OH and the NN groups. In conclusion, occlusion of the bilateral common carotid arteries in WKY rats causes partial forebrain ischemia, in which both Tr and Tp are prolonged. These prolongations of Tr and Tp can be normalized by isovolemic hemodilution. However, the ischemic forebrain remains hypoxic after hemodilution.

A simple method for diagnosing traumatic occlusion of the vertebral artery at the craniovertebral junction.

STUDY DESIGN: A simple method, thin-slice contrast-enhanced computed tomographic (CT) scan, was evaluated as a first-line rapid screening procedure for diagnosing traumatic occlusion of the vertebral artery at the craniovertebral junction. OBJECTIVES: This procedure was performed in patients suffering from injuries of the high cervical spine or the craniovertebral junction. Vertebral angiography was undertaken after this procedure to confirm the diagnosis. SUMMARY OF BACKGROUND DATA: Well-enhanced vertebral arteries can be demonstrated clearly in normal subjects by using this method. Occlusion of the vertebral artery produces delayed contrast enhancement of the proximal artery and abrupt interruption of its course. METHODS: Thin-slice CT scan was performed from the atlas to the occipital condyles after an intravenous injection of angiograffin. The plane of the CT scan was aligned in a parallel manner to the upper margin of the atlas. The CT scanning was repeated until the contrast enhancement of the vertebral arteries became faint. RESULTS: Occlusion of the unilateral vertebral artery was successfully diagnosed in a patient with Jefferson's fracture by using the present technique. A subsequent vertebral angiography confirmed the diagnosis. CONCLUSIONS: The present technique should be performed as a routine screening procedure in patients suffering from injuries to the craniovertebral junction.

[Experimental study on prevention of the colorectal cancer by China medical stone and the organgermanium compound].

To compare the effect of cancer prevention of China medical stone (CMS) and Ge-132, rats were subcutaneously injected with dimethylhydrazine for 15 weeks and orally administered with 10% china medical stone soak and Ge-132 for 27 weeks. Colorectal cancer incidence in CMS was found significantly lower than in Ge-132 and controls (P < 0.05-0.01). In Ge-132 only the mean cancer foci and the mean cancer volumes/rat were found significantly less than controls (P < 0.01). It was shown by endoscopy that a precancerous lesion of the bowel resulted from carcinogen was more mild in CMS and Ge-132 than in controls. Serum gamma-interferon titer and NK activity of spleen cells were significantly elevated in CMS and Ge-132. Researches explained that the effect of cancer prevention of CMS was better than that of Ge-132.

[Determination of naoning pian by multi-wavelength linear regression method].

Assay of naoning pian was reported by multi-wavelength linear regression method in this paper. The program was edited by BASIC. The recoveries and RSD of pyramidon and caffeine were 98.03%-100.9%, 1.0% and 97.77%-99.39%, 0.61%, respectively. This method could be used for the determination of two components in naoning pian without separation. The method was simple, rapid, and results were satisfactory.

Overlapping allograft in reconstructive surgery for malignant bone tumours in paediatric patients: a preliminary report.

The use of allografts for the treatment of bone tumours in children is limited by nonunion and the difficulty of finding a suitable graft. Furthermore, appositional growth can't be expected of an allograft. We used an overlapping allograft in 11 children, with a mean age of ten years (4 to 15), with a mean follow-up of 24.1 months (20 to 33). There were five intercalary and six intra-articular resections, and the tumours were in the femur in six cases and the humerus in five. Rates of union, times to union, remodelling patterns and allograft-associated complications were evaluated. No allograft was removed due to a complication. Of the 16 junctional sites, 15 (94%) showed union at a mean of 3.1 months (2 to 5). Remodelling between host and allograft was seen at 14 junctions at a mean of five months (4 to 7). The mean Musculoskeletal Tumor Society score was 26.5 of 30 (88.3%). One case of nonunion and another with screw protrusion required re-operation. Overlapping allografts have the potential to shorten time to union, decrease rates of nonunion and have positive appositional growth effect.

Prognosis of extremity osteosarcoma in patients aged 40-60 years: a cohort/case controlled study at a single institute.

BACKGROUND: The outcome of older osteosarcoma patients with multi-disciplinary management has not been clearly defined. METHODS: We conducted a cohort (n=375) and a case-control (n=78) study on 26 older age patients (40-60 years) with localized osteosarcoma of extremity. In the case-control study, controls were matched for location and initial tumor volume. RESULTS: Compared to 349 younger patients, older age patients showed an osteolytic pattern on plain radiographs (P=0.05), fibroblastic subtype (P<0.01), and poor histologic response (P=0.03). Multivariate analysis revealed that a large absolute tumor volume (P<0.01), a tumor location in the proximal humerus (P=0.02), and a poor histologic response to preoperative chemotherapy (P<0.01) independently predicted poorer metastasis-free survival. However, an older age showed marginal significance (P=0.09). A case-control study showed a higher proportion of the fibroblastic subtype and poor histologic response in the case group. Five-year metastasis-free survival rates for the 26 cases and 52 controls were 40.1+/-10.1% and 61.5+/-6.8%, respectively (P=0.02). CONCLUSIONS: Older age osteosarcoma patients showed an unfavorable histologic response to chemotherapy and lower survival than younger patients. Nevertheless, a further larger-scale study is required to confirm our observations.

Different radiological findings with the same pathologic diagnosis due to different age in primary osteosarcoma.

PURPOSE: To examine the imaging characteristics of osteoblastic osteosarcoma in older patients, we compared them with those in adolescents because the radiological features of osteosarcoma can be atypical in elderly patients. MATERIAL AND METHODS: 29 cases of adolescent patients and 12 patients older than 40 years of age were reviewed. All cases were pathologically confirmed as osteoblastic osteosarcoma. The comparative factors were tumor location, plain radiological features including periosteal reactions, and the degree of soft tissue mass with magnetic resonance (MR) imaging. RESULTS: Older patients demonstrated frequent osteolytic findings (83.3%), and none of the tumors showed a significant major periosteal reaction. Seven (58.3%) of the 12 tumors had no soft tissue mass (grade 0) and only three (25%) had a grade 3 mass. The differences in the two groups were statistically significant (P<0.001). CONCLUSION: In older patients, primary osteosarcoma should be considered when making a differential diagnosis of osteolytic lesions without any periosteal reactions and small soft-tissue extensions. In cases with atypical findings, the morphology of specimens (aspiration, core, or surgical biopsy) from the lesion should be recommended when making an accurate diagnosis.

Hemodilution accelerates the passage of plasma (not red cells) through cerebral microvessels in rats.

BACKGROUND AND PURPOSE: Hemodilution lowers the total circulatory red cell mass and blood viscosity and thereby may alter the time of passage of red cells and plasma through cerebral microvessels. This study was designed to clarify this question. METHODS: Adult Wistar-Kyoto rats, aged approximately 32 weeks, were divided into hemodilution and control groups. Local cerebral blood flow and microvascular red cell and plasma volumes in 14 brain structures were measured with the use of [14C]iodoantipyrine, 55Fe-labeled red cells, and [14C]inulin, respectively. RESULTS: In the control group, the hematocrit in cerebral microvessels ranged from 0.29 to 0.45 with a mean of 0.36, which was 71% of the systemic hematocrit (0.51). The mean transit times of blood, red cells, and plasma through microvessels were 0.62 to 1.77 seconds (mean, 0.92 second), 0.44 to 1.15 seconds (mean, 0.65 second), and 0.78 to 2.5 seconds (mean, 1.25 seconds), respectively. In the hemodilution group, the mean hematocrit in microvessels was 0.28, which was 89% of the systemic hematocrit (0.32). Local cerebral blood flow was approximately 59% higher (P < .01) than that of the control animals. The rate of oxygen delivered to the brain was slightly increased (9%) after hemodilution. Blood volume in cerebral microvessels was similar to that of the control group. Mean transit time of blood was 0.62 second (68% of the control), transit time of red cells was 0.53 second (85% of the control), and transit time of plasma was 0.67 second (54% of the control). CONCLUSIONS: These findings indicate that isovolemic hemodilution accelerates the plasma (not red cell) flow velocity in cerebral microvessels.

Transdural cortical stabbing facilitates the drainage of edema fluid out of cold-injured brain.

Recent experimental results indicate that cerebral glia lining and glia limitans may be barriers for plasma protein extravasated from injured cerebral microvessels flowing into the adjacent subarachnoid space. Therefore, it has been hypothesized that a transdural cortical stabbing which opens both the pia lining and glia limitans may facilitate drainage of edema fluid into the subarachnoid space and minimize brain edema. This hypothesis was tested in Sprague-Dawley rats with a transdural cold-injury on the right parietal cortex. The animals were sacrificed 24 hours later. One hour before being sacrificed 0.6 ml of 2% Evans blue was intravenously injected to determining the Evans blue distribution area. For measuring the inulin retention volume in the brain, 14C-inulin (10 microCi) in 1 ml of saline was injected intravenously at 10 min before sacrifice. The extent of brain edema was assessed by measuring the water content, the inulin retention volume, and the distribution area of Evans blue in the brain. Our results showed that the transdural cortical stabbing did not alter the water content of the cerebral hemisphere with cold lesion. However, it did effectively diminish the inulin retention volume by 26% as well as the distribution area of Evans blue by 22% in the cerebral hemisphere with cold lesion. In conclusion, a transdural cortical stabbing on the injured cortex may be beneficial for vasogenic brain edema.

Combined treatment with nicardipine, phenobarbital, and methylprednisolone ameliorates vasogenic brain edema.

Free radicals formed around the edematous areas of the brain can cause lipoperoxidation of the cellular membrane, followed by calcium influx into the cell through calcium channels. These secondary insults may aggravate vasogenic brain edema. Since phenobarbital is a free radical scavenger, methylprednisolone has an antilipoperoxidation effect; and nicardipine is a calcium channel blocker, we hypothesized that combined treatment with phenobarbital, methylprednisolone, and nicardipine would be beneficial in vasogenic brain edema. This hypothesis was tested in Sprague-Dawley rats with a transdural cold-injury on the right parietal cortex. The animals were randomly divided into two groups. Animals in the treatment group were injected intraperitoneally with phenobarbital (4 mg/kg), methylprednisolone (50 mg/kg), and nicardipine (10 micrograms/kg) at 5 min and 8 hours after the cold-injury. The control animals were injected with saline. These animals were sacrificed 24 hours after the injury. The extent of brain edema was assessed by measuring the water content, the inulin distribution volume, and the distribution area of Evans blue in the brain. Our results showed that the water content of the edematous hemisphere was similar in the control and the treatment groups. However, Evans blue distribution area and inulin distribution volume of the treatment group were less than those of the control group by 12% and 31%, respectively. In conclusion, the combined treatment with phenobarbital, methylprednisolone and nicardipine is beneficial in vasogenic brain edema.