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Biomedical subjects

Y Terashima

Publications and source records attributed to Y Terashima.

At least 19 recordsLinked to original sources

[Secondary hepatic resections in a case of sigmoid colon cancer with multiple liver metastasis (H3) after successful continuous hepatic artery infusion chemotherapy oriented by in vitro chemosensitivity test].

A 43-year-old woman was admitted to our hospital for sigmoid colon cancer with multiple liver metastasis (H3). As preoperative CTAP (CT during arterial portography) examination showed 23 metastatic nodules in the whole liver, hepatic resections were not indicated. Angiographic findings showed that right and left hepatic arteries branched separately from the celiac artery. Sigmoid colon resection with D3 lymph node dissection and catheterization to the right hepatic artery via gastroduodenal artery were undertaken as a first operation. Continuous hepatic artery infusion chemotherapy with MMC, 5-FU oriented by in vitro chemosensitivity test (SDI test: Succinic Dehydrogenase Inhibition test) of primary tumor was performed 7 days after the first operation. After administration of MMC (40 mg) and 5-FU (16,500 mg), metastatic nodules in the right lobe almost disappeared except for the one tumor of S7, but the size and number of the nodules in the left lobes increased. At 10 months after the first operation, the left hepatic lobectomy and extirpation of only one tumor in the right lobe (S7) underwent. This case showed the usefulness of continuous hepatic artery infusion chemotherapy oriented by in vitro chemosensitivity test for multiple liver metastasis from colon cancer.

Adenocarcinoma

[Combination chemotherapy with nedaplatin, bleomycin and ifosfamide for advanced cervical cancer of the uterus--a preliminary study for phase III clinical study].

A preliminary co-operative study by 7 institutes was conducted to determine the optimal dosage of the combination regimen with nedaplatin, bleomycin and ifosfamide, which is used in a phase III clinical study, to investigate its efficacy as neoadjuvant chemotherapy against advanced cervical cancer of the uterus. The drug administration consisted of 3 step; in the first step, nedaplatin and bleomycin were administered in a single dose at 80 mg/m2 and a 6-day dose at 7.5 mg/body/day, respectively, and this combination treatment was repeated every 4 weeks. After confirming the safety and efficacy of this combination regimen, the second-step treatment was started in which a 5-day dose of ifosfamide at 600 mg/m2/day was added to the combination regimen of the first step. In the third step, this three-drug combination regimen was used with the daily dose of ifosfamide increased up to 1,200 mg/m2. The drug administration was conducted in a total of 16 cases, consisting of 3 cases in the first step, 7 in the second step and 6 in the third step, which were all evaluable for tumor response and safety. Regarding tumor response, a 33.3% (1/3) of response rate was obtained in the first step, 71.4% (5/7) in the second step and 66.7% (4/6) in the third step. As for safety, bone marrow suppression indicated by grade 4 abnormal clinical laboratory test values was found in one case each in the second step (leukopenia and thrombocytopenia) and the third step (leukopenia). Thus, bone marrow suppression, mainly leukopenia and thro mbocytopenia, was regarded as the dose limiting factor of this three-drug combination regimen. The leucocyte and thrombocyte counts reached their nadirs at two weeks after administration with recovery in about two weeks. The other abnormal changes in clinical laboratory test values such as those indicating the effects on renal function were slight even in the third step. Nausea and vomiting, anorexia and fever were found in every step with high incidences. Alopecia was found in all cases of the third step. Based on the above results, the dosage of the third step (combination regimen with a single dose of nedaplatin at 80 mg/m2, 6-day dose of bleomycin at 7.5 mg/body/day and 5-day dose of ifosfamide at 1,200 mg/m2/day, repeated every 4 weeks) was considered to be the optimal dosage in the phase III clinical study for advanced cervical cancer of the uterus.

Adult

Bioavailability and diuretic effect of furosemide following administration of tablets and retarded capsules to human subjects.

Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were compared in vitro dissolution profile and in vivo absorption studies. The dissolution of F from retarded capsules was extremely restricted in the first fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F from tablets and retarded capsules in the second fluid of JP XII disintegration test were both complete. Metabolite specific assay of F showed F, conjugation of F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or plasma. The mean cumulative urinary excretion of F following administration of the tablets during 24 h was twice that of retarded capsules. The mean area under the plasma concentration-time curve (AUC) of F following administration of tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume during 24 h, however, was not significantly different between the two dosage forms. Clockwise hysteresis relationships between the diuretic response and the urinary excretion rate of F was observed after administration of retarded capsules. A straight relation between logarithm of the diuresis and logarithm of the urinary excretion of F was observed after maximum excretion rate of F following administration of both dosage forms.

Absorption

[Left cardiac output curve and pulmonary venous return curve in patients with various heart diseases].

This study assessed the cardiac function of humans by drawing simultaneous left cardiac output and pulmonary venous return curves using radionuclide angiocardiography and right heart catheterization which allows recording of the pressure-flow relationship. Thirty-one subjects with various cardiac diseases were divided into two groups [18 patients with New York Heart Association (NYHA) functional class I and 13 patients with NYHA classes II or III]. Mean pulmonary filling pressure (Pmp) was calculated from the formula of Guyton, using pulmonary arterial compliance which was measured by Reuben's method and pulmonary venous compliance measured as reported previously. On the pressure-flow plane, the down slope of the pulmonary venous return curve was drawn by joining the points of (Pmp, 0) and (mean pulmonary capillary wedge pressure, cardiac output). To construct the cardiac output curve, two levels of lower body negative pressure were used to regulate the venous return to the heart. Pmp and the resistance to pulmonary venous return in NYHA II or III patients were significantly higher than those in NYHA I patients (Pmp: 16.3 +/- 1.5 vs 9.0 +/- 0.5 mmHg, p < 0.01; resistance to pulmonary venous return: 0.75 +/- 0.09 vs 0.43 +/- 0.04 mmHg/l/min, p < 0.01, respectively). The slope of pulmonary venous return curve in NYHA II or III patients was smaller than that in NYHA I patients and the pulmonary venous return curve in NYHA II or III patients shifted rightward. The slope of cardiac output curve in NYHA II or III patients was significantly smaller than that in NYHA I patients. This curve in NYHA II or III patients shifted downward and rightward. These results indicate that simultaneous cardiac output and pulmonary venous return curves may be a useful method for assessing the cardiac function in patients with various heart diseases.

Adult

[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion].

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adult

[Methotrexate in gynecologic oncology].

Methotrexate produced the first remission in leukemia and the first cure of a solid tumor, choriocarcinoma. Methotrexate tightly binds to dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic acid, the active form of folic acid. Methotrexate also directly inhibits the folate-dependent enzymes of de novo purine and thymidylate synthesis. Resistance to methotrexate may develop as a result of elevated DHFR activity or defective transport of methotrexate into malignant cells. Increased DHFR enzyme levels may also result from amplification of the DHFR gene, which is now clinically significant in selected patients. Methotrexate is an active drug in the first-line treatment of gestational trophoblastic disease (GTD) and in metastatic squamous cell carcinoma of the cervix. Since the introduction of methotrexate chemotherapy for malignant GTD, most hospitals have reported almost 100% cure rates for patients with nonmetastatic disease using single-agent regimens. Patients with low-risk metastatic disease have been treated with methotrexate and folinic acid and over 50% complete remission rates have been reported. Patients with metastatic GTD who had one or more high-risk factors benefited from initial multiagent chemotherapy, rather than waiting for acquisition of drug-resistance to single-agent therapy to start multiagent treatment. Using multiagent combination chemotherapy such as MAC (methotrexate, actinomycin D, cyclophosphamide) or EMA-CO (etoposide, methotrexate, actinomycin D and cyclophosphamide, vincristine), most investigators have reported remission in approximately 60 to 80% of patients with high-risk metastatic GTD. Although the role of chemotherapy in carcinoma of the cervix has been limited for several reasons, trial of combination chemotherapy including methotrexate has been reported. However, it is still impossible to draw definite conclusions as to whether methotrexate combined with another clearly active drug may yield a superior response rate and survival.

Adult

Plasma insulin and glucagon responses to acute challenges of acetate, propionate, n-butyrate and glucose in growing gilts (Sus scrofa).

A supraphysiological dose (2.5 mmol kg-1 body weight) of acetate, propionate, n-butyrate or glucose was intravenously injected to measure plasma insulin and glucagon responses in growing gilts. Plasma insulin concentrations remained constant after injection of the volatile fatty acids. Plasma glucagon concentrations increased (P < 0.05) after n-butyrate injection following an initial temporary decrease (P < 0.05), and showed a similar tendency after acetate or propionate injection. These results suggest that a supraphysiological dose of acetate, propionate or n-butyrate may stimulate a plasma glucagon response in growing piglets.

Acetates

The effect of propylthiouracyl-induced low thyroid function on secretion response and action of insulin in sheep.

The effect of propylthiouracyl (PTU)-induced low thyroid function on insulin responsiveness to glucose and glucose responsiveness to insulin in sheep was studied by performing hyperglycemic and euglycemic clamp experiments. All sheep were maintained at a level of 125% daily metabolizable energy intake and were housed in an environmental room that was maintained at 20 degrees C with a 16-hr lighting period. In the first study, eight female Suffolk sheep were divided equally into two groups and were subjected to oral PTU treatments of 4 mg/kg body weight (BW) per day for 7 d (low PTU) and 8 mg/kg BW per day for 14 d (high PTU). A hyperglycemic clamp experiment was conducted in each group on both control and PTU treatment periods. Plasma concentrations of triiodothyronine and thyroxine decreased (P < 0.05) in high PTU-treated sheep compared with those of low PTU-treated and control sheep. Both PTU treatments did not significantly influence basal insulin and glucose levels. Results of the hyperglycemic clamp experiment indicated that the mean plasma insulin increment and the ratio of mean plasma insulin increment to glucose infusion rate were significantly higher (P < 0.01) in high PTU-treated sheep than in low PTU-treated and control sheep. In the second study, the PTU treatment (8 mg/kg BW per day) was applied for 17 d in four male Suffolk sheep. A euglycemic clamp experiment with two insulin infusion rates (1.0 and 10.0 mU/kg per minutes) for two sequential periods of 2 hr each and thyroid hormone responses to intrajugular injection of thyrotropin-releasing hormone (1 microgram/kg BW) were performed in each sheep on both control and PTU treatment periods. In the euglycemic clamp experiment, the glucose infusion rate and the ratio of glucose infusion rate to mean plasma insulin increment were significantly reduced (P < 0.05) during the PTU treatment period for 10.0 mU/kg BW per minute of insulin infusion rate. The response areas of plasma thyroxine and triiodothyronine to thyrotropin-releasing hormone injection were blunted (P < 0.01) in PTU-treated sheep compared with those of control sheep. The high PTU treatment induced low thyroid function, enhanced insulin secretion response, and impaired insulin action in sheep.

Animals

Zona manipulation in an assisted reproductive technologies (ART) programme.

We investigated whether the aged oocytes maintain the ability to fuse with spermatozoa when the oocyte investment is removed. In the first study, 87 two-days-old oocytes provided from IVF-ET programme were treated with pronase to dissolve the zona pellucida. The oocytes were then inseminated with 100, 10 or 1 per microliters sperm and the incidence of monospermic and polyspermic fertilization was determined. In the second study 100 one-day-old unfertilized oocytes obtained from 18 IVF patients with "zero fertilization" at initial insemination were treated in the same way to either remove or thinning of the zona pelucida. They were then re-inseminated with 10 motile sperm per microliter of the husband. The incidence of monospermic and polyspermic fertilization were 0.0% (0/13) and 61.6% (8/14), respectively, with a sperm count of 100/microliters, 7.3% (3/41) and 31.6% (13/41) with 10/microliters, and 14.2% and 11.9% (5/33) with 1/microliter. The incidence of monospermic and polyspermic fertilization with reinsemination of one day old oocytes were 12.5% (3/24) and 25.0% (6/24) after zona removal and were 18.3% (9/49) and 10.2% (5/49) after zona thinning. The incidence of fertilization by zona removal was significantly higher than the results of conventional reinsemination (p < 0.001). It appeared that human aged oocytes maintain the ability to fuse spermatozoa after even two days. A higher rate of monospermic fertilization was obtained by carefully controlling the number of spermatozoa for insemination. We concluded that zona manipulation might improve fertilization in vitro in case of severe male factor infertility.

Female

Human pulmonary vascular and venous compliances are reduced before and during left-sided heart failure.

Human pulmonary vascular and venous compliances were measured in 41 patients with or without left-sided heart failure. Two methods were used. Method 1 was based on analysis of pulmonary capillary wedge (PCW) pressure tracings according to Cv,PCW = (SF/100)(0.075PCW + 0.90)SV/[(v - d)PCW + 1], where Cv,PCW is compliance of pulmonary venous system, SF is systolic fraction of pulmonary venous flow [related to pulmonary capillary wedge pressure (PCW) as SF = 82 - 2.01PCW], (v - d)PCW is pulse pressure in PCW position, and SV is stroke volume. The (0.075PCW + 0.90) term equals k", i.e., systolic run-off ratio. Method 2 was used to measure to pulmonary vascular volume-pressure (V-P) relationship and pulmonary vascular compliance (Cvasc) and is based on measurement of pulmonary blood volume (PBV) and its increase with passive elevation of the legs to calculate Cvasc. Assuming the proportion of blood entering pulmonary venous system (in increase of PBV) during passive leg elevation to be 0.8, pulmonary venous compliance (Cv,PBV) was calculated as Cv,PBV = 0.8Cvasc. Cv,PCW correlated fairly closely with Cv,PBV (r = 0.81, coefficient of variation = 31%). This fair agreement between two independent methods suggests strongly that both methods may be valid, although other interpretations are possible. Cv,PCW, Cvasc, and Cv,PBV decreased going from New York Heart Association class I to classes II and III. When PBV was plotted vs. PCW, average V-P line for class II patients was flatter and shifted downward to the right compared with that for class I. This suggests pulmonary vasoconstriction as well as other factors. Average V-P line for class III patients is flatter but not displaced compared with that for class II. Another previously reported series of 50 patients, most of whom had ischemic heart disease, are included in this study.

Blood Pressure

Dose response of plasma insulin and glucagon to intravenous n-butyrate infusion in sheep.

n-Butyrate (0, 1, 2, 4, 8, 16, 32, and 64 mumol.kg BW-1.min-1) was infused i.v. for 30 min to investigate the physiological effects of n-butyrate on plasma insulin and glucagon responses in sheep. Blood n-butyrate concentrations during n-butyrate infusion increased (P < .01) with increasing infusion rates. At the greater infusion rates of n-butyrate, plasma glucose concentrations increased (P < .01) during infusion, and then they decreased (P < .05) to less than the preinfusion values. Plasma insulin concentrations increased (P < .01) dose-dependently during n-butyrate infusion at rates of > or = 2 mumol.kg BW-1.min-1. Plasma glucagon concentrations increased (P < .05) during n-butyrate infusion at rates of 32 and 64 mumol.kg BW-1.min-1. It is possible that, in sheep, n-butyrate may have a physiological role in controlling insulin secretion; however, it does not seem to have a role in glucagon secretion.

Animals

Plasma insulin and glucagon responses to propionate infusion into femoral and mesenteric veins in sheep.

Propionate (1, 2, 4, 8, 16, 32, and 64 mumol.kg BW-1.min-1 for 30 min) was infused into the femoral and mesenteric veins of adult sheep to investigate the physiological significance of propionate in regulating plasma insulin and glucagon concentrations. The increments in arterial blood propionate concentrations during propionate infusion increased (P < .001) with increasing infusion rates for both infusion sites, and they were smaller (P < .001) for the mesenteric vein infusion than for the femoral vein infusion. Plasma insulin concentrations during propionate infusion increased (P < .10) from preinfusion values with infusion rates of > or = 8 mumol.kg BW-1.min-1 for both infusion sites. The response areas of plasma insulin concentration above basal tended to be smaller (P < .112) for the mesenteric vein infusion than for the femoral vein infusion. Plasma glucagon concentrations during propionate infusion increased (P < .05) from preinfusion values with infusion rates of > or = 8 and 64 mumol.kg BW-1.min-1 for the femoral and mesenteric vein infusions, respectively. The response areas of plasma glucagon concentration above basal were smaller (P < .011) for the mesenteric vein infusion than for the femoral vein infusion. We conclude that in sheep propionate absorbed from the alimentary tract has a physiological role in regulating circulating concentrations of insulin and glucagon.

Animals

Effect of cold exposure on profiles of metabolic and endocrine responses and on responses to feeding and arginine injection in sheep.

The effect of cold exposure (0 degrees C) on profiles of total heat production (HP), energy metabolism, and blood metabolite and hormone concentrations were measured in nine shorn Suffolk rams. Blood metabolite and hormone responses to feeding and to i.v. arginine injection (.625 mmol/kg BW) and postprandial changes in HP were also measured. Heat production was greater (P < .05) during cold exposure than in the thermoneutral environment due to enhanced (P < .05) nonprotein oxidation. Protein oxidation and nitrogen balance remained unchanged during cold exposure. Plasma glucagon concentrations increased (P < .05) during the initial period of cold exposure. Heat production increased (P < .01) after the initiation of feeding in both environments. Heat production returned gradually to prefeeding values in the thermoneutral environment, but it remained close to the higher levels during cold exposure. Plasma insulin and glucagon concentrations increased (P < .05), and plasma growth hormone concentrations decreased (P < .10) after the initiation of feeding in both environments. Plasma glucagon responses to feeding (P < .05) and plasma insulin responses to arginine injection (P < .01) were reduced by cold exposure. We suggest that 1) enhanced HP in sheep exposed to cold is maintained by enhanced nonprotein oxidation and 2) endocrine responses to stimulants are influenced by cold exposure, even though profiles after cold exposure change little.

Acetates

[Surgery in ovarian carcinoma].

Surgery remains one of the important factors in the treatment of the ovarian cancer. Ovarian cancer spreads primarily by exfoliating malignant cells from the tumor surface that in turn implant throughout the peritoneal cavity. On the basis of the patterns of this spread, a stage-specific operation for ovarian cancer is currently being established. In early ovarian cancer, the initial operation allows a complete assessment of the spread of the disease. For stage I ovarian cancer, uni- or bi-lateral salpingo-oophorectomy was performed when a patient showed grade I well-differentiated tumor, no extra capsular proliferation, and intact capsule. For patients with advanced disease, the initial cytoreductive operation with the compulsory resection of involved portions of the bowel reduces tumor bulk and produces increased sensitivity to chemotherapy for the remaining tumor. Survival time increases further in proportion to decrements in tumor size below 2 cm in its maximum diameter. Even within the optimal group of patients, in whom the maximum diameter of residual disease was < or = 1 cm, there was a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm. Among with suboptimal group of patients, in whom the maximum diameter of residual disease is > 1 cm, and who receive the following platinum containing chemotherapy, those who have a small diameter of residual disease (< 2 cm) tend to survive longer than those with larger residual disease. Among those with the larger residual disease, the size of the tumor does not affect the prognosis. Optimal or suboptimal tumor resection is associated with a more complete response to chemotherapy. The principles of cellular kinetics provide good theoretical evidence of the benefit of cytoreductive surgery.

Chemotherapy, Adjuvant

Observer disagreement in histological classification of ovarian tumors in Japan.

Histological slides of 789 cases of ovarian tumor registered by the Japanese Gynecologic Oncology Group, sponsored by the Ministry of Health and Welfare, Japan, were reviewed by three certified pathologists in order to evaluate the observer disagreement among the pathologists and the reproducibility of the histological classification. In 53.0% of the cases, all observers agreed upon the diagnosis. At least two of them agreed in 88.4% of the cases. The observer disagreement was highest for low potential malignancy (borderline malignancy) tumors (44.4%), including serous, mucinous, and endometrioid tumors. The results of the study clearly indicate the necessity of establishing a slide review system in order to obtain reliable data for comparative research. Moreover, the histological criteria, especially of tumors of borderline malignancy, should be more clearly defined to obtain high reproducibility of ovarian tumor diagnosis.

Carcinoma

Characterization of an etoposide-resistant human ovarian cancer cell line.

Etoposide (VP-16) is one of the most important anticancer agents available and is used in many chemotherapeutic regimens. To characterize resistance to this drug, we established a VP-16-resistant human ovarian cancer cell line, SKOV3/VP, by continuous stepwise exposure of SKOV3 cells to VP-16. The degree of resistance to VP-16 of SKOV3/VP was about 25 times that of the parent cell line (SKOV3), and SKOV3/VP showed cross-resistance to teniposide, adriamycin, CPT-11, and vincristine. The accumulation of [3H]-VP-16 observed in SKOV3/VP cells was about half that seen in SKOV3 cells, and the accumulation of Adriamycin by this resistant cell line was also lower than that of its parent. Overexpression of neither the multidrug resistance gene mdr-1, the multidrug-resistance-associated protein (mrp) gene, nor P-glycoprotein was detected using reverse transcriptase-polymerase chain reaction analysis and flow cytometry with MRK-16, a monoclonal antibody against P-glycoprotein. The topoisomerase II activity of nuclear extracts from SKOV3/VP cells was lower than that from the parental cells, as was the amount of DNA topoisomerase II, demonstrated by immunoblotting. These results suggest that the mechanism responsible for the multidrug resistance of this cell line may be attributable to changes on its DNA topoisomerase II and to its reduced accumulation of the drugs as compared with the parental line SKOV3.

ATP Binding Cassette Transporter, Subfamily B, Mem

Prognostic factor analysis and treatment results of ovarian cancer in Japan.

Prognostic factors were analyzed among women with ovarian cancer. Stage, histologic subtype and grade, age, performance status, residual tumor size, and platinum-based chemotherapy were factors that significantly influenced the survival rate. Based on these findings, we performed maximal cytoreductive surgery and gave dose-intensified platinum-based chemotherapy to patients with advanced disease and were able to improve survival rate significantly.

Cisplatin

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary.

The correlation between histological subtype [endodermal sinus (ES), polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From 1964 to 1989, 35 patients with YSTs were treated with primary surgery and adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14 patients had a single subtype, either ES (12) or G (2); 12 patients had two subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes. Multivariate analysis showed that important predictors were FIGO stage, chemotherapeutic regimen and residual tumour size. However, for stage I, multivariate analysis showed that the histological subtype was a superior predictor to the subclassification of FIGO stage I, age or chemotherapeutic regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an admixture of three or four subtypes was associated with a better prognosis than those composed of one or two subtypes (P < 0.01), other variables being constant.

Adolescent