A phase II study of concomitant hyperfractionated radiation therapy and double dose intra-arterial cisplatin for squamous cell carcinoma of the head and neck

This successor phase II study evaluates the tolerability and efficacy of concomitant hyperfractionated radiation therapy (HFX-RT) and double dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In doing so, this study represents further resurgence of the potential use of IA chemotherapy in the management of SCCHN. This has been enabled by the evolution of angiographic catheter/microcatherter technology. Between 1997 and 1999, 24 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8- 81.6 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150mg/m2 given at the start of and during RT boost treatment [start of week 6 and 7]). Twenty-two patients (92%) had T4 disease and 14 (58%) N2/ N3 disease. Acute toxicity was limited to two grade 4 (8%) and 19 grade 3 (79%) mucosal events; and single grade 3 hematologic, infectious and skin events. Eight patients (33%) were unable to receive the second planned dose of IA cisplatin. Twenty-two patients had complete response (92%) at the primary site. Among 17 patients with positive neck disease 12 (71%) achieved complete response in the neck. Follow-up ranges from 7-30 months (median = 18 months) with 14 patients alive without disease, 2 alive with disease, 7 dead of disease and 1 dead of intercurrent disease. While concomitant HFX-RT and double dose IA cisplatin as used in this study is associated with encouraging response rates in this highly unfavorable subset of patients with locally advanced SCCHN it was not feasible. Future investigation of this novel treatment strategy utilizing modern angiographic catheter/microcatherter technology will involve a single dose of IA cisplatin with HFX-RT and dose intensification using neoadjuvant therapy.     

Interval pathologic assessments in patients treated with concurrent hyperfractionated radiation and intraarterial cisplatin (HYPERRADPLAT)

BACKGROUND: To minimize surgical morbidity, surgery should be performed within 2 to 3 months of completion of radiation therapy with or without chemotherapy. Pathologic demonstration of cancer at this interval is commonly used to justify early surgical salvage of residual primary head and neck cancer. These assumptions regarding head and neck cancer in patients treated with concurrent hyperfractionated radiation therapy and intraarterial supradose cisplatin (HYPERRADPLAT) have never been evaluated. METHODS: Post-HYPERRADPLAT clinical and pathologic findings in 42 patients with stage III and IV head and neck cancer were compared with their disease outcomes. All patients underwent an interval analysis of response at 6 to 10 weeks after completion of therapy, 28 of these patients had biopsies of the primary tumor site performed. RESULTS: Clinical findings of cancer with pathologic confirmation up to 4 months after therapy can be associated with eventual complete response (CR). Pathologic CR's from deep incisional biopsies can be associated with recurrent disease within 2 months. Six HYPERRADPLAT-treated patients underwent interval surgical resection of primary disease, and only the four patients with cancer identified in the resection specimen died of recurrent disease. CONCLUSION: In patients treated with HYPERRADPLAT, interval clinical and pathologic assessments may be misleading. Only observation of progressive disease is an accurate predictor of local failure. New evaluation techniques such as metabolic imaging and molecular analysis warrant exploration as tools for interval cancer evaluations.     

老年性骨质疏松所致骨折患者血清钙磷和TGF-β 1分析

1临床资料2003-06／2004—12收治髋部骨质疏松性骨折患20(男14，女6)例，年龄58—80(平均68．5)岁，股骨颈骨折13例，粗隆间骨折7例．对照组为老年性骨关节病或颈腰椎病患20例．均抽空腹静脉血4mL，3000r／min离心5min分离血清，4h内测定血清钙、磷，留血清-20℃保存备用，测定TGF-β1．用Au-2700全自动生化分析仪测定血清钙、磷，试剂由日本欧林巴斯公司提供．血清TGF-β1检测采用ELISA法，     

胰岛素样生长因子-I和人绒毛膜促性腺激素对成年大鼠Leydig细胞葡萄糖转运蛋白基因表达调控

目的:研究胰岛素样生长因子I(IGF I)和人绒毛膜促性腺激素(hCG)对成年大鼠睾丸Leydig细胞中葡萄糖转运蛋白(GLUT)基因表达的影响,为进一步探讨Leydig细胞中睾酮的合成、分泌与葡萄糖代谢的关系提供依据。方法:采用改良的Klinefelter方法从成年大鼠睾丸中分离获得Leydig细胞;用反转录聚合酶链技术检测IGF I和hCG对原代培养的Leydig细胞中GLUT基因表达的调控作用。结果:分离得到纯度为98%的大鼠Leydig细胞,并与对照组比较,hCG可显著增加Leydig细胞中GLUT8基因mRNA的表达水平(P<0.001),且此作用具有剂量依赖性与时效性。当在试验组细胞中单独加入IGF I或IGF I和hCG作用于细胞后,发现IGF I(100ng mL)可显著增加Leydig细胞中GLUT8基因mRNA的表达(P<0.01),也可与hCG协同作用显著提高GLUT8基因的mRNA表达,该结果与IGF I(100ng mL)和hCG(10ng mL)能协同作用极显著增加睾酮合成水平(P<0.001)的结果是相吻合的。在大鼠Leydig细胞中,无论10ng mL或100ng mL还是两者同时作用于细胞,都不能影响GLUT1和GLUT3基因的mRNA水平。结论:在成年大鼠Leydig细胞中,IGF I和hCG对细胞中的GLUT8基因表达的调节作用具有特异性,其协同作用能显著提高细胞中GLUT8基因mRNA水平,增强细胞摄取葡萄糖的能力,给细胞提供更多的代谢能源,最终增加Leydig细胞睾酮的合成与分泌。     

The role of dose size in a chemotherapy regimen (ProMECE-CytaBOM) for the first-line treatment of large B-cell lymphomas: a randomized trial by the Gruppo Italiano Studio Linfomi (GISL).

BACKGROUND: It is still unclear the actual contribute of dose intensity (DI), dose size (DS) and dose density (DD) in the conventional chemotherapy of large, B-cell non-Hodgkin lymphomas. METHODS: A prospective, randomized trial compared the cyclic schedule of ProMECE-CytaBOM chemotherapy (cyc-PC, 6 cycles) with a modified version of it, which administered the same drugs sequentially (seq-PC), with the same planned cumulative DI and an 83% DD, within the same time frame (113 days), but with three times higher DS of all the drugs except vincristine. RESULTS: Fifty-six patients received cyc-PC and 52 seq-PC. The actual mean cumulative DI was 0.79 +/- 0.15 with cyc-PC, 0.78 +/- 0.17 with seq-PC. Response was complete in 59% and 52%, partial in 20% and 21%, null in 5% and 6%, respectively. There were four toxic deaths (two per arm). Relapses occurred in 36% and 37%, respectively. Toxicity was similar in both arms. Overall, failure-free, progression-free and disease-free survival (median follow-up: 54 months) were statistically indifferent. CONCLUSIONS: The very similar DI actually delivered in both arm seems to be the main common determinant of the indifferent results recorded. Increasing DS--at least within the limits clinically attainable without stem cell rescue--does not improve results.     

Calf pseudohypertrophy in a patient with double neurogenic pathology

A pseudohypertrophy of the calf can be rarely associated with neurogenic pathologies as S-1 radiculopathy, poliomyelitis, spinal muscular atrophy, traumatic lesions of peripheral nerves, intraspinal neurinoma. The causes of this particular phenomenon are unknown. The authors present the case of a 52-year-old man with an enlargement of the left calf suffering from a mild form of spinal paralytic poliomyelitis in the early childhood and episodes of severe left sciatica in the last four years. Electromyography demonstrated a pattern of denervation in both legs and an H-reflex absent when the left tibial nerve was stimulated. An open muscle biopsy of the left calf was performed. Light microscopic and ultrastructural examination of the muscle confirmed the presence of a pattern of "neurogenic type" pseudohypertrophy. Our results could be interesting for the understanding of the mechanism of neurogenic pseudohypertrophy. This case suggests that timing of stimulus or "dose" of denervation may be important factors in such a phenomenon.     

Peripheral blood stem cell transplantation: Impact on procedure load and workload in an apheresis unit

Peripheral blood stem cells (PBSC) reinfusion appears to hasten hematologic reconstitution following myeloablative therapy. While procurement of PBSC adds apheresis procedures, rapid engraftment could decrease the demand for platelet transfusions. To determine the impact of PBSC collection on workload in our apheresis unit, we studied 3 consecutive groups of patients with metastatic breast cancer given comparable high-dose chemotherapy and autologous bone marrow transplant, with or without PBSC or granulocyte-colony stimulating factor (G-CSF). Forty-one transplants were performed with bone marrow cells only: 31 patients (Group A) did not receive G-CSF, while the following 10 patients (group B) received daily G-CSF until neutrophil engraftment. Bone marrow cells and PBSC were used for the most recent 11 transplants (group C), followed by daily G-CSF until engraftment. PBSC were mobilized with cyclophosphamide (4 g/m²) and etoposide (1 g/m²), followed by G-CSF, 8 μg/kg/day. PBSC collection was carried out on a Fenwal CS3000 + cell collector, using modified procedure 1, to obtain a minimum of 5 × 10⁸ mononuclear cells/kg. The times to neutrophil count over 500/μL, platelet count over 20,000/μL, and discharge from the hospital after transplant were significantly shorter for patients in group C (medians of 8, 8, and 21 days, respectively) compared to group A (medians of 14, 14, and 29 days; P = 0.001) or group B (medians of 11, 24, and 32 days; P < 0.001). The number of single-donor platelet equivalents transfused (1 SDE = 1 unit of single-donor platelets or 8 pooled random-donor platelets) was significantly decreased in group C (median = 4) compared to group A (median = 19) and group B (median = 11; P = 0.001 for both comparisons). The total apheresis procedure load (the sum of SDE and PBSC collection for each transplant) was significantly decreased in group C (median = 6) compared to groups A and B combined (median = 14; P = 0.001). The apheresis unit workload assessing apheresis durations per patient, calculated as 2 × SDE + 4 × PBSC, was also significantly reduced in group C (median = 16) compared to groups A and B (median = 28; P = 0.002). Thus, PBSC were advantageous in terms of faster engraftment, reduced platelet transfusions, and shorter hospitalization, while decreasing both procedure load and net workload per patient in the apheresis unit. © 1992 Wiley-Liss, Inc.