Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.

PURPOSE: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study. RESULTS: The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear. CONCLUSION: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

The effect of independent collimator misalignment on the dosimetry of abutted half-beam blocked fields for the treatment of head and neck cancer.

BACKGROUND AND PURPOSE: Independent collimation conveniently allows for the junctioning of abutting fields with non-diverging beam edges. When this technique is used at the junction of multiple fields, e.g. lateral and low anterior fields in three-field head and neck set-ups, there should be a dosimetric match with no overdose or underdose at the matchline. We set out to evaluate the actual dosimetry at the central match plane. MATERIALS AND METHODS: Independent jaws were used to mimic two half-beam blocked fields abutting at the central axis. X-Ray verification film was exposed in a water-equivalent phantom and the dose at the matchline was evaluated with laser densitometry. Collimators were then programmed to force a gap or overlap of the radiation fields to evaluate the effect of jaw misalignment within the tolerance of the manufacturer's specification. Diode measurements of the field edges were also performed. Four beam energies from four different linear accelerators were evaluated. RESULTS: Small systematic inhomogeneities were found along the matchline in all linear accelerators tested. The maximum dose on the central axis varied linearly with small programmed jaw misalignments. For a gap or overlap of 2 mm between the jaws, the matchline dose increased or decreased by 30-40%. The region of overdose or underdose around the matchline is 3-4 mm wide. The discrepancy between the width of jaw separation and the width of the region of altered dose is explained by a penumbra effect. CONCLUSION: We recommend that independent jaw alignment be evaluated routinely and provide a simple method to estimate dose inhomogeneity at the match plane. If there is a field gap or overlap resulting in a clinically significant change in dosimetry, jaw misalignment should be corrected. If it cannot be corrected, part of the benefit of asymmetric collimation is lost and other methods of field junctioning may have to be considered. We routinely use a small block over the spinal cord at the mono-isocenter set-up plane for three-field head and neck treatments to prevent an overdose.     

Is there an incremental rise in the risk of obstetric intervention with increasing maternal age?

Objective To determine whether increasing maternal age increases the risk of operative delivery and to investigate whether such a trend is due to fetal or maternal factors.
Design Analysis of prospectively collected data on a maternity unit database.
Setting A postgraduate teaching hospital.
Population 6410 nulliparous women with singleton cephalic pregnancies delivering at term (37–42) weeks of gestation) between 1 January 92 and 31 December 95.
Main outcome measures Mode of delivery, rates of prelabour caesarean section, induction of labour and epidural usage.
Results There was a positive, highly significant association between increasing maternal age and obstetric intervention. Prelabour (  P < 0.001  ) and emergency (   P < 0.001  ) caesarean section, instrumental vaginal delivery (spontaneous labour   P < 0.001  ; induced labour   P = 0.001  ), induction of labour (   P < 0.001  ) and epidural usage in spontaneous labour (  P = 0.005  ) all increased with increasing age. In the second stage of labour fetal distress and failure to advance, requiring instrumental delivery, were both more likely with increasing maternal age (in both   P < 0.001  ). Epidural usage in induced labour and the incidence of small for gestational age newborns did not increase with increasing maternal age (P = 0.68 and  P = 0.50  , respectively).
Conclusions This study demonstrates that increasing maternal age is associated with an incremental increase in obstetric intervention. Previous studies have demonstrated a significant effect in women older than 35 years of age, but these data show changes on a continuum from teenage years. This finding may reflect a progressive, age-related deterioration in myometrial function.     

下咽癌淋巴引流的活体显像研究

目的：探讨下咽癌颈淋巴结转移时肿瘤区域引流淋巴结的活体显像方法，从肿瘤活体淋巴引流的角度观察下咽癌前哨淋巴结和颈淋巴结转移的方式，为颈淋巴结清扫术提供指导信息。方法：在表面麻醉和喉内镜引导下，用特制的注射针将^99mTc标记的人球蛋白注入20例下咽癌的肿瘤部位，在注射后不同时间采用SPECT扫描观察放射性核素通过淋巴扩散的过程及其在引流淋巴结内的浓集，以明确前哨淋巴结的位置和肿瘤颈淋巴结引流过程。同时对颈淋巴清扫标本进行病理检查。结果：20例肿瘤引流淋巴结均获得满意活体显像，显像的淋巴结最大3．5cm，最小1．0cm；12例梨状窝癌的颈部引流淋巴结位于肿瘤侧，其余8例中线结构的肿瘤颈部引流淋巴结均具有明显的优势偏向，即单侧颈部引流现象，没有出现双侧对称引流的病例。20例肿瘤引流淋巴结主要分布在Ⅱ、Ⅲ、Ⅳ区，未发现Ⅰ区和Ⅴ区显像的淋巴结。术后病理证实20例中有16例发现病理阳性淋巴结，且均位于引流优势侧，未出现对侧和双侧颈淋巴结转移的病例。结论：无论是中线结构或偏中线结构的下咽部癌肿，其向颈部的淋巴引流具有明显的优势偏向特点，术前进行引流淋巴结的活体显像对预测肿瘤转移部位和有目的地进行择区性颈淋巴结清扫术具有重要意义。     

Mechanisms of systemic hypertension during acute elevation of intraabdominal pressure

INTRODUCTION: In previous studies we described mechanisms by which acute elevation of the intraabdominal pressure (IAP) induces intracranial hypertension (ICHTN). Here we sought to define the role of ICHTN in mediating systemic hypertension (HTN) during CO(2) pneumoperitoneum (PNP). METHODS: Six large animals (swine) were hyperventilated to buffer hypercarbia. Intracranial pressure (ICP) was monitored with a Camino intraparenchymal ICP monitoring system. A Foley catheter was introduced intracranially via a separate burr hole. At phase 1, changes in ICP, central venous pressure (CVP), and mean arterial pressure (MAP) were recorded during periods of CO(2) PNP at IAP levels of 15, 20, 25, and 30 mm Hg. At phase 2, ICHTN was produced directly by inflating the intracranial balloon to the same ICP levels that had been measured in phase 1 for each degree of IAP. CVP and MAP were recorded. Repeated measures analysis of variance was applied. RESULTS: At phase 1, the mean DeltaCVP, DeltaICP, and DeltaMAP increased relative to the degree of IAP (P = 0.0001, 0.0004, and 0.024, respectively). At phase 2, the increments in DeltaMAP were significant (P = 0.024) and in the same direction and amplitude as at phase 1. CONCLUSIONS: In this study, increasing the IAP with CO(2) PNP with a consequent increase of ICP and direct manipulation of the ICP produced a comparable systemic HTN. We believe that this further supports our hypothesis: Elevated IAP produces an immediate increase in the CVP, which impairs venous drainage from the central nervous system (CNS), increases the ICP, and initiates a CNS-mediated response and systemic HTN.     

Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease

OBJECTIVE: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. METHODS: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme-linked immunosorbent assay. RESULTS: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P =.04) and systemic artery (P =.02) but not in the inferior vena cava (P =.2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P =.03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P =.02). CONCLUSION: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.     

Pulmonary microvessel density is a marker of angiogenesis in children after cavopulmonary anastomosis

OBJECTIVE: Pulmonary arteriovenous malformations cause progressive cyanosis in children after cavopulmonary anastomosis and may be due to abnormal angiogenesis. We determined the microvessel density, a marker of angiogenesis, in the lungs of children after cavopulmonary anastomosis. METHODS: Lung biopsy specimens were obtained from 8 children after cavopulmonary anastomosis and from 4 control patients. Three of the 8 children undergoing cavopulmonary anastomosis had clinical and angiographic evidence of pulmonary arteriovenous malformations, whereas the other 5 were free of symptoms. Routine histologic and immunohistologic stains were performed with a primary antibody to von Willebrand factor. Microvessel staining for von Willebrand factor was determined for 10 fields (200x) per patient. RESULTS: Patients with and without pulmonary arteriovenous malformations after cavopulmonary anastomosis demonstrated significantly increased microvessel density compared with control subjects (32.7 +/- 2.8 vs 9.3 +/- 4.6, P =.02, and 31.5 +/- 15.7 vs 9.3 +/- 4.6, P =.01, respectively). There was no difference in microvessel density in children with and without clinically apparent pulmonary arteriovenous malformations after cavopulmonary anastomosis (P =.9). The children with pulmonary arteriovenous malformations had numerous greatly dilated vessels that were absent in the asymptomatic children after cavopulmonary anastomosis. CONCLUSIONS: After cavopulmonary anastomosis, pulmonary microvessel density is increased even in the absence of clinically apparent pulmonary arteriovenous malformations, supporting the presence of a constant angiogenic stimulus. Children with clinically apparent pulmonary arteriovenous malformations possess large numbers of greatly dilated pulmonary microvessels, which are absent in asymptomatic children after cavopulmonary anastomosis. These results suggest that the transition to clinically apparent pulmonary arteriovenous malformations may be due to mechanisms that lead to vessel dilation and remodeling.     

硬膜外阻滞麻醉分娩镇痛配合Doula式分娩及连续胎心监护的临床分析

目的:观察硬膜外腔阻滞麻醉分娩镇痛配合Doula式分娩及连续胎心监护的临床效果及对产科质量的影响。方法:将低浓度罗哌卡因和小剂量含芬太尼的混合液注入硬膜外腔。配合Doula式分娩及连续胎心监护,用于76例没有产科并发症及麻醉禁忌症进入活跃期的初产妇作为观察组,将单纯采用Doula式分娩的89例相同条件的初产妇作为对照组,比较两组的镇痛效果及其对产科质量的影响。结果:两组镇痛效果有极显著性差异(P<0.01),催产素使用有显著性差异(P<0.05),产程时间、分娩方式、产后出血量、胎儿窘迫、胎心监护异常发生率及新生儿窒息发生率无显著性差异(P>0.05)。结论:硬膜外腔阻滞麻醉用于分娩镇痛,效果可靠,对母婴无不良影响,配合Doula式分娩及连续胎心监护,安全有效。