Clinical Assessment Of Stereotactic IGRT: Spinal Radiosurgery

The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. Its use for the treatment of spinal lesions has been limited because of the availability of effective target immobilization devices. Recent advances in stereotactic IGRT have allowed for spinal applications. Large clinical experience with spinal radiosurgery to properly assess clinical outcomes has previously been limited. At our institution, we have developed a successful multidisciplinary spinal radiosurgery program in which 542 spinal lesions (486 malignant and 56 benign lesions) were treated with a single-fraction radiosurgery technique. Patient ages ranged from 18 to 85 years (mean 56 years). Lesion location included 92 cervical, 234 thoracic, 130 lumbar, and 86 sacral. The most common metastatic tumors were renal cell (89 cases), breast (74 cases), and lung (71 cases). The most common benign tumors were neurofibroma (24 cases), schwannoma (13 cases), and meningioma (7 cases). Eighty-nine cervical lesions were treated using skull tracking. Thoracic, lumbar, and sacral tumors were tracked relative to either gold or stainless steel fiducial markers. The maximum intratumoral dose ranged from 12.5 to 30 Gy (mean 20 Gy). Tumor volume ranged from 0.16 to 298 mL (mean 47 mL). Three hundred thirty-seven lesions had received prior external beam irradiation with spinal cord doses precluding further conventional irradiation. The primary indication for radiosurgery was pain in 326 cases, as a primary treatment modality in 70 cases, for tumor radiographic tumor progression in 65 cases, for post-surgical treatment in 38 cases, for progressive neurological deficit in 35 cases, and as a radiation boost in 8 cases. Follow-up period was at least 3 to 49 months. Axial and/or radicular pain improved in 300 of 326 cases (92%). Long-term tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality and in 88% of lesions treated for radiographic tumor progression. Thirty of 35 patients (85%) with progressive neurological deficits experienced at least some improvement after treatment. Spinal stereotactic radiosurgery is now a feasible, safe, and clinically effective technique for the treatment of a variety of spinal lesions. The potential benefits of radiosurgical ablation of spinal lesions are short treatment time in an outpatient setting with essentially no recovery time and excellent symptomatic response. This technique offers a new therapeutic modality for the primary treatment of a variety of spinal lesions, including the treatment of neoplasms in medically inoperable patients, previously irradiated sites, for lesions not amenable to open surgical techniques, and as an adjunct to surgery.     

Pancreatic resection for locally advanced primary and metastatic nonpancreatic neoplasms

We conducted a retrospective review of our single-institution experience with pancreas resection for locally advanced primary malignancy or metastases from other organs. From January 1989 through April 2001 35 patients underwent pancreatic resection for locally advanced primary (17) and recurrent nonpancreatic (18) tumors. Patient records were examined for recurrence and survival. Seventeen patients with locally advanced primary tumors presented with pancreatic extension either into the head/body (six) or tail (11). Pancreatic resections were completed as en bloc procedures with the primary disease of stomach (five), colon (four), sarcoma (five), adrenal gland (one), or spleen (one). Procedures performed included pancreaticoduodenectomy for proximal lesions and distal pancreatectomy for disease limited to the pancreatic tail. Median overall survival was 56 months. Fourteen of 17 patients remain alive: three with disease and 11 without evidence of recurrence. Eighteen patients presented with recurrent tumor from a previously resected right upper quadrant tumor (nine) or metastases from an intra-abdominal source (nine). The primary source was colon (eight), biliary (three), sarcoma (three), melanoma (two), ovary (one), and unknown primary (one). Patients underwent pancreaticoduodenectomy, distal pancreatectomy, or resection of residual pancreas. Overall median survival was 46 months. In this group of 18 patients there was no increased survival in those patients with a time to recurrence from their primary tumor resection greater than 2 years. We conclude that pancreatic resection for locally advanced nonpancreatic or recurrent intra-abdominal malignancies is possible in properly selected patients. The ability to obtain disease-free margins through en bloc resection is a key component of therapy.     

抗体介导的排斥反应与临床

随着器官移植体液免疫理论的发展与抗体检测技术的进步,抗体介导的排斥反应(AMR)已逐渐被认识和引起关注。其治疗难度大、逆转率较低,已成为导致移植物失功的重要原因。本文较为系统地介绍了AMR的免疫机制、诊断与防治进展,以及供者特异性抗体的检测技术和临床意义,从而提出供者特异性抗体是引起移植物排斥反应特别是慢性排斥反应的主要原因,移植受者需常规监测抗体以利及时干预和治疗。     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Transverse plane pelvic rotation in adolescent idiopathic scoliosis: primary or compensatory?

Several studies have suggested that the pelvis is involved in the etiology or pathogenesis of adolescent idiopathic scoliosis (AIS). The purpose of this retrospective, cross-sectional radiographic study is to identify any correlation between the transverse plane rotational position of the pelvis in stance and operative-size idiopathic or congenital scoliosis deformities, using Scheuermann’s kyphosis and isthmic spondylolisthesis patients for comparison. The hypothesis tested was that the direction of transverse pelvic rotation is the same as that for a thoracic scoliosis. As a group, AIS patients had a significant transverse plane pelvic rotation in the same direction as the thoracic curve. When subdivided into the six Lenke curve patterns, this was true for the groups with a major thoracic curve: thoracic (1), double thoracic (2) and double curve patterns (3). It was not true for patterns with a major thoracolumbar/lumbar curve: single thoracolumbar/lumbar (5) and double thoracic-thoracolumbar/lumbar (6). Nor was it true for triple (4) curves. The Lenke 1 and 2 major thoracic curves without compensatory thoracolumbar/lumbar curves did not have the predicted pelvic rotation. All congenital scoliosis patients studied had main thoracic curves and significant transverse plane pelvic rotation in the same direction as the thoracic curve. There was no transverse plane pelvic rotation in the Scheuermann’s kyphosis or isthmic spondylolisthesis patients. We interpret these findings as consistent with a compensatory rotation of the pelvis in the same direction as the main thoracic curve in most patients with a compensatory thoracolumbar/lumbar curve as well as in patients with main thoracic congenital scoliosis.     

Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry’s Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma.     

金属对金属大头径微创全髋关节置换术治疗青中年股骨头坏死的临床研究

目的探讨金属对金属（金对金）大头径假体微创全髋关节置换术（THA）治疗青中年股骨头坏死Ⅲ、Ⅳ期的临床疗效。方法本组32例（35髋）青中年股骨头缺血性坏死Ⅲ、Ⅳ期患者,年龄24～59岁,平均45岁,术前髋关节Harris评分平均（37．9±7．5）分;以改良后外侧小切口、肌间隙人路、充分保留关节动力性组织结构为特征的金对金大头径微创THA治疗。术中严格采取正确的假体植入技术,术中保留完整的软骨下骨和髋臼横韧带,击入臼杯时一次性安装成功,正确运用万古霉素预防感染。术后口服利伐沙班片抗凝,术后12h开放负压引流及卧床行功能锻炼,术后第2天拔除引流管后扶拐下地部分负重行走,术后2—3周患者即可弃拐完全负重行走。结果本组32例35髋患者均获随访,随访时间为12个月～6年,平均为4年。所有患者切口均一期愈合,无深静脉血栓形成、关节脱位、坐骨神经损伤、髋臼及股骨疲劳骨折、关节疼痛等严重并发症,X线片示髋关节假体位置均良好,无松动、移位、股骨柄下沉、假体周围骨折等表现。末次随访Harris评分由术前平均（37．9±7．5）分,提高至术后平均（92．2±4．6）分,前后比较有统计学意义（t=44．341,P〈0．05）。所有患者末次随访时髋关节功能明显优于术前,均对治疗效果满意,完全恢复正常生活及工作。结论采用金对金大头径微创THA治疗青中年股骨头坏死Ⅲ、Ⅳ期患者,能够明显降低手术风险,缩短卧床时问,迅速恢复髋关节功能,减少手术并发症,取得了满意的近期临床疗效。随着基础和临床研究的不断深入,金对金大头径髋关节假体的长期疗效还需要进一步探讨。