Computer-assisted surgery in orthopedic oncology: Technique,indications, and a descriptive study of 130 cases

Background and purpose —

In orthopedic oncology, computer-assisted surgery (CAS) can be considered an alternative to fluoroscopy and direct measurement for orientation, planning, and margin control. However, only small case series reporting specific applications have been published. We therefore describe possible applications of CAS and report preliminary results in 130 procedures.

Patients and methods —

We conducted a retrospective cohort study of all oncological CAS procedures in a single institution from November 2006 to March 2013. Mean follow-up time was 32 months. We categorized and analyzed 130 procedures for clinical parameters. The categories were image-based intralesional treatment, image-based resection, image-based resection and reconstruction, and imageless resection and reconstruction.

Results —

Application to intralesional treatment showed 1 inadequate curettage and 1 (other) recurrence in 63 cases. Image-based resections in 42 cases showed 40 R0 margins; 16 in 17 pelvic resections. Image-based reconstruction facilitated graft creation with a mean reconstruction accuracy of 0.9 mm in one case. Imageless CAS was helpful in resection planning and length- and joint line reconstruction for tumor prostheses.

Interpretation —

CAS is a promising new development. Preliminary results show a high number of R0 resections and low short-term recurrence rates for curettage.Oncological surgical treatment can be considered to be a trade-off between margins and function, with margins being the most important factor to consider. Accuracy is needed to achieve an efficient but oncologically safe result. To assist in this, most procedures in bone tumor surgery require intraoperative imaging with fluoroscopy and/or measurements with rulers for anatomical orientation and margin control. The best examples of this are pelvic resections. Cartiaux et al. (2008) demonstrated that 4 experienced surgeons could achieve a 10-mm resection margin, with 5-mm tolerance, on pelvic sawbones in only half of the resections. The supportive imaging and measuring modalities have, however, remained more or less unchanged for many years. In a 2-dimensional (2D) workflow such as fluoroscopy, there is still the requirement for an accurate frame of reference based on anatomical landmarks for adequate 3-dimensional (3D) margin control.In recent years, the use of computer-assisted surgery (CAS) in orthopedic surgery has become more common as an alternative for intraoperative imaging and measurements, providing the necessary precision in bone tumor surgery. The technique that is mostly used in orthopedic oncology is image-based navigation. The patient’s own anatomy (MRI and/or CT) is entered into the system and used during surgery. This provides real-time, continuous, 3D imaging feedback and may lead to more precise margin control, better tissue preservation, and new approaches to reconstruction while remaining oncologically safe. Several publications have supported CAS as being a safe navigation platform for planning and performing resections (Wong et al. 2007, So et al. 2010, Cho et al. 2012). A recent publication describes lessons in the technological approach and offers comments on CAS workflow (Wong 2010). However, to date the largest case series have involved only 20 and 31 cases (Cheong and Letson 2011, Jeys et al. 2013). The reported use has mostly been limited to complex tumor resections (e.g. pelvic), and due to the novelty of the technique, applications, approaches, and set-up times differ greatly (Saidi 2012). Here we describe possible applications of CAS in bone tumor surgery (also outside of complex resections), consider their usefulness, and report preliminary results from 130 CAS procedures performed at a single institution.     

Intracellular unesterified arachidonic acid signals apoptosis

Cyclooxygenase-2 (COX-2) is up-regulated in many cancers and is a rate-limiting step in colon carcinogenesis. Nonsteroidal antiinflammatory drugs, which inhibit COX-2, prevent colon cancer and cause apoptosis. The mechanism for this response is not clear, but it might result from an accumulation of the substrate, arachidonic acid, an absence of a prostaglandin product, or diversion of the substrate into another pathway. We found that colon adenocarcinomas overexpress another arachidonic acid-utilizing enzyme, fatty acid-CoA ligase (FACL) 4, in addition to COX-2. Exogenous arachidonic acid caused apoptosis in colon cancer and other cell lines, as did triacsin C, a FACL inhibitor. In addition, indomethacin and sulindac significantly enhanced the apoptosis-inducing effect of triacsin C. These findings suggested that unesterified arachidonic acid in cells is a signal for induction of apoptosis. To test this hypothesis, we engineered cells with inducible overexpression of COX-2 and FACL4 as "sinks" for unesterified arachidonic acid. Activation of the enzymatic sinks blocked apoptosis, and the reduction of cell death was inversely correlated with the cellular level of arachidonic acid. Inhibition of the COX-2 component by nonsteroidal antiinflammatory drugs restored the apoptotic response. Cell death caused by exposure to tumor necrosis factor alpha or to calcium ionophore also was prevented by removal of unesterified arachidonic acid. We conclude that the cellular level of unesterified arachidonic acid is a general mechanism by which apoptosis is regulated and that COX-2 and FACL4 promote carcinogenesis by lowering this level.     

清开灵与利巴韦林治疗小儿呼吸道合胞病毒肺炎的比较：单盲、随机、平行对照试验

目的:比较清开灵与利巴韦林对呼吸道合胞病毒肺炎患儿治疗效果的差异。方法:选择2005-02/2006-04在北京儿童医院分中心治疗的小儿呼吸道合胞病毒肺炎97例,患儿法定监护人知情同意。采用单盲、随机、平行对照试验的原则,按区组随机化方法分为2组,清开灵注射液组49例,利巴韦林组48例。①清开灵注射液组:清开灵注射液静脉滴注加口服中成药。②利巴韦林组:利巴韦林注射液静脉滴注加口服复方愈创木酚磺酸钾口服液。两组疗程均为10d,比较两组患儿的疗效。结果:清开灵注射液组脱落3例,利巴韦林组脱落1例,进入结果分析清开灵注射液组46例,利巴韦林组47例。①清开灵注射液组发热患儿体温恢复正常时间比利巴韦林组短[(2.72±1.86)d,(6.29±2.41)d(P<0.01)]。②清开灵注射液组患儿咳嗽、痰壅、气促症状积分改善方面优于利巴韦林组(P<0.05～0.01)。③清开灵注射液组的呼吸道合胞病毒转阴时间明显优于利巴韦林组。④咳嗽、痰壅、病毒转阴时间、气促均进入Logistic模型,其中前两个症状的回归系数绝对值较大。结论:清开灵注射液治疗小儿呼吸道合胞病毒肺炎在退热、止咳平喘、呼吸道合胞病毒转阴时间等方面均具有明显优势,咳嗽、痰壅这两个症状更能反映清开灵注射液的疗效优于利巴韦林。     

人羊膜间充质细胞具有分化成软骨及成骨细胞的潜能

目的:人羊膜间充质细胞具有比骨髓间充质干细胞更强的扩增能力和免疫原性低等优势。建立体外适宜的诱导培养条件,观察人羊膜间充质细胞定向分化为软骨细胞和成骨细胞的能力。方法:实验于2005-09/2006-12在贵州省细胞工程重点实验室完成。①材料来源:经产妇知情同意,无菌采集健康足月分娩新生儿胎盘6份,实验经医院医学伦理委员会批准。②实验方法:采用机械法剥离羊膜组织,二步酶消化法分离收获人羊膜间充质细胞,按2.2×10~8L~(-1)密度接种,传至第1～2代用于诱导分化实验。向软骨细胞诱导分化时,人羊膜间充质细胞按3×10~8L~(-1)密度接种,诱导培养液为含体积分数0.01的胎牛血清、10 mg/L转化生长因β1、100 nmol/L地塞米松、50 mg/L抗坏血酸、1%培养基添加物。向成骨细胞诱导分化时,人羊膜间充质细胞按6×10~7L~(-1)密度接种,诱导培养液为含体积分数0.1的胎牛血清、100 nmol/L地塞米松、50 mg/L抗坏血酸、5 mmol/Lβ-甘油磷酸。③实验评估:原代细胞用流式细胞仪分析表型,免疫细胞化学染色进行波形蛋白表达鉴定。分别于体外诱导第7,14,21,28天采用免疫细胞化学法检测软骨特异性Ⅱ型胶原的表达,细胞化学法检测蛋白聚糖的表达,钙-钴法检测成骨细胞特异性碱性磷酸酶的表达,茜素红S检测钙盐沉积情况。结果:①免疫组化与表型特征:人羊膜间充质细胞高表达间充质干细胞表面标志CD29、CD44和间充质细胞标志波形蛋白。②向软骨细胞诱导分化:诱导14 d后,人羊膜间充质细胞由长梭型逐渐变为多角形,可检测到Ⅱ型胶原蛋白表达及软骨细胞特异性细胞外基质蛋白聚糖。③向成骨细胞诱导分化:诱导21 d后,可观察到人羊膜间充质细胞的胞浆内有碱性磷酸酶表达,且可见钙盐沉积。结论:人羊膜间充质细胞具有分化成软骨细胞和成骨细胞的特性,可作为骨及软骨组织工程种子细胞的新来源。     

PSNAV2.0-TNFα重组质粒的构建及其在体外的表达

目的:在前期微囊化基因工程细胞制备平台的基础上,构建分泌型人肿瘤坏死因子α的真核表达载体PSNAV2.0-TNFα重组质粒,并鉴定其蛋白的体外瞬时表达,为进一步利用该基因进行微囊化细胞移植治疗和改善疾病奠定基础。方法:实验于2006-06/2007-05在解放军总医院老年医学研究所细胞生物学实验室完成。①以含有人肿瘤坏死因子αcDNA序列的质粒为模板,通过PCR扩增获得人肿瘤坏死因子α基因片段;将其定向插入真核表达载体PSNAV2.0中,获得重组质粒PSNAV2.0-TNFα。采用SalⅠ和EcoRⅠ双酶切法、PCR法及插入片段序列测定法鉴定该质粒。②利用阳离子脂质体介导法,将其转染到人胚胎肾细胞HEK-293细胞中,构建可持续分泌人肿瘤坏死因子α的基因工程细胞,采用RT-PCR法和Western blot法检测转染细胞培养上清液中人肿瘤坏死因子蛋白的体外瞬时表达。结果:①通过SalⅠ和EcoRⅠ双酶切、PCR及测序鉴定证明:在HEK-293中插入片段正确。②采用RT-PCR和Western blot法检测表明HEK-293细胞培养上清中有人肿瘤坏死因子α蛋白,Mr17000。结论:成功构建了重组质粒PSNAV2.0-TNFα真核表达载体,转染HEK-293细胞后可有效分泌人肿瘤坏死因子α蛋白,并能分泌到细胞外。     

Assessment of a daily online implanted fiducial marker‐guided prostate radiotherapy process

The aims of this study were to investigate whether intrafraction prostate motion can affect the accuracy of online prostate positioning using implanted fiducial markers and to determine the effect of prostate rotations on the accuracy of the software‐predicted set‐up correction shifts. Eleven patients were treated with implanted prostate fiducial markers and online set‐up corrections. Orthogonal electronic portal images were acquired to determine couch shifts before treatment. Verification images were also acquired during treatment to assess whether intrafraction motion had occurred. A limitation of the online image registration software is that it does not allow for in‐plane prostate rotations (evident on lateral portal images) when aligning marker positions. The accuracy of couch shifts was assessed by repeating the registration measurements with separate software that incorporates full in‐plane prostate rotations. Additional treatment time required for online positioning was also measured. For the patient group, the overall postalignment systematic prostate errors were less than 1.5 mm (1 standard deviation) in all directions (range 0.2–3.9 mm). The random prostate errors ranged from 0.8 to 3.3 mm (1 standard deviation). One patient exhibited intrafraction prostate motion, resulting in a postalignment prostate set‐up error of more than 10 mm for one fraction. In 14 of 35 fractions, the postalignment prostate set‐up error was greater than 5 mm in the anterior–posterior direction for this patient. Maximum prostate rotations measured from the lateral images varied from 2° to 20° for the patients. The differences between set‐up shifts determined by the online software without in‐plane rotations to align markers, and with rotations applied, was less than 1 mm (root mean square), with a maximum difference of 4.1 mm. Intrafraction prostate motion was found to reduce the effectiveness of the online set‐up for one of the patients. A larger study is required to determine the magnitude of this problem for the patient population. The inability in the current software to incorporate in‐plane prostate rotations is a limitation that should not introduce large errors, provided that the treatment isocentre is positioned near the centre of the prostate.     

Covering the costs of care in neonatal intensive care units.

The continued rise of health care costs, despite private and governmental control efforts, has sustained cost containment as a central issue for health care researchers and policy makers. In keeping with these concerns, the Florida Health Care Cost Containment Board conducted a study of neonatal intensive care units (NICUs) in Florida to ascertain the costs, charges, and net revenues associated with NICU services in individual hospitals, to document cost shifting and cross-subsidization as a means of financing NICU care for indigent populations, and to assess the fiscal impact of NICUs in state-sponsored vs non-state-sponsored Regional Perinatal Intensive Care Center hospitals providing NICU care. Hospitals in the state-sponsored program reported a loss of approximately $16.5 million in contrast to the non-state-sponsored hospitals, which reported a gain of $1 million. Payment being generated by private-pay patients amounted to almost 60% of total revenues but constituted less than one third of the costs in state-sponsored hospitals, indicating a high level of cost shifting. Government support of state-sponsored NICUs, while substantial, has been insufficient; increasing constraints on this funding source would likely worsen the deficit and increase the necessity of cost shifting.     

移植肾功能延迟恢复的护理体会

1临床资料我院1997-11/2004-11共行肾移植562(男386,女176)例,期中87例患者出现移植肾功能延迟恢复(DGF),男性58例,女性29例,年龄16～62(平均38.5)岁.术后常规服免疫抑制剂:环孢素,强的松,骁悉.发生DGF最早术后第4日,最晚20 d,均采用综合治疗措施,纠正水、电解质紊乱,控制血压,预防感染等,同时对不同原因引起的DGF采用相应的治疗、护理.85例患者均在术后3wk左右肾功能恢复,2例因并发症死亡.