外科手术可改善脊柱转移瘤患者的功能预后,提高患者生活质量,甚至让患者获得长期生存机会.然而,脊柱转移瘤外科手术的并发症仍较高,这极大地打击了患者后续治疗信心,患者功能与生存预后也因此受到影响.脊柱转移瘤手术并发症的种类繁多,综合预防难度较大.目前认为,多学科联合治疗有利于预防并发症发生,每一种并发症都有其风险因素,了解与掌控脊柱转移瘤手术并发症发生的风险因素对并发症的预防与治疗具有重要意义.临床医师应根据每一位患者的具体情况进行术前评估与风险管控,以确定理想的预防措施和治疗策略.

Spinal metastasis is one of the common complications of prostate cancer.Skeletal related event (SRE) caused by spinal metastases seriously affect patients' quality of life,increase the risk of death.There is no standard treatment for spinal metastasis of prostate cancer.This paper briefly describes the advance of radiotherapy,surgery and support care,bone targeted agents for spinal metastases of prostate cancer.The authors think that the treatment of spinal metastases strategy should be interdisciplinary and individualized.

To identify potential prognostic factors for postoperative overall and progression-free survival and analyze pain and function outcome after decompressive surgery of painful malignant spinal cord compression (MSCC) in breast cancer patients. Ten preoperative characteristics for postoperative survival in a series of thirty-nine patients with breast cancer who were operated with decompressive surgery for MSCC were retrospectively analyzed, including age, hormone receptor status at the time of diagnosis, preoperative ambulatory status, extraspinal bone metastases, Eastern Cooperative Oncology Group (ECOG) performance status, visceral metastases, preoperative chemotherapy, time developing motor deficits before surgery, pathologic compression fracture in the spine and preoperative albumin. Worst pain, average pain, and pain interference were assessed using the visual analog scale (range, 0-10) for each patient at baseline and following surgery. Function outcome was also evaluated. In the multivariate analysis, hormone receptor status at the time of diagnosis (P = 0.04), preoperative ambulatory status (P = 0.01), and visceral metastasis (P = 0.04) were significant associated with postoperative overall survival; hormone receptor status (P < 0.01), preoperative ambulatory status (P = 0.04), and time developing motor deficits (P = 0.02) were found to be significantly independent prognostic factors for progression-free survival. The average pain score in a 24-hour period was 7.2 before the operation, whereas at 1, 3, 6, and 12 months after surgery, average pain scores decreased to 3.0, 2.6, 1.9, and 2.2 (all P < 0.001 vs. baseline), respectively. There was significant difference between the distribution of pre- and post-operative Frankel grades (P = 0.24). In details, 66.7% (26/39) patients was ambulatory before operation and 87.2% (34/39) after surgery (P = 0.03). Surgical treatment of breast cancer patients with MSCC was found to be effective in terms of neurological recovery. Hormone receptor status at the time of diagnosis, preoperative ambulatory status, visceral metastasis, and time developing motor deficits should be considered to help physicians to select the best treatment option especially for breast cancer patients with MSCC.

BACKGROUND: At present, traditional interbody fusion is still the main method for lumbar degeneration, and non-fusion treatment has achieved rapid development in recent years, but the effects of two kinds of methods on the lumbar biomechanics deserve a further study. OBJECTIVE: To explore the load distribution on the degenerative lumbar vertebrae, and pathogenesis of lumbar spine degeneration through finite element analysis; and to compare the stress distribution on the lumbar vertebrae and treatment outcomes after fusion and non-fusion surgeries. METHODS: The finite element models of four groups were established, respectively, based on the CT images, including normal lumbar spine, lumbar intervertebral disc herniation, and lumbar spine after fusion and non-fusion surgeries. The four groups were modeled in neutral position, lateral flexion, flexion and rotation by workbench 17.0, and the finite element analysis of stress and statics was conducted. RESULTS AND CONCLUSION: (1) The finite element analysis of degenerative lumbar spine showed that the stress of intervertebral disc mainly concentrated on the posterior part of the annulus fibrosus. The degenerative annulus fibrosus easily became thin under stress, thus affecting the lumbar stability. (2) The comparative analysis results found that the finite element results of the lumbar spine after non-fusion surgery were closer to those of the normal lumbar spine. Therefore, non-fusion surgery can achieve better repair outcomes in the treatment of lumbar vertebral degeneration.

Objective To explore postoperative outcome of ambulation function and prognosis-associated factors for metastatic spinal cord compression(MSCC) from lung cancer. Methods The clinical data of 56 patients who were operated for MSCC from January 2010 to May 2015 were retrospectively analyzed. The visual analogue scale(VAS) score and Frankel classification were used to evaluate the pain intensity and dysfunction of spinal cord,respectively. The physical status was assessed by the Karnofsky performance status(KPS) scale. Logistic regression analysis was applied to explore the possible correlation between histology,preoperative motor status(Frankel classification),pathologic fractures of responsible vertebral body,number of spinal metastases,the time interval of motor status impairment and surgery,location of spinal compression, surgical procedure and postoperative motor status. Results The VAS score decreased from preoperative 6.4±1.2 to postoperative 2.3±1.1,and the difference was statistically significant(P < 0.05). The KPS score increased from preoperative 62 to postoperative 70,and the difference was statistically significant(P < 0.05). The pre- and postoperative ratio of patients who were able to walk was 46%(26/56) and 75%(42/56),respectively. The grade of Frankel classification was increased in 31 cases,unchanged in 22 cases and decreased in 3. The postoperative Frankel classification was significantly higher than that before operation,and the difference was statistically significant(P < 0.05). Logistic regression analysis showed that there was a correlation between the preoperative motor status and postoperative motor status and between the motor function impairment and surgical interval. Conclusion Better preoperative motor status and shorter interval between motor function impairment and surgery would have a better postoperative motor status in the patients with MSCC from lung cancer. On the premise of reducing complications,symptomatic MSCC patients are recommended to surgery as soon as possible.

To identify potential prognostic factors predicting postoperative survival and function outcome and to analyze surgical outcome after decompressive surgery of metastatic spinal cord compression (MSCC), especially in aged patients. Eleven preoperative characteristics for postoperative survival and functional outcome in a series of fifty-four aged patients with MSCC who were operated on with decompressive surgery were retrospectively analyzed. These characteristics included gender, primary site, preoperative ambulatory status, ECOG performance status, number of involved vertebrae, visceral metastases, preoperative chemotherapy, bone metastasis at cancer diagnosis, the time developing motor deficits, preoperative albumin, and radical surgery at primary site. In multivariate analysis, primary site (HR, 2.33, 95% CI: 1.50-3.62; P<0.01) and visceral metastases (HR, 4.58, 95% CI: 2.21-9.48; P<0.01) were significantly associated with postoperative survival. Preoperative ambulatory status (HR, 4.98, 95% CI: 1.10-22.55; P=0.04) and visceral metastases (HR, 6.41, 95% CI: 1.43-28.77; P=0.02) were found to be significantly independent prognostic factors for postoperative function outcome. There was no significant consistency between the distribution of pre-operative and post-operative Frankel grades (P=0.20). The distribution of the total of Frankel grades after surgery was significantly different as compared with those before surgery (P=0.01). Eighteen complications were recorded within four weeks of surgery in 27.8% (15/54) of patients. Surgical treatment of aged patients with MSCC was found to be effective in terms of neurological recovery with a tolerable rate of complications. Primary site, visceral metastases, and preoperative ambulatory status should be considered to help physicians select the best treatment option, especially for aged patients with MSCC.

Objective: This study aimed to evaluate the efficacy of percutaneous pedicle screw fixation (PPSF) for instability of spinal metastases. Methods: This is a retrospective study of patients with spinal metastases from January 2013 to March 2016. PPSF was performed for twenty-five patients. Thirty-one patients were treated by radiotherapy alone. Visual analog scale (VAS) score was used to assess pain status. The activities of daily living (ADL) scale was used to evaluate functional ability of patients. Results: There were significant differences in the VAS score before and after operation. Multiple linear regression analysis showed that postoperative VAS score was concerned with the treatment method. Surgery was significantly superior to radiation in pain relief and postoperative ADL evaluation was related to the treatment method and pre-operative ADL evaluation. The results show that good post-operative life quality is related to surgery and good pre-operative life quality. Conclusion: For some patients with spinal metastases, PPSF is a good option for alleviating pain and improving quality of life.

Objective To explore the influencing factors in traditional single large channel core decompression and multiple drilling technique in the treatment of early osteonecrosis of the femoral head with the methods of finite element analysis.Methods The right femur of healthy adults were choosen as the research object,and CT scanning was conducted to get the images of cross sections.The images were then inputted into computer to get contour of femur and rebuild 3D model.Distal end of femur was completely fixed, and 570N pressure on the femoral head was applied according to the three-dimensional space distribution of femur force under physiological state.Three-dimensional finite element models were founded with the necrotic range of 15% and 30%, then the stress distributions of cancellous bone and cortical bone of femoral head were obtained through the models.Results Different methods of decompression and different numbers of channel cores would lead to a different stress value: stress concentration would appear on femoral head after core decompression.Multiple drilling technique would get a more stress concentration comparing to traditional single large channel core decompression, the stress value was summit of cortical bone and cancellous bone would both less than their yield strength and tensile strength of femoral hard.Conclusions Multiple drilling technique is more effective and feasible in the treatment of early osteonecrosis of the femoral head comparing to traditional single large channel core decompression.

Objective To evaluate the postoperative functional outcome and prognostic factors influcencing the survival time in the patients with spinal metastases after surgery for breast cancer. Methods The clinical data of 65 breast cancer patients with spinal metastases operated in 307th Hospital of Chinese PLA from January 2010 to May 2015 were retrospectively analyzed. The patients were divided into the spinal cord compression(SCC) group (29 cases) and non SCC(NSCC) group(36 cases). Improvement of visual analogue scale(VAS) score,Eastern Cooperative Oncology Group(ECOG) score and neurological function Frankel classifation were assessed. The influence of operation method,standard medical treatment (chemotherapy and/or targeted therapy and/or endocrinotherapy),postoperative radiation therapy,preoperative visceral metastases,postoperative ambulatory status(Frankel classification),preoperative performance status(ECOG score) and the number of invaded vertebrae on postoperative survival time were explored. Results In SCC group,VAS score decreased from preoperative 5.7±1.4 to postoperative 2.0±0.9;in NSCC group,VAS score decreased from preoperative 6.2±1.5 to postoperative 2.1±1.2;there was significant difference between pre-operation and post-operation in each group(P<0.05). In SCC group,Frankel classification of postoperative neurological function was improved in 15 cases(52%),remained unchanged in 14 cases(48%). Eleven of 18 patients(61%) unable to walk regained their ambulatory ability. Multivariable Cox proportional hazards model showed standard medical treatment,preoperative visceral metastases and preoperative ECOG score had significant effect on the postoperative survival. Conclusion Percutaneous vertebroplasty can timely and effectively relieve pain,and posterior decompression can improve and/or postpone neurological deficits. Besides,standard medical treatment, preoperative visceral metastases and preoperative performance status are the main factors influcencing the prognosis of breast cancer patients with spinal metastases.

With the aging population and the improvement in the diagnosis and treatment of cancer, the incidence of spine metastasis is increasing.The treatment paradigm for spinal metastases involves a multidisciplinary cooperative medicine.Orthopedics doctor is one member of the team.Their role is important and cannot be replaced.Surgery can relive refractory pain, maintain or regain ambulatory status, and improve patients'' quality at last.Therefore, patients can receive the following systematic treatment of tumor in a better status.The clinical manifestations, stability of spine, number and locations of spine metastasis, sensitivities of radiation and chemotherapy, expected survival prognosis, and radiology need to be considered in the decision-making to maximize the efficacy and minimize the risk of surgery.Although en bloc and total en bloc spondylectomy can achieve favorable survival outcome, those methods have narrow surgical indication, high risk and complication rate.Thus, those methods are still under debate.Minimally invasive surgery is the trend of surgery, many minimally invasive surgeries are booming.This review discusses the advancement and principles of surgery in patients with spine metastasis.

Implantation of radioactive seeds into tumor tissues belongs to the inner irradiation, which is permanent brachytherapy seed implantation, and is also the precise conformal radiotherapy. Implantation of radioactive seeds has gradually been used in the treatment of spinal metastasis and promising results have been obtained. It can remarkably relieve pain, prevent the progression of local disease, reduce the burden of tumor, and improve patients' quality of remaining life. The therapeutic methods include radioactive seed implantation, radioactive seed implantation combined with percutaneous vertebroplasty, and radioactive seed implantation combined with surgical decompression and stabilization. Currently, it has been reported in many investigations about the outcomes of radioactive seed implantation or combined with percutaneous vertebroplasty in the treatment of spinal metastasis. Radioactive seed implantation combined with surgical decompression and stabilization is gradually booming. This review aims to explore the recent status of radioactive seed implantation in the treatment of spinal metastasis and analyze the advantages and disadvantages of these therapeutic methods.

创伤评分系统可以将伤情严重程度转化为一组数字,对伤员总体伤情严重的评价是很重要的,客观而准确的评分不仅对创伤诊断分类,对抢救治疗及预后的判断都有积极的意义.近年来,临床上对创伤严重的评分标准及评定方案的研究十分活跃,反映了对创伤认识的不断深入.创伤评分在国外已经广泛使用,国内也逐渐应用了评分系统.本文就其临床应用近况与研究进展作一综述.

>Dear Editor,Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide(Li and Satomura,2015).Early diagnosis and treatment are vital for reducing mortality.Currently,biomarkers such as serum alpha fetoprotein(AFP),AFP-L2,and carcinoembryonic antigen are widely used tumor markers for managing HCC in patients(Shi et al.,2016).However,because of their low diagnostic sensitivity and specificity,novel biomarkers with high sensitivity and specificity for early HCC diagnosis are needed.

The incidence of spine metastasis is increasing due to the aging demography and improvement of cancer diagnosis and treatments.Spine metastasis is one of the serious complications of advanced cancers,and its treatment should pay attention to patients' quality of life and consider interdisciplinary cooperation.Expected life span can guide doctors to select the appropriate treatment for spine metastasis patients,and various scoring systems have been developed.We elicited relevant literatures in WanFang,CNKI,PubMed and Embase databases.Articles aiming at developing model for spine metastasis or describing the clinical effectiveness and pitfalls of the existed systems were included.As a result,48 articles were carefully reviewed.In this review,thosc scoring systems were stratified into two groups:Traditional scoring systems,which were published before or in 2005,including original/revised Tokuhashi scoring systems,Tomita scoring system,Bauer scoring system,Linden scoring system,and Sioutos scoring system;and new scoring systems,which were designed during the last three years,including Lei & Liu scoring system,Bollen scoring system,Rades scoring system,Oswestry spinal risk index (OSRI),and Katagiri scoring system.The usefulness of the traditional scoring systems has been validated by many studies.However,the applicability of those scoring system were controversial due to improvement of cancer treatment and survival period in recent years.Although the improvement of life span was considered,those new scoring systems have not penetrated into clinical routine because of the lack of validation.Currently,which system has the highest accuracy rates still remains unclear.Next generation of scoring systems should take into account the practicality and reliability at the same time.In this review,we introduced above mentioned scoring systems,described the validity and limitation of those scoring system,and suggested the future directions of next generation of scoring systems.

Objective To investigate the efficacy of surgical decompression and spine stabilization combined with permanent 125I brachytherapy seed implantation in the treatment of metastatic epidural spinal cord compression(MESCC). Methods MESCC patients treated with surgical decompression and spine stabilization combined with permanent 125I brachytherapy seed implantation(study group,n=20) or surgical decompression and spine stabilization followed by radiotherapy(control group,n=40) were retrospectively analyzed between January 2012 and November 2014. Visual analogue scale(VAS) score,Karnofsky performance scale(KPS) score,neurological outcome,survival prognosis,and rates of complications were compared between the 2 groups. Results Postoperative VAS scores were significantly lower than preoperative those,and postoperative KPS scores were significantly higher than preoperative those in both groups(P <0.05). The VAS scores in the study group were significantly lower than the those in the control group at 1 week,1 months, and 3 months after surgery(P<0.05),and similar in both groups at postoperative 6 months. The KPS scores in the study group were significantly higher than those in the control group at 1 week,and 1 months after surgery(P < 0.05),and similar in both groups at postoperative 3 and 6 months. There were 18(90.0%) and 30(75.0%) patients having the ability to walk after surgery in the study and control group,respectively,with no significant difference. The median survival time was 7.0 months (95% confidence interval:4.3-13.7 months) and 6.6 months(95% confidence interval:3.8-9.0 months) in the study and control group,respectively,with no significant difference(P < 0.05). Complication occurred in 2(10.0%) patients in the study group and 15.0%(6/40) in the control group,with no significant difference(P > 0.05). Conclusion Surgical decompression and spine stabilization combined with permanent 125I brachytherapy seed implantation is superior to the treatment with decompressive surgery followed by radiotherapy in MESCC patients in terms of short term pain relief and improvement of performance status.

BACKGROUND CONTEXT: Several clinical features have been proposed for the prediction of postoperative functional outcome in patients with metastatic epidural spinal cord compression (MESCC). However, few articles address the relationship between preoperative imaging characteristics and the postoperative neurologic status.PURPOSE: This study aims to analyze the postoperative functional outcome and to identify new imaging parameters for predicting postoperative neurologic status in patients with MESCC.STUDY DESIGN: This study is a retrospective consecutive case series of patients with MESCC who were treated surgically.PATIENT SAMPLE: We assessed 81 consecutive patients who were treated with decompressive surgery for MESCC between 2013 and 2015.OUTCOME MEASURES: Eight imaging characteristics were analyzed for postoperative motor status by logistic regression models. Neurologic function was assessed using the Frankel grade preoperatively and postoperatively.METHODS: The following imaging characteristics were assessed for postoperative motor status: location of lesions in the spine, lamina involvement, retropulsion of the posterior wall, number of vertebrae involved, pedicle involvement, fracture of any involved vertebrae, T2 signal of the spinal cord at the compression site, and circumferential angle of spinal cord compression (CASCC).RESULTS: The postoperative neurologic outcome was better than the preoperative neurologic status (p<.01). In the entire group, 40.7% of the patients were non-ambulatory before the surgical procedure, whereas 77.8% of the patients could walk after surgery (p=.01). In the multivariate analysis, the location of the lesions (odds ratio [OR]: 3.89, 95% confidence interval [CI]: 1.19-12.77, p=.02) and CASCC (OR: 2.31, 95% CI: 1.44-3.71, p<.01) were significantly associated with postoperative neurologic outcome. A CASCC of more than 180 degrees was associated with an increased OR that approached significance, and the larger the CASCC, the higher the risk of poor postoperative neurologic status.CONCLUSIONS: The postoperative neurologic status was dependent on the location of spine lesions and the CASCC. Patients with upper thoracic or cervicothoracic junction spine metastases or CASCC over 180 degrees were at higher risk of relatively poor postoperative neurologic outcome. Timely, adequate surgical decompression is urgently warranted in these patients. (C) 2016 The Author(s). Published by Elsevier Inc.

Study Design.A retrospective study.Objective.This study aims to develop a new scoring system that can guild surgeons to select the best candidates for decompressive surgery in patients with metastatic spinal cord compression (MSCC).Summary of Background Data.Predicting survival and functional outcome is essential when selecting the individual treatment for patients with MSCC. The criteria for identifying MSCC patients who are most likely to benefit from decompressive surgery remain unclear.Methods.We retrospectively analyzed 12 preoperative characteristics for postoperative survival in a series of 206 patients with MSCC who were operated with decompressive surgery and spine stabilization. Characteristics significantly associated with survival in the multivariate analysis were included in the scoring system. Postoperative function outcome was also analyzed on the basis of the scoring system.Results.According to the multivariate analysis, primary site (P<0.01), preoperative ambulatory status (P<0.01), visceral metastases (P<0.01), preoperative chemotherapy (P=0.02), and bone metastasis at cancer diagnosis (P=0.03) had a significant impact on postoperative survival and were included in the scoring system. According to the prognostic scores, which ranged from 0 to 10 points, three risk groups were designed: 0 to 2, 3 to 5, and 6 to 10 points. The corresponding 6 months survival rates were 8.2%, 56.5%, and 91.5%, respectively (P<0.01), and postoperative ambulatory rates were 35.7%, 73.3%, and 95.9%, respectively (P<0.01).Conclusion.We present a new scoring system for predicting survival and function outcome of MSCC patients after surgical decompression and spine stabilization. This new scoring system can help surgeons select the best candidates for surgical treatment.Level of Evidence: 4

This study aims to systematically compare the surgical results and prognostic factors between the older and the younger patients after decompressive surgery for metastatic epidural spinal cord compression (MESCC). Fifty-four older patients and sixty-five relatively younger patients with MESCC who were operated with decompressive surgery and spine stabilization were retrospectively analyzed in this study. Postoperative survival time, ambulatory outcome, and surgery-related complications were compared between the two groups. Besides, we retrospectively analyzed eleven preoperative characteristics for postoperative ambulatory outcome in both groups. The younger group (10.2 months, 95% CI, 6.2-12.8 months) had a relatively longer median overall survival than the older group (6.6 months, 95% CI, 4.5-10.8 months), but it reached no significance (P=0.24). The median overall ambulatory time of the older and younger groups was 3.7 months (95% CI, 3.0-6.6 months) and 6.0 months (95% CI, 3.7-8.6 months), respectively (P=0.03). In the multivariate analysis, primary site (P<0.01), preoperative ambulatory status (P<0.01) and visceral metastases (P<0.01) were significant associated with postoperative ambulatory outcome in the older group, while preoperative ambulatory status (P=0.01), preoperative chemotherapy (P=0.02), time developing motor deficits (P=0.03), and radical surgery at primary site (P<0.01) were found to be significantly independent prognostic factors in the younger group. Surgery-related complications occurred in 27.8% patients in the older group and 10.8% patients in the younger group (P=0.02). MESCC in the older patients had a poorer ambulatory outcome and a relative higher surgery-related complication as compared with MESCC in the younger patients. Primary site, preoperative ambulatory status and visceral metastases were independent prognostic factors for postoperative ambulatory outcome especially in the older patients with MESCC. Preoperative ambulatory status, preoperative chemotherapy, time developing motor deficits, and radical surgery at primary site were independent predictive factors in the younger patients with MESCC.

随着肿瘤患者生存期延长,脊柱转移瘤的发病率也越来越高.从解剖部位来看,硬膜外转移瘤发病率远远大于硬膜内转移瘤,前者常常导致脊柱机械稳定性的破坏,大大增加了病理性骨折的风险.此外脊柱转移瘤外科手术不断开展,在肿瘤切除、椎管减压的同时也带来了术后椎体不稳等问题.脊柱的不稳意味着在正常载荷下易出现异常活动和位移.脊柱不稳目前尚无明确的定义,作者认为这一概念应主要包括以下两方面的内容,生物力学方面:创伤、感染、肿瘤、退行性变等多种原因导致的脊柱运动节段的刚度下降、活动度增加,相同负荷下较正常椎体发生更大的位移;临床表现上,不稳脊柱在正常和(或)过度活动时出现疼痛,存在病理性骨折的风险,可能导致脊髓及神经根的压迫损伤.如果可以早期识别脊柱不稳,预测病理性骨折风险,即时采取固定术,会大大改善脊柱转移瘤患者的生活质量,延长生存期.因此,医生需要对脊柱不稳和将要发生的病理性骨折有着很好的预见性.本文主要对脊柱转移瘤椎体不稳相关研究进行综述.

Tumor cells can secrete various cytokines which can enhance the activity of osteoclast in the bone microenvi?ronment, and osteoclast can promote the release of many growth factors buried in bone matrix which would promote the growth and invasion of tumor cells. Thus, a‘vicious cycle’of bone destruction is developed in the bone metastatic microenvironment. Bone metastatic microenvironment facilitate this‘vicious cycle’, while it also provides potential targets for the treatment of bone metas?tases. Osteoprotegerin, receptor activator of nuclear factor?κB and its ligand system are the typicality of molecular targets. Bone metastasis can promote the secretion of RANKL and the expression of OPG. The disbalance of RANKL/OPG is an important induc?ing factor for bone destruction. Many studies have shown that transforming growth factor?βwhich is produced by osteoclast plays an important role in mediating‘vicious cycle’. Src family tyrosine kinase, endothelin A receptor, matrix metalloproteinase, and ca?thepsin K are the potential targets of bone metastasis. Pharmacologic agents such as denosumab, can inhibit the‘vicious cycle’of bone metastasis. In addition to suppress bone destruction by Pharmacologic agents, they also can produce direct antitumor effect. They can delay the occurrence of skeletal related events, prolong the overall survival, and play an important role in patient ’s quali?ty of life at last. Patients with bone metastasis have already benefited from systemic molecular targeted therapies, and further re?searches would be of great importance in improving patient therapeutically selections and enhancing the effect.