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Video-Assisted Thoracoscopic Surgery and Minimal Access Spinal Surgery Compared in Anterior Thoracic or Thoracolumbar Junctional Spinal Reconstruction: A Case-Control Study and Review of the Literature.

1. Introduction

Video-assisted thoracoscopic surgery (VATS) and minimal access spinal surgery (MASS) have been considered primarily as minimally invasive surgery (MIS) for anterior thoracic (T) and thoracolumbar junction (TLJ) spine surgery [1]. VATS was first described by Mack et al. in 1993 [2]; it allows for biopsy, anterior release, abscess drainage, and discectomy [3, 4]. VATS has been used to treat anterior thoracic diseases at our hospital since 1995. Over the next 10 years, we used VATS in many spinal procedures: decompression, corpectomy, reconstruction, and stabilization. The microsurgical miniopen anterolateral approach was first introduced in 1997 by Mayer [5] for minimally invasive anterior lumbar interbody fusion. Kossmann et al. [6] reported in 2001 that the anterior column of the thoracic spine could easily be assessed and reconstructed using a minithoracotomy and a table-mounted retractor. At that time, we developed a new VATS approach [7-10], which we called the "extended manipulating channel method." It allowed us to use a combination of conventional spinal instruments and VATS to enter the chest cavity and to manipulate those instruments as we would for standard open surgical procedures. Furthermore, at our hospital, a refined MASS has been evolving since 2000 from our extended manipulating channel method without VATS [11, 12]. MASS has been used to treat vertebral metastasis, osteomyelitis, and fractures. It is generally believed that because MASS allows direct three-dimensional vision of the surgical field, which seems to make the procedure familiar to spine surgeons used to standard open surgical procedures, it has become more popular than VATS. Thus, we compared the outcomes of MASS in anterior T and TLJ spinal reconstruction and fusion with those of VATS.

2. Patients and Methods

2.1. Patients. We identified, in our hospital's Spine Operation Registry, all patients who underwent VATS (Figures 1 and 2) and MASS (Figure 3). We previously published reports which described both VATS [7, 8, 10, 13] and MASS [12, 14] techniques for anterior T or TLJ spinal reconstruction between 1995 and 2012 and retrospectively reviewed their records. The inclusion criteria were anterior intervertebral fusion after a discectomy with a partial or a total corpectomy for treating spinal fractures, vertebral malignancy, infectious spondylitis, thoracic disc herniation, and degenerative spinal diseases. Patients with pediatric scoliosis, a discectomy without fusion, or a biopsy were excluded from the study. All included patients had undergone minimally invasive anterior spine reconstruction performed by one senior surgeon (T. J. Huang). We reviewed the patients' medical records and recorded data on operating time, estimated blood loss, need for intensive care, conversion to standard open thoracotomy, and complications in patients with T and TLJ spinal disorders. Approval for this study was obtained from the Ethics Committee and Institutional Review Board of our hospital (IRB number 101-1238B).

2.2. Review of Published Literature. The English language literature published between 1995 and 2012 was systematically reviewed. The Cochrane Review Database, EMBASE, Medline, PubMed, and Google Scholar were searched. The reference lists of the selected articles were checked. Search terminology included miniopen, MASS, VATS, anterior T spinal surgery, TLJ (T11-L2) spinal surgery, and anterior spinal fusion. We excluded studies associated with pediatric spine surgery, disc excision without fusion, and anterior lumbar surgery (L3-L5). Technical notes, case reports, anatomical descriptions, or a combined surgery of thoracoscopic surgery and thoracotomy was not included. The articles were screened and selected by two independent reviewers (Y. Y. Li and C. C. Cheng) based on the inclusion and exclusion criteria. Disagreements were resolved by discussion or by a consultation with a third reviewer (Ching-Yu Lee). The data of the selected articles were extracted and analyzed in detail by two independent reviewers (M. H. Wu and Chien-Yin Lee). Because data on the surgical complications were going to be analyzed, the interrater agreement about these data was analyzed using the kappa statistic. Disagreements were resolved by discussion or by a consultation with a senior spine surgeon (T. J. Huang).

2.3. Data Analysis. The perioperative parameters of our included sample were operating time, estimated blood loss, complications, conversion to standard thoracotomy, and the need for postoperative admission to the intensive care unit. They were recorded and compared between our VATS and MASS patients. The perioperative data of the selected articles were average operating time, average estimated blood loss, complication rates, and conversions to thoracotomy.

Data of clinical complications and conversions to standard thoracotomy, which were recorded from our cases and the selected articles, were compared between VATS and MASS patients. A minor complication was defined as a minor risk event with no treatment, with medical treatment, or with intraoperative repair but without long-term sequelae. A major complication was defined as a life-threatening or irreversible event requiring invasive treatment or revision surgery. Death was mortality because of associated perioperative complications.

An approach-related complication was defined as intercostal neuralgia, pleural effusion, or air leakage causing subcutaneous emphysema or pneumothorax [15, 16].

3. Statistical Methods

All statistical analyses were done using SPSS 12.0 for Windows. An independent Student f-test was used for numerical data. An analysis or a Fisher exact test was used for categorical data. Significance was set at p < 0.05. The observed interrater agreement for the data extracted from the selected publications was analyzed using the kappa statistic.

4. Results

We reviewed the medical records of 187 patients who had undergone minimally invasive surgery (MIS) for anterior T or TLJ spinal fusion at our hospital between 1995 and 2012. VATS was used in 111 patients, and MASS was used in the other 76 patients (Table 1). Operating time was longer in the VATS group than in the MASS group (p < 0.001). There was a significantly higher incidence of conversion to standard open thoracotomy in the VATS group than in the MASS group (p = 0.022). There were no significant differences in average blood loss or the need for postoperative admission to the intensive care unit (ICU).

5. Literature-Reported Results

There were 16 articles about MIS for anterior T/TLJ spinal fusion (Table 2): 6 VATS articles [17-22] and 10 MASS articles [6,23-31]. Of the 6 VATS articles, the median average operating time was 223 minutes (range: 155-347 minutes), the median average estimated blood loss was 585 mL (range: 310-1117 mL), the median complication rate was 25.9% (range: 9.4-34%), and the median conversion rate was 0.5% (range: 0-6.2%). Of the 10 MASS articles, the median average operating time was 170 minutes (range: 101-210 minutes), the median average estimated blood loss was 423 mL (range: 290-912 mL), the median complication rate was 14.9% (range: 0-33%), and there were no conversions to standard open procedure.

Perioperative complications were collected from 187 patients of our institute and 1024 patients of the 16 selected publications (Table 3). The assessment score agreement between the reviewers was good (kappa statistic: 0.62, p < 0.001). There were 126 (17%) perioperative complications in VATS patients and 71 (15%) in MASS patients (p = 0.317): there was not significantly different distribution of no, minor, and major complication (p = 0.567). Revision surgery was the most common major complication in both groups: 11 VATS patients and 8 MASS patients. There were 6 mortalities in this study, 3 in each cohort of VATS and MASS: 1 with pneumonia, 1 with acute thromboembolism, and 1 with intraoperative arrhythmia and acute cardiac infarction in VATS patients; 1 with pneumonia and 2 with acute thromboembolism in MASS patients. The incidence of approach-related complications was significantly higher in VATS patients than MASS patients (p = 0.011). There was no significant difference in the prevalence of pulmonary infection or iatrogenic cardiovascular injury between both surgical procedures.

The overall conversion rate from MIS to standard thoracotomy in VATS patients was 2% (n = 15) and 0% in MASS patients (p = 0.001) (Table 4). The most common cause for unplanned conversion to standard open thoracotomy was severe intrathoracic adhesion (40%), followed by iatrogenic cardiovascular injury (20%) and excessive uncontrollable bleeding from cancellous bone or soft tissue (20%).

6. Discussion

VATS and MASS are well-known MIS methods for anterior spinal surgeries [1]. It is generally believed that using VATS for spinal surgery entails a learning curve more difficult to negotiate than does using MASS [19]; however, few studies focus on analyzing the advantages and disadvantages of using VATS and MASS to treat anterior spinal disorders. In this study, VATS required longer operating time and a higher incidence of conversion to standard open thoracotomy than did MASS at our hospital. Similarly, our review of the VATS and MASS literature for anterior T and TLJ spinal reconstruction showed that VATS was more likely to need operating time and to increase blood loss. In addition, Molina et al. [32], in a systematic review of MIS in the management of metastatic spine disease, reported that VATS was associated with longer operating time, a longer length of stay in the hospital, and more blood loss than was MASS. We found that since MASS seems more familiar to most surgeons it yields faster and safer decompression, stabilization, and reconstruction than does VATS.

We found that the overall MIS complication rate for anterior T and TLJ spinal reconstruction in the 1211 patients analyzed in the selected articles and in our hospital was 16.2%: 126 perioperative complications in VATS patients (17%) and 71 complications in MASS patients (15%). VATS and MASS patients had similar minor and major complication rates; however, VATS is more associated with approach-related complications. Consistent with the results of previous case series [3, 16, 19, 33], approach-related complications are most common in patients undergoing VATS. This might be true because trocar placement sometimes injures an intercostal nerve or pleural membrane, which leads to intercostal neuralgia, pleural effusion, pneumothorax, or subcutaneous emphysema [15]. Hence, the first thoracoscopic portal, which is not made using endoscopic visualization, is created using a minithoracotomy to make a 1.5 cm skin incision that precludes blind trocar insertion [16, 34, 35].

Conversion to standard open thoracotomy occurred more frequently in VATS patients than in MASS patients in our hospital and in the selected literature. Consistent with our findings, other studies [35, 36] have reported that VATS is restricted because of severe pleural adhesion, poor tolerance of one-lung ventilation, and difficulty with endoscopic control of bleeding. In addition, the conversion rate from VATS to standard open thoracotomy was 7.2% in our hospital and 1.1% in the selected articles. Metastatic vertebral tumors and infectious spondylitis occurred in most of our VATS patients whereas vertebral fracture and herniation of intervertebral disc were the majority of spinal disorders in VATS patients from the selected articles. Chronic inflammation, infection, and metastatic tumor are well-known causes of intrathoracic adhesion [37], which might explain the relatively higher incidence of conversion to open thoracotomy in our VATS patients than in the patients in the reviewed literature. Severe pleural adhesion encountered in metastatic chronically infected diseases of the thoracic spine, but thoracoscopic adhesiolysis is a technically demanding procedure that must be done by an expert thoracic surgeon. Besides, intraoperative bleeding was more directly and easily controlled using cauterization, hemoclips, or suture ligation in MASS. Therefore, MASS is a reasonable MIS method for treating anterior T and TLJ spinal reconstruction and fusion, especially for metastatic and infectious spinal diseases.

This study has some limitations. First, this is a retrospective study. To minimize the statistical bias, we included patients who had undergone MIS spinal surgery done by the same surgeon (T. J. Huang) at our hospital. Second, the evidence level of the systemic review in this study is low. This is because there is still a paucity of reports that a meta-analysis needs, those that show comparative data of VATS and MASS for treating anterior spinal diseases. Additional comparative VATS and MASS studies that focus on treating anterior spinal diseases are required.

In conclusion, VATS and MASS are effective MIS methods for treating anterior T and TLJ spinal reconstruction, and they have equivalent complication rates. MASS requires less operating time and has fewer approach-related complications. VATS is more likely to have a higher conversion rate from MIS to standard open thoracotomy when severe pleural adhesion and difficulty in endoscopically controlling bleeding are encountered.

http://dx.doi.org/10.1155/2016/6808507

Competing Interests

All authors declare that they have no conflict of interests regarding the publication of this paper.

Acknowledgments

The authors thank Chia-Hao Chang, Ph.D., who is specialized in statistics, for statistical assistance. The authors also thank the Research Committee of Chang Gung Memorial Hospital, Taiwan, for assistance (no. CMRPG6F0131) in the Spine Operation Registry.

References

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Ching-Yu Lee, (1, 2, 3) Meng-Huang Wu, (3, 4, 5) Yen-Yao Li, (1, 2) Chin-Chang Cheng, (1, 2, 3) Chien-Yin Lee, (1) and Tsung-Jen Huang (4, 5)

(1) Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan

(2) College of Medicine, Chang Gung University, Taoyuan, Taiwan

(3) Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

(4) Department of Orthopedic Surgery, Taipei Medical University Hospital, Taipei, Taiwan

(5) Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Correspondence should be addressed to Tsung-Jen Huang; tjdhuang@tmu.edu.tw

Received 31 July 2016; Revised 16 November 2016; Accepted 1 December 2016

Academic Editor: Wiliam B. Rodgers

Caption: Figure 1: Video-assisted thoracoscopic surgery (VATS) for treating tuberculous spondylitis of T7-8 in a 74- year-old woman. (a) and (b) Vertebral destruction and collapse in T8. (c) and (d) Gadolinium-enhanced magnetic resonance imaging (MRI) shows osteomyelitis in T7-8 vertebral bodies and anterior epidural abscess spreading under the anterior longitudinal ligament. (e) The incisional wound was 2.5-3.0 cm long to allow a three-portal video-assisted thoracoscopic debridement, curettage, and harvested tricortical iliac strut bone graft for anterior spinal reconstruction on T7-8. (f) and (g) Solid bone fusion was noticed on T7-8 at the 2-year follow-up.

Caption: Figure 2: Video-assisted thoracoscopic surgery (VATS) spinal approach to tuberculous spondylitis of T7-8. (a) and (b) The lesion site was identified using fluoroscopy and was displayed on the video monitor. The lesion site was initially covered with the visceral pleura because of inflammation. (c) The infected vertebral body and soft tissue were removed using pituitary rongeurs and elongated curettes. (d) Column reconstruction with intervertebral fusion was initiated using an autogenous tricortical iliac strut graft (white arrow).

Caption: Figure 3: Anterior minimal access spinal surgery for treating thoracic disc herniation of T11-12 in a 41-year- old woman. (a) and (b) Narrowing disc space with endplate sclerosis on T11-12 level was noticed. (c) and (d) Magnetic resonance imaging (MRI) shows left paracentral disc herniation on T11-12 level. (e) A 7 cm skin incision in the patient's left lateral thoracic cage. (f) and (g) Anterior retropleural and retroperitoneal approach for thoracic discectomy and fusion was performed using a double-barreled rib strut graft and anterior vertebral instrumentation. No intraoperative one-lung ventilation, a postoperative chest tube, or ICU care was given. Solid bone fusion on T11-12 was noticed at the 2-year follow-up.
Table 1: MIS for anterior T and TLJ spinal reconstruction in 187
patients at our Institution.

                                               VATS

Number of patients                             111
Male/female                                   68/43
Mean age (year)                         57.1 [+ or -] 14.5
Number of pathologic regions
T                                            59 (53)
TLJ                                          52 (47)
Number of pathologic types
Fracture                                     25 (23)
Infectious spondylitis                       31 (28)
Spinal malignancy                            49 (44)
Disc herniation or degeneration                6(5)
Perioperative data
Operating time (#) (mins)               224.5 [+ or -] 68.6
Estimated blood loss (#) (ml)           916.0 [+ or -] 660.3
Conversion to standard thoracotomy             8(7)
Need for postoperative ICU care                9(8)

                                               MASS           p value

Number of patients                              76
Male/female                                   39/37            0.177
Mean age (year)                         60.4 [+ or -] 14.8     0.133
Number of pathologic regions                                   0.085
T                                            50 (66)
TLJ                                          26 (34)
Number of pathologic types                                     0.253
Fracture                                      9(12)
Infectious spondylitis                       24 (32)
Spinal malignancy                            36 (47)
Disc herniation or degeneration                7(9)
Perioperative data
Operating time (#) (mins)              183.5 [+ or -] 33.2    <0.001 *
Estimated blood loss (#) (ml)          933.8 [+ or -] 847.6    0.879
Conversion to standard thoracotomy              0             0.022 *
Need for postoperative ICU care               4 (5)            0.565

Data are expressed as mean [+ or -] standard deviation or number (%).
* p < 0.05.

(#) Patients undergoing conversion thoracotomy were not included.

MIS: minimally invasive surgery; VATS: video-assisted thoracoscopic
surgery; MASS: minimal access spinal surgery; T: thoracic; TLJ:
thoracolumbar junction; ICU: intensive care unit.

Table 2: A literature review of MIS for anterior T and TLJ spinal
reconstruction.

Authors            Years   PT no.

Dickman et al.     1996      17
Khoo et al.        2002     371
Kapoor et al.      2005      16
Le Huec et al.     2010      50
Lu et al.          2012      50
Wait et al.        2012     121
Kossmann et al.    2001      58
El Saghir          2002      21
Scheufler          2007      38
Payer and Sottas   2008      37
Smith et al.       2010      52
Uribe et al.       2010      21
Khan et al.        2012      20
Deviren et al.     2011      12
Baaj et al.        2012      80
Uribe et al.       2012      60

Authors                            Study design

Dickman et al.          VATS for reconstruction in T spine
Khoo et al.         VATS in treating T or TL spinal fractures
Kapoor et al.            VATS in treating TB spondylitis
Le Huec et al.           VATS for treating TLJ fractures
Lu et al.            VATS in treating thoracic TB spondylitis
Wait et al.         VATS for discectomy and fusion in T spine
Kossmann et al.    MASS for reconstruction in T/TLJ(58) + L(7)
El Saghir              MASS for reconstruction in TL spine
Scheufler             MASS for reconstruction in T/TLJ spine
Payer and Sottas       MASS for reconstruction in TL spine
Smith et al.              MASS in treating TLJ fractures
Uribe et al.             MASS in treating T spinal tumor
Khan et al.        MASS for reconstruction in T/TLJ(20) + L(4)
Deviren et al.          MASS for reconstruction in T spine
Baaj et al.            MASS for reconstruction in TL spine
Uribe et al.        MASS for discectomy and fusion in T spine

Authors            AOT (min)   ABL (ml)   CR (%)    TCR(%)

Dickman et al.        347        1117      29.4       0
Khoo et al.           240        650        9.7      1.1
Kapoor et al.         223        497       31.2      6.2
Le Huec et al.        155        620       20.0       0
Lu et al.             210        550       34.0       0
Wait et al.           NA         310       22.3      1.7
Kossmann et al.       170        912       7.7%       0
El Saghir             101        724        33%       0
Scheufler             167        652        18%       0
Payer and Sottas      181        632       16.2%      0
Smith et al.          128        300       13.5%      0
Uribe et al.          117        291       4.8%       0
Khan et al.           188        423         0        0
Deviren et al.        210        400       16.7%      0
Baaj et al.           NA          NA       12.5%      0
Uribe et al.          182        290        25%       0

MIS: minimally invasive surgery; T: thoracic; TLJ: thoracolumbar
junction; PT no.: patient number; AOT: average operating time; ABL:
average estimated blood loss; CR: complication rate; TCR:
thoracotomyconversion rate; VATS: video-assisted thoracoscopic
surgery; MASS: minimal access spinal surgery.

Table 3: A summary of perioperative complications in MIS for anterior
T and TLJ spinal surgery.

                                                        VATS (n = 736)
Number of patients
Complications in authors' institute                           27
Complications in review articles                              99
A total number of complications                            126 (17)
No complication                                              610
Minor complication                                           102
Major complication                                            24
Minor complication                                         102 (80)
Pleural effusion, pneumothorax, and intercostal               52
  neuralgia
Superficial wound infection                                   12
Incidental durotomy                                           8
Pulmonary infection s/p medical treatment                     8
Lung atelectasis or poor pulmonary function                   7
Hypesthesia or transient motor dysfunction                    3
Paralytic ileus                                               0
Laceration of lung parenchyma s/p repair                      4
Deep vein thrombosis                                          0
Pharyngeal pain                                               3
Subcutaneous emphysema                                        2
Implant malposition                                           1
Splenic contusion                                             1
Iatrogenic rib fracture                                       1
Urinary tract Infection                                       0
Major complication                                         24 (20)
Revision                                                      11
Graft dislodgment or implant failure or                       7
  pseudoarthrosis
Incomplete decompression (residual disc                       3
  herniation)
Wrong level                                                   1
Dehiscent muscular layers in the flank                        0
Pneumonia with requiring intubation                           4
Iatrogenic cardiovascular injury                              3
Deep wound infection                                          1
Permanent neurogenic deterioration                            1
Postoperative acute myocardial infarction                     1
Death                                                         3
Pneumonia                                                     1
Intraoperative arrhythmia                                     1
Acute thromboembolism                                         1
Specific complications in MIS for anterior T and TLJ
spinal Surgery
Approach-associated complications                             54
Pulmonary infections                                          13
Iatrogenic cardiovascular injury                              3

                                                        MASS (n = 475)
Number of patients
Complications in authors' institute                           11
Complications in review articles                              60
A total number of complications                            71 (15)
No complication                                              404
Minor complication                                            59
Major complication                                            12
Minor complication                                         59 (83)
Pleural effusion, pneumothorax, and intercostal               18
  neuralgia
Superficial wound infection                                   3
Incidental durotomy                                           15
Pulmonary infection s/p medical treatment                     3
Lung atelectasis or poor pulmonary function                   4
Hypesthesia or transient motor dysfunction                    5
Paralytic ileus                                               5
Laceration of lung parenchyma s/p repair                      0
Deep vein thrombosis                                          4
Pharyngeal pain                                               0
Subcutaneous emphysema                                        0
Implant malposition                                           1
Splenic contusion                                             0
Iatrogenic rib fracture                                       0
Urinary tract Infection                                       1
Major complication                                         12 (17)
Revision                                                      8
Graft dislodgment or implant failure or                       5
  pseudoarthrosis
Incomplete decompression (residual disc                       2
  herniation)
Wrong level                                                   0
Dehiscent muscular layers in the flank                        1
Pneumonia with requiring intubation                           0
Iatrogenic cardiovascular injury                              0
Deep wound infection                                          1
Permanent neurogenic deterioration                            0
Postoperative acute myocardial infarction                     0
Death                                                         3
Pneumonia                                                     1
Intraoperative arrhythmia                                     0
Acute thromboembolism                                         2
Specific complications in MIS for anterior T and TLJ
spinal Surgery
Approach-associated complications                             18
Pulmonary infections                                          4
Iatrogenic cardiovascular injury                              0

                                                          P
Number of patients
Complications in authors' institute                     0.263
Complications in review articles
A total number of complications                         0.317
No complication                                         0.567
Minor complication
Major complication
Minor complication                                      0.708
Pleural effusion, pneumothorax, and intercostal
  neuralgia
Superficial wound infection
Incidental durotomy
Pulmonary infection s/p medical treatment
Lung atelectasis or poor pulmonary function
Hypesthesia or transient motor dysfunction
Paralytic ileus
Laceration of lung parenchyma s/p repair
Deep vein thrombosis
Pharyngeal pain
Subcutaneous emphysema
Implant malposition
Splenic contusion
Iatrogenic rib fracture
Urinary tract Infection
Major complication
Revision
Graft dislodgment or implant failure or
  pseudoarthrosis
Incomplete decompression (residual disc
  herniation)
Wrong level
Dehiscent muscular layers in the flank
Pneumonia with requiring intubation
Iatrogenic cardiovascular injury
Deep wound infection
Permanent neurogenic deterioration
Postoperative acute myocardial infarction
Death
Pneumonia
Intraoperative arrhythmia
Acute thromboembolism
Specific complications in MIS for anterior T and TLJ
spinal Surgery
Approach-associated complications                       0.011 *
Pulmonary infections                                    0.218
Iatrogenic cardiovascular injury                        0.284

Data are expressed as mean [+ or -] standard deviation or number (%).
* p < 0.05.

MIS: minimally invasive surgery; VATS: video-assisted thoracoscopic
surgery; MASS: minimal access spinal surgery; T: thoracic; TLJ:
thoracolumbar junction.

Table 4: Causes of conversion thoracotomy in MIS for anterior spinal
surgery.

                                           VATS (n = 736)

Conversion to standard open procedure          15 (2)
  Severe intrathoracic adhesion                  6
  Iatrogenic cardiovascular injury               3
  Excessive uncontrollable bleeding              3
  Poor tolerance of one-lung ventilation         2
  Extremely narrow intercostal space             1

                                           MASS (n = 475)    P

Conversion to standard open procedure            0         0.001 *
  Severe intrathoracic adhesion                  0
  Iatrogenic cardiovascular injury               0
  Excessive uncontrollable bleeding              0
  Poor tolerance of one-lung ventilation         0
  Extremely narrow intercostal space             0

Data are expressed as mean [+ or -] standard deviation or number (%).
* p < 0.05.

MIS: minimally invasive surgery; VATS: video-assisted thoracoscopic
surgery; MASS:minimal access spinal surgery.
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Title Annotation:Clinical Study
Author:Lee, Ching-Yu; Wu, Meng-Huang; Li, Yen-Yao; Cheng, Chin-Chang; Lee, Chien-Yin; Huang, Tsung-Jen
Publication:BioMed Research International
Article Type:Report
Date:Jan 1, 2017
Words:5061
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