Annals of Thoracic Medicine Official publication of the Saudi Thoracic Society, affiliated to King Saud University
 
Search Ahead of print Current Issue Archives Instructions Subscribe e-Alerts Login 
Home Email this article link Print this article Bookmark this page Decrease font size Default font size Increase font size


 
Table of Contents   
ORIGINAL ARTICLE
Year : 2023  |  Volume : 18  |  Issue : 1  |  Page : 39-44
Application of single-port laparoscopic retrograde gastric mobilization during McKeown esophagectomy for esophageal cancer


Department of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China

Date of Submission29-May-2022
Date of Acceptance05-Nov-2022
Date of Web Publication25-Jan-2023

Correspondence Address:
Dr. Ming-Lian Qiu
Department of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical University, #20 Chazhong Road, Fuzhou 350005, Fujian
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/atm.atm_205_22

Rights and Permissions

   Abstract 


BACKGROUND: As a novel alternative to the conventional minimally invasive esophagectomy (MIE) to treat esophageal cancer, single-port laparoscopic retrograde three-step gastric mobilization (SLRM) for esophageal reconstruction during MIE to treat esophageal cancer was attempted in our department. The aim of the present study was to explore the preliminary clinical outcomes and feasibility of this innovative surgery.
METHODS: From March 2020 to November 2021, patients undergoing SLRM combined with four-port thoracoscopic McKeown esophagectomy for their esophageal cancers were reviewed. Gastric mobilization with abdominal lymph node dissection was performed through SLRM. The clinical characteristics and short-term outcomes were analyzed retrospectively.
RESULTS: A total of 120 patients underwent R0 resection without conversion to open surgery. The mean times needed for the thoracic part, abdominal part, and total operation were 43 ± 6 min, 60 ± 18 min, and 230 ± 20 min, respectively. The numbers of mediastinal and abdominal lymph nodes harvested were 13.2 ± 2.7 and 10.2 ± 2.5, respectively. Postoperative pneumonia was encountered in 10 (8.3%) patients. Anastomotic leakage occurred in 3 (2.5%) cases. Temporary vocal cord paralysis was reported in 20 (16.6%) cases. The mean length of hospital stay was 8.5 ± 4.6 days.
CONCLUSIONS: The SLRM is a technically feasible and safe treatment for patients with esophageal cancer. It can be considered an alternative method for patients, especially for the ones with obesity and gastric distension.


Keywords: Esophageal cancer, McKeown esophagectomy, Retrograde three-step gastric mobilization, Single-port laparoscopic


How to cite this article:
Liu B, Li X, Yu MJ, Xie JB, Liao GL, Qiu ML. Application of single-port laparoscopic retrograde gastric mobilization during McKeown esophagectomy for esophageal cancer. Ann Thorac Med 2023;18:39-44

How to cite this URL:
Liu B, Li X, Yu MJ, Xie JB, Liao GL, Qiu ML. Application of single-port laparoscopic retrograde gastric mobilization during McKeown esophagectomy for esophageal cancer. Ann Thorac Med [serial online] 2023 [cited 2023 Mar 24];18:39-44. Available from: https://www.thoracicmedicine.org/text.asp?2023/18/1/39/368495




Surgery is the mainstay treatment for resectable esophageal cancer. While ensuring the same radical treatment outcomes, minimally invasive esophagectomy (MIE) could significantly limit surgical trauma, reduce the incidence of postoperative complications, and improve the postoperative quality of life.[1] At present, thoracoscopy combined with laparoscopic esophagectomy is routinely performed in most centers. However, the optimal operative position, number of trocars, and layout are still controversial.[2],[3]

Single-port thoracic technology has been applied successfully during lung operations[4],[5] by reducing postoperative pain and improving esthetics. However, few institutions have performed esophagectomy through single-port thoracoscopy, since esophageal mobilization and lymph node dissection are difficult through single-port thoracoscopy, and most esophagectomies have been performed in the thoracic part.[6],[7],[8] Yuan et al.[9] reported the preliminary comparisons between the single-port and four-port esophagectomy approaches. The average surgical time in the single-port group was 30–40 min longer than in the multi-port group. The report performing MIE with a single-incision approach using thoracoscopic and laparoscopic procedures simultaneously is even rarer.[10] To reduce the difficulty of surgery, they[11],[12] often make one more auxiliary port outside the abdominal cavity in the single-port laparoscopic procedure.

Thus, since March 2020, our center has innovatively adopted a pure single-port without an auxiliary port to complete abdominal procedures. For the reduction of incisions increases the difficulty of endoscopic operation, the protocol of gastric mobilization is rearranged and we call it retrograde three-step gastric mobilization. Herein, we report our preliminary experience performing single-port laparoscopic retrograde three-step gastric mobilization (SLRM) for esophageal reconstruction during MIE to treat esophageal cancer and describe the procedure details. The results of this study will be helpful to local hospitals that are planning to adopt this procedure.


   Methods Top


Patients data

We retrospectively analyzed the patients with esophageal cancer who received single-port laparoscopy combined with thoracoscopic McKeown esophagectomy from March 2020 to November 2021. The study was approved by the Local Ethics Committee (No.{2021} 300). Preoperative esophagogastroduodenoscopy and pathological examinations confirmed the diagnosis of esophageal squamous cell carcinoma in these patients. All patients received computed tomography (CT) and ultrasound for staging studies. For patients with advanced disease (T3+ or N+), postoperative chemoradiation therapy was followed by surgery 4–6 weeks later. All procedures were performed by the same surgical team.

Surgical procedures

All the surgeries were performed under general anesthesia and a single-lumen endotracheal tube with an enclosed bronchial blocker was inserted. The thoracic part was performed first.

Thoracic procedure – Minimally invasive esophagectomy and mediastinal lymph node dissection

The patient was placed in the left lateral prone position. The thoracic area of the operation was carried out under the left single-lung ventilation (details of the position and the port design are described in our previous report[13]). The esophagus was mobilized from the side of the spine upward to the thoracic inlet and downward to the diaphragmatic hiatus. Then, lymph nodes and soft tissues of the recurrent laryngeal nerve (RLN) were dissected with the esophagus and trachea being pressed anteriorly using a special trachea retractor, lymph node dissection was conducted along the left RLN up to the thoracic inlet. The remaining mediastinal lymph nodes in the tracheobronchial region and the upper, middle, and lower paraesophageal regions were dissected. Finally, the whole thoracic part of the esophagus was mobilized. A 22-French thoracic tube was inserted into the 6th costal cavity, and an Abel drainage tube was inserted into the 8th costal cavity and clamped.

Abdominal procedure – Single-port laparoscopic retrograde three-step gastric mobilization

After the patient was placed in the supine position, a 3–4 cm vertical incision [Figure 1]a was made in the middle between the umbilicus and the xiphoid process. Next, a single-port incision protector (Hangzhou Kangji Medical Devices Co, Ltd, disposable casing puncture, kit BA, Hangzhou, China) was placed, through which two or three surgical instruments and a standard 10-mm 30° laparoscope were inserted. Laparoscope was at the 6 o'clock position; chief ports were at the 9 and 12 o'clock positions, respectively. The assistant port was introduced at the 3 o'clock position [Figure 1]b and [Figure 1]c. CO2 was insufflated at 13 mm Hg. To expose the surgical field by the gravity retractions from the body weight, the patient's position was changed frequently from the Trendelenburg to the reverse Trendelenburg position and by tilting from the right to the left side. The lymph nodes were dissected, and the stomach was mobilized during the SLRM [Figure 2].
Figure 1: The single-port protector and incision. (a and b) Single-port device and laparoscopic instruments placement in the single-port incision, (c) Single-port abdominal incision after surgical suture

Click here to view
Figure 2: The operating direction schematic diagram of SLRM. SLRM: Single-port laparoscopic retrograde three-step gastric mobilization

Click here to view


In brief, first, the hepatogastric ligament was dissected to the esophageal hiatus. The left liver lobe was retracted by a modified combined suture technique using 2–0 polypropylene stitches on a straight needle (Prolene®; Ethicon, Somerville, NJ, USA) and 5-mm hemoclips (Weck®; Teleflex, Morrisville, NC, USA) with a self-retaining fixing stitch passed through the diaphragmatic hiatus and tightened extracorporeally [Figure 3]a. The lymph nodes at lesser curvature, left gastric artery, celiac trifurcation, and the hiatus were dissected during mobilization of the stomach. The left gastric vessels were then dissected [Figure 3]b. Second, the esophageal hiatus and the abdominal esophagus were dissociated [Figure 3]c and [Figure 3]d. The cardia was cutoff using a 60-mm linear stapler (Endo GIA 60 mm–3.5 mm, Covidien, Mansfield, MA, USA). Finally, the cardia was pulled down by the assistant. The gastric fundus and greater curvature were mobilized by dividing the short gastric vessels and gastrosplenic ligament, preserving the right gastric and gastroepiploic artery [Figure 3]e and [Figure 3]f. The mobilization continued toward the left colon. The pylorus and duodenum were released. The lymph nodes at the greater curvature were dissected. During this step, a part of the pedicled omentum from the mid-to-upper third of the greater curvature was kept intact to wrap around the esophagogastric anastomosis [Figure 4]a. After the stomach was pulled out through the abdominal incision, a 3–4-cm diameter gastric conduit was constructed using 60-mm linear staplers. The gastric conduit was pulled in a plastic protective sleeve and put back into the abdominal cavity [Figure 4]b.
Figure 3: The abdominal process of surgery. (a) The left liver lobe was retracted. (b) The lymph nodes at lesser curvature and the left gastric artery were dissected. (c and d) The cardia was cutoff. (e and f) The gastric fundus and greater curvature were mobilized

Click here to view
Figure 4: A 3–4 cm gastric conduit was constructed and pulled in a plastic protective sleeve. (a) The yellow arrow indicates pedicled omentum. (b) The yellow arrow indicates a plastic protective sleeve. (c) The tubular stomach with pedicled fat of gastroomentum was pulled to the neck, the colored arrows indicate the following: black, esophagus, blue, stomach, yellow, pedicled omentum. (d) the anastomosis was embedded with fat pad

Click here to view


Cervical procedure

An approximate 4-cm incision was made along the anterior border of the left sternocleidomastoid muscle. The gastric conduit was pulled up to the left neck through the posterior mediastinum. During this process, the gastric conduit was protected by a plastic bag, and the pulling was facilitated by laparoscopic manipulations.

A side-to-side anastomosis of esophagogastric anastomosis was performed by the linear stapler. After being reinforced by interrupted 5–0 silk sutures, the anastomotic area was encircled by the pedicled fat [Figure 4]c and [Figure 4]d, and a closed suction drain was placed in the anastomotic region. 12-French and 14-French nasogastric tubes were inserted into the gastric conduit for decompression and duodenum for nutrition, respectively. An abdominal drain tube was not placed.

Statistical analysis

The continuous data were by the mean and standard deviation. All the analyses were performed using SPSS software, version 21.0 (SPSS, Inc., Chicago, IL, USA).


   Results Top


A total of 120 patients (88 males and 32 females) were included in the present study. The median age was 64 ± 2.3 years. The clinical characteristics of the patients are shown in [Table 1]. None of them required conversion to thoracotomy or laparotomy. There was no additional port placement. No death occurred during surgical and the hospital stays. One patient suffered from abdominal wall bleeding due to an accidental intraoperative puncture by a straight needle. The bleeding was stopped after electrocoagulation. The perioperative outcomes and surgical complications are shown in [Table 2]. The numbers of mediastinal and abdominal lymph nodes harvested were 13.2 ± 2.7 and 10.2 ± 2.5, respectively. The mean time for the entire procedure was 230 ± 20 min, including the thoracic part (60 ± 18 min) and abdominal part (43 ± 6 min). The mean entire blood loss was 65 ± 16 ml, including abdominal blood loss of 15 ± 5 ml. The timing to start to ambulate was on the 2nd–3rd day after the surgery. The thoracic and cervical drainage tubes were removed on an average of 2 days after the operation. The thoracic Abel drainage tube was removed about 5 days after the operation. Postoperative pneumonia occurred in 10 (8.3%) patients, which was successfully treated by antibiotics. Anastomotic leakages were reported in 3 (2.5%) patients, which were recovered by fully draining the neck incision and wet dressing. Temporary vocal cord paralysis occurred in 20 (16.6%) patients, which recovered within 6 weeks. No anastomotic stenosis was recorded in this study. All the patients were discharged after they tolerated the semifluid diet. The mean postoperative hospital stay was 8.5 ± 4.6 days.
Table 1: Baseline characteristics of patients

Click here to view
Table 2: Operative and postoperative outcomes of patients

Click here to view


Detailed outcomes were reviewed in these patients at a mean follow-up duration of 13 months (range, 3–20) by hospital visits or telephone. No tumor recurrence occurred, and none of the patients had dysphagia. None of the patients died during the follow-up period.


   Discussion Top


Since Cuschieri et al.[14] first reported thoracoscopic esophagectomy in 1992, laparothoracoscopic esophagectomy has been routinely performed to treat patients with esophageal cancer.[15] However, due to the narrow operating space, lacking of triangular vision of traditional endoscopy, difficult cooperation between the master and assistant, and studies[16],[17],[18] on the single-port laparoscopic esophagectomy are still extremely limited. Moreover, the surgical approach of SLRM has hardly been mentioned before. In the present study, we sought to evaluate the effectiveness and feasibility of the novel procedure and shared our experience.

In 2020, the SLRM was developed in our center. All the patients underwent the McKeown procedure. This study focuses on the abdominal step, operative advantages, and perioperative complications. The procedure can be summarized into three steps: (1) retraction, which includes liver lobe retraction, the lesser curvature mobilization, left gastric vessel dissection, and lymph node dissection; (2) dissection, which involves the dissection of the cardioesophageal junction. In patients with a tumor at the lower location, we should cutoff the lower esophagus in the thoracic cavity; and (3) mobilization, which includes mobilization of the gastric fundus and the hilum of the spleen, along with lymph node dissection of the greater curvature.

The SLRM has the following obvious advantages. First, compared with the traditional five-port laparoscope, the single-port laparoscope reduced the number of abdominal incisions to one. The nerve and muscle compressions caused by the instrument operation were also limited to a 3-cm incision, which suggests less trauma, less postoperative stress and pain, and better cosmetic effects.

Second, we optimized the surgical procedure. Conventional laparoscopic gastric mobilization starts from the greater curvature. The space is limited by the upper diaphragm. The risk of bleeding from the spleen is high, especially in patients with obesity or bloat. However, the SLRM mobilized the gastric tissue reversely from the lesser curvature to the gastric fundus and the greater curvature. The omental adipose tissue on the greater curvature can be avoided, and the operation is not affected even if bloating and the gastrosplenic ligament are exposed clearly. The operation of the upper pole of the spleen, such as cutting off the gastrosplenic ligaments and short gastric vessels, is unimpeded.

Third, when the gastric conduit is constructed and placed back into the abdominal cavity, it is easier to reestablish the pneumoperitoneum with the single-port operation. The gastric conduit can be pulled up through the mediastinum under laparoscopic surveillance. In contrast, the reestablishment of traditional laparoscopic pneumoperitoneum is slightly troublesome.

Meanwhile, we have several considerations to share about this novel technique. (1) Our approach benefits from the use of a multichannel single-port incision protector which contains four moderately sized ports and they are flexible and interchangeable. The base is locked in the abdominal wall. The upper part can be disassembled and assembled freely. (2) The skilled implementation of single-port abdominal surgery also requires a period of training and experience. After the surgical procedure was standardized, the laparoscopic time was reduced to 40 min, whereas the time is about 60 min in the multi-port laparoscopic procedure.[13] (3) Some surgical techniques are worth special attention. The first one is the site of the incision. The most appropriate location for a 3-cm long incision is in the middle between the umbilicus and the xiphoid process. If the incision location is too low, the vision well be remote, and the operating instruments can interfere with each other frequently. If the incision location is too high, retracting the liver lobe will be difficult, which can obstruct the surgical field. The second important technique is the retraction process of the left liver lobe. Lakdawala et al.[19] routinely used a grasping forceps to elevate the left lobe. Huang et al.[20] recommended inserting needles into the edge of the liver for retraction. We used a 2–0 prolene needle and thread to enter from the left margin of the costal arch, then removed the needle through the abdominal wall on the left of the falciform ligament. The left liver lobe was then retracted and fixed at the hiatus, which offered a better exposure to the lesser curvature and the cardia. (4) The other important part is the skill of the laparoscope holder. The laparoscope should be placed at the lower pole of the incision and pressed down as far as possible. Other surgical instruments should be kept parallel and leveled up without crossing. A small field of vision aperture can enlarge the overall field of vision and reduce the limitation of a narrow surgical space.

In our series, the average number of harvested abdominal lymph nodes was about 10.2, which is similar to previous meta-analyses.[21],[22] In terms of intraoperative complications, only one patient with an abdominal wall bled from an accidental puncture by the needle. For postoperative complications, the reports of McKeown MIE from Japan indicate that the median incidences of pneumonia, anastomotic leakage, and RLN palsy were 12.0%, 7.2%, and 19.8%, respectively[23] and our result were 8.3%, 2.5%, and 16.8%, respectively, which were lower.

We note that this is just our personal opinion, and currently there is no sufficient data to compare SLRM with traditional laparoscopic surgery; therefore, a single-center randomized controlled study about the comparison is being conducted at our institution and has been registered at the Clinical Trials Registry (No. ChiCTR 2100043730). We look forward to further results.


   Conclusion Top


The preliminary results demonstrate that the SLRM is a technically feasible and safe procedure with the optimal operating process and a single incision. The SLRM can be considered an alternative method for patients with esophageal cancer, especially the ones with obesity and gastric distension. However, it is still in the exploratory stage and requires more investigation.

Financial support and sponsorship

This study was funded by the Natural Science Foundation of Fujian Province, China (Grant numbers 2020J01953), Scientific Research Project from the Education Department of Fujian Province, China (Grant numbers JAT190212).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Straatman J, van der Wielen N, Cuesta MA, Daams F, Roig Garcia J, Bonavina L, et al. Minimally invasive versus open esophageal resection: Three-year follow-up of the previously reported randomized controlled trial: The time trial. Ann Surg 2017;266:232-6.  Back to cited text no. 1
    
2.
Li NL, Peng WL, Liu CC, Shih CH. Comparison of the short-term postoperative results of prone positioning and lateral decubitus positioning during thoracoscopic esophagectomy. Wideochir Inne Tech Maloinwazyjne 2015;10:37-43.  Back to cited text no. 2
    
3.
Kawasaki K, Oshikiri T, Kanaji S, Nakayama S, Kominami H, Tanaka K, et al. Thoracoscopic esophagectomy in prone position: Advantages of five ports over four ports. Hepatogastroenterology 2015;62:69-72.  Back to cited text no. 3
    
4.
Ji C, Xiang Y, Pagliarulo V, Lee J, Sihoe AD, Kim H, et al. A multi-center retrospective study of single-port versus multi-port video-assisted thoracoscopic lobectomy and anatomic segmentectomy. J Thorac Dis 2017;9:3711-8.  Back to cited text no. 4
    
5.
Wang Y, Wang Z, Yao F. The safety and feasibility of three-dimension single-port video-assisted thoracoscopic surgery for the treatment of early-stage lung cancer. J Thorac Dis 2020;12:7257-65.  Back to cited text no. 5
    
6.
Caronia FP, Arrigo E, Failla AV, Sgalambro F, Giannone G, Lo Monte AI, et al. Uniportal thoracoscopy combined with laparoscopy as minimally invasive treatment of esophageal cancer. J Thorac Dis 2018;10:E265-9.  Back to cited text no. 6
    
7.
Wang Q, Ping W, Cai Y, Fu S, Fu X, Zhang N. Modified McKeown procedure with uniportal thoracoscope for upper or middle esophageal cancer: Initial experience and preliminary results. J Thorac Dis 2019;11:4501-6.  Back to cited text no. 7
    
8.
Hu W, Yuan Y, Chen L. Single-port thoracoscopic minimally invasive esophagectomy for esophageal cancer. World J Surg 2019;43:567-70.  Back to cited text no. 8
    
9.
Liu B, Li X, Yu MJ, Xie JB, Liao GL, Qiu ML. Utility of single-port laparoscopic retrograde gastric mobilization during McKeown esophagectomy for esophageal cancer: A2-year experience with 120 cases in a single institution. J Thorac Dis 2022;14:3983-91.  Back to cited text no. 9
    
10.
Lee JM, Chen SC, Yang SM, Tseng YF, Yang PW, Huang PM. Comparison of single and multi-incision Minimally Invasive Esophagectomy (MIE) for treating esophageal cancer: A propensity-matched study. Surg Endosc 2017;31:2925-31.  Back to cited text no. 10
    
11.
Xin N, Wei R, Huang K, Chen Z, Liu C, Fang Y, et al. Comparative study on short-term efficacy of single incision plus one (SI+1) port and multiportal 3D laparoscopic Minimally Invasive Esophagectomy. J Gastrointest Oncol 2021;12:1277-84.  Back to cited text no. 11
    
12.
Guo W, Ma L, Zhang Y, Ma X, Yang S, Zhu X, et al. Totally minimally invasive Ivor-Lewis esophagectomy with single-utility incision video-assisted thoracoscopic surgery for treatment of mid-lower esophageal cancer. Dis Esophagus 2016;29:139-45.  Back to cited text no. 12
    
13.
Li X, Lai FC, Qiu ML, Luo RG, Lin JB, Liao B. Minimally Invasive Esophagectomy in the Lateral-prone position: Experience of 226 cases. Surg Laparosc Endosc Percutan Tech 2016;26:60-5.  Back to cited text no. 13
    
14.
Cuschieri A, Shimi S, Banting S. Endoscopic oesophagectomy through a right thoracoscopic approach. J R Coll Surg Edinb 1992;37:7-11.  Back to cited text no. 14
    
15.
Bao T, Wang YJ, Li KK, Liu XH, Guo W. Short- and long-term outcomes of prophylactic thoracic duct ligation during thoracoscopic-laparoscopic McKeown esophagectomy for cancer: A propensity score matching analysis. Surg Endosc 2020;34:5023-9.  Back to cited text no. 15
    
16.
Huang YH, Chen KC, Lin SH, Huang PM, Yang PW, Lee JM. Robotic-assisted single-incision gastric mobilization for minimally invasive oesophagectomy for oesophageal cancer: Preliminary results. Eur J Cardiothorac Surg 2020;58:i65-9.  Back to cited text no. 16
    
17.
Omar MA, Redwan AA, Mahmoud AG. Single-incision versus 3-port laparoscopic cholecystectomy in symptomatic gallstones: A prospective randomized study. Surgery 2017;162:96-103.  Back to cited text no. 17
    
18.
Evers L, Bouvy N, Branje D, Peeters A. Single-incision laparoscopic cholecystectomy versus conventional four-port laparoscopic cholecystectomy: A systematic review and meta-analysis. Surg Endosc 2017;31:3437-48.  Back to cited text no. 18
    
19.
Lakdawala M, Agarwal A, Dhar S, Dhulla N, Remedios C, Bhasker AG. Single-incision sleeve gastrectomy versus laparoscopic sleeve gastrectomy. A 2-year comparative analysis of 600 patients. Obes Surg 2015;25:607-14.  Back to cited text no. 19
    
20.
Huang CK, Tsai JC, Lo CH, Houng JY, Chen YS, Chi SC, et al. Preliminary surgical results of single-incision transumbilical laparoscopic bariatric surgery. Obes Surg 2011;21:391-6.  Back to cited text no. 20
    
21.
Wang J, Hu J, Zhu D, Wang K, Gao C, Shan T, et al. McKeown or Ivor Lewis minimally invasive esophagectomy: A systematic review and meta-analysis. Transl Cancer Res 2020;9:1518-27.  Back to cited text no. 21
    
22.
Guo W, Ma X, Yang S, Zhu X, Qin W, Xiang J, et al. Combined thoracoscopic-laparoscopic esophagectomy versus open esophagectomy: A meta-analysis of outcomes. Surg Endosc 2016;30:3873-81.  Back to cited text no. 22
    
23.
Ozawa S, Koyanagi K, Ninomiya Y, Yatabe K, Higuchi T. Postoperative complications of minimally invasive esophagectomy for esophageal cancer. Ann Gastroenterol Surg 2020;4:126-34.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (2,528 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Methods
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed425    
    Printed20    
    Emailed0    
    PDF Downloaded66    
    Comments [Add]    

Recommend this journal