Comparison of LigaSure to Conventional Electrocoagulation in Video-assisted Thoracoscopic Surgery Lobectomy
Condition: Lung Cancer; Complication of Surgical Procedure
Study type: Interventional

Summary: 
      Surgical treatment of lung cancer consists of two elements: anatomical lung resection
      (segmentectomy, lobectomy or pneumonectomy) followed by mediastinal lymph node dissection
      (MLND). Since over last 15 years the growing rate of resection is performed by minimal
      invasive approach - video-assisted thoracoscopic surgery (VATS). The study is focused on the
      clinical and technical aspects of MLND during VATS lobectomy. The extension of lymph nodes
      resection is strictly specified. The main benefit of MLND for the patient is precise
      histopathological staging, which allows choosing the best therapeutic option of adjuvant
      therapy. MLND is related with potential minor and major complications (bleeding, increased
      volume of chest tube drainage, prolonged chest tube duration and hospital stay, chylothorax,
      left recurrent laryngeal nerve injury, injury of the bronchus, injury of the esophagus). The
      majority of complications are caused by thermal injury resulting from the use of
      heat-generating monopolar electrocautery that is commonly used during lymph nodes dissection.
      In addition, thermal energy generation in case of monopolar electrocautery may lead to
      systemic inflammatory response and increased surgical injury. High-energy sealing devices
      like LigaSure™ allow for dissection, coagulation and cutting with the single instrument.
      Compared to mechanical ligation techniques (vessel loops, clips) or monopolar electrocautery,
      LigaSure™ technology has been shown to reduce: intraoperative blood loss (in colorectal,
      gynecologic and urologic surgery), surgery time (in colorectal, gynecologic and urologic
      surgery), length of hospital stay (in gynecologic and urologic surgery). Investigators
      hypothesize that application of LigaSure™ in VATS anatomical resection may lead to diminished
      complications rate, lower systemic inflammatory response and shorter length of stay compared
      to monopolar electrocautery.
    

Detailed description: 
      Summary

      Surgical treatment of lung cancer consists of two elements: anatomical lung resection
      (segmentectomy, lobectomy or pneumonectomy) followed by mediastinal lymph node sampling
      (MLNS) or mediastinal lymph node dissection (MLND). Since over last 15 years the growing rate
      of resection is performed by minimal invasive approach - video-assisted thoracoscopic surgery
      (VATS). This technique is used in at least 60% of patients with lung cancer operated on in
      the leading centers. The study project is focused on the clinical and technical aspects of
      MLNS/MLND during VATS lobectomy. Lymphadenectomy has to be performed obligatory in case of
      lung cancer resection. The extension of lymph nodes resection or sampling is strictly
      specified and should be the same independently from the surgical approach (thoracotomy or
      VATS). The main benefit of MLNS/MLND for the patient is precise histopathological staging,
      which allows choosing the best therapeutic option of adjuvant therapy. It was proved that
      MLND is superior to MLNS in its accuracy however the improvement of local control of the
      disease is not proved.

      Mediastinal lymphadenectomy is related with potential minor and major complications. The risk
      of complications is low but in case of their occurrence hospital stay is usually
      significantly prolonged, quality of life decreases and additional surgery may be needed. In
      very small group of patients complications may lead to severe disability or death.

      The most frequent complications related with MLND are:

        1. Bleeding, sometimes requiring redo surgery;

        2. Increased volume of chest tube drainage with prolonged chest tube duration and hospital
           stay;

        3. Chylothorax;

        4. Left recurrent laryngeal nerve injury;

        5. Injury of the bronchus (especially of posterior part of right main bronchus during
           dissection of subcarinal lymph nodes);

        6. Injury of the esophagus (dissection of subcarinal and paraesophageal lymph nodes).

      The majority of the above mentioned complications are caused by thermal injury resulting from
      the use of heat-generating monopolar electrocautery that is commonly used during lymph nodes
      dissection. Bleeding or chylothorax are usually caused by incomplete blood or lymphatic
      vessels closure. Esophageal or bronchial wall injury can be caused by thermal injury followed
      by ischemia, necrosis and finally perforation. The diagnosis is frequently delayed. In
      addition, thermal energy generation in case of monopolar electrocautery may lead to systemic
      inflammatory response and increased surgical injury. Extent of surgical injury measured by
      acute phase proteins levels (c-reactive protein, alpha-1-antitrypsin, alpha-1-acid
      glycoprotein, haptoglobin) and interleukin levels was proved to be correlated to long-term
      results in patients with colorectal cancer.

      Introduction of new high-energy sealing devices like LigaSure™ to clinical practice allows
      for dissection, coagulation and cutting with the single instrument. Compared to mechanical
      ligation techniques (vessel loops, clips) or monopolar electrocautery, LigaSure™ technology
      has been shown to significantly reduce:

        -  Operative blood loss in colorectal, gynecologic and urologic surgery

        -  Perioperative blood transfusions in gynecologic, urologic and general surgery

        -  Procedure time in colorectal, gynecologic and urologic surgery

        -  Length of hospital stay in gynecologic and urologic surgery.

      There have been no randomized studies comparing the use of traditional electrocautery and
      LigaSure for lymphadenectomy during VATS resection due to non-small cell lung cancer.

      Investigators hypothesize that application of LigaSure™ in VATS anatomical resection may lead
      to diminished complications rate, lower systemic inflammatory response and shorter length of
      stay compared to monopolar electrocautery.

      Study design

      Patients with early stage NSCLC who are routinely operated on by VATS will be randomized into
      two groups. First group called electro-VATS (Monopolar electrocautery) will be operated on
      with the use of traditional electrocautery and the second called liga-VATS (LigaSure) with
      the use of LigaSure. In the first group during the whole procedure (dissection of pulmonary
      ligament, mediastinal pleura and adhesions, as well as hilar dissection and lymphadenectomy)
      only traditional monopolar electrocautery will be used. In the liga-VASTS patients only
      LigaSure will be applied,no monopolar electrocautery will be used. The procedure of VATS
      lobectomy or segmentectomy will be performed in standardized fashion with separate stapling
      of hilar vessels and bronchus and lung parenchyma division. The hilar dissection and
      mediastinal lymphadenectomy will be performed using either monopolar electrocautery or
      LigaSure according to the randomization. The extent of lymphadenectomy will be the same in
      both groups and will include stations 2R,4R,7,8R,9R,10R,11R on the right side and stations
      5,6,7,8L,9L,10L,11L on the left side. The number of removed lymph nodes will be counted. The
      extension of lymphadenectomy will be controlled and supervised by main investigator. Deep
      temperature inside the esophagus at the level approximately 2-3 cm below the carina will be
      measured during lymphadenectomy in order to assess the differences in the exposure of the
      surrounding tissues to the thermal energy generated by either LigaSure or electrocautery. The
      temperature measurement should in some part reflect the potential risk of thermal injury to
      the esophagus caused by different energy devices.

      Investigators plan to enroll 200 patients, 100 patients in each group. Initial assessment
      will include age, gender, comorbidities (Charlson Comorbidity Index, CCI and Thoracic Revised
      Cardiac Risk Index, thRCRI scores) and pulmonary function tests. The following
      factors/parameters will be measured/compared in both groups: 24-hour, 48-hour and total
      volume of chest tube drainage, chest tube duration and hospital stay, rate of the prolonged
      air leak, rate of redo surgery due to bleeding, rate of postoperative complications related
      to the procedure, intraoperative blood loss and time of the surgery, local thermal effect,
      systemic inflammatory response after surgery.

      Statistical analysis

      The analyzed data will be presented as means, standard deviations, minimum and maximum
      values, medians, interquartile ranges (lower quartile, upper quartile) or percentage, as
      appropriate. Normality of the distribution will be tested with the Shapiro-Wilk's test, and
      the equality of variances will be checked with the Levene's test. For comparison of groups,
      unpaired t test or one-way ANOVA (for data which follow normal distribution and homogeneity
      of variances) or Welch test will be applied. In case data will not normally distributed
      nonparametric tests will be used - Mann-Whitney U test or the Kruskal-Wallis test with the
      Dunn's post-hoc test. Categorical data will be analyzed with the χ2 test or the
      Fisher-Freeman-Halton test. The relationship between variables will be analyzed with the
      Pearson's linear correlation coefficient or the Spearman's rank correlation coefficient or
      (and) by multivariate linear regression. All the results will be considered significant at
      p<0.05. Statistical analyses will be performed with statistical packages: STATISTICA 10.0 PL
      (StatSoft. Inc.) or StatXact 9.0 (CytelStudio) software.
    

Intervention name(s): LigaSure™; Monopolar electrocautery
Intervention type(s): Device; Device
Intervention description(s): LigaSure™ is supposed to provide improved closure of lymphatic and blood vessels during mediastinal lymph nodes dissection.; Monopolar electrocautery will be used according to the standard technique for the mediastinal lymph node dissection.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: video-assisted thoracic surgery; LigaSure; mediastinal lymph node dissection