Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Behaviors and Mental Disorders

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Pain

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Quality of Life

Anterolateral vs. posterolateral thoracotomy

Video assisted thoracic surgery (VATS) vs. anterolateral thoracotomy

Anterolateral thoracotomy

Standard muscle sparing posterolateral thoracotomy

Posterolateral thoracotomy

Standard video assisted thoracic surgery, no use of rib-spreader.

VATS

Anterolateral Thoracotomy

Peter B Licht, Professor

Morten Bendixen, MD

Is thoracoscopic surgery better than traditional open surgery for lung cancer?

Video assisted thoracoscopic surgery for lung cancer (VATS) is presumed to be less traumatic than traditional open surgery for lung cancer but this has never been documented in a randomized trial. Some surgeons hesitate to use VATS because it is technically more demanding, others question if the two methods are oncologically equal. Regardless, VATS has been implemented as a routine method for lung cancer surgery several places around the world including Odense University Hospital. The investigators have launched the first randomized controlled trial in the world comparing the two surgical methods to investigate any differences in length of hospitalization, postoperative pain, life quality within the first year, and health economics.

The investigators include patients with stage I and II lung cancer, and randomize between VATS and open surgery in a design where both the patient and doctors doing general rounds in the ward are blinded until discharge because the dressing on the surgical wound is identical, regardless of the surgical method. The surgeon cannot influence clinical decisions including time to discharge, which is decided by other specialist surgeons. Pain evaluation is performed 6 times daily using the VAS-score, life quality is evaluated continuously during the first 12 months using EQ5D and EORTC QLQC-30 questionnaires, and the consumption of analgetics in both groups are monitored via the national prescription database.

Parallel to this trial a similar clinical study, which is also the first of its kind in the world, has been launched for patients with lung cancers not eligible for VATS. They are randomized between the two traditional open surgical methods (anterolateral and posterolateral thoracotomy) - this is also blinded to both patient and doctors doing rounds until discharge from hospital, and endpoint are similar in the two studies.

206 patients have been randomized in the first substudy (VATS vs. open) and 88 in the second substudy (posterolateral vs. anterolateral).

Is minimally invasive surgery for non small cell lung cancer better than traditional open surgery?

Surgical resection remains the best treatment for non small cell lung carcinoma (NSCLC),but unfortunately many patients suffer major postoperative morbidity - pain being the most frequent. It is assumed that newer minimally invasive surgical techniques (Video Assisted Thoracoscopic Surgery - VATS) reduces postoperative morbidity but there is no level 1 evidence available in the literature. This prompted us to perform the present ongoing study, which is the first of its kind in the world.

The investigators compare VATS with traditional open surgery for early stage lung cancer in a clinical randomized double blinded trial. Our aims are to evaluate differences in postoperative pain, life quality, and health economical aspects. The results of this trial could influence future surgical decisionmaking internationally on the surgical treatment for lung cancer.

Likewise, in patients with larger tumours of the lung, which are not suitable for minimally invasive surgery, different techniques are available. The most widely used techniques are the posterolateral thoracotomy and the anterolateral thoracotomy. So far no randomized controlled trail has shown which of these techniques to be superior. This has led us to also randomize between anterolateral and the posterolateral thoracotomy (muscle sparing). The same endpoints are used.

Pain following lung surgery has been a much discussed topic for a long time in the field of thoracic surgery. Depending on the reference, up to 50% of patients develop chronic pain after open lung surgery. Therefore, different surgical approaches have been developed including anterior, lateral or posterior thoracotomy with or without sparing the chest wall muscles. The intercostal nerve is also of concern because of trauma from the rib retractor which is believed to be a cause of both acute and chronic pain. Other concerns are the amount of divided tissue, extend of rib displacement by the rib retractor, type of analgesics, administration form of analgesics, and administration time of the analgesics and it is generally accepted that pain in lung cancer patients is multifactorial.

VATS was introduced in an attempt to reduce the surgical trauma with less tissue damage, avoidance of the rib retraction and the consequently intercostal nerve injury, but never the less several patients develop chronic pain after lung surgery by VATS.

Information on quality of life and health economical aspects following surgery for lung cancer are scarce. No randomized controlled trial has been published. Very little is known if lung cancer patients regain their workability and if so to what extent following surgery.

Likewise, it is not known if VATS is more costly than open procedures, as the opponents say, or if increased expenses during hospitalization are saved by earlier return to work.

End points

1. Postoperative pain evaluated using the VAS-score and the need for prescription analgetics 2, 4, 8, 12, 26 and 52 weeks after surgery.
2. Health related life quality and workability and -efficiency in the same period, using three different questionnaires: two concerning life quality (EORTC-QLQC-30 and EQ5D) and one concerning workability (WPAI).
3. Health economical aspect such as application for pension, visits to general practitioner, readmitted to hospital, number of days away from work due to postoperative morbidity, etc.

All gathered from different databases managed by "Danmarks Statistik" here among the "Landspatientregistret(LPR)", "Sygesikringsstatistikregistret" ,and "Lægemiddelstatistik-registret".

206 patients admitted to the department of cardiothoracic surgery, Odense University Hospital, for elective surgery for lung cancer will be included in each study.

Design

This research project has three sub studies: Two randomized controlled and double blinded clinical trials, and one registry study. One clinical trial randomizes patients with small peripheral lung cancer between VATS (Video Assisted Thoracoscopic Surgery) and standard open anterolateral thoracotomy. The second clinical trial randomizes between anterolateral and posterolateral open thoracotomy in patients not eligible for VATS. The registry sub study monitors patients use of analgetics during the first 12 months (lægemiddelstatestik-registret), their use of other health services, and return to work.

All patients will be operated in general anaesthesia with a double lumen tracheal tube and an epidural catheter. The epidural catheter will be removed when all chest tubes has been removed, but no later than postoperative day 4.

As a standard all patients will be given paracetamol and NSAID in standard doses, and if needed opioids (oxycontin/oxynorm) can be added.

All surgical techniques will be performed as routine operations.

Three different surgical techniques will be used.

1. The VATS approach: one camera port and three assistance ports one of which is enlarged to 5 cm. and rib retractors are never used.
2. Anterolateral thoracotomy: The incision is made from the posterior axillary fold following the linea inframammary to a point below the papilla.
3. Posterolateral thoracotomy. The incision is made from the anterior axillary fold backwards towards the inferior angle of the scapula, without dividing the dorsal latissimus muscle.

In both clinical trials postoperative pain is evaluated by a visual analog scale (VAS). Pain is measured during rest and during coughing. Measurements are done preoperatively and 6 times daily during their hospital stay. After discharge measurements are recorded after 2, 4, 8, 12, 26, and 52 weeks by mail questionnaire.

Both patients and the staff doing general rounds postoperatively will be blinded. In the operating room a dressing will be placed so that it covers the entire hemithorax whereby the incision is hidden. This is done identically regardless of surgical technique. This dressing is left in place until discharge. If changing of the dressing is needed, either the project-nurse or a nurse for another team will assist.

The surgical note is kept in a sealed envelope, which is always placed in the patients chart and can be opened in case of emergency. The chart will only include information about which lobe was resected, no details on the surgical access, but this information is added when the patient is discharged.

The surgeon who has performed the operation will be allowed to check up on their own patients, and to be consulted by the other doctors doing rounds, but they are not allowed to influence on decision-making regarding pain relief or discharge, during the postoperative period.

Timeline

This project is a combination of a ph.d-study and a residency/fellowship in cardiothoracic surgery because this allows for a longer inclusion period. The timeline is divided into three research periods and three clinical periods.

This research project has already been accepted as a ph.d.-project at the University of Southern Denmark, and approved by the local ethical board.

Minimally Invasive or Open Surgery for Lung Cancer: Pain, Quality of Life and Economics.

Aim is to asses the development of acute and chronic pain after lobectomy.

Three questionnaires are used. EQ5D, QLQC-30 and WPAI.

An economical evaluation will be done. Including in-hospital expences, use of sociale-security, readmissions to hospital, use of family practioner, use of and duration of prescription analgetics, wether or not patients are able to return to work, the effect this type of surgery has on the patients quality of life, including a QALY evaluation and cost utility analysis.

Peter B Licht

Professor, MD, pHd.

Nervous System Diseases

Rare Diseases

Neuralgia

Chronic Pain

Acute Pain

Neurologic Manifestations

Peripheral Nervous System Diseases

Neuromuscular Diseases

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Central Nervous System Depressants

All Drugs and Chemicals

Analgesics

Anesthetics

Ketamine

Propofol

Atracurium

Remifentanil

Anesthetics, Dissociative

Anesthetics, Intravenous

Anesthetics, General

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

The patients in this Group underwent General anaesthesia with total intravenous anaesthesia containing remifentanil (0,02-0,04 mg/kg ideal Body weight), propofol (4-6 mg/kg ideal Body weight) and atracurium.

Ketamine 0,2 mg/kg ideal Body weight per hour for 24 hours.

The patients in this Group underwent General anaesthesia with total intravenous anaesthesia containing remifentanil (0,02-0,04 mg/kg ideal Body weight), propofol (4-6 mg/kg ideal Body weight) and atracurium.

Placebo (normal Saline) for 24 hours.

Normal saline applied by bolus before operation started, followed by a continuous application of normal saline for 24 hours.

Placebo

Application of Ketamine 0,2mg/kg ideal Body weight by Bolus before the Operation started, followed by application of 0,2 mg/kg ideal Body weight for 24 hours.

Chronic Pain, especially neuropathic pain, are adverse events after posterolateral thoracotomy for lung resection. The continuous application of ketamine may have a prophylactic effect and helps to prevent chronic pain. The investigators record the incidence and severity of acute pain and neuropathic pain during a seven day period after thoracotomy as well as the incidence of chronic pain and neuropathic pain after one and three month period. Parallel Group design, comparing one Group with a continuous application (24 hours) of ketamine against a Placebo Group.

Acute and Chronic Pain, Especially Neuropathic Pain, After Thoracotomy and Continuous Application of Ketamine.

Effects of Prophylactic Administration of Ketamine on Acute and Chronic Pain After Thoracotomy for Lung Cancer, a Double Blind Randomised Trial.

The patients consumption of opioids is recorded once a day for a period of 7 days after operation.

The incidence and severity of pain will be measured using a numeric analog scale (NAS) once a day for a period of seven days after Operation.

The incidence of neuropathic pain will be measured using the LANSS Pain Scale (Leeds assessment of neuropathic symptoms and signs) three and seven days after operation

The incidence and severity of pain will be measured using a numeric analog scale (NAS). Pain scale is requested by phone one and three month after Operation.

The incidence of neuropathic pain will be measured by using the LANSS Pain Scale (Leeds assessment of neuropathic symptoms and signs) one month after operation

The incidence of neuropathic pain will be measured by using the LANSS Pain Scale (Leeds assessment of neuropathic symptoms and signs) three month after operation

Time between stopping intravenous anaesthesia and first eye opening of the Patient in minutes

Dr. Horst Schmidt Klinik GmbH

Pulmonary lobectomy via VATS. VATS starts with a utility incision, approximately 4 cm in length, anterior to the latissimus dorsi muscle at the 4th intercostal space. Muscle fibers are split without cutting and a wound protector is regularly placed in site. The camera port is placed in the 6th or 7th intercostal space at the anterior axillary line and a third 10-mm access is made at the same intercostal space at the posterior axillary line. The hilum is approached anteriorly

Pulmonary lobectomy via posterolateral thoracotomy (PLT). PLT consists in a standard 10-15 muscle-sparing incision at 4th intercostal space, rib divaricators are utilized and the hilum is approached posteriorly as previously described

Pulmonary lobectomy

The standard operative approach to pulmonary lesions has been via postero-lateral thoracotomy and direct vision. This technique has some advantages but its morbidity is significant. Some surgeons advocate a resection by video-assisted thoracic surgery (VATS) to reduce the impact on chest wall and the impairment on respiratory mechanic. However, an evidence for superiority of the approach minimally invasive is lacking, particularly for the difficult assessment of the change in pulmonary function. The aim of this study is to compare VATS- over open lobectomy regarding the differences of chest wall kinematic, analyzed by optoelectronic plethysmography (OEP).

Rationale: The standard operative approach to pulmonary lesions has been via postero-lateral thoracotomy and direct vision. This technique has some advantages but its morbidity is significant. Some surgeons advocate a resection by video-assisted thoracic surgery (VATS) to reduce the impact on chest wall and the impairment on respiratory mechanic. However, an evidence for superiority of the approach minimally invasive is lacking, particularly for the difficult assessment of the change in pulmonary function and its relation with chest wall modifications.

Objective: The aim of this study is to compare VATS- over open lobectomy regarding the differences of chest wall kinematic analyzed by optoelectronic plethysmography (OEP).

Study design: A prospective mono-centre single blind trial. Study population: Adult patients of either gender candidate for pulmonary lobectomy for non small cell lung cancer.

Intervention: Patients are submitted to pulmonary lobectomy by video-assisted technique or by postero-lateral thoracotomy. This decision follows the usual clinical evaluations, regardless of whether or not the study enrollment. In particular, they are candidates for postero-lateral thoracotomy if: tumors were close to the hilum or other relevant anatomical structures, or the computed tomography demonstrated hilar calcific lymph-nodes or the lesions were of greater than 4 cm diameter.

Endpoint is evaluation of modification of respiratory kinematic after pulmonary lobectomy, assessed by OEP. In particular, the volume variation of pulmonary rib cage of the treated side versus the relative untreated side and the differences. Respiratory movements and thoracic and abdominal volume changes will be recorded continuously by analyzing the movements of retro-reflective markers using 8 video-cameras connected to an automatic optoelectronic motion analyzer. Subjects are prepared for OEP (markers). Baseline spirometry is take prior to exercise test. All exercise take place on an electromagnetically braked cycle-ergometer. Throughout the protocol heart rate, oxygen saturation and dyspnoea with the Borg scale are recorded. Ventilatory kinematics are monitored throughout exercise using OEP. This OEP analysis involves compartmentalization of the chest into three sections: pulmonary rib cage, abdominal rib cage, and abdomen to determine the contribution of each component to total chest wall volume.

VATS Versus Open Pulmonary Lobectomy in the Limelight of OEP

VATS Versus Open Pulmonary Lobectomy for Lung Cancer: a Prospective Analysis of Different Impacts on Ribcage Kinematics With Optoelectronic Plethysmography

Compare VATS- over open pulmonary lobectomy regarding the differences of chest wall kinematic, analyzed by optoelectronic plethysmography (OEP)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Minimally Invasive or Open Surgery for Lung Cancer: Pain, Quality of Life and Economics.	NCT01278888	Nonsmall Cell L...	Anterolateral t... Posterolateral ... VATS Anterolateral T...	18 Years -	Odense University Hospital
Acute and Chronic Pain, Especially Neuropathic Pain, After Thoracotomy and Continuous Application of Ketamine.	NCT03105765	Acute Pain Chronic Pain Neuropathic Pai...	Placebo Ketamine	18 Years -	Dr. Horst Schmidt Klinik GmbH
VATS Versus Open Pulmonary Lobectomy in the Limelight of OEP	NCT02910453	Lung Cancer	Pulmonary lobec...	18 Years -	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Spots Global Cancer Trial Database for posterolateral thoracotomy