Trial Information

A Phase Ⅲ Study of Respiratory Complications Associated With Esophagectomy Through Either Ivor-Lewis or Sweet Approach for the Treatment of Middle or Lower Third Intrathoracic Esophageal Carcinoma

Background:

Esophageal cancer is a common malignant tumor in China and worldwide with poor prognosis.
Although the surgical resection combined with adjuvant therapy constitutes the mainstay of
the treatment the esophagectomy-associated complications are still life-threatening.
Postoperative pulmonary complications (PPCs), including pulmonary infection, atelectasis,
edema and ARDS (acute respiratory distress syndrome) are the leading causes of the eventful
postoperative episodes.

The diaphragm is the well known essential respiratory muscle whose normal function
guarantees more than 30% of pulmonary function. Esophagectomy through left thoracotomy would
inevitably cut off the left diaphragm for the abdominal procedure and thus greatly damage
the diaphragmatic function. It has been assumed that Ivor-Lewis esophagectomy would save the
pulmonary function to a great extent by retaining the intact diaphragm but the addition of a
laparotomy would be unavoidable. However, this hypothesis has not been confirmed by any
randomized controlled trial with adequate operation volume. At present, a large part of
thoracic surgeons, for example in China, still prefer esophagectomy through Sweet approach
believing that it is less traumatic. So far, there is presently no convincing evidence to
guide the esophagectomy approach selection on the aspect of prevention of PPCs.

Objectives:

1. To compare the PPCs rates after Ivor-Lewis esophagectomy and Sweet esophagectomy

2. To compare the degrees of diaphragm function deficiencies between two groups.

3. To compare the pulmonary function results between two groups

4. To compare the degrees of gastric emptying between two groups

Diagnostic Criteria for PPCs: any one of the followings and not because of anastomotic leak,
massive pleural effusion and non-pulmonary origin infection:

1. postoperative hypoxemia (PaO2≤ 60mmHg and/or PaCO2≥ 50mmHg) or dyspnea

2. transfer to intensive care unit due to hypoxemia or dyspnea

3. purulent pulmonary secretions requiring bronchoscopic suction

4. dependence on oxygen mask or nasal tube for more than 5 days

5. infiltrating or atelectasis in one pulmonary lobe or multiple segments identified by
chest X-ray film or CT scan)

6. postoperative hiatal hernia associated pulmonary dysfunction

7. dependence on ventilator support for more than 48h

Degree of diaphragm function: The distance of diaphragmatic movement in centimeters

Pulmonary function measurement: FEV1, FVC and MMV

Gastric emptying function: Radioactivity remained at 15 minutes after ingestion of 100ml
Tm99-labelled radioactive milk

Design:

Prospective randomized controlled trial.

Setting:

Thoracic Surgery Department, West China Hospital of Sichuan University, Chengdu, China

Patients and methods:

All patients with histologically confirmed esophageal carcinoma located at the middle or
lower thoracic esophagus presenting to our hospital will be considered for the study

Termination criteria:

1. Intolerance of any of the treatment modality,

2. Development of PPCs

3. Development of any other severe complication, such as progressive bleeding, large
pleural effusion, empyema

4. Death

Staging investigations will be standard and will include

1. Computed Tomography (CT) of Chest in all patients

2. Fibroesophagoscopy in all patients

3. Esophagogram by barium swallow in all patients

4. Endoscopic Ultrasonography (EUS) wherever possible Further investigation likes
bronchoscopy, PET scan, or MRI will be applied if indicated.

Randomization:

Complete randomization will be done using a computer generated sheet. Randomization will be
performed after confirming resectability of the primary tumor and enlarged lymph nodes.

All surgeries will be performed under general anesthesia with epidural analgesia. The
surgery will be performed either by Dr. Longqi Chen or Dr. Yidan Lin who is the faculty and
professor of the thoracic surgery department of West China Hospital. Thoracic esophageal
mobilization and mediastinal lymphadenectomy will be done by open thoracotomy. Stomach
dissection and gastric tube making will be done either through the left diaphragm incision
when left thoracotomy is applied or through the laparotomy when Ivor-Lewis approach is
applied. Operative time, blood loss, blood product replacement and all intraoperative
details will be recorded in the proforma. Patients will be shifted postoperatively to the
intensive care unit (ICU) for observation and subsequently to the recovery or high
dependency ward once stabilized. Postoperative details including period of postoperative
ventilation, hemorrhage, pulmonary and cardiac complications, arrhythmias, thoracic duct
leak, anastomotic leak, wound infection and recurrent laryngeal nerve paresis or palsy will
be recorded. Postoperative mortality will be defined as 30-day mortality plus death before
discharge after surgery. Patients will be started on oral feeds between the 8th and 10th day
in the absence of an anastomotic leak. The total duration of ICU stay and hospital stay will
also be recorded.

Sample size:

The sample size considering an improvement of morbidity of sever pulmonary complications
from 15% to 5% will be 280 patients (140 in each arm). The trial will aim at enrolling 320
patients in order to adjust for protocol violations. Interim analyses will be done when ½
(160 events) of the estimated events occur. We expect to complete accrual of patients in
three years.

Follow up:

No follow up after discharge. The long-term pulmonary function is not the concern of this
clinical trail.

Data management:

All collected data will be entered into a statistical software package for subsequent
analysis