Abstract
Background: Minimally invasive esophagectomy is an evolving alternative to the open technique with the goal of providing efficient oncological therapy while minimizing morbidity by diminishing surgical trauma. Patients and Methods: Fifty-five consecutive esophagectomies with a minimally invasive approach were included in the calculations. The patients' demography, surgical, histopathological and survival outcomes were analyzed, and surgical/ non-surgical morbidity rates calculated. Results: In 47% of the patients, a laparoscopic-thoracoscopic approach, and in 53% minimally invasive hybrid procedures were performed. The overall conversion rate to open surgery was 5.5%. Major surgical complications occurred in 26% and major non-surgical morbidity in 13% of the patients. The curative resection rate was 87% with a median number of investigated lymph-nodes of 17.5. The 1-year disease-free survival and overall survival were 73% and 88%, respectively. No hospital mortality occurred. Conclusion: Minimally invasive oncological resection in patients with esophageal cancer is feasible and provides the potential of reducing postoperative morbidity and enhancing the oncological outcome even when a learning curve is included.
Esophageal resection is the mainstay of treatment in resectable oesophageal cancer. However, even though operative mortality and morbidity associated with esophageal surgery has been decreasing with advances in surgical techniques and equipment, postoperative complications remain a major cause of a potentially fatal outcome. Morbidity and mortality rates from 40 to 60% and 5 to 20%, respectively, after esophagectomy, have been reported by many centres recently (1, 2).
Minimally invasive surgical techniques for the treatment of gastrointestinal and thoracic diseases were introduced in the late 1980s. Meanwhile, laparoscopic surgery became the standard approach to various surgical treatments such as symptomatic cholecystectomy, gastroesophageal reflux disease, morbid obesity, achalasia, or benign gastric tumors (3, 4). These endoscopic approaches proved to successfully diminish surgical trauma and postoperative morbidity, providing improved postoperative recovery and a faster return to normal activities. The need for analgesics was lower and long-term complications such as incisional hernia and mechanical ileus were substantially less when compared with conventional open surgery (5, 6).
Currently, the minimally invasive approach to esophageal resection is an evolving alternative to the open technique with the goal of providing efficient oncological therapy while minimizing morbidity by diminishing surgical trauma (7-13).
Since the first report about thoracoscopic oesophagectomy in the early 1990s, numerous centers have reported about the feasibility and their experience in endoscopic oesophageal resection (7, 8, 10-19).
However, minimally invasive approaches still lack the proof, in addition their technical feasibility, of their oncological equality, including the extent of lymphadenectomy and survival (7, 20).
Here the first 55 cases of minimally invasive esophagectomy in a single center, university teaching hospital are reported.
Patients and Methods
Patients. The data from all the 55 patients treated with a minimally invasive approach to resection of cancer of the esophagus or the esophagogastric junction at the Department of Surgery, Medical University of Vienna, between the years 2004 and 2008 were collected into a prospective computer database and applied to this analysis. Due to the broad definition of minimally invasive esophagectomy, all the patients in whom at least one part of the surgery, the abdominal or the thoracal part, was performed in a minimally invasive manner were considered.
The preoperative diagnostic workup included physical examination, chest X-ray, standard laboratory tests, lung function, electrocardiogram (ECG) and anesthesiological assessment. In some cases, barium swallow and in all cases upper gastrointestinal endoscopy was performed to assess the tumor features, flexible bronchoscopy and otolaryngological evaluation were included for tumors of the cervical, upper and middle esophagus as well as for all the squamous cell carcinomas. Computed multidetector tomographic scans of the chest and abdomen were obtained in all cases to rule out any metastatic disease. In selected cases and upon the indication of the cardiologist, the preoperative evaluation also included echocardiography and/or dynamic tests to estimate the patient's ventricular function.
Comorbidities were subgrouped into cardiovascular (peripheral arterial disease/arterial disease, hypertension), metabolic (diabetes), hepatic disorders and pulmonary (chronic obstructive pulmonary disease, COPD) disease.
Surgery. Due to the individual patient requirements, the minimally invasive approaches performed were subdivided into three categories: thoracoscopic and laparoscopic esophagectomy; laparoscopy and thoracotomy and thoracoscopy and laparotomy. Open maneuvers were carried out as described previously (21).
All patients with potentially curative resectable cancer of the thoracic or abdominal esophagus were suitable candidates for minimally invasive esophagectomy exluding patients with previous major upper abdominal or thoracic surgery, cT4-tumors, no informed consent signed by the patient, and patients with contraindications for single lung ventilation. The laparoscopic and thoracoscopic procedures were performed as follows.
Minimally invasive abdominal approach. In an anti-Trendelenburg position, the patient is placed supine with legs apart, the right arm away from the body and the left one along the patient's side. The operator stands between the patient's legs and the assistants stand on the left and right (camera). After abdominal insufflation (12-15 mm Hg) using a Veress needle is achieved, trocars are positioned at the following sites: i) (12 mm) along the midline about 2-5 cm above the umbilicus for the camera, ii) (5 mm) subxyphoidal, iii) (12 mm) on the right side along the mid-clavicular line 5 cm subcostal, iv) (12 mm) on the left side along the mid-clavicular line 5 cm subcostal, and v) (5 mm) on the left side along the anterior axillary line directly subcostal.
The operation starts with exploration of the abdominal cavity to exclude the presence of any distant disease. The greater curvature of the stomach is mobilized carefully preserving the right gastroepiploic vessels. Adhesions in the posterior aspect of the stomach are divided before the gastric fundus is mobilised by dividing the short gastric vessels. By dissecting the hepatogastric ligament the lesser sac is entered. After Kocher's maneuver, an upper abdominal lymphadenectomy including the paracardiac, the lesser curvature and the left gastric artery nodes is carried out. Neither pyloroplasty nor pyloromyotomy is performed. The left gastric artery is isolated and divided after clipping at the origin (see Figure 1A). The gastric tube is formed by linear stapling starting at the angulus of the antrum and advancing toward the angle of His. In this fashion a gastric tube of 3-5 cm in diameter is created before the top of the tube is sutured to the lesser curvature. Now the dissection of the distal-third esophagus with en bloc lymphadenectomy of the paraesophageal and mediastinal lymph nodes, including the mediastinal pleura bilaterally, is carried out. This is the abdominal procedure for the Ivor Lewis operation. If the anastomosis is to be placed in the neck, the minimally invasive procedure is conducted laparoscopically assisted after the thoracic part. After thoracic mobilization of the esophagus, the cervical esophagus is divided and a 5 cm midline minilaparotomy is created. This is followed by specimen retieval under protection of the minilap and extracorporal gastric tubulisation. The port sites are closed without placing drainage.
Minimally invasive thoracic approach. The patient is turned to the left lateral decubitus position for thoracoscopy, the surgeon facing the patient's back and opposite to the assistants. Left-sided single lung ventilation is introduced before the thoracic trocars are applied as follows. The first trocar for the camera (10 mm) is placed in the 8th intercostal space at the posterior axillary line. The subsequent trocars are placed in the 9th intercostal space (10 mm) middle axilary line, 6th intercostal space below the tip of the scapula and the 4th and 8th intercostal space anterior axilary line (5 mm). After the lung lobes are retracted anteriorly, the pleural cavity, and the surface of the lung are inspected for the presence of metastatic disease. Afterwards, the inferior pulmonal ligament is divided by ultrasonic dissection and the mediastinal pleura covering the esophagus is divided to expose the intrathoracic esophagus. The crossing part of the azygos vein is isolated and divided by linear stapling before the thoracic duct is located supradiaphragmatically and dissected after clipping. The esophagus is circumferentially mobilised en bloc with the periesophageal and infracarinal lymph nodes and the thoracic duct after a Penrose drain is placed around the esophagus to facilitate esophageal retraction (see Figure 1B). For the intrathoracic anastomosis, the esophagus is divided at the level of the azygos vein crossing. The gastric tube is pulled up into the thorax by means of removing the specimen through a 5 cm minithoracotomy using a wound protector. After a gastric tube with an attached 25-mm anvil (Autosuture, Norwalk, CT, USA) is positioned transorally, a 25-mm circular stapler is inserted through the tip of the gastric conduit and the circular esophagogastric anastomosis is created (see Figure 1C). In cases of thoracotomy the anastomosis is performed in the same manner except the introduction of the anvil which is conducted transthoracically. Two 24-F chest tubes are inserted. For cervical anastomoses, one layer of hand-sewn single-knot suture in the neck, after completion of the mobilization of the cervical oesophagus via the left cerviotomy is performed after gastric pull up, preferentially by the orthotopic route.
In the present study microscopic lateral or deep margin of less than 1 mm was considered a positive margin, and proximal and distal margins of at least 2 cm beyond the gross tumor were aspirated.
The resection was defined as curative (R0) when all gross disease was removed with negative margins. Incomplete resection was defined as residual gross disease (R2) or positive surgical margins (tumor less than 1 mm from any margin) histologically (R1).
All the patients were managed in the intensive care unit (ICU) for the immediate postoperative period. Postoperatively early extubation, pain control, vigorous respiratory therapy and early mobilization and ambulation were aspired. A methylen-blue swallow test was performed 24 hours after surgery in the cases of intrathoracic anastomosis. Food intake was allowed, after a contrast swallow showing no evidence of leakage, on postoperative days 3-5.
The patients were followed up by the surgical team 1, 3, 6, 9 and 12 months after the operation and every 6 months thereafter. Hospital mortality was defined as death within the same hospital admission.
A) Location and division of the left gastric vein (VGS) and artery (AGS) during gastric mobilization and lymphadenectomy. B) Intraoperative situs during the intrathoracic mobilisation of the esophagus (ES) with en bloc lyphadenectomy (LN). Note the complete lymphadenectomy at the bifurcation (TB) and the trachea (T). C) Situs after the gastric conduit (GC) has been pulled into the thorax and the anastomosis (AN) is performed with a circular stapler. Note the height of the anastomosis at the divided crossing part of the azygos vein (VA).
Outcome-parameters. Major surgical morbidity was noted and valid when one or more of the following complications occurred: postoperative hemorrhage; anastomotic or suture line leak, chyle leak that could not be handled conservatively and gastric necrosis.
Considered as minor surgical morbidity were: hoarseness due to unilateral vocal cord palsy; chyle leak without the need for reoperation and temporary gastric outlet syndrome.
Non-surgical complications were noted and subcategorised into: respiratory complications (pneumonia, major atelectasis and pulmonary edema), neurological complications (mild epilepsy and alcohol withdrawal) and other complications (renal failure, systemic inflammatory response syndrome (SIRS) and artrial fibrillation).
Statistics and survival analysis. Spearman's coefficient of correlation, the Kruskal-Wallis test and Mann-Whitney test were used as appropriate.
The univariate analysis of overall survival (OS) and disease-free survival (DFS) was performed as outlined by Kaplan and Meier. For all the tests, a p-value of <0.05 was considered significant. All the p-values given are the results of two-sided tests.
OS was defined from the day of surgery until the death of the patient. The data on the patients who had survived until the end of the observation period were censored at their last follow-up visit. Death from a cause other than esophagus cancer or survival until the end of the observation period were considered censoring events. DFS was defined from the end of primary therapy until the first evidence of progression of disease.
Results
Patient demography and pathology. Details are shown in Table I. Thirty-one of the patients presented with swallowing problems while 24 patients did not complain of any. In 11 (20%) patients with neoadjuvant treatment (according to ongoing study protocols) (21), preoperative esophageal stenting due to dysphagia was temporarily necessary.
Surgical parameters. Due to the process of implementation, the expected learning curve and individual oncological situations and preconditions, various different kinds of minimally invasive approaches and hybrid procedures were performed during the study period. Thoracoscopic mobilization and resection of the esophagus with an open construction of the gastric conduit (in 27% of the cases) was followed by the introduction of laparoscopic assisted gastric mobilisation and gastric-tube formation (in 26% of the cases) and finally the complete endoscopic Ivor Lewis procedure for the lower esophageal malignancies (in 47% of the cases). Thus finally, about half of the patients were operated on with a totally minimally invasive laparoscopic-thoracoscopic approach, and the remainder underwent hybrid operations. Details of the surgery performed are shown in Table II.
Overall patient demographic and pathology (n=55).
The dominant organ used for reconstruction was the stomach but open colonic interposition was necessary in two patients since the stomach was not appropriate due to previous surgery.
Morbidity and mortality. The perioperative parameters are shown in Table III.
With 11 patients (20%), a re-intervention (5 re-operations, 6 re-interventions) was necessary.
Complications related to surgery were reported in 22 patients (40%), while minor complications were recorded in 8 patients; 14 patients experienced major surgical morbidity. (see Table III).
Oncological outcome parameters and survival. The datails are shown in Table III.
Surgical parameters.
Outcome-parameter and survival.
The median follow-up was 13.8 months (range 0.6-51). With a median DFS of 22.1±6.4 months, a 73% 1-year DFS and 46% 2-year DFS was calculated. Median OS was 33.3±11.6 months with 88% 1-year OS and 58% 2-year OS. (also see Table III and Figure 2).
Conclusion
With an overall conversion rate of 5.5%, where two were due to intrathoracic bleeding and the third to an unclear surgical situation (R2 at the left bronchus) during the peri-bifurcal lymphadenectomy, the present data were in good correlation with published conversion rates, ranging between 4.7 and 7%, depending on the type of procedure (7, 8, 12, 22, 23).
Fortunately, no 30-day postoperative mortality occurred and an overall surgical complication rate of 40% was observed. However, due to the ambigous definition of surgical morbidity, comparing the incidence to other published rates, ranging from 18% to almost 100%, is hardly reliable (7). The rate of major surgical morbidity, necessiting major treatment or re-intervention, was 26%, which was more than comparable with the data shown from other institutions (1, 7, 8, 14, 16, 18). The relatively high number of re-interventions, of 20%, compared to the rates provided in the literature (3% to 10%), might be explained by the fact that in the present calculations, all the re-interventions, including endoscopic procedures, such as stenting, fibrin-glue application or drainage, were included.
In the cases of distal esophageal cancer, the optimal site for the anastomosis is still highly controversial being the subject of several clinical investigations (24, 25, 26). Some authors favour cervical esophagogastric anastomoses, allowing large margins of resection and less dangerous leakage, but an increased risk of injury to the recurrent nerve, more late stenosis and a higher leak rate. Others prefer an anastomosis in the thorax, with lesss esophagus removed, better swallowing function and a lower, but more ominous leakage rate. The inauguration of minimally invasive approaches to esophageal resection has not diminished this ongoing discussion, as both, cervical and thoracic anastomoses can be performed by minimally invasive approaches. In the present series, depending on the tumor localization, both, cervical and thoracic anastomoses, were performed for reconstruction. An overal leakage rate of 12.7% was recognized, while the leakage rate for the cervical anastomoses was noticeably higher with 15.2% compared to the thoracic anastomosis with a leakage rate of 9.1%. which was in good correlation with the leakages rates described by other centers, ranging from 7 to 13% (7).
Less than 20 years ago, a postoperative mortality of up to 20% and morbidity rates of about 50% were not uncommon after esophageal cancer surgery. Despite substantial changes toward better short-term mortality and morbidity rates, pulmonary complications remained a major problem after esophagectomy with rates still up to 40%. In this study a major non-surgical morbidity rate of 13% was observed with a pulmonary complication rate of 22%, which was at least comparable with the data shown in the literature, even though the present definition of pulmonary complication was quite wide-ranging and included any pulmonary event.
(A) Disease free survival (DFS) in 55 patients undergoing minimally invasive esophagectomy (MIE), with a 1-year-DFS of 73% and a 2-year-DFS of 46%. (B) Overall survival in 55 patients undergoing MIE, with a 1-year-OS of 88% and a 2-year-OS of 58%.
Concerns have been raised regarding minimally invasive esophageal resections in the setting of cancer and their adequacy as an oncological procedure. The number of lymph nodes resected and the lymph node ratio have been utilised as a surrogate for oncological completeness of the surgical technique and even though no convincing data documenting any survival benefit from extented lymph node dissection exists awareness of the importance of accurate nodal staging related to the prognosis of esophageal cancer has increased (27, 28). One potential benefit of the minimally invasive technique may be the visualization via thoracoscopy and laparoscopy allowing for a more precise lymphadenectomy. The median lymph node retrieval rates published for minimally invasive procedures range from 10 to 20, favouring the transthoracic approaches over minimally invasive transhiatal procedures (7). In the present study during the two-field lymphadenectomy that was performed in all the patients, a median harvest of 17.5 lymph nodes was achieved. This as well as the R2 rate of 9% was in good accordance with published data on open esophagectomy with median harvests between 11 and 26 lymph nodes, and R1 rates between 4 and 15%, as well as with recent reports on minimally invasive esophagectomy with a median harvest rate of 14 (range 5 to 62) (7). However, the long-term oncological outcome of minimally invasive esophagectomy is difficult to gauge because the length of follow-up and the number of patients operated on using this approach is still limited, and there are no data from prospective randomized trials available. The reported overall 1-year and 3-year survival rates range from 33-91% and 35-69%, respectively (7, 13, 22, 29). The present cohort was in the published range with 1- and 2-year survival rates of 88 and 58% respectively. This analysis was conducted as a pilot-calculation for a scheduled randomized trial.
In summary, the data provide further evidence that oncological resection in cancer patients is feasible with the laparoscopic approach and provides the potential of reducing postoperative morbidity and enhancing the oncologcal outcome. However, minimally invasive approaches to esophagectomy, are technically demanding and prospective data on surgical, oncological and overall outcomes are still lacking and strongly desired.
- Received January 16, 2009.
- Revision received March 17, 2009.
- Accepted April 2, 2009.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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