Introduction
The upper gastrointestinal (GI) tract comprises the mouth, esophagus, stomach, and duodenum. The incidence of such cancers is rising, and improved operative safety and successes of neoadjuvant chemotherapy have increased the number of patients who are candidates for curative resection. Resection of tumors involving the upper GI tract carries high intraoperative risk, and due to shared anatomy, close concert between the anesthesiologist and surgeon. The goals of intraoperative management include optimal fluid management, appropriate multimodal analgesia, reduction of postoperative pulmonary complications, and optimizing the physiologic milieu to promote anastomotic healing.
Chemotherapeutic Toxicity
Patients receiving neoadjuvant chemotherapy for upper esophageal cancer may suffer from chemotherapeutic toxicity of which the intraoperative team should be aware. Chemotherapeutic agents can cause dysrhythmias (anthracycline, pembrolizumab), myocarditis (cyclophosphamide, busulfan), dilated cardiomyopathy (doxorubicin), and prolonged QT interval (oxaliplatin, tamoxifen, anthracycline, 5-fluorouracil, paclitaxel). Patients receiving these agents may have pericardial effusions, restrictive cardiomyopathy, and congestive heart failure. All patients who have received chemotherapy agents and who express symptoms of dyspnea on exertion should receive a preoperative echocardiogram to screen for cardiomyopathy.
Esophageal Cancer
Epidemiology
The incidence of esophageal cancer in the United States is 0.7% in men and 0.2% in women, making it the 18th most common type of cancer and the 11th in terms of risk of death. Ninety-five percent of esophageal cancers are squamous cell carcinoma (SCC) and adenocarcinoma. The incidence of adenocarcinoma, once considered to be quite rare, now accounts for more than 60% of esophageal cancers, largely due to the increase in incidence of Barrett’s esophagus. In southern and eastern Africa and eastern Asia, the incidence of esophageal cancer is much higher and predominantly due to SCC. Small cell cancers, leiomyosarcomas, leiomyomas, and GI stromal tumors account for a very small portion of esophageal cancers. Due to improved treatment modalities, the 5-year survival rate has increased from 5% in the 1960s to 20% in the modern day.
Behavioral risk factors for squamous cell esophageal cancer include smoking and alcohol consumption. Dietary factors include red meat consumption, low fiber diets, hot beverage consumption, zinc deficiency, and selenium deficiency. History of achalasia or caustic injury are additional predisposing factors. Human papilloma virus (HPV) has not been definitively linked to esophageal cancer. The increasing prevalence of adenocarcinoma is linked to higher rates of obesity, gastroesophageal reflux disease, and diets low in fruits and vegetables. A history of Barrett’s esophagus increases the risk of developing esophageal cancer by 30-fold. Adenocarcinoma is more prevalent among Caucasians, and six times more prevalent in males than females.
The most common location of SCC in the esophagus is at the midportion, arising from small plaques that can be missed on endoscopy. Local lymph node infiltration occurs early due to the close proximity of the lymph nodes to the lamina propria of the esophagus. It eventually progresses to invade adjacent organs, including the celiac artery and aorta, which can present with massive upper GI bleeding.
Adenocarcinoma most commonly arises in the gastroesophageal junction and most commonly spreads to the celiac and perihepatic nodes.
Diagnosis and Staging
Early esophageal cancer is usually asymptomatic and only detected during endoscopy for alternative purposes or during surveillance for Barrett’s esophagus. Symptoms for more advanced cancers are usually dysphagia (often manifested in the early stage by the “sticking” of hard foods), weight loss, and iron-deficiency anemia. Severely advanced cases can progress to cause tracheobronchial fistulas. Rarely, recurrent laryngeal nerve involvement can cause hoarseness. Endoscopic biopsy is required to confirm the diagnosis.
At the time of presentation, 22% of esophageal cancers are localized to the esophagus. Regional spread is present 30% of the time, and the remaining present as advanced disease.
Staging to evaluate regional and advanced spread is done via endoscopic ultrasound (EUS, which can diagnose local lymph nodes and liver metastases), bronchoscopy, and whole-body positron emission tomography (PET), and occasionally diagnostic laparoscopy. Laparoscopy is reserved for patients who have responded to chemotherapy and are surgical candidates but the extent of disease is unknown, or in whom extent of peritoneal disease is unclear from imaging. Tumor extending into the stomach for more than 5 cm is considered unresectable.
Treatment
Disease that is limited to the mucosa or submucosa is of a diameter of <2 cm, and does not involve the entire circumference of the esophagus can be treated with surgery or endoscopic therapy. For cancers that have invaded into the esophageal wall or are node-positive, treatment involves chemotherapy and surgery.
Endoscopic Ultrasound
Endoscopy with the use of ultrasound is becoming standard of care for diagnosis, biopsy, and occasionally treatment of small, localized esophageal tumors. Deep sedation may be appropriate for a small subset of patients who are asymptomatic at the time of presentation; general anesthesia with a protected airway is the method of choice due to aspiration risk.
Surgical Treatment and Intraoperative Considerations
Surgical Candidacy
Patients with stage T4b disease that is invasive to the aorta, trachea, or spine are considered unresectable, as are those who present with tracheoesophageal fistula. These patients can be candidates for radiation and chemotherapy, and reassessed for candidacy after demonstrating the appropriate response.
For early esophageal cancer, surgery is the mainstay of treatment, with or without neoadjuvant chemotherapy and radiation. Chemotherapy and/or radiation are considered before surgery for patients with full thickness involvement of the esophagus, or with local invasion to structures that can be easily resected. These patients undergo posttreatment radiologic staging to reassess resectability and undergo surgery 4–6 weeks after. Severe cardiac or pulmonary comorbid disease and advanced age are relative contraindications to surgery. Chronic obstructive pulmonary disease portends a higher risk of postoperative pulmonary complications, but several prehabilitation guidelines have been proposed to reduce this risk. Preoperative nutrition optimization is critical, as malnutrition is immunosuppressive and negatively impacts survival.
Relevant Anatomy
The esophagus consists of four layers: the mucosa, submucosa, muscularis propria, and adventitia. The arterial supply consists of the thyroid artery, the left gastric artery, the inferior phrenic artery, and the aorta. Lymphatic drainage is to the cervical, tracheobronchial, gastric, celiac, and mediastinal nodes.
Type of Surgery
Esophageal cancers involving more than two-thirds of the esophagus or the proximal portion of the esophagus typically require resection of the entire esophagus. Distal tumors, or tumors at the level of the gastroesophageal junction, can be treated with a partial resection, using intraoperative surgical pathology to ensure that the margins do not contain carcinoma or Barrett’s esophagus changes.
A gastric interposition is the most common organ used to reconstruct the esophagus, although a colonic or jejunal segment can also be used. The latter is suboptimal when compared with a gastric interposition because it requires multiple anastomoses and involves a more complex surgical resection. Additionally, blood supply via the mesenteric arteries limits the distance that this segment can be moved.
There are three commonly used approaches. The Ivor Lewis esophagectomy (ILE) starts with a laparotomy for mobilization of gastric structures and conduit construction. This is followed by a right thoracotomy for esophageal mobilization, resection, and intrathoracic anastomosis. This approach is intended for lower-third esophageal cancers, and allows for a full visualization of the thoracic esophagus and full thoracic lymphadenectomy. For tumors involving the gastroesophageal junction (GEJ), a thoracoabdominal approach can be used in which the entire procedure is performed via a left thoracic incision. This limits visualization of the proximal esophagus.
The three-hole approach (also known as the McKeown method) involves an abdominal incision, thoracic incision, and a cervical incision. In this approach, the esophageal anastomosis is made via the cervical incision. In this approach, the left neck should be free of invasive lines to make room for surgical dissection of the neck.
A transhiatal esophagectomy (THE) uses a midline upper laparotomy incision to mobilize the stomach and esophagus and a cervical incision to pull up the stomach. This does not require a thoracotomy and instead mobilizes the esophagus via dissection from the neck. This technique does not allow for extensive lymph node dissection in the chest and is not ideal for patients with cancers in the mid-esophagus. It is advantageous for patients with crippling pulmonary disease owing to its lack of a thoracotomy.
Outcomes for the above techniques are roughly similar, with a postoperative mortality rate of around 3% at high-volume centers. These approaches can be performed partially or completely using a laparoscopic or video-assisted thoracoscopic (VATS) approach. A laparoscopic and video-thoracoscopic esophagectomy is referred to as minimally invasive esophagectomy (MIE). Studies comparing MIE to the open approach have demonstrated a reduced rate of pulmonary infections, intensive care unit (ICU) length of stay, improved quality of life scores, improved physical function, superior analgesia, and decreased fluid requirements. The TIME trial (traditional invasive vs. minimally invasive esophagectomy) demonstrated superior postoperative outcomes for patients undergoing MIE as compared with open esophagectomy, and similar oncologic outcomes to open esophagectomy when patients were followed up within 3 years for cancer recurrence. , Additionally, it had equivalent specimen quality and a similar number of lymph nodes removed. Similar studies have demonstrated improved postoperative outcomes, or noninferior outcomes, as well as similar 3-year survival rates. At this time, MIE is recognized as a safe and ideal option to reduce the physiologic impact of esophageal surgery. However, data are not yet sufficient to recommend MIE as a full replacement for open esophagectomy.
Lymph node dissection is standard in all esophagectomies; however, the extent to which this is performed is subject to debate. Lymph node dissection is typically performed in the mediastinum, upper abdomen, and occasionally cervical nodes (for thoracic esophageal cancers). Paratracheal and paraaortic lymph nodes are commonly dissected.
A feeding jejunostomy is placed for the purpose of nutritional support during chemotherapy and radiation therapy.
Cervical esophageal cancer (between the posterior pharynx and upper one-third of the esophagus) is usually treated with radiation and chemotherapy, but those who fail may be candidates for surgical resection. Surgical resection is highly complex and involves a bilateral neck dissection, potential tracheostomy (if laryngectomy is required), and a thoracic and abdominal incision. It may also require removal of the pharynx, larynx, and thyroid gland.
Intraoperative Considerations
Induction and Airway Management
Patients with esophageal carcinoma often have symptoms of reflux and dysphagia, but these are not often bothersome when presenting for elective surgery. However, gastric outlet obstruction from GEJ tumors can lead to residual gastric volumes. Additionally, reflux symptoms in patients with Barrett’s esophagus may be more pronounced when lying flat. For this reason, intubation should be performed with slight head of bed elevation at 30 degrees, and mask ventilation should not exceed pressures of 20 mmHg. Patients with significant upper GI symptoms should additionally be considered for a rapid sequence intubation.
Mask ventilation, as well as noninvasive positive pressure ventilation (NIPPV) via mask, is contraindicated in the immediate postesophagectomy phase due to risk of air insufflation into the newly anastomosed esophagus. Patients with esophageal leaks or anastomotic complications who return to the operating room after esophagectomy should be treated with similar caution. At all times in the perioperative phase, even after discharge, patients with esophageal conduits are considered to be at high risk of aspiration.
Clear communication must occur between the anesthesiologist and surgeon at all times with regard to any foreign bodies in the esophagus. Orogastric tube insertion may be requested by the surgeon at the start of the case, which may be placed via endoscopic guidance. Care should be taken when removing the orogastric tube during the abdominal phase, and it should not be removed under suction to prevent esophageal shearing. Placement of the nasogastric tube during the thoracic portion should be performed under surgical instruction and very slowly to prevent esophageal rupture. Avoidance of any other monitoring devices (temperature probe, pressure monitors, etc.) in the oropharynx or esophagus is essential. Communication regarding orogastric and nasogastric tube placement and timing is perhaps the most critical element to esophagectomy ( Fig. 24.1 ).
One-lung ventilation is necessary for the thoracic portion of the procedure and is best achieved via the placement of a double-lumen endotracheal tube. In most cases, it is desirable to place the double-lumen endotracheal tube at the start of the case; however, in the appropriate patient, a single-lumen tube may be used for the abdominal portion and exchanged for a double-lumen tube for the thoracic portion.
Maintenance of Anesthesia
Controversy has emerged regarding volatile anesthetics versus total intravenous agents, with some evidence that volatile agents may impair function of neutrophil and T-cell activity, making them a desirable choice for cancer resection. Other studies have correlated improved cancer-free survival rates with total intravenous agents. Neither volatile anesthetics nor intravenous anesthetics has any clinically significant effect on oxygenation during one-lung ventilation. Complete pharmacologic muscle paralysis is required for all portions of esophagectomy.
Intravenous Access
Large bore intravenous access and radial arterial monitoring are necessary. Central line insertion is indicated if adequate peripheral large bore access is unattainable, or if a patient’s cardiac comorbidity makes vasopressor use more likely. Central venous pressure (CVP) measurement has not been demonstrated to be accurate for volume status assessment and is confounded by an open chest cavity, one-lung ventilation, and occasional surgical manipulation of the inferior vena cava (IVC).
Fluid
Surgical resection involving a major body cavity is associated with major fluid shifts. Patients with upper GI cancers may experience prolonged periods of poor oral intake, and those with advanced cancer may be undernourished. Complications such as anastomotic leak and pulmonary infections may cause a vasodilatory state and relative intravascular hypovolemia. Surgical stress is associated with a release of vasopressin, aldosterone, catecholamines, and acute-phase reactants that cause a proinflammatory state. Tachycardia, hypotension, and oliguria can make it difficult to distinguish between surgical-related inflammation and true hypovolemia.
Open esophagectomy with thoracotomy puts the fluid-sparing approach at odds with appropriate fluid resuscitation to compensate for evaporative losses from the abdomen. Evidence-based practice suggests a general trend toward minimizing fluid , ; however, studies are highly variable in what constitutes a “sparing” or “liberal approach.” For esophageal surgery, evidence suggests a trend toward a restrictive fluid management approach in which fluid is only administered for signs of hypovolemia, rather than utilizing a predetermined calculation for “fluid deficit.” Avoidance of volume overload has been clearly associated with fewer infectious complications, improved wound healing, faster extubation times, and thinner bronchoscopic secretions.
As it has become clear that invasive pressure measurements in the form of central venous and Swan-Ganz catheters carry far higher risk than benefit (and additionally confer the risk of misinterpretation), newer, less invasive approaches are recommended. Systolic pressure variation, FloTrac, and transthoracic echocardiography have been demonstrated to be useful for intraoperative fluid management, but these may be of limited benefit in the setting of an open chest, an open abdomen, and the presence of chest tubes. Esophageal Doppler measurements of cardiac output are clearly contraindicated in surgery involving the esophagus.
The first stage of esophagectomy, particularly during use of the minimally invasive laparoscopic technique, often requires steep reverse Trendelenburg position. This pooling of the blood in the lower extremities can cause postural hypotension over time and, in prolonged cases, lead to metabolic acidosis. Judicious use of fluids and vasopressors, as well as frequent arterial blood gas measurements, are warranted to prevent this.
Vasopressor Use
Phenylephrine and norepinephrine, due to their selective alpha-1 receptor agonism, are commonly used intraoperatively as vasoconstrictors to counteract anesthetic-induced vasodilation. In euvolemic patients, for whom vasopressors are used solely for this purpose, perfusion to peripheral vascular beds is maintained. However, in the setting of hypovolemia, vasopressors can impair microvascular perfusion. In patients who are bleeding or dry, efforts should be taken to restore intravascular volume prior to initiating vasopressor therapy. Fluid restrictive strategies should be used with careful titration to avoid “masking” hypovolemia with vasopressors.
Patients who are elderly, frail, or have significant cardiovascular disease may have increased susceptibility to the vasodilatory effects of anesthesia. Furthermore, evidence exists to suggest that intraoperative deviations of more than 20% from a patient’s baseline blood pressure are associated with increased perioperative mortality. After optimization of volume status, it is appropriate to use vasopressors to maintain appropriate perfusion pressure to satisfy these demands.
Pain Management
Use of thoracic epidural catheters for open esophagectomy is considered standard of care, with clear benefits for pain control, more rapid extubation times, decreased ICU length of stay, and possibly improved blood flow to the anastomosis due to local anesthetic-mediated vasodilatory effects. , There is also evidence that neuraxial anesthesia, with or without general anesthesia, is associated with prolonged survival in patients undergoing cancer resection. Thoracic epidurals are generally placed at the T7/8 level to provide adequate coverage of abdominal and thoracic incisions.
The goal of intraoperative epidural management serves to minimize opiate administration and ensure proper spread of local anesthetic to produce an effective block upon extubation. The addition of an opioid to the epidural solution is recommended to allow for lower doses of local anesthetic to prevent excess epidural-mediated sympathectomy. It may be prudent to delay initiation of the epidural infusion until closure to minimize hypotension during the case. Close monitoring of epidural analgesia should be provided by an acute pain service, in conjunction with the surgical and postanesthetic recovery room team. Epidural-mediated sympathectomy resulting in undesirable hypotension should be mitigated by dilution or cessation of the epidural infusion, rather than continuous fluid-bolusing.
Additional regional anesthetic techniques for patients who have contraindications for neuraxial anesthesia or in whom attempts were unsuccessful include paravertebral, erector spinae, serratus, and intercostal blocks. Transversus abdominus plane (TAP) blocks have demonstrated success for laparotomy incisions in one study showing similar efficacy to epidurals with regard to reduction in pulmonary complications. Serratus anterior blocks have also been shown to be comparable to neuraxial anesthesia in terms of postoperative opiate consumption in patients undergoing thoracotomy and thus in conjunction with TAP blocks represent an ideal backup choice for those who are not candidates for neuraxial anesthesia.
Minimally invasive surgical techniques allow for smaller, less painful incision sites. For such cases, multimodal anesthetic techniques using acetaminophen, gabapentinoids, intercostal nerve blocks, and intravenous opioids are appropriate.
Emergence
Provided there is no significant acidosis and usual extubation criteria are met, efforts should be taken to extubate in the operating room. This is achievable in most esophagectomy patients. Early extubation is paramount to preventing pulmonary infections, early ambulation, and pulmonary toilet.
Intraoperative Complications
Pneumothorax is common during the abdominal portion of esophagectomy ( Fig. 24.2 ). The esophagus is covered by the pleura on both sides, and bulky tumors can be adherent. A pneumothorax is most often first noted by the surgeon and then followed by increased airway pressure. Hypotension and tachycardia herald the progression to tension pneumothorax. This is more common during laparoscopic surgery due to the increased intraabdominal pressures from carbon dioxide (CO 2 ) insufflation. Upon detection of tension pneumothorax, fraction of inspired oxygen should be increased to 100%, the table should be flattened, insufflation pressures reduced, and hemodynamics supported with vasopressors.
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