**2.1. The optimal patient**

Patient optimization and use of appropriate selection criteria are key to minimizing postoperative morbidity. Unfortunately, those risk factors for the development of esophageal cancer may also put patients at an increased risk for postoperative complications. Risk factors include age, elevated BMI, ECOG score/functional status, dyspnea, diabetes, chronic obstructive pulmonary disease, smoking, alkaline phosphatase level elevations, low serum albumin, and increased complexity score [5–11]. However, age and performance status continue to be the most commonly reported. Neoadjuvant treatments have not been consistently proven to be a risk factor. While fibrosis often occurs after chemoradiation, potentially making surgical resection more difficult, data showing optimal timing to surgery after neoadjuvant chemoradiation and its affect on postoperative morbidity are mixed [12].

endoscopic, or surgical placement of feeding gastrostomy or jejunostomy tubes. Esophageal stent placement has the benefit of being placed during endoscopic ultrasound, a common staging procedure. While it may improve dysphagia in the neoadjuvant setting, chest pain can occur and stent migration can be seen in up to 46% of patients [20]. although stent migration can be problematic, it is often a sign of tumor response to neoadjuvant therapy, and therefore the stent may not always need to be replaced. Other reported complications of stent placement in the neoadjuvant setting include perforation, mediastinitis, bowel perforation from

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Jejunostomy and gastrostomy tube placement have been proven safe and effective for perioperative nutrition. These can be placed in the laparoscopic, open, endoscopic, or even percutaneous settings. Endoscopic placement may be difficult if a patient has a severe malignant stricture/obstruction, which is often the case when a patient is suffering from severe malnutrition and unable to pass food or liquids through the site of tumor. Gastrostomy tubes have the advantage of bolus feeding, which may improve quality of life. While gastrostomy tube placement has been proven to be safe without increasing the risk of postoperative morbidity, jejunostomy tube placement is often preferred given the stomach is the preferred organ for a neo-esophagus. Jejunostomy tubes are often placed at the time of esophagectomy as well for supportive care. However, some data support that the placement of jejunostomy tubes during esophagectomy is not always necessary [22–24]. Unfortunately, tube feeds cannot be given in boluses with jejunostomy tubes, which, if occurs, can lead to diarrhea and further dehydra-

Smoking cessation is crucial to improving morbidity from esophagectomy. This may be most beneficial if performed greater than 90 days before surgery [25]. Active smoking has also been shown to increase recurrence rates of cancer after esophagectomy [26]. Therefore, smoking cessation counseling and supportive programs are necessary when patients are being

When deciding the optimal surgeon, it is important to understand that outcomes depend on two major factors: experience and resources. It is well known that with increasing numbers of esophagectomies performed, postoperative morbidity and mortality are improved. In addition, long-term survival can also improve [27]. While data show improved outcomes at higher volume centers, this is inconsistent and may depend further on individual surgeon volumes and hospital resources [28]. Begg et al. described low-volume hospitals as 1–5 esophagectomies/year, medium volume 6–11 esophagectomies/year, and high-volume centers as those performing >11 esophagectomies/year, with an improved mortality with increasing hospital volumes [29]. Later, Birkmeyer et al. divided hospital volumes to <2 esophagectomies/year as low-volume and high-volume centers as >19 esophagectomies/year [30]. The 2003 Leapfrog Group recommended 13 esophagectomies/year as a minimum volume standard [31]. However, esophagectomies at mid-volume centers can also be safely performed, especially with a two-surgeon approach [32]. Hospital type may also be important where improved reoperation rates and mortality are seen when surgery is performed at University centers or

migration, tracheo-esophageal fistula, and bleeding [21].

assessed for esophagectomy.

**2.3. The optimal surgeon/hospital**

institutions centralizing esophageal cancer care [33–35].

tion. Patients therefore require an ongoing pump connection for feedings.

## **2.2. How to optimize the patient**

Malnutrition has been reported in 57–80% of patients with esophageal cancer [13, 14]. Many factors can be attributed to malnutrition prior to surgery and include patient factors, chemotherapy, radiation therapy, and tumor-related causes [15]. It is important to recognize that even obese patients can suffer from malnutrition. While laboratory values and anthropometric measurements can be useful, their values can vary and therefore may not be clinically relevant. Therefore, a weight loss of greater than 10% for 6 months or 5% for 1 month is considered malnourished [16].

For the malnourished patient, preoperative optimization of nutrition through the advice of a dietician is key, but other measures should be considered as well if a patient is unable to tolerate at least 50–75% of their caloric needs [15]. The preferred intervention should be handled in a multidisciplinary setting and be initiated as early as possible. This decreases the amount of weight loss, increases chances of completion of neoadjuvant therapies, and decreases hospital admissions [17].

Recommendations to maximize oral nutrition intake include dividing daily oral intake into five to six small meals where the patient is given enough time to eat, eating only foods with a high nutritional content, paying attention to presentation and preparation of meals to make food as desirable as possible, enriching meals and drinks and taking advantage of those days where the patient feels like eating, modifying the consistency of foods to ease swallowing, preventing fatigue, decreasing the risk of aspiration, eating non-irritating soft and smooth foods at room temperature and maintaining oral hygiene for those with mucositis [15]. Patients should also be advised to supplement meals with dietary supplements. The preoperative intake of combined "immunonutrition" products consisting of arginine, glutamine, polyunsaturated omega-3 fatty acids, nucleotides, and antioxidant micronutrients has been shown to decrease postoperative infectious complications and length of hospital stay [15, 18, 19].

For those unable to tolerate adequate nutrition, even with optimization and supplementation, other interventions are needed. These include either stent placement or percutaneous, endoscopic, or surgical placement of feeding gastrostomy or jejunostomy tubes. Esophageal stent placement has the benefit of being placed during endoscopic ultrasound, a common staging procedure. While it may improve dysphagia in the neoadjuvant setting, chest pain can occur and stent migration can be seen in up to 46% of patients [20]. although stent migration can be problematic, it is often a sign of tumor response to neoadjuvant therapy, and therefore the stent may not always need to be replaced. Other reported complications of stent placement in the neoadjuvant setting include perforation, mediastinitis, bowel perforation from migration, tracheo-esophageal fistula, and bleeding [21].

Jejunostomy and gastrostomy tube placement have been proven safe and effective for perioperative nutrition. These can be placed in the laparoscopic, open, endoscopic, or even percutaneous settings. Endoscopic placement may be difficult if a patient has a severe malignant stricture/obstruction, which is often the case when a patient is suffering from severe malnutrition and unable to pass food or liquids through the site of tumor. Gastrostomy tubes have the advantage of bolus feeding, which may improve quality of life. While gastrostomy tube placement has been proven to be safe without increasing the risk of postoperative morbidity, jejunostomy tube placement is often preferred given the stomach is the preferred organ for a neo-esophagus. Jejunostomy tubes are often placed at the time of esophagectomy as well for supportive care. However, some data support that the placement of jejunostomy tubes during esophagectomy is not always necessary [22–24]. Unfortunately, tube feeds cannot be given in boluses with jejunostomy tubes, which, if occurs, can lead to diarrhea and further dehydration. Patients therefore require an ongoing pump connection for feedings.

Smoking cessation is crucial to improving morbidity from esophagectomy. This may be most beneficial if performed greater than 90 days before surgery [25]. Active smoking has also been shown to increase recurrence rates of cancer after esophagectomy [26]. Therefore, smoking cessation counseling and supportive programs are necessary when patients are being assessed for esophagectomy.

#### **2.3. The optimal surgeon/hospital**

**2. Selection of the appropriate patient and surgeon**

diation and its affect on postoperative morbidity are mixed [12].

Patient optimization and use of appropriate selection criteria are key to minimizing postoperative morbidity. Unfortunately, those risk factors for the development of esophageal cancer may also put patients at an increased risk for postoperative complications. Risk factors include age, elevated BMI, ECOG score/functional status, dyspnea, diabetes, chronic obstructive pulmonary disease, smoking, alkaline phosphatase level elevations, low serum albumin, and increased complexity score [5–11]. However, age and performance status continue to be the most commonly reported. Neoadjuvant treatments have not been consistently proven to be a risk factor. While fibrosis often occurs after chemoradiation, potentially making surgical resection more difficult, data showing optimal timing to surgery after neoadjuvant chemora-

Malnutrition has been reported in 57–80% of patients with esophageal cancer [13, 14]. Many factors can be attributed to malnutrition prior to surgery and include patient factors, chemotherapy, radiation therapy, and tumor-related causes [15]. It is important to recognize that even obese patients can suffer from malnutrition. While laboratory values and anthropometric measurements can be useful, their values can vary and therefore may not be clinically relevant. Therefore, a weight loss of greater than 10% for 6 months or 5% for 1 month is

For the malnourished patient, preoperative optimization of nutrition through the advice of a dietician is key, but other measures should be considered as well if a patient is unable to tolerate at least 50–75% of their caloric needs [15]. The preferred intervention should be handled in a multidisciplinary setting and be initiated as early as possible. This decreases the amount of weight loss, increases chances of completion of neoadjuvant therapies, and decreases hospital

Recommendations to maximize oral nutrition intake include dividing daily oral intake into five to six small meals where the patient is given enough time to eat, eating only foods with a high nutritional content, paying attention to presentation and preparation of meals to make food as desirable as possible, enriching meals and drinks and taking advantage of those days where the patient feels like eating, modifying the consistency of foods to ease swallowing, preventing fatigue, decreasing the risk of aspiration, eating non-irritating soft and smooth foods at room temperature and maintaining oral hygiene for those with mucositis [15]. Patients should also be advised to supplement meals with dietary supplements. The preoperative intake of combined "immunonutrition" products consisting of arginine, glutamine, polyunsaturated omega-3 fatty acids, nucleotides, and antioxidant micronutrients has been shown to decrease

For those unable to tolerate adequate nutrition, even with optimization and supplementation, other interventions are needed. These include either stent placement or percutaneous,

postoperative infectious complications and length of hospital stay [15, 18, 19].

**2.1. The optimal patient**

30 Esophageal Cancer and Beyond

**2.2. How to optimize the patient**

considered malnourished [16].

admissions [17].

When deciding the optimal surgeon, it is important to understand that outcomes depend on two major factors: experience and resources. It is well known that with increasing numbers of esophagectomies performed, postoperative morbidity and mortality are improved. In addition, long-term survival can also improve [27]. While data show improved outcomes at higher volume centers, this is inconsistent and may depend further on individual surgeon volumes and hospital resources [28]. Begg et al. described low-volume hospitals as 1–5 esophagectomies/year, medium volume 6–11 esophagectomies/year, and high-volume centers as those performing >11 esophagectomies/year, with an improved mortality with increasing hospital volumes [29]. Later, Birkmeyer et al. divided hospital volumes to <2 esophagectomies/year as low-volume and high-volume centers as >19 esophagectomies/year [30]. The 2003 Leapfrog Group recommended 13 esophagectomies/year as a minimum volume standard [31]. However, esophagectomies at mid-volume centers can also be safely performed, especially with a two-surgeon approach [32]. Hospital type may also be important where improved reoperation rates and mortality are seen when surgery is performed at University centers or institutions centralizing esophageal cancer care [33–35].

Early recognition and treatment of complications appears to be just as important as prevention to improve mortality [36]. The recognition of postoperative problems improves with experience, making hospital volumes as well as surgeon volumes important. With morbidity rates being high, early intervention is of utmost importance to prevent further adverse outcomes or even death. In fact, even in low-volume hospitals, mortality may remain low if adequate resources are available [28, 37]. Therefore, these surgeries should only be performed at institutions well equipped to handle the possible complications [38–40]. Ancillary departments that should be available in the postoperative care may include gastroenterology, interventional radiology, cardiology, an astute critical care team, and others. Resources readily available and proven to improve complications also include nurse-to-patient ratios, where the incidence of pulmonary and infectious complications was shown to be increased when nurses had more than two patients [41].

hemodynamic instability as well as put patients at an increased risk for stroke. Atrial Fibrillation may also be an early warning sign for morbidity, especially anastomotic leak [49]. The mechanism and pathophysiology of postoperative atrial fibrillation is incompletely understood, although we know predisposing factors include advanced age, coronary artery disease, heart failure, hypertension, mitral valve disease, and previous history of atrial fibrillation [50]. One randomized, controlled trial showed that the preoperative use of amiodarone via IV infusion significantly reduced the incidence of atrial fibrillation; however, no differences were seen in median hospital stay, ICU stay, or adverse events [51]. In a study evaluating amiodarone administration through the jejunostomy tube postoperatively, there was only a trend towards lower occurrence and a shorter length of stay [52]. Beta-blockers should be continued for the prevention of atrial fibrillation as well if a patient is already taking them, but may require a reduced dose for the prevention of hypotension, especially with epidural anesthesia. Calcium channel blockers, particularly diltiazem, can also be used for the prevention of atrial fibrillation and may have less effect on blood pressure than other calcium channel blockers or beta-blockers [53]. If atrial fibrillation occurs, amiodarone, calcium channel blockers, and beta-blockers are all

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Respiratory complications in patients undergoing esophagectomy can be problematic and are often causes of mortality. When patients need to be reintubated, many require bag ventilation or positive pressure prior to intubation, which may cause insufflation of the esophagus and stomach, placing pressure on the anastomosis or staple lines. For that reason, CPAP is often avoided as well. Direct airway visualization during reintubation is also important to prevent mechanical injury in case the esophagus is intubated rather than the trachea, especially if a

Pneumonia has been shown to significantly increase mortality compared to other complications, even anastomotic leak [6, 8]. Unfortunately, it can also be the most common postoperative complication and cause for respiratory failure and prolonged ventilation [7]. The American Thoracic Society and American Infections Diseases Society define pneumonia into hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-careassociated pneumonia (HCAP) [54]. The revised Uniform Pneumonia Score aims to define pneumonia occurring after esophagectomies and includes temperature, leukocyte count, and pulmonary radiographic findings [55]. Prevention, early recognition, and treatment as well as

Aspiration is a major cause of pneumonia. This occurs more often with a cervical anastomosis, especially with recurrent laryngeal nerve injury. Recurrent laryngeal nerve palsy can occur secondary to stretching, thermal injury, or even compression. If occurs, patients may suffer from hoarseness as well as pulmonary complications such as dyspnea and aspiration, which puts them at an increased risk for pneumonia and reintubation/prolonged ventilation. However, recurrent laryngeal nerve injury may not always present as obvious hoarseness, as we know from thyroid surgery data, and therefore its occurrence may be underreported. The ECCG defines vocal cord injury/palsy as a vocal cord dysfunction postresection where confirmation and assessment are achieved by direct examination [3]. There are three types

treatments to be considered, depending on the patient's hemodynamics.

**3.2. Respiratory failure/pneumonia/prolonged ventilation**

cervical anastomosis is performed.

correction of causes are key.
