Palliative care is an approach to care that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and assessment and treatment of pain and other problems—physical, psychosocial, and spiritual.¹ As with many health care disciplines, there are both medical and surgical components to palliative care. Palliative medical care employs expertise on the assessment and management of problems including pain, cachexia, delirium, fatigue, dyspnea, and end-of-life issues. Although palliative care has long been demonstrated to improve symptom control and quality of life, recent evidence suggests it may also be associated with longer survival.^2,3 Therefore, the American Society of Clinical Oncology has recently issued a statement suggesting that palliative care should be considered early in patients with metastatic disease and/or high symptom burden.⁴ Palliative surgery is defined as surgery for which the major intent is alleviation of symptoms and improving patient’s quality of life.⁵

The need for palliative surgery in cancer patients is frequent. Palliative surgery comprises approximately 20% of surgical practice and over 1000 procedures per year at major cancer centers.^6,7 In addition, almost half of all inpatient consultations at cancer centers meet the criteria for palliative care.⁸ Although formal training in palliative surgery is infrequently provided during surgical residency, palliative surgeries are among the most high-risk surgical procedures performed and require some of the most time-intensive preoperative discussions. Surgical decision-making and risk assessment are critical as morbidity and mortality rates for palliative surgical procedures are commonly estimated at 30% and 10%, respectively. The risk–benefit ratio is often narrow and the considerable risks of surgery must be balanced against the prognosis and estimated remaining length of life.

Pancreatic cancer represents the 12th most common cancer type but the 4th most common cause of cancer death in the United States.⁹ An individual’s lifetime risk of developing pancreatic cancer is approximately 1.5%. The majority of patients with pancreatic cancer are diagnosed with unresectable or metastatic disease at presentation, and the 5-year survival rate of pancreatic cancer is only 6%.¹⁰ In addition, curative-intent pancreatic resection only offers an expected long-term survival rate of approximately 20%.⁹ In light of the dismal rate of cure for pancreatic cancer surgery, a nihilistic approach would be to consider all pancreatic cancer surgery primarily palliative. However, as defined above, palliative surgery is defined as surgery in patients with advanced or incurable malignancy with the intent of improving quality of life or symptoms. Although improved quality of life may lead to improved length of life, all surgeries performed with an intent to cure, including for patients with resectable pancreatic cancer, are by definition excluded from classification as palliative surgery.

The more complex concept of preemptive palliation must also be addressed in discussions of palliative surgery for pancreatic cancer, as interventions to prevent subsequent potential symptoms have also been labeled as palliative surgery.¹¹ This issue has particular relevance to pancreatic cancer due to considerations for the performance of, for example, prophylactic gastrojejunostomy or celiac-plexus block during noncurative pancreatic cancer surgery, sometimes even in the absence of current symptoms of gastric outlet obstruction or pain, respectively. Although surgical interventions performed for possible symptoms that may develop later in the disease course can be controversial, we believe they are relevant to palliative care of patients with pancreatic adenocarcinoma and therefore include discussion of the relevant surgical techniques and research surrounding this issue.

The most common indications for surgical palliation of pancreatic cancer are obstructive conditions (gastric outlet obstruction and obstructive jaundice), clearly predicted on the location and adjacent anatomy of the pancreas. The pancreatic head, lodged within the curve of the duodenum, is the most common site of adenocarcinoma. The bile duct extends through the head of the pancreas, joins with the pancreatic duct, and terminates in the descending portion of the duodenum. Another common indication for palliative consultation, pain, can also be seen as an anatomic consequence of the anatomically adjacent celiac ganglion in combination with the propensity of pancreatic cancer for perineural invasion. The pancreas is well vascularized through the superior pancreaticoduodenal branches of the gastroduodenal artery and the inferior pancreaticoduodenal branches of the superior mesenteric artery. Therefore, gastrointestinal hemorrhage secondary to pancreatic tumors, including pancreatic cancer, can cause upper gastrointestinal hemorrhage which can be difficult to control. Large bowel obstruction, a rare palliative scenario with pancreatic cancer, can develop either through the association of the anterior surface of the pancreas with the transverse mesocolon or rarely from peritoneal carcinomatosis. Remaining palliative situations for which surgical consultation is requested include malignant ascites and malignant small-bowel obstruction, both a function of the aggressive metastatic potential of pancreatic cancer and its propensity to spread as carcinomatosis.

There is no clear data on the frequency of surgical palliation in pancreatic data, although there are older reports in the literature that up to 50% of patients may require surgical palliation.¹² Approximately 15% to 20% of patients with pancreatic adenocarcinoma develop gastric outlet obstruction. The reported rates of the need for palliative intervention for obstructive jaundice in patients with pancreatic cancer vary, but 30% to 60% of patients with unresectable or metastatic disease present with jaundice, depending on the anatomic site of the tumor.¹³ Pain is the most common symptom at presentation and reported in 80% of patients with locally advanced unresectable disease, and in 85% of patients with metastatic disease. Establishing an accurate estimate of prognosis is an essential part of the risk–benefit analysis in determining the advisability of palliative surgical intervention. The median survival rate for patients with metastatic disease is approximately 3 months, and it is as little as 7 months for patients with locally advanced unresectable disease.¹⁴ These estimates of median survival provide important background in determining the potential benefit of palliative surgery; with these estimates in mind, we can proceed with analysis of data supporting various palliative interventions. Also of note in reviewing the indications for palliation of the clinical scenarios of obstructive jaundice, duodenal obstruction, and celiac plexus–related pain is that palliative care decision making falls primarily into two categories: palliation in patients who are clearly not candidates for resection and palliation in patients who are deemed unresectable at exploration.

Medical Palliation

As there are effective surgical and endoscopic methods to alleviate obstructive jaundice, medical palliation is typically only required as a temporizing measure prior to definitive palliation. Topical agents are generally ineffective for pruritus secondary to obstructive jaundice. Antihistamines are often the initial treatment modality and although there is little supportive evidence, the sedating effects of H1 antihistamines are often beneficial for nocturnal pruritus. Mirtazapine, a selective norepinephrine reuptake inhibitor with antihistaminic properties, as well as opioid receptor antagonists have been associated with improvement in pruritus secondary to malignant cholestasis. Cholestyramine, a bile acid sequestrant, is also occasionally administered, but is of minimal benefit as the duct obstruction results in little bile entering the gastrointestinal tract for binding and subsequent excretion.

Procedural Palliation

Nonoperative palliation of obstructive jaundice can involve either endoscopic biliary stent placement, typically by gastroenterology specialists or surgeons with advanced endoscopic skills, or percutaneous transhepatic biliary drainage catheter placement by interventional radiology. As percutaneous transhepatic biliary drainage is more invasive and painful, and has a higher complication rate, this procedure is reserved for clinical situations in which endoscopic stent placement is not an option. Malignant strictures of the mid to lower bile ducts are usually amenable to endoscopic drainage, while strictures involving the hilum can be more challenging and may require a percutaneous approach.

ENDOSCOPIC BILIARY STENT PLACEMENT

There are several randomized controlled trials comparing plastic endobiliary stents to surgical biliary bypass in patients with pancreatic cancer requiring palliation of obstructive jaundice.¹⁵ The risk of complications was higher in the surgical group but this was offset by a higher rate of recurrent biliary obstruction in the patients undergoing endoscopic plastic stent placement. These trials were included in a recent meta-analysis demonstrating a 40% decrease in complications but 19-fold increased risk of recurrent biliary obstruction with stent placement.¹⁵ Table 143-1 contains the prospective randomized trials comparing the two approaches with the corresponding outcomes. In addition, there are also several randomized controlled trials comparing self-expanding metallic stents (SEMS) to plastic stents, and a recent meta-analysis of these trials demonstrated that the risk of recurrent obstruction with SEMS was approximately half that of plastic stents.^15,16 The obvious implication of these studies is that SEMS would likely improve upon the high risk of recurrent obstruction when compared to surgical bypass. A single randomized controlled trial of surgery compared to SEMS has been performed for patients with metastatic pancreatic cancer. Although limited by size (N = 30) and not inclusive of patients with locally advanced disease, the study demonstrated improved cost and quality-of-life scores at 60 days for patients undergoing endoscopic drainage.¹⁷

Various recommendations for stent type have been suggested based on prognostication. As an example, the European Society of Gastrointestinal Endoscopy recommends that if patient life expectancy is shorter than 4 months, initial insertion of a plastic stent is most cost-effective, but if expected survival is longer than 4 months then initial insertion of a SEMS is more cost-effective.¹⁸ Importantly, self-expanding metallic stents do not necessarily preclude subsequent pancreaticoduodenectomy in patients ultimately considered candidates for resection. Although it is always prudent to involve the surgeon in discussions prior to endobiliary stent placement, a short-segment stent can typically be removed at the time of surgery and is often within the field of resection. There is also some debate as to the application of covered versus uncovered SEMS. The current standard of care for endoscopic stenting favors placement of uncovered SEMS, as randomized trials indicate that covered stents are associated with higher rates of migration and other adverse events without an associated increase in stent patency.¹⁹

PERCUTANEOUS TRANSHEPATIC BILIARY CATHETER PLACEMENT

Percutaneous transhepatic biliary drainage is most often performed by an interventional radiologist under conscious sedation with local anesthetic administration. Unilateral drainage is often sufficient to provide symptomatic palliation of obstructive jaundice. Technical decision making by the radiologist can include approaching the side with less disease or away from an atrophic hemi-liver. The right-sided approach may also benefit from an easier angle of catheter placement and avoidance of the fluoroscopic field, while the left-sided approach may be less painful and easier for the patient to manage than a right intercostal catheter. Technical details involve first confirming access to the bile ducts through aspiration of bile or through injection of contrast and performance of a percutaneous transhepatic cholangiogram. External drainage is performed when a catheter is placed above the site of obstruction and connected to gravity drainage. External drainage alone is not ideal as patients are prone to infections, dehydration, and electrolyte abnormalities. External–internal drainage is performed when a catheter is placed through the obstruction, and allows for at least some drainage of bile into the duodenum. Although external loss of bile can be improved through this approach, patients are still prone to developing cholangitis. Strictures that do not allow immediate external–internal drainage may require a period of external drainage and a second procedure to allow passage through the stricture. Finally, conversion to internal drainage is completed when an internal stent is placed through the stricture, allowing bile drainage into the duodenum, without the need for an external catheter. Another option when an internal–external catheter is in place is to perform a combined transhepatic and endoscopic procedure, also known as a rendezvous procedure. The rendezvous procedure allows for the endoscopist to place an endoscopic stent via a wire passed through the transhepatic catheter, which may allow for decreased risk of bleeding and bile leakage compared to transhepatic dilation for stent placement. Postprocedural care for patients undergoing transhepatic drainage procedures is important for surgeons, as patients undergoing interventional procedures are often placed on surgical inpatient services. Patients should be hospitalized for at least 24 hours following transhepatic drainage to monitor for complications, and catheters should be flushed with sterile saline every 12 to 24 hours.²⁰ Patients should be well educated on the signs and symptoms of cholangitis including pain, fever, nausea/vomiting, and malaise, and should be informed that pericatheter leakage can indicate catheter occlusion.²⁰ Complications of transhepatic catheter placement can include hemobilia, cholangitis, pancreatitis, pericatheter leakage, pneumothorax, and cholecystitis due to blockage of the cystic duct. Technical and drainage success rates are routinely reported as greater than 80% and mortality rates vary widely, depending on the indication for placement and patient functional status and comorbidities.

Surgical Palliation

Only a minority of patients with obstructive jaundice require surgical palliation. Potential surgical candidates include patients for whom an endoscopic approach is not possible, patients who live remote from endoscopic and interventional expertise, and patients with concomitant duodenal obstruction. Consideration should also incorporate prognosis and performance status. Local expertise can factor heavily into the risk–benefit analysis, as patients who fail an endoscopic attempt at palliation must be considered for an interventional percutaneous procedure that may require multiple procedures to drain both sides of the liver without a guarantee that the drain can be internalized. The debate regarding the optimal approach to palliation remains active as demonstrated by a recent meta-analysis of randomized trials revealing no significant difference in major complications or death between biliary stent placement and surgical bypass, albeit with significantly lower rates of recurrent biliary obstruction in the surgical bypass group.²¹ Regardless, the most frequent current indication for surgical palliation of biliary obstruction is the patient identified with unresectable disease at laparotomy. Roux-en-Y hepaticojejunostomy/choledochojejunostomy is the most widely accepted surgical technique, while cholecystojejunostomy and choledochoduodenostomy are infrequently performed due to concerns over ineffective palliation and recurrent jaundice with tumor progression. After cholecystectomy has been performed, the common bile/hepatic duct is dissected and transected. A 60-cm Roux-en-Y limb is created and an end to side hepaticojejunostomy is performed in an interrupted fashion with 4-0 absorbable suture. Other suitable options include a loop hepaticojejunostomy rather than a roux limb. Also, some authors elect to perform a side-to-side hepaticojejunostomy without dividing the bile duct. A loop gastrojejunostomy can be added to either approach if there are coexisting concerns regarding the presence or development of duodenal obstruction.

Cholecystojejunostomy is frequently described in laparoscopic approaches to biliary bypass but is infrequently performed as an open operation due to the requirement for cystic duct patency. Although endoscopic studies of the hepatocystic junction suggest only half of patients with obstructive jaundice will be candidates based on cystic duct patency, recent case reports on laparoscopic cholecystojejunostomy have reported low rates of recurrent biliary obstruction.^22,23 Perhaps the best evidence regarding this issue can be found from a study that utilized Surveillance, Epidemiology, and End Results (SEER) Medicare claims data and demonstrated that patients treated with a gallbladder bypass had a subsequent biliary intervention rate at 1 year of 7.5%, compared to 2.9% for patients treated with a bile duct bypass.²⁴ The discrepancy in the rates of recurrent jaundice between the reports of open gallbladder bypass and newer reports of laparoscopic gallbladder bypass will need to be addressed prior to considering the laparoscopic approach a valid option. Similarly, choledochoduodenostomy is not routinely utilized for palliation due to concerns regarding recurrent jaundice with tumor progression. There are few studies comparing this approach to other forms of biliary bypass; however, small series suggest a low rate of recurrence and cholangitis.^25,26