Top Ten Tips Palliative Care Clinicians Should Know About Interventional Symptom Management Options When Caring for Patients with Gastrointestinal Malignancies

Introduction

Gastrointestinal (GI) malignancies are common and deadly. The most recent Surveillance, Epidemiology, and End Results Program data indicate that colorectal cancer, pancreatic cancer, and esophageal cancer are the second, third, and eleventh leading causes of cancer-related deaths in the United States, respectively. ¹ Most symptoms from GI malignancies relate to obstruction at their primary tumor sites, although GI obstruction from metastatic disease also occurs.

The predominant interventions to palliate malignant obstruction were previously surgical–esophagectomy for esophageal cancer, surgical bypass for duodenal obstruction due to pancreatic cancer, or diverting colostomy for colorectal cancer. These procedures carry significant morbidity and mortality, particularly for patients with advanced disease.^2–4 Given the risks of surgical approaches for palliation, advanced endoscopic procedures, such as endoscopic retrograde cholangiopancreatography (ERCP) and biliary and enteral stenting, have now moved to the forefront in the palliation of advanced disease.

There is increasing evidence supporting the important role of specialty palliative care in the usual care of patients with GI malignancies.^5–7 Therefore, palliative care specialists should have familiarity with endoscopic and other options for symptom management used as an adjunct to medical management. In this article, our team of interventional gastroenterologists and palliative care physicians review endoscopic management approaches to ease symptom burden and improve quality of life for patients suffering from several common sequelae of GI malignancies.

Tip 1: Self-Expandable Metal Stents Provide Durable Relief of Dysphagia from Advanced Esophageal Cancer

Nearly two-thirds of patients with advanced or inoperable esophageal cancer report dysphagia with subsequent unintentional weight loss and malnutrition. Other complications include odynophagia, tracheoesophageal fistula, and aspiration. Endoscopic management should be considered in patients who are not candidates for surgical palliation or palliative chemoradiation therapy or for those who continue to be symptomatic despite chemoradiation. ⁸

Endoscopic palliation of esophageal obstruction includes dilation, esophageal stenting, and enteral feeding tube placement. Dilation typically provides temporary relief of dysphagia with several studies noting recurrence of symptoms between 12 and 28 days ⁹ ; patients often require multiple sessions which carry an increased risk for perforation. Therefore, dilation alone is not first line for palliation of malignant esophageal obstruction.

With the development of self-expandable metal stents, palliation of esophageal cancer with endoscopic stenting has become the most common option for nonsurgical candidates. Self-expandable metal stents are composed of metal alloys, typically nitinol, which come in a variety of lengths and diameters. Stent placement is successful in the hands of experienced interventional endoscopists in 95–96% of cases of obstruction.

Complications from esophageal stents can occur in up to 30% of patients. ¹⁰ Complications can be divided into early (periprocedure and up to one week post-procedure) or delayed (beyond one week post-procedure) complications. Early complications include aspiration, malposition of the stent, esophageal perforation, chest pain, and airway compromise. Delayed complications include stent migration, tumor ingrowth leading to stent occlusion, bleeding, tracheoesophageal fistula, and gastroesophageal reflux and aspiration if the stent is placed across the gastroesophageal junction. ¹¹ After stent placement, patients should remain on a liquid or low-residue soft diet to avoid food impaction and should adhere to antireflux and aspiration precautions.

Tip 2: There Are Many Ways to Manage Gastric Outlet Obstruction with the Primary Goal of Decompression and Symptom Control

Gastric outlet obstruction (GOO) is manifested by post-prandial nausea and vomiting, abdominal distension, and abdominal pain. The incidence of GOO has been reported in up to 20% of patients with pancreatic cancer although a variety of malignant as well as nonmalignant conditions can lead to obstruction of the pylorus and proximal duodenum. ¹² If a patient presents with typical symptoms of GOO, obtaining a plain film X-ray is a reasonable first step. If this is unrevealing, cross-sectional imaging with computerized tomography (CT) can then be considered. Radiology findings suggestive of GOO include gastric distension, air fluid levels above the site of obstruction, and decompressed small bowel. IV contrast can be used to identify the etiology of the obstruction. Care should be taken with the use of oral contrast or barium in the setting of complete obstruction given the risk of aspiration.

Once GOO has been confirmed, initial management includes making the patient nothing by mouth (NPO), placing a nasogastric tube for decompression, and beginning intravenous hydration. If the obstruction is due to an underlying malignancy, there are several options that can be considered for relief of the obstruction, including endoscopic stent placement, surgical bypass, percutaneous gastrostomy tube placement, or endoscopic ultrasound (EUS)-guided gastrojejunostomy (GJ). Endoscopic stent placement will be outlined later in the text (see Tip 3). A surgical approach offers the patient definitive long-term relief and should be considered in patients who are estimated to have longer than six months to live. However, surgical intervention is also the most invasive option and requires that the patient be a suitable surgical candidate. ¹³ Placement of a gastrostomy tube can be considered to allow for venting of gastric secretions and symptom control. If possible, a jejunal feeding tube can be placed at that time as well. More recently, EUS-guided GJ has been described. ¹⁴ This has many of the same advantages of a surgical bypass, but is less invasive. Initial reports are encouraging, however, this technique is not available at most centers.

Tip 3: Duodenal Stenting Allows Reinitiation of Enteral Nutrition in Patients with Duodenal Obstruction

Pyloric or duodenal stenting is indicated when the tumor leads to symptomatic obstruction of the pylorus or duodenum for a patient with an estimated life expectancy of six months or less. Technical and symptomatic response rates vary; however, large studies have demonstrated an approximately 90% technical success rate with an 80% symptomatic response rate.^15,16

Duodenal stenting is accomplished by endoscopic placement of a self-expandable metal stent over a wire under fluoroscopic guidance or direct visualization. Stent placement is typically not indicated for benign strictures, as the majority of stents available in the United States of America cannot be removed once placed. If technical expertise is not available, the obstruction cannot be traversed during upper endoscopy, the length of the stricture exceeds approximately 8 cm, or there is a more distal stricture, then other therapeutic options should be considered. Other options in the management of gastric outlet or duodenal obstruction include surgical bypass, percutaneous GJ tube placement, or EUS-guided GJ (see Tip 2). Stent expansion typically occurs within one to two days following placement and the patient should be aware that their symptoms may not improve immediately following stent placement. ¹⁷ Once a stent has been placed, the patient's diet can be advanced from a clear diet to a low-residue diet. Patients should be advised to indefinitely avoid fresh fruits and vegetables, vegetable and fruit skins, pulpy fruits, and tough meats.

Tip 4: There Are Immediate and Delayed Risks of Duodenal Stenting That Clinicians and Patients Should Understand

Most duodenal and pyloric stents are successfully placed without complication; however, there are both immediate and delayed risks. Immediate risks include those associated with sedation, stent placement, and endoscopy, including perforation, bleeding, infection, aspiration, and stent malposition. The incidence of perforation, stent malposition, and bleeding with stent placement varies; however, large case series have reported a range of 0–4%. ¹⁷

Delayed complications include perforation, stent migration, and stent occlusion either by tumor ingrowth or obstruction with food products. If the patient develops recurrent symptoms of GOO after initial improvement, stent migration or obstruction should be suspected. A plain abdominal film can confirm stent placement as well as reveal evidence of obstruction or perforation. If migration is seen or outlet obstruction is suspected, a repeat endoscopy may be warranted. Retrieval of a migrated stent with an upper endoscopy may be possible, however, it is often technically challenging and surgical intervention may be required. Food products can often be removed endoscopically and tumor ingrowth can be treated by placing a stent within a stent and/or endoscopic ablation of the malignant tissue. If the stent is in the correct position and patent, other etiologies such as impaired motility should be considered.

Tip 5: Biliary Obstruction Can be Relieved with Stenting, Although the Type of Stent Does Matter

Biliary obstruction is most often caused by tumors of the pancreas or bile duct and less commonly by metastases from a variety of malignancies. The patient typically presents with jaundice, which is frequently painless, and sometimes pruritus. Loss of both appetite and weight is also common. The diagnosis of biliary obstruction should be confirmed with serum tests (total bilirubin, alkaline phosphatase) and imaging, most commonly ultrasound and/or CT scan to evaluate for biliary ductal dilatation.

Unless surgical resection is imminent, the first-line approach to obstruction is generally endoscopic stent placement. Percutaneous transhepatic cholangiogram with placement of a percutaneous biliary drain (PBD) is also an established method for drainage and may be first line depending on local expertise. If the decision is made to proceed with endoscopic stent placement, an ERCP is performed, during which either a metal or plastic stent can be inserted.

Plastic stents require removal and insertion of a new stent every three to six months to avoid occlusion, whereas metal stents do not require routine exchanges (see Tip 6 for further discussion). Metal stents are typically considered for patients with longer life expectancies given longer stent patency time. ¹⁸ If a stent does become occluded, changing the stent or placing another stent within the metal stent is indicated.^19,20 If ERCP stent placement is unsuccessful, palliative options typically include PBD or EUS-guided stent placement rather than biliary bypass surgery. EUS-guided biliary drainage is an evolving technique that currently is largely limited to tertiary referral centers. Determination of the initial approach should be based on overall treatment planning and local expertise.

Tip 6: Each Type of Biliary Stent Comes with Its Own Set of Complications

For patients who require biliary stenting by ERCP, the complications include the risk of anesthesia and sedation and the risks inherent to ERCP itself, such as bleeding, perforation, and ERCP-related pancreatitis. Post-ERCP pancreatitis can occur in 3–5% of cases, depending on the center's expertise. ²¹

Stent specific complications include stent migration and stent occlusion. Many of the stent-specific complications are related to the type of stent used. Plastic stents are smaller in diameter and therefore occlude much sooner than metal stents. Occlusion of plastic stents tends to occur at around three to six months, so require scheduled stent exchanges. Stent occlusion is typically characterized by rise in liver enzymes, primarily total bilirubin, dilation of the intrahepatic and extrahepatic biliary ducts proximal to the previously placed stent on ultrasound or CT imaging, and/or signs and symptoms of cholangitis (such as fever, elevated white blood cell count, and right upper quadrant pain).

Metal stents are mainly composed of nitinol in a lattice type configuration and come in several varieties–fully covered, partially covered, and uncovered. Polyurethane or silicone can be used to cover the stents, but varies with the brand of stent used. Uncovered stents tend to occlude due to ingrowth of tumor through the metal lattice. Stent migration can also occur at varying rates depending on the type of stent placed. Covered metal and plastic stents tend to have higher rates of stent migration (∼5–7%) compared with uncovered or partially covered metal stents (∼1–2%).^22,23 Lastly, much care is often taken to ensure that the stent is positioned downstream the cystic duct takeoff. Occlusion of the cystic duct with either a plastic or covered metal stent can lead to cholecystitis. ²⁴

Tip 7: Biliary Stent Occlusion Can be Managed with Several Techniques

Plastic stent occlusion is managed by endoscopic removal of the occluded stent and placement of another plastic stent or a metal stent. As discussed previously, plastic stent occlusions tend to occur as early as three months after insertion so should be reserved for patients with prognosis of less than four months, whereas covered metal stents can remain patent longer [HR 0.35 (0.27–0.46) p < 0.001]. ²⁵ While metal stents are more difficult to remove endoscopically than plastic stents, the most challenging to remove are partially covered or uncovered stents since their occlusion typically occurs due to tumor ingrowth that leads the stent to be anchored to the bile duct epithelium.

There are several techniques to manage occlusions by tumor ingrowth. Most often, the initial step is sweeping the stent of debris, dilating with a balloon, then placing another stent within the previously placed stent. A newer technique for the management of tumor ingrowth has been the use of radiofrequency ablation (RFA) within the bile duct. RFA causes coagulation and necrosis of malignant tissue thereby decreasing tumor ingrowth into the stent. ²⁶ RFA may only be available at tertiary centers with specialized endoscopists. If these endoscopic measures still do not alleviate occlusion of a previously placed stent, percutaneous drainage by interventional radiology for decompression of the biliary tree is typically required.

Tip 8: Endoscopic Stenting of Colonic Obstruction Due to Obstructive Advanced Colorectal Cancer Is Typically Very Successful

Approximately 15–20% of patients with advanced colorectal cancer can present with colonic obstruction. Also, patients with pelvic masses, such as gynecologic malignancies, can have bulky tumors leading to extrinsic compression of the colonic lumen. Symptoms of colonic obstruction include obstipation, abdominal distension, nausea, and vomiting. Colonic obstruction is often confirmed with abdominal X-ray or CT scan, then evaluated with colonoscopy.

Management of colonic obstruction can be done surgically, with diverting colostomy or ileostomy, but surgical intervention carries significant morbidity and mortality if done urgently and patients are often poor surgical candidates at presentation. Endoscopic decompression is appropriate in patients who are deemed poor surgical candidates. Endoscopic palliation of colonic obstruction includes placement of a self-expandable metal stent, a procedure that is successful in 90–93% of cases with a complication rate of <5%. Complications can include stent occlusion and stent migration. Perforation is also a concern, particularly for right-sided obstructing colon cancer. Enteral stenting for rectal cancers can also be done by skilled endoscopists. Stenting is contraindicated in rectal cancers that are less than 5 cm from the anal verge due to risk of incontinence, migration, and rectal pain. ²⁷

Colonic stenting for extracolonic malignancy is controversial. Obstruction from extracolonic masses is most often encountered in patients with gynecologic malignancies or significant peritoneal disease. Given that the technical success rate is lower and the complication rate is higher than stenting for primary colon malignancy, the role of enteral stenting in this group remains unclear. ²⁸ It is important to note that as of mid 2018, all colonic stents available in the United States are uncovered and should be considered permanent once placed.

Tip 9: Managing Pain in Pancreatic Cancer Can Also Include the Use of Celiac Plexus Neurolysis

Abdominal pain is a common symptom from pancreatic adenocarcinoma. It is usually chronic, continuous and dull and often requires opioids for relief. Opioids can provide adequate relief but can be associated with constipation, sedation, drowsiness, nausea, and vomiting. It is postulated that refractory abdominal pain is due to tumor invasion into the celiac plexus or neural alterations within the pancreas itself. ²⁹

With EUS guidance, relief of abdominal pain symptoms with celiac plexus neurolysis and blocks can be accomplished. The neurolysis procedure involves identification of the celiac artery takeoff from the aorta by EUS and injection of a solution of absolute alcohol adjacent to the ganglion to permanently ablate neural tissue of the celiac ganglion (neurolysis). Alternatively, a solution of triamcinolone can be used for more temporary analgesia (celiac plexus block), although this is a less suitable option for patients with refractory abdominal pain from pancreatic cancer. ²⁹ The treatment effect is approximately four to five weeks, but reports indicate effects can last up to three months. Side effects of celiac plexus neurolysis include bleeding, infection, diarrhea, and hypotension. There are rare reports of paralysis. Given its reasonable efficacy and favorable safety profile, early consideration of EUS-guided neurolysis is recommended for patients with unresectable pancreatic adenocarcinoma who have abdominal pain requiring regular use of opiates or pain that is refractory to medical management.

Tip 10: There Is a Potential Role for GJ Tube Placement in Malignancy-Associated Gastroparesis

Similar to symptoms of GOO, many patients with advanced pancreatic cancer can present with symptoms related to gastroparesis. Gastroparesis is defined as delayed gastric emptying without any evidence of obstruction. Symptoms of gastroparesis include early satiety, nausea, vomiting, and anorexia. Although the pathophysiology is unclear, it is thought that gastroparesis in pancreatic cancer may be secondary to micrometastatic invasion of the retroperitoneal nerves and/or vagus nerve due to a paraneoplastic process. ³⁰ Impairment of gastric motility can also be worsened by opioid therapy, which is commonly used in this patient population.

Diagnosis of gastroparesis can be made with a solid phase gastric emptying study after mechanical luminal obstruction has been excluded. Medical management with promotility agents, such as metoclopramide 5–10 mg orally three times daily or erythromycin 50–250 mg orally three times daily, can be used to treat gastroparesis, but they do carry significant side effects (irreversible tardive dyskinesia, tachyphylaxis) that must be discussed in detail with the patient. If symptoms do not improve despite maximal promotility agents, palliative care providers can consider referral for GJ tube placement. ³¹ This tube can be placed endoscopically, surgically, or by interventional radiology. The decision for the placement of a GJ tube would allow for decompression and venting of the stomach with the gastric tube and provision of enteral nutrition through the jejunostomy tube. ³² Unfortunately, there are no standardized guidelines for management of this disease entity. Although we recognize that the placement of enteral feeding tubes for patients with advanced malignancy is controversial, a multidisciplinary discussion regarding the use of GJ tubes for malignancy-associated gastroparesis should be considered.

Conclusions

Gastrointestinal malignancies often present at late stages of disease and can cause tremendous symptoms. It is important to recognize many of the symptoms related to late stages of disease. Improved technologies and advanced endoscopic techniques provide less invasive options for palliation of gastrointestinal malignancies compared with precursor surgical interventions. Symptoms related to GI tract obstruction can often be managed endoscopically and should be referred to and discussed with experienced interventional endoscopists. A multidisciplinary discussion is often necessary and may ultimately lead to symptom relief and improved quality of life.