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Gastrointestinal malignancies account for over 35% of cancer-related deaths with a projected 73% increase by 2040. Recent advances in endoscopic technique and devices have created exponential growth in the field of therapeutic gastroenterology and have enhanced diagnostic and treatment potential. As a result, palliative endoscopic therapies have experienced an equally tremendous amount of gain. Palliative endoscopy refers to maneuvers performed during gastrointestinal procedures with the intent to minimize patient suffering and discomfort. These procedures can be highly effective in providing rapid, non-operative relief and, as such, occupy an important role in the ability to alleviate symptoms of advanced malignancies throughout the gastrointestinal tract. Complications of end-stage malignances can result in tremendous discomfort, emotional trauma, and social embarrassment for the patient. Throughout the length of the gastrointestinal tract, there are a wide variety of endoscopic procedures that can provide relief in a minimally invasive fashion. The aim of this chapter is to provide insight into the current landscape of endoscopic procedures with the intent to minimize suffering, and provide a review of the indications, practice, and outcomes of endoscopic palliative therapies available.
NewYork-Presbyterian/Brooklyn Methodist Hospital, Brooklyn, NY, USA
Navim Mobin
NewYork-Presbyterian/Brooklyn Methodist Hospital, Brooklyn, NY, USA
Nicholas Gregory Brown*
NewYork-Presbyterian/Brooklyn Methodist Hospital, Brooklyn, NY, USA
Weill Cornell Medical College, New York, NY, USA
*Address all correspondence to: nb2931@cumc.columbia.edu
1. Introduction
Gastrointestinal malignancies account for over 35% of cancer-related deaths with a projected 73% increase by 2040 [1]. Recent advances in endoscopic technique and devices have created exponential growth in the field of therapeutic gastroenterology and have enhanced diagnostic and treatment potential. As a result, palliative endoscopic therapies have experienced an equally tremendous amount of gain. Palliative endoscopy refers to maneuvers performed during gastrointestinal procedures with the intent to minimize patient suffering and discomfort. These procedures can be highly effective in providing rapid, non-operative relief and, as such, occupy an important role in the ability to alleviate symptoms of advanced malignancies throughout the gastrointestinal tract. Complications of end-stage malignances can result in tremendous discomfort, emotional trauma, and social embarrassment for the patient. Throughout the length of the gastrointestinal tract, there are a wide variety of endoscopic procedures that can provide relief in a minimally invasive fashion. The aim of this chapter is to provide insight into the current landscape of endoscopic procedures with the intent to minimize suffering, and provide a review of the indications, practice, and outcomes of endoscopic palliative therapies available.
Esophageal cancer is the 7th leading cancer worldwide, with over 600,000 cases in 2020 [2]. Squamous cell carcinoma accounts for 85% of disease burden with the remaining 15% attributed to adenocarcinoma. The highest incidence of esophageal cancer has been reported in Eastern Asia and Africa, with the lowest incidence being reported in Central America and Western Africa [3].
Dysphagia, due to either intrinsic esophageal tumor or extrinsic compression, occurs in up to three-fourth of all patients and is increasingly pronounced as the disease progresses [4]. Solid food dysphagia can be severe though compensatory patient mechanisms can also make this a challenging symptom to uncover. Dysphagia to liquids typically occurs during the end-stage of the disease, hence, malnutrition is a common concern in these patients [5]. In fact, dysphagia and loss of appetite are independent predictors of poor quality of life and potential targets for endoscopic therapy [6]. Endoscopic techniques such as placement of a self-expanding metal stent (SEMS) allows patients with esophageal cancer to maintain oral food intake and improve their quality of life [7].
2.1 Self-expanding metal stents
Esophageal stent placement is preferred in patients with a short-term survival as it has been shown to induce rapid relief of dysphagia symptoms [8]. A variety of esophageal stents are available and ordinarily consist of self-expanding metal stents (SEMS), which come with an array of diameters, anti-migration features and can be covered or uncovered. Fully covered self-expandable stents (FCSEMS) and partially covered self-expandable stents (PCSEMS) are the most commonly available and are the only stents recommended for clinical practice in patients suffering from malignant dysphagia [9]. Placement of either a partially or fully covered SEMS is the core palliative therapy for these patients, however, adjunct therapies exist, including photodynamic therapy [2].
When considering placement of an esophageal stent, SEMS are generally preferred over self-expanding plastic stents (SEPSs) as they carry lower rates of symptom recurrence and adverse events [10]. There has been no difference in outcome when comparing FCSEMS and PCSEMS placement, and choice of either stent should be performed based on endoscopist preference and availability [11]. In addition, the endoscopist must also consider proximity of the malignant lesion to the airways as well as the upper esophageal sphincter. Lesions near the upper esophageal sphincter may not accommodate the proximal flange of the stent and can elevate the risk for aspiration, contributing to morbidity. Lesions with compression of, or risk of post-stent compression of the mainstem bronchus, should have collaboration with interventional pulmonary for prophylactic endobronchial stent placement in the affected airways.
Established recommendations also include SEMS placement alone with or without brachytherapy as first line therapy. Alternatively, brachytherapy alone could be considered for patients who present with dysphagia who are not candidates for resection [2, 12]. To add, a 2018 meta-analysis and systematic review of 8 RCTs found that placement of a SEMS in combination with either radiation or chemotherapy resulted in more rapid relief of dysphagia [12, 13]. Despite success in the literature, access to brachytherapy may be limited and the availability of regional services will influence the clinical treatment algorithms.
The role of esophageal stent placement in operative candidates currently is limited. A landmark 2015 study by Mariette and colleagues compared 38 candidates with resectable disease, who underwent SEMS placement compared to 152 placebo-controlled candidates found SEMS negatively impacted surgical and oncologic outcomes [14]. Palliative stent placement prior to considering resection also has temperate data and is not generally recommended [2].
In addition to obstruction, a tracheoesophageal fistula (TEF) is a common occurrence in up to 5–15% of patients with esophageal cancer and is a result of direct penetration of tumor into the airway or as a complication of radiation therapy [15]. Placement of a covered SEMS can be used to provide palliation of malignant tracheoesophageal fistulas as SEMS placement occludes the fistula and prevents extravasation of esophageal contents to the airways [16]. Clinical success rates of SEMS placement for TEF range widely, between 56 and 100%. Factors associated with potential stent failure include large fistula (>1 cm), and a proximal fistula location [17]. TEF recurrence has been reported to occur in up to 39% of cases after initial SEMS placement, though this is typically successfully managed endoscopically with repositioning or replacement of the stent [18].
Finally, placement of SEMS for relief of malignant extrinsic compression of the gut lumen is often considered less than for intrinsic disease. Although, retrospective data of 105 patients (85 intrinsic, 20 extrinsic) demonstrated the 4, 8, and 12-week patency rates of SEMSs were 90.5%, 78.8%, and 63.9%, in patients with intrinsic malignant obstruction, while the stents in the extrinsic compression group were patent until the patient expired. Thus, SEMSs in the esophagus should be considered effective management for both malignant intrinsic and extrinsic compression [19].
2.2 Adverse events
Though generally safe, adverse events must be considered when counseling patients about esophageal SEMS, including chest pain, heartburn, stent migration, tumor ingrowth, bleeding, fistula formation, food impaction and perforation [18, 20, 21]. Though tumor ingrowth and overgrowth are common in up to 14% of cases, successful management can be achieved with the stent-in-stent technique which involves placement of a covered SEMS within the existing stent to restore patency [22].
As mentioned, SEPS are not recommended due to increased incidence of stent migration when compared to their metal counterparts. To mitigate risks of reintervention due to SEMS migration, which has been estimated as high as 50% for cSEMS, partially covered SEMS and/or stent fixation should be considered. Technical and clinical success rates of fixation are high with significant reduction in migration, which can reach a nadir of 9% [23, 24].
Lastly, gastroesophageal reflux has been reported in 70–100% of patients after SEMS placement. Heartburn is a result of gastric contents refluxing into the esophagus and can especially be a concern if the SEMS spans the GE junction and disrupts the barrier of the diaphragmatic pinch and lower-esophageal sphincter. Management is with acid-suppression is effective, though SEMS with anti-reflux valves are under investigation [25].
2.3 Palliative dilatation
Palliative stent placement for benign strictures in patients who fail to reach a target diameter of 14 mm after dilation every other week over 5 sessions or fail to maintain the target diameter up to 4 weeks after the last dilation could be considered [26]. No such recommendation exists for malignant disease and dilation for malignant strictures is recommended against due to high complication rates [27].
Gastric outlet obstruction is a reduction in the caliber of the gut lumen at the level of the pylorus or duodenum. Malignant tumor invasion is one of the most common causes of GOO in the United States and it unfortunately occurs with distressing frequency in up to in up to 70% of pancreatic cancer cases and as many as 15% of patients with gastric cancer [28, 29, 30]. Symptoms include nausea/vomiting, early satiety, weight loss and heartburn are often nonspecific and require a sensitive clinician. Re-establishing continuity of the gut lumen for these patients can improve quality of life, nutritional status, discomfort, and may allow for resumption of systemic therapy [31].
3.1 Gastroduodenal stenting
As described above for symptomatic esophageal malignancy, self-expanding metal stent placement is also the mainstay therapy used to alleviate a solitary malignant gastroduodenal obstruction. Endoscopic stent placement is highly technically successful in up to 97% of cases with a near 90% clinical success, defined as symptom resolution and ability to tolerate soft solid or full liquid diet [32]. When compared to surgical gastrojejunostomy, which was the preferred therapy for malignant GOO in years past, gastroduodenal SEMS placement provides more rapid symptom relief with an average of 1.5 days to oral intake compared to 8.1 days in patients who underwent operative management. Endoscopic stent placement also results in shorter duration of hospital stay at 5.1 days vs. 12.1 days in the surgically managed cohort [33, 34, 35].
Gastroduodenal stents are manufactured as covered (cSEMS) and uncovered SEMS (uSEMS) varieties. The advantages of cSEMS and uSEMS are predictable, with higher rates of stent migration utilizing cSEMS, up to 28%, compared to 3% in uSEMS. The advantage of a cSEMS is reduced obstruction due to tumor ingrowth through the stent struts at 6.9% and 7.2% with cSEMS and uSEMS, respectively [36]. Though uSEMS are the cornerstone of therapy, stent selection varies regionally. During pre-procedure preparation, concomitant biliary stenting should be considered at the time of enteric stent placement due to difficulty of reaching the ampulla following SEMS insertion and the potential for biliary occlusion after SEMS placement. Mean hospital stays after insertion of luminal stents are typically 7 days with a mean overall survival of 100 days after stent placement [37].
Adverse events of gastroduodenal stenting are rare but including bleeding (4%), perforation, (2%), stent migration (5%), pancreatitis (<1%), and stent obstruction due to tumor ingrowth, overgrowth, or food impaction (18%) [32, 38]. When compared to surgical gastrojejunostomy, delayed complications occurred at a rate of 6.7% in the SEMS group and 13.8% in surgical group, which included post-surgical bowel obstruction, and wound infections [39].
Comparisons to surgical bypass have long been made. SEMS afford patients shorter procedure duration, more rapid symptom relief and shorter duration of hospitalization but with caveat of more frequent intervention due to stent dysfunction [39, 40, 41, 42]. Retrospective data is mixed and unsettled on which method offers increased survival, with vacillating data touting survival of one method over the other, a definitive conclusion cannot be reached. Yet, in the retrospective literature that implies a survival benefit of surgical gastrojejunostomy over SEMS, the surgical cohorts are comprised of significantly higher functional status and lower Eastern Cooperative Oncology Group (ECOG) scores with a mean ECOG of only 1 [43]. Therefore, SEMS placement remains the pillar of therapy but, in patients with excellent functional status or those with multi-focal obstruction, surgical bypass could be considered as an alternative to endoscopic SEMS placement.
3.2 Additional management strategies
Most patients with malignant gastroduodenal obstruction are appropriately managed with either SEMS placement or surgical gastroenterostomy. In clinical practice, though, situations arise where both SEMS and surgical management are either not effective or advisable. In these challenging cases, alternative therapies such as decompressive gastrostomy tube insertion or EUS-directed gastroenterostomy may be offered.
Placement of a percutaneous endoscopic gastrostomy (PEG) tube for bowel decompression is an established therapeutic option for gastric outlet obstruction. This is accomplished during an upper endoscopy following a small skin incision on the abdominal wall. A trocar and guidewire are introduced, the wire is grasped endoscopically and fastened to the PEG tube which is then withdrawn through the abdominal wall. PEG placement obviates the need for nasogastric tube decompression which is a source of significant physical and social discomfort for the patient. Gastric decompression tubes provide relief of obstructive symptoms in 95% of cases with median survival of 63 days following PEG insertion [44].
An EUS-directed gastroenterostomy is the creation of a fistulous tract under the guidance of endoscopic ultrasound between portions of the gut lumen, typically stomach and jejunum. This fistulous tract bypasses the malignant obstruction via placement of a fully covered lumen-apposing metal stent (LAMS) which connects the stomach and the loop of bowel distal to the diseased portion of the gut lumen [45]. Mounting evidence has demonstrated the safety and efficacy of EUS-guided gastroenterostomy in these clinical scenarios and it has been shown can be a technical success in over 90% of GOO cases with comparable morbidity, mortality, and hospital length of stay to a surgical gastrojejunostomy [46, 47]. It should be noted that use of LAMS in these cases, though supported by a growing body of evidence, remains an off-label indication. After multidisciplinary discussion, in cases where conventional methods of relieving GOO are not in the patient’s best interest, the treatment team should consider either decompressive gastrostomy tube or referral to a high-volume center for EUS-guided gastroenterostomy for this unique patient population near the end-of-life.
3.3 Enteral access
The decision to pursue artificial enteric nutrition in patients with advanced malignancy with late-stage malignancy can include ethical dilemmas, especially when the prospect of recovering from illness does not exist. Nutritional supplementation is provided with the intent to ameliorate suffering involved with starvation; however, it is not clear feeding via PEG tubes achieve this goal in patients with terminal malignancy [44, 48, 49]. Supporting literature in this setting also suggests that artificial enteric nutrition via PEG or NG tube also do not prolong survival, though again, data is a bit varied. Thus, with respect to achieving the goal of providing comfort and ameliorating suffering and providing comfort to family members, PEG placement for nutritional supplementation may fall short and unduly prolong suffering.
However, if enteric nutrition is desired, it can be accomplished via a nasogastric tube or a percutaneous tube such as a PEG with or without jejunal extension (PEG-J) or direct percutaneous endoscopic jejunostomy (PEJ). The method for PEG placement is briefly described earlier. PEJ tube placement mirrors that of a PEG tube placement with the exception that the percutaneous tube is placed in the jejunum rather than the anterior wall of the gastric body, a higher risk procedure with more technical challenges. A PEG-J is a PEG tube that has an external Y-port with access for venting and the other leads to a small caliber (often 9Fr or 12Fr) tube that is guided into the small bowel for feeding.
The use of a PEG-J or PEJ is reserved for patients with delayed gastric emptying and/or to theoretically decrease the risk of aspiration. Robust data is lacking and mixed, though, very small retrospective studies suggest distal feeds via a PEG-J or PEJ may potentially decrease the risk for aspiration, though more sturdy data is certainly needed to inform decision-making [48].
Minor complications after a PEG placement include PEG site pain, and cellulitis. Major complications can include bleeding, peritonitis, aspiration pneumonia, and perforation. Adverse events after PEG placement in this scenario is accompanied by major and minor complication incidence of 8.7% and 37%, respectively, with high ASA score (>/=4) as a significant predictor of adverse events [49]. Lastly, tumor seeding must be considered as well in patients with pharyngoesophageal malignancy with varying reports of tumor seeding rates to the PEG site (<0.5 to 3%) [50]. Direct access PEG or gastrostomy tube placement should be considered in these patients.
Like all medical interventions, the potential burdens and benefits, the care goals, religious practices, and medical situation must be weighed when considering PEG placement for artificial nutrition in this vulnerable patient population. Like all medical interventions, percutaneous enteral access can be ethically withheld in the proper clinical environment.
Unresectable pancreatic and hepatobiliary malignancies create unabating difficulties including debilitating pain, obstructive pruritis and jaundice, which often require intervention. Historically, surgical and percutaneous modalities were the mainstay of palliation. However, since the first endoscopic retrograde cholangiopancreatography (ERCP) in 1988 for biliary stenting of malignant bile duct obstruction, the applications of endoscopic therapies have continued to expand as have their role in palliation.
With 78% of pancreatic malignancy located in the pancreatic and a rising incidence of pancreatic head malignancy, especially in you women, early identification and management of local complications is critical [51, 52, 53]. Alleviating biliary obstruction and the associated symptoms of jaundice and pruritis can have a profound improvement on quality of life and the accompanying social discomfort. ERCP-directed therapy is the foundation of managing malignant biliary disease. In this section, we will review endoscopic management strategies in pancreatic and hepatobiliary malignancies.
4.1 Palliation with plastic stents
Since the 1970’s, plastic stents (PS) have been used for relief of malignant biliary obstruction and, over the years, have evolved into various materials including polyurethane, polyethylene, and Teflon [54]. Sizes and shapes of plastic stents range from 5 Fr to 12 Fr in diameter to up to 22 cm in length with varying shapes from straight, single, and double pigtail [55]. Plastic stents are low-cost and effective for short-term drainage with an average time to stent dysfunction being 73 days (median 62–165 days) [56, 57, 58]. Thus, they are typically used for patients with for patients with overall expected survival of less than 3–4 months, or those patients who prefer to avoid repeat ERCP and stent exchange within this time frame [57]. Plastic stent exchange is usually recommended within 3 months, though alternatively, patients may elect for “on-demand” stent changes, which can diminish the burden to the patient and the cost associated with elective ERCP.
Stent dysfunction can occur for a variety of reasons, most commonly due to lumen occlusion by biliary sludge and bacterial biofilm, with stent migration being the second most likely cause of stent-related dysfunction. PS have a significantly higher stent dysfunction rate (41%) compared to alternative options (SEMS) [59]. Most commonly, PS accumulate biliary debris and sludge, resulting clogging of the small-caliber stent lumen (33%) [59].
4.2 Palliation with self-expanding metal biliary stents
In addition to PS above, the endoscopist may also select from a variety of metal options. Self-expanding metal stents (SEMS), which have demonstrated superior patency compared to plastic stents, are available in a variety of different forms including covered (cSEMS), partially covered (pcSEMS) and uncovered (uSEMS) [60, 61, 62, 63, 64]. The primary difference between the types of self-expanding metal stents is the ability and time to removal or exchange. Placement of uSEMS is typically reserved for patients with unresectable disease as uSEMS are permanent; pcSEMS are also not indicated for removal. The chronic inflammatory response to the stent mesh along with tumor ingrowth through the wire struts, prohibits stent removal, but with the added benefit of reduced stent migration. Conversely, cSEMS have an interior coating that prevents tumor infiltration, though they are more prone to stent migration.
Stent patency of uSEMS is typically 111–273 days. uSEMS dysfunction includes a low migration rate at 0–2%, though higher occlusion rates (due to tumor ingrowth) in approximately 17% [58, 59, 62, 65, 66, 67, 68, 69, 70]. Overall uSEMS dysfunction rate is 27% [59]. A variety of remedies exist to address stent occlusion, including a stent-in-stent technique and intraductal radiofrequency ablation [61]. Other complications include acute cholangitis, persistent abdominal pain, liver abscess at 0.6–1% [61].
In contrast, cSEMS and pcSEMS have a coating to prevent infiltration of tumor and thereby prolonging lumen patency and avoiding repetitive endoscopic manipulation [8]. Covered SEMS are indicated in benign and malignant disease, and most are approved for removal. Stent patency of cSEMS is comparable to uSEMS with different mechanisms of dysfunction. Tumor ingrowth rate is nearly 0% with very few reported cases, tumor overgrowth can occur [59, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71]. However, cSEMS dysfunction includes a higher migration rate at 17% of patients [59, 67]. Overall cSEMS stent dysfunction rate is 20% [59].
Historically, cSEMS were selected for benign or resectable malignancies and uSEMS had been reserved for patients with unresectable disease. This notion has been overturned more recently and has liberated the endoscopist to select either covered or uncovered SEMS for palliation as adverse events are similar (Figure 1 and Table 1) [58, 59, 65, 66, 67, 68, 69, 70, 72, 73]. Appropriate stent selection requires consideration of patient factors (stricture size and location, presence of metastatic disease, performance status) that predict patient survival, anatomic factors and endoscopist preference. SEMS placement is not always feasible or advisable in each patient and each situation is individualized. As such, there are no universally accepted recommendations for stent selection based on survival benefit. Traditionally, endoscopists favored SEMS in patients expected to survive more than 3–6 months (Figure 1). However, that has also been challenged more recently [58, 73]. Many endoscopists suggest that SEMS should be utilized regardless of life expectancy for malignant biliary obstruction as they possess superior patency even at 30 days, improve quality of life by curtailing reintervention, reduce hospitalization, and are the more cost-effective option (Table 2 and Figure 1) [58, 61, 65, 66, 67, 68, 71, 73, 74, 75, 76].
Figure 1.
Biliary stent algorithm for malignant obstruction.
If proactive stent management is desired; PS = plastic stent; SEMS = self-expanding metal stent.
4.3 ERCP failures and alternative biliary drainage maneuvers
Due to its high success rate, ERCP remains the standard technique to restore biliary patency in malignant obstruction. However, failed ERCP can still occur in up to 40% of cases, particularly with surgically altered anatomy, tumor obstruction, duodenal diverticula, or gastroduodenal obstruction [77]. In such cases, percutaneous biliary drainage has been proven to be technically and clinically successful and is the most widely utilized next step in therapy. However, drain site discomfort and drain dysfunction, risk for recurrent infection and cholangitis, and the cosmetically unpleasant experience of having an external drainage bag have driven alternative methods [60, 78, 79]. Endoscopic ultrasound guided biliary drainage (EUS-BD) is a rapidly evolving therapeutic option in select cases not amenable to traditional biliary stenting [80, 81].
4.4 EUS-guided biliary drainage
EUS-BD has begun to emerge at the forefront of therapeutic options in patients who have had unsuccessful biliary drainage during ERCP [82, 83]. The method of achieve EUS-BD is highly dependent on patient anatomy with the intent of creating a fistulous tract from bowel to the biliary tree that cannot be decompressed with conventional methods. This often takes the form of choledochoduodenostomy or hepaticogastrostomy.
EUS-guided choledochoenterostomy is performed by puncturing the bile duct via either the gastric antrum (choledochogastrostomy) or the duodenal bulb (choledochoduodenostomy) under EUS and fluoroscopic guidance. A guidewire is passed into the bile duct, and a lumen-apposing metal stent (LAMS) or cSEMS is then placed to create a permanent fistulous connection, thus, permitting biliary drainage via the gut lumen, bypassing the obstructed or inaccessible portion of the biliary tree [84, 85].
For patients with hilar or intrahepatic obstruction, an EUS-guided hepaticogastrostomy may be applied as this utilizes a transgastric approach to puncture the left intrahepatic biliary system. The new connection between the stomach and the left intrahepatic system can then be stented in a similar manner as described above, with a covered biliary SEMS. EUS guidance can also be employed to drain the gallbladder in patients who are not candidates for cholecystectomy and place emphasis on avoiding percutaneous drainage [86].
Though informed by relatively few RCTs, current literature demonstrates high technical (94.1–100%) and clinical success (87.5%–94.0%) of EUS-BD when compared to a percutaneous approach [85, 87]. Additionally, EUS-BD procedures required fewer reinterventions (1.67 vs. 3.44) while resulting in lower adverse event rate. EUS-BD was associated has demonstrated safety with low rates of bleeding (2.7%), bile leaks (3%) and pain (1.5%) [88, 89]. Efficacy and safety of the EUS-BD approaches are not significantly different therefore, the most suitable method is dictated by patient anatomy (Figure 2) [90, 91].
Figure 2.
Suggested algorithm to restore biliary patency.
EUS directed rendezvous is an additional therapeutic in the can be used to help achieve access to the biliary after conventional methods have failed. In an EUS guided rendezvous, the bile duct is accessed from either in the stomach or the duodenum under EUS guidance. Once confirmation of the puncture is made, a guidewire is passed into the bile duct and across the papilla into the duodenum. At this time, a standard ERCP can then be performed using the existing wire for transpapillary stent placement [60].
Further studies are necessary to determine the optimal technique and tools maximize the potential of EUS-BD. Nevertheless, in established guidelines EUS-BD was substantiated as the recommended procedure of choice for biliary drainage in patients with failed ERCP—in the right clinical center, with appropriate endoscopist expertise [82, 83]. Percutaneous drainage remains an alternative if EUS-BD is unsuccessful, not feasible or not available [82]. A proposed treatment algorithm is below (Figure 2).
4.5 Radiofrequency ablation
Due to the relentless nature of pancreaticobiliary malignancies, the efforts above may be insufficient and adjunct therapies are often necessary. Radiofrequency ablation (RFA) may be used as a primary or adjunctive therapy to reduce tumor burden and improve quality of life. Endoscopic RFA utilizes radiofrequency waves at 450–500 kHz applied directly to malignant tissue to induce irreversible hyperthermic tissue injury and necrosis. Endobiliary RFA for the palliation of malignant biliary obstructions has been reported with successful restoration of biliary patency, reduced stent occlusion, and an increase in overall mean survival time [92, 93, 94, 95]. There remains a need to collect further data comparing RFA to alternative therapies (plastic stent, SEMS) for malignant biliary obstruction.
Endoscopic RFA also appears to be an effective method for restoration of malignant biliary stent obstruction. RFA therapy alone compared to PS placement for the treatment of occluded metal stents showed a significant increase in biliary patency following RFA as well as low risk of short-term adverse events stents [96, 97, 98].
While the emerging data surround RFA has been largely positive, more recent data has moderated enthusiasm for endobiliary RFA for stent occlusion. Recent studies have not demonstrated any significant difference in biliary stent patency nor overall survival versus SEMS placement alone [99]. More importantly, life-threatening complications including cholangitis, hemobilia, hepatic infarction and fistula formation have been reported following use of RFA [93, 100, 101, 102]. The use of RFA is still a relatively novel concept and consideration for use should remain dependent on institution resources and endoscopist expertise. Although early data invited some hope, there remains a significant need for additional investigation before RFA can be regularly included in the standard of palliative endoscopic care.
4.6 Photodynamic therapy
Photodynamic therapy (PDT) is another adjunctive palliative option for patients with pancreatobiliary and hepatic malignancies. PDT is the creation of selective tissue injury by systemic injection of a photosensitizing agent. This agent is preferentially taken up by the target tumor, activated by light exposure, which induces tissue necrosis of the malignant lesion. Injection of the photosensitizing agent can be achieved by ERCP or EUS. PDT has been shown to be a safe and effective method for selective tumor tissue destruction in advanced biliary malignancies [103, 104, 105]. Randomized trials comparing PDT with stenting alone have demonstrated a significantly prolonged median survival time, improved biliary drainage and improved quality of life compared to those with stenting alone [103, 106, 107]. Additionally, the benefit of PDT can be maximized with SEMS placement immediately following PDT. The median survival time in patients who underwent PDT and stent placement was 493 days compared to 98 days in patients with stent placement alone [103, 106]. Notwithstanding the reported advantages of PDT, this therapy must be discussed with the care team and patient. It is not yet commonplace in most centers due to cost burdens and side effects and, in addition, data demonstrated comparable efficacy of RFA, which is more widely available [105, 106, 108].
Despite advances in medical and surgical oncology for pancreatic ductal adenocarcinoma, only 15% of patients have resectable disease at the time of presentation [109]. Over 90% of patients with stage IV pancreatic cancer experience intense, debilitating pain. The origin of pain is poorly understood but believed to be multifactorial and principally attributed to perineural infiltration, pancreatic duct obstruction, and nodal tumor metastases. The primary goal for both patient and caregivers is effective support with proper pain control. Following the WHO recommendations, the cornerstone of symptom management is pharmacologic and is often approached using a stepwise analgesic approach beginning with NSAIDs and acetaminophen, followed by escalating doses of opiates [110, 111]. Despite this, symptoms can remain difficult to control and treatment can be accompanied by side effects including kidney injury, altered sensorium, dry mouth, pruritus, and constipation, which can be distressing and have a profound impact on patient satisfaction. In such situations, EUS-guided celiac plexus neurolysis can be an effective adjunctive therapy [112].
5.1 Celiac plexus neurolysis
EUS-guided celiac plexus neurolysis (CPN) and celiac plexus block (CPB) are often used interchangeably though they carry different indications. CPB implies the injection of a local anesthetic and steroid (i.e., bupivacaine and triamcinolone) and is typically reserved for pain from benign disease, such as chronic pancreatitis. CPN involves the injection of a local anesthetic and a neurolytic agent (i.e., bupivacaine and ethanol) to defunctionalize pain signaling from the afferent nerves of the celiac plexus to the central nervous system and offer a more prolonged and effective interruption of pain transmission.
EUS-CPN has been shown to significantly reduce pain up to 3 months following the procedure and lower narcotic consumption. Though much of the data forming the foundation of this procedure is retrospective. RCT’s have demonstrated small but significant reduction in pain 4 and 8 weeks as well as a significant reduction in narcotic use and its associated constipation without any serious adverse events [113, 114]. Successful pain reduction has also been demonstrated up to 12 weeks utilizing EUS-CPN but without any observed impact on survival or quality of life [114].
Despite decades of mostly positive data on efficacy, studies with rigorous methodology were somewhat lacking and the efficacy of CPN has now been called into question [115, 116]. A more recent RCT and retrospective study of EUS-CPN versus aggressive oral opiate dosing found a significant reduction in pain in both groups but no statistical difference appreciated between the two arms. Patients did not experience any benefit in quality or life nor reduction in narcotic consumption.
Though considered a low-risk procedure, it is important to be cognizant of the potential complications of CPN. Common procedure-related adverse events include back pain, experienced by up to 96% of patients post-procedure, transient hypotension, and diarrhea (40–60%) which are easily managed pharmacologically [114, 117, 118]. Due to the unopposed parasympathetic activity following CPN, bowel hypermobility is frequently reported and thus highlights bowel obstruction as a key contraindication to CPN [118]. Lastly, rare, but serious reported complications have been reported and include retroperitoneal bleeding, ischemia and nerve injury.
Despite recent, more humbling data for EUS-CPN, it remains a safe endoscopic modality with potential benefits. Patient factors are important to consider to maximize the benefit of CPN. Metastatic disease, pain originating from beyond the celiac plexus, and direct tumor invasion into the celiac plexus may be difficult to control, even with CPN [110, 118, 119]. During discussions with the patient and care team, EUS-CPN should be given consideration with the intent of augmenting pharmacologic therapy, reducing narcotic-induced side effects, and slowing the rate of narcotic escalation rather than with the ambition of obviating the need for pharmacologic therapy altogether.
Colorectal cancer presents as metastatic disease in up to 30% of patients, with up to 13% of all colorectal cancer patients experiencing obstructive symptoms [120, 121, 122]. Since 1991, when colonic stent placement was first introduced, reestablishing colonic patency with self-expanding metal stent has become the standard of care for malignant colonic obstruction owing to the high technical success, low complication rates, short hospitalization, improved quality of life and obviating the need for surgical management, including ostomy creation [120, 123].
The procedure mimics that of enteric stents previously described in this chapter. The endoscope is inserted to the level of the obstruction, a guidewire is used to traverse the culprit lesion and, over the wire a catheter containing a sheathed SEMS is deployed under fluoroscopic guidance. There are two main colonic stent considerations—covered and uncovered. In keeping with established guidelines, uSEMS are recommended due to lower rates of stent migration, more durable stent patency and reduced need for reintervention [122, 124].
Colonic stent placement is successful both technically and clinically, though randomized data for stent placement proximal to the splenic flexure is lacking [121, 125]. Stent patency in the palliative setting is also favorable, with median patency of 3–6 months and a robust 82% patency rate at 6 months and 50–65% at 12 months [122, 126, 127, 128].
Enteral stenting may also be feasible in patients with obstruction due to extracolonic malignancy (ECM). Though technical success rates may be high, clinical success rates, defined as resolution of obstructive symptoms, of 25–87.5%, are less impressive [129]. SEMS for ECMs are known to pose a higher risk for non-functioning immediately after placement and re-obstruction at shorter intervals compared to stenting for primary colonic malignancies [125]. In fact, given the lower clinical success rates, a larger portion of such patients will require surgical diversion [130]. Nonetheless, colonic stenting remains the cornerstone and first-line therapy which is consistent with practice guidelines [122].
Though colonic SEMS placement is a low-risk procedure adverse events can occur, including decompression failure, tumor ingrowth (3–29%), stent migration (1–10%), perforation (5–7%), bleeding (0–6%), pain [131, 132, 133, 134]. When addressing stent migration or obstruction, endoscopic reassessment with stent-in-stent placement for stent obstruction is the first line choice though many endoscopists also recommend low-residue diet and indefinite laxative use to reduce the likelihood of stent obstruction [122]. Concurrent chemotherapy administration of anti-angiogenic chemotherapy (i.e., bevacizumab) may play a role in increased risk for stent migration due to ongoing shrinkage of the tumor. Additionally, bevacizumab has been reported to increase risk of stent perforation and its use during stent placement is generally regarded as a contraindication, though SEMS are safe following cessation of the medication [122, 135].
In the troublesome cases where luminal SEMS placement is not feasible, EUS-guided therapies, such as the previously mentioned EUS-guided enteroenterostomy, can be considered in the appropriate patient. In small series, tertiary care centers have demonstrated the efficacy of EUS-guided colo-colonic LAMS therapy to bypass the occluded large bowel [136, 137]. EUS-directed colo-colonic LAMS is part of a growing armamentarium of therapeutic options, and may be considered based on local expertise, multidisciplinary discussion, and patient wishes.
Colorectal cancer is one of the most common malignancies and complications related to this unfortunate disease are certain to be encountered. Fortunately, endoscopic management for symptomatic malignant large bowel obstruction is technically and clinically successful with few adverse events. The decision to proceed with stent placement should be made after multidisciplinary discussion and including the surgical and oncological teams. With exception of a pre-existing colonic perforation, SEMS placement is the preferred treatment for the palliation of malignant colonic obstruction with clear quality of life benefits and should be offered as first-line therapy [122].
Advanced gastrointestinal malignancies are a sobering set of diseases with intensely troublesome side effects. All such patients should be treated in multidisciplinary setting with early involvement of palliative care discussions. Owing to developments in technology and evolution of endoscopic interventions, we now have greater support than ever before for patients with gastrointestinal malignancies near the end of life. The above chapter should serve as a guide to understand the data and endoscopic treatment options available for compassionate and individualized care.
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Written By
Karthik Chandrasekaran, Navim Mobin and Nicholas Gregory Brown
Submitted: 08 September 2023Reviewed: 15 September 2023Published: 06 January 2024
Open access peer-reviewed chapter
