**5. Palliative endoscopic interventions**

Given that up to 80-85% of pancreato-biliary cancers are unresectable and the survival benefit of chemo-radiation therapy is very modest, palliative treatment plays a very important role in the care of these patients. Relief of symptoms secondary to gastroduodenal obstruction, jaundice and pain are essential to improve their quality of life and overall survival. In the past, surgical palliative approaches, such as gastric bypass and hepatico-enteric decompression, are more common used as the diagnosis of unresectable disease is frequently made in the operating room. With the recent improvement in preoperative staging, diagnostic laparotomy is rarely performed and biliary or gastro-duodenal obstruction is mostly managed by minimally invasive endoscopic interventions.

#### **5.1 Alleviation of biliary obstruction**

Currently, endoscopic biliary stenting is the treatment of choice for unresectable pancreatobiliary cancers with obstructive jaundice (Figure 4). Endoscopic placement of plastic stent(s) was equally effective as surgical technique in palliating obstructive jaundice, but endoscopic stent was associated with fewer procedural complications and death (Taylor et al., 2000). More recently, the invention of larger diameter self-expandable metallic (SEM) biliary stents provides longer stent patency for drainage. Compared to plastic stents, SEM stents are significantly less likely to be occluded and thus, minimized the number of repeated ERCP. As with plastic stents, endoscopic placement of SEM stents has been shown to provide similar overall survival to surgical decompression but is more cost-effective and better quality of life (Knyrim et al., 1993; Prat et al., 1998). The concurrent use of chemotherapeutic agents in patients palliated with SEM stents does not increase the risk for ascending cholangitis (Nakai et al., 2005).

Percutaneous trans-hepatic stenting (PTHS) is often reserved for patients in whom ERCP has failed due to a higher complication rate as well as poorer quality of life (Pinol et al., 2002). More recently, the advent of EUS assisted ductal drainage and stenting has significantly improved the success rate of endoscopic approach and thus, reduced the need for PTHS. This approach involves puncturing a dilated intra-hepatic duct, under direct EUS

Vinciguerra 2011). A recent systematic review evaluating retrospective and prospective studies on neo-adjuvant chemo-radiotherapy from 1966 to 2009 included a total of 111 studies and 4,394 patients suggests that up to one third of patients with previously borderline resectable cancers are eligible for resection after neoadjuvant treatment (Gillen et al. 2010). More importantly, these patients were found to have comparable median survival as those who undergoing resection followed by adjuvant therapy (20.1 vs. 23.6 months, respectively). In contrast, neoadjuvant therapy did not seem to improve overall outcome for

In contrast to pancreatic cancer, cholangiocarcinoma has been shown to be resistant to common chemotherapy (Anderson and Kim, 2009). Numerous drugs have been tested alone and in combination, and thus far, the response rate has been unacceptably low. Although gemcitabine chemotherapy is often given to patients with unresectable cholangiocarcinoma, the survival benefit has not been proven in a randomised controlled

Given that up to 80-85% of pancreato-biliary cancers are unresectable and the survival benefit of chemo-radiation therapy is very modest, palliative treatment plays a very important role in the care of these patients. Relief of symptoms secondary to gastroduodenal obstruction, jaundice and pain are essential to improve their quality of life and overall survival. In the past, surgical palliative approaches, such as gastric bypass and hepatico-enteric decompression, are more common used as the diagnosis of unresectable disease is frequently made in the operating room. With the recent improvement in preoperative staging, diagnostic laparotomy is rarely performed and biliary or gastro-duodenal

Currently, endoscopic biliary stenting is the treatment of choice for unresectable pancreatobiliary cancers with obstructive jaundice (Figure 4). Endoscopic placement of plastic stent(s) was equally effective as surgical technique in palliating obstructive jaundice, but endoscopic stent was associated with fewer procedural complications and death (Taylor et al., 2000). More recently, the invention of larger diameter self-expandable metallic (SEM) biliary stents provides longer stent patency for drainage. Compared to plastic stents, SEM stents are significantly less likely to be occluded and thus, minimized the number of repeated ERCP. As with plastic stents, endoscopic placement of SEM stents has been shown to provide similar overall survival to surgical decompression but is more cost-effective and better quality of life (Knyrim et al., 1993; Prat et al., 1998). The concurrent use of chemotherapeutic agents in patients palliated with SEM stents does not increase the risk for ascending

Percutaneous trans-hepatic stenting (PTHS) is often reserved for patients in whom ERCP has failed due to a higher complication rate as well as poorer quality of life (Pinol et al., 2002). More recently, the advent of EUS assisted ductal drainage and stenting has significantly improved the success rate of endoscopic approach and thus, reduced the need for PTHS. This approach involves puncturing a dilated intra-hepatic duct, under direct EUS

obstruction is mostly managed by minimally invasive endoscopic interventions.

patients with resectable cancer at presentation (Gillen et al. 2010).

trial (Gruenberger et al. 2010).

**5. Palliative endoscopic interventions** 

**5.1 Alleviation of biliary obstruction** 

cholangitis (Nakai et al., 2005).

Fig. 4. Examples of biliary obstruction from pancreatic cancer requiring biliary drainage using plastic biliary stent (panel A) and SEM biliary stent (panel B).

guidance, to pass a guide wire into the duodenum, which then allows successful canulation of the biliar tree via ERCP and stenting (Shami and Kahaleh, 2007). In cases of duodenal obstruction, direct biliary drainage from a dilated intrahepatic duct into the stomach or duodenum via a SEM is an effective alternative for palliation with reasonable safety profile (Iwamuro et al., 2010; Nguyen-Tang et al. 2010). Surgical biliary bypass is only considered for patients who have relatively preserved functional status with obstructive jaundice and have failed on endoscopic stent placement.

#### **5.2 Alleviation of gastro-duodenal obstruction**

Although gastric bypass is commonly performed for unresectable patients with gastroduodenal obstruction, the introduction of self-expanding metallic duodenal stents has changed the options for palliation (Figure 5). Current data suggest that placement of selfexpandable metallic duodenal stents for malignant gastric outlet obstruction is successful in 98% of cases with a median duration of patency of 10 months (van Hooft et al., 2009). Serious complications from duodenal stenting, such as gastrointestinal bleeding or perforation, are rare with long-term stent dysfunction occurs in 14% of patients and migration in only 2% (van Hooft et al., 2009). Compared with palliative surgery, stent placement provides a shorter hospital stay, earlier resumption of oral intake, fewer complications and lower hospital costs (Maetani et al., 2004; Maetani et al., 2005). Currently, surgical palliation is often reserved for patients who are expected have a long lifeexpectancy and need both biliary and gastric bypass.

Pancreato-Biliary Cancers – Diagnosis and Management 471

(Figure 6). A recent double-blind randomized controlled study has also found that celiac plexus block is superior than systemic analgesic therapy in providing pain relief and improving quality of life (Wong et al., 2004). Thus, EUS-guided celiac neurolysis should be considered in all patients who have abdominal pain related to the pancreato-biliary cancer.

Despite the recent advances in diagnostic modalities, chemo-radiotherapy, surgical and post-operative care, the overall prognosis of pancreato-biliary malignancies has barely changed over the last few decades. The management of these patients is often complex and requires expertise in many fields. Thus, multidisciplinary teams are necessary to optimize the overall care. As the majority of these patients are diagnosed in advanced stages, good palliative care measures are essential to the management. Fortunately, a number of advances in endoscopic techniques have been made to improve the quality of life of these

Anderson, C. and R. Kim (2009). "Adjuvant therapy for resected extrahepatic

Andren-Sandberg, A., A. Viste, A. Horn, D. Hoem and H. Gislason (1999). "Pain

Balzano, G. and V. Di Carlo (2008). "Is CA 19-9 useful in the management of pancreatic

Beger, H. G., F. Treitschke, F. Gansauge, N. Harada, N. Hiki and T. Mattfeldt (1999). "Tumor

Binmoeller, K. F., S. Boaventura, K. Ramsperger and N. Soehendra (1993). "Endoscopic snare

Bohnacker, S., U. Seitz, D. Nguyen, F. Thonke, S. Seewald, A. deWeerth, R. Ponnudurai, S.

Brennan, M. F. (2004). "Adjuvant therapy following resection for pancreatic

Cameron, J. L., T. S. Riall, J. Coleman and K. A. Belcher (2006). "One thousand consecutive

Chang, D. K., N. D. Merrett and A. V. Biankin (2008). "Improving outcomes for operable

Chang, D. K., N. Q. Nguyen, N. D. Merrett, H. Dixson, R. W. Leong and A. V. Biankin

pancreatic cancer: is access to safer surgery the problem?" *J Gastroenterol Hepatol*

(2009). "Role of endoscopic ultrasound in pancreatic cancer." *Expert Rev* 

management of pancreatic cancer." *Ann Oncol* 10 Suppl 4: 265-8.

consecutively treated patients." *Arch Surg* 134(5): 526-32.

adenocarcinoma." *Surg Oncol Clin N Am* 13(4): 555-66, vii.

pancreaticoduodenectomies." *Ann Surg* 244(1): 10-15.

cholangiocarcinoma: a review of the literature and future directions." *Cancer Treat* 

of the ampulla of Vater: experience with local or radical resection in 171

excision of benign adenomas of the papilla of Vater." *Gastrointest Endosc* 39(2): 127-

Omar and N. Soehendra (2005). "Endoscopic resection of benign tumors of the duodenal papilla without and with intraductal growth." *Gastrointest Endosc* 62(4):

**6. Conclusions** 

**7. References** 

31.

551-60.

23(7 Pt 1): 1036-45.

*Gastroenterol Hepatol* 3(3): 293-303.

patients and avoid unnecessary surgery.

*Rev* 35(4): 322-7.

cancer?" *Lancet Oncol* 9(2): 89-91.

Fig. 5. A case of duodenal obstruction caused by locally advanced pancreatic cancer (A) and was successfully treated with a SEM duodenal stent (B).This patient also had a SEM biliary stent inserted for biliary drainage prior to the duodenal stent placement (C).

### **5.3 Alleviation of pain**

Approximately 70% of patients with unresectable pancreato-biliary cancer develop clinically important pain, which can significantly reduce the quality and quantity of life of these patients (Andren-Sandberg et al., 1999). Good pain relief is, therefore, an essential part of effective palliative care. Although opioid analgesics are most commonly used as the first line pain relieved medication, one third of patients experience inadequate control of pain with significant side effects such as constipation and drowsiness (Andren-Sandberg et al., 1999). In these patients, neurolytic celiac plexus block under radiological or surgical guidance with absolute alcohol can be performed with up to 90% success rate (Mercadante et al., 2003; Wong et al., 2004; Noble and Gress, 2006). Recent studies have shown that EUS-guided neurolysis is equally effective but has significantly fewer serious complications associated with surgical or percutaneous approaches (O'Toole and Schmulewitz, 2009; Puli et al., 2009)

Fig. 6. Celiac ganglia can be visualized clearly on EUS imaging (panel A). Examples of EUS guided celiac ganglion blockage with alcohol injection (panel B).

(Figure 6). A recent double-blind randomized controlled study has also found that celiac plexus block is superior than systemic analgesic therapy in providing pain relief and improving quality of life (Wong et al., 2004). Thus, EUS-guided celiac neurolysis should be considered in all patients who have abdominal pain related to the pancreato-biliary cancer.
