Overview

Pancreatic and periampullary tumors are the fifth most common cause of cancer-related death in the Western world (DiMagno et al, 1999; Greenlee et al, 2000). The incidence in the United States is approximately 10 per 100,000 persons per year. Most of these tumors are pancreatic adenocarcinoma, and the survival is poor (DiMagno et al, 1999; Greenlee et al, 2000; Gudjonsson, 1995, 2009; Kuhlmann et al, 2004). Despite surgical treatment with or without radiotherapy and chemotherapy, the overall 5-year survival is approximately 4% and has barely improved over the last few decades (Fig. 63B.1; Gudjonsson, 2009; Kuhlmann et al, 2004). Most patients are seen initially with “incurable” disease, owing to extensive local disease or metastases at the time of diagnosis (Sener et al, 1999). Confusion surrounds the terminology, however, with the words incurable, inoperable, and unresectable having a variety of interpretations. Use of the term unresectable partly depends on the local surgical philosophy (e.g., accepting a resection of the mesenteric artery portal vein and macroscopically nonradical R2 resections). This surgical philosophy is not only a country-related or regional pattern, it also may be influenced by the experience at the center and the local tradition of the surgeons. The strong relationship between outcome and hospital mortality may play a role in the indication for resection and acceptance of palliative resections (Alexakis et al, 2004; Birkmeyer et al, 2003; Gouma et al, 2000).

FIGURE 63B.1 Kaplan-Meier survival curves of patients who underwent a resection (n = 160) or a palliative bypass (n = 183) between 1992 and 2002. The median survival after resection and bypass were 17 and 7.5 months, respectively (P < .01).

(Modified from Kuhlmann KF, et al, 2004: Surgical treatment of pancreatic adenocarcinoma: actual survival and prognostic factors in 343 patients. Eur J Cancer 40:549-558.)

It has been questioned whether cure is possible at all in patients with pancreatic cancer (Gudjonsson, 1995, 2009). Gudjonsson summarized the literature, and after adjusting for calculations and duplications, suggested that the total number of 5-year survivors is hardly more than 700 to 800.

There is consensus, however, that patients who undergo resection have the best chance for long-term survival (Alexakis et al, 2004). A recent study showed up to 20 years survival after resection (Adham, 2008). Survival data for patients with distal bile duct carcinoma do not differ from data for patients with pancreatic cancer. Patients with ampullary tumors have a 5-year survival of 20% to 45%, and only a few go straight to palliative treatment (de Castro et al, 2004).

Overall, most patients have palliative treatment, and palliation of symptoms is still the major focus. According to the World Health Organization (WHO, 2002), palliative care is aimed at the improvement of the quality of life (QOL) of patients who face a life-threatening illness and at the prevention or relief of pain and symptoms. The three most important symptoms that should be treated in advanced pancreatic and periampullary cancer are 1) obstructive jaundice, 2) duodenal obstruction, and 3) pain.

The decision to aim for palliative treatment can be made at two different points during the disease (Nakakura & Warren, 2007). The first decision generally is made after staging procedures, and a selection is made for potential curative surgery, palliative surgery, or nonsurgical (endoscopic) palliation. Recently, another option, preoperative radiochemotherapy and subsequent exploration, has been introduced for patients with borderline resectable lesions in an attempt to reduce local tumor ingrowths (Abrams et al, 2009; Bjerregaard et al, 2009).

The second decision is the selection of treatment strategy made during surgery, which can be an attempt for a resection with curative intent (R0/RI), a resection for palliation (RII), or other surgical procedures for palliative treatment, such as drainage.

Accurate initial staging is the crucial step for the selection of surgical and nonsurgical (palliative) treatment. Radiologic imaging techniques have evolved rapidly in the last decade. Various methods, such as contrast-enhanced spiral computed tomography (CT) and endoscopic ultrasonography (EUS), have enhanced the accuracy of radiologic staging, and noninvasive staging procedures are currently the first choice (Alexakis et al, 2004; McMahon et al, 2001; Phoa et al, 2000). Recent evaluation has identified the “new group” of patients, the borderline resectable patients, for pretreatment assessment, and criteria have been described (Callery et al, 2009). Endoscopic retrograde cholangiopancreatography (ERCP) is no longer used as a diagnostic procedure.

The role of diagnostic laparoscopy in combination with laparoscopic sonography has been studied extensively in the past (Bemelman et al, 1995; Friess et al, 1998; Nieveen van Dijkum et al, 2003; Pisters et al, 2001; Tilleman et al, 2004), but its role has diminished. A review showed that no data justify the routine use of staging laparoscopy (Pisters et al, 2001). In a recent series, however, metastasis or local ingrowth was found in 27%. Some authors therefore suggest that it should be used selectively for patients with larger tumors and tumors located in the body and tail (Chang, 2009).

Depending on local philosophy, patients who are found to have a resectable tumor at preoperative noninvasive diagnostic workup should undergo an exploratory laparotomy immediately without preoperative biliary drainage (van der Gaag et al, 2010). Patients with unresectable or incurable disease found during exploration (11% to 50%) are generally considered to be best treated with surgical palliation (Nieveen van Dijkum et al, 2003; Pisters et al, 2001; Sohn et al, 1999). This chapter evaluates the current knowledge of different aspects of surgical and nonsurgical palliative treatment for the symptoms mentioned above: obstructive jaundice, duodenal obstruction, and pain.

Obstructive Jaundice

At the time of diagnosis, 90% of patients with pancreatic and periampullary tumors present with obstructive jaundice. Obstructive jaundice is associated clinically with jaundiced skin and sclerae, nausea, pruritus, dark-colored urine, and decoloring of the stool. More severe consequences are liver dysfunction and eventually hepatic failure secondary to bile stasis and cholangitis, which is found more frequently in patients with ampullary lesions compared with patients with pancreatic cancer. Relief of obstructive jaundice causes a dramatic increase in the QOL of patients and should always be achieved (Abraham et al, 2002; Crippa et al, 2008).

Biliary drainage can be achieved nonsurgically by placement of a biliary stent (endoscopic or percutaneous; see Chapter 18) or surgically by performing a biliary bypass (see Chapter 29). The success rate for short-term relief of biliary obstruction is comparable for surgical and nonsurgical biliary drainage procedures and ranges from 80% to 100%.

In the past, endoscopic biliary drainage was widely performed with plastic stents (polytef [Teflon] and polyethylene). Plastic stents can cause complications such as migration and occlusion, reported in 40%. A new stent type for endoscopic treatment is the self-expandable, covered metallic stent. Compared with plastic stents, expandable stents have a longer patency, but they generally cannot be removed after placement (Davids et al, 1992; Kaassis et al, 2003; Weber et al, 2009).

A surgical bypass can be performed by a hepaticojejunostomy alone or by a double bypass including a gastroenterostomy. In earlier studies, surgical bypass was associated with high rates of morbidity and mortality (Watanapa & Williamson, 1992).

Surgical or Endoscopic or Percutaneous Drainage of Obstructive Jaundice

Five prospective, randomized controlled trials have been performed, four of which compared surgical biliary drainage and endoscopic drainage (Andersen et al, 1989; Bornmann et al, 1986; Nieveen van Dijkum et al, 2003; Shepherd et al, 1988; Smith et al, 1994). In the first trial by Bornmann and associates (1986), percutaneous biliary drainage was used, and no differences were found between percutaneous and surgical palliation (Table 63B.2). The other studies were performed between 1988 and 1994, except for the study done by Nieveen van Dijkum and colleagues (2003), in which patients underwent a diagnostic laparoscopy as a final staging procedure, and randomization was performed after pathology had proven metastasis. The small number of patients randomized hampered the studies by Shepherd and associates (1988) and Andersen and colleagues (1989). Shepherd and colleagues predominantly used 7-Fr endoprotheses, which are known to have a higher occlusion rate than 10- or 12-Fr endoprotheses or Wallstents currently used (Davids et al, 1992). A study by Shepherd and colleagues (1988) had a relatively high rate of recurrent jaundice and cholangitis. The length of follow-up in both studies was unclear, and the registration of complications and the readmission rate were limited. In the study by Smith and coworkers (1994), 201 patients were randomized. A higher procedure-related mortality rate was found after bypass compared with stenting (14% vs. 3%), and the 30-day mortality rate was not significantly different (8% vs. 15%) but was still relatively high. Major complications after bypass versus stenting were significantly different (29% vs. 11%), but minor complications were comparable (29% vs. 18%). The recurrence of jaundice and cholangitis during follow-up was significantly higher after stenting (36% vs. 2%), but survival was comparable between groups (Smith et al, 1994).

Table 63B.2 Prospective Randomized, Controlled Trials Comparing Percutaneous or Endoscopic Drainage with Surgical Biliary Drainage

Taylor and associates (2000) conducted a meta-analysis using the three above-mentioned studies of endoscopic stenting and concluded that more treatment sessions were required after stent placement than after surgery, with a common odds ratio (OR) estimated to be 7.23. This ratio indicates a more than sevenfold increased risk of additional treatment sessions after stenting. No significant difference between the two treatment strategies was found concerning 30-day mortality rate.

The more recent randomized study by Nieveen van Dijkum and colleagues (2003) analyzed the value of diagnostic laparoscopy for patients with a periampullary carcinoma. Patients who were found to have incurable disease owing to pathology-proven metastases were allocated to either surgical (double bypass) or endoscopic palliation by a Wallstent. No difference was found in procedure-related morbidity or number of readmitted patients between the surgically and endoscopically palliated patients (see Table 63B.2). The survival was 192 days and 116 days in the surgical and endoscopic groups, respectively (P = .05; Fig. 63B.2). This study concerns a select group of patients who were believed to have a resectable tumor after conventional radiologic staging, leading to a low (zero) procedure-related mortality.

FIGURE 63B.2 Survival in patients with unresectable peripancreatic carcinoma allocated to endoscopic (n = 14) or surgical palliation (n = 13). Dark gray areas under the curve represent the time spent in the hospital.

(Modified from Nieveen Van Dijkum EJ, et al, 2003: Laparoscopic staging and subsequent palliation in patients with peripancreatic carcinoma. Ann Surg 237:66-73.)

So far, a few general conclusions can be drawn from the available studies. Surgical treatment of biliary obstruction in unresectable pancreatic cancer is associated with higher early morbidity, a longer hospital stay, and probably a higher initial mortality rate, but long-term results are better. Endoscopic treatment is associated with lower initial mortality and morbidity, but it more frequently leads to late biliary complications and reinterventions resulting from clotting of the stent, infection, and gastric outlet obstruction (GOO).

Gastric Outlet Obstruction

Symptoms of GOO, such as nausea and vomiting, are reported in 11% to 50% of patients with pancreatic cancer at the time of diagnosis (DiMagno et al, 1999). For the optimal palliative treatment, it is important to determine the origin of these symptoms. The first cause is motility dysfunction of the stomach and duodenum secondary to tumor infiltration of the celiac nerve plexus (Thor et al, 2002) or probably dysfunction of the small bowel owing to tumor infiltration around the mesenteric artery. The second cause of GOO is mechanical obstruction of the duodenum from direct tumor ingrowth into the duodenum or secondary to compression of the duodenum by a tumor in the direct vicinity. At presentation, mechanical obstruction is reported in only approximately 5% of patients with pancreatic or periampullary tumors.

Surgical palliation should be performed only when GOO has a mechanical cause. When there is no mechanical cause, pharmaceutical treatment options should be investigated (Yeo et al, 1993). It is important to confirm mechanical GOO radiologically or endoscopically. Approximately 3% to 20% of patients with unresectable pancreatic cancer eventually develop mechanical GOO (Espat et al, 1999; Lillemoe et al, 1999). In a review by Watanapa and Williamson (1992) that included 1086 patients, 17% developed mechanical GOO, and an additional gastrojejunostomy was performed on these patients. In patients who are found to have an unresectable tumor at laparotomy, a gastrojejunostomy, in addition to a biliary bypass, is often performed and is not associated with increased morbidity and mortality (see Table 63B.1).

Endoscopic duodenal stenting also is accepted as a nonsurgical palliative treatment of duodenal obstruction (Holt et al, 2004; Telford et al, 2004). In a multicenter study, the success rate after stent placement was 84%, and oral intake in patients with successful stent placement resumed for a median time of 146 days (Telford et al, 2004). Recently, a systematic review was performed to analyze medical outcome and costs of gastrojejunostomy and stent placement. No difference was found in technical success rate (96% vs. 100%), early and late major complications (7% vs. 6% and 18% vs. 17%, respectively), and persisting symptoms (8% vs. 9%). Hospital stay was longer after surgical gastrojejunostomy, 13 versus 7 days after stent placement. The mean survival time after gastrojejunostomy was 164 days versus 105 days after stenting. The authors concluded that a stent should be used for patients with a relatively short life expectancy, and gastrojejunostomy should be performed for patients with a prolonged prognosis (Jeurnink et al, 2007).

Among surgeons and gastroenterologists, it is debated whether a prophylactic gastrojejunostomy should be performed. This is an important topic because only 40% to 80% of patients with pancreatic cancer who initially undergo an exploratory laparotomy with the intention to perform a pancreatoduodenectomy undergo a resection (Alexakis et al, 2004; Kuhlmann et al, 2004; Pisters et al, 2001; Sohn et al, 1999). Two randomized controlled trials evaluated the role of a prophylactic gastrojejunostomy in patients who were found to have an unresectable periampullary or pancreatic tumor during exploratory laparotomy (Lillemoe et al, 1999; Van Heek et al, 2003). Lillemoe and colleagues (1999) analyzed 87 patients who were found to have an unresectable tumor and were believed to not be at risk for duodenal obstruction. These patients received either a prophylactic retrocolic gastrojejunostomy and a biliary (double) bypass or a biliary (single) bypass alone. Both groups also underwent a chemical splanchnicectomy during the laparotomy. The addition of a prophylactic gastrojejunostomy did not increase procedure-related mortality and morbidity rates and did not extend hospital stay (Table 63B.3). None of the patients who received a gastrojejunostomy developed late GOO during follow-up compared with 19% of patients who did not undergo a gastrojejunostomy in the initial procedure, which was a significant difference. No significant difference in survival was found between both groups.

Van Heek and colleagues (2003) also randomly assigned patients found to have a resectable tumor during exploration to either a single bypass or a double bypass in a multicenter trial. The outcome of the interim analysis after 50% (n = 70) of the inclusion was comparable with the outcome of the study by Lillemoe and colleagues (1999), and it was decided to discontinue the trial. During follow-up, clinical GOO was diagnosed in 5.5% of patients after double bypass and in 41.4% of patients after single bypass, which was a significant difference (Fig. 63B.3). The study by Van Heek and colleagues (2003) also longitudinally evaluated the QOL of these two patient groups using the EORTC-C30 and Pan 26 questionnaires. Overall, no major differences were observed in the QOL between the two surgical treatment groups (Fig. 63B.4). After surgery, most QOL scores deteriorated temporarily and were restored to their preoperative levels within 4 months. This pattern of a temporary deterioration of the different domains of QOL score and restoration after a few months also was found in patients undergoing a Whipple procedure and was comparable to the temporary deterioration of QOL after bypass surgery (Nieveen van Dijkum et al, 2005).

FIGURE 63B.3 A, Gastric outlet obstruction caused by a stenosis due to local tumor ingrowth 6 months after a palliative gastroenterostomy. B, Treatment with the introduction of a Wallstent through the previous gastrojejunostomy.

FIGURE 63B.4 Quality of life graphs representing the 12 months after surgery of patients randomized to receive a double or single bypass. The left side of the graph represents the time of the operation. The nonimputated subscales of the following subscales are presented: A, Global health status. B, Physical functioning. C, Emotional functioning. D, Pain. E, Digestive symptoms.

(Modified from van Heek NT, et al, 2003: The need for a prophylactic gastrojejunostomy for unresectable periampullary cancer: a prospective randomized multicenter trial with special focus on assessment of quality of life. Ann Surg 238:894-902.)

The results of a recent meta-analysis also favor prophylactic gastroenterostomy. The chance of GOO during follow-up was significantly lower (OR, 0.06; 95% CI, 0.02 to 0.21; P < .001) with no difference in postoperative morbidity and mortality rates (Hüser, 2009). In these studies, endoscopic stenting of duodenal obstruction during follow-up was not attempted routinely, which could influence the outcome in the near future. A new trial should focus on nonsurgical palliation, including stenting of the common bile duct and the duodenum and adding a celiac plexus block by EUS versus the “optimal” surgical palliation described above, including the double-bypass procedure.

Pain Management

At the time of diagnosis, approximately 40% to 80% of patients report pain. As the disease progresses, more than 90% of patients eventually have moderate to severe pain. The pain of advanced pancreatic cancer is located most frequently in the upper abdomen (epigastric region) and the back and may be caused by tumor ingrowth into the mesenteric and celiac nerve plexus.

Another phenomena, such as neurogenic inflammation, well known from patients with chronic pancreatitis, could also lead to pain generation in this group of patients. These different mechanisms have been summarized nicely in a recent report on pain generation (di Mola & di Sebastiano, 2008). Initial pain management should be pharmacologic and should be composed of analgesics such as nonsteroidal antiinflammatory drugs (NSAIDs) and oral or transdermic narcotic analgesics (Cruciani & Jain, 2008). Side effects of these drugs are frequently reported, however, and eventually pharmaceutical pain management alone may be insufficient (Caraceni & Portenoy, 1996). The next step is a celiac plexus nerve block, which was first described by Kappis in 1914. The nerve block interrupts the innervation of the pancreas and prevents painful stimuli from reaching the brain. This is a relatively straightforward procedure, but it can cause side effects, such as diarrhea and orthostatic hypotension, in approximately 40% of patients (Eisenberg et al, 1995). Currently, the celiac plexus block can be performed percutaneously, by EUS, or during laparotomy. Permanent paraplegia is uncommon (0.15%) but is the most dramatic complication of this procedure, which results from an infarct/occlusion of the art spinalis anterior (Abdalla & Schell, 1999).

Celiac Plexus Block During Surgery

Celiac plexus block during surgery has been performed for many years. Lillemoe and colleagues (1993a) conducted a double-blind, randomized, controlled trial that compared a chemical splanchnicectomy during laparotomy with alcohol versus saline placebo. Chemical splanchnicectomy was performed perioperatively by injection of 20 mL of either 50% alcohol or saline solution on each side of the aorta at the level of the celiac axis. No differences were observed between the two groups concerning mortality rate, procedure-related complications, and hospital stay. Long-term complications and side effects were not investigated. Compared with the placebo group, alcohol injection significantly reduced the mean pain score for surviving patients at 2, 4, and 6 months (Fig. 63B.5). In the alcohol group, significantly more patients never reported pain (56% vs. 34%). However, the analgesic effect was not permanent: 10% of patients in the alcohol group required an additional percutaneous celiac axis block compared with 12% in the saline group. The time interval between the initial operative and additional percutaneous block varied significantly (11.8 ± 3.2 vs. 4 ± 1.1 months) in the alcohol group and saline group, respectively. Actuarial survival was improved in the subgroup of patients who reported significant preoperative pain and underwent a splanchnicectomy with alcohol (P < .001). The authors suggested that the difference could be caused by the progressive physical deterioration secondary to persistent pain, which eventually leads to impaired survival. These findings confirm other reports that state the presence of pain is associated with a poor prognosis (Kelsen et al, 1997).

FIGURE 63B.5 Mean pain scores (visual analog scale) measured preoperatively at 2, 4, and 6 months with final assessments for all randomized patients surviving at each point.

(Modified from Lillemoe KD, et al, 1993: Chemical splanchnicectomy in patients with unresectable pancreatic cancer: a prospective randomized trial. Ann Surg 217:447-455.)

The Amsterdam group retrospectively analyzed pain in 74 patients who underwent a palliative bypass for pancreatic adenocarcinoma (Van Geenen et al, 2002). The investigators found a significant difference in survival between patients who reported preoperative pain and patients who did not (4.9 vs. 9.5 months, respectively; P = .01; Fig. 63B.6). The association of persistent pain with a more advanced stage of the tumor could also explain this difference.

FIGURE 63B.6 Survival of 74 patients with or without preoperative pain who underwent a palliative bypass for nonresectable pancreatic adenocarcinoma.

(Modified from Van Geenen RC, et al, 2002: Pain management of patients with unresectable peripancreatic carcinoma. World J Surg 26:715-720.)

Another strategy to palliate pain is the thoracoscopic splanchnicectomy. A bilateral thoracoscopic splanchnicectomy or a unilateral left-sided thoracoscopic splanchnicectomy can be performed. Ihse and colleagues (1999) performed a prospective study analyzing the follow-up of patients with pancreatic cancer (n = 23) or chronic pancreatitis (n = 21) who underwent a bilateral thoracoscopic splanchnicectomy. Within 1 week, the average pain scores were reduced by more than 50% and remained stable throughout the follow-up period of 4 months. Four patients (9%) required a thoracotomy because of a bleeding complication. Leksowski (2001) showed adequate and consistent pain relief in 26 patients who underwent a unilateral splanchnicectomy. Follow-up was also limited to 6 months, and recurrent pain after that period was not analyzed.

Radiotherapy can also be applied to reduce pancreatic cancer pain. It may take several weeks before pain relief is achieved, however, and side effects are common. Most studies are limited because of small patient numbers and poor pain assessment methods. Ceha and colleagues (2000) investigated the feasibility of high-dose conformal radiotherapy (70 to 72 Gy, 35 to 36 fractions) in 44 patients with nonresectable pancreatic cancer. Pain relief was experienced in 68% of patients, with a median duration of 6 months to pain progression.

In accordance with the results from previous studies, a chemical splanchnicectomy should be considered during the initial double-bypass procedure for patients with nonresectable pancreatic carcinoma. In other patients, pharmacologic pain management as described earlier is the first step, followed by percutaneous or US-guided celiac plexus block. For recurrent pain problems, radiotherapy and incidental thoracoscopic splanchnicectomy are performed.

Pancreatoduodenectomy For Palliation

Several reports have discussed the indications to perform a pancreatoduodenectomy as a palliative treatment option (Fusai et al, 2008; Gouma et al, 1999; Köninger et al, 2008; Lavu et al, 2009; Lillemoe et al, 1996; Reinders et al, 1995; Schniewind et al, 2006). This controversial question results from the observation of reduced morbidity and mortality associated with pancreatoduodenectomy in high-volume centers (Cameron et al, 1993; Kuhlmann et al, 2004; Lillemoe et al, 1996). This decreased mortality rate is partly due to improved management of severe complications (de Castro et al, 2005), but mainly to a hospital volume effect (Alexakis et al, 2004; Cameron et al, 1993; Gouma et al, 2000).

Frequently, the term palliative resection has been used to describe patients in whom the palliative resection was regarded as a macroscopically radical resection, which appeared to be microscopically nonradical after pathologic examination, a so-called R1 resection (Table 63B.4). Although the resection was undertaken with a curative intention, it can be considered palliative (Fig. 63B.7). In this case, the resection is called palliative in retrospect. The percentage of these patients from cohort studies depends heavily on the quality of the pathology examination of the specimen. It is debatable whether these patients should be included, if the role of a palliative resection per se is discussed, because these patients underwent a resection with a curative intent. The term palliative resection probably should be used only for R2 resections, those with macroscopically residual tumor. In a few of these situations, the tumor is found to be nonresectable after a point of no return (e.g., after transection of the pancreatic neck), or resection is required because of preoperative tumor bleeding. As a result of improved staging strategies by CT and MRI, and the nonsurgical management of bleeding by selective embolization, this indication is limited in current practice (Alexakis et al, 2004; de Castro et al, 2005; Phoa et al, 2000; WHO, 2002). However, some authors consider this an optimal palliative treatment (Köninger et al, 2008). No prospective studies in which a resection was performed or planned as a palliative procedure after adequate preoperative staging showed advanced disease leading to R2 resection.

FIGURE 63B.7 Obstructive jaundice after a palliative pylorus-preserving pancreaticoduodenectomy. A, Stenosis occurred secondary to recurrence at the bifurcation. B, Palliative treatment was given for another 4 months by a percutaneous Wallstent and three percutaneous drainage catheters. Eventually the patient died as a result of recurrent cholangitis.

The benefit of surgical resection in the subset of patients with advanced pancreatic cancer, including those with vascular ingrowth in portal vein and/or mesenteric vein, should be balanced against the potential benefits and complications of palliative chemoradiotherapy. Because no randomized controlled trials have been done, a decision analysis was provided comparing the survival after pancreatic resection, including portal vein resection, for locally advanced pancreatic cancer with survival after palliative chemoradiotherapy. It was concluded that surgical resection might confer a survival advantage over palliative chemoradiotherapy in selected patients with presumed local venous ingrowth. However, it was also found that if the probability of an R1 or R2 resection is greater than 77%, resection is no longer the favored strategy (Abramson et al, 2009). Another group of patients is a very small, well-selected group in which (palliative) resection is performed: patients with metastatic disease, mainly patients with solitary (small) liver metastasis, limited peritoneal metastasis, or interaortacaval/intermesenteric lymph node metastasis. A few small studies have been published that show combined pancreatic resection with hepatic resection is technically possible and relatively safe (Gleisner et al, 2007; Shrikhande et al, 2007). These studies showed no long-term survival, and it might be questioned whether survival in this highly selected group of patients is better compared with that of patients who receive other palliative procedures. The study from Hopkins (Fleiser, 2007) showed similar overall survival of the combined resection, compared with palliative bypass alone, but increased morbidity and hospital stay.

It can be concluded that controversy remains regarding the role of pancreatic resection for palliation. The available data confirm that, in the case of questionable radical resectability, a resection will offer relatively good palliation and longer survival compared with chemoradiotherapy, so a more aggressive approach can be advocated in patients whose tumor resectability is doubtful. R2 resections should only be performed in a highly select patient group and after passing the point of no return because no data prove a survival benefit. In addition, no data support resection in patients who are found to have liver metastasis at the preoperative diagnostic workup.

Laparoscopic Palliation

Diagnostic laparoscopy has been frequently used in the diagnostic workup for patients with suspected pancreatic tumors. The use of diagnostic laparoscopy also facilitated the introduction of the minimally invasive approach for subsequent palliation if metastases or local ingrowth of tumors is found. The procedures include palliation of obstructive jaundice by cholecystojejunostomy or choledochojejunostomy and palliation of GOO by gastroenterostomy.

Although a cholecystojejunostomy as a biliary bypass is considered to be less suitable because of the higher incidence of recurrent jaundice, this strategy is easier and safer compared with a hepaticojejunostomy (see Chapter 29). To prevent short-term obstruction of the cholecystojejunostomy, the tumor status in relation to the cystic junction anatomy always should be assessed by performing cholangiography; otherwise, a laparoscopic common bile duct exploration and bypass is indicated. The available data from five relatively small studies showed that laparoscopic double bypass can be performed safely with acceptable morbidity and low mortality rates (Table 63B.5). The long-term follow-up concerning recurrent jaundice and GOO is highlighted only briefly in these studies, however (Hamade et al, 2005; Kuriansky et al, 2000; Rhodes et al, 1995; Rothlin et al, 1999; Suzuki et al, 2007). As previously mentioned, new endoscopic techniques, including duodenal stenting for GOO (Mittal et al, 2004; Nassif et al, 2003; Wong et al, 2002), should be compared with new, minimally invasive laparoscopic approaches.

Conclusion

Although new treatment modalities for pancreatic cancer are being continuously developed, survival remains poor. Because symptoms develop late in the course of the disease, more than 80% of patients are not eligible for treatment with a curative intent. Survival of patients with unresectable tumors is even worse, and the best efforts must be made in the optimal palliative treatment of these incurable patients. The most common symptoms that must be palliated are obstructive jaundice, GOO, and pain.

To palliate obstructive jaundice, a biliary bypass should be performed in relatively fit patients. Compared with endoscopic biliary stenting, a biliary bypass provides optimal long-term prevention of biliary obstruction, but it is associated with higher initial morbidity. Stents are preferred in patients in whom survival is expected to be relatively short (3 to 6 months). In addition to biliary bypass, gastric bypass should be performed routinely to prevent GOO secondary to tumor ingrowth or compression of the duodenum. Novel techniques for palliation of GOO are being developed, such as endoscopic duodenal stenting. These techniques still must be validated, however.

More than 90% of patients have severe pain during the course of their disease. Initial treatment may be analgesic, but when the disease progresses, this is insufficient. NCPB can be performed percutaneously or during laparotomy. When the tumor is found to be unresectable during exploration, a plexus block is a relatively straightforward procedure. Radiotherapy also can be applied to treat pain, but data are limited. Palliative R1 resections for patients with borderline resectable tumors are generally accepted now as palliative care; however, so far the role for R2 palliative resection and resection for patients with metastatic disease is limited.