39 PANCREATIC CANCER
Nathan W. Pearlman M.D.

1. What are the general features of pancreatic cancer?

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There are about 30,000 new cases per year in the United States, and more than 29,000 deaths, so it is a highly lethal disease. In most cases, histology is adenocarcinoma. About 80% arise in the head of the gland, and 20% arise in the body and tail. About 20% of patients have localized (potentially curable) disease at diagnosis; the remainder are inoperable either because of regional spread (portal vein, superior mesenteric artery) or widespread metastases (liver, peritoneum).

2. What are the presenting signs of pancreatic cancer?

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* Painless jaundice: 40% of patients
* Pain (epigastric, right upper quadrant, back) with jaundice: 40%
* Metastatic disease (e.g., hepatomegaly, ascites, lung nodules) with or without jaundice: 20%.

3. Why is there such a high rate of advanced disease at diagnosis?

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The pancreas is retroperitoneal and relatively insensate, and symptoms of disease are uncommon unless the pancreatic or biliary duct is obstructed or the process (pancreatitis, cancer) extends outside the gland.
4. A previously healthy 73-year-old patient presents with pruritus, dark urine, and icteric sclerae after recent overseas travel. What is a reasonable differential diagnosis? Show answer

1. Gallstones
2. Cancer of the extrahepatic bile ducts
3. Cancer of the pancreas
4. Hepatitis

5. What is the first step in evaluating the patient?

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The first step is liver function tests to determine the degree of jaundice and hepatic dysfunction. Then ultrasound is done to determine whether the cause is intrahepatic (normal bile ducts) or extrahepatic (dilated bile ducts). Ultrasound can detect stones in the gallbladder or common duct with about 95% accuracy. Thus, if a jaundiced patient has normal bile ducts on ultrasound, the problem is intrahepatic cholestasis, probably from hepatitis.

6. What if an ultrasound shows dilated extrahepatic bile ducts?

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Proceed to endoscopic retrograde cholangiopancreatography (ERCP) or transhepatic cholangiogram to determine whether the obstruction is high or low in the common bile duct and to determine its likely cause (stricture, stone, tumor). The biliary tract can be decompressed with an internal stent at this time, allowing liver function to improve before major surgery. If stones are present, endoscopic sphincterotomy should be performed, allowing the stones to pass and simplifying future surgery.

7. When should computed tomography (CT) scan be used instead of ERCP?

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ERCP is best for determining intraluminal anatomy. CT scan provides other information, such as size of the tumor (if one is present), degree of regional spread (portal vein, lymph nodes), and presence or absence of liver metastases.

8. In this case, ultrasound, ERCP, and CT scan show dilated extrahepatic bile ducts, a mass in the head of the pancreas, and no obvious cause other than cancer. The tumor seems separate from the portal vein, and there are no liver metastases. What should be done next?

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If the patient is a poor operative risk, one should consider percutaneous or endoscopic ultrasound-guided fine-needle aspiration (FNA) to document cancer, if possible, and endoscopic stenting of the bile duct; surgery probably is not a good option. If the patient is a good operative risk, the next step is surgery. The clinical picture is accurate in at least 90% of cases, and FNA adds no useful information at this time. If no malignant tissue is obtained, surgery is still indicated because the needle may have missed the lesion, sampling only the pancreatitis that surrounds all such tumors.
KEY POINTS: DIAGNOSTIC WORK-UP OF JAUNDICED PATIENT

1. Liver function tests: determine degree of jaundice (obstructive versus nonobstructive) and hepatic dysfunction.
2. Ultrasound of right upper quadrant: rules out gallstones, evaluates intrahepatic vs. extrahepatic ductal dilatation.
3. If hepatic ducts are dilated: ERCP or PTC to delineate site of mechanical obstruction.
4. CT: evaluates size of tumor if present, degree of regional spread, and/or liver metastases

9. We are in the operating room, the abdomen is open, and the discussion revolves around taking out the tumor. What is a Whipple procedure?

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This is a removal of the gallbladder, distal common duct, duodenum, and the portion of pancreas to the right of the portal vein-in essence, a proximal pancreatectomy. In some centers, it is also routine to remove the gastric antrum, with or without a vagotomy.

10. What is distal pancreatectomy? A total pancreatectomy?

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Distal pancreatectomy removes the portion of gland to the left of the portal vein, along with the spleen. Total pancreatectomy combines both procedures-again, with antrectomy in some centers.

11. Why remove gallbladder, duodenum, and stomach if the problem is in the pancreas?

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After the ampulla of Vater is removed, the gallbladder does not function well and forms gallstones. The second and third portions of the duodenum share a blood supply with the head of the pancreas and are usually devascularized when the head is removed. Historically, the gastric antrum was removed to improve resection margins. Vagotomy was added to reduce the incidence of marginal ulceration at the anastomosis between the gastric remnant and jejunum.

Removing the antrum adds little to the scope of the operation, however, and marginal ulceration can be prevented by placing the gastrojejunostomy downstream from where bile and pancreatic secretions enter the gut. Thus, many surgeons now perform a pylorus-preserving Whipple procedure whenever possible, preserving the vagus nerve as well. Survival is the same as with more radical procedures, and the long-term function is somewhat better.

12. How does one determine whether to perform a Whipple procedure, distal pancreatectomy, or total pancreatectomy? What is the cure rate?

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Whipple procedures are used for mobile tumors in the head without signs of lymph node metastases at the celiac axis or root of mesentery. Distal pancreatectomy is used for lesions of the body and tail unaccompanied by signs of spread. Total pancreatectomy is generally reserved for a few select situations in which cancer involves most of the gland but nowhere else; this is a rare event. Median survival with each procedure is about 20 months, and 5-year survival is about 15%. This procedure has about 3% operative mortality and 25% morbidity in centers with extensive experience; in other settings, the operative risk and complication rate can be much higher.

13. What should be done if there are nodal metastases at the celiac axis or root of mesentery?

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The patient cannot be cured with surgery, so the goal is palliation. If obstructive jaundice is present, a biliary-enteric bypass should be performed. If a tumor obstructs the duodenum, a gastroenterostomy should also be carried out. Some surgeons believe gastroenterostomy should be done routinely for cancers of the pancreatic head, regardless of whether duodenal compromise is present, because ≤ 30% of patients without this problem at the time of surgery may require gastroenterostomy for problems of gastric emptying in the future.

14. Do any other signs of inoperability exist?

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Most pancreatic tumors lie near the portal vein and adhere to or invade the vein as they expand. Most surgeons consider attachment to the portal vein a sign of incurability. Some surgeons, however, remove the affected portion of vein, if this is the only sign of inoperability, and bridge the gap with a graft. Survival in such patients is actually about the same as in similar patients undergoing resection but without vein involvement.

15. A patient is found to have unsuspected spread to the celiac axis. You carry out a biliary and gastric bypass. Is there anything else you can offer the patient, either surgically or nonsurgically?

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Some of these patients, if suffering from preoperative back pain, can be relieved of this by intraoperative alcohol celiac ganglion block. Alternatively, such treatment can be carried out postoperatively by an interventional radiologist. Most patients with locally advanced disease (i.e., no liver or peritoneal metastases) benefit from postoperative radiotherapy combined with chemotherapy, either 5-fluorouracil or gemcitabine. Many of them will achieve pain relief with this regimen, and median survival is now about 10-15 months (almost as good as with resection).

16. What about patients with liver or peritoneal metastases? What happens to them?

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Unfortunately, the best that we have to offer this group is palliative chemotherapy. They have a median survival of about 6 months.

17. With cure rates so low, why are surgeons so eager to do Whipple procedures?

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Unfortunately, this represents the only chance for cure. In addition, pancreatic resection-when carried out safely-probably offers the best long-term palliation in those destined to die of their disease. Finally, the outlook after pancreatic resection may improve in the future with preoperative chemoradiotherapy or newer forms of postoperative adjuvant therapy, so the future does have at least some hope.

References
WEB SITE
http://www.ascsurgery.com/abstracts/acs/acs0304/htm
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