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Treatment

 

At present, pancreatic cancer is treated either surgically, with chemotherapy, or a combination of radiation and chemotherapy.

Surgery

Surgery, which currently offers the greatest potential for prolonged survival, and is always required for cure, is generally only performed if the malignancy has not spread beyond the pancreas. In cases where tumors have been deemed resectable (capable of being surgically removed) the standard operation is the Whipple pancreaticoduodenectomy or a modification of it. This procedure involves partial removal of the stomach, complete removal of the gallbladder, part of the main bile duct, head of the pancreas, a small portion of the small intestine, and regional lymph nodes. Rarely, the entire pancreas may be removed.

Due to concern that the standard Whipple was associated with excessive weight loss and nutritional problems, many surgeons use a modified version of the procedure in which the stomach is preserved. This is called the pylorus preserving Whipple operation. It was believed this approach minimized postoperative nutritional problems and today this is the most commonly performed operation for patients with cancers in the head of the gland.

When tumors aren't resectable, surgical intervention may still be appropriate to relieve an intestinal blockage, or to relieve bile duct obstruction with resultant jaundice.

Surgical Questions

If the tumor is large, can it still be removed?

Small pancreatic tumors (less than 2 cm diameter) are more likely to be resectable than larger ones. Nevertheless, the majority of pancreatic cancers located in the head of the gland are larger than that by the time the diagnosis is made and an operation is performed.

At the University of Erlangen in Germany, of all resections of tumors in the head of the gland:

• 15% were 1- 2 cm in diameter
• 33.4% were 2 -3 cm
• 23.3% were 3 -4 cm
• 27.8% were larger than 4 cm.

At UCLA Medical Center in a recent review:

• 26% of the resections were for tumors 1 -2 cm in diameter
• 17% were 2 -3 cm
• 22% were 3 -4 cm
• 26% were 4 -5 cm
• 9% were larger than 5 cm in diameter.

Thus, it should be apparent that no patient should be denied the chance for a resection because of a tumor that is considered "too large."

What are the findings at the time of operation that make you decide against resection?

In the absence of distant metastases (e.g., peritoneum, surfaces of other organs, lymph nodes outside the usual limits of the resection, liver), resectability depends on whether the tumor has invaded major blood vessels. We usually will not operate to resect the cancer if the preoperative data (e.g., from the CT, MRI, EUS, etc.) show that it has invaded the superior mesenteric or portal vein, the superior mesenteric artery or the hepatic artery. However, in some cases, such patients may be treated with chemotherapy +/- radiation which can shrink the tumor and that part of it which was involving the blood vessel(s). Then we may operate and remove the tumor. In some cases we remove tumors with venous invasion, and excise the involved segment of the vein with the tumor. Vascular continuity is restored by reconnecting the ends of the vessels.

Occasionally, when the preoperative discussion has convinced us of the patient's desire for an aggressive approach to the problem, we will undertake the resection with prior knowledge that the vein is involved. In other cases, lateral or posterior involvement of the vein only becomes apparent after the neck of the pancreas has been transected as part of the Whipple. There is evidence that venous resections in those circumstances are associated with a similar survival as seen in patients who undergo resection when the vessels are not involved. Nevertheless, we view this as a palliative resection, and recommend adjuvant treatment with chemotherapy later.

Is advanced age a contraindication to operation?

The morbidity and mortality rates for the standard operations for pancreatic cancer in patients over 70 years of age do not vary significantly from results for younger patients. However, each patient at every age must be assessed individually, and an evaluation made of the associated risks due to coexistent cardiovascular, pulmonary, and renal disease. Many of our patients who have undergone Whipple resection are over the age of 80; some patients under age 65 have been unacceptable operative risks. At UCLA, the overall operative mortality rate for pancreatic resection since 1995 is less than 1%.

Should the tumor be removed if cure is not possible?

Since the Whipple resection is now done around the world with operative mortality rates less than 5%, pancreatic surgeons have discussed the possibility that it might be done for palliation, knowing that cure was not possible. Indeed, there is anecdotal evidence that patients may live longer and enjoy a better quality of life if the tumor is removed than if it is not. 

Several recent reports which supported the performance of the Whipple for palliation were not appropriately designed to answer the question, however. One recent study from Japan in which patients with liver metastases underwent simultaneous resection of both the tumor and the liver lesions failed to show any benefit of resection. We have not performed resections in patients with hepatic, peritoneal, or other distant metastases, although there may be rare indications for this.

What kind of operation should be done?
Standard Whipple versus Pylorus-preserving Whipple versus Radical Resection?

The standard operation for resectable pancreatic cancer in the head of the gland is the Whipple pancreaticoduodenectomy. This involves a partial removal of the stomach, removal of the gallbladder and distal common bile duct, head of the pancreas, duodenum, proximal jejunum and regional lymph nodes. Reconstruction requires a pancreaticojejunostomy, hepaticojejunostomy, and a gastrojejunostomy.

Because of concern that the standard Whipple resection was associated with excessive weight loss, and nutritional problems, many surgeons have adopted the pylorus preserving modification. Here the stomach and pylorus are preserved, which maintains gastric reservoir function, and postoperative gastric emptying is closer to normal. It is widely believed that the modified procedure minimizes the nutritional disturbances, and that it can be done more quickly and easily. It has generally been accepted that this does not compromise the chance for cure of the cancer. 

However, most surgeons now believe there are no differences in any of the postoperative complications, nutritional parameters, the frequency or type of gastrointestinal symptoms, weight loss, or in the ease or time required to perform the two operations. Thus, the procedures appear to be equivalent. We and other experienced surgeons now perform the two operations interchangeably, and usually select the pylorus preserving modification in patients with smaller, less extensive tumors.

A more radical resection has been advocated by a number of surgeons in Japan. This operation involves a wider resection of peripancreatic soft tissue and lymph nodes, often with routine removal of segments of the superior mesenteric and portal veins, as well. Operative mortality rates were not increased significantly by this more aggressive approach.  But a critical analysis of the data does not suggest that survival is improved by this more radical approach. Studies in Europe and the United States have come to the same conclusion, so the operation is not done by most Western surgeons.

Radiation and Chemotherapy

For patients whose tumors cannot be completely removed surgically, treatment generally focuses on the prevention and/or management of symptoms through radiation and/or chemotherapy.
Radiation therapy is most often used to relieve painful disease sites, while chemotherapy is prescribed to reduce the rate of tumor growth and thus prolong survival. In some instances, radiation and chemotherapy are utilized together.

Additionally, in a new approach developed by City of Hope Cancer Center in Duarte, Calif., radiation, chemotherapy and surgery are combined. The approach consists of 24-hour treatment with the chemotherapeutic agent gemcitabine, followed by surgical removal of the tumor, and radiation therapy administered locally during the operation. Post-operative treatment includes gemcitabine and external radiation.