Knife’s Edge: Pancreatic Cancer & the Whipple Procedure

For those diagnosed with pancreatic cancer early enough, the difficult Whipple surgery remains the best option.

Few cancers are as deadly as pancreatic cancer. A silent killer, it often causes no symptoms during its early stages and is typically found only after it has already spread to nearby organs or into the bloodstream. More than half of patients will not survive a full year with the diagnosis; just 6% last five years or more, according to the American Cancer Society.

Even those who are diagnosed early, before the cancer has spread, however, have a difficult road ahead of them. Any chance at a cure requires surgery — and all of the available options are difficult, both in terms of the surgery itself and in terms of a long prognosis.

By far the most common option is the pancreatoduodenectomy (commonly called the Whipple procedure), in which surgeons remove the head of the pancreas, the gallbladder, and the bile duct, as well as portions of the stomach and small intestine. Roughly 2% to 3% of patients will die as a result of the surgery itself, never having a chance to leave the hospital due to infections, bleeding, or other acute complications.

A high rate of complications and the potential return of the cancer create additional problems. Roughly half of pancreatic cancer surgery patients will develop some sort of complication, and 10% to 20% manifest a severe complication, most commonly a pancreatic fistula in which pancreatic secretions begin leaking. Overall, surgical patients have only a 20% to 25% chance of surviving five years.

“Even the smallest, earliest detected lesions can have bad outcomes,” says Eugene P. Ceppa, an assistant professor of surgery at Indiana University School of Medicine in Indianapolis. “The pancreas is a very fickle organ. It doesn’t like to be operated on.”

The difficult decisions facing pancreatic cancer patients highlight the disease’s persisting stubbornness. Unlike most other major cancers, including lung, colorectal, breast, and prostate cancer, pancreatic cancer death rates have slowly crept upward in the United States in the past decade.

No Good Surgical Alternatives

In addition to hiding deep within the body, where it can avoid most forms of imaging, pancreatic cancer also affects a vital organ. Th e pancreas produces several important hormones and digestive enzymes, including insulin.

These vital functions help explain the significant number of pancreatic cancer patients who aren’t initially eligible for surgery due to malnourishment. In addition to the cancer competing with healthy cells for nutrients, these patients typically suffer from a combination of appetite loss and an inability to properly digest fat, Ceppa says.

But the lack of good surgical alternatives to the Whipple underscores the overall importance of the pancreas even more. Although the exact surgery used is determined by the location of the pancreatic tumor and other factors, by preserving enough of the organ to maintain the production of insulin and digestive juices, Whipple patients face fewer metabolic complications than patients undergoing full removal of the pancreas, known as total pancreatectomy.

“We try to avoid them at all costs,” says Matthew Katz, an assistant professor of surgical oncology at the University of Texas MD Anderson Cancer Center. “It leads to diabetes, malnutrition, and other complications. Patients just don’t do very well afterwards. It’s a harder operation chronically to manage.” He performs just one to two such surgeries each year, compared to 80 or more Whipple procedures.

Of particular concern from total pancreatectomies is a very brittle form of diabetes characterized by large, unpredictable, and dangerous swings in blood glucose levels. “Managing this is awful,” Ceppa says. “It really negatively affects the patient’s quality of life.”

Small Steps

Despite the challenges, physicians are exploring adjustments in treatment and technique to help improve outcomes for Whipple surgery patients, as well as ways to minimize the complications patients face afterwards.

As with many other surgeries, research has demonstrated that surgeon experience is a key factor. As surgeons gain experience with the Whipple, their patients tend to develop pancreatic fistulas at lower rates, for example. Katz says MD Anderson, as “a very experienced center,” sees fistula rates one-half to one-third the national average.

Alone, however, a surgeon is likely to have only a limited impact. Rather, for complex, multi-system operations such as the Whipple, ready access to multidisciplinary teams of highly trained physicians are likely to factor heavily on patient outcomes. “You need a multidisciplinary team to provide cancer care other than surgery,” Katz says. “It’s not just technical performance that matters.” Without adjuvant therapy, perioperative care, nutritionists, and geriatricians, “you are not going to reap the full benefits of the operation.”

“The outcomes are better [with a multidisciplinary team],” Ceppa adds. “Timeliness is better; coordination is better; all of the critical captains are present in the conversation simultaneously. It’s definitely recommended. It would be like getting a travel agent to plan a vacation to a foreign country for you, that you are not familiar with or speak the language of, versus trying to plan it yourself.”

Many Options, One Outcome

Other developments include more aggressive use of pre-operative therapies to improve surgical outcomes. Pancreatic cancer surgeries are normally followed by adjuvant chemotherapy to kill lingering or new cancer cells, but more centers are now starting newly diagnosed pancreatic cancer patients on a round of chemotherapy prior to surgery. “We give a lot more therapy before surgery,” Katz says. “A lot more.”

However, there is “no census” on whether to use preor post-operative chemotherapy and the topic remains controversial, Ceppa says, with about 50% of doctors using each strategy. Success at shrinking tumors preoperatively, moreover, can be caused by strong responses to the medications and less aggressive cancer strains. Research has found little difference in the strategies, with the exception that patients that present with tumors not amenable to surgery be reevaluated after chemotherapy in case their tumors shrink to more manageable sizes.

Equally ambiguous are the impacts of robot-assisted and laparoscopic techniques for Whipple surgery. Such techniques are being used more often, but remain a small fraction of the overall number of pancreatic cancer surgeries performed in the United States. Studies have found similar outcomes between traditional and laparoscopic techniques, with some of the benefits of minimally invasive techniques counterbalanced by the longer operation time. Th e average open Whipple takes four to six hours, while a laparoscopic operation takes six to eight, Ceppa says. Th is might improve significantly in coming years, he says, as surgeons gain more expertise in applying minimally invasive surgical techniques to Whipple surgery.

Ultimately, though, researchers have made little improvement in pancreatic cancer treatments over the past decades, and the outcomes — even for those eligible for potentially curative surgery — remain grim. Because of its deep location in the body, a lack of early symptoms, and limited biomarkers to detect, pancreatic cancer remains difficult to diagnose during its initial stages. “Unfortunately,” Katz says, “in recent years there have been only a few major developments in treating pancreatic cancer.”

— Mehta is a freelance writer based in Cambridge, Mass. He
wrote about EDCs and childhood illnesses in the April issue.

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