Surgery for Pancreatic Cancer
Surgery for cancer of the pancreas is performed in order to remove the cancer and learn additional information about the cancer. Surgery is an important treatment for patients with pancreatic cancer. However, optimal treatment of patients with pancreatic cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving surgeons, medical oncologists, radiation oncologists, medical gastroenterologists, and nutritionists.
Surgery can be performed with curative intent for some patients with cancer localized to the pancreas. Patients with more-advanced cancer may undergo surgery for reduction of symptoms and prevention of obstruction of the bile duct. Obstruction of the bile duct is a common complication of pancreatic cancer that may lead to jaundice (a yellow discoloration of the skin). Less frequently, surgery is performed to treat or prevent obstruction of the stomach outlet.
Surgery for pancreatic cancer is difficult in part because of the location of the pancreas. The pancreas is located in the middle of the abdomen between the liver and the spleen, just below and behind the stomach. The pancreas is a “retro-peritoneal” organ, meaning it is located behind and outside the abdominal cavity. The pancreas consists of a head and a tail. The head of the pancreas is connected to the last part of the stomach (the pylorus) and the first portion of the small intestine (the duodenum). The pancreas has a duct that carries digestive enzymes into the duodenum at the same location where the bile duct empties bile from the liver. Cancer in the head of the pancreas can block the bile duct and the outlet from the stomach. In all operations for pancreatic cancer, the bile duct has to be relocated to the middle section of the small intestine, called the jejunum, or less commonly, into the stomach. In some operations the bile duct is kept open with an artificial tube called a stent.
Choosing a Surgeon
Some, but not all, clinical studies suggest that hospitals that treat a relatively large number of patients with cancer (high-volume hospitals) report lower surgical in-hospital death rates than hospitals that treat a small number of patients (low-volume hospitals). This is thought to be due to experience and to the presence of surgical teams with sub-specialty expertise. For example, in one clinical study involving more than 5,000 patients, the risk of dying following pancreatectomy and other major cancer surgeries was evaluated. Centers that performed more surgeries reported fewer patient deaths following pancreatectomy and other major cancer surgeries compared with cancer centers that performed these surgeries less frequently. For pancreatectomy, the death rate in the 30 days following surgery was 13% for low-volume hospitals and 6% for high-volume hospitals.1 However, in another clinical study reported from the City of Hope Medical Center (Duarte, CA), there were no post-operative deaths in 54 patients undergoing pancreatectomy during an 11-year period. In this clinical setting, nine different surgical oncologists performed an average of six pancreatectomies during 11 years.2 These doctors concluded that in the setting of an exclusive oncology practice, operative mortality rates following pancreatectomy could remain low despite small numbers of treated patients. In order to receive the best treatment, patients should specifically inquire about the experience of the surgeons and the hospital, and ask to be informed about the risk of major complications by the surgeons performing the operation.
Pancreaticoduodenectomy (Whipple Resection): The usual operation for pancreatic cancer consists of removing the pancreas with the first part of the small intestine (duodenum) and the pylorus, or last part of the stomach. The stomach is then connected back to the middle of the small intestine (the jejunum) in a procedure called a gastrojejunostomy. The bile duct is rerouted into the jejunum. Recent clinical studies suggest that connections of the bile duct and pancreatic duct to the stomach (pancreaticogastrostomy) may be preferable to connection to the jejunum (pancreaticojejunostomy).
Partial Pancreatectomy: When cancer involves only the first part or head of the pancreas, the tail, which is uninvolved with cancer, can be preserved. This is called a partial pancreatectomy and requires that the pancreatic duct be rerouted to the stomach or jejunum. This is an important consideration as digestive juices from the remaining pancreas help in digestion, nutrition, and general well-being.
Pylorus-preserving procedure: In standard pancreatic surgery, the pylorus, or “valve” that controls emptying of the stomach, is removed. Rapid entry of food from the stomach to the small intestine can result in discomforting symptoms and leads to poor absorption of nutrients. This is referred to as the “dumping syndrome” and is caused by the removal of the pylorus. By preserving the pylorus, rapid emptying or dumping of food into the small intestine can probably be reduced; however, it is important that adequate removal of the cancer is not compromised by this procedure. Many surgeons, especially in Japan, are using pylorus-sparing surgery, although absolute documentation of benefit is currently lacking.
Complications of Surgery for Pancreatic Cancer
The most frequent early complications of surgery include infections in the abdomen, bleeding in the abdomen, leakage of bile and/or digestive juices from the rerouted bile and pancreatic ducts into the abdomen, inflammation of the bile ducts, and rapid emptying of the stomach (dumping syndrome). The most frequent late complications include: diabetes, diarrhea, and malnutrition.
Timing of Surgery
Surgical removal of the pancreas has historically been performed as initial treatment, with chemotherapy and/or radiation therapy administered after surgery. Pancreatic cancer, however, often involves the area around the entry of the pancreatic and bile ducts into the small intestine, and many patients who undergo initial exploratory surgery with the intent to perform curative surgery are found to have widespread cancer that cannot be removed. Most of these patients can only have a procedure to divert the bile duct and stomach to the jejunum to palliate symptoms and/or prevent obstructions without removing the cancer.
More recently, some doctors have advocated the administration of chemotherapy and/or radiation therapy before surgery. This use of radiation therapy and chemotherapy to shrink the cancer before surgery is referred to as “neoadjuvant therapy.” Patients with cancers that are “borderline” resectable may benefit from partial shrinkage of the cancer, which may allow a greater chance for complete removal of the cancer. Neoadjuvant therapy has been evaluated in clinical trials in an attempt to increase the likelihood of complete removal of pancreatic cancer with surgery. While it is currently unclear whether neoadjuvant therapy improves survival rates, there are several potential advantages to administering neoadjuvant therapy before attempting surgical removal of the cancer.
The side effects following surgery to remove pancreatic cancer are substantial and may delay the administering of post-operative (adjuvant) therapy. Approximately 25% to 33% of patients are unable to receive chemotherapy or radiation treatment following surgery. Additionally, some patients experience very rapid growth (recurrence) of pancreatic cancer following surgery. By administering neoadjuvant therapy, all patients are able to receive therapy for their cancer, while patients unlikely to benefit from treatment due to rapid growth of the cancer are spared the complications of surgery. Patients who experience cancer regression following neoadjuvant therapy are more likely to have their remaining cancer completely removed with surgery. Efforts are currently underway to determine the best combination of chemotherapy and radiation that will result in maximal shrinkage of the cancer before surgery.
The pancreas has a duct that carries digestive enzymes into the small intestine at the same location as the bile duct empties bile from the liver. When cancer in the area of the bile and pancreatic ducts grows, it can obstruct the bile duct and the outlet from the stomach. Because many patients will experience an obstruction or blocking of the bile duct, some doctors have advocated routinely diverting the bile duct at the time of initial surgery. The alternative to routine diversion is to wait until an obstruction occurs and perform a second surgery.
Researchers at the Johns Hopkins Medical Institutions in Baltimore have evaluated routine diversion of the bile duct in patients with inoperable pancreatic cancer.3 Exploratory surgery was performed on 194 patients with inoperable cancer of the head of the pancreas. Eighty-seven patients were deemed not in imminent danger of obstruction of the bile duct or stomach and were treated with either routine diversion or no further immediate surgery. The average survival among those who received the routine bile duct diversion was 8.3 months, with no patients developing obstruction of the stomach. The average survival of patients not receiving the routine diversion surgery was also 8.3 months, however, almost 20% of patients subsequently developed stomach and/or bile duct obstruction and all these patients required a bypass surgery or a stent placement. The average time from the initial surgery until the additional therapeutic intervention was only two months. These doctors concluded that routinely bypassing the bile duct and stomach significantly reduced the risk of gastric outlet and bile duct obstructions. Because performance of a routine bypass at the time of initial surgery did not increase surgical complications over exploration alone, they have advised that this procedure be performed at the time of initial surgical exploration in patients with unresectable cancer of the head of the pancreas.
Strategies to Improve Treatment
The progress that has been made in the treatment of pancreatic cancer has resulted from improved surgical techniques, development of adjuvant treatments, and participation in clinical trials. Future progress in the treatment of pancreatic cancer will result from continued participation in appropriate clinical trials. There are several areas of active exploration aimed at improving the treatment of pancreatic cancer.
Portal Vein Chemotherapy Infusion: Because many patients develop cancer recurrence in the liver, chemotherapy delivered directly into the blood supply of the liver has been used in an attempt to eradicate cancer cells. By infusing chemotherapy over several days or weeks through the portal vein, the chemotherapy is delivered directly to the cancer. Cancer cells appear to be killed more effectively. Portal vein infusion is being evaluated in clinical trials at many cancer centers.
New Radiation Therapy Modalities: Intraoperative radiation therapy (IORT) is a single dose of radiation therapy that is delivered directly to the area of surgery during the operation. IORT is performed in specially-equipped operating rooms. During IORT, the radiation doctor can see the area being treated and move sensitive normal structures, such as the small bowel, away from the radiation beam. Results from some studies evaluating IORT indicate that cancer may recur less often in the area of the surgery.
Three-dimensional conformal radiation therapy can precisely target radiation to the areas where cancer cells may be located and therefore minimize side effects from radiation to normal structures such as the liver, stomach, and kidneys. Because many patients develop areas of cancer cells in the liver, low-dose radiation therapy aimed at the entire liver has been used in an attempt to destroy cancer cells.
Extended Pancreaticoduodenectomy: More-extensive operations for pancreatic cancer have been advocated by some surgeons to obtain wider surgical margins with the goal of removing all cancer cells in the area and preventing cancer recurrences in the area of the surgery. Regional or extended pancreaticoduodenectomy involves removal of surrounding veins and wider dissection of lymph nodes around the pancreas. This procedure has been popularized by some institutions in the United States and surgeons from Japan. The use of extended lymph node dissection is being tested in a clinical trial at the Mayo Clinic Cancer Center.
Endoscopic Surgery: In order to avoid complications associated with surgical entry into the abdomen and retroperitoneal space, doctors have attempted to use endoscopic surgery. An endoscope is a flexible tube through which the surgeon can visualize, sample, and operate inside various body cavities. Laparoscopy is the term for using an endoscope in the abdomen.
Surgeons in Spain have evaluated the feasibility of performing a bypass of the stomach and bile duct through a laparoscope in patients with obstruction of the bile duct and stomach.4 These doctors treated 12 patients successfully with simultaneous biliary and gastric bypass. The average age of these patients was 72 years (ranging from 50-82 years). All had obstruction of the stomach and bile duct with jaundice. The average time of the procedure was an hour and a half. Complications included infections in two and pneumonia in one. One patient died two days after laparoscopic surgery. The average stay in the hospital was one week. None of the patients had recurrence of jaundice and all were able to maintain oral nutrition. The average survival was three months. These doctors concluded that gastric and biliary bypass by laparoscopic surgery was a safe procedure and effective treatment of stomach obstruction in patients with unresectable pancreatic cancer.
1 Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of Hospital Volume on Operative Mortality for Major Cancer Surgery. JAMA. 1998;280:1747-1751.
2 Schwarz RE, Ellenhorn JDI. Influence of Hospital Volume on Mortality Following Major Cancer Surgery Letter. JAMA. 1999;281: 1374.
3 Lillemoe KD, Cameron JL, Hardacre JM et al. Is Prophylactic Gastrojejunostomy Indicated for Unresectable Periampullary Cancer? A Prospective Randomized Trial. Annals of Surgery. 1999;230(3):322.
4 Kuriansky J, SáenzA, Astudillo E, Cardona V Fernández-Cruz L. Simultaneous laparoscopic biliary and retrocolic gastric bypass in patients with unresectable carcinoma of the pancreas. Surg Endosc. 2000.14: 179–181.
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