PANCREATICODUODENECTOMY

Current surgical treatment is based on the procedure of pancreaticoduodenectomy as described in 1935 by Whipple and coworkers. Their two-stage pancreaticoduodenectomy consisted of biliary diversion and gastrojejunostomy during a first operation and, after the patient recovered (usually about 3 weeks later), resection of the duodenum and pancreatic head.By 1941, the world experience totaled 41 cases, and the perioperative mortality rate was 30%. Before 1940, the pancreatic remnant was not reanastomosed to the small bowel, and the high mortality rate was largely due to pancreatic fistula from the oversewn pancreatic remnant. In 1941, Whipple modified his reconstruction to include a pancreaticojejunostomy, with the entire procedure done in one operation. In 1946, Waugh and Clagett from the Mayo Clinic described their modification of the one-stage procedure to its current form. The goals of surgical therapy outlined by Waugh and Clagett have not changed in the past 50 years: (1) there should be reasonable opportunity for cure, (2) the risk of death should not outweigh the prospects for cure, and (3) the patient should be left in as normal a condition as possible.

Recent advances in operative technique, anesthesia, and critical care have resulted in a 30-day in-hospital mortality rate of less than 2% for pancreaticoduodenectomy when performed at major referral centers by experienced surgeons. At such centers, mortality rates remain less than 2% despite the use of multimodality therapy, the frequent need for complex vascular resection and reconstruction, and the referral of many patients following an initial unsuccessful attempt at tumor resection. Recently reported mortality rates from other institutions, including university centers and the Department of Veterans Affairs hospitals, range from 7.8% to more than 10%. Data from New York State have demonstrated that hospitals performing fewer than nine pancreatic resections per year have an unacceptably high perioperative mortality rate (12%). Patient outcome will be optimized and costs minimized by the referral of patients requiring major pancreatic resections for malignant disease to centers with active multidisciplinary treatment programs. Surgical resection, however, benefits only patients who undergo a negative-margin resection. Therefore, it is essential that surgery be done only on patients with localized, potentially resectable pancreatic cancer. In the absence of significant innovations in systemic therapy, the only potential for major improvements in the quality of life of patients with pancreatic cancer lies in our ability to limit surgery-related morbidity to those patients most likely to benefit from surgical intervention (i.e., to avoid laparotomy in patients with unresectable disease). Therein lies the importance of how the clinician defines resectability. CT criteria for resectability include the following: (1) the absence of extrapancreatic disease, (2) a patent SMPV confluence, and (3) no direct tumor extension to the celiac axis or SMA.

ADJUVANT ELECTRON-BEAM INTRAOPERATIVE RADIATION THERAPY

EB-IORT is a means of delivering a higher dose of radiation to the pancreatic bed and high-risk nodal groups to decrease the risk of local tumor recurrence. The effectiveness of EB-IORT in controlling the primary tumor in patients with unresectable disease, combined with early results from Japan utilizing EB-IORT after pancreaticoduodenectomy, served as the foundation for a study from MDACC of preoperative chemoradiation, extended pancreaticoduodenectomy, and adjuvant EB-IORT. To improve local-regional tumor control in patients with resectable disease, EB-IORT was delivered following resection of the specimen but before initiating gastrointestinal reconstruction. Using a dedicated operating suite containing radiotherapy equipment, the MDACC system of EB-IORT required only an additional 30 to 40 minutes of operating room time because patient relocation was not necessary. The dose of EB-IORT delivered varied from 10 to 15 Gy; these radiation doses were based on preclinical and clinical studies demonstrating the safety of 20 Gy or less. The EB-IORT treatment field included the retroperitoneum and tumor bed extending from the transected bile duct superiorly, to the right kidney laterally, and to the pancreatic remnant medially. The pancreatic remnant and bile duct were excluded from the EB-IORT field. The major retroperitoneal blood vessels (aorta, celiac axis, SMA, SMV, portal vein, and inferior vena cava) included in the EB-IORT field are not as susceptible to radiation injury as are hollow visceral and solid organs. Initial results support the safety of adjuvant EB-IORT and suggest improved rates of local-regional disease control. However, these results are likely multifactorial, being due to accurate preoperative imaging, a standardized approach to surgical resection, and chemoradiation.