Original articleSurgery for Pancreatic Cancer: Recent Controversies and Current Practice
Section snippets
Presentation
Most patients with pancreatic cancer present late in the course of their disease. The most common presenting symptoms include epigastric abdominal pain (often radiating to the back), weight loss, fatigue, and anorexia. Such symptoms generally reflect the presence of locally advanced and/or metastatic disease; thus, once patients develop symptomatic disease, they are rarely candidates for surgical resection. The classic presentation of painless jaundice is associated with cancers of the
Clinical and pathologic staging
Pancreatic cancer staging is problematic in that accurate pathologic staging is possible only for patients who undergo surgical resection. For all other patients, clinical staging is based on diagnostic imaging. The American Joint Committee on Cancer (in cooperation with the TNM committee of the International Union Against Cancer) staging system is depicted in Table 1.Although this system is prognostic for overall survival, it is not particularly useful in guiding treatment, because some
Diagnosis and assessment for surgical resection
Staging is a critical part of pancreatic cancer management, as it is for all solid tumors. For pancreatic cancer patients, however, the principal goal of staging is the determination of resectability. Even with the most effective standard therapies, patients with locally advanced and metastatic pancreatic cancer have a median survival of approximately 10–12 months and 4–6 months, respectively. Given the significant morbidity and quality of life lost after nontherapeutic laparotomy, it is
Magnetic resonance imaging
Magnetic resonance imaging (MRI) has been used with increasing frequency in the diagnosis of pancreatic masses; this may be due to its increased availability. MRI is capable of providing staging information similar to that from a CT scan and can be performed in patients with allergies to CT contrast. It is more expensive, and the procedure takes longer. Although previously the ability of MRI to provide images in multiple planes was a clear advantage over CT, the introduction of multidetector CT
Endoscopic ultrasonography
When tumors are small or poorly visualized on CT scan, endoscopic ultrasonography (EUS) provides a minimally invasive, accurate method of defining the extent of the primary tumor/vessel relationships and evaluating surrounding lymph nodes. EUS is currently the method of choice for obtaining a pathologic diagnosis of malignancy. Numerous reports have documented the safety and accuracy of EUS-guided biopsy in the evaluation of pancreatic cancer.11, 12, 13, 14 Pretreatment confirmation of
Endoscopic retrograde cholangiopancreatography
The role of endoscopic retrograde cholangiopancreatography (ERCP) in the evaluation of pancreatic cancer is confined to palliation of obstructive jaundice, particularly in patients who are not candidates for surgery. ERCP has no role in staging pancreatic cancer except as a means to rule out alternative causes of biliary obstruction such as choledocholithiasis and benign stricture. A recent National Institutes of Health consensus conference concluded that ERCP and stent placement should not be
Diagnostic laparoscopy
The limits of CT remain its poor sensitivity in detecting small-volume peritoneal surface metastases and hepatic metastases <1 cm. This lack of sensitivity led surgeons to investigate additional means to clinically stage patients, and this coincided with the exponential growth of laparoscopic surgery in the early 1990s. Laparoscopy is now considered a fundamental part of the armamentarium of the pancreatic cancer surgeon. In the early 1990s, intracorporeal ultrasound was used in conjunction
Positron emission tomography
The use of positron emission tomography (PET) for clinical staging is under active investigation in pancreatic cancer. An initial study by Rose et al24 found that PET had a sensitivity of 92% and a specificity of 85% in diagnosing pancreatic cancer. PET was able to clarify diagnoses that were uncertain and to document metastatic disease where CT findings were equivocal. The principal question surrounding PET for pancreatic cancer remains how it should fit into overall disease management. It is
Percutaneous biopsy
As previously mentioned, in patients who present with a low-density solid mass in the pancreas and who have resectable disease, a histological diagnosis of malignancy is generally unnecessary. It is necessary to obtain tissue when patients are believed to be inoperable according to preoperative imaging or in the circumstance of planned neoadjuvant therapy. Again, EUS-guided biopsy is clearly the preferred method to obtain tissue in these instances. In the rare case in which EUS-guided biopsy is
Surgery for pancreatic cancer
Walter Kausch initially described the technique of pancreaticoduodenectomy in 1912. Two decades later (1935), Allen O. Whipple performed a 2-stage pancreaticoduodenectomy that consisted of biliary diversion and gastrojejunostomy during the initial operation followed by resection of the pancreatic head and duodenum up to 3 weeks later. In 1941, Whipple modified the procedure to a 1-stage pancreaticoduodenectomy with a concomitant pancreaticojejunostomy.28 Although major advances have been made
Technical aspects of pancreaticoduodenectomy
The operation may be divided into several well-defined steps, as described by Tyler and Evans29 and others. First, the gastrocolic ligament is opened, the transverse and right colon are mobilized, and the duodenum is exposed. At this point, a segment of infrapancreatic SMV is exposed by dissection down the middle colic and gastroepiploic vessels. In step 2, an extended Kocher maneuver (medial mobilization of the duodenum) is performed to expose the left renal vein and aorta. Some surgeons
Biliary drainage
To alleviate jaundice, preoperative biliary stents are often used in patients with benign and malignant biliary obstruction. In the past, preoperative biliary drainage was performed routinely because of concerns about the morbidity of pancreaticoduodenectomy in the jaundiced patient. These concerns have been shown by randomized trials to be unfounded, and stenting is now used primarily to palliate symptoms of jaundice (such as pruritus) or in the setting of neoadjuvant therapy when resection is
Standard pancreaticoduodenectomy versus pylorus-preserving pancreaticoduodenectomy
In 1944, Watson reported a pancreaticoduodenectomy for ampullary carcinoma, in which the entire stomach and 1 inch of duodenum were preserved. Gastrointestinal continuity was preserved with a duodenojejunostomy.35 He hypothesized that preservation of the stomach would lead to better digestion and improved nutrition and that a duodenojejunostomy would prevent marginal ulceration. The modern pylorus-preserving pancreaticoduodenectomy was popularized by Traverso and Longmire.36, 37 Since its
Extended lymphadenectomy
As for nearly all epithelial malignancies, the presence of nodal metastases is a significant prognostic factor in pancreatic cancer. In a standard pancreaticoduodenectomy, peripancreatic nodes and the subpyloric nodes are generally removed. The high risk of locoregional recurrence after pancreaticoduodenectomy prompted the hypothesis that a more extensive lymphadenectomy may favorably affect recurrence and overall survival. One prospective, randomized multicenter trial compared standard (n =
Vascular resection
Traditionally, tumor extension to the SMV/PV, SMA, or branches of the celiac axis has been considered a contraindication to surgical resection. This idea was first challenged by Fortner et al45 in the 1970s with the introduction of the regional pancreatectomy. This procedure included a total pancreaticoduodenectomy and resection of the SMV/PV, as well as resection of the SMA in selected cases. The rationale for regional pancreatectomy was the hypothesis that much of pancreatic cancer recurrence
Pancreatic anastomotic leak and the use of octreotide
A wealth of surgical literature has been devoted to various technical aspects of pancreaticoduodenectomy. Before the 1980s, mortality rates of >20% were common, and morbidity rates were even higher.50 The most frequent source of major morbidity after pancreaticoduodenectomy is leakage at the site of pancreatic anastomosis: this most often results in peripancreatic fluid collection, abscess, or the development of pancreatic fistula. Countless methods have been described to reduce leak rates,
Operative mortality and regionalization
As discussed previously, even at major academic centers, operative mortality rates after pancreaticoduodenectomy routinely approached and often exceeded 20% until the 1980s. Since then, advances in operative techniques, anesthesia, and perioperative care have resulted in significant improvements in mortality, morbidity, and length of hospital stay. Mortality rates at most high-volume centers are <5%, and numerous centers have reported rates <2%. Centers with less experience continue to report
Palliative surgery
A critical tenet of pancreatic cancer surgery is that, in general, operations should be performed with curative intent only. The use of laparotomy and gastric and biliary bypass as routine palliative measures is no longer justified in most pancreatic cancer patients. The ability to palliate disease with endoscopic stenting combined with the extremely limited survival of patients with advanced pancreatic cancer has made most palliative surgery obsolete and not in the patient’s best interests.
Adjuvant therapy
The current practice of using adjuvant 5-fluorouracil (5-FU)–based CRT in the United States is based primarily on the results of a small prospective randomized trial from the Gastrointestinal Study Group (GITSG).75 In this study, patients received adjuvant CRT (500 mg/m2 per day of 5-FU for 6 days and 4000 cGy of external beam radiation) vs observation alone after pancreaticoduodenectomy. The GITSG trial showed a survival advantage for multimodality therapy over surgical resection alone (20 vs
Neoadjuvant therapy
The underlying principles of neoadjuvant treatment make it particularly attractive in pancreatic cancer given the morbidity of surgery and the generally poor prognosis for patients with resectable disease. The rationale for neoadjuvant therapy in pancreatic cancer is as follows. (1) The goal of neoadjuvant therapy is downstaging of the tumor and, in combination with an R0 resection, increasing the chances of survival. With effective therapy, a certain percentage of potentially unresectable
Summary
Pancreatic cancer remains a lethal disease with an overall poor outcome after “curative” surgery. Despite this, surgical resection offers the only possibility of long-term cure. The morbidity and mortality associated with pancreatic surgery have declined significantly in the last 2 decades. Advances in diagnostic imaging and laparoscopy have contributed to limiting the number of pancreatic cancer patients who are subjected to nontherapeutic laparotomy. Even resection of the SMV/PV can be
References (105)
- et al.
Imaging of pancreatic adenocarcinoma with emphasis on multidetector CT
Clin Radiol
(2004) - et al.
Laparoscopy in the staging and planning of therapy for pancreatic cancer
Am J Surg
(1986) - et al.
The role of laparoscopy in the preoperative staging of pancreatic carcinoma
J Gastrointest Surg
(1997) - et al.
Staging laparoscopy with laparoscopic ultrasonographyoptimizing resectability in hepatobiliary and pancreatic malignancy
J Am Coll Surg
(1997) - et al.
Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA
Gastrointest Endosc
(2003) - et al.
Is intra-abdominal drainage necessary after pancreaticoduodenectomy?
J Gastrointest Surg
(1998) - et al.
Randomized prospective trial of pylorus-preserving vs. classic duodenopancreatectomy (Whipple procedure)initial clinical results
J Gastrointest Surg
(2000) - et al.
Does fibrin glue sealant decrease the rate of pancreatic fistula after pancreaticoduodenectomy? Results of a prospective randomized trial
J Gastrointest Surg
(2004) - et al.
Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resectionsa prospective, controlled, randomized clinical trial
Surgery
(1995) Does prophylactic octreotide benefit patients undergoing elective pancreatic resection?
J Gastrointest Surg
(1999)