Timothy L. Frankel
Christopher J. Sonnenday
Presentation
A 58-year-old man with a 50-pack-year smoking history presents to his primary care doctor after family members noted that his eyes were turning yellow. He notes that over the past 2 weeks, he has developed pruritus and clay-colored stools. He describes darkening of his urine and a 15-lb weight loss over the past 2 months. Vital signs are within normal limits. On examination, he appears jaundiced with scleral icterus. He has no abdominal pain and no palpable masses. He has no prior medical problems and is a construction worker.
Differential Diagnosis
Jaundice can be caused by either altered metabolism of bilirubin (i.e., overproduction of bilirubin, impaired uptake of bilirubin by the liver, or decreased conjugation of bilirubin) or ineffective excretion of bile into the gastrointestinal tract. Serum bilirubin can be fractionated into direct and indirect values, which correspond to conjugated and unconjugated bilirubin, respectively. Causes of unconjugated hyperbilirubinemia include increased production from hemolysis, congenital diseases (such as Crigler-Najjar and Gilbert’s syndrome), and intrinsic liver failure such as cirrhosis or hepatitis. Conjugated or direct bilirubin elevation results from obstruction of biliary outflow from benign causes (such as chronic pancreatitis or choledocholithiasis) or malignancy including cholangiocarcinoma or periampullary tumors. Painless jaundice in a middle-aged or elderly person without overt liver disease should be assumed to be a malignancy until proven otherwise.
Workup
Initial evaluation of the jaundiced patient should include a detailed history and physical exam, with attention paid to risk factors for, or evidence of, underlying chronic liver disease, pancreatitis, or gallstone disease. Progressive jaundice, particularly of a malignant cause, may be associated with weight loss and malnutrition. The patient’s overall health status and fitness for diagnostic and therapeutic procedures should be assessed. On physical exam, assessment should be done for lymphadenopathy, ascites, abdominal masses, and organomegaly that may indicate more advanced malignant disease and/or hepatic insufficiency.
Laboratory evaluation should include a complete blood count, which may provide signs of infection, anemia, and/or thrombocytopenia, as well as a comprehensive metabolic panel and a PT/INR. In addition to assessment of the liver profile for confirmation of hyperbilirubinemia and an obstructive pattern, attention should be paid to electrolyte deficiencies, evidence of dehydration, and any hypoalbuminemia. Patients with obstructive jaundice, particularly when long-standing, will have a relative vitamin K deficiency from poor absorption and therefore may have an elevated INR and bleeding risk.
The least invasive initial imaging test is an abdominal ultrasound, which allows for the assessment of liver contour and morphology that may indicate occult liver disease, assessment for biliary ductal dilatation, identification of gallbladder pathology and documentation of gallstones, and may allow assessment for periampullary masses depending on image quality. Cross-sectional imaging, typically with a high-resolution thin-slice CT scan, is the most appropriate test to assess the patient with obstructive jaundice who appears to have a distal biliary obstruction. MRI with magnetic resonance cholangiopancreatography is another reasonable alternative and may augment CT findings in some cases, particularly when complex biliary pathology is present.
Patients with a documented distal biliary obstruction, particularly when a malignant cause is suggested by imaging, should undergo an evaluation by a surgeon with expertise in diseases of the liver and pancreas. Decisions about the need for more invasive procedures aimed at palliating jaundice or providing a tissue diagnosis should be made in the context of the patient’s operative candidacy and resectability. Malnourished or debilitated patients, and patients with marked hyperbilirubinemia (total bilirubin > 12 mg/dL), would benefit from biliary decompression and optimization of nutritional and functional status prior to consideration of surgical therapy. Patients with clearly resectable disease and good overall health status, who have a periampullary mass with obstructive jaundice and no evidence of metastases, may appropriately be taken to the operating room for resection without a tissue diagnosis in many cases. Preoperative biliary decompression has been associated with an increased risk of postoperative infection and therefore should be avoided if not indicated.
When biliary decompression is warranted, or in cases where the etiology of biliary obstruction is not clear by noninvasive means, direct cholangiography is necessary. The most common initial technique is endoscopic retrograde cholangiography (ERC), with percutaneous transhepatic cholangiography (PTC) reserved for patients in whom endobiliary access is either not possible (e.g., following gastric bypass) or unsuccessful. ERC allows placement of an endobiliary stent across the distal biliary obstruction which typically leads to prompt resolution of jaundice, and biliary strictures may be brushed or biopsied intraluminally to achieve a tissue diagnosis. In the case of ampullary or duodenal masses associated with distal biliary obstruction, the tumors may be biopsied directly at the time of endoscopy. Biliary decompression and tissue sampling from biliary strictures may also be accomplished by PTC.
When a tissue diagnosis is needed and cannot be established by endobiliary means, endoscopic ultrasound (EUS), with fine needle aspiration of any identified periampullary mass, is the preferred modality. EUS allows assessment of the pancreatic parenchyma for endosonographic evidence of chronic pancreatitis and careful inspection for small or subtle pancreatic masses, and may allow evaluation of the relationship of periampullary tumors to the mesenteric and hepatic vessels, which can add to the information gathered from contrast-enhanced cross-sectional imaging regarding resectability.
In cases where a malignant diagnosis is established, staging for metastatic disease should include a CT scan of the chest. Positron emission tomography scan should be reserved for patients with extrapancreatic CT findings that may be suggestive of metastases, especially when not amenable to percutaneous biopsy. A serum CA 19-9 level may assist in providing additional prognostic information, and may be followed to assess response to treatment, but its absolute value is not helpful in determining a malignant diagnosis or establishing the presence or absence of metastatic disease. The serum CA 19-9 should ideally be drawn after the patient’s jaundice is palliated, as it may be falsely elevated in cases of biliary obstruction or cholangitis.
Presentation Continued
In the patient presented in this scenario, a more thorough history fails to identify any risk factors for viral hepatitis. Initial laboratory values are remarkable for an elevated bilirubin to 12 mg/dL with fractionation revealing primarily direct hyperbilirubinemia. Abdominal ultrasound identifies both intrahepatic and extrahepatic biliary ductal dilation and fails to find stones in either the gallbladder or the common bile duct (CBD). A CT scan is obtained which reveals a mass in the head of the pancreas causing dilation of both the CBD and the pancreatic duct (Figure 1). ERC confirms a malignant-appearing distal CBD stricture (Figure 2), and an endobiliary stent is placed, with resolution of the patient’s jaundice over the ensuing week. EUS confirms a 3-cm pancreatic head mass, and fine needle aspiration biopsy is consistent with adenocarcinoma.
FIGURE 1 • Pancreatic protocol CT of patient with obstructive jaundice. Hypodense mass (arrow) is noted in the head of the pancreas, with abutment of the adjacent SMV.
FIGURE 2 • ERC of patient with a malignant-appearing distal bile duct stricture in a patient with a mass in the head of the pancreas.
Diagnosis and Treatment
The diagnostic evaluation in this case confirms the presence of a pancreatic adenocarcinoma. As curative treatment for pancreatic adenocarcinoma must include definitive surgical resection, the initial decision making in regard to treatment must include assessment of the patient’s appropriateness for surgery. Metastatic disease should be ruled out as mentioned above. In addition to assessing the patient’s overall health status and comorbid disease, resectability must be definitively assessed by an experienced surgeon. If not already obtained, a dedicated pancreatic protocol CT with distinct arterial and mesenteric venous phases should be obtained. Involvement or abutment of the superior mesenteric artery (SMA) and vein, hepatic artery, and portal vein (PV) should be assessed. Direct arterial involvement is most often considered a contraindication to surgical resection, and the degree of mesenteric venous involvement and options for venous reconstruction must be considered carefully as well. In patients considered “borderline” resectable due to either long segment venous involvement or questionable arterial involvement, neoadjuvant chemoradiation may be given in order to improve the likelihood of a margin-negative resection. Unresectable patients, or patients with obvious metastatic disease, should be referred for palliative systemic chemotherapy or appropriate clinical trials.
Surgical resection, while necessary for cure of pancreatic cancer, should not be considered sufficient. A multidisciplinary approach to pancreatic malignancy, combining surgical therapy with systemic chemotherapy and radiation therapy, has been shown to provide the optimal patient outcomes for this complicated disease. Decision making regarding offering neoadjuvant chemoradiation for pancreatic cancer is best made in a collaborative manner, considering patient performance status, comorbidity, and tumor resectability. Given the high recurrence rate of pancreatic cancer even for patients with optimal pathology, all patients with appropriate performance status should be considered for adjuvant chemotherapy ± radiation. Ideally, adjuvant therapy should be started within 6 to 10 weeks of the date of surgical resection.
Surgical Approach
With advances in cross-sectional imaging, the likelihood of finding occult metastatic or locally unresectable disease at the time of surgical exploration has decreased significantly. While CT is quite sensitive in determining local tumor extent and visceral metastatic disease, it often misses small volume peritoneal disease. Thus, some surgeons advocate beginning any planned operative intervention with a laparoscopic exploration with or without peritoneal washings. Once obvious peritoneal metastases have been excluded, open operative intervention should proceed. If the laparoscopic exploration is not performed initially, an upper midline incision should be made, which is large enough to allow visualization of omental and mesenteric surfaces and palpation and inspection of the liver. Any lesions suspicious for metastatic disease should be biopsied and sent for frozen section analysis prior to proceeding with resection of the primary tumor.
The pancreaticoduodenectomy dissection begins with mobilization of the hepatic flexure, exposing the duodenum and proximal pancreas. This allows reflection of the hepatic flexure and transverse colon inferiorly. Care should be taken not to avulse the middle colic vein or its distal branches when reflecting the transverse mesocolon off the pancreatic head; there is often a small crossing branch that connects the middle colic vein with the gastroepiploic venous drainage which can be inadvertently injured at this stage of the operation. Next, a complete Kocher maneuver is performed separating the duodenum and posterior aspect of the pancreatic head from retroperitoneum, which exposes the anterior surface of the inferior vena cava. This dissection should be carried medially until the origin of the SMA is encountered. A helpful landmark in identifying the origin of the SMA is the left renal vein, which crosses immediately inferior to the SMA origin as it crosses anterior to the aorta. Tumor involvement that obliterates the plane between the SMA and the uncinate process of the pancreas is most often considered a contraindication to surgical resection and should prompt aborting the resection and consideration of operative palliation.
Continuation of the Kocher maneuver along the third portion of the duodenum until one encounters the root of the small bowel mesentery crossing the duodenum allows access to the lateral aspect of the superior mesenteric vein (SMV). With the transverse mesocolon retracted inferiorly and ventrally, the course of the middle colic vein should indicate the location of the SMV as it approaches the inferior border of the pancreas. Careful dissection of the mesenteric adventitial tissue at this level will expose the anterior and lateral aspects of the SMV. If tumor infiltration or other aberrant anatomy makes exposure of the SMV difficult, the lesser sac should be opened broadly by taking the omentum off the transverse mesocolon. Filmy attachments between the posterior wall of the stomach and the retroperitoneum are divided, exposing the anterior aspect of the pancreas. Dissection along the inferior border of the pancreas from the proximal pancreatic body toward the head should bring the anterior aspect of the SMV into view. Again the course of the middle colic and gastroepiploic veins can provide clues to the location of the SMV, particularly in obese patients in whom the SMV may be obscured by mesenteric fat.
Once the SMV is identified, dissection should proceed meticulously toward the inferior border of the pancreas (Figure 3). The drainage of the middle colic and gastroepiploic veins should be identified; in some patients, they will merge as a common trunk. Ideally, the middle colic vein should be preserved if not involved with tumor. The gastroepiploic should be divided, which opens the space between the SMV and inferior border of the pancreas nicely and will allow rotation of the distal stomach and duodenum completely off the pancreatic neck. With gentle retraction on the inferior edge of the pancreas with a vein retractor or similar instrument, the space between the anterior aspect of the SMV and the posterior aspect of the pancreatic neck should be developed, typically by pushing the anterior aspect of the vein gently dorsally. As one proceeds cephalad, the confluence with the splenic vein and the drainage of the inferior mesenteric vein can often be identified. Once this plane is developed, attention is turned to the superior border of the pancreas and the portal dissection. If SMV invasion is encountered at this level, plans for venous reconstruction should be made or the operation aborted and referral to an appropriate institution made.
FIGURE 3 • Illustration of the critical landmarks allowing safe dissection of the SMV at the inferior border of the pancreas (A), and the PV at the superior border of the pancreas after division of the GDA (B). Panel C demonstrates passing an umbilical tape behind the neck of the pancreas after the inferior and superior dissection planes are connected.
With the duodenum gently retracted inferiorly, the peritoneum over the portal structures is divided, allowing the duodenum to roll off the superior border of the pancreas at the pancreatic head. The right gastric artery and vein are often encountered at the medial aspect of the porta and should be ligated and divided. The gastroduodenal artery (GDA) is identified as it enters the pancreatic head and dissected free from surrounding tissues back to its origin at the common hepatic artery. Safe division of the GDA without compromise of hepatic arterial blood flow is facilitated by two maneuvers: (1) dissection of the GDA origin completely with exposure of a short distance of the proper hepatic artery proximally and the common hepatic artery distally and (2) test occlusion of the GDA with confirmation of a retained pulse in the hepatic artery distally near the liver hilum. Once the GDA is definitively identified by these techniques, it is suture ligated and divided. Division of the GDA exposes the anterior aspect of the PV immediately posteriorly, as it passes behind the superior border of the pancreas (Figure 3). Immediately laterally to this space is the distal CBD. The CBD is encircled and elevated with a vessel loop, further exposing the anterior PV. Care should be taken at this point to inspect carefully for a replaced right hepatic artery that typically traverses laterally and posteriorly to the CBD. When present, a replaced right hepatic artery can be often dissected completely off the posterior aspect of the pancreatic head, freeing it down to its origin at the proximal SMA.
Cholecystectomy is then performed. The CBD is divided above the level of the pancreatic head, with a margin sent for frozen section analysis. A Bulldog or similar atraumatic small clamp may be used to control the proximal CBD and prevent bile spillage. The distal CBD is then reflected inferiorly, further rolling the head and neck of the pancreas off the anterior aspect of the PV. The plane between the anterior aspect of the PV and posterior aspect of the pancreatic neck is developed bluntly until the previous area of the inferior pancreatic dissection is encountered, thus completing the retropancreatic tunnel. An umbilical tape or Penrose drain is passed through this tunnel, allowing elevation of pancreatic neck off the PV-SMV confluence.
Depending on surgeon preference and the condition of the proximal duodenum, either proximal duodenal transection with pylorus preservation or distal gastrectomy may be performed next. Contraindications to pylorus preservation include direct tumor involvement of the proximal duodenum or gastric outlet, clinical evidence of gastric outlet obstruction, extensive primary duodenal tumors, and treatment with preoperative radiation therapy. When preserving the pylorus, the duodenum should be divided no closer than 2 to 4 cm from the pylorus. This prevents the subsequent duodenojejunostomy from being immediately adjacent to the pylorus, which may contribute to pyloric edema and delayed gastric emptying.
Once the foregut is divided, the pancreatic neck is transected. The superior and inferior pancreatic vascular arcades are controlled with figure of eight sutures at the inferior and superior border of the pancreas, placed proximally and distally to the line of transection. The pancreatic neck is divided sharply with a fresh scalpel, and a pancreatic neck margin sent for frozen section. When the margin returns positive, the proximal pancreatic body may need to be mobilized off the splenic vein to allow resection of additional pancreatic parenchyma. The cut pancreatic margin often bleeds initially; small arterial vessels should be controlled with sutures with other hemostasis obtained by pressure, avoiding the temptation to excessively cauterize the cut pancreatic surface.
The proximal jejunum is then divided and the mesentery of the distal duodenum taken with clamp and ties or a surgical energy device. Encroaching on the SMV or SMA with the mesenteric transection is avoided by staying immediately adjacent to the small bowel wall when dividing the mesentery. The proximal jejunum is then passed through the defect at the ligament of Treitz toward the right upper quadrant. The remainder of the resection phase includes division of the uncinate process attachments to the retroperitoneum. This portion of the case has the most potential for blood loss or mesenteric vessel compromise, and therefore it should be accomplished methodically. Freeing of the SMV and its initial branches from the specimen allows the SMV to be elevated off the uncinate process and SMA. Finding the plane immediately adjacent to the SMA adventitia is actually the safest plane and provides the most definitive retroperitoneal margin. Typically there are two pancreaticoduodenal branches (superior and inferior) off the SMA entering the uncinate process that should be ligated with fine suture. Once the specimen is freed completely, the uncinate process margin should be marked and the specimen sent to pathology. The right upper quadrant is irrigated and inspected for hemostasis.
Reconstruction begins with closure of the defect at the ligament of Treitz, which is best accomplished with a continuous nonabsorbable suture. The proximal jejunum is then brought through a defect in the bare area of the transverse mesocolon just to the right of the middle colic vessels. A number of techniques exist for the pancreaticojejunostomy including a two-layer duct-to-mucosa anastomosis, invagination of the pancreatic remnant end to side into the jejunum, or end-to-end intussusception technique. No method of pancreaticojejunostomy has been definitively shown to be superior in terms of preventing pancreatic fistula, and each method may have its place depending on the size and texture of the pancreatic remnant and the caliber of the pancreatic duct. The biliary reconstruction is accomplished next, typically 10 to 20 cm distal to the pancreaticojejunostomy. Circumferential bile duct to mucosal stitches are placed using a monofilament suture. The mesenteric defect in the transverse mesocolon is then closed around the jejunum using interrupted absorbable sutures.
Gastrojejunostomy or duodenojejunostomy is the final stage of the pancreaticoduodenectomy reconstruction. This is best accomplished in an antecolic position, approximately 50 cm distal to the biliary anastomosis. Closed suction drains are typically placed adjacent to the pancreatic anastomosis, though some centers have debated the necessity of drainage in all patients. Surgeons who favor use of perioperative drains typically value the practice of testing the drain effluent for amylase in the postoperative period, allowing the diagnosis of pancreatic fistula early before infectious or other complications occur. Opponents of routine drain usage argue that most pancreatic fistula likely resolve without intervention, and monitoring of drain output and amylase content can extend length of stay unnecessarily in some patients (Table 1).
TABLE 1. Key Technical Steps and Potential Pitfalls in Pancreaticoduodenectomy Procedure
Special Intraoperative Considerations
Improvements in surgical technique and patient selection have allowed the gradual expansion of Pancreaticoduodenectomy to patients previously considered unresectable, specifically those patients with locally advanced tumors and mesenteric vascular involvement. Resection and reconstruction of the SMV, hepatic artery, and SMA have all been described during pancreaticoduodenectomy, typically in the context of comprehensive treatment strategies that include neoadjuvant chemoradiation. In experienced hands, vascular reconstruction can be performed safely and may improve the ability to obtain a margin-negative outcome. However, the ability of pancreaticoduodenectomy with vascular resection and reconstruction to produce improved overall survival has not been definitively proven. Therefore, the addition of vascular resection to pancreaticoduodenectomy should only be performed by surgeons experienced in these procedures and ideally in the context of a multidisciplinary neoadjuvant treatment protocol. SMV resection and reconstruction is the most well-studied and proven adjunct to pancreaticoduodenectomy, with major pancreatic centers demonstrating perioperative and oncologic outcomes in SMV resection patients equivalent to patients without vascular involvement. Reconstruction options for the SMV can include primary repair, patch venoplasty, segmental resection and primary anastomosis, and resection with interposition vein graft. Synthetic conduits for SMV reconstruction have also been utilized, though are typically avoided due to concerns about diminished long-term patency and increased infection risk.
In recent years, some surgeons and institutions have begun to gather experience with minimally invasive approaches to pancreaticoduodenectomy. Both completely laparoscopic and robotic approaches have been developed, with good perioperative outcomes in limited series. Purported advantages of minimally invasive pancreaticoduodenectomy include decreased postoperative pain, decreased wound complications, and faster return to normal activities. At this point, there are no data to suggest that minimally invasive techniques diminish the rate of the most common and problematic complications of pancreaticoduodenectomy, including pancreatic fistula and delayed gastric emptying.
Postoperative Management
Patients are ideally monitored on a dedicated surgical unit following pancreaticoduodenectomy. Intensive care unit stay may be indicated in patients with significant comorbidities or a complicated intraoperative course, depending on institutional resources. As with all major operative procedures, early mobilization facilitated by appropriate postoperative analgesic strategies is paramount to avoiding pulmonary and thromboembolic complications. Unfractionated or low molecular weight subcutaneous heparin should be administered preoperatively and continued in the postoperative period.
Nasogastric decompression is typically utilized during the first 24 to 48 hours postoperatively, though some centers have debated the necessity of this historic standard. Oral intake is typically advanced sequentially and gradually, with patients encouraged to eat small frequent portions until gastric function improves. Up to 20% of patients will experience delayed gastric emptying, manifest by persistent postoperative nausea, emesis, and gastric distention. Most patients will gradually improve with observation and antiemetics, though nasogastric decompression may be necessary in patients with persistent emesis. Supplemental nutrition, given parenterally or ideally via a nasojejunal tube placed fluoroscopically, may be necessary in patients unable to resume oral intake within the first postoperative week. Prospective clinical trials of prophylactic postoperative medications such as metoclopramide or the motilin agonist erythromycin have failed to demonstrate a profound impact on the incidence of delayed gastric emptying, and no clear advantage to pylorus preservation or distal gastrectomy during pancreaticoduodenectomy has been shown in randomized clinical trials.
Pancreatic fistula, defined as high-output amylaserich drain fluid after postoperative day 5, occurs in approximately 8% to 20% of patients, and may be associated with the texture of the pancreas found at the time of resection. In patients without associated infectious complications, management includes adequate drainage and observation. Enteral nutrition may be maintained in patients without septic complications and low-output fistulae (typically defined as <200 mL per 24-hour period). Low-output fistulae will typically resolve spontaneously, and can often be managed as an outpatient following hospital discharge, with drain removal once fistula output is consistently <30 mL per 24-hour period. In patients with high-volume fistulae, and/or associated infectious complications, bowel rest with subcutaneous octreotide administration should be initiated. Parenteral nutrition is often necessary in these patients. Pancreatic fistula can be associated with other postoperative complications including ileus and delayed gastric emptying, wound infection or dehiscence, or bleeding complications. Pseudoaneurysm formation at the GDA stump can occur as a complication of a known or occult pancreatic fistula; management for this potentially life-threatening complication includes appropriate resuscitation and angiographic intervention with occlusion or exclusion of the GDA pseudoaneurysm. All but rare catastrophic complicated pancreatic fistulae can and should be managed nonoperatively. Revision pancreaticojejunostomy is likely a futile procedure, and completion pancreatectomy can be a near-impossible procedure in a reoperative and contaminated field. In patients without adequate percutaneous drainage and uncontrolled sepsis, surgical intervention for washout and placement of additional peripancreatic drains may be appropriate.
Case Conclusion
The patient underwent successful pancreaticoduodenectomy with negative margins. The postoperative course was complicated by a pancreatic fistula, diagnosed by low-volume amylaserich drain output. The patient was sent home postoperative day 7, on a low-fat diet with the surgical drains in place. Drain output was minimal by the third postoperative week, and drains were removed. The patient completed adjuvant chemotherapy and at 18 months postoperatively has no evidence of recurrent disease.
TAKE HOME POINTS
· Painless obstructive jaundice should be considered indicative of a malignancy until proven otherwise.
· Obstructive jaundice with intrahepatic and extrahepatic biliary ductal dilatation, consistent with a distal biliary obstruction, should first be evaluated with a pancreatic protocol CT when possible.
· In a patient with a pancreatic head mass, decisions about the need for biliary decompression and/or biopsy should be made by an experienced hepatopancreaticobiliary surgeon while considering resectability and the overall treatment plan.
· Surgical resection is necessary, but not sufficient, as curative therapy for pancreatic adenocarcinoma. Definitive treatment for pancreatic cancer should include multidisciplinary oncologic care including surgery, systemic chemotherapy, and radiation therapy.
· Venous resection and reconstruction can be performed safely with appropriate oncologic outcomes in appropriately selected patients by experienced surgeons.
· All operations for pancreatic cancer should begin with a thorough exploration to assess for metastatic disease and to determine resectability.
· Postoperative complications, including delayed gastric emptying and pancreatic fistula, can be safely managed when recognized early and treated comprehensively.
SUGGESTED READINGS
Abrams RA, Lowy AM, O’Reilly EM, et al. Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1751–1756.
Bassi C, Dervenis C, Butturini G. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138(1):8–13.
Evans DB, Farnell MB, Lillemoe KD, et al. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol. 2009;16(7):1736–1744.
Simeone DM. Complications of pancreatic surgery. In: Doherty GM, ed. Complications in Surgery. 1st ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2006:463–476.
van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:129–137.