Continuing Education Activity

Pancreatic cancer is increasing worldwide and contributes significantly to global cancer mortality. Pancreaticoduodenectomy, commonly known as the Whipple procedure, stands as the preferred surgical option for adenocarcinomas affecting the pancreatic head and uncinate process, notorious for a dismal 5-year survival rate. Although surgical intervention remains pivotal for resectable cases, the procedure's historical intricacies correlate with elevated mortality and perioperative morbidity. Originating in 1898, Alessandro Codivilla pioneered the surgery, subsequently refined by Walter Kausch in 1912 and Allen Whipple in 1940. Medical, anesthetic, and surgical care advancements have significantly reduced mortality rates, especially in high-volume hospitals with adept pancreatic surgery teams, achieving rates below 3%. The procedure entails the removal of the pancreatic head, duodenum, distal stomach, gallbladder, and distal bile duct, offering both open and minimally invasive options. Prudent patient selection is crucial due to the surgery's complexity and potential postoperative complications.

This comprehensive course explores the surgical anatomy, indications, contraindications, technical steps, and clinical implications of pancreaticoduodenectomy, emphasizing its critical role in addressing the increasing global burden of pancreatic cancer. By engaging in this course, interprofessional team members, including surgeons, oncologists, anesthesiologists, nurses, and allied healthcare professionals, enhance their competence in collaborative patient care. Ultimately, the interprofessional team's collective expertise ensures optimal patient outcomes and contributes to advancing the standard of care for pancreaticoduodenectomy.

Objectives:

• Identify anatomical structures associated with the pancreas and surrounding areas to enhance surgical precision during a pancreaticoduodenectomy.
• Assess postoperative complications promptly, employing effective strategies to mitigate risks and optimize patient recovery after a pancreaticoduodenectomy.
• Communicate effectively with patients, providing clear information about the procedure, potential risks, and expected outcomes to facilitate informed decision-making.
• Collaborate with multidisciplinary team members to improve outcomes in patients undergoing pancreaticoduodenectomy.

Introduction

Pancreaticoduodenectomy, commonly referred to as the Whipple procedure, is the preferred surgical intervention for tumors affecting the pancreatic head and uncinate process (see Image. Pancreaticoduodenectomy (Whipple Procedure).[1] The primary indication for this procedure is pancreatic head or uncinate process adenocarcinoma, a particularly aggressive tumor associated with a dismal 5-year survival rate.[2] Surgical intervention remains the cornerstone for treating patients with resectable disease, leading to enhanced survival outcomes. However, the intricacies of pancreaticoduodenectomy have historically correlated with elevated mortality and perioperative morbidity.[1]

The Italian surgeon Alessandro Codivilla conducted the inaugural pancreaticoduodenectomy in 1898, with subsequent modifications by Walter Kausch in 1912. Allen Whipple further refined the operative technique into a 1-stage operation in 1940.[3][4] Initial reports highlighted prohibitive mortality rates, but advancements in medical, anesthetic, and surgical care have significantly ameliorated morbidity and mortality rates. In high-volume hospitals with an adept pancreatic surgery team, the mortality rate can drop below 3%.[5][6] 

Pancreaticoduodenectomy involves the excision of the pancreatic head, duodenum, distal stomach, gallbladder, and distal bile duct and can be conducted through open surgery or minimally invasive techniques.[7] Prudent patient selection is crucial, given the procedure's complexity and the potential for postoperative complications. This article explores the surgical anatomy, indications, contraindications, technical steps of pancreaticoduodenectomy, and its clinical implications.

Anatomy and Physiology

The pancreas is a retroperitoneal organ lying posterior to the stomach and is divided arbitrarily into the head, neck, body, tail, and uncinate processes, with the head lying within the C-loop of the duodenum (see Image. Pancreas and Duodenum, Anterior View).[8] The gland receives arterial supply from the superior mesenteric artery and the celiac axis. The gastroduodenal artery, a branch of the common hepatic division of the celiac axis, arises at the superior border of the pancreatic head and runs inferiorly behind the pancreatic head. This artery gives rise to the anterior and posterior superior pancreaticoduodenal arteries. The middle colic branch of the superior mesenteric artery gives rise to the anterior and posterior inferior pancreaticoduodenal arteries. These pancreaticoduodenal arteries supply the pancreatic head and uncinate process and form a rich anastomotic network within the gland, with branches of the splenic artery (dorsal pancreatic artery, greater pancreatic artery, transverse pancreatic artery, and several unnamed branches) that supply the rest of the gland.

The pancreaticoduodenal veins follow the arteries and drain the proximal pancreas into the superior mesenteric or portal vein. The pancreas' neck, body, and tail have venous drainage into the splenic vein via small tributaries. The pancreatic head lies anterior to the inferior vena cava and left renal vein. The portal vein, formed by the confluence of the splenic and superior mesenteric veins, lies posterior to the pancreatic neck. The superior mesenteric vein lies to the left of the superior mesenteric vein, anterior to the abdominal aorta. The tortuous splenic artery runs along the superior border of the pancreas; the splenic vein runs posteriorly to the body and tail of the pancreas.[9] Lymphatic drainage mirrors the blood supply, with lymph nodes along the named vessels and in the peripancreatic and retropancreatic tissue (see Image. Lymphatics and Drainage of the Pancreas).

Exocrine pancreatic secretions empty into the second portion of the duodenum via the pancreatic ducts. The main duct begins in the tail, runs the entire length of the pancreas, and is joined by the common bile duct before opening into the duodenum at the major papilla through the ampulla of Vater. The common bile duct, which runs posterior to the duodenum, joins the main pancreatic duct within the pancreatic parenchyma. The accessory pancreatic duct drains the inferior portion of the pancreas and empties through the minor papilla. 

There are several critical anatomical considerations in pancreatic surgery, the understanding of which helps surgical dissection in the correct plane. The pancreas shares the same blood supply with the C-loop of the duodenum, necessitating the removal of the C-loop of the duodenum together with the pancreas. The uncinate process, which arises from the lower part of the head of the pancreas, extends superiorly and posteriorly behind the superior mesenteric vein to the lateral border of the superior mesenteric artery.[10] Skeletonizing the superior mesenteric vein and the right edge of the superior mesenteric artery is critical to complete resection. The transverse mesocolon is attached to the anterior surface of the pancreas and must be dissected off to expose the inferior border of the gland. The pancreas must be separated from the superior mesenteric vein/portal vein before pancreatic transection. A vein resection may be required when this step is impossible. A pancreaticoduodenectomy must include an adequate lymphadenectomy when performed for cancer. 

Variations in vascular anatomy are critical to identify preoperatively. A replaced right hepatic artery arising from the superior mesenteric artery occurs in around 12% of the population.[11] A replaced right hepatic artery can be problematic as it often courses behind the pancreatic head and bile duct near the gland. Other variants include accessory right hepatic arteries, accessory left hepatic arteries, and several other less common variants.[11][12]

Indications

The following are the indications for performing a pancreaticoduodenectomy: 

• Tumors involving the pancreatic head or uncinate process:
• • Pancreatic ductal adenocarcinoma [13]
  • Pancreatic neuroendocrine tumors [14]
  • Duodenal gastrointestinal stromal tumor [15]
  • Intraductal papillary mucinous neoplasms [16][17]
  • Periampullary cancer [18]
  • Adenocarcinoma of the ampulla of Vater [19]
  • Duodenal adenocarcinoma and other duodenal tumors [19] 
• Chronic pancreatitis [20] 
• Severe pancreatic trauma [21]

The resectability of pancreatic head neoplasms is based on radiographic criteria, which divides lesions into resectable, borderline resectable, and unresectable tumors. 

Resectable Disease

• No distant metastasis
• No radiographic evidence of portal vein or superior mesenteric vein distortion
• Clear dissection planes around the celiac axis, hepatic artery, and superior mesenteric artery

Borderline Resectable Disease

• Superior mesenteric vein/portal vein involvement with distortion, narrowing, or occlusion, but the presence of suitable proximal and distal vessels for reconstruction
• Gastroduodenal artery encasement up to the hepatic artery with short segment encasement or abutment of the hepatic artery without extending to the celiac axis
• Tumor abutment of the superior mesenteric artery less than 180° of the vessel wall circumference [22][23]

Unresectable Disease

• Distant metastases
• Tumor encasement of superior mesenteric artery more than 180°
• Celiac axis abutment
• Inferior vena cava involvement
• Aortic involvement
• Irreparable superior mesenteric vein or portal vein occlusion [22]

Contraindications

Anatomic contraindications to a pancreaticoduodenectomy include unresectable disease and metastatic disease. Additionally, due to the notable morbidity and mortality associated with the procedure, a meticulous evaluation of a patient's capacity to withstand a pancreaticoduodenectomy is imperative. Individuals with significant comorbidities or other life-limiting illnesses may not be optimal candidates for surgery.

Equipment

Standard equipment used for an open pancreaticoduodenectomy includes the following:

• Instruments for diagnostic laparoscopy and biopsy to be performed before the open procedure
• A self-retaining retractor
• Laparotomy instrument set
• Surgical clips
• Suture materials, including fine monofilament sutures for potential vascular injury
• Scalpel
• Electrocautery
• Intestinal staplers
• Surgical drains
• A vessel-sealing device
• Vascular surgical instruments if vascular reconstruction is required
• Intraoperative ultrasound

Personnel

In addition to the surgeon, a scrub tech, an operating room nurse, an anesthesiologist, and a second surgeon or a first assistant will be required to perform the procedure. 

Preparation

Preoperative preparation includes:

• An extensive review of the patient's radiographic studies must be done to confirm resectability. 
• The surgeon and surgical team must discuss the risks and benefits of the procedure and the expected postoperative recovery course with the patient.
• The surgeon must obtain informed consent for the procedure from the patient. 

Perioperative preparation includes:

• Antibiotic prophylaxis within 30 minutes of skin incision
• Deep vein thrombosis prophylaxis
• Invasive monitoring if required (central venous access, arterial line)
• Octreotide administration depending on surgeon preference
• Available grafts or other potential conduits for vascular resections, if planned

Technique or Treatment

This paragraph outlines the procedure of an open pancreaticoduodenectomy. Acknowledging the sequence of steps presented here does not necessarily dictate the order of operation. Anatomic factors and surgeon preferences may influence different approaches. Furthermore, the techniques employed for reconstruction exhibit significant variability.

Staging Laparoscopy

Before proceeding to laparotomy for pancreatic adenocarcinoma, a staging laparoscopy is conducted to exclude metastatic disease and ensure resectability.[24] Staging laparoscopy has shown high success rates, ranging from 94% to 100% in various studies. Technical challenges primarily stem from dense adhesions hindering inspection and ultrasound probe examination. Despite adhesions, examinations are possible, albeit with compromised extent and yield. Conversions to open surgery are rare. Typically performed under general anesthesia with 15 mm Hg insufflation pressures, the procedure involves a comprehensive assessment of disease extent to determine resectability with various anatomical areas scrutinized and bed position changes made to facilitate thorough inspection. First, the entire liver is examined and palpated for potential metastases, and any suspicious findings are further evaluated using intraoperative ultrasound. The meticulous examination is then extended to the parietal and visceral peritoneal surfaces, the ligament of Treitz, the omentum, and the entire small and large intestine to detect metastases. Peritoneal washings, ascitic fluid cytology, and biopsies of suspected lesions contribute to the comprehensive evaluation. Laparoscopic ultrasound aids in examining not only hepatic parenchyma but also blood vessels, the pancreas, and lymph nodes, with color flow Doppler enhancing vascular patency assessment. Suspicious lymph nodes outside the planned dissection field undergo biopsy, prompting procedure cessation if positive.

Pancreatic Resection

Once resectability is confirmed and the decision is made to proceed to an open procedure, a vertical midline or bilateral subcostal incision is used. A self-retaining retractor is applied. A Kocher maneuver is performed by elevating the duodenum and head of the pancreas out of the retroperitoneum, separating the filmy attachments between the pancreatic head and the inferior vena cava posteriorly until the left renal vein's origin is identified. A Cattell-Braasch maneuver (extensive mobilization of the entire right colon and small bowel mesentery) is usually unnecessary except for cases where the superior mesenteric vein needs to be mobilized and resected or if the tumor extends into the fourth part of the duodenum.[25] The tumor is palpated, and resectability is once again reconfirmed.[26] Next, the lesser sac is entered by opening the gastrocolic omentum lateral to the gastroepiploic arcade. The anterior surface of the pancreas is visualized, and retrogastric pancreatic attachments are released to mobilize the stomach. Next, the transverse mesocolon is dissected off the anterior surface of the pancreas, taking care not to enter the mesocolic tissue. The thickness and vascularity of the mesocolon and omentum are highly variable and are closely linked to the patient's body mass index. Once the mesocolic dissection is complete, the middle colic vein is identified and traced back to where it joins the superior mesenteric vein. Alternatively, the right gastroepiploic vein can also be identified and traced backward. A significant proportion of patients have a common insertion of the right gastroepiploic and middle colic veins, known as a trunk of Henle.[27] Identifying the anterior superior mesenteric vein surface precedes the creation of a retropancreatic tunnel through gentle dissection in a loose areolar plane behind the pancreatic neck.

To access the common hepatic artery and its accompanying lymph node, the stomach is retracted upward, allowing for careful dissection along the arterial surface until reaching the origin of the gastroduodenal artery, which is then encircled. Essential before gastroduodenal artery division is a critical test clamping of the artery, carefully assessing the pulse in the proper hepatic artery to ensure adequate hepatic blood flow via the celiac axis (see Image. Celiac Artery.). If gastroduodenal artery occlusion causes the pulse to vanish, collateral flow through the superior mesenteric artery feeding the hepatic artery requires arterial reconstruction before ligating the gastroduodenal artery. Dividing the gastroduodenal artery unveils the anterior portal vein surface, facilitating the visualization of the CBD, portal vein, and hepatic arteries. Confirming the absence of a pulse posterior to the portal vein is crucial, indicating an accessory or replaced right hepatic artery. A top-down cholecystectomy starts at the gallbladder fundus. It dissects toward the hilum, often passing off the gallbladder as a separate specimen after clipping and dividing the cystic duct and artery. The common bile duct is encircled and divided, usually just proximal to the cystic duct insertion. The proximal common bile duct margin should be sent for frozen section analysis in cancer cases. Bile duct division enhances portal vein visualization. Completing the retropancreatic tunnel involves dissecting the portal vein off the pancreatic gland and communicating with the tunnel initiated over the superior mesenteric vein, with potential vein resection required if the gland cannot be separated from the portal vein or superior mesenteric vein.

A linear stapler divides the stomach at the proximal antrum in a classic pancreaticoduodenectomy. Alternatively, a pylorus-preserving pancreaticoduodenectomy preserves the pylorus, with the proximal duodenum divided 2 to 3 cm distal to the pylorus using a linear stapler. Subsequently, the jejunum is divided between 15 to 20 cm distal to the ligament of Treitz, and the jejunal mesentery is divided, staying close to the specimen until the jejunal specimen can be passed into the supramesocolic compartment through the ligament of Trietz. Preparing for pancreatic transection involves placing stay sutures on either side of the proposed line, and the pancreas is then divided, either sharply or with electrocautery. Caution is exercised to avoid injuring the underlying superior mesenteric vein/portal vein, and small bleeders on the cut pancreatic surface are typically cauterized. The pancreatic remnant ductal margin is sent for frozen histopathology. If vascular resection is necessary, the pancreas is not divided until proximal and distal control of the superior mesenteric, portal, and splenic veins is established. The pancreas is gently separated from the superior mesenteric vein and portal vein, with attention to draining venous branches in the uncinate process, and dissection continues until the superior mesenteric vein and the right border of the superior mesenteric artery are skeletonized, culminating in specimen removal.

Reconstruction

Reconstruction begins once the pancreatic and bile duct margins are tumor-free on the frozen section, although the benefit of this practice has been questioned.[28] The cut end of the jejunum is brought to the pancreatic remnant through a mesocolic window, ensuring no tension on the jejunal loop. The pancreatic duct is identified. In very small ducts, a temporary pancreatic stent may be used. External drainage of the pancreatic duct is sometimes used to reduce pancreatic leak rates, although the data are inconclusive.[29][30] A duct-to-mucosa anastomosis is typically performed, ensuring the pancreatic duct is directly approximated to the jejunal mucosa. Several variations of the technique are described, which are beyond the scope of this chapter. The variety of these techniques helps to improve the rate of pancreatic fistula formation, but there is no single superior technique.[31] The reconstruction is followed by end-to-side hepaticojejunostomy, performed 10 to 15 cm distal to pancreaticojejunostomy with interrupted single-layer absorbable suture. A loop of jejunum, roughly 30 cm distal to the hepaticojejunostomy, is brought in an antecolic fashion to the cut end of the stomach. A gastrojejunostomy (or duodenojejunostomy in pylorus-preserving pancreaticoduodenectomy) is then performed.

Reconstruction begins once the frozen section confirms tumor-free margins for both the pancreatic and bile duct, though the efficacy of this practice is debated.[28] The jejunum's cut end is carefully brought to the pancreatic remnant through a mesocolic window, ensuring a tension-free loop. Identifying the pancreatic duct is crucial, and a temporary pancreatic stent may be employed in cases of very small ducts. External drainage of the pancreatic duct is occasionally used to reduce pancreatic leak rates, though conclusive data are lacking.[29][30] A duct-to-mucosa anastomosis is typically conducted, ensuring a direct approximation of the pancreatic duct to the jejunal mucosa. Beyond the chapter's scope, various techniques aim to enhance pancreatic fistula formation rates, but no single superior technique exists.[31] Following reconstruction is the end-to-side hepaticojejunostomy, performed 10 to 15 cm distal to pancreaticojejunostomy using interrupted single-layer absorbable sutures. A loop of jejunum, approximately 30 cm distal to the hepaticojejunostomy, is brought in an antecolic fashion to the cut end of the stomach. Finally, a gastrojejunostomy (or duodenojejunostomy in pylorus-preserving pancreaticoduodenectomy) is performed.

Closure and Postoperative Care

Following reconstruction, closed suction drains are strategically placed near the pancreatic and biliary anastomosis to monitor postoperative drainage.[32] The necessity of a feeding jejunostomy is contingent on the surgeon's preference. The abdominal closure is conducted in layers. Overnight post-surgery, the stomach is decompressed using a nasogastric tube, typically removed the following morning unless excessive output exists. The use of a nasogastric tube is not obligatory.[33] On postoperative days 1 and 3, the content of abdominal drains is assessed for amylase. Elevated amylase levels (exceeding 3 times the upper limit of normal serum values) suggest a pancreatic leak, prompting tailored management based on leak volume, drain content, and the patient's clinical condition.[34] Gradual drain removal occurs once the output is minimal, there is no evidence of a pancreatic fistula, and the patient tolerates a normal diet.

Complications

Some of the complications explicitly seen after pancreaticoduodenectomy are listed below:

Delayed gastric emptying 

• This is the inability to discontinue the nasogastric tube and tolerate a solid diet after the surgery.[35] 
• This is significantly higher in the presence of a pancreatic leak and is typically managed with nasogastric decompression, prokinetic agents, and by addressing the underlying cause.[36] 
• Nasogastric decompression should be initiated when the diagnosis is suspected. 

Pancreatic fistula

• This is defined as drain output on postoperative day 3 or beyond with an amylase content over 3 times the upper limit of serum amylase.[37] 
• They are graded based on severity as follows:
• • Grade A - biochemical leak, no clinical relevance
  • Grade B - persistent amylase-rich drainage that alters postoperative management, usually persisting beyond 3 weeks
• Grade C - fistula with organ failure 
• These can be managed nonoperatively through resuscitation, antibiotics, somatostatin analog usage, and external or internal pancreatic drainage. Surgery is rarely indicated.[38]

Postoperative bleeding

• This can be from raw surfaces or inadequate hemostasis during the operation.

Visceral artery pseudoaneurysm

• This is the most severe complication.
• It most commonly involves the GDA.
• These can rupture, resulting in exsanguination and death if not managed with embolization immediately.[39]

Wound infection [39][40]

Intra-abdominal abscess [41]

Biliary complications 

• Bile leaks 
• • These usually manifest in the early postoperative period and are related to technical issues.

Biliary strictures at the hepaticojejunostomy

• These are late complications from a narrow anastomosis, ischemia, or tumor recurrence.[36] 

Exocrine insufficiency

• This develops in over half of the patients undergoing pancreaticoduodenectomy.
• Enzyme supplementation is usually adequate to replete the lost enzymes.[42]

Pancreatic endocrine insufficiency

• Diabetes develops in approximately 20% of patients postoperatively, with the rate much higher in patients who have impaired glucose tolerance preoperatively.[43][44]

Clinical Significance

Pancreatic cancer is the fourth leading cause of cancer-related mortality, with a mere 12% 5-year survival rate, despite advancements in medical care, chemotherapy, radiotherapy, and molecular biology.[45][46] Pancreaticoduodenectomy is the sole curative treatment option for the majority of tumors affecting the pancreatic head and neck. A comprehensive understanding of anatomy, diagnostic imaging, interventions, surgical procedures, perioperative and postoperative management, and early recognition and treatment of complications is paramount for optimal patient outcomes. Adequate education for physicians, nurses, and the entire healthcare team is imperative, emphasizing the necessity of a multidisciplinary approach.

Enhancing Healthcare Team Outcomes

Effective patient-centered care during pancreaticoduodenectomy necessitates a collaborative and well-coordinated effort among various healthcare professionals. Surgeons must exhibit advanced surgical skills, a profound understanding of anatomical complexities, and adept decision-making abilities. Advanced practitioners contribute through comprehensive patient assessments, ensuring continuity of care. Nurses are pivotal in monitoring patient well-being, managing postoperative care, and fostering patient education. Pharmacists contribute expertise in medication management, preventing adverse drug interactions. Interprofessional communication is paramount, facilitating seamless information exchange and decision-making. Additionally, health professionals must collectively coordinate care plans, emphasizing the importance of shared responsibilities to enhance patient safety, optimize outcomes, and improve overall team performance in pancreaticoduodenectomy.

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Disclosure: Jason D'Cruz declares no relevant financial relationships with ineligible companies.

Disclosure: Subhasis Misra declares no relevant financial relationships with ineligible companies.

Disclosure: Shafeek Shamsudeen declares no relevant financial relationships with ineligible companies.