Pylorus-Preserving Pancreaticoduodenectomy (PPPD)

Pancreaticoduodenectomy has evolved since Kausch performed the first successful procedure as a two-stage operation in 1912. He was preceded by Codivilla in Italy, who performed the first pancreaticoduodenectomy in the 1890s; however, the patient unfortunately died in the immediate postoperative period.

The modern colloquial name for this operation (ie, Whipple procedure) refers to Dr Allen Oldfather Whipple, the surgeon who reported his series of pancreaticoduodenectomies in 1935. He had performed the procedure on three patients as a two-stage operation for periampullary neoplasms, then later refined his methodology to a one-stage procedure.

In 1937, Brunschwig extended the indications for pancreaticoduodenectomy by performing the operation for pancreatic head lesions.

In 1946, Waugh and Clagett described a formal en-bloc resection of the gallbladder with the common bile duct (CBD), gastric antrum, duodenum, and pancreatic head performed as a one-stage procedure, which we recognize today as the classic pancreaticoduodenectomy. However, the operation, though refined since Codivilla and Kausch, was utilized sparingly; perioperative mortality continued to be prohibitive, estimated as being close to 25% into the 1960s.

As advances in medicine yielded better perioperative outcomes across surgical applications, interest in the Whipple procedure was revitalized, and the procedure was performed increasingly often. In an effort to decrease postgastrectomy syndromes, especially nutritional, in post-Whipple patients, Traverso and Longmire described a pylorus-preserving modification in 1978.  Important subsequent advances included the application of new technologies (ie, laparoscopic and robotic approaches to pancreaticoduodenectomy).[1, 2, 3, 4, 5, 6, 7]  More recently, a pylorus-resecting pancreaticoduodenectomy (PRPD) was described, intended mainly to address the issue of delayed gastric emptying (DGE).

Although innumerable details of pancreaticoduodenectomy yield to continued innovation, a comprehensive discussion of intraoperative variants (ie, duct to mucosa vs invagination of the pancreaticojejunal anastomosis, diverse approaches to vein resection and reconstructions, nuances of each enteric anastomosis, and modifications of Roux-en-Y reconstructions, to name a few) is beyond the scope of this article. We will focus on the technical aspects and perioperative impacts of the Traverso modification of pancreaticoduodenectomy.

See also Ampullary Carcinoma, Pancreatic Cancer, Pancreatic Trauma, and Carcinoma of the Ampulla of Vater.

Pylorus-preserving pancreaticoduodenectomy (PPPD) is indicated for the following benign conditions:

• Benign periampullary neoplasms not amenable to local resection with ampullectomy
• Benign duodenal neoplasms not amenable to local resection
• Pancreatoduodenal trauma (rare)

PPPD is also indicated for the following malignant conditions:

• Pancreatic ductal adenocarcinoma (PDAC)
• Ampullary carcinoma
• Distal CBD carcinoma (cholangiocarcinoma)
• Duodenal carcinoma
• Pancreatic islet cell carcinoma
• Malignant intraductal papillary-mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN)

Resectability is best described as the absence of contraindications for resection (see Technical Considerations). Pancreatic-protocol computed tomography (CT) with thin collimation will detect anatomic contraindications for surgical resection.

Anatomy

The pancreas is prismoid in shape and appears triangular in cut section, with superior, inferior, and anterior borders as well as anterosuperior, anteroinferior, and posterior surfaces.

The head of the pancreas lies in the duodenal C loop in front of the inferior vena cava (IVC) and the left renal vein (see the images below). The uncinate process is an extension of the lower (inferior) half of the head toward the left; it is of varying size and is wedged between the superior mesenteric vessels (vein on the right, artery on the left) in front and the aorta behind it.

For more information about the relevant anatomy, see Pancreas Anatomy.

See Pancreatic Adenocarcinoma Imaging: What You Need to Know, a Critical Images slideshow, to help identify which imaging studies to use to identify and evaluate this disease.

Procedural planning

Head-to-head comparison between the classically described pancreaticoduodenectomy and PPPD has not detected any significant differences with regard to operating time, perioperative morbidity, perioperative mortality, and long-term survival at 1, 3, and 5 years. Operative blood loss is slightly lower with PPPD, but the clinical significance of this is not clear.

Thus, PPPD can be considered a technical variant of pancreaticoduodenectomy, in which blood supply to the proximal duodenum is preserved. Therefore, it is important to emphasize that broad indications for resection will not differ between the two approaches.[1, 2, 3, 4]  The two main points of difference between classical pancreaticoduodenectomy (ie, the Whipple procedure) and PPPD that merit discussion are the following:

• Achievement of R0 oncologic resection (ie, surgical margins negative for tumor)
• Postoperative DGE

From an oncologic perspective, PPPD should not be performed with large, bulky tumors or with any tumor that may involve the first or second portion of the duodenum. In addition, with the gastric antrectomy performed in classic pancreaticoduodenectomy, an average of four more nodes are harvested than would be harvested with PPPD. These will be positive for nodal metastases approximately 5% of the time. The question therefore arises as to whether the incidence of non-R0 resection in this small cadre of patients should bias the surgeon against PPPD.

Patients who undergo PPPD have a much higher incidence of DGE than those who undergo classic pancreaticoduodenectomy. This is the primary morbidity with PPPD patients, leading to more medical interventions and thus increased cost postoperatively, related to hospital stay, cost of jejunal feedings, and jejunal tube maintenance (eg, home nursing for tube care, emergency department [ED] visits for dislodgment, and tube replacement for dysfunction). If aspiration then complicates the matter, there can be a threat to the patient's life as well.

In view of the aforementioned considerations and the lack of statistical difference between classic pancreaticoduodenectomy and PPPD with regard to patient morbidity, mortality, and survival, the surgeon’s choice of approach should be based on the individual patient profile and the specific characteristics of the tumor.

Determination of resectability

Tumor resectability must be assessed well before the patient arrives at the operating room. The tumor is considered resectable if it is locally confined (ie, if there is no distant disease). Preoperative imaging studies are the cornerstone of evaluation.

As noted, pancreatic-protocol contrast-enhanced CT with thin collimation is the most effective tool for identifying local extension. The tumor can be evaluated in relation to important vascular structures. A fat plane should be seen between the low-density tumor and surrounding structures.

The disease is considered resectable if the following conditions are met:

• The tumor does not encase the celiac axis or SMA (does not involve >180º of circumference)
• The superior mesenteric vein (SMV), the portal vein (PV), and the SMV-PV confluence are all patent (with no thrombosis)
• There is no extraregional nodal disease
• There is no distant metastatic disease

Additional imaging is usually not necessary, but in certain cases, endoscopic ultrasonography (EUS), fine-needle aspiration cytology (FNAC), or both may be employed for tissue diagnosis before the initiation of neoadjuvant therapy.

Complication prevention

The following are considerations in preventing complications:

• Thorough preoperative evaluation (see Periprocedural Care)
• Intravenous antibiotics for cholangitis or biliary sepsis
• Prophylactic mechanical bowel preparation
• Sequential compression devices for deep venous thrombosis (DVT) prevention
• Preoperative biliary decompression if delay to surgery or preoperative cholangitis
• Nasogastric decompression
• Promotility agents, selective mu-receptor antagonists, pancreatic enzyme replacement

A 2014 Cochrane review examined six randomized controlled trials (RCTs) comparing classic Whipple pancreaticoduodenectomy with PPPD in a total of 465 patients with periampullary or pancreatic carcinoma.[8] The authors found no significant differences in mortality, morbidity, or survival between the two operations.

This review was updated in 2016 to include eight RCTs with a total of 512 participants.[9]  Again, the investigators found no evidence of any significant differences in mortality, morbidity, and survival between the two operations, though some perioperative outcome measures favored PPPD to a significant degree.

History and physical examination

Key elements of the patient's history and physical examination include the following information:

• Unintended weight loss
• Pancreatitis
• Biliary obstruction
• Painless jaundice
• Social (smoking, tobacco)
• Family history of pancreatic cancer
• Familial syndromes ( Peutz-Jeghers syndrome, familial atypical multiple mole melanoma [FAMMM], hereditary nonpolyposis colorectal cancer [HNPCC])
• Body habitus (temporal wasting, cachexia)
• Icterus, jaundice
• Lymphadenopathy
• Ascites, hypoalbuminemia
• Elevated tumor markers (elevated CA 19-9 in the absence of biliary obstruction)

Workup

The following laboratory and imaging studies should be obtained to help determine the patient's fitness for surgery:

• Complete blood count (CBC), basic metabolic panel (BMP), liver function tests (LFTs), and a coagulation panel
• Tumor markers, such as CA 19-9 and carcinoembryonic antigen (CEA)
• Abdominal ultrasonography (US) - Primary imaging modality for evaluation of biliary obstruction and/or ascites
• Pancreatic-protocol contrast-enhanced computed tomography (CT) - Thin cuts are needed to assess criteria for tumor resectability (see  Determination of resectability in  Technical Considerations)
• Chest x-ray (CXR) or chest CT - Metastatic workup

Endoscopic US (EUS), fine-needle aspiration (FNA), or both are occasionally performed in a patient who is being considered for PPPD. EUS, though not routinely employed, is helpful when pancreatic head masses are poorly detected on CT. Tumor aspiration is not routinely employed for preoperative tissue diagnosis, because FNA results do not affect surgical decision-making; however, confirmation of malignancy can be useful in the setting of neoadjuvant therapy. Also, there is a finite risk of seeding the peritoneum with malignant disease from percutaneous needle biopsy.

Endoscopic retrograde cholangiopancreatography (ERCP) may be performed for preoperative endobiliary stent placement in the setting of cholangitis or biliary obstruction with anticipated delay to surgery or need for neoadjuvant therapy.

Patients will be restaged after neoadjuvant therapy before the surgical procedure.

Equipment needed for pylorus-preserving pancreaticoduodenectomy (PPPD) includes the following:

• Arterial and central venous lines for hemodynamic monitoring
• Nasogastric tube
• Foley catheter
• Closed-suction transcutaneous drains

The patient and surgical team should also be prepared for total pancreatectomy if intraoperative pathologic analysis reveals evidence of malignancy at the pancreatic margin.

The procedure is performed with the patient under general anesthesia. Preoperative anesthesia evaluation includes the following:

• Nutritional status
• Functional status
• Cardiac risk factors
• American Society of Anesthesiologists (ASA) class

For this procedure, the patient is placed in the supine position.

After the operation, obtain the following laboratory and radiologic studies as needed:

• CBC, BMP, serum amylase, drain amylase, LFTs to monitor total bilirubin, and albumin; other laboratory tests may be indicated in the specific clinical setting
• CT for persistent fever, leukocytosis, or sepsis with concern for pancreatic anastomotic leak

Close follow-up of the patient by the surgeon is mandated for at least 6 months postoperatively. However, patient follow-up also takes place in a multidisciplinary manner that involves surgical, medical, and hematologic/oncologic specialists.

The steps for completion of a pylorus-preserving pancreaticoduodenectomy (PPPD) can be thought of as a clockwise journey. The surgeon begins at the ascending colon and hepatic flexure to obtain exposure of the superior mesenteric vein (SMV), then moves to the porta hepatis for cholecystectomy and portal lymph node dissection, followed by transection of the stomach or proximal duodenum. He or she then proceeds to jejunal transection and, finally, pancreatic transection, with completion of retroperitoneal dissection and removal of the specimen en bloc.

The reconstructions can be performed in a counterclockwise direction: The surgeon starts with creation of jejunal feeding access and then proceeds to creation of the pancreaticojejunal, choledochojejunal, and enterojejunal anastomoses. Venous reconstructions are also undertaken in select patients who need venous resection for involvement by the tumour.

An example of a PPPD is shown in the video below.

Laparotomy and abdominal exploration

Laparotomy is performed with a generous midline incision or bilateral subcostal incisions. The liver is palpated, the peritoneum is inspected, and the paraortic lymph nodes and the root of the mesentery are evaluated.

Intraoperative hepatic ultrasonography (US) may be used when preoperative imaging is not definitive. In addition, abdominal exploration may be undertaken as staging laparoscopy before laparotomy in patients with advanced disease (eg, a large tumor or very high carbohydrate antigen [CA] 19.9 level) who are suspected of being at risk for radiographically silent metastatic disease.

Exposure of superior mesenteric artery and extended kocherization

A self-retaining retractor facilitates general exposure of the operative field. The falciform ligament is identified and preserved for later use (to protect the gastroduodenal artery [GDA] stump). The ascending colon and hepatic flexure are mobilized by using a Cattell-Brasch maneuver or right medial visceral rotation to expose the third and fourth portions of the duodenum.

The lesser sac is then opened and entered. Here, the middle colic vein is encountered and ligated, facilitating exposure of the SMV. The gastroepiploic vein is often seen entering the gastrocolic trunk (GCT) with the middle colic vein and can be ligated when encountered.

Next, an extended Kocher maneuver is performed from the right ureter and right gonadal vein junction (which may be ligated and mobilized) until the aorta and the crossing left renal vein are identified. Intervening lymphatic tissues should be mobilized as well. Here, the superior mesenteric artery (SMA) should be identifiable.

Cholecystectomy and portal dissection

The celiac axis is located, and the left gastric artery is identified and preserved. The node of the common hepatic artery is removed, and the common hepatic artery is dissected proximal and distal to the GDA takeoff. This is done carefully (because the common hepatic artery is fragile), and the GDA is transected. Cholecystectomy is performed with transection of the specimen at the common hepatic duct (CHD) just above the joining of the cystic duct. The CHD margin undergoes intraoperative pathologic analysis and is extended if necessary.

Given the anatomic variability of hepatic arterial circulation, the surgeon must look for a replaced right hepatic artery or replaced common hepatic artery. After the origins of the aforementioned are identified, medial retraction applied to the common hepatic artery exposes the anterior surface of the portal vein (PV). The PV is followed to its junction with the SMV behind the pancreatic neck, with the surgeon taking great care to avoid traction injury to the posterior pancreatic duodenal vein.

Duodenal transection if PPPD permissible

In concordance with accepted oncologic principles, bulky neoplasms of the pancreatic head, tumors progressing to the first or second part of the duodenum, or clinically positive regional lymph nodes noted at this juncture preclude pylorus preservation. If PPPD is implementable, then the duodenum is transected 2-3 cm distal to the pylorus. This duodenal cuff must be made long enough to withstand later revision during creation of the duodenojejunal anastomosis.

The gastroepiploic artery and vein are divided, and the right gastric artery is once again identified and protected. The duodenum is divided 2-3 cm distal to the pylorus. The jejunum is transected at least 10 cm distal to the ligament of Treitz. The mesenteries of both transected small-bowel stumps are divided as well, and the duodenum and jejunum are reflected below the mesenteric vessels.

Division of pancreas

The pancreas is transected at the level of the PV, thus exposing the underlying SMV-PV confluence. If the tumor is adherent to the PV, SMV, or SMV-PV confluence, the pancreatic division plane may have to be revised more distally (ie, toward the tail) in order to accommodate vein reconstruction. The tumor is carefully separated from the named venous structures. If the first jejunal branch of the SMV gets injured here, the venous injury is difficult to control, and attempted repair of such an injury can damage the SMA.

The tumor is reflected rightward and separated from the right lateral border of the SMA; it is important to completely resect the uncinate process in order to achieve an R0 resection (ie, surgical margins negative for tumor). The SMA is then exposed by the retracted SMV-PV confluence, and it is dissected carefully to visualize the inferior pancreaticoduodenal artery. This must be ligated securely; failure to do so can cause retroperitoneal hemorrhage.

Removal and orientation of specimen

The specimen is removed en bloc and oriented for pathology. The retroperitoneal margin is inked for pathologic frozen section analysis. A grossly positive retroperitoneal margin represents a technical failure to achieve the intended R0 resection goal. A microscopically positive retroperitoneal margin can occur with 10-20% of pancreaticoduodenal resections for pancreatic head cancer.

Vascular reconstruction

Vascular reconstruction after PPPD is extensive and beyond the scope of this discussion. The reader is directed to the resources in the References section.

Pancreatic reconstruction

The pancreatic remnant is first mobilized along its length for a few centimeters. Then, the transected jejunum is brought through a defect in the transverse mesocolon adjacent to the middle colic vessels. A pancreaticojejunal anastomosis is created with the understanding that pancreatic fistula formation depends on the technical integrity of the anastomosis, as well as the quality of the pancreatic tissue.

A two-layer end-to-side pancreaticojejunostomy, also known as a duct-to-mucosa reconstruction, is performed. This indicates full-thickness pancreatic duct–to–jejunal wall closure.

First, the posterior outer row of interrupted seromuscular sutures is placed between the jejunal side wall and the pancreatic parenchyma. The jejunum is opened longitudinally anterior to this. The inner circumferential layer of interrupted full-thickness sutures reapproximates the cut end of the pancreatic duct with jejunal wall. The posterior sutures are tied inside the anastomosis, a pancreatic stent is placed, and the remaining sutures are tied on the outside. The anterior outer layer of sutures is placed as a row of interrupted seromuscular sutures.

Alternatively, invagination of the distal pancreatic stump into the jejunum can be performed in an end-to-end or end-to-side manner. The inner layer of sutures is placed as described above, and the outer layer of sutures is placed to invaginate the pancreatic remnant. This is useful when the pancreatic duct is not dilated and when the parenchyma is too soft to hold against jejunal seromuscular sutures.

Biliary reconstruction

Hepaticojejunostomy is performed as a one-layer end-to-side anastomosis between the CHD remnant and a site on the jejunum distal to the pancreaticojejunal anastomosis. It is critical to align the bile duct and the jejunum without tension before suture placement.

Enteric reconstruction

The jejunum is traced distal to the biliary reconstruction and brought to lie antecolically. The cuff of duodenum is revised, with preservation of at least 1.5 cm of postpyloric duodenum to maintain the blood supply to the anastomosis. An antecolic end-to-side anastomosis between the duodenum and the jejunum is created with a single layer of continuous suture. Some have found antecolic gastrointestinal (GI) reconstruction to be associated with a lower incidence of delayed gastric emptying (DGE; see Complications) than retrocolic reconstruction[10] ; however, others have not.[11, 12]

Closing maneuvers

A feeding jejunostomy is created distal to the duodenojejunal anastomosis by using a Witzel technique to maintain postoperative enteral feeding access. Then, the falciform ligament is located and used to cover the GDA stump so as to prevent GDA pseudoaneurysm formation in the event of pancreatic leak (see Complications). A vascularized flap of omentum has also been described for coverage of the GDA stump. As a rule, closed-suction transcutaneous drains are placed at the pancreatic anastomosis and biliary anastomosis, with additional drains per surgeon preference. The abdomen is closed in the standard fashion.

A study by Gupta et al suggested that negative-pressure wound therapy (NPWT) may help lower the incidence of surgical-site infection (SSI) after PPPD.[13]

Perioperative morbidity

The presence of DGE may necessitate prolonged nasogastric decompression or total parenteral nutrition (TPN) with enteral feeding access failure.[14, 15] Jejunal feedings should be given for as long as is necessary, with care taken to avoid aspiration.

Pancreatic leak (also called postoperative pancreatic fistula [POPF]) may occur and lead to pancreatic fluid collection, pancreatic fistula formation,[16] intra-abdominal abscess, or sepsis.

GDA complications that may develop include pseudoaneurysm resulting in postpancreatectomy hemorrhage (PPH), GDA-enteric fistula, and GDA stump blowout with massive hemorrhage (eg, bleeding from abdominal drains, massive GI bleeding). GDA stump blowout with massive hemorrhage is initiated by inflammation from pancreatic leak and rarely occurs before postoperative day 10. This condition is treated with selective angiography with stenting or embolization of the hepatic artery. Reoperation is performed only as a last resort.

Other perioperative problems include the following:

• Feeding jejunal tube management failures (luminal rotation, dislodgment, obstruction)
• Prolonged ileus
• Small-bowel obstruction
• Internal herniation of bowel
• Small-bowel volvulus
• Critical illness such as sepsis, respiratory failure, GI bleeding, renal failure, and multisystem organ failure
• Death (< 4%)

Long-term morbidity

The following are included in the possible long-term morbidity of PPPD:

• Recurrence of malignancy, such as local recurrence at the retroperitoneal margin or distant recurrence in the liver, peritoneum, or lungs
• Pancreatic insufficiency - Exocrine (~40%), endocrine (~20%)
• Pancreatic anastomotic stricture (recurrent pancreatitis, chronic pancreatic pain)
• Anastomotic failure (any)
• Anastomotic stricture (any)
• Small-bowel obstruction
• Internal herniation of bowel
• Small-bowel volvulus