Surgery for Pancreatic and Periampullary Cancer: Principles and Practice

© Springer Nature Singapore Pte Ltd. 2018

Mallika Tewari (ed.)Surgery for Pancreatic and Periampullary Cancerhttps://doi.org/10.1007/978-981-10-7464-6_1

1. Surgical Anatomy of the Pancreas and the Periampullary Region

Keishi Sugimachi¹, ²  , Yuki Bekki², Tomohiro Iguchi¹, Masaru Morita¹, Yasushi Toh¹ and Kenji Takenaka²

(1)

Department of Hepatobiliary-Pancreatic Surgery, National Kyushu Cancer Center, Fukuoka, Japan

(2)

Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan

Keishi Sugimachi

Email: [email protected]

Keywords

Surgical anatomyPancreasAnomalyArtery

Abbreviations

AIPDV

Anterior inferior pancreaticoduodenal vein

ASPDA

Anterior superior pancreaticoduodenal artery

ASPDV

Anterior superior pancreaticoduodenal vein

GDA

Gastroduodenal artery

IPDA

Inferior pancreaticoduodenal artery

PIPDA

Posterior inferior pancreaticoduodenal artery

PLphI

Pancreatic head plexus I

PLphII

Pancreatic head plexus II

PSPDA

Posterior superior pancreaticoduodenal artery

PSPDV

Posterior superior pancreaticoduodenal vein

SMA

Superior mesenteric artery

SMA

Superior mesenteric vein

1.1 General Anatomy of the Pancreas

The pancreas is a composite organ derived from dorsal and ventral buds that arise from either side of the distal foregut endoderm in embryonic development [1]. The pancreas lies transversely in the retroperitoneal sac with rotation of the duodenum. The duodenum is located on the right, the spleen on the left, and the stomach and the omental bursa above. The anterior surface of the pancreatic body and tail is overlapped by the peritoneum of the omental bursa.

The pancreas spreads in the mesoduodenum and is fixed to the retroperitoneum with various fused fasciae (Fig. 1.1) [2]. The anterior wall of the pancreatic head is covered by the mesoduodenum. The posterior wall of the mesoduodenum forms retropancreatic fusion fascia called the Treitz fascia with the posterior parietal peritoneum. The Treitz fusion fascia becomes the left Toldt fusion fascia at the body and tail of the pancreas, and the superior mesenteric artery (SMA) penetrates the fascia (Figs. 1.1 and 1.2). At the anterior surface of the pancreatic head, the transverse and ascending mesocolon forms fusion fascia with the mesoduodenum. This is continuous to the right Toldt fusion fascia, which is formed by the ascending mesocolon and parietal peritoneum. Posteriorly, the pancreatic bed in the retroperitoneal space contains the hilum of the right kidney, the inferior vena cava, the aorta, the left kidney, and the hilum of the spleen, from right to left (Fig. 1.2). Pancreaticoduodenal arteries and veins are present between pancreatic parenchyma and fused fasciae. Therefore, these fasciae have to be dissected for pancreatectomy.

Fig. 1.1

Fused fasciae related to the pancreas. (a) The pancreatic head is covered by the mesoduodenum. The mesoduodenum and retroperitoneum form the Treitz fusion fascia. (b) The mesocolon (transverse colon) forms fusion fascia with the mesoduodenum. (c) The mesocolon (ascending colon) and parietal peritoneum form the right Toldt fusion fascia. (d) The left Toldt fusion fascia is formed by the retroperitoneum and peritoneum of the bursa omentalis. Modified from Perlemuter L et al: Cashiers d’Anatomie. Abdomen (I), 3rd ed, Masson & Cie, Paris, 1975

Fig. 1.2

The retroperitoneal fusion fascia of the pancreas. The pancreas and the duodenum rotate and attach to the retroperitoneum forming fusion fascia, and the superior mesenteric artery penetrates the fascia. Left renal vein locates between aorta and fusion fascia (light blue). Modified from Skandalakis, JE et al: The Pancreas, vol 1, Blackwell Science, London, 1998

1.2 Arteries

The celiac trunk and SMA provide the arterial supply to the pancreas. Variations are common, but for the most part, the body and tail are supplied by branches of the splenic artery. However, the pancreatic head and uncinate process receive arterial supply through arcades originating from the gastroduodenal artery (GDA) and the first branch of the SMA (Fig. 1.3).

Fig. 1.3

Arterial supply of the pancreas. The pancreas has a rich arterial supply that is derived from the celiac trunk and superior mesenteric artery. The superior and inferior pancreaticoduodenal arteries form arcades and supply the pancreatic head. The dorsal pancreatic artery descends posterior to the pancreas and supplies the pancreatic body and tail. Modified from Netter FH: Atlas of Human Anatomy, 3rd ed. Icon Learning Systems, New Jersey, 2004

The GDA, the branch of the common hepatic artery, ramifies the posterior superior pancreaticoduodenal artery (PSPDA) at the superior edge of the pancreas and becomes the anterior superior pancreaticoduodenal artery (ASPDA). The ASPDA runs along the anterior surface of the pancreas and branches to the right gastroepiploic artery at the site of the pyloric ring. The PSPDA runs above the common bile duct from left to right and travels down the posterior surface of the pancreas. The PSPDA supplies the papilla of Vater and finally forms an arcade with the posterior inferior pancreaticoduodenal artery (PIPDA). The arcade of the PSPDA and PIPDA forms a spiral formation around the lower common bile duct in an anti-clockwise manner (Fig. 1.3) [3].

The right and left hepatic arteries usually arise from the celiac trunk and common hepatic artery. However, there are common variations where the right hepatic artery or common hepatic artery originates from the SMA (Fig. 1.4). A replaced left hepatic artery originates from the left gastric artery. A replaced right hepatic artery arising from the SMA is commonly observed, but a replaced common hepatic artery is relatively rare. This replaced right hepatic artery is the artery that needs to be preserved during pancreaticoduodenectomy to preserve hepatic arterial flow. However, this artery usually runs behind the pancreatic head and is thus easily invaded by adenocarcinoma of the pancreas. Avoiding injury of the right hepatic artery when the extrahepatic bile duct is divided is also important. The right hepatic artery usually runs transversely from left to right behind the bile duct, in front of the portal vein. A replaced right hepatic artery ascends behind the portal vein and bile duct and can be identified by pulsation behind the portal vein. A replaced left hepatic artery from the left gastric artery lies in the upper portion of the lesser omentum and thus may be injured during mobilization of the stomach.

Fig. 1.4

Variants of the hepatic artery. A replaced hepatic artery is a vessel that does not originate from the proper hepatic artery and provides sole supply to the liver. A replaced right hepatic artery originating from the superior mesenteric artery or a replaced left hepatic artery from the left gastric artery is commonly observed. A replaced common hepatic artery is relatively rare. (a) no replaced hepatic artery, (b) replaced right hepatic artery, (c) replaced left hepatic artery, (d) replaced right and left hepatic arteries, (e) replaced common hepatic artery. Modified from Gray’s Anatomy. 4th ed. Standring S. ed, Churchill Livingston, Elsevier, 2008

The inferior pancreaticoduodenal artery (IPDA) branches from the posterior side of the SMA and forms a common trunk with the first branch of the jejunal artery. The IPDA then branches into the anterior IPDA and posterior IPDA (Fig. 1.5) [4]. In pancreaticoduodenectomy, pancreaticoduodenal branches from the SMA must be identified and divided to resect the pancreas and duodenum. The common branch of the IPDA and the first branch of the jejunal artery usually arise from the SMA. However, in some cases, the IPDA and the first branch of the jejunal artery independently arise from the SMA (Fig. 1.5). In addition to the main IPDA, the pancreatic head and duodenum are usually supplied from minor branches from the proximal SMA. The IPDA possibly arises from a replaced hepatic artery, which is a branch of the SMA (Figs. 1.4 and 1.5). Identifying and preserving a replaced hepatic artery are important, while the IPDA has to be sacrificed during surgery. Dissecting the IPDA at the first stage of pancreaticoduodenectomy prevents congestion of the pancreatic head and duodenum and thus may result in less blood loss during surgery [5].

Fig. 1.5

Variation of the inferior pancreaticoduodenal artery. Typically, the inferior pancreaticoduodenal artery (IPDA) and the first branch of the jejunal artery form a common trunk. In minor variations, the IPDA directly arises from the superior mesenteric artery, or the anterior and inferior IPDAs independently arise from the SMA and the first branch of the jejunal artery. (a) common trunk of IPDA and J1A arises from SMA (major variation), (b) IPDA directly arised from SMA, (c) PIPDA and AIPDA independently arise from SMA

When the pancreatic parenchyma at the pancreatic neck above the superior mesenteric vein (SMV) is divided, two arteries at the cranial and caudal sides of the pancreas are usually seen. The dorsal pancreatic artery arises from the splenic artery, the celiac trunk, or the common hepatic artery. The dorsal pancreatic artery then travels down the posterior surface of the pancreas and forms an arcade with the branch from the GDA (suprapancreatic branch). The inferior pancreatic artery branches from the ASPDA and runs transversely and forms an arcade with the dorsal pancreatic artery or the great pancreatic artery (peripancreatic arcade).

1.3 Portal Vein

Venous drainage from the pancreas goes to the splenic vein, SMV, and portal vein. The posterior superior pancreaticoduodenal vein (PSPDV) runs along the PSPDA at the posterior surface of the pancreatic head and drains into the portal vein. The anterior superior pancreaticoduodenal vein (ASPDV) collects venous drainage from the anterior surface of the pancreas and the duodenum. The superior right colic vein, the right gastroepiploic vein, and the ASPDV form the common venous trunk called the gastrocolic trunk of Henle, which drains into the SMV (Fig. 1.6).

Fig. 1.6

Venous drainage system of the pancreas. The venous system of the pancreas primarily travels into the portal vein. The head drains into the superior and inferior pancreaticoduodenal veins. The body and tail drain via small veins that run directly into the splenic vein. Modified from Netter FH: Atlas of Human Anatomy, 3rd ed. Icon Learning Systems, New Jersey, 2004

Pancreatic adenocarcinoma often invades the portal vein and its branches, thus requiring combined resection and reconstruction of the portal vein or SMV. In the NCCN Guidelines, contact with the most proximal draining jejunal branch into the SMV is classified as unresectable pancreatic adenocarcinoma [6]. Usually the first jejunal branch of the SMV branches from the posterior surface of the SMV, merges with the anterior inferior pancreaticoduodenal vein (AIPDV), and runs transversely from right to left behind the SMA. There is a minor variation where the first jejunal branch of the SMV arises from the surface of the left side of the SMV and runs from right to left in front of the SMA (Fig. 1.7). The inferior mesenteric vein drains into the splenic vein, SMV, or the confluence of the splenic vein and SMV (Fig. 1.8).

Fig. 1.7

Venous drainage of the pancreatic head and variations of the inferior pancreaticoduodenal vein. The first branch of the jejunal vein runs behind the superior mesenteric artery (SMA), anastomoses the posterior inferior pancreaticoduodenal vein (PIPDV), and drains into the posterior surface of the superior mesenteric vein (SMV). In a minor variation, the first branch of the jejunal vein runs in front of the SMA and drains into the left surface of the SMV, and the PIPDV solely drains into the SMV. (a) jejunal vein runs behind SMA, (b) jejunal vein runs in front of SMA (minor variation)

Fig. 1.8

Variation of the merging confluence of the inferior mesenteric vein. (a) The inferior mesenteric vein drains into the splenic vein, the superior mesenteric vein, or (b) the confluence of the splenic vein and (c) the superior mesenteric vein. Modified from Kimura W. Surgical anatomy of the pancreas for limited resection. J Hepatobiliary Pancreat Surg, 2000

The draining veins of the pancreatic body and tail go to the splenic vein or to the SMV. The left gastric vein drains into the splenic vein or the portal vein. The anatomy of the portal vein and its branches for portal vein resection and reconstruction should be evaluated preoperatively. The inferior mesenteric vein and left gastric vein might be drainage vessels of the remnant pancreas and the spleen when portal vein resection without splenic vein reconstruction is planned.

1.4 Pancreatic Ducts

The main pancreatic duct, the duct of Wirsung, arises in the tail of the pancreas and runs through the pancreatic parenchyma. The duct of Wirsung terminates at the papilla of Vater in the duodenum with the common bile duct in Oddi’s sphincter muscle (Fig. 1.9). The minor or accessory pancreatic duct, the duct of Santorini, is smaller than the main duct. The duct of Santorini extends from the main duct to enter the duodenum at the lesser papilla. This papilla usually lies approximately 1–2 cm proximal and slightly anterior to the major papilla. The duct of Wirsung belongs to the ventral pancreas, and the duct of Santorini does the dorsal pancreas in development. The accessory pancreatic duct drains the uncinate process and inferior part of the head of the pancreas. Several variations are encountered because of the developmental origin of the two pancreatic ducts. The accessory pancreatic duct usually communicates with the main duct and both ducts open into the duodenum. There is another variation where the end of the accessory duct is closed and not open to the duodenum. In some cases, the main pancreatic duct is smaller than the accessory pancreatic duct, and the two are not connected. In those cases, the accessory duct carries most of the pancreatic juice (pancreatic divisum) (Fig. 1.9).

Fig. 1.9

Variations of the pancreatic ducts. (a) The ducts of Wirsung and Santorini open into the duodenum. (b) The duct of Santorini ends blindly in the duodenal wall. (c) The duct of Wirsung is smaller than the duct of Santorini and these ducts are not connected. The duct of Santorini carries the entire secretion (pancreatic divisum). Modified from Skandalakis LJ et al. Surgical embryology and anatomy of the pancreas. Surg Clin North Am, 1993

1.5 Duodenal Papilla

The duodenal papilla (the papilla of Vater) lies at the end of the intramural portion of the common bile duct. There is a complex of sphincter musculature that is composed of circular or spiral smooth muscle fibers surrounding the intramural portion of the common bile and pancreatic ducts (Fig. 1.10). A duodenal diverticulum lying close to the papilla may be present, and the papilla has been found in a diverticulum. The pancreatic duct and the common bile duct usually merge in the duodenal wall, and this is covered by the sphincter of ampulla and opens in the duodenal papilla (Fig. 1.10). There is a variation where the pancreatic and common bile ducts open into the duodenum at separate points. In some cases, the main pancreatic duct and the common bile duct merge outside of the duodenal wall, and the conjunct duct is covered by sphincter musculature (pancreaticobiliary maljunction) (Fig. 1.10). In these cases, pancreatobiliary juice reflux possibly causes biliary inflammation and malignancy [7].

Fig. 1.10

Diagram of the relations of the pancreatic and common bile ducts. (a) In normal anatomy, the ampulla is the common pancreaticobiliary channel below the junction of the ducts within the papilla. The pancreatic duct opens into the common bile duct at a variable distance from the orifice of the major duodenal papilla. (b) The pancreatic duct anastomoses the common bile duct outside of the duodenal wall, and thus there is a long conjunct duct. In this case, pancreatic juice refluxes into the bile duct (pancreaticobiliary maljunction). (c) The pancreatic and common bile ducts open separately on the major duodenal papilla

1.6 Nerves

The pancreas is innervated by the sympathetic (the greater and lesser splanchnic nerves) and the parasympathetic (vagus nerve) nervous systems. These nerve fibers collect and form the celiac ganglia. Nerve fibers from the right and left celiac ganglia merge at the root of the celiac trunk and SMA and form the celiac plexus. The plexus originates from the celiac-superior mesenteric plexus and directly reaches the pancreatic head or uncinate process. There are no identical nerve plexuses at the pancreatic body and tail. According to the General Rules for the Study of Pancreatic Cancer by the Japan Pancreas Society, the plexus behind the pancreatic head can be differentiated into two parts (Fig. 1.11). The region that mainly includes nerve tissue that is distributed to the dorsal surface of pancreatic head and the cranial edge of the uncinate process from the right of the celiac ganglia is named the pancreatic head plexus I (PLphI). The wide plexus that is distributed to the uncinate process from the superior mesenteric ganglia is called the pancreatic head plexus II (PLphII) (Fig. 1.11). The PLphII includes the IPDA and is continuous to the plexus of the mesojejunum. There is usually no clear septum or space between the PLphI and PLphII. Para-SMA lymph nodes are present at the ventral and dorsal sides of the plexus. In pancreaticoduodenectomy, the pancreatic head and SMA have to be removed by dissecting these pancreatic plexuses.

Fig. 1.11

The plexus of the pancreatic head. The pancreatic head plexus I extends to the dorsal surface of the pancreatic head and the cranial edge of the uncinate process from the right of the celiac ganglia. The pancreatic head plexus II is a wide plexus that extends to the uncinate process from the superior mesenteric ganglia. (a) a schematic diagram of pancreatic plexsus from cross section, (b) plexsus of pancreatic head and arteries. Modified from Japan Pancreas Society: The General Rules for the Study of Pancreatic Cancer. 6th ed. Kanehara, Tokyo, Japan 2013

Areolar tissue surrounding the PLphII is considered to be anatomically consistent with the mesopancreas [8]. However, the concept and nomenclature of the mesopancreas is unclear and controversial. Some authors consider that the mesopancreas cannot be called a true mesentery because it does not have a fascial envelope attaching the pancreas to the posterior wall of the abdomen. Additionally, the mesopancreas does not contain all of its blood vessels and all its primary draining lymphatics and lymph nodes of the pancreas [9]. The mesopancreas or PLphII consists of not only nerve fibers but fibrous tissue, fat, lymphatics, and minor vessels.

Acknowledgment

The authors thank Mr. Shinya Fukamachi for medical illustrations.

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© Springer Nature Singapore Pte Ltd. 2018

Mallika Tewari (ed.)Surgery for Pancreatic and Periampullary Cancerhttps://doi.org/10.1007/978-981-10-7464-6_2

2. Overview of Resections for Pancreatic and Periampullary Cancer

June S. Peng¹ and Gareth Morris-Stiff¹  

(1)

Department of Hepato-Pancreato-Biliary Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Gareth Morris-Stiff

Email: [email protected]

Keywords

PancreatectomyWhipplePancreatoduodenectomyPancreatic cancerPeriampullary cancerHistory of surgery

2.1 Early Pancreatic Surgery

Surgery of the pancreas was made feasible in the 1800s with the rise of anesthesia and acceptance of antisepsis. The earliest reports involved management of pancreatic cysts through drainage and marsupialization [1].

The first intentional resections of the pancreas involved the pancreatic tail, as it was perceived to be less complex due to simpler anatomy, fewer adjacent vascular structures, and lack of need for complex reconstruction. Friedrich Trendelenburg [FIG] is widely credited with performing the first distal pancreatectomy and splenectomy in 1882 (Bonn, Germany) for a large retroperitoneal mass which pathology revealed to be a spindle cell sarcoma. The patient suffered from a wound infection and malnutrition and expired a few weeks after surgery. Early experience with distal pancreatic resection was sparse, with 24 surgeries performed by 21 surgeons between 1882 and 1905, with a mortality rate of 53% [2–4].

2.2 Pancreatic Head Resections

Despite the perceived challenges of proximal pancreatic resections, the first pancreatic head and partial duodenal resection was performed by Alessandro Codivilla [FIG] in February 1898 (Imola, Italy), published after the fact by his successor Bartolo dal Monte [5]. Codivilla at that stage of his career was interested in abdominal operations and had experience performing gastric surgeries, although he would later shift to orthopedic surgery. The patient was explored for epigastric distension and vomiting and found to have a tumor involving the distal stomach and pancreatic head. The operation necessitated resection of the distal stomach, portion of the duodenum, pancreatic head, and distal common bile duct (CBD). Reconstruction was performed with a Roux-en-Y gastrojejunostomy and cholecystojejunostomy [FIG]. The pancreatic stump was likely closed [5, Codvilla]. Pathology revealed a pancreatic cancer, and postoperatively, the patient appeared to develop a pancreatic fistula that drained via the incision. Unfortunately, the patient developed steatorrhea, hyperglycemia, and malnutrition and expired approximately 3 weeks after the operation. Although the extent of this operation was not anatomic by today’s standards and was not reported to the surgical community at the time, it remains an important landmark in the history of pancreatic surgery.

In the same year in the United States, William Halsted [FIG] performed the first transduodenal ampullary resection in 1898 (Baltimore, Maryland) for presumed choledocholithiasis but found to be a periampullary cancer intraoperatively [6, 7]. This cancer was excised locally with reimplantation of the pancreatic duct and CBD into the duodenum. The patient required re-exploration for recurrent jaundice. Halsted was unable to pass a probe from the CBD to the duodenum and performed a cholecystoduodenostomy. The patient expired several months later with recurrent jaundice and autopsy confirmed recurrent cancer.

Early experience of periampullary excision also yielded poor outcomes with an operative mortality ranging from 30 to 70% of the 109 cases reported through 1941 [1, 8]. The management of the pancreatic duct, and usage of additional biliary drainage, was variable in this series. Overall mortality of transduodenal periampullary excisions was 29.0%, with marked improvements over time, from 43.3% prior to 1925 to 14.9% subsequent to 1925. The cumulative series also included 15 patients who underwent resection of the duodenum and pancreatic head, with a mortality of 26.6%.

The management of the pancreatic remnant provided a perplexing problem in the early era of pancreatic resections. A handful of reports described traumatic disruption and resections, where the pancreatic capsule was approximated but almost all were complicated by leaks which were anticipated and drained prophylactically [1]. Laboratory work in human cadavers by Abel Desjardins in 1907 (Paris, France) [1] and canine model by Robert Coffey in 1909 (Portland, Oregon) [9] would inform later work in live humans. Coffey noted that the pancreas remains technically almost a stranger to the surgeon and performed pancreatoduodenectomy (PD) in a dog model which included partial pancreatic resection with reconstruction using a two-layer invaginating pancreaticojejunostomy (PJ), choledochoduodenostomy, and loop gastrojejunostomy (GJ) [FIG].

A number of surgeons subsequently made forays into pancreatic resections. Oskar Ehrhardt in 1907 (Konigsberg, Prussia) performed a gastrojejunostomy for a patient with gastric outlet obstruction related to a pancreatic tumor [1]. When the patient developed recurrent obstruction, Ehrhardt performed a distal gastrectomy, duodenectomy of the second portion, and partial pancreatic head resection without re-approximation of the capsule. The patient had a pancreatic leak and died 5 months later of recurrent cancer.

The first successful PD was performed in two stages by Walther Kausch in 1909 (Berlin, Germany). The preference for a two-stage operation was due to the need for biliary-enteric bypass to resolve jaundice, malnutrition, and impaired coagulation in patients with long-standing jaundice, which resulted in malnutrition and coagulopathy. The first stage included a loop cholecystojejunostomy with a Braun anastomosis [FIG], and the second stage was performed 2 months later, with resection of the distal stomach, proximal duodenum, distal CBD, and portion of the pancreatic head [1, 3]. Kausch performed the reconstruction with a pancreaticoduodenostomy in two layers, closure of the CBD and a retrocolic loop gastrojejunostomy [FIG]. Pathology revealed a pancreatic adenocarcinoma. The patient developed a leak postoperatively which resolved spontaneously but subsequently died of cholangitis 9 months later.

The first successful one-stage non-anatomic PD was performed by Georg Hirschel [FIG] in 1912 (Heidelberg, Germany) for an ampullary carcinoma. The resection included portions of the duodenum, head of the pancreas, and distal CBD [6]. Reconstruction was performed with a pancreaticoduodenostomy, posterior GJ, and drainage of the CBD into the lower duodenum by means of a rubber tube [6, 10]. The patient died 1 year later of unclear reasons.

Ottorino Tenani in 1922 (Florence, Italy) performed a two-stage operation, similar to Whipple’s initial case over a decade later. The first stage included a posterior GJ and ligation of the distal CBD, and a choledochoduodenostomy was performed. A month later, the duodenum and head of the pancreas were resected, and the stump of the pancreatic head was implanted into the lower end of the transected duodenum [10]. The performance of a choledochoduodenostomy by Tenani was the first, as well as the utilization of perioperative blood transfusion and postoperative enzyme replacement [11]. In total, seven partial PDs were performed by early surgeons in the era prior to Allen Whipple, with an operative mortality of 43% [1].

Allen Whipple performed his first PD in 1934 (New York City, New York). He is well known as the namesake of both the Whipple operation and Whipple’s triad. He continued the work of his predecessors and was critical in transitioning the operation from the hands of the rare few into the mainstream. His work came at a critical historical time and was enabled by the experience and errors of others before him, as well as medical advances including vitamin K and blood storage and transfusions [10]. Whipple recognized the challenges of pancreatic surgery, the destructive nature of pancreatic enzymes, and the disease process itself which rendered patients jaundiced, malnourished, and prone to coagulopathy [12]. He summarized a total of 65 cases reported previously, which included 60 one-stage operations for periampullary lesions with a 38% mortality rate and 5 two-stage operations with a 16.6% mortality rate. The operative principles outlined by Whipple included a two-stage operation in order to optimize the patient. The first stage was a bypass procedure with a posterior loop gastroenterostomy, CBD ligation, and an anterior cholecystogastrostomy [FIG]. The second stage was performed 3–4 weeks later with vascular ligation of the GDA and pancreaticoduodenal arteries, resection of the second and third portions of the duodenum, partial pancreatic head resection, ligation of the ducts of Wirsung and Santorini with closure of the pancreatic capsule, and drain placement [FIG]. Whipple’s first pancreaticoduodenostomy patient unfortunately died 30 hours after the second stage of operation. In a latter reflection, Whipple attributed the death to duodenal leak with a diffusing peritonitis presumably due to leak from the pancreaticoduodenal anastomosis [10, 13]. The three patients presented in the original 1935 series set the basis for resections of the periampullary region. Whipple highlighted the need for en bloc resection of the tumor with a margin, the benefits of a two-stage operation in order to resolve jaundice and improve nutrition, and he made a case for occlusion of the pancreatic duct, noting that the two surviving patient had relatively normal fat absorption and weight gain. His technique evolved from there, including the use of silk suture and omission of a pancreatico-enteric anastomosis for several years. Over the following years, he made several adjustments and changes based on the complications experienced. He avoided performing cholecystogastrostomy due to ascending cholangitis in his second and third patients and used a Roux-en-Y cholecystojejunostomy instead [14].

The first one-stage operation performed by Whipple was in March 1940 [10, 15]. The patient underwent exploration for a diagnosis of distal gastric carcinoma, but after transection of the mid-stomach, the mass was noted to be in the head of the pancreas. Whipple proceeded with pancreatoduodenectomy given the patient did not have jaundice and thus was not coagulopathic. Reconstruction was performed with an end-to-side GJ and end-to-end choledochojejunostomy in a loop fashion and closure of the pancreatic stump [14, 15]. The pathology revealed a nonfunctioning islet cell tumor. The patient was diagnosed with liver metastases 4 years later and survived 9 years after the initial operation. Subsequently, Whipple’s preference was to perform a distal gastrectomy and complete duodenectomy with resection of the head of the pancreas. Reconstruction was performed by pulling up the jejunum through the mesocolic defect, with an end-to-end choledochojejunostomy, a two-layered PJ, and an end-to-side GJ [FIG from 1946 paper].

After initially abandoning a PJ anastomosis, Whipple noted that a large number of patients developed fistulae following pancreatic stump closure [10]. In 1942, he again constructed a PJ using a duct-to-mucosa inner layer and an outer layer for invagination. By 1945, he advocated a one-stage surgery, pancreaticojejunostomy rather than occlusion, with the use of an internal stent, and choledochojejunostomy rather than cholecystogastrostomy [6, 13].

In later reflections of his work, Whipple attributes progress in pancreatic surgery to vitamin K, blood transfusion, and other shock prevention therapy and the use of silk technique [13]. Although his case series was relatively small with an operative mortality rate of 33% that well exceeds modern standards [11], he paved the way for those to follow. Perhaps his most important contribution was that he aroused a wave of optimism among surgeons which led to an aggressive application of this operation to overcome the wave of pessimism of such proportion that it appeared for a while that the operation … would abandoned entirely [16].

Shortly after Whipple’s first one-stage PD, Ridgeway Trimble in 1940 performed a one-stage PD (Baltimore, Maryland). His rationale for one rather than two stages was that all the work is done in a clean operative field as opposed to a field masked and obscured by trauma of a preliminary operation and because it was possible to avoid injury to these structures and to effect the delicate restorative anastomoses with proper vitamin therapy and … transfusion at the very beginning of the operation [17]. The patient underwent operative exploration for jaundice and abdominal pain and found to have an ampullary mass. An en bloc resection was performed on the pylorus, duodenum, and head of pancreas. The pancreatic stump was closed. A choledochojejunostomy was created 20 cm distal to the GJ. The patient recovered well postoperatively except for one episode of hemorrhage managed with a blood transfusion and had no long-term nutritional deficiencies related to the ligation of the pancreatic duct.

The one-stage PD became increasingly common as experience increased, with variations that brought the operation closer to the modern iteration. Verne Hunt in 1940 (Los Angeles, California) performed a one-stage PD for a patient with painless jaundice due to an ampullary cancer [8]. Hunt resected 3 in. of the second and third portions of the duodenum, distal CBD, and head of the pancreas. The pancreatic duct was ligated, and the cut parenchymal edge was closed with an omental patch. Reconstruction was performed with a posterior GJ, cholecystogastrostomy, and a T-tube was placed in the CBD. The patient developed a pancreatic fistula and bilious fluid that drained via the incision, both resolved with packing and wound care. She subsequently recovered well and was alive without recurrence at 1 year.

Hunt subsequently performed in 1941 another resection for ampullary carcinoma, this time including a total duodenectomy with resection of a portion of the pancreatic head. Reconstruction was performed by pulling the jejunum up through the mesocolic defect, and in addition he performed a pancreaticojejunostomy and choledochojejunostomy and a distal DJ [FIG].

Warren Cole and John Reynolds reported a series of five PDs in 1944 (Chicago, Illinois) [18]. Three were performed in one stage, and two were performed in two stages. The authors stressed starting the operation with an evaluation for metastatic disease, followed by kocherization of the duodenum and evaluation of venous involvement. They proceed with ligation of the gastroduodenal artery (GDA) and inferior pancreaticoduodenal artery. Four cases were performed with antrectomy, while one was pylorus preserving. In their variation, the distal duodenum or jejunum was oversewn and left in situ, a distal loop of the jejunum was brought into the right upper quadrant for reconstruction of the choledochojejunostomy most proximally, and an end-to-side GJ distal to that, with the pancreatic stump being closed. Reconstruction for the five cases varied, with three undergoing a loop GJ distal to the biliary anastomosis and two using Roux-en-Y configuration. Similar to Hunt and Child, they intentionally created the GJ distal to the biliary anastomosis, with the intention of avoiding cholangitis. Two patients developed persistent pancreatic fistulae, and there was one postoperative death. The authors also summarized the reconstructions utilized by other authors around the same time [FIG].

Many of the early PDs were non-anatomic due to concerns that the duodenum itself and pancreatic secretions were essential for life [14]. The first anatomic PD was performed in two stages by Alexander Brunschwig in 1937 (Chicago, Illinois) [19]. The first operation was a posterior loop GJ, a cholecystojejunostomy distal to the GJ, and a Braun jejunojejunostomy. The second stage was performed a few weeks later with resection of the entire duodenum and pancreatic transection at the neck over the superior mesenteric vein (SMV), with ligation of the pancreatic stump. The CBD was ligated, and no further reconstruction was required as the patient had undergone enteric and biliary bypass during the first operation. Pathology revealed pancreatic cancer. The patient developed an enteric leak, which was controlled with a drain placed into the prior drain site. The patient spent almost 3 months in the hospital and developed recurrent jaundice before he expired. Autopsy revealed carcinomatosis and ascites and confirmed a distal duodenal stump leak.

In 1944 Charles Child (New York City, New York) reported a series that included six PDs [20]. He described an end-to-end invaginating pancreaticojejunostomy, which was performed in the latter four cases, with only one pancreatic fistula. Child also advocated for reconstruction which placed the GJ distal to the biliary anastomosis.

As the anatomic definition of a PD became accepted, the evolution of pylorus-preserving PD warrants mention. Although multiple early surgeons attempted to preserve the duodenum, Whipple had advocated for a distal gastrectomy in his latter publications. It is likely that this practice stemmed from his initial one-stage PD in which he had already transected the stomach. The first modern, anatomic pylorus-preserving PD was performed in 1944 by Kenneth Watson (Surrey, United Kingdom) for ampullary cancer [21]. The operation was performed in two stages as the patient had long-standing jaundice. First, a cholecystojejunostomy was performed using a loop, followed a month later by resection. The duodenum was divided 1 inch distal to the pylorus, with reconstruction of a Roux limb to the hepaticojejunostomy (HJ) and duodenojejunostomy (DJ) and closure of the pancreatic stump. Watson intentionally avoided partial gastrectomy in order to ensure maximal gastric digestion of protein and carbohydrate and to prevent the formation of an anastomotic ulcer. However, the patient had difficulty with enteral intake and required jejunostomy tube placement, as well as operative drainage of an abscess, and was hospitalized over 3 months.

Over three decades later in 1978, William Traverso and William Longmire renewed interest in pylorus-preserving pancreatoduodenectomy (PPPD) [22], especially when performing the operation for benign disease. They cited a goal to decrease the rate of marginal ulceration and improve nutrition and reported two cases of pylorus preservation with transection 4 cm distal to the pylorus. This variation was first attempted in 1977 but intraoperatively converted to a classic PD due to ischemia. Their first successful PPPD underwent the operation for an obstructing pseudocyst in the setting of acute or chronic alcoholic pancreatitis and the second patient for a duodenal cancer. Both patients gained weight after discharge, and neither reported steatorrhea although both took pancreatic enzymes. In their follow-up of 18 patients who underwent PPPD, no marginal ulcer or postgastrectomy syndrome was noted, and the operation is widely used today [23].

It is worth emphasizing that