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Whipple Procedure for Carcinoma of the Pancreas - Part 2

Martin Goodman MD
Tufts University Medical Center

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the ninth most common cancer in the United States, but due to symptoms – such as back pain, jaundice and unexplained weight loss – usually only presenting when the disease has already moved beyond the pancreas, it is highly lethal, representing the fourth most common cause of cancer death.  As a result of widespread abdominal imaging, more early stage pancreatic cancers are being diagnosed, and these patients are candidates for a pancreaticoduodenectomy, more commonly known as the Whipple procedure.  The Whipple procedure is used to treat four types of cancer – periampullary, cholangiocarcinoma, duodenal, and pancreatic ductal adenocarcinoma – but is most well known in the setting of PDAC.  Although there are only a few basics steps to the procedure – removal of  the pancreatic head, distal bile duct, duodenum and either distal gastrectomy or plyloric preservation.  Next is the reconstruction with bringing up the stapled end of jejunum to the pancrease, then the hepatic duct, and lastly to the stomach.   The multiple crucial anatomic structures in the same region, as well as the unforgiving nature of the structures involved in the operation itself, lead to high morbidity and necessitate complex postoperative care.  Due to this, most Whipple procedures are performed at higher volume centers.

Clinical Presentation

Focused history
Most patients with PDAC present with painless jaundice followed by weight loss.  Midepigastic abdominal pain which radiates to the back between the shoulder blades is a late symptom usually representing nerve involvement.  Other symptoms include new onset diabetes, steatorrhea, nausea with or without vomiting due to the tumor causing a partial blockage, and pruritus which is a result of deposition of bile salts in the skin with jaundice.
Physical Findings
The physical examination is in most cases unremarkable, aside from jaundice and scleral and conjunctival icterus.  Physical signs in more extensive disease can include a palpable gallbladder – known as Courvoisier's sign – which is the result of distention due to obstruction of the bile duct from cancer.  Also seen is a palpable left supraclavicular lymph node, the eponym of which is Virchow’s node, as well as Sister Mary Joseph’s node, which is an enlarged periumbilical node.
Imaging/Staging
Once the patient presents with symptoms concerning for a pancreatic head mass, a pancreatic protocol CT scan is usually performed.  This includes noncontrast, arterial, and portal venous phases with 3 mm cuts through the pancreas.  This will help determine the extent of disease including metastatic as well as lymph node involvement.  It is also helpful to determine if the superior mesenteric vessels are involved.  Magnetic resonance imaging (MRI) is also just as useful.  In addition, an endoscopic retrograde cholangiopancreatography (ERCP) is often performed with brushings of the bile duct and possible stent placement.  Endoscopic ultrasound is also performed to evaluate the size of the mass, as well as lymphatic and mesenteric vessel involvement.  A needle biopsy can also be performed at this time if needed.  If there is any concern for metastatic disease a positron emission tomography (PET) scan is also considered.
Natural History
The natural history of pancreatic ductal adenocarcinoma is one of both local extension and metastatic spread.  Due to the aggressive nature of the disease, as well as the typical delay in diagnosis until advanced disease is present, less than five percent of patients live longer than five years after diagnosis.
Treatment Options
Treatment is dependent on where the tumor is in the pancreas as well as the extent of disease, including local/regional involvement.  For tumors in the tail of the pancreas distal pancreatectomy with or without splenectomy can be performed, in either open or laparoscopic fashion.  Unfortunately the majority of patients with tumors of the tail of the pancreas present late, due to the lack of symptoms, and are therefore not resectable.  In these cases palliative treatments are indicated which include pain management and chemotherapy. Tumors of the head of the pancreas are treated slightly differently.  The only option for cure is resection, which involves pancreaticoduodenectomy.  This option is only available for 20% of patients at presentation.  The majority of patients with pancreatic head tumors have locally advanced disease with mesenteric vessel involvement or metastatic disease including peritoneal or liver involvement, with the latter being the most common. For locally advanced tumors, also known as borderline tumors, systemic chemotherapy with gemcitabine or a combination of 5-FU, leucovorin, oxaliplatin, and irinitecan (FOLFIRINOX) are used first to shrink the tumor to make it resectable.  In 50% of cases, there is enough reduction in tumor burden that resection is possible. For patients with metastatic disease, systemic chemotherapy and palliative treatments are the only options.  These are used to decrease symptoms as well as hopefully prolong the patient's life; however, they are not curable. Surgery, with removal of the tumor and reconstruction of the biliary drainage system when necessary, is the mainstay of treatment in resectable disease, and still offers the only chance at cure. In masses that involve the tail of the pancreas, a distal pancreatectomy, possibly through a laparascopic approach, is an option, though these cancers tend to present later, due to absence of symptoms until very advanced disease, and the vast majority of patients with cancers in the tail of the pancreas have unresectable disease. In tumors involving the head of the pancreas, pancreatoduodenectomy is considered the standard procedure, and no other therapy offers the same chance at cure.
Treatment Rationale
Pancreaticoduodenectomy was elected for this patient due to the localized nature of the disease on CT scan – the mass was found incidentally, with no associated signs or symptoms.  In addition, the patient was overall in good health and appeared robust enough to tolerate the rigors of the procedure, which has been associated with a 30-50% complication rate and a mortality of 2 – 4%.
Special considerations
Drains are placed at the discretion of the surgeon, but are not obligatory.  In addition, the surgeon may elect to place a gastrostomy tube or jejunostomy tube to aid in enteral feedings postoperatively.

Discussion

Pancreatic ductal adenocarcinoma is a fearsome disease, one where the vast majority of patients will die from the disease or associated complications, most commonly within five years of diagnosis.  It has been particularly recalcitrant to new forms of treatment such as chemotherapy, and despite other cancers showing real advances in survival, pancreatic cancer continues to cause the demise of sufferers in large numbers.  In addition, the Whipple procedure used to treat PDAC is also associated with significant morbidity in its own right, with post-operative complication rates approaching fifty percent in tertiary care centers1.  Even in those patients who are candidates for surgery, the survival rate is poor, with around twenty percent of patients living five years. In an attempt to improve survival, treatment strategies complementary to the Whipple procedure have been explored. Adjuvant chemotherapy, where chemotherapy is given after the patient has recovered from surgery,  has shown a significant survival advantage for patients with PDAC over observation, and is generally recommended for all those who can undergo the treatment2-4. Radiation therapy, once a mainstay, is now more controversial, with at least one large randomized study suggesting a survival disadvantage for those undergoing radiation therapy2, leading European centers to abandon it completely as a treatment option. Neoadjuvant chemotherapy, where chemotherapy is given before the operation, is also gaining in popularity, specifically in patients where the cancer has involved the great vessels of the abdomen5.  However, it is recommended that this latter course be taken only within the context of a multi-specialty team approach and an ongoing clinical trial. In cases where the cancer is deemed unresectable – which constitute the majority of patients with PDAC – diversion procedures to alleviate symptoms such as biliary or gastric obstruction, and even celiac plexus nerve block for uncontrollable pain are available.  These former procedures can include the previously mentioned ERCP, as well as percutaneous biliary drains.  Overall, pancreatic cancer remains a stubborn foe to those who treat cancer.

Citations

  1. Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg. 2006 Nov;10(9):1199-210; discussion 1210-1.
  2. Neoptolemos JP, Stocken DD et al.  A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.  N Engl J Med. 2004 Mar 18;350(12):1200-10.
  3. Kalser MH, Ellenberg SS. Pancreatic cancer.  Adjuvant combined radiationand chemotherapy following curative resection. Arch Surg. 1985 Aug;120(8):899-903.
  4. Oettle H, Post S, Neuhaus P, et al. Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer: A Randomized Controlled Trial. JAMA. 2007;297(3):267-277.
  5. 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 Jul;16(7):1751-6.

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