A 58-year-old woman presents to your office complaining of generalized itching. On examination, she appears jaundiced. During your interview, you learn that she has experienced a 10-lb (4.5-kg) weight loss over the past several months and recently has noted the passage of tea-colored urine. Her past medical history is significant for type 2 diabetes mellitus that was diagnosed 5 months previously, and she denies any history of hepatitis. She smokes one pack of cigarettes a day but does not consume alcohol. Her temperature and the remainder of her vital signs are within normal limits. The abdomen is soft and nontender. The gallbladder is palpable but without tenderness. Her stool is Hemoccult negative. The laboratory evaluation reveals a normal complete blood count. Other laboratory findings are total bilirubin 12.5 mg/dL, direct bilirubin 10.8 mg/dL, aspartate aminotransferase (AST) 120 U/L, alanine aminotransferase (ALT) 109 U/L, alkaline phosphatase 348 mg/dL, and serum amylase 85 IU/L.
What is the most likely diagnosis?
How would you confirm the diagnosis?
ANSWERS TO CASE 35: Periampullary Tumor
Summary: A 58-year-old woman presents with painless obstructive jaundice, weight loss, and recent-onset diabetes mellitus.
• Most likely diagnosis: Obstructive jaundice caused by a periampullary tumor.
• Confirmation of diagnosis: Begin with ultrasonography to rule out biliary stones as the source of obstruction and assess the anatomic location of the biliary obstruction. Even though this patient’s clinical and laboratory findings are more compatible with chronic biliary obstruction from a periampullary tumor, calculus disease is far more common in the general population and should be ruled out first. A CT scan should be obtained subsequently to evaluate the periampullary region if indicated by ultrasonography findings.
ANALYSIS
Objectives
1. Be familiar with the diagnostic approach to suspected periampullary tumors.
2. Be familiar with the roles and outcomes of surgical and palliative therapies in the treatment of periampullary tumors.
Considerations
Mechanisms contributing to jaundice can be broadly categorized as disorders of bilirubin metabolism, liver disease, and biliary tract obstruction. This patient’s predominance of direct bilirubinemia suggests biliary obstruction as the cause. Her clinical presentation strongly suggests malignant extrahepatic biliary obstruction because she has painless jaundice with a palpable, nontender gallbladder (Courvoisier sign), weight loss, and recent-onset type 2 diabetes mellitus. Ultrasonography of the right upper quadrant is an inexpensive and noninvasive imaging modality that should be used initially in this patient’s evaluation. The study may reveal cholelithiasis, thus suggesting choledocholithiasis (common bile duct stone) as the cause of biliary obstruction. Ultrasonography may also help identify the anatomic location of the biliary obstruction (eg, the presence of dilated intrahepatic ducts and a nondilated distal common bile duct implies obstruction of the midportion of the common bile duct). If the ultrasound findings suggest obstruction not related to gallstone disease, a computed tomography (CT) scan would be useful to further differentiate between extrinsic compression and stricture and to stage the tumor. A periampullary tumor that invades the superior mesenteric artery (SMA) is considered unresectable; similarly, the presence of distant metastasis indicates disseminated disease and precludes the possibility of a surgical cure. When a CT scan cannot clearly visualize whether tumor involvement of the vascular structures is present, endoscopic ultrasonography can be useful for visualization of the interphase between the pancreas and the vascular structures. Involvement of the superior mesenteric vein (SMV) or portal vein by tumor was traditionally considered a sign of unresectability and a contraindication to pancreaticoduodenectomy (PD); however, this is considered by many as a relative contraindication to surgery because a number of centers have now achieved acceptable complication rates and long-term survival following PD with portal vein and/or SMV resection and reconstruction. It has been shown that patients have delayed disease recurrences when they are treated with surgery and adjuvant chemotherapy in comparison to those treated with surgery alone. It is unclear at this time whether patients receiving chemoradiation therapy prior to surgery (neoadjuvant therapy) have additional survival benefits compared to those receiving postoperative therapy. Despite the advances in treatment, the 5-year survival reported by most centers for patients after pancreaticoduodenectomy and adjuvant therapy for pancreatic adenocarcinoma remains only 10% to 25%.
APPROACH TO: Periampullary Tumors
DEFINITIONS
PERIAMPULLARY CANCERS: Commonly cancers of the pancreas, distal bile duct (cholangiocarcinoma), duodenum, and ampulla of Vater. Some of the less common periampullary tumors are mucinous cystic tumors of the pancreas and pancreatic lymphoma.
PANCREATICODUODENECTOMY: An operation involving resection of the duodenum, the head of the pancreas, the common bile duct, and sometimes the distal stomach. PD is indicated for the treatment of patients with tumors and benign disease localized in the area surrounding the ampulla of Vater. The classic form of the operation is called a Whipple resection. The operative mortality of PD has improved significantly over the past decade (approaching 0%-2%), but the complication rates are still quite high (20%-40%).
GEMCITABINE: A chemotherapy agent (a deoxycytidine analogue) that appears to prolong the survival of patients with pancreatic carcinoma and other periampullary carcinomas. Gemcitabine is an effective radiation sensitizer; therefore, it is sometimes given in conjunction with external beam radiation therapy. In addition to the oncologic benefits, gemcitabine appears to help relieve symptoms related to pancreatic cancers.
CLINICAL APPROACH
Carcinoma of the Pancreas
Pancreatic cancer is the most common periampullary cancer, but it carries the worst prognosis. Overall, carcinoma of the pancreas is an uncommon tumor, consisting of only 2% of newly diagnosed cancers in the United States. This cancer, however, is the fourth leading cause of cancer deaths in men and the fifth leading cause of cancer deaths in women; it is responsible for 5% of all cancer deaths. Tumor staging is performed according to the tumor-node-metastasis (TNM) classification (Table 35–1), which also predicts patient survival. Roughly 70% of the carcinomas are located in the head of the pancreas. Common clinical manifestations of carcinoma in the head of the pancreas include obstructive jaundice, weight loss, diabetes mellitus, abdominal pain, and gastric outlet obstruction. Patients with tumors located in the body and tail of the pancreas typically present only after tumor growth has caused obstruction or chronic pain from splanchnic nerve invasion. In terms of prognosis, a patient who has significant weight loss and chronic abdominal and/or back pain tends to have more advanced disease and a worse prognosis.
Table 35–1 • TNM STAGING OF ADENOCARCINOMA OF THE PANCREAS
Patient Treatment
Figure 35–1 illustrates the initial evaluation of a patient presenting with biliary obstruction. When CT imaging demonstrates a mass in the head of the pancreas without evidence of liver or intraperitoneal metastases, or a chest radiograph (CXR) reveals pulmonary metastases, some groups have advocated CT-guided biopsy to confirm the diagnosis and initiate induction of chemoradiation therapy. Other investigators believe that patients with potentially resectable cancers should proceed directly to laparoscopy, followed by open exploration and resection. Proponents of neoadjuvant therapy think that chemoradiation given preoperatively is better tolerated so that patients are more likely to complete the course of therapy. It is possible that the additional benefits of neoadjuvant therapy may be in selecting out those patients whose disease rapidly progresses or undergoes clinical deterioration during therapy and therefore would not benefit from surgical resection (only a third to a half of patients ultimately undergo resection). Issues regarding preoperative versus postoperative systemic therapy remain unresolved at this time.
Figure 35–1. Algorithm for the treatment of a patient with obstructive jaundice. CBDS, common bile duct stone; CT, computed tomography; CXR, chest radiograph; ERCP, endoscopic retrograde cholangiopancreatography.
The early outcomes following pancreaticoduodenectomy have improved over the past two decades where many centers are reporting very low in-hospital mortality following the procedure. The major difficulty in the management of patients with pancreatic cancers is that despite improvement in surgical outcomes, the 5-year mortality following resection of pancreatic carcinoma continues to range from 8% to 15%. Unfortunately, these figures would not likely improve until significant improvements in adjuvant systemic therapy can be implemented.
Palliative Therapy
The majority of patients with pancreatic carcinoma have unresectable disease at the time of diagnosis, and these patients have limited survival ranging from months to 1 to 2 years. Surgical, endoscopic, or percutaneous interventions are frequently indicated to relieve biliary obstruction, gastric outlet obstruction, and pain. For patients with locally advanced and/or metastatic disease, endoscopic placement of a biliary stent is often feasible to provide effective relief of biliary obstruction and improves the quality of life by relieving the itching and the metabolic and cosmetic effects of obstructive jaundice. When endoscopic approach is not feasible, percutaneous and/or operative approaches can be used to facilitate biliary drainage. Approximately 10% to 20% of the patients may develop gastric outlet obstruction and may benefit from the creation of an internal bypass (gastrojejunostomy). There is evidence to support the creation of prophylactic gastrojejunostomy for patients who are found to have unresectable disease during surgical exploration, because the morbidity associated with this procedure is low and the procedure may help maintain patients’ quality of life. The development of severe, persistent abdominal and back pain is frequently seen in patients with tumor infiltration of the splanchnic nerves. This is a difficult problem to resolve. Some surgeons have reported good results with the injection of alcohol into the celiac plexus during abdominal exploration, whereas others have achieved only limited success. Alternatively, percutaneous celiac injections have been used with less effective results for nonoperative patients.
COMPREHENSION QUESTIONS
35.1 A 42-year-old woman is evaluated and diagnosed with probable adenocarcinoma of the pancreas. Which of the following is most accurate regarding this condition?
A. A majority of patients have unresectable tumors at presentation.
B. Anemia is a common presenting symptom.
C. Patients with isolated liver metastasis can often be cured with surgical resection.
D. It is usually associated with a predominantly elevated indirect serum bilirubin level.
E. Smoking is not a risk factor for this disease.
35.2 Pancreaticoduodenectomy is indicated for which one of the following patients?
A. A 55-year-old man with a history of alcoholism who presents with jaundice and an isolated mass in the head of the pancreas. Biopsy of the mass has been nondiagnostic.
B. A 60-year-old man with cirrhosis and cancer of the head of the pancreas. A CT scan indicates the presence of ascites.
C. A 40-year-old man with carcinoma of the head of the pancreas with tumor invasion of the superior mesenteric vein and artery.
D. A 50-year-old man with Gardner syndrome and a 2-cm adenoma of the second portion of the duodenum.
E. A 38-year-old woman with an 8-cm pseudocyst involving the head of the pancreas.
35.3 A 33-year-old man has been diagnosed with widely metastatic pancreatic cancer. He has severe itching and hyperbilirubinemia. Which of the following is the best therapy?
A. Administration of cholestyramine
B. Radiation therapy directed to the head of the pancreas
C. Pancreaticoduodenectomy (Whipple procedure)
D. Operative decompression of the biliary tract
E. Placement of an endoscopic stent
35.4 A 45-year-old woman is noted to be diagnosed with pancreatic cancer, and the histology appears to be adenocarcinoma. Which of the following is most accurate regarding this type of malignancy?
A. Most of these cancers are located in the head of the pancreas.
B. Right upper quadrant pain, fever, and jaundice are commonly seen.
C. Most of these cancers are located in the tail of the pancreas.
D. Curative surgery is typically obtained when the malignancy is located in body of the pancreas.
E. This tumor is highly chemosensitive.
35.5 A 50-year-old man is noted to have painless jaundice that on CT scan reveals a periampullary tumor. Which of the following is the most common periampullary cancer?
A. Pancreatic adenocarcinoma
B. Cholangiocarcinoma
C. Ampullary carcinoma
D. Duodenal adenocarcinoma
E. Pancreatic lymphoma
ANSWERS
35.1 A. Weight loss and the presence of back pain are generally indicative of disseminated and locally advanced tumors, respectively. Unlike colon cancer, pancreatic cancer is not commonly associated with anemia. Resection is not indicated for any patient with metastatic disease. Smoking is associated with at least a twofold increase in pancreatic cancer risk.
35.2 A. Pancreaticoduodenectomy can be performed when reasonable attempts at tissue biopsy have not revealed cancer and the clinical suspicion of cancer is high. Benign adenomas may be treated with local resection. The presence of ascites is a contraindication to surgery, as the ascites likely indicate poor hepatic reserve or disseminated cancer. Invasion of the SMA by tumor is a contraindication to surgery, as the risks associated with arterial reconstruction have not been demonstrated to be acceptable. An adenoma of the duodenum is a benign lesion that may be amendable by local resection. A symptomatic pseudocyst in the head of the pancreas should be managed by internal drainage that is associated with less morbidity than pancreaticoduodenectomy.
35.3 E. A patient with widely metastatic disease will not benefit from a pancreaticoduodenectomy (Whipple procedure). The placement of an endoscopic biliary stent will bring relief with minimum morbidity and thus ameliorate the symptoms. Operative decompression is effective for biliary obstruction, but for this patient, an operative approach would not provide the patient with the most expeditious relief of symptoms.
35.4 A. Seventy percent of pancreatic cancers are located in the head of the pancreas. Some patients with tumor involvement of the SMV or portal vein are candidates for pancreaticoduodenectomy with en bloc resection of the venous structures, followed by venous reconstruction. Adjuvant chemotherapy following resection is associated with increased length of survival. Right upper quadrant pain, fever, and jaundice are associated with cholangitis, whereas painless jaundice is more likely to be associated with pancreatic cancer. Adenocarcinomas of the body or tail of the pancreas typically will have spread by the time of diagnosis. Unfortunately, currently available chemotherapeutic agents and targeted molecular therapies are not very effective for the treatment of this tumor.
35.5 A. Pancreatic adenocarcinoma is the most common of the periampullary tumors. These tumors can give rise to painless jaundice, which is a common sign of pancreatic cancer, specifically the head of the pancreas.
CLINICAL PEARLS
The classic presentation of malignant extrahepatic biliary obstruction is painless jaundice and a palpable nontender gallbladder.
Pancreatic cancers typically are not diagnosed until late and are usually unresectable.
In general, pancreaticoduodenectomy should be reserved for patients with localized malignancies near the ampulla of Vater.
REFERENCES
Fisher WE, Andersen DK, Bell RH, Saluja AK, Brunicardi FC. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:1167-1243.
Lavu H, Yeo CJ. Periampullary cancer. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 10th ed. Philadelphia, PA: Elsevier Mosby; 2011:422-429.
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;297:267-277.