Case Report #1

A 54-year-old woman with a history of a cholecystectomy, presented to her primary care physician for ten days of diffuse abdominal pain, especially in the epigastric region. The pain was intermittent, frequently associated with food, and radiated to her back. She occasionally felt relief with an antacid. Associated symptoms included anorexia, malaise, nausea and bloating. The patient denied any association with drinking alcohol. She denied any weight loss, fever/chills, emesis, shortness of breath, chest pain, change in bowel habits, or urinary symptoms. She denied having similar symptoms in the past, any association with position, history of acid reflux, or regurgitation of sour material.

Past medical/surgical history was significant for a cholecystectomy and a cerebral aneurysm repair twelve years prior. She has smoked half a pack of cigarettes per day for ten years, and drinks 3-4 glasses of wine per week. She has been taking Maalox occasionally for the past ten days; otherwise she takes no other medications. There is no known family history of gastrointestinal disorders.

In the clinic, her vital signs were: blood pressure 112/72, pulse 88, respiratory rate 18, and temperature 97.0° F. The patient was mildly overweight, and in no apparent distress. Skin was not jaundiced and sclerae were anicteric. Lungs were clear to auscultation bilaterally. Heart exam revealed a regular rate and rhythm, with no murmurs appreciated. Abdomen was soft, non-distended, with normoactive bowel sounds. There was mild epigastric and right upper quadrant tenderness present on deep palpation, without rebound tenderness or guarding. Extremities had no edema. Neurologically, she had no focal deficits.

In the clinic, leading differential diagnoses included dyspepsia, gastroesophageal reflux disease (GERD), or peptic ulcer disease because the patient had post-prandial epigastric pain associated with bloating, which was occasionally relieved with an antacid. The patient was instructed to avoid alcohol, smoking and aggravating foods. She was placed on a therapeutic trial with the proton pump inhibitor esomeprazole. She was told that if she had no relief with the medication and lifestyle modifications, a gastrointestinal workup with imaging studies would then be undertaken.

Pancreatitis was also included among the differential diagnoses because the patient had epigastric pain that radiated to the back. A complete blood count and serum amylase were ordered.

Biliary pathology was also considered because the patient had right upper quadrant tenderness on physical examination. A complete metabolic profile was ordered.

Four days after being seen in the clinic, the patient called the clinic to report that she was not improved with esomeprazole. Laboratory values from her visit had returned and were significant for:

WBC count	7,800/mm³
Hemoglobin	14.7 gm/dL
Hematocrit	43.0%
Albumin	4.2 gm/dL
Total bilirubin	2.8 mg/dL (H)
Alkaline phosphatase	306 IU/L (H)
AST	754 IU/L (H)
ALT	1402 IU/L (H)
Amylase	147 IU/L (H)

*Note: (H) indicates high.

The patient was then sent to the emergency room, where she stated that in addition to the symptoms reported in clinic, she had also recently noted that her eyes were becoming yellow, skin was pruritic, stools were lighter in color, and urine was darker.

Vital signs on admission were blood pressure 98/52, pulse 68, respiratory rate 16, and temperature 98.4° F. In general, she was anxious and jaundiced, with scleral icterus. The abdomen was soft, non-distended, with normoactive bowel sounds. She had epigastric tenderness without rebound tenderness or guarding. The liver edge was palpable 2-3 cm below the right costal margin. Rectal examination was reported to be mildly heme positive. Admission laboratory values were as follows:

WBC count	8,200/mm³
Hemoglobin	14.4 gm/dL
Hematocrit	42.1%
Prothrombin time	10.1 seconds
INR	0.9
PTT	26.5 seconds
Albumin	4.1 gm/dL
Total bilirubin	7.4 mg/dL (H)
Direct bilirubin	5.0 mg/dL (H)
Indirect bilirubin	2.4 mg/dL
Alkaline phosphatase	400 IU/L (H)
AST	298 IU/L (H)
ALT	727 IU/L (H)
Amylase	126 IU/L
Lipase	258 IU/L (H)
Hepatitis panel	negative

Radiographic findings were significant for a CT scan of the abdomen and pelvis done on admission (Figure 1). The abdominal CT scan showed a 2.5 x 2 cm hypodense pancreatic head mass most likely representing carcinoma, with secondary intrahepatic bile duct (1 cm), common bile duct (1.5 cm), and pancreatic ductal (3.7 mm) dilatation. No stones or calcifications were seen. No surrounding inflammatory changes or lymphadenopathy was reported. There were multiple liver hypodensities present, possibly representing cysts or metastatic lesions. The pelvis CT scan showed sigmoid diverticulosis.

The patient was admitted for obstructive jaundice supported by the increased total and direct bilirubin, and increased alkaline phosphatase, as well as the common bile duct dilatation seen on CT scan. This extrahepatic biliary obstruction may have been secondary to compression of the common bile duct by the mass at the head of the pancreas or by a biliary stricture.

The mass at the head of the pancreas could have represented a malignancy, a pseudocyst or an abscess. An abscess was less likely as the patient appeared non-toxic, was afebrile, and had a normal white blood cell count.

The liver hypodensities could represent metastases from a primary pancreatic malignancy, cysts or hemangiomas.

The patient was placed on bowel rest, started on intravenous fluids, administered pain medications as needed, and started on antibiotics to cover for any intraabdominal infection. The gastroenterology service performed an Endoscopic Retrograde Cholangiopancreatography (ERCP) which showed a common bile duct stricture that was biopsied and brushed/needled for cytology. The common bile duct was dilated proximal to the stricture (Figure 2). The stricture was treated with dilatation and stent placement (Figure 3). The pancreatic duct was diffusely irregular at the head of the pancreas. No stones were seen.

Figure 2 – ERCP showing distal common bile duct stricture with proximal dilation.

After placement of the stent, the patient’s bilirubin, alkaline phosphatase and AST/ALT all followed downward trends. The patient’s abdominal discomfort also improved. Brushings of the common bile duct showed markedly atypical cells, suspicious for adenocarcinoma, therefore making the diagnosis of pancreatic carcinoma likely. Fine needle aspiration (FNA) showed rare atypical appearing glandular cells.

The patient was discharged from the hospital, to return as an outpatient for her liver biopsy. Liver biopsy results were negative for malignant cells. Upon follow-up of the case, the patient was to be seen by a surgical specialist in the field of pancreatic tumors for further management. It was recommended that she undergo a laparoscopy to exclude any intraabdominal metastases prior to having a laparotomy. If metastases were to be found, then a laparotomy would not be performed.

The incidence of pancreatic cancer in the United States has increased significantly as the median life expectancy of the American population has lengthened. The disease is more common in men than in women, and it rarely develops before the age of 50. Cancer of the pancreas is the fourth leading cause of cancer-related deaths in the United States and is second only to colorectal cancer as a cause of gastrointestinal cancer-related death. The tumor results in the death of more than 98 percent of afflicted patients.¹ Ductal adenocarcinoma of the pancreas accounts for 90 percent of pancreatic cancers.² This cancer is deadly and is an increasing public health problem. It has the lowest five-year survival rate of any cancer. The dismal survival rate of patients with pancreatic cancer is caused by late diagnosis and low resection rates.

Early diagnosis of cancer has been hindered because populations at risk for developing pancreatic cancer have not been identified until recently. Although there is debate about the risk of pancreatic cancer in patients with chronic pancreatitis, the strongest evidence for this association is in hereditary pancreatitis. Onset of diabetes mellitus may herald the appearance of pancreatic cancer, particularly if the diabetes occurs during or beyond the sixth decade of life. Diabetes mellitus is present in 60 to 81 percent of patients with pancreatic cancer.^3,4 There is increasing evidence that some pancreatic cancer is inherited. In familial adenomatous polyposis (FAP) syndrome and familial atypical multiple mole melanoma (FAMMM) there is an increased risk for pancreatic cancer.⁵ Ideally, all patients at risk for pancreatic cancer should be investigated and followed up closely for development of pancreatic cancer. However, it is unknown when screening should begin and whether any of the current methods can detect early pancreatic cancer. It seems prudent to initiate screening 10 years before the age at which pancreatic cancer has been first diagnosed in familial pancreatic cancer and in FAP and FAMMM, and at age 35 in hereditary pancreatitis. Spiral CT and endoscopic ultrasonography (EUS) have the best sensitivity for detection of pancreatic cancer and are imaging tests that could be considered for screening. Many environmental factors that are associated with increased risk for pancreatic cancer may be related to exposure to aromatic amines. Cigarette smoking is a significant risk factor, with the disease being two to three times more common in heavy smokers than in nonsmokers.¹ There is also an association between meats and fish consumption and the risk of pancreatic cancer. Conversely, ingestion of fruits and vegetables may confer protection against the development of pancreatic cancer. Obesity is a risk factor, directly related to increased calorie intake. Alcohol abuse and cholelithiasis are not risk factors for pancreatic cancer.

A diagnosis of pancreatic cancer is often suspected on the basis of history; there are few confirmatory physical findings. With the exception of jaundice, the initial symptoms associated with pancreatic cancer are often insidious and are usually present for more than 2 months before the cancer is diagnosed. Contrary to the popular belief that “painless jaundice” is pathopneumonic for pancreatic carcinoma, most patients with pancreatic cancer actually do experience pain, as in the case presented above. Pain is present in 80 to 85 percent of patients with locally advanced or advanced disease.² The pain is usually felt in the upper abdomen as a dull ache that radiates to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it may be associated with anorexia, early satiety, diarrhea or steatorrhea. Jaundice due to biliary obstruction is found in more than 80% of patients having tumors in the pancreatic head and is typically accompanied by dark urine, acholic stools and pruritis.¹ Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion. The initial presentation also tends to vary with the location of the tumor. Tumors in the body or tail of the pancreas usually present with pain and weight loss as the primary symptoms, while tumors in the head of the gland typically present with steatorrhea, weight loss and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau’s syndrome), or previous attacks of pancreatitis are sometimes noted. An abdominal mass or ascites is occasionally noted at presentation in patients with pancreatic cancer. A nontender but palpable gallbladder may be seen or felt in those with jaundice (Courvoisier’s sign). The presence of an enlarged gallbladder in a jaundiced patient without biliary colic should suggest malignant obstruction of the extrahepatic biliary tree.

Despite the availability of serologic tests for tumor-associated antigens, such as the carcinoembryonic antigen (CEA) and CA 19-9, and noninvasive imaging techniques, such as CT and ultrasonagraphy, the early diagnosis of a potentially resectable pancreatic cancer remains extremely difficult. Routine laboratory tests may reveal a rise in the serum bilirubin concentration and alkaline phosphatase activity, and the presence of a mild anemia. The serum concentration of many tumor markers may be increased in pancreatic cancer, but they all lack sensitivity and tumor specificity. CA 19-9 has been found to have the greatest sensitivity (70 percent) and specificity (87 percent) for the diagnosis of pancreatic cancer.⁶

Currently, conventional or single-phase spiral CT is the initial test being used to diagnose pancreatic tumors. CT is an appropriate initial imaging test because it detects tumor in the pancreas and can be used to stage for resectability and to detect liver metastases. The sensitivity of conventional CT for the diagnosis of tumors more than 3 cm is 53 percent,⁷ but the sensitivity of dual-phase spiral CT for resectable tumors is higher - 85 to 95 percent.^8,9,10 Therefore, it is likely that dual-phase spiral CT will be found to be the best test to diagnose and stage pancreatic tumors and become the standard.

EUS is best used to search for small resectable tumors not seen by CT (less than 2-3 cm in diameter). EUS can also be used to evaluate the possibility of nodal and major vascular involvement by pancreatic tumors, thereby assessing potential resectability. EUS also may be used to obtain a tissue diagnosis at the time of examination, particularly in patients with inconclusive CT results.

ERCP is most useful for patients in whom CT does not reveal a mass lesion within the pancreas, and those in whom the differential diagnosis includes chronic pancreatitis and choledocholithiasis. ERCP has a sensitivity and specificity of 90 to 95 percent for diagnosing pancreatic cancer.² Findings suggestive of a malignant tumor include superimposable strictures or obstruction of the common bile and pancreatic ducts (the “double duct” sign), a pancreatic duct stricture in excess of 1 cm in length, and the absence of changes suggestive of chronic pancreatitis.

Laparoscopy is indicated if there is a high likelihood of unresectability that has not been confirmed by imaging tests. Examples include CT evidence of liver or other metastases not proven by fine-needle aspiration, as in the case presented above, pancreatic body or tail cancers, and ascites. Laparoscopy allows for viewing of the liver and peritoneal surfaces and for biopsy of any suspicious areas before laparotomy. If a metastatic tumor is found, laparotomy is not done unless gastric and biliary bypasses are required for palliation.

Surgical resection is the only potentially curative treatment for pancreatic cancer. According to the 1995 National Cancer Data Base Report on Pancreatic Cancer,¹¹ of the 17,490 patients with pancreatic cancer surveyed, 52 percent had stage IV disease at diagnosis, and the overall curative resection rate (pancreatectomy) was only 14 percent. Overall, survival was longer in patients who underwent tumor resection than in those who did not. The median survival for patients whose pancreatic cancers are surgically unresectable is 6 months.¹ The five-year survival rate following pancreaticoduodenectomy (Whipple resection) is only about 25 to 30 percent for node-negative, and 10 percent for node-positive tumors.² More recent data suggests that outcomes may be improving over time. In a multivariate analysis, one of the strongest predictors for survival was the use of adjuvant fluorouracil-based chemoradiotherapy after surgical resection; the three-year survival rate was significantly higher among those who received it compared to those who did not.²

If resection of the primary tumor is not possible (e.g. locally advanced, metastatic disease), management is directed at palliation of symptoms. Patients having pancreatic head tumors should be considered for surgical diversion of the biliary system. To relieve obstruction of the duodenum by tumor, a surgical or laparoscopic gastric bypass procedure is recommended. If jaundice has developed, therapeutic options include either nonoperative biliary decompression by endoscopic or percutaneous, transhepatic biliary drainage or surgical biliary bypass. Chemotherapy with fluorouracil and external beam radiation has increased survival time for these patients. Gemcitabine produces improvement in the quality of life for patients with advanced pancreatic cancer. However, duration of survival is only moderately improved. Newer forms of treatment are currently being evaluated with hopes of improving survival.

1. Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL. Pancreatic Cancer. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL. Harrsion’s Principles of Internal Medicine. 15^th Edition. McGraw Hill, 2001: 591-593

2. Steer ML. Clinical manifestations, diagnosis, and surgical staging of exocrine pancreatic cancer. Up To Date. 2004.

3. Permert, J, Larsson, J, Westermark, GT, et al. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med 1994; 330:313.

4. Schwarts, SS, Zeidler, A, Moossa, AR, et al. A prospective study of glucose tolerance, insulin, C-peptide, and glucagon responses in patients with pancreatic carcinoma. Am J Dig Dis 1978; 23:1107.

5. Lynch, HT, Fusaro, RM. Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome. Pancreas 1991; 6:127.

6. Pleskow, DK, Berger, HJ, Gyves, J, et al. Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer. Ann Intern Med 1989; 110:704.

7. Muller, MF, Meyenberger, C, Bertschinger, P, et al. Pancreatic tumors: Evaluation with endoscopic US, CT and MR imaging. Radiology 1994; 190:745.

8. Bluemke, DA, Cameron, JL, Hruban, RH, et al. Potentially resectable pancreatic adenocarcinoma: Spiral CT assessment with surgical and pathologic correlation. Radiology 1995; 197:381.

9. Legman, P, Vignaus, O, Dousser, B, et al. Pancreatic tumors: Comparison of dual-phase helical CT and endoscopic sonography. Am J Radiol 1998; 170:1315.

10. Lu, DS, Reber, HA, Krasny, RM, et al. Local staging of pancreatic cancer: Criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT. AJR Am J Roentgenol 1997; 168:1439.

11. Niederhuber, JE, Brennan, MF, Menck, HR. The National Cancer Data Base report on pancreatic cancer. Cancer 1995; 76:1671.

12. DiMagno, EP, Reber, HA, Tempero, MA. AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. Gastroenterology 1999; 117:1464.

13. AGA guideline: Epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. Up To Date. 2004

Case Report - A 54-year-old Woman with Post-prandial Epigastric Pain

Case Report -
A 54-year-old Woman with Post-prandial Epigastric Pain