Kaohsiung J Med Sci August 2010 • Vol 26 • No 8 448
Pancreatic cancer is one of the most lethal human can-cers and continues to be a major clinical problem, even in the 21stcentury [1]. It rarely develops in the first five decades of life [2,3]. Pancreatic cancer may initially present with dull epigastric pain radiating to the back, along with weight loss or jaundice; however, pan-creatitis is not included in the list of common clinical
manifestations. In this report, we describe a young man in whom relapsed acute pancreatitis was the initial feature of subsequently confirmed pancreatic cancer with multiple metastases. To our knowledge, this is the youngest case of pancreatic cancer with the uncom-mon initial feature of acute pancreatitis to be reported in the literature.
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ASEP
RESENTATIONA 31-year-old man without any remarkable family his-tory of systemic disease or malignancy and without any remarkable past medical history, except for smok-ing 0.5 packs per day and alcohol consumption (on Received: Nov 19, 2009 Accepted: Jan 28, 2010
Address correspondence and reprint requests to: Dr Zu-Yau Lin, Division of Hepato-Biliary-Pancreatic Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1stRoad, Kaohsiung 807, Taiwan.
E-mail: [email protected]
In this report, we describe a 31-year-old man in whom acute pancreatitis was the initial feature of a subsequently diagnosed pancreatic adenocarcinoma with multiple metastases. He initially pre-sented at our hospital with acute pancreatitis. Abdominal ultrasonography revealed a mildly dilated pancreatic duct and an enlarged pancreatic head. Although a follow-up abdominal ultrasonography revealed a progressively dilated pancreatic duct and a progressively enlarged pancreatic head, he refused further investigation and was lost to follow-up. Four months later, he returned to our hospital with relapsed acute pancreatitis. Obstructive jaundice was noted and drainage was performed. Because choledochoplasty with multiple balloon catheters was not fully effective, biliary tract bypass surgery was carried out. Intraoperative biopsy confirmed pancreatic adeno-carcinoma with multiple metastases. The patient died of massive gastrointestinal bleeding a few weeks later. To our knowledge, this is the youngest case of pancreatic cancer with the uncommon initial presentation of acute pancreatitis reported in the literature. For a patient with acute pan-creatitis, particularly recurrent episodes, but with no known risk factors for panpan-creatitis, a pancreatic neoplasm should be considered as a potential underlying cause, even in a young man.
Key Words:adenocarcinoma, pancreatic cancer, pancreatic neoplasms, pancreatitis (Kaohsiung J Med Sci 2010;26:448–55)
average, about 700 mL of beer, 3 times a week) for more than 10 years, presented at the emergency department of our hospital owing to intermittent abdominal pain in the left upper quadrant over 2 days. He reported having some sensation of acid regurgitation and hun-ger pain for several days, but he denied experiencing any nausea, vomiting or diarrhea. He was afebrile, with normal vital signs, a soft abdomen without any abdominal tenderness, and hyperactive bowel sounds. Because his clinical presentation and plain abdominal roentgenogram suggested stool impaction, he was discharged with the prescription of some laxatives.
He returned to the emergency department 2 days later with nausea and worsened abdominal pain in the left upper quadrant and epigastric area. His abdomen was still soft, but tender in the left upper quadrant. Acute pancreatitis was diagnosed based on elevated serum lipase level (970 IU/L; normal, 7–58 IU/L) and computed tomography (CT) findings (Figure 1A). He rejected admission owing to a rapid resolution of
abdominal pain soon after management performed in the emergency department.
Six days later, he returned to the emergency depart-ment because of severe abdominal pain with radiation to the back after consumption of about 350 mL of beer. His vital signs were normal and his abdomen was soft with normoactive bowel sound. Laboratory tests re-vealed a persistently elevated (although lower than that 6 days earlier) serum lipase level of 411 IU/L. He was admitted under the diagnosis of acute pancreatitis. Abdominal ultrasonography performed during hos-pitalization showed a mildly dilated pancreatic duct and an enlarged pancreatic head. He was discharged 11 days later after successful conservative treatment.
At a follow-up visit at our outpatient department 5 days later, he reported experiencing mild abdomi-nal pain after a heavy meal which subsided after a few days. His serum lipase level at that time was 423 IU/L. An elevated carbohydrate antigen 19-9 (CA19-9) level (82.8 U/mL; normal,< 37 U/mL) was also noted.
A B
C Figure 1.Contrast-enhanced axial abdominal computed
tomog-raphy revealed (A) a swollen pancreas with relatively poor enhancement, surrounded by inflammatory infiltration (arrows) initially. The pancreatic duct was mildly dilated. (B) Six months later, a progressively swollen head and uncinate process of the pancreas (*) with poor enhancement, surrounded by peripancre-atic inflammatory infiltration (arrows) and focal fluid collection was observed. Progressive dilatation of the pancreatic duct and emerging nodules (arrowhead) with soft tissue density in the peri-pancreatic region were also noted. (C) Seven months later, pro-gressive enlargement of the irregular hypodense mass lesion in the head and uncinate process of the pancreas (*) with poor enhance-ment, as previously noted, was observed and was later confirmed to be pancreatic cancer. Progressive dilatation of the pancreatic duct, increasing nodules (arrowheads) in the peripancreatic region and the mesenteric spaces, and emerging hypodense nodules in the liver (not shown) were also noted.
pancreatitis was diagnosed, based on the elevated serum lipase level and CT findings (Figure 1B). He was readmitted to our hospital for conservative treatment and was discharged 8 days later with good tolerance to a soft diet.
Five days later, he reported dull epigastric pain and diarrhea after a large meal. He also noticed that he was becoming icteric and passing dark urine, but without clay-colored stool. He did not have fever, chills or tenderness in the right upper quadrant of his abdomen. He was readmitted for further investigation and management. Laboratory examination showed elevated levels of total bilirubin (9.00 mg/dL; nor-mal, 0.2–1.0 mg/dL), direct bilirubin (5.42 mg/dL; normal, 0–0.2 mg/dL), serum aspartate aminotrans-ferase (347 U/L; normal, 10–35 U/L), serum alanine aminotransferase (668 U/L; normal, 10–40 U/L), serum alkaline phosphatase (321 U/L; normal, 32–92 U/L), serum γ-glutamyl transferase (171 U/L; normal, 7– 64 U/L), serum lipase (326 IU/L), and serum amylase (299 U/L; normal, 63–123 U/L). Abdominal ultraso-nography revealed dilatation of the common bile duct, common hepatic duct and gallbladder. Percutaneous transhepatic biliary drainage was performed to relieve his jaundice. Percutaneous transhepatic cholangiog-raphy revealed complete obstruction of the distal com-mon bile duct. External compression by pancreatitis or pancreatic cancer was considered.
Follow-up abdominal CT (Figure 1C) revealed fur-ther enlargement of the pancreatic head lesion with lymphadenopathy and a few hepatic nodules. Thus pancreatic cancer with liver metastases and lymph-adenopathy was suspected.
Choledochoplasty with multiple balloon cathe-ters was performed to dilate the distal common bile duct, but the follow-up cholangiography 1 week later showed narrowing of the previously dilated distal
carried out. Choledochojejunostomy, Roux-en-Y an-astomosis, gastrojejunostomy, and T-tube choledo-chostomy were performed. Pathological examination of the surgical specimens (Figure 2) confirmed pan-creatic adenocarcinoma with metastases to the liver and omentum. He was discharged 2 weeks after the operation.
Two days after discharge, he presented at the emergency department with hematemesis. Esopha-gogastroduodenoscopy showed suspected duodenal invasion of the pancreatic cancer with ulceration and hemorrhage. Endoscopic biopsy could not be perfor-med at that time owing to the possibility of inducing further bleeding. He was admitted for further manage-ment with blood transfusion, proton pump inhibitors and sucralfate. He was discharged 19 days later with no evidence of hemorrhage. However, 3 weeks later, the hematemesis recurred. Emergency esophagogas-troduodenoscopy failed to localize the source of bleed-ing due to the large amount of fresh blood that had accumulated in the prepyloric area and fundus. The patient died of massive bleeding the next day.
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ISCUSSIONPancreatic cancer is a devastating disease with poor prognosis, an overall 5-year survival rate of less than 1%, and a medium survival of approximately 5–6 months after tumor detection [4]. In Taiwan, it is the eighth leading cause of cancer-related deaths in men and the seventh in women [5]. It is now ranked fourth as the cause of death from cancer in the United States, Europe, and Japan, and is second only to colorectal cancer as a cause of digestive cancer-related death [2,6]. Many risk factors for pancreatic cancer have been identified, including old age, male sex, family history,
chronic pancreatitis, obesity, low physical activity, a “Western” dietary pattern (high intake of fat and/or meat, particularly smoked or processed meats), and cigarette smoking [1,3,6–9]. However, the only risk fac-tors to be consistently reported are age and cigarette smoking [1,8]. Smoking was the only risk factor noted in our case. The risk for developing pancreatic cancer increases with age, with a mean age of onset in the sev-enth and eighth decades of life [9]. Pancreatic cancer rarely develops before the age of 50, but the inci-dence rises sharply thereafter [2,3]. Our patient was only 31 years old. About 5–10% of patients have a family history of pancreatic cancer and seem to pres-ent earlier than sporadic cases [3]. Certain syndromes with a specific germline may increase the risk of pan-creatic cancer. For example, a recent study showed that
the risk of pancreatic cancer was increased in families with germline DNA mismatch repair gene mutation, as compared with the general population [10]. Although no malignancy was noted in the family members of our patient, it is possible that genetic factors may have played a role in the carcinogenesis of this case at this young age.
The initial presentations of pancreatic cancer vary according to tumor location [1–3]. Abdominal pain, weight loss, jaundice and the development of diabetes mellitus have been reported as the initial presenta-tions for pancreatic cancer [1–3]. Abdominal pain is often felt as a dull ache in the upper abdomen and may radiate to the back, and often improve on leaning for-ward [3]. Uncommonly, such pain may be severe and transient, along with associated hyperamylasemia,
A
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Figure 2.(A) Tissue specimens from the pancreas showed nests of cancer cells and neoplastic glands infiltrating in the fibrotic tissue (hematoxylin and eosin; original magnification, 20×). (B) Immunohistochemical stains revealed diffuse positive reactions for cytoker-atin 7 (original magnification, 20×) and carcinoembryonic antigen, but were negative for CK20. (C) Liver tissue specimens showed hepatic parenchyma with neoplastic glands (hematoxylin and eosin; original magnification, 20×), (D) which revealed diffuse positive reaction with cytokeratin 7 (original magnification, 20×) and CK20, but was negative for hepatocyte stain. Similar neoplastic glands were found in the tissue specimen from the omentum. The features were consistent with pancreatic adenocarcinoma with metastases to the liver and omentum.
episode of pancreatitis subsided might suggest super-imposed pancreatic cancer. Follow-up CT performed after resolution of acute pancreatitis would be useful to evaluate the possibility of superimposed cancer or to locate the suspected lesion for biopsy. Unfortunately, this patient did not accept our suggestion and was lost to follow-up. As in the first CT scan, the second and third CT scans were also performed during episodes of pancreatitis. The findings of these scans could still be explained by the process of pancreatitis but could be used to diagnose superimposed cancer.
Magnetic resonance imaging is becoming more widely used for acute pancreatitis. A recent study showed no differences in the ability to detect acute pancreatitis between diffusion-weighted imaging, an increasingly used sequence of magnetic resonance imaging, and CT imaging [13]. However, diffusion-weighted imaging can detect acute pancreatitis more clearly than CT without using enhancing material and can detect pancreatic cancer as a cause of acute pancreatitis [13]. Meanwhile, magnetic resonance cho-langiopancreatography can detect choledocholithiasis and pancreas divisum as a cause of acute pancreatitis and can offer an alternative to endoscopic retrograde cholangiopancreatography, at least for diagnosis [13,14]. Although CA19-9 is frequently elevated in patients with various benign pancreaticobiliary disorders, it is still useful for diagnosis of pancreatic cancer [2,15–18]. Since its first description in 1979, studies have sug-gested that a serum concentration> 37 U/mL repre-sents the most accurate cutoff value for discriminating pancreatic cancer from benign pancreatic disease, with a sensitivity of up to 90% and a specificity ap-proaching 98% [9,16–19]. In practice, a very high CA19-9 level (e.g. > 1,000 U/mL) along with a clinical presentation consistent with pancreatic cancer is essen-tially diagnostic for malignancy and is often associated
safe modality for confirming the pathologic diagnosis in patients with unresectable pancreatic cancer [20]. In clinical practice, however, a CT-guided biopsy of pancreatic tumor is more widely performed because air interference limits the utility of ultrasound-guided biopsy. Endoscopic ultrasound-guided fine-needle aspiration has recently emerged as a diagnostic adjunct for pancreatic lesions [21]. In a large, well-controlled study, endoscopic ultrasound-guided fine-needle aspi-ration with aspiaspi-ration cytology was an accurate test for detecting pancreatic adenocarcinoma [22]. Some experts have also advocated biliary biopsy via tran-shepatic tracts when performed during percutaneous biliary drainage [23]. In our patient, because bypass surgery was warranted for the extensively long seg-mental stenosis of the common bile duct, preoperative image-guided biopsy was not arranged. Furthermore, image-guided biopsy was difficult to perform in this patient because it was not easy to differentiate between tumor tissue and inflammatory tissue on images. Therefore, we arranged an intraoperative biopsy for our patient.
Immunohistochemistry is often useful to reach a diagnosis of a malignancy. Cytokeratin (CK) 7 and CK20 expression was present in 96% and 63% of cases of pancreatic adenocarcinoma, respectively [24]. CK20 is an excellent marker for metastatic pancreatic cancer [25] and overexpression of CK20 indicates a subtype of pancreatic adenocarcinoma with decreased overall survival [24,26]. Therefore, metastatic adenocarcinoma of the liver positive for both CK20 and CK7, as in our case, indicates that the primary tumor was localized in the pancreaticobiliary system [27].
In addition to traditional treatment with bypass surgery, biliary stricture may also be treated by stent-ing. Percutaneous metallic biliary stenting was shown to provide good palliation for malignant jaundice [28].
However, owing to a lack of data on long-term pa-tency, the use of metallic endobiliary stents for the treatment of benign biliary strictures remains contro-versial [29,30]. Some experts have even suggested that metallic endobiliary stents should not be used for benign strictures in patients with a predicted life expectancy > 2 years [29]. Furthermore, lesions such as strictures due to chronic pancreatitis are more dif-ficult to treat, and endoscopic therapy with gradual dilation and insertion of multiple plastic stents is re-served for patients who are not candidates for surgery [31]. In our case, no definitive evidence was available to determine whether the stricture of the common bile duct was caused by a benign disorder or by a malig-nancy. Therefore, placement of a biliary stent was not indicated owing to his young age and the diagnostic uncertainty.
Invasive pancreatic cancer as a cause of massive gastrointestinal hemorrhage is exceedingly rare [32– 35]. Mechanisms responsible for massive gastrointes-tinal hemorrhage caused by a pancreatic tumor may include gastric variceal hemorrhage secondary to sp-lenic vein occlusion [36–39], a fistula from the blood vessel to the duodenum (wirsungorrhage), direct tumor hemorrhage via the pancreatic duct (hemosuccus), or hemorrhage from the tumor invading into the gastro-intestinal tract [32–35]. In a review of 859 endoscopies in patients with upper gastrointestinal hemorrhage, only three patients had a pancreatic tumor invading the duodenum [40]. Furthermore, patients with mas-sive gastrointestinal hemorrhage from invamas-sive pan-creatic cancer usually present with hematochezia or tarry stool, rarely with hematemesis, as in our patient [32,34].
Despite the recent advances in early diagnosis and surgical treatment, the prognosis of patients with pan-creatic cancer has not improved substantially. Surgical resection is the only potentially curative treatment. Unfortunately, due to the late presentation of the dis-ease and the early dissemination of tumor cells, only 15–20% of patients are candidates for pancreatectomy, and the prognosis of pancreatic cancer is even dis-couraging in those with potentially resectable disease [2]. To date, the 5-year survival rate for adenocarci-noma of the pancreas is less than 5%, and most patients die within the first 2 years [9]. Therefore, further stud-ies are needed to identify high risk individuals, to develop strategies for early detection, and to optimize treatments.
In conclusion, we report a young man with ad-vanced pancreatic cancer and multiple metastases who initially presented with relapsing acute pancreatitis, an uncommon initial presentation for pancreatic cancer. Although young cases of pancreatic cancer have been reported before [41,42], to our knowledge, this is the youngest case of pancreatic cancer presenting ini-tially with relapsing acute pancreatitis. For a patient with acute pancreatitis, particularly one who has re-current bouts and who has no known risk factors for relapsing pancreatitis, a pancreatic neoplasm should be considered as a potential underlying cause, even in a young man.
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CKNOWLEDGMENTWe thank Dr Joanna Ying-Jiin Chen for her assistance in editing this article.
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收文日期： 98 年 11 月 19 日 接受刊載： 99 年 1 月 28 日 通訊作者：林子堯醫師 高雄醫學大學附設醫院內科部肝膽胰內科 高雄市 807 自由一路 100 號
