Cancer, Pancreas


Article Author:
Yana Puckett


Article Editor:
Karen Garfield


Editors In Chief:
Scott Klenzak
Barry Liskow
Brian Farah


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/11/2019 10:48:57 PM

Introduction

Pancreatic cancer refers to the carcinoma arising from the pancreatic duct cells, pancreatic ductal carcinoma. It is the fourth leading cause of cancer deaths in the United States. The 5-year survival rate in the United States ranges from 5% to 15%. The overall survival rate is only 6%. Surgical resection is the only current option for a cure, but only 20% of pancreatic cancer is surgically resectable at the time of diagnosis.[1][2][3][4]

Close cooperation among various specialties including surgeons, oncologists, radiation oncologists, pathologists, and radiologists is extremely important for the chance of survival in patients with resectable disease and borderline resectable disease.

Etiology

Pancreatic Cancer Risk Factors

  • Smoking (20% of pancreatic cancers are caused by smoking)
  • Age older than 55 years old
  • Diabetes
  • Obesity
  • Chronic pancreatitis
  • Cirrhosis of the liver
  • Helicobacter pylori infection
  • Work exposure to chemicals in the dry cleaning and metalworking industry
  • Males more than females
  • African Americans more than whites
  • Family history

Ten percent have a genetic cause such as genetic mutations or association with syndromes such as Lynch syndrome, Peutz-Jeghers syndrome, VonHipaul Lindau syndrome, MEN1 (multiple endocrine neoplasia type 1).

Possible risk factors include heavy alcohol consumption, coffee consumption, physical inactivity, high red meat consumption, and two or more soft drinks per day.

Epidemiology

Based on the GLOBOCAN 2012 estimates, pancreatic cancer kills more than 331,000 people per year and ranks as the seventh principal cause of cancer death in both genders. The estimated global, 5-year survival rate for pancreatic cancer is about 5%.

Incidence rates for pancreatic cancer for both genders were highest in Northern America, Western Europe, Europe, and Australia/New Zealand. The lowest incidence rates are in Middle Africa and South-Central Asia.

There are some gender differences globally. In men, the greatest risk of developing pancreatic cancer is in Armenia, Czech Republic, Slovakia, Hungary, Japan, and Lithuania. The lowest risk for men is in Pakistan and Guinea.  In women, the highest incidence rates are in Northern America, Western Europe, Northern Europe and Australia/New Zealand. The lowest rates for women are in Middle Africa and Polynesia.

The incidence rates for both genders increase with age; the highest is older than 70 years. Approximately 90% of all cases of pancreatic cancer are among people over 55 years of age.

Pathophysiology

Pancreatic cancer can be of adenocarcinoma origin, serous, seromucinous, or mucinous.

Histopathology

More than 90% of adenocarcinoma of the pancreas are duct cell adenocarcinomas with other types being cystadenocarcinoma and acinar cell carcinoma. Two-thirds arise in the pancreatic head; one-third arise in the rest (body and tail of pancreas). Several research articles have evaluated the genetic nature of various subtypes of pancreatic cancer, providing an overall genetic makeup of pancreatic cancer. These genetic patterns can later be used to create targeted therapy, potentially improving survival in pancreatic cancer patients.

Toxicokinetics

Tumor markers associated with pancreatic cancer include CEA and CA 19-9.

History and Physical

Patients with adenocarcinoma of pancreas typically present with painless jaundice (70%) usually due to obstruction of the common bile duct from the pancreatic head tumor. Weight loss occurs in about 90% of patients. Abdominal pain occurs in about 75% of patients. Weakness, pruritus from bile salts in the skin, anorexia, palpable, non-tender, distended gallbladder, acholic stools, and dark urine. Sometimes, patients may present with recurrent deep vein thrombosis (DVT) due to hypercoagulability that prompts clinicians to suspect cancer and a full workup of cancer.

Patients can also present with recent-onset diabetes.

Lab findings will include elevation in liver function tests, direct and total bilirubin levels, elevated amylase and lipase, and elevated pancreatic tumor markers (CA 19-9 and CEA).

Evaluation

If adenocarcinoma of the pancreas is suspected, multidetector computed tomography, MDCT, is the best imaging modality to diagnose and evaluate the extent of disease including perivascular extension and distant metastasis. MDCT is 77% accurate in predicting resectability and 93% accurate in predicting unresectability.

Multidetector CT protocol for pancreatic imaging utilizes a multiphase imaging technique, which includes a late arterial phase and a portal venous phase after administration of intravenous contrast material.  The late arterial or pancreatic phase is acquired at 35 to 50 seconds after the injection and allows optimum evaluation of the pancreatic parenchyma. The portal venous phase is acquired at 60 to 90 seconds after the injection of intravenous (IV) contrast and allows for optimum assessment of the venous anatomy and is best for the detection of hepatic and distant metastatic disease. Water can be used as oral contrast. Barium-based oral contrast is generally not used, as it will interfere with the evaluation of vascular anatomy and encasement. Multiplanar reformatted images in the coronal and sagittal plane, maximum intensity projection images, and volume-rendered images are helpful to delineate vascular encasement and narrowing better.

PET CT scan can be useful in detecting distant metastatic disease.

Abdominal MRI /MRCP with IV contrast is as good in the preoperative evaluation of pancreatic cancer and the assessment of vascular invasion. MRI is more sensitive to detect metastatic hepatic disease with a sensitivity approaching 100% as compared with 80% for CT. MRI also employs a standard multiphase post contrast imaging protocol. There is a small subset of pancreatic adenocarcinoma which will provide the same attenuation on CT scan so that it will be more conspicuous on MRI. If pancreatic cancer is highly suspected and the CT scan is negative, that would be an indication to order further imaging with MRI of the abdomen with IV contrast. The downside to MRI is that if the patient cannot follow breathing instructions or has difficulty holding their breath, the images will be of poor quality.  CT images are much faster to obtain and do not require significant breath hold ability.

Ultrasound is of limited value in pancreatic imaging. Often the pancreas will be poorly visualized sonographically secondary to bowel gas.  Ultrasound can detect the secondary biliary ductal dilatation associated with pancreatic head cancer but it not so useful in visualizing the pancreatic mass itself.

ERCP with endoscopic ultrasound can be performed, and fine needle aspiration biopsies can be done of suspicious lesions for the pathologic specimen. However, with a mass in the pancreas, biopsy confirmation is not necessary, and one can proceed directly to excision given that full workup has been performed.

Endoscopic ultrasound, a test performed by gastroenterologists, can delineate the pancreatic mass and can be used to biopsy the mass under ultrasound guidance.

Endoscopic retrograde cholangiopancreatography (ERCP) is a test in which a contrast dye is injected into the biliary ducts and pancreatic duct with an endoscope. The level of biliary or pancreatic obstruction can be delineated. In some case, placement of a biliary stent can help relieve symptoms of jaundice.

Treatment / Management

If the adenocarcinoma of the pancreas is located in the head of the pancreas, then the Whipple procedure (pancreaticoduodenectomy) is the procedure of choice. If the tumor is in the body or tail of the pancreas, the distal resection is needed. Postoperatively, patients may receive chemotherapy with 5-FU, gemcitabine, and radiotherapy. If the hepatic artery is involved in the tumor, then the tumor is considered to be unresectable. However, if the superior mesenteric vein is involved in the tumor, then resection and vascular reconstruction. The same is true for portal vein involvement. It can be resected and reconstructed with graft.[5][6][7][8][9]

Differential Diagnosis

Typically, at the time of diagnosis of pancreatic cancer, 52% have distant metastasis, and 23% have local spread.

Differential diagnosis before imaging and biopsy includes the following: acute pancreatitis, chronic pancreatitis, cholangitis, cholecystitis, choledochal cyst, peptic ulcer disease, cholangiocarcinoma, and gastric cancer.

Radiation Oncology

There is a role for radiation therapy in combination with chemotherapy to treat locally advanced pancreatic cancer. Radiation therapy was originally used to alleviate the pain, but its use is currently becoming more widespread to shrink tumors and increase survival.

Medical Oncology

Most patients that are deemed possibly resectable for pancreatic cancer should receive neoadjuvant chemotherapy. The two main regimens used are FOLFIRINOX and gemcitabine plus protein-bound paclitaxel. Many patients who are younger, fit, and have minimal comorbidities are offered FOLFIRINOX (a combination of 5-fluorouracil, oxaliplatin, and irinotecan). This regiment is extremely toxic and only fit, young patients can withstand it. For patients who are older and/or not as healthy might be offered gemcitabine and protein-bound paclitaxel. Protein-bound paclitaxel is a taxane that is an albumin conjugate and has a lower risk profile than FOLFIRINOX. Of note, these two regimens were initially used for postoperative use. Now, however, these regiments are considered before and after surgery. The typical duration of each regimen is 4 months. 

Pain management is extremely important. Pancreatic cancer is one of the most painful malignancies. Opioids, antiepileptics, and corticosteroids all are effective for pain relief.

Staging

Stage I: Tumor is located in the pancreas and does not extend elsewhere

Stage II: Tumor infiltrates bile duct and other near structures, however lymph nodes are negative

Stage III: Any positive lymph nodes

Stage IVA: Metastases into nearby organs such as stomach, liver, diaphragm, adrenals

Stage IVB: Tumor infiltrates distant organs

Inoperability is signified on imaging by superior mesenteric artery encasement, liver metastases, peritoneal implants, distal lymph node metastases, and distant metastases.

Prognosis

Prognosis for pancreatic adenocarcinoma remains poor despite advances in cancer therapy. The 5-year survival rate is approximately 20%. Prognosis after 1 year of diagnosis is dismal, with 90% of patients dying at 1 year despite surgery. However, palliative surgery can be of benefit.

Complications

Postoperative complications of pancreatic surgery include pancreatic fistulas, delayed gastric emptying, anastomotic leaks, bleeding, and infection.

Postoperative and Rehabilitation Care

For patients with metastatic, stage IV, pancreatic cancer, discussions with the patient regarding treatment are essential. One can receive chemotherapy. However, the life prolongation will be at best months, yet affected the toxicity and effects of the chemotherapy. It is important to keep nutrition on the forefront of the patient's care as nutrition can affect wound healing.

Consultations

Palliative and/or supportive care, hospice, dietary, nutrition, physical therapy, occupational therapy

Deterrence and Patient Education

It is important to discuss with the patient all the treatment options before discussing surgery.

Pearls and Other Issues

Delayed gastric emptying is a common complication of Whipple procedure. Similarly, anastomotic leaks pose significant morbidity to the patient.

Enhancing Healthcare Team Outcomes

The diagnosis and management of pancreatic cancer is with a multidisciplinary team that consists of an oncologist, general surgeon, radiologist, pain specialist, gastroenterologist, palliative care nurse, and an internist. By far the majority of cases of pancreatic cancer are advanced at the time of presentation and these patients have a very short life expectancy. Palliative care and a pain specialist should be involved in the care of these patients. Coordination of education of the family by the palliative nurse or provider is key because survival is severely reduced in most patients. The surgery for pancreatic cancer is complex and technically demanding. Even those who undergo successful resection may develop serious life-threatening complications which may alter the quality of life. [10] (Level V)


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Cancer, Pancreas - Questions

Take a quiz of the questions on this article.

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A 71-year-old male presents with complaints of pruritus, dark urine, and abdominal pain. Physical examination shows jaundice. Laboratory tests include a total bilirubin of 6.3 mg/dL, alkaline phosphatase 4 times the upper limit of normal, and mild elevations in serum transaminases. Ultrasonography shows dilated extrahepatic and intrahepatic bile ducts but no gallstones. There is a 3 cm mass in the head of the pancreas, presumed pancreatic cancer. Which CT finding would indicate that the cancer is not resectable?



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Which of the following risk factor is most strongly associated with ductal adenocarcinoma of the pancreas?



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A 59-year-old presents with jaundice and is found to have pancreatic cancer. Which of the following is true about this malignancy?



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A 56-year-old has pancreatic cancer. Which of the following is false about the disorder?



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Which diagnosis should be considered in a 65-year-old male who presents with weight loss, anorexia, back pain, and migratory thrombophlebitis?



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A 55-year-old male is seen with a 3-month history of jaundice, lack of appetite, and weight loss. He had been complaining of back pain for many weeks but was too weak to go see a physician. Examination reveals an ill-looking male with scleral icterus, a palpable gallbladder, and jaundice. Which of the following is a true statement about this condition?



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Which of the following is not a tumor of the pancreatic endocrine glands?



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Where do the majority of pancreatic cancers occur?



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Which organ system is least likely to have metastases in patients with pancreatic cancer?



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What is the 5-year survival rate for pancreatic cancer?

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Which of the following is the major risk factor for pancreatic cancer?



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Levels of cancer antigen 19-9 usually are elevated in patients who have which of the following conditions?



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An adult presents with painless jaundice and nausea. She has lost 10 pound in 3 months. CT scan reveals a 2.5 cm solid mass on the head of the pancreas. Which of the following treatment options provides the best chance for long-term survival?



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Which of the following is most likely to cause obstructive jaundice?



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Which vessel is compressed by a tumor on the uncinate process of the pancreas?



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From the image shown, the most likely cause is?

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Biopsy of a 4 cm unresectable pancreatic mass shows high nuclear to cytoplasmic ratio and hyperchromatic nuclei. There are some glands made up of these cells. What is the 5 year survival rate?



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An elderly diabetic male presents with jaundice and weight loss. The gallbladder is palpable. What is the most likely diagnosis?



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Which carcinoma most commonly causes generalized pruritus?



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Which of the following statements about pancreatic cancer is incorrect?



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A patient has been treated with gemcitabine and erlotinib for stage IV pancreatic cancer but CT shows growth of the mass over the 16 weeks of treatment. Stents have been placed in the biliary duct and the patient is active and ambulatory. Which of the following is the best treatment for this patient?



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A patient is found to have a 2.2 cm spiculated mass in the tail of the pancreas on a CT scan. There is no local extension or lymphadenopathy. A CA 19-9 level and bilirubin are normal. What is the best next step in the management of this patient?



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A 65-year-old male smoker comes to the provider reporting loss of energy. He describes depressive symptoms as well, but he has no prior history of depression. When asked about physical complaints, he describes frequent and prominent abdominal pain. Which of the following disorders should be considered first?



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A patient is admitted with pancreatic cancer and jaundice. What should be the highest nursing priority?



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A 72-year-old female smoker with type 2 diabetes and alcoholic cirrhosis dies of complications from her chronic illnesses. Autopsy shows a mass in the pancreas that is hard and infiltrative. The rest of the pancreas shows fibrosis with acinar loss, dilation of ducts, moderate infiltration of lymphocytes, but normal islets. Select the most likely findings for the pancreatic mass.



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A 65-year-old female diabetic reports a 6-month history of right upper quadrant pain decreased by leaning forward. She has recurrent superficial thrombophlebitis and jaundice. What is the most probable diagnosis?



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You are told you "missed" a neuroendocrine tumor of the pancreas on reading your abdominal CT. Which of the following is the most likely problem?



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Which of the following lists contain pancreatic neoplasms that can contain both solid and cystic components?



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A 71-year old female presents with a 2-month history of weight loss, jaundice, vague abdominal pain, and itching. She has recently been diagnosed with diabetes mellitus type 2. Physical exam reveals vague abdominal pain, skin excoriations, and a positive Courvoisier sign. Which one of the following would contraindicate surgery in this patient?



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The image below is from a 69-year-old male. What physical sign does this CT scan reflect?

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    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD



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Cancer, Pancreas - References

References

Kanno A,Masamune A,Hanada K,Kikuyama M,Kitano M, Advances in Early Detection of Pancreatic Cancer. Diagnostics (Basel, Switzerland). 2019 Feb 5;     [PubMed]
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De Luca L,Repici A,Koçollari A,Auriemma F,Bianchetti M,Mangiavillano B, Pancreatoscopy: An update. World journal of gastrointestinal endoscopy. 2019 Jan 16;     [PubMed]
Bausch D,Keck T, Minimally Invasive Surgery of Pancreatic Cancer: Feasibility and Rationale. Visceral medicine. 2018 Dec;     [PubMed]
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