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Subsections
Pancreatic Cancer

Pancreatic Cancer

Pancreatic Cancer

Background

  1. Definition
    • Pancreatic cancer (PC) can arise either from the exocrine or endocrine pancreas
    • This monograph refers to cancer of the exocrine pancreas mainly infiltrating ductal adenocarcinoma
    • Malignant tumor of the pancreas, accounting for approximately 90% of all pancreatic carcinomas
    • Most tumors (about 60-70% occur in the head of the pancreas
  2. Synopsis
    • Pancreatic cancer is one of those with the poorest prognosis with about 6% 5-year survival rate in advanced disease, while most die within the first year
    • It is the fourth leading cause of cancer deaths in the United States
    • Of all the GI cancer deaths, it is next to colorectal cancer
    • Infiltrating ductal adenocarcinoma (IDA) is the most common form of exocrine pancreatic cancer
    • Most pancreatic IDAs arise in the head of the pancreas where they are located to the right of the superior mesenteric artery and portal vein confluence
    • It may occur sporadically or have familial clusters
    • Majority of pancreatic cancers are exocrine (> 95%) in origin

Pathophysiology

  1. Etiology
    • The exact etiology is unknown
    • Multifactorial where genetic and environmental factors interplay
    • Genetic pancreatic cancer may be inherited as
      • Familial pancreatic cancer
      • Familial multiorgan cancer syndromes
      • Genetic chronic diseases
    • Commonly encountered genetic abnormalities include
      • KRAS mutation
      • Inactivation of tumor suppressor genes like P53, P 16 and SMAD4
    • Some other genes that are implicated include BRCA2 12
      • STK11
      • P16/CDKN2
      • PALB2
      • ABO blood group locus
  2. Risk Factors/Predisposition
    • Tobacco use including pipe and cigar increase risk
      • Smoking is the most important risk factor 1
      • Attributing to about 20% of cases
      • Risk increases with increase in the amount and duration of smoking
      • Environmental tobacco smoke exposure is also associated with increased risk 10
    • Obesity
      • Abdominal obesity, especially in women
    • Heavy alcohol intake 7
    • Low plasma 25-hydroxyvitamin D
    • Positive family history of pancreatic cancer increases risk by 2-fold
      • One first degree relative with pancreatic cancer (parent or sibling) 7 to 9-fold increased risk
      • 3 or more first degree relatives with pancreatic cancer, 17 to 32-fold increased risk
      • First degree relative diagnosed before the age of fifty
    • Hereditary pancreatitis 4, 5
    • Inherited cancer syndromes like
    • None "O" blood group is associated with increased risk 6
    • Chronic pancreatitis 8
    • Diabetes mellitus 9
    • Hepatitis B and H pylori are also possible risk factors, though additional data is needed 11
    • Occupational exposure to beta-naphthylamine and benzidine exposure
  3. Epidemiology 2
    • According to the 2013 American Cancer Society, Facts and Figures report in 2013 in the USA
      • There will be about 45,220 new cases of pancreatic cancer (22,740 males and 22,480 females)
      • There will be estimated deaths of about 38,460 (19,480 males and 18,980 females)
    • According to the 2008 global cancer statistics, it is the 8th and 9th leading cause of cancer deaths worldwide in males and females respectively
    • In the past decade, the number of pancreatic cancer deaths is increasing in both sexes in the US
    • Age-adjusted incidence rate is 13.6 and 10.5 per 100,000 for men and women respectively
    • Male: female ratio = 1.3:1
    • Lifetime risk of having pancreatic cancer is about 1.5% for both sexes
    • Incidence increases with advancing age and median age at diagnosis is about 71 years
    • A higher incidence in African Americans at all ages and lowest in Asian Americans and Pacific Highlanders
    • Pancreatic cancer deaths are higher in low socioeconomic status
  4. Pathology of Disease
    • Pancreatic cancers can be endocrine or exocrine
    • Pancreatic tumors can be benign, usually cured by surgery alone
      • Serous cyst adenoma
    • 85% of patients present with an advanced unresectable disease
      • Nearly 70% are located in the head
      • Around 25% are located in the body and tail
      • The remaining involving the entire gland
    • Exocrine tumors may be related to the pancreatic ducts or acini
    • Currently there are 3 histologic lesions recognized as precursors of pancreatic cancer 13
      • Pancreatic intraepithelial neoplasia (Pan INs)
        • They are <0.5 mm noninvasive epithelial neoplasms
        • Are of ductal origin
        • Histologically characterized by mucin containing cuboidal to columnar cells
        • Classified into 3, types I, II and III
        • Type III is included as carcinoma in situ
      • Intraductal papillary mucinous neoplasm (IPMNs)
        • A premalignant lesion
        • Can be low, intermediate or high-grade dysplasia
        • Mucin-producing epithelial tumors
        • Papillary histologic architecture
        • May originate from the main or branch pancreatic ducts
      • Mucinous cystic neoplasm (MCNs)
        • A premalignant lesion
        • Can be low, intermediate or high-grade dysplasia
        • More common in women
        • Not of ductal origin
        • Are often associated with an ovarian type stroma
    • Histologic variants of malignant pancreatic cancer include
      • Ductal Adenocarcinoma, most common, > 85%
      • Adenosquamous carcinoma, about 4%
      • Colloid carcinoma
      • Medullary carcinoma
      • Signet ring cell carcinoma
      • Undifferentiated carcinoma
      • Undifferentiated carcinoma with osteoclast-like giant cells
      • Serous cystadenocarcinoma
      • Pancreatoblastoma
      • Acinar cell carcinoma
    • Pancreatic tumors in the head are detected earlier as they cause biliary obstruction and painless jaundice

Diagnostics 14, 15, 16

  1. History
    • Symptoms vary according to tumor location
    • In cancer of the head of the pancreas painless jaundice is common
    • Patients commonly present with
      • Asthenia, abdominal pain
      • Anorexia and weight loss
      • Jaundice and black colored urine
      • Floating stools
      • Bloating
      • Nausea
    • Itching
    • Sleep disturbance and unusual heartburn
    • Depression
    • History of recent onset of diabetes
    • Unexpected, unusual, migratory thrombophlebitis (Trousseau's syndrome)
  2. Physical Examination
    • Cachexia and jaundice
    • Courvoisier’s sign- a palpable, non-tender gallbladder in a jaundiced patient
    • Patients may also have hepatomegaly and epigastric mass
    • Scratch marks
    • Patients may have signs of distant metastasis including
      • Ascites
      • Abdominal mass
      • Virchow’s node – left supraclavicular lymphadenopathy
      • Sr. Mary Joseph’s node – periumbilical lymphadenopathy
    • Various cutaneous manifestations like
      • Bullous pemphigoid
      • Migratory superficial thrombophlebitis
      • Pancreatic panniculitis which are nodular areas of subcutaneous fat necrosis
  3. Laboratory evaluation
    • CBC
    • Platelet count
    • Hemoglobin/hematocrit
    • AST/ALT
    • Bilirubin, total and direct
    • Alkaline phosphatase
    • PT
    • Albumin
    • Serum amylase and lipase
    • Other tests to determine cause of jaundice may be done accordingly
    • CA 19-9 17
      • Elevated in more than 70% of patients with pancreatic cancer
      • Both preoperative staging and prognostic value
      • No role in screening asymptomatic people
      • In one study, among patients with symptomatic heterogeneous pancreatic lesions, for pancreatic cancer, it had a
        • Sensitivity of about 80.8%
        • Specificity of about 89.1%
        • Positive predictive value of about 93.7%
        • Negative predictive value of about 89.2%
      • Limitations include 18
        • Non-specific, being expressed in several benign and malignant diseases
        • False negative in people with Lewis negative genotype
        • High false positive result in obstructive Jaundice
      • Recommended measurement
        • Before surgery if bilirubin levels are normal
        • After surgery before adjuvant therapy
        • For surveillance of recurrence
  4. Diagnostic Imaging
    • Imaging is highly valuable in diagnosing and staging pancreatic adenocarcinoma
    • CT of the pancreas/pancreatic protocol CT
      • It is highly validated
      • Limited sensitivity in detecting small metastasis to the liver and peritoneum
    • Pancreas protocol MRI
      • Has an equal importance to pancreas protocol CT in detecting pancreatic cancer
      • Better in detecting extra pancreatic lesions
    • Chest x-ray
    • Endoscopic U/S (EUS)
      • A useful diagnostic tool
        • In evaluating patients when vascular invasion is questionable
        • When CT/MRI are negative, despite strong suspicion of pancreatic cancer
        • When cytologic confirmation is necessary
      • May show severe stenosis and marked proximal dilatation in malignancy
      • May also be used to evaluate periampullary masses
      • Also helpful in characterizing cystic pancreatic lesions
    • ERCP (endoscopic retrograde cholangiopancreatography) / MRCP (magnetic resonance cholangiopancreatography)
      • When brush cytology is recommended
        • In patients without a pancreatic mass and no evidence of metastasis
      • Stent placement
    • Combined PET/CT scanning
      • Increases sensitivity of CT
  5. Other Studies
    • Laparoscopy
      • Useful for staging
      • Look for peritoneal, hepatic or serosal malignant infiltrates
    • Biopsy
      • Not needed before surgery
      • It can be U/S guided or CT guided
      • It is needed before Neoadjuvant therapy
  6. Staging
    • Based on TNM classification definition and The American Joint Committee on Cancer (AJCC) designated staging 26
    • TNM definitions
      • Primary tumor (T)
        • TX primary tumor cannot be assessed
        • T0 No evidence of primary tumor
        • Tis carcinoma in situ
          • Also includes the “PanIN-III” classification
        • T1 Tumor limited to the pancreas
          • 2 cm or less in greatest dimension
        • T2 Tumor limited to the pancreas
          • More than 2 cm in greatest dimension
        • T3 Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery
        • T4 Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor)
      • Regional lymph nodes (N) definitions
        • NX Regional lymph nodes cannot be assessed
        • N0 No regional lymph node metastasis
        • N1 Regional lymph node metastasis
      • Distant metastasis
        • M0 No distant metastasis
        • M1 Distant metastasis
    • AJCC stage groupings
      • Stage 0
        • Tis, N0, M0
      • Stage IA
        • T1, N0, M0
      • Stage IB
        • T2, N0, M0
      • Stage IIA
        • T3, N0, M0
      • Stage IIB
        • T1, N1, M0
        • T2, N1, M0
        • T3, N1, M0
      • Stage III
        • T4, Any N, M0
      • Stage IV
        • Any T, Any N, M1

Table 1. Eastern Cooperative Oncology Group (ECOG) Performance Status 29

Performance Status Grade

Description

0

Fully active
All pre-disease performance is present without restriction

1

Physically strenuous activity is restricted but remains ambulatory
Able to carry out light or sedentary work (e.g., light housework, office work)

2

Ambulatory
Capable of all self-care
Unable to carry out any work activities
Up and about more than 50% of waking hours

3

Capable of limited self-care
Confined to bed or chair more than 50% of waking hours

4

Completely disabled
Unable to provide self-care
Totally confined to bed or chair

5

Deceased

Testing and Management of Hereditary Pancreatic Cancer: American College of Gastroenterology (ACG) Clinical Guidelines 27

  1. Surveillance of patients with a genetic predisposition for pancreatic adenocarcinoma should be performed in experienced multidisciplinary centers under research conditions
  2. These patients should be known mutation carriers from hereditary syndromes associated with increased risk of pancreatic cancer, such as
    • Peutz–Jeghers
    • Hereditary pancreatitis
    • Familial atypical multiple melanoma and mole syndrome
    • Or have a first-degree relative with pancreatic cancer
  3. There is a lower relative risk for pancreatic adenocarcinoma development in BRCA1, BRCA2, PALB2, ATM, and LS families
    • Surveillance should be limited to mutation carriers with a first or second-degree relative affected with pancreatic cancer
  4. Surveillance for pancreatic cancer should be with endoscopic ultrasound and/or MRI of the pancreas
    • Annually starting at age 50 years, or
    • 10 years younger than the earliest age of pancreatic cancer in the family
  5. Patients with Peutz–Jeghers syndrome should start pancreatic cancer surveillance at age 35 years
  6. Cystic lesion(s) of the pancreas detected during surveillance of a hereditary pancreatic cancer-prone family member requires evaluation by centers experienced in the management of these high-risk patients
  7. It is difficult to determine the timing for surgery for a pancreatic lesion, and it is best individualized after multidisciplinary assessment

Differential Diagnosis

  1. Key Differential Diagnoses
    • Autoimmune pancreatitis
      • Associated with elevated serum IgG
    • Chronic pancreatitis
    • Pancreatic pseudocyst and other benign cystic lesions
    • Other causes of obstructive jaundice
    • Pancreatic neuroendocrine tumor
    • Pancreatic lymphoma
    • Metastatic pancreatic cancer (rarely)
  2. Extensive Differential Diagnoses

Therapeutics

  1. Multidisciplinary approach is strongly recommended in the diagnosis and treatment of pancreatic cancer
    • Pancreatic tumor therapy depends on the stage of the disease
    • It can be locally resectable, borderline or unresectable
    • Surgical resection
      • Potentially curative
      • Used in tumors limited to the pancreas and peripancreatic lymph nodes
      • Surgical resection is contraindicated when there is
        • Extra abdominal spread
        • Liver involved
        • Omentum and peritoneum are involved
      • Tumor is deemed unresectable when there is 20
        • Metastasis to distant structures
        • Involvement or encasement of major blood vessels including the aorta, inferior vena cava, superior mesenteric vein or portal vein
        • When > 180° of the circumferences of the superior mesenteric artery or celiac artery is involved
        • Beyond the peripancreatic lymph node involvement
      • Different approaches are available 16
        • Pancreatectomy
          • Distal pancreatectomy is the procedure of choice for cancer of the body and tail
        • Pancreaticoduodenectomy
          • Pylorus preserving pancreaticoduodenectomy (modified Whipple's procedure) is the procedure of choice in pancreatic cancer involving the head and uncinate process
  2. Surgical resections are preferably done in high volume hospitals 21
    • Low-volume centers are more likely to have margin-positive resections
    • Margin-positive resections are associated with poor prognosis
  3. Adjuvant (post resection)/neoadjuvant (prior to resection) therapy
    • Can be chemotherapy, radiotherapy or chemoradiotherapy (CRT), a combination of both
    • Neoadjuvant therapy has not been proven to increase survival in locally advanced or borderline resectable pancreatic cancer 23
    • Commonly used chemotherapeutic agents include
  4. Locally advanced, unresectable pancreatic cancer
    • Chemotherapy is recommended
    • Patients may also benefit from radiotherapy
  5. Guideline update on metastatic pancreatic cancer by ASCO
    • Initial Assessment
      • perform multiphase CT of the chest, abdomen/pelvis to assess the extent of disease
      • Evaluate the patient's baseline performance status (PS), symptom burden and comorbidity profile
      • Discuss the goals of care including:
        • Advanced directive
        • Patient preferences
        • Support systems
      • Multidisciplinary collaboration to formulate treatment, care plan and disease management should be the standard of care
      • Early testing for actionable genomic alterations should be recommended to help guide patients in treatment decisions
        • Especially for patients who are potential candidates for additional Rx after first-line therapy
        • Both germline and somatic testing for the following are recommended:
          • microsatellite instability/mismatch repair deficiency
          • BRCA mutations with known significance
          • NTRK gene fusions
    • First-Line Treatment
      • FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is recommended for patients who meet all the following criteria:
        • Eastern Cooperative Oncology Group (ECOG)PS 0-1
        • Favorable comorbidity profile
        • Patient preference and a support system for aggressive medical therapy
        • Access to chemotherapy port and infusion pump management services
      • Gemcitabine plus nab-paclitaxel is recommended for patients who meet all the following criteria:
        • ECOG PS 0-1
        • Relatively favorable comorbidity profile
        • Patient preference and a support system for relatively aggressive medical therapy
      • Gemcitabine alone is recommended for patients who have:
        • Either an ECOG PS of 2 or a comorbidity profile that precludes more aggressive regimens and
        • Wish to pursue cancer-directed therapy
        • Addition of nab-paclitaxel or capecitabine or erlotinib to gemcitabine may be offered, with proactive dose and
        • Schedule adjustments to minimize toxicities
  6. Palliation and supportive care
    • Management of pancreatic insufficiency
    • Management of depression and emotional support
    • Appropriate nutritional evaluation and intervention
    • Relieving biliary obstruction in jaundiced patients
    • Relieving intestinal obstruction
    • Management of abdominal pain 24
      • Palliative radiotherapy or
      • Celiac plexus neurolysis
    • Prevention of thromboembolic diseases

Pancreatic Cancer Management Guidelines - European Society for Medical Oncology (ESMO) 28

  1. Localized disease
    • Multidisciplinary team is needed
    • Tumor clearance for all seven margins (identified by surgeon)
    • Removal of > 15 lymph nodes for adequate disease staging
    • Adjuvant therapy with either gemcitabine or 5-FU folinic acid
    • Chemoradiation should be reserved for clinical trials only
  2. Borderline resectable disease
    • Patients should be included in clinical trials if possible
    • If a clinical trial is not possible, the best treatment option is a period of chemotherapy (gemcitabine or Folfirinox) followed by chemoradiation and then surgery
  3. Locally advanced disease
    • 6 months of gemcitabine is the standard of care
    • A minor role of chemoradiation in this population of patients has been observed
    • The classic combination of capecitabine and radiotherapy is recommended
  4. Palliative and supportive care in advanced/metastatic disease
    • Duodenal obstruction should be managed by endoscopic placement of an expandable metal stent; this is favored over surgery
  5. Oncological treatment of advanced/metastatic disease
    • Endoscopic approach for biliary stenting is safer than percutaneous insertion and is as successful as surgical hepaticojejunostomy
    • Pain control necessary and frequent pain specialist assistance should be expected
    • Patients with an ECOG performance status of 3 or 4, with significant morbidities and a short life span should be considered for symptomatic treatment only
    • In some patients with heavy tumor load and an ECOG performance status 2, gemcitabine and nab-paclitaxel may be considered
    • If the bilirubin level is > 1.5x the upper limit of normal, and/or the ECOG performance status is 2, consider monotherapy with gemcitabine
    • If the bilirubin level is < 1.5x the lower limit of normal, and the ECOG performance status is 0 or 1, consider one of two types of combination therapy
      • The FOLFIRINOX regimen or
      • The combination of gemcitabine and nab-paclitaxel

Follow-Up

  1. Surveillance directed towards detecting local or distant recurrence
  2. Impact of follow up surveillance on survival has not been proven
  3. No consensus has been reached on routine surveillance
  4. Follow-up involves
    • History and physical examination
    • CA-19-9 determination
    • CT scans

Prognosis

  1. Prognosis for the most part depends on tumor stage
  2. Rarely curable
  3. It has an overall survival rate of < 6%
  4. Under the most optimal conditions after surgery 22
    • Median survival is about 18 months
    • 5-year survival is about 18%
    • Factors associated with worse survival include
      • Tumor size
      • Lymph node ratio
      • Positive margins
  5. Elevated serum CEA level at diagnosis is associated with poor overall survival 19
  6. CEA level before starting therapy may predict the prognosis of patients with pancreatic cancer

Prevention

  1. There are no guidelines on pancreatic cancer prevention
  2. Avoiding risk factors is a proposed approach
  3. The most important avoidable risk factor is cigarette smoking
  4. The most effective strategy to reduce risk of pancreatic cancer is avoiding or cessation of smoking 1
  5. Other cancer prevention strategies
  6. Control of diabetes
  7. Even though early detection is linked to prolonged survival, currently there are no proven screening guidelines 25

References

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  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90.
  3. American Cancer Society. Cancer Facts and Figures: Available at http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf Accessed January 2016
  4. Rebours V, Levy P, Ruszniewski P. An overview of hereditary pancreatitis. Dig Liver Dis. 2012;44(1):8-15.
  5. Rebours V, Boutron-Ruault MC, Schnee M, et al. Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series. Am J Gastroenterol. 2008;103(1):111-119.
  6. Wolpin BM, Kraft P, Xu M, et al. Variant ABO blood group alleles, secretor status, and risk of pancreatic cancer: results from the pancreatic cancer cohort consortium. Cancer Epidemiol Biomarkers Prev. 2010;19(12):3140-3149.
  7. Lucenteforte E, La Vecchia C, Silverman D, et al. Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2012;23(2):374-382.
  8. Duell EJ, Lucenteforte E, Olson SH, et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2012;23(11):2964-2970.
  9. Chiu CC, Huang CC, Chen YC, et al. Increased risk of gastrointestinal malignancy in patients with diabetes mellitus and correlations with anti-diabetes drugs: a nationwide population-based study in Taiwan. Intern Med. 2013;52(9):939-946.
  10. Vrieling A, Bueno-de-Mesquita HB, Boshuizen HC, et al. Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2010;126(10):2394-2403.
  11. Risch HA. Pancreatic cancer: Helicobacter pylori colonization, N-nitrosamine exposures, and ABO blood group. Mol Carcinog. 2012;51(1):109-118.
  12. Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012;51(1):14-24.
  13. Hong SM, Park JY, Hruban RH, Goggins M. Molecular signatures of pancreatic cancer. Arch Pathol Lab Med. 2011;135(6):716-727.
  14. Holly EA, Chaliha I, Bracci PM, Gautam M. Signs and symptoms of pancreatic cancer: a population-based case-control study in the San Francisco Bay area. Clin Gastroenterol Hepatol. 2004;2(6):510-517.
  15. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood. 2007;110(6):1723-1729.
  16. Irene Chong &David Cunningham. Chapter 93: Pancreatic Cancer. Harrison's Principles of Internal Medicine 18th ed., McGraw-Hill 2012; pp.786-789.
  17. Cwik G, Wallner G, Skoczylas T, Ciechanski A, Zinkiewicz K. Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions. Arch Surg. 2006;141(10):968-973; discussion 974.
  18. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence-based appraisal. J Gastrointest Oncol. 2012;3(2):105-119.
  19. Lee KJ, Yi SW, Chung MJ,et al.Serum CA 19-9 and CEA levels as a prognostic factor in pancreatic adenocarcinoma.Yonsei Med J. 2013;54(3):643-9.
  20. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16(7):1727-1733.
  21. La Torre M, Nigri G, Ferrari L, Cosenza G, Ravaioli M, Ramacciato G. Hospital volume, margin status, and long-term survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am Surg. 2012;78(2):225-229.
  22. Mayo SC, Nathan H, Cameron JL, et al. Conditional survival in patients with pancreatic ductal adenocarcinoma resected with curative intent. Cancer. 2012;118(10):2674-2681.
  23. Barugola G, Partelli S, Crippa S, et al. Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy. Am J Surg. 2012;203(2):132-139.
  24. Seicean A, Cainap C, Gulei I, Tantau M, Seicean R. Pain palliation by endoscopic ultrasound-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer. J Gastrointestin Liver Dis. 2013;22(1):59-64.
  25. Poruk KE, Firpo MA, Adler DG, Mulvihill SJ. Screening for pancreatic cancer: why, how, and who? Ann Surg. 2013;257(1):17-26.
  26. Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9.
  27. Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223-262; quiz 263.
  28. Ducreux M, Cuhna AS, Caramella C, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26 Suppl 5: v56-68.
  29. ECOG Performance Status. ECOG-ACRIN Website. Available at: http://ecog-acrin.org/resources/ecog-performance-status. Accessed November 2, 2016.
  30. Metastatic Pancreatic cancer: ASCO Guideline Update. Available at: https://ascopubs.org/doi/full/10.1200/JCO.20.01364

Contributor(s)

Updated/Reviewed: November 2020