Summary
Pancreatic cancer is the fourth leading cause of cancer deaths in the US and typically affects older individuals in the sixth to eighth decades of life. Underlying risk factors include smoking, obesity, heavy alcohol consumption, and chronic pancreatitis. Pancreatic carcinomas are mostly ductal adenocarcinomas and frequently located in the pancreatic head. The disease is commonly diagnosed at an advanced stage because of the late onset of clinical features (e.g., epigastric pain, painless jaundice, and weight loss). In many cases, the tumor has already spread to other organs (mainly the liver) when it is diagnosed. Treatment is often palliative as surgical resection is only possible in approx. 20% of cases. The most commonly used surgical technique is the pancreaticoduodenectomy (Whipple procedure). Five-year survival rates range from 3–40% depending on the extent, spread, and resectability of the tumor.
Epidemiology
- Age of onset: 60–80 years [1][2]
-
Incidence
- ∼ 3% of all new cancers in the US
- In 2020, 57,600 individuals in the US will be newly diagnosed with pancreatic cancer (♂ > ♀)
- Mortality: accounts for ∼ 8% of all cancer deaths in the US
-
High-risk groups [3][4]
- African Americans
- Individuals of Jewish ancestry
Epidemiological data refers to the US, unless otherwise specified.
Etiology
Exogenous risk factors [5][6][7]
- Smoking
- Chronic pancreatitis (especially when present for more than 20 years)
- High alcohol consumption
- Type 2 diabetes mellitus
- Obesity
- Occupational exposure to chemicals used in the dry cleaning and metalworking industries
- Possibly infections with:
- H. pylori (and excess stomach acid)
- Hepatitis B
Endogenous risk factors [5][8]
- Age > 50 years
-
Inherited genetic syndromes (10% of pancreatic cancers)
- Familial atypical multiple mole melanoma (FAMMM) syndrome
- Hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutations)
- HNPCC
- Von-Hippel-Lindau syndrome
- Neurofibromatosis type 1
- Multiple endocrine neoplasia type 1
- Familial pancreatic carcinoma
- Hereditary pancreatitis (mutations in the PRSS1 gene)
- Peutz-Jeghers syndrome
Clinical features
In most cases, there are no early symptoms suggestive of pancreatic cancer. [9]
Constitutional symptoms
- Poor appetite
- Weight loss
- Weakness
Gastrointestinal symptoms
- Belt-shaped epigastric pain which may radiate to the back
- Nausea
- Malabsorption, diarrhea (possibly steatorrhea secondary to exocrine pancreatic insufficiency)
-
Jaundice caused by obstruction of extrahepatic bile ducts (especially in tumors of the pancreatic head)
- Courvoisier sign: enlarged, nontender gallbladder and painless jaundice
- Pale stools, dark urine, and pruritus
- Impaired glucose tolerance (rarely)
Hypercoagulability
-
Trousseau syndrome: superficial thrombophlebitis (in 10% of cases)
- Recurring thrombophlebitis in changing locations (migratory)
- Red, tender extremities
- Classically associated with pancreatic cancer
- Thrombosis (e.g., phlebothrombosis, splenic vein thrombosis)
A thrombosis of unknown origin may be caused by an undiagnosed malignancy (especially pancreatic cancer, but also pulmonary, and prostatic carcinoma, the "3P's").
The symptoms of pancreatic cancer may be similar to those of chronic pancreatitis. Differential diagnosis is difficult since carcinoma may be accompanied by pancreatitis.
Diagnostics
Blood
- No screening tests available
- Tumor markers: used to monitor the progression of cancer and treatment efficacy
- Possibly ↑ lipase
Imaging
-
Approach:
- Patients usually first undergo an ultrasound, especially if jaundice as the initial symptom.
- If abdominal pain and weight loss are the initial presenting symptoms, a CT scan is preferred. A contrast-enhanced abdominal CT is the investigation of choice to confirm pancreatic carcinoma and determine its resectability.
- If abdominal CT is inconclusive, or if the abdominal CT shows a borderline resectable or unresectable tumor, endoscopic ultrasonography (EUS) and EUS-guided biopsy should be performed to histologically confirm the diagnosis.
- In some cases, ERCP/MRCP may be considered to rule out choledocholithiasis and asses if biliary decompression is indicated.
-
Initial tests
- Abdominal ultrasound: usually the first test: , especially if jaundice is the presenting symptom
-
Contrast-enhanced CT: usually confirms the diagnosis
-
Indications
- If abdominal pain and weight loss are the initial presenting symptoms.
- If ultrasound reveals a pancreatic mass, a contrast-enhanced CT is performed.
-
Indications
-
Findings
- Poorly defined, hypodense/hypoechoic and hypovascular mass
- Double-duct sign: With increasing size, tumors of the pancreatic head may block bile drainage in both the common bile duct and the pancreatic duct, leading to dilatation of both structures.
-
Endoscopic/magnetic resonance cholangiopancreatography (ERCP/MRCP)
- To rule out choledocholithiasis
- To assess if biliary decompression is indicated (e.g., in palliative treatment to alleviate symptoms)
-
Endoscopic ultrasound (EUS)
- Used when other diagnostic tests are inconclusive or to perform fine needle aspiration
- Findings similar to transcutaneous ultrasound
-
Fine needle aspiration: can be done via EUS (preferred) or percutaneously (US or CT-guided)
- Performed in case of unresectable disease to obtain a tissue sample for cytological evaluation
- Can help to differentiate pancreatic cancer from pancreatitis (e.g., chronic or autoimmune)
Pathology
Location [10]
- Pancreatic head: 65% of cases
- Pancreatic body and tail: 15% of cases
- Diffuse: 20% of cases
Pancreatic exocrine tumors [11]
-
Most common: ductal adenocarcinoma (95%)
- Altered ductal structures
- Cellular infiltration
-
Less common
- Acinar adenocarcinoma (acinar cells produce digestive enzymes)
- Mucinous cystadenocarcinoma
The majority of pancreatic malignancies are located in the head of the pancreas and originate from epithelial cells within the tubules.
Pancreatic endocrine tumors (neuroendocrine tumors/NET) [12]
- Insulinomas (result in hypoglycemia)
- Gastrinomas
- Vasoactive intestinal peptide-producing tumors (VIPomas)
- Pancreatic polypeptide-secreting endocrine tumors of the pancreas
- Glucagonomas
- Somatostatinomas
Differential diagnoses
Pancreatic cyst
-
Overview
- Epithelium-lined cyst, filled with serous or mucous liquid, often associated with the rare von-Hippel-Lindau syndrome
- Can be benign, precancerous or cancerous.
- Clinical features
-
Diagnostics
- CT scan: Cyst appears as a well-circumscribed hyperdense mass in comparison to the surrounding tissue.
- ERCP: Cyst shows contrast-enhancement.
-
Treatment
- Asymptomatic cyst: no surgical treatment
- Symptomatic cyst: CT-guided, endoscopic, or surgical drainage
Other
The differential diagnoses listed here are not exhaustive.
Treatment
As the only curative treatment option for pancreatic cancer is surgical resection, patients with operable tumors (∼ 20%) are always recommended for surgery. If surgical tumor resection is not possible or distant metastasis is present, a palliative approach is chosen.
Curative approach [13][14]
Surgery
-
Pancreatic head carcinoma: pancreaticoduodenectomy (Whipple procedure)
- Resection of pancreatic head, distal stomach, duodenum, gallbladder, and common bile duct
- Lymphadenectomy
- Reconstruction by enteroenterostomy or Roux-en-Y anastomosis
- Pylorus-preserving pancreaticoduodenectomy (Traverso-Longmire procedure)
-
Pancreatic body and tail carcinoma
- Resection of the left side of the pancreas with splenectomy
- In some cases, duodenopancreatectomy with splenectomy (in a curative treatment approach if partial removal of the pancreas is insufficient)
Neoadjuvant or adjuvant chemoradiotherapy
- To reduce tumor size, improve symptoms, and prolong life
- Chemotherapy or radiation therapy without surgery cannot cure the patient.
Palliative approach [13][14]
Palliative chemotherapy
- Indication: patients with advanced or metastatic pancreatic cancer
-
Chemotherapy regimens
- Gemcitabine as monotherapy is typically used as first-line therapy.
- Combination with tyrosine kinase inhibitor erlotinib shows better efficacy compared to monotherapy.
Pain management
- Pharmacotherapy: analgesia according to the WHO step-by-step plan
- Radiotherapy: used in patients with symptomatic metastasis, especially to the brain and bones (rare)
-
Celiac ganglion block (celiac plexus block): when pain management according to the WHO step-by-step plan fails
- CT-guided radiological or endosonographic transgastric puncture of the celiac ganglion
- Installation of test dose local anesthetic
- Followed by installation of 95% ethanol to destroy the nerve tissue
Management of gastrointestinal complications
-
Cholestasis
- ERCP with stent implantation
-
Percutaneous transhepatic bile duct drainage (PTCD): if endoscopic access path is complicated (e.g., in duodenal stenosis, duodenal resection, and inaccessibility of the biliodigestive anastomosis)
- Initially, external drainage in a collection bag
- May be changed into an internal drainage over time by using specific drainage systems and Bougies.
-
Percutaneous transhepatic bile duct drainage (PTCD): if endoscopic access path is complicated (e.g., in duodenal stenosis, duodenal resection, and inaccessibility of the biliodigestive anastomosis)
-
Gastric outlet stenosis: gastroenterostomy
- Best supportive care in patients with gastric outlet stenosis
- Stomach is anastomosed with the small intestine bypassing the duodenum
- Ileus/subileus: percutaneous endoscopic gastrostomy (PEG) tube as a relief tube
-
Cachexia: nutrition counseling
- Easily digestible foods (carbohydrates, little dietary fiber)
- Small, frequent meals
- Pancreatic enzyme supplements
Complications
- Lymphogenic and hematogenous metastases: often already present at time of diagnosis
-
Stenosis
- Gastric outlet stenosis
- Stenosis of the common bile duct
- Other complications
We list the most important complications. The selection is not exhaustive.
Prognosis
-
Very aggressive course [1]
- Overall 5-year survival rate: 10%
- 5-year survival rate of metastatic pancreatic cancer: ∼ 3%
- Median survival for patients who undergo successful resection: ∼ 18 months (5-year survival rate: ∼ 20%) [15]