胰臟癌 (Pancreatic cancer)

General information

Description:

malignant tumor of the pancreas, most commonly adenocarcinoma

most tumors occur in head of pancreas

Types:

Ÿ   adenocarcinoma (ductal) 90%

Ÿ   cystadenocarcinoma (women)

Ÿ   nonfunctional islet cell tumor

Ÿ   sarcoma

Ÿ   neuroendocrine tumors

Ÿ   pancreatoblastoma (a rare juvenile adenocarcinoma of pancreas)

Ÿ   papillary cystic and solid tumor of the pancreas (PCSTP):
a rare primary neoplasm typically found in young women, low-grade malignant tumor, often asymptomatic

Ÿ   intraductal papillary mucinous tumors (IPMN) of pancreas (benign or malignant lesions)

Who is most affected:

78% of patients ≥ 60 years old, rarely occurs in persons < 50 years old, risk increases with age

M = F equally affected

Incidence/Prevalence:

10^th most common cancer and 4^th leading cause of cancer deaths in United States

13.2 per 100,000 men, 9.6 per 100,000 Asian

Cause and Risk factors

Causes:

transformation of pancreatic ductal epithelium

Pathogenesis:

abnormal palladin gene in familial pancreatic cancer and overexpression of palladin protein in sporadic pancreatic cancer reported to cause cytoskeletal changes

Risk factors:

1.           Likely risk factors:

a.           tobacco use, heavy alcohol use

b.          DM. obesity

2.           Possible risk factors:

a.           Sulfonylureas, metformin

b.          Helicobacter pylori infection’

c.           families with germline mismatch repair (MMR) gene mutations

d.          nonsteroidal anti-inflammatory drug (NSAID) use (including aspirin)

Complications and associated Conditions

Complications

Ÿ  obstructive cholestasis

Ÿ  gastric outlet obstruction

Ÿ  more rarely duodenal obstruction or gastrointestinal bleeding

Associated conditions:

1.           syndrome of inappropriate antidiuretic hormone secretion (SIADH)

2.           depression

3.           acute pancreatitis

4.           intraductal papillary mucinous neoplasm (IPMN) of the pancreas may be associated with pancreatic and extra-pancreatic cancers

History:

Chief concern (CC):

depends on size of tumor, location and stage of disease

1.           abdominal pain (67%)
pain often described as vague abdominal discomfort or dull, deep upper abdominal pain localized to tumor area

2.           weight loss > 10 lbs (4.5 kg) (56%)

3.           jaundice (45%)

4.           back pain (26%)

5.           vomiting (24%)

6.           indigestion (19%)

7.           pruritus (12%)

8.           diabetes mellitus (8%)

other symptoms may include:

1.           nausea, malaise

2.           weakness

3.           anorexia

4.           diarrhea

5.           early satiety

6.           bruising

7.           steatorrhea

biliary obstruction may cause

1.           dark urine

2.           pale stool

3.           pruritus

Past medical history (PMH):

1.           migratory thrombophlebitis (Trousseau's phenomenon, tissue thromboplastic factor)
consider diagnosis of pancreatic cancer if deep vein thrombosis and increased pTT

2.           new-onset diabetes

Family history (FH):

ask about family history of pancreatitis (5%-10% of cases)

Social history (SH):

1.        ask about history of cigarette smoking and exposure to toxic chemical including dichlorodiphenyltrichloroethane (DDT)

Physical:

General physical:

1.           peripheral lymphadenopathy

2.           ascites

3.           less common manifestations include

a.       deep and superficial venous thrombosis

b.       panniculitis
inflammation of subcutaneous adipose tissue, tender skin nodules

Skin:

1.           jaundice (less likely with body and tail tumors)

Abdomen:

1.           palpable epigastric mass

2.           distended palpable gallbladder (Courvoisiers sign)

3.           liver may be enlarged and tender with advanced disease

4.           increased abdominal girth

Diagnosis:

Making the diagnosis:

Weight loss + Abdominal pain + Jaundice

Ÿ   imaging tests used to identify lesions requiring further evaluation

1.           cancers usually can be seen with dual-phase helical computed tomography (CT)

2.           endoscopic ultrasound if negative or unclear CT and high clinical suspicion

Ÿ   tissue needed for confirmation of diagnosis

1.           tissue biopsy may be obtained by:

a.       endoscopic retrograde cholangiopancreatography (ERCP)

b.        image-guided fine needle aspiration

c.        endoscopic ultrasound-guided fine needle aspiration

2.           biopsy not needed if patient determined to be surgical candidate based on CT

3.           confirmation of diagnosis needed prior to starting chemotherapy or radiation therapy

Differential diagnosis:

Ÿ   other types of cancer including

1.           duodenal cancer

2.           lymphoma

3.           sarcoma

4.           cholangiocarcinoma

Ÿ   pancreatitis

1.           acute pancreatitis

2.           chronic pancreatitis

3.           autoimmune pancreatitis

Ÿ   insulinoma

Ÿ   intraductal papillary mucinous neoplasm (IPMN) of pancreas

Ÿ   gastric duplication cyst

Blood tests:

Ÿ   may see evidence of:

1.           mild abnormalities in liver function tests, such as elevated conjugated bilirubin (due to biliary obstruction)

2.           elevated alkaline phosphatase (due to biliary obstruction)

3.           hyperglycemia

4.           anemia

Ÿ   Biomarkers:

1.           cancer antigen (CA) 19-9:

a.       for therapeutic monitoring

b.        may indicate advanced disease

c.        for early detection of recurrent disease following treatment

*high levels of CA-19-9 may predict unresectable cancer

*cancer antigens 19-9 and 125 may predict cancer in pancreatic mass lesions

2.           serum amyloid A (SAA) and haptoglobin

3.           whole blood microRNA panels

Imaging studies:

Imaging tests

Ÿ   computed tomography (CT) imaging modality of choice for initial evaluation:

1.           endoscopic ultrasound - with no visible mass on CT

2.           endoscopic retrograde cholangiopancreatography (ERCP) - require endoscopic stent to relieve obstruction

3.           magnetic resonance imaging cholangiopancreatography (MRCP)
*more useful than ERCP in diagnosing pancreatic cance

4.           staging laparoscopy controversial:

a.           large (> 3 cm) primary tumors

b.          tumors in neck, body or tail of pancreas

c.           high-quality imaging tests suggest possible occult metastatic disease

d.          clinical signs that may indicate advanced disease including significant weight loss and pain, hypoalbuminemia, elevated cancer antigen (CA) 19-9 levels to properly stage disease to determine need for radiation therapy as part of multimodal treatment

Ÿ   tissue biopsy may be obtained by ERCP, image-guided fine needle aspiration, or endoscopic ultrasound-guided fine needle aspiration

 Staging:

American Joint Committee on Cancer (AJCC) staging for exocrine and endocrine pancreatic cancer, seventh edition:

primary tumor (T)

TX - primary tumor cannot be assessed

T0 - no evidence of primary tumor

Tis - carcinoma in situ (also includes "PanInIII" classification)

T1 - tumor limited to the pancreas, ≤ 2 cm in greatest dimension

T2 - tumor limited to the pancreas, > 2 cm in greatest dimension

T3 - tumor extends beyond pancreas but without involvement of celiac axis or superior mesenteric artery

T4 - tumor involves celiac axis or superior mesenteric artery (unresectable primary tumor)

regional lymph nodes (N)

NX - regional lymph nodes cannot be assessed

N0 - no regional lymph node metastasis

N1 - regional lymph node metastasis

distant metastasis (M)

M0 - no distant metastasis (no pathologic M0; use clinical M to complete stage group)

M1 - distant metastasis

Treatment: 

Treatment overview:

Ÿ   for resectable and potentially resectable tumors (stage I, stage II, and selected stage III cancers)

1.           surgery is treatment of choice for resectable tumors, though not all patients are surgical candidates

2.           adjuvant therapy (chemotherapy or chemoradiation)

a.           adjuvant chemotherapy may improve survival following pancreatic resection

b.          Gemcitabine (first-line therapy)

c.           Fluorouracil + Folinic acid
may be as effective as adjuvant gemcitabine for improving survival in patients with resected pancreatic adenocarcinoma

d.          chemoradiation does not appear effective in randomized trials although some cohort studies suggest improved survival

Ÿ   for unresectable tumors (most stage III and all stage IV cancers)

1.           chemotherapy improves survival over 6-12 months in patients with advanced pancreatic cancer

a.           FOLFIRINOX first-line chemotherapy may increase survival but with more adverse events compared with gemcitabine in patients with metastatic pancreatic cancer

b.          gemcitabine-based chemoradiation

c.           erlotinib + gemcitabine

d.          capecitabine + gemcitabine

e.          bevacizumab + gemcitabine + erlotinib

2.           celiac plexus block may reduce opioid use and constipation and slightly reduce pain in adults with pancreatic cancer pain

3.           chemical splanchnicectomy reduces pain in patients with unresectable pancreatic cancer

Ÿ   psychotherapeutic support during inpatient stay for gastrointestinal cancer surgery appears to increase 2- and 10-year survival

Prognosis:

Ÿ   survival rate 25% at 1 year and 5% at 5 years

Ÿ   15% 3-year survival after pancreaticoduodenectomy for pancreatic cancer

Ÿ   prognostic score may predict risk of major complications after pancreaticoduodenectomy:

4 risk factors significantly associated with major complications in derivation cohort used to define risk score (total score 0-15 points)

1.           pancreatic texture - 0 points if hard, 4 points if soft

2.           pancreatic duct diameter - 0 points if > 3mm, 1 point if ≤ 3 mm

3.           operative blood loss - 0 points if < 700 mL, 4 points if ≥ 700 mL

4.           American Society of Anesthesiologist score - 0 points if I, 2 points if II, 6 points if III

ICD-9 codes:

157.0 malignant neoplasm of head of pancreas

157.1 malignant neoplasm of body of pancreas

157.2 malignant neoplasm of tail of pancreas

157.3 malignant neoplasm of pancreatic duct

157.4 malignant neoplasm of islets of langerhans

157.8 malignant neoplasm of other specified sites of pancreas

157.9 malignant neoplasm of pancreas, part unspecified

ICD-10 codes:

C25 malignant neoplasm of pancreas

C25.0 head of pancreas

C25.1 body of pancreas

C25.2 tail of pancreas

C25.3 pancreatic duct

C25.4 endocrine pancreas

C25.8 overlapping lesion of pancreas

C25.9 pancreas, unspecified

Reference: Dynamed