Pancreatic cancer

Discuss pancreatic cancer?

Carcinoma of the pancreas has markedly increased in incidence over the past several decades, and ranks as the fifth leading cause of cancer death in the United States.

What are the risk factors for pancreatic cancer?

The major risk factors include chronic pancreatitis, smoking, diabetes mellitus, and hereditary predisposition to pancreatic cancer.

What are the clinical features?

  • Pancreatic cancer occurs in the 60–80 year age group. Most patients with pancreatic cancer experience pain, weight loss, or jaundice.
  • Dull aching upper abdominal pain radiating through to the back and worsened by eating.
  • Weight loss may be associated with anorexia, early satiety, diarrhea, or steatorrhea.
  • Jaundice may be painful or painless. Painful jaundice is usually associated with locally unresectable disease.
  • The diagnosis of pancreatic cancer should be considered in cases of
    • Idiopathic acute pancreatitis (no gallstones, no alcohol) in patients over 50 years of age.
    • Unexplained diabetes in patients over 50 years of age (no family history, obesity, or steroids).

What are the sites of pancreatic cancer?

Sixty-five per cent of tumours are located within the head, 15% in the body, 10% in the tail and 10% are multifocal. Tumors in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present early with steatorrhea, weight loss, and jaundice.

What are the diagnostic tests?

  • US abdomen/ CT scan abdomen
  • MRI produces similar results to contrast-enhanced multislice CT and is useful for patients who cannot receive intravenous contrast.
  • EUS
  • Tumour markers- Ca 19-9. Ca 19-9 may be raised in other benign and malignant conditions.
  • EUS- guided FNA biopsy is used in patients with resectable tumours. This is less likely to cause intraperitoneal spread of the tumor since the biopsy is obtained through the bowel wall rather than percutaneously.
    When a mass lesion of the pancreas is detected on CT, it is likely to be a malignant process. Attempts to make a tissue diagnosis in such patients are not useful since a benign sample does not exclude the presence of a neighboring malignancy. Thus, surgically fit patients may be operated without attempting to establish a preoperative diagnosis of malignancy. However, it must be recognized that some patients with benign lesions may be subjected to the radical resections.
  • Staging laparoscopy may be needed in the case of equivocal findings of locally advanced or metastatic disease on CT scan.

Discuss TNM staging for pancreatic cancer?

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 coeliac axis or SMA
T4= Tumor involves the coeliac axis or the SMA (unresectable primary tumor)

N0- No regional lymph node metastasis N1- Regional lymph node metastasis
M0- No distant metastasis M1- Distant metastasis

Stage I- T1-2, N0 M0
Stage IIA- T3, N0, M0
Stage IIB- T1-3, N1, M0
Stage III- T4, Any N, M0
Stage IV- Any T, Any N, M1

Discuss the differential diagnosis of pancreatic cancer?

  • Endocrine tumours and lymphomas can be confused clinically and radiologically with pancreatic carcinoma. The possibility of a clinically silent endocrine tumour should be considered when a mass is identified in the absence of other clinical features characteristic of pancreatic cancer. A tissue diagnosis is thus important in the management of a patient with a mass in the pancreas.
  • Focal chronic pancreatitis and autoimmune pancreatitis are the two benign processes most commonly mistaken for pancreatic malignancy on the basis of CT or US. These diagnoses can sometimes be suspected on the basis of history (eg, extreme young age, prolonged ethanol abuse, history of other autoimmune diseases).

Discuss the treatment of pancreatic cancer?

When is surgery indicated in pancreatic cancer?

Only 15 to 20 percent of patients are candidates for curative resection. Disease that is limited to the pancreas and peripancreatic nodes (stage I-IIB disease) is most likely to be cured by radical resection.

What are the types of surgery done?

  • Standard pancreaticoduodenectomy — The standard operation for pancreatic cancer within the head or uncinate process of the pancreas is pancreaticoduodenectomy, also called the “Whipple procedure”. The standard Whipple procedure involves removal of the pancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, and gallbladder. A partial gastrectomy is also performed.
  • Left sided resection (with splenectomy) is appropriate for localised carcinomas of the body and tail of the pancreas. Involvement of the splenic vein or artery is not in itself a contraindication to such resection. Prognosis is generally worse than pancreatic head tumours.

What are the contraindications for resection?

Contraindications for resection include

  • Presence of metastases in the liver, peritoneum, omentum or any extra abdominal site
  • Superior mesenteric, coeliac or hepatic artery encasement
  • Major venous encasement: > 2cm in length,>50% circumference involvement
  • Cirrhosis with portal hypertension
  • Uncertain whether distant lymph node metastases influence prognosis

Not a contraindication to surgery

  • Lymph node metastases within the operative field or para aortic lymph node involvement
  • Venous impingement or minimal invasion of superior mesenteric and hepatic portal veins
  • Gastroduodenal artery encasement
  • Continuous invasion of duodenum, stomach or colon

What is the surgical morbidity and mortality?

The standard Whipple procedure is associated with a perioperative mortality rate of less than 4 percent.

What is the role of preoperative stenting?
Clearly, patients with pancreatic cancer who are jaundiced at presentation are at risk for associated coagulopathy, malabsorption, and malnutrition.
But, there is little evidence of benefit from routine stenting of jaundiced patients before resection. However, if definitive surgery must be delayed more than 10 days, it is reasonable to obtain internal biliary drainage with a plastic stent.

What is the role of role of adjuvant therapy?

Adjuvant chemotherapy is used after resection of a pancreatic or ampullary neoplasm. Radical resection alone will result in a 5-year survival of only 10% owing to recurrence after surgery. Adjuvant systemic chemotherapy will increase the 5-year survival from 9% to 12% with resection alone to 23% with gemcitabine. Median survival is 10-20 months.

What are the palliative treatment options?

  • Treatment of metastatic pancreatic cancer-Single agent gemcitabine remains the standard of care in 2006 for the treatment of patients with advanced pancreatic cancer. Although the objective response rate for patients with measurable disease was only 11 percent, a clinical benefit like improvement in pain and weight loss was observed in 27 percent.
  • Pain can be a significant feature of advanced pancreatic cancer. Often, palliation of pain can be successfully achieved by opioid analgesics alone. The results of percutaneous CT-guided or EUS neurolytic coeliac plexus block are disappointing. The main analgesic method is the use of modern oral opiate preparations; neurolytic coeliac plexus block should be considered as complementary in selected cases. Radiation therapy may also significantly alleviate pain due to local invasion of pancreatic cancer.
  • Fat maldigestion may also contribute to abdominal pain, bloating and weight loss. Relief of biliary obstruction and pancreatic enzyme supplementation will alleviate these symptoms. Compared with untreated patients, patients with advanced pancreatic cancer who are given pancreatic enzyme supplements enjoy a better quality of life and improved symptom score.
  • Palliative stent placement- Metal stents should be used for patients with a good performance status and favourable prognosis (locally advanced primary tumour <3 cm) and plastic ones for those patients with metastases and tumours 3 cm in diameter. The cost of a plastic prosthesis is approximately 3% or 4% of the cost of a self expanding metal prosthesis.

What is the prognosis of pancreatic cancer?

Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months and 6–10 months for locally advanced disease, which increases to around 11–15 months with resectional surgery

What is the role of surveillance in high risk patients?

Some patients with pancreatic cancer have a family history of the disease. The best surveillance strategy for such patients is unknown. The optimal timing and frequency of screening for pancreatic cancer in individuals at risk is uncertain. The American Gastroenterological Association (AGA) recommends that screening begin at age 35 for those with hereditary pancreatitis, and 10 years before the age at which pancreatic cancer was first diagnosed in individuals with a positive family history. The AGA recommends the use of spiral CT and EUS.

Discuss peri-ampullary cancers?
In about 20% of cases it is not possible to distinguish the tissue of origin of cancers arising in the head of the pancreas, and the term “peri-ampullary cancer” is often applied.

  • Periampullary cancers can be broadly considered as those tumours arising out of or within 1 cm of the papilla of Vater and include ampullary, pancreatic, bile duct, and duodenal cancer. There is a high incidence of these tumours in patients with FAP.
  • Pancreatic ductal adenocarcinoma must be distinguished from carcinomas of the intrapancreatic bile duct, ampulla of Vater or duodenal mucosa as these tumours have a much better prognosis.

Ref

  1. British Society of Gastroenterology Guidelines for the Management of Patients with Pancreatic Cancer, Periampullary and Ampullary carcinomas
  2. Ghaneh P et al. Biology and management of pancreatic cancer. Gut. 2007; 56(8):1134-52.

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