Makindo Medical Notes

Related Subjects: |Neutropenic Sepsis |Oncological emergencies |Spinal Cord Compression |Brain Tumours |Cancer of Unknown Primary |Head and Neck Cancers |Colorectal cancer |Colorectal polyps |Cancer Frequency and Red flags |Pancreatic Cancer

Pancreatic cancer is challenging to diagnose early due to its deep anatomical location and vague symptoms. Diagnosis is often delayed unless a periampullary lesion causes jaundice. It is important to note that a normal abdominal ultrasound (USS) does not rule out pancreatic cancer.

About

• Most patients present with advanced, incurable disease by the time of diagnosis.
• Cancers of the ampulla often present earlier with symptoms of obstructive jaundice.
• Periampullary and endocrine tumours tend to have a better prognosis compared to ductal adenocarcinomas.

Risk Factors

• Smoking: A major risk factor for pancreatic cancer.
• Alcohol consumption.
• High coffee intake has been suggested as a possible risk factor, although evidence is inconclusive.
• Obesity and chronic pancreatitis are also associated with an increased risk.

Genetic Risk Factors: Applicable in a amall minority of cases

While most cases of pancreatic cancer are sporadic, a small percentage have a genetic component:

• BRCA2 mutation: Individuals with this mutation have a higher risk of developing pancreatic cancer.
• Familial atypical multiple mole melanoma (CDKN2A): Associated with both melanoma and pancreatic cancer.
• Peutz-Jeghers syndrome: Characterized by gastrointestinal polyps and increased cancer risks, including pancreatic cancer.
• Von Hippel-Lindau disease: Linked to various types of tumours, including pancreatic neuroendocrine tumours.
• Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP): Both syndromes increase the risk of pancreatic cancer.
• Multiple Endocrine Neoplasia (MEN) syndrome: A rare genetic condition that increases the risk of pancreatic neuroendocrine tumours.

Pathology

• Location: 70% of tumours occur in the head or neck of the pancreas (periampullary region), 20% in the body, and 10% in the tail.
• Spread: Pancreatic cancer typically spreads locally along the pancreatic duct, into the duodenum, local lymph nodes, portal vein, nerve sheaths, and eventually to the liver.

Histology

• Ductal adenocarcinoma: The most common type of pancreatic cancer.
• Adenosquamous carcinoma: A rare variant with both glandular and squamous cell features.
• Mucinous cystadenocarcinoma: A cystic form of cancer, often arising from premalignant mucinous cystic neoplasms.
• Neuroendocrine tumours: Insulinomas, glucagonomas, and gastrinomas, which have distinct clinical features and better prognosis than ductal adenocarcinomas.

Clinical Presentation

• Anorexia and weight loss: Unexplained weight loss is a common symptom.
• Painless jaundice: Caused by bile duct obstruction, typically with periampullary tumours. Courvoisier’s law may apply (painless jaundice with a palpable gallbladder suggests malignancy).
• Pancreatitis: New or recurrent pancreatitis, particularly in younger patients without obvious cause, may be a red flag.
• Venous thrombosis: Patients may present with deep vein thrombosis (DVT) or pulmonary embolism (PE).
• Migratory thrombophlebitis (Trousseau’s sign): A clinical marker of malignancy, especially pancreatic cancer.
• Secondary diabetes: New-onset diabetes, particularly in older adults, can be a sign of pancreatic cancer.
• Upper abdominal pain and backache: Pain radiating to the back, especially without gallstones or with normal upper GI investigations, should raise suspicion.
• Unexplained pancreatitis or new diabetes with upper GI symptoms should be further investigated.

Investigations

• FBC and U&E: May show anaemia and electrolyte disturbances.
• Liver function tests (LFTs): Raised alkaline phosphatase (ALP), elevated bilirubin, and possibly an increased prothrombin time suggest biliary obstruction.
• Tumor markers: CA19-9 and CEA are often elevated, but these are non-specific and should not be used alone for diagnosis.
• Ultrasound (USS): May reveal biliary obstruction or a mass in the head of the pancreas but is often poor at visualizing the retroperitoneal pancreas. A normal USS does not exclude pancreatic cancer.
• Endoscopic retrograde cholangiopancreatography (ERCP): The investigation of choice in cases of jaundice, allowing for diagnostic brushing, biopsy, and placement of a biliary stent.
• Contrast-enhanced CT scan: Useful for determining operability and staging the cancer. It provides detailed imaging of the pancreas and surrounding structures.
• Percutaneous biopsy: May be performed if imaging is inconclusive, but there is a risk of seeding cancer cells along the biopsy tract.
• Histological confirmation: Biopsy is essential to differentiate pancreatic cancer from lymphoma or neuroendocrine tumours, which have different treatments and prognoses.

Complications

• Obstructive jaundice and pruritus: Often relieved by stenting or surgical bypass.
• Duodenal obstruction: Stenting or surgical bypass may be required for relief.
• Venous thromboembolism: High risk of DVT and pulmonary embolism.
• Significant pain: Pain control may require narcotics, radiotherapy, or coeliac plexus block.
• Splenic vein thrombosis: Can lead to gastric varices and gastrointestinal bleeding.
• Cholangitis: Infection of the biliary tract due to bile duct obstruction.
• Malignant ascites: Fluid accumulation in the abdomen due to peritoneal spread.
• Secondary diabetes: Often results from pancreatic insufficiency.
• Surgical complications: Hemorrhage, infection, or anastomotic leaks following surgery.

Management

• Surgical resection: Only a small percentage of patients are candidates for surgery. A Pancreaticoduodenectomy (Whipple’s procedure) is the preferred surgery for tumours in the head of the pancreas. It involves removal of the head of the pancreas, part of the duodenum, stomach, and bile duct, followed by reconstruction.
• Advanced tumours: Tumors of the body and tail often present late, and the resection rate is low.
• Preoperative management: Vitamin K is administered to correct clotting abnormalities, and low molecular weight heparin (LMWH) is used to reduce the risk of venous thromboembolism.
• Palliative chemotherapy: Can prolong survival in advanced cases but is not curative.
• Palliation of symptoms: ERCP with stenting or choledochojejunostomy can relieve biliary obstruction. Gastrojejunostomy can be performed for duodenal obstruction. Pain relief may require radiotherapy or a coeliac plexus block.
• Prognosis: The prognosis is generally very poor, with a median survival of less than 12 months in most cases.