Pancreatic cancer refers to malignant tumors originating from the ductal epithelium or acinar cells of the pancreas. It is characterized by high malignancy, an insidious onset, rapid progression, and poor prognosis. Early symptoms of pancreatic cancer are nonspecific, while advanced stages may present with abdominal discomfort or pain, weight loss, and gastrointestinal symptoms. By the time typical symptoms appear, the disease is often in its late stages, and treatment outcomes are generally unsatisfactory.
The incidence of pancreatic cancer is increasing worldwide, predominantly affecting individuals over 40 years old, with a slightly higher prevalence in males than females. The overall 5-year survival rate is approximately 10%.
Pathogenesis
The exact cause of pancreatic cancer remains unclear, but it is generally considered to result from the combined effects of genetic and environmental factors. High-risk factors and populations include:
- Long-term heavy smoking.
- Obesity.
- Chronic pancreatitis, particularly familial pancreatitis.
- Diabetes mellitus.
- Males and postmenopausal females.
- A family history of pancreatic cancer.
- Certain hereditary conditions, such as Peutz-Jeghers syndrome, familial atypical multiple mole-melanoma syndrome, autosomal recessive ataxia-telangiectasia, autosomal dominant mutations in the BRCA2 and PALB2 genes, Lynch syndrome, and familial adenomatous polyposis.
Pathological Anatomy and Pathophysiology
The majority (90%) of pancreatic cancers are ductal adenocarcinomas, most commonly located in the pancreatic head. These tumors can compress the bile duct, invade the duodenum, and obstruct the main pancreatic duct. The tumors are firm in texture, with gray-yellow cut surfaces, and may exhibit hemorrhage and necrosis. A minority of cases involve acinar cell carcinoma, which can occur in the head, body, or tail of the pancreas. These tumors are often lobulated, brown or yellow in color, soft in texture, and may show focal necrosis. Other rare pathological types include squamous cell carcinoma and cystadenocarcinoma.
Pancreatic cancer progresses rapidly and tends to metastasize early. Metastatic pathways include direct invasion, lymphatic spread, hematogenous dissemination, and perineural invasion. The cancer may directly invade the distal common bile duct, stomach, duodenum, left kidney, spleen, and adjacent major blood vessels. Lymphatic metastasis occurs to nearby organs and lymph nodes around the mesentery and aorta. Hematogenous metastasis involves the liver, lungs, bones, brain, and adrenal glands. Perineural invasion may infiltrate or compress nearby nerves, such as those in the duodenum, pancreas, and gallbladder wall.
Clinical Manifestations
Pancreatic cancer has an insidious onset, a short course, and rapid progression. By the time significant symptoms appear, the disease is often in an advanced stage.
Abdominal Discomfort or Pain
This is often the initial symptom. Most patients experience abdominal discomfort or pain, which worsens after eating or when lying supine, and may be relieved by bending forward or curling the knees. In advanced stages, tumor invasion of the celiac plexus can cause persistent, severe abdominal pain and/or back pain.
Weight Loss
Weight loss may occur even in the early stages, often accompanied by fatigue. In late stages, patients frequently present with cachexia.
Gastrointestinal Symptoms
Tumor obstruction of the distal common bile duct and pancreatic duct prevents bile and pancreatic juice from entering the duodenum, leading to symptoms of indigestion. In advanced stages, tumor invasion of the stomach and duodenal wall may result in gastrointestinal obstruction and/or bleeding.
Jaundice
Approximately 90% of patients present with jaundice.
Symptomatic Diabetes Mellitus
Around 50% of patients are diagnosed with diabetes at the time of pancreatic cancer diagnosis. A minority may develop diabetes symptoms in the early stages, or pre-existing diabetes symptoms may suddenly worsen.
Psychological Symptoms
Some patients develop anxiety and/or depression.
Other Symptoms
Some patients exhibit persistent or intermittent low-grade fever, migratory thrombophlebitis, or arterial thrombosis.
Auxiliary Examinations
Laboratory Tests
Blood Biochemistry Tests
In the early stages, there are no specific abnormalities. When the tumor obstructs the pancreatic duct, transient elevations in blood amylase, fasting and/or postprandial blood glucose levels, and abnormal glucose tolerance tests may occur. Liver involvement or bile duct obstruction can lead to elevated alanine transaminase (ALT), aspartate transaminase (AST), bile acids, and bilirubin levels.
Tumor Marker Tests
Levels of CA19-9 are often elevated and can serve as an important tool for auxiliary diagnosis, treatment evaluation, and recurrence monitoring. In patients who do not express CA19-9, other tumor markers such as CA125 and/or CEA may be used as supplementary diagnostic tools.
Imaging Examinations
Abdominal Ultrasound
This is widely used for pancreatic cancer screening but susceptible to interference from gastrointestinal gas and the operator's level of experience.
CT Scanning
Non-contrast CT often shows hypodense or isodense changes, while contrast-enhanced CT typically reveals marked hypodense changes. CT can also demonstrate the relationship between the tumor and surrounding structures, as well as assess vascular involvement.
MRI
MRI may show slightly hypointense T1 and slightly hyperintense T2 signals with unclear boundaries and irregular shapes. Diffusion-weighted imaging (DWI) shows hyperintense signals, while apparent diffusion coefficient (ADC) signals are reduced. Dynamic contrast-enhanced scans reveal lower enhancement in the arterial phase compared to surrounding pancreatic tissue. MRI can evaluate tumor infiltration into surrounding tissues, vascular involvement, and lymph node metastasis.
Endoscopic Ultrasound (EUS)
EUS provides clearer images than abdominal ultrasound, showing localized hypoechoic areas with heterogeneous echoes and irregular margins. EUS-guided fine-needle aspiration (EUS-FNA) can obtain tissue samples for histopathological analysis, improving tumor detection rates.
Endoscopic Retrograde Cholangiopancreatography (ERCP)
ERCP findings include narrowing, dilation, obstruction, and distortion of the main pancreatic duct and its major branches. It also allows for cytological or histopathological examination of pancreatic juice or bile.
Magnetic Resonance Cholangiopancreatography (MRCP)
MRCP provides clear visualization of the pancreatic and biliary duct systems without the need for contrast agents.
Histopathological and Cytological Examinations\
Tissue and cytological samples can be obtained through EUS-FNA, CT- or ultrasound-guided percutaneous fine-needle aspiration biopsy, or intraoperative biopsy during exploratory laparotomy.
Diagnosis and Differential Diagnosis
Early diagnosis of pancreatic cancer is challenging. By the time patients present with significant symptoms such as upper abdominal pain, progressive weight loss, loss of appetite, or jaundice, or when imaging reveals signs of pancreatic cancer, most cases are already in advanced stages.
The clinical manifestations of pancreatic cancer lack specificity and need to be differentiated from conditions such as chronic pancreatitis, ampullary carcinoma, and cholangiocarcinoma.
Chronic Pancreatitis
Chronic pancreatitis typically follows a chronic course with a history of recurrent acute episodes. Diarrhea, particularly steatorrhea, is more prominent, while jaundice is rare. Imaging may reveal pancreatic calcifications. EUS-FNA can aid in establishing the diagnosis.
Ampullary Carcinoma
Jaundice occurs early and may fluctuate. Stool occult blood tests are often positive. Endoscopic examination may reveal a cauliflower-like mass at the duodenal papilla.
Cholangiocarcinoma
Cholangiocarcinoma is highly malignant. When the tumor causes narrowing or obstruction of the common bile duct, jaundice progressively worsens, often accompanied by clay-colored stools.
Treatment
A multidisciplinary treatment (MDT) approach is currently recommended for pancreatic cancer. Common treatment modalities include surgery, chemotherapy, radiotherapy, interventional therapy, and supportive care.
Surgical Treatment
Early surgical resection is the only effective method for achieving a cure and long-term survival in patients with pancreatic cancer. The main surgical procedures include pancreaticoduodenectomy (Whipple procedure) and distal pancreatectomy with splenectomy.
Chemotherapy
Chemotherapy can be applied to patients at different stages of pancreatic cancer. Commonly used drugs include 5-fluorouracil, gemcitabine, and albumin-bound paclitaxel.
Radiotherapy
Radiotherapy is an important local treatment option for pancreatic cancer. It can be used in patients with unresectable pancreatic cancer, as neoadjuvant therapy for borderline resectable cases, or in the treatment of locally advanced pancreatic cancer.
Interventional Therapy
Interventional therapies include intra-arterial infusion chemotherapy, ablative therapy, percutaneous transhepatic biliary drainage, biliary stent placement, gastrointestinal stent placement, embolization for bleeding, and celiac plexus block for cancer-related pain management.
Supportive Care
Supportive care mainly focuses on pain relief and nutritional improvement, aiming to prevent or alleviate related clinical symptoms and enhance the quality of life for patients.
Prognosis
Pancreatic cancer has a poor prognosis, with an overall 5-year survival rate of approximately 10% and a median survival time of about 3 to 6 months. The 5-year survival rate after surgery is only around 20%.
Prevention
Primary prevention of pancreatic cancer involves addressing high-risk factors. Secondary prevention focuses on early detection, diagnosis, and treatment in high-risk populations. Tertiary prevention emphasizes the implementation of active and effective treatment measures to prolong survival and improve quality of life for patients.