Pancreatic cancer was first described by Mondiare and Battersdy. In 1888, Bard and Pis published a clinical report in the literature. In 1935, the renowned American surgeon Whipple first reported the successful pancreaticoduodenectomy, establishing the surgical approach for treating malignant tumors of the pancreas, duodenum, and ampulla. In 1943, Rockeg performed the first total pancreatectomy. In China, Yu Wenguang reported the first case of pancreaticoduodenectomy in 1954. In recent years, the incidence of pancreatic cancer has been rising annually. In the United States, the incidence rate in 1988 was 9.0 per 100,000, with a male-to-female ratio of 1.3:1, predominantly affecting individuals over 45 years old. Sweden has a relatively high incidence rate of 125 per 100,000, which has remained stable over the past 20 years. The rates in the UK and Norway have each doubled. Compared to the 1960s, the standardized incidence rates in Canada, Denmark, and Poland increased by over 50% in the 1970s. In China, pancreatic cancer has become one of the top ten malignant tumors causing death. The number of pancreatic cancer patients admitted to Peking Union Medical College Hospital in recent years has increased five to sixfold compared to the 1950s. Moreover, an analysis of 354 cases from seven hospitals in Beijing showed that 80% of patients were aged 41–70. In recent years, there has been a noticeable increase in younger pancreatic cancer patients compared to a decade ago, with higher malignancy and poorer prognosis. Regarding the location of pancreatic cancer, the head of the pancreas remains the most common site, accounting for about 70%, followed by the body and then the tail. Some cases involve the entire pancreas, classified as diffuse or multicentric lesions.

Currently, the exact cause of pancreatic cancer remains unclear, but several environmental factors have been identified as being associated with its development. The primary established risk factor is smoking. Smokers have a relative risk of developing pancreatic cancer that is 1.5 times higher than non-smokers, and this risk increases with the amount of smoking. Other significant risk factors include diabetes, gallbladder stones, alcohol consumption (including beer), and chronic pancreatitis. Additionally, a diet high in fat and protein, consumption of refined flour products, and having undergone a gastrectomy 20 years prior are also considered risk factors for pancreatic cancer.

bubble_chart Pathological Changes

Pancreatic cancer has an extremely high mortality rate, likely due to its insidious and concealed onset, often diagnosed at an advanced stage. Early metastasis to regional lymph nodes (90%) is common, and it can even spread to mediastinal and supraclavicular lymph nodes. At diagnosis, over half of patients already have liver metastases, more than a quarter have peritoneal seeding, and one-third have duodenal invasion with potential ulceration. The most common histological type of pancreatic cancer is ductal cell carcinoma, accounting for about 90%. There is no unified histological classification system, but the following categories can serve as a reference: ① Ductal cell carcinoma: including papillary adenocarcinoma, tubular adenocarcinoma, cystadenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, mucinous carcinoma, etc.; ② Acinar cell carcinoma; ③ Islet cell carcinoma; ④ Others, such as undifferentiated carcinoma, pancreatoblastoma, and carcinosarcoma.

(1) Upper abdominal discomfort and dull pain are the most common initial symptoms of pancreatic cancer. The tumor often causes obstruction of the pancreatic or bile ducts. Even if jaundice has not yet occurred, the impaired excretion of bile leads to increased pressure in the biliary tract, resulting in varying degrees of dilation of the bile ducts and gallbladder. Patients may experience abdominal discomfort and dull pain. It was previously emphasized that the typical symptom of pancreatic head cancer is painless jaundice, but in reality, painless jaundice as the initial symptom occurs in only 10–30% of patients. Abdominal pain is still a very common symptom in patients with pancreatic head cancer. As for pancreatic body and tail cancer, the incidence of abdominal pain is even higher, and it may manifest as significant upper abdominal pain and back pain due to involvement of the celiac plexus. The appearance of these symptoms often indicates that the disease has entered an advanced stage.

(2) Loss of appetite and weight loss are also common manifestations of pancreatic cancer. The tumor often obstructs the excretion of pancreatic juice and bile, thereby affecting the patient's appetite and causing malabsorption, leading to significant weight loss.

(3) Obstructive jaundice is a prominent feature of pancreatic head cancer. If the tumor is located near the ampulla of Vater, jaundice may appear earlier. The jaundice is usually persistent and progressively worsens. Stool color becomes lighter, even clay-colored. The skin takes on a brown or bronze hue, accompanied by cutaneous pruritus.

(4) In addition to causing obstructive jaundice, pancreatic head cancer often leads to gallbladder enlargement, which can be clearly palpated in the right upper abdomen. Obstructive jaundice accompanied by gallbladder enlargement often suggests the possibility of a periampullary tumor.

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bubble_chart Diagnosis

In addition to paying attention to the above clinical manifestations, the following auxiliary diagnostic measures can be selected.

(1) Laboratory Tests: Serum bilirubin is significantly elevated, sometimes exceeding 342 μmol/L, with direct bilirubin being the predominant component. Blood alkaline phosphatase levels are also markedly elevated. The urine bilirubin test is positive or strongly positive. Blood amylase measurement may show transient elevation in a few early-stage pancreatic cancers due to pancreatic duct obstruction; in the late stage [third stage], pancreatic tissue atrophy occurs, and blood amylase levels remain unchanged. Patients with pancreatic cancer may exhibit elevated fasting blood glucose, with a high positive rate in glucose tolerance tests. Carcinoembryonic antigen (CEA) measurement shows elevation in about 70% of pancreatic cancer patients, but it is not specific. The gastrointestinal cancer-associated antigen CA19-9 is considered an indicator for diagnosing pancreatic cancer.

(2) B-mode Ultrasound: Direct imaging of pancreatic cancer may reveal hypoechoic tumors, while indirect findings often serve as clues for detecting small pancreas cancer
, such as dilated pancreatic ducts or bile ducts. In addition to the main pancreatic duct, careful observation of its branches is necessary. Some small pancreas cancers may first cause localized dilation of pancreatic duct branches, such as dilation of the uncinate process duct. Endoscopic ultrasonography, with the probe scanning the pancreatic body, tail, and head through the stomach and duodenal walls without interference from gastrointestinal gas, can clearly delineate pancreatic structures and detect early lesions.

(3) CT Scan: CT scans can accurately display the location, size of pancreatic masses, and their relationship with surrounding blood vessels. However, imaging changes may not be detected in about one-third of pancreatic masses <2 cm, aside from the high cost factor. CT scans should be considered the primary method for diagnosing pancreatic cancer currently. CT images of pancreatic cancer include: ① Pancreatic masses appearing as generalized or localized tumors. The center of the mass may have irregular, poorly defined low-density areas; if the low-density area is large, it may indicate tumor necrosis or liquefaction. ② Invasion or compression of the bile duct or pancreatic duct by the tumor may cause dilation. ③ The tumor may invade the retroperitoneal fat layer and encase the superior mesenteric vessels or inferior vena cava.

(4) Magnetic Resonance Imaging (MRI): MRI can reveal abnormal pancreatic contours. Based on signal intensity in T1-weighted images, early local invasion and metastasis can be assessed. For evaluating pancreatic cancer, especially small pancreas cancer confined to the pancreas, as well as peripancreatic spread and vascular invasion, MRI is superior to CT scans and serves as a better preoperative predictive method for pancreatic cancer. However, it is expensive.

(5) Endoscopic Retrograde Cholangiopancreatography (ERCP): ERCP can simultaneously display the pancreatic duct, bile duct, and ampulla, making it valuable for diagnosing obstructive jaundice of unknown cause. Additionally, it allows direct observation of the duodenal papilla and collection of pancreatic fluid for cytological examination. However, performing ERCP in cases of existing obstructive jaundice carries the risk of biliary tract infection, so the quantity, speed, and pressure of contrast agent injection must be carefully controlled. ERCP findings for pancreatic cancer include: ① Irregular narrowing or obstruction of the main pancreatic duct, with a rat-tail-shaped cutoff at the end. ② Destruction, rupture, sparsity, or displacement of main pancreatic duct branches. ③ Contrast agent leakage into the tumor area. ④ The common bile duct may show encasement, narrowing, or obstruction; if accompanied by pancreatic duct narrowing or obstruction, it presents as a "double duct sign."

(6) Gastrointestinal Barium Meal Examination (GI): The diagnostic value of conventional GI for pancreatic cancer is limited. In advanced-stage pancreatic head cancer, the duodenal loop may enlarge or exhibit an inverted "3" shape. Hypotonic GI examination relaxes duodenal smooth muscle and reduces peristalsis, facilitating observation of changes in the duodenal mucosa, such as texture disorder, mucosal interruption, and wall rigidity.

(7) Cytological Examination Currently, it is widely recommended to perform preoperative fine-needle aspiration cytology (FNAC) of pancreatic masses under B-ultrasound or CT guidance. This method holds high diagnostic value for pancreatic cancer and is a simple, safe, and effective approach. Its primary diagnostic role lies in confirming the diagnosis for advanced-stage patients who are ineligible for surgery. Fine-needle aspiration cytology can also be applied intraoperatively and may replace pancreatic biopsy, thereby avoiding complications such as bleeding, pancreatic fistula, and acute pancreatitis caused by biopsy. IV. Early Diagnosis of Pancreatic Cancer The early detection and diagnosis of pancreatic cancer have long been subjects of ongoing exploration and efforts to find solutions. The author believes that the following aspects should be addressed to achieve this goal.

bubble_chart Treatment Measures

(1) Perioperative Management Patients with pancreatic cancer often have poor overall condition, and radical surgery, especially pancreaticoduodenectomy, is highly traumatic, involves significant blood loss, has numerous complications, and carries a high surgical mortality rate. Therefore, proper and proactive perioperative management is crucial.

1. Preoperative Improvement of the Patient’s General Condition

(1) Enhanced nutrition and correction of hypoalbuminemia: A diet high in protein, carbohydrates, and vitamins but low in fat is recommended, supplemented with digestive aids such as pancreatic enzymes. (2) Maintain fluid and electrolyte balance. (3) Supplement vitamin K: Patients often have varying degrees of liver dysfunction. Those with grade III obstructive jaundice cannot absorb fat-soluble vitamin K normally due to the absence of bile entering the intestines, leading to insufficient prothrombin synthesis. Thus, vitamin K injections should be administered from admission until surgery, alongside liver-protective therapy. (4) Control diabetes: The incidence of diabetes in pancreatic cancer patients is much higher than in the general population. Once confirmed, regular insulin should be used to maintain blood glucose levels between 7.2–8.9 mmol/L and urine glucose within the (+) to (−) range.

2. Preoperative Biliary Decompression: Biliary obstruction caused by pancreatic cancer does not routinely require decompression. For patients with short-term jaundice, relatively good overall condition, and normal digestive function, coagulation mechanism, and kidney function, initial-stage [first-stage] pancreaticoduodenectomy can be performed without decompression. However, decompression should be considered for patients with poor general condition, bilirubin levels above 342 μmol/L, negative fecal urobilinogen, jaundice lasting over two weeks with worsening symptoms, and signs of impending renal insufficiency. Specific methods include cholecystostomy, PTCD, nasobiliary drainage via duodenoscopy, or biliary-enteric drainage.

3. Prevention of Postoperative Complications

(1) Prophylactic use of antibiotics: If there is no infection preoperatively, antibiotics need not be administered too early. A single dose of broad-spectrum antibiotics should be given intravenously 30 minutes before surgery. An additional dose is required if the surgery exceeds four hours.

(2) Respiratory preparation: Postoperative pulmonary complications are quite common in pancreatic cancer patients, so preventive measures should be taken preoperatively. Strict smoking cessation is advised, ideally for more than two weeks. Training patients in deep thoracic breathing exercises helps prevent postoperative alveolar collapse, pulmonary infections, and hypoxemia. These measures are simple and effective but often overlooked by doctors.

4. Enhanced Intraoperative Management: During surgery, stable blood pressure, adequate oxygenation, relaxed abdominal muscles, and effective analgesia must be maintained. Blood glucose and urine glucose should be monitored and kept within reasonable limits. Pancreatic cancer patients often have underlying coagulation deficiencies. Significant intraoperative blood loss and massive transfusions may lead to coagulation disorders. In addition to meticulous surgical techniques to minimize bleeding, fresh blood (within three days) should be transfused whenever possible, avoiding blood stored for over a week.

5. Postoperative Management

(1) Continue antibiotic therapy.

(2) Prevent pancreatic fistula: In addition to proper management of pancreatic duct and abdominal drainage, octreotide (a somatostatin analog) can be used to inhibit pancreatic secretion, significantly reducing the risk of pancreatic fistula.

(3) Provide appropriate nutritional support.

(4) Emphasize drainage tube management: Closely monitor gastric, biliary, pancreatic duct, and abdominal drainage, ensuring patency. Accurately record drainage volume and observe changes in its characteristics, addressing any issues promptly.

(2) Surgical Resection Surgical treatment is the mainstay for pancreatic cancer, but many patients present at an advanced stage and are ineligible for radical resection. The resection rate for pancreatic head cancer is around 15%, while for pancreatic body and tail cancer, it is even lower, below 5%. Common surgical procedures for pancreatic cancer include the following.

1. Pancreaticoduodenectomy (PD): This is the preferred radical resection procedure for pancreatic head cancer, first pioneered by Whipple in 1935. Although many scholars have made numerous reforms regarding post-resection digestive tract reconstruction over the next 50 years, pancreaticoduodenectomy is still commonly referred to as the Whipple procedure to this day.

Indications: Patients with good general condition, age <70 years, no liver metastasis, no ascites, and pancreatic head cancer without infiltration of surrounding blood vessels are all suitable for PD.

2. Total Pancreatectomy (TP): Indications: Cancer involving the entire pancreas without liver metastasis or peritoneal seeding is an absolute indication for total pancreatectomy. The advantages of total pancreatectomy include not only the complete removal of multiple pancreatic lesions but also facilitating more thorough clearance of peripancreatic lymph nodes. After total pancreatectomy, there is no need for pancreaticojejunal anastomosis, completely avoiding pancreatic fistula. However, total pancreatectomy also presents several issues, such as secondary diabetes and digestive malabsorption, requiring lifelong insulin and digestive enzyme therapy. Therefore, strict adherence to indications is necessary. Thus, the decision to perform TP should not be based solely on the local pancreatic condition but must also consider the patient’s

understanding of the disease, whether the patient and family fully comprehend postoperative diabetes, the ability to self-administer insulin, whether family members can assist in diabetes management, and financial circumstances. Only when these conditions are met can TP be considered.

3. Distal Pancreatectomy (DP): Suitable for pancreatic body or tail cancer without metastasis. The procedure involves en bloc resection of the spleen, pancreatic body and tail tumor, and surrounding lymph nodes. The operation is technically simple, with fewer complications and low surgical mortality. Pancreatic body or tail cancer is often diagnosed only when abdominal masses or back pain occur, usually at an advanced stage. Fewer than 5% of cases are eligible for radical resection. Due to extrapancreatic metastasis at the time of resection, postoperative survival is often less than one year.

4. Pylorus-Preserving Pancreaticoduodenectomy (PPPD): PPPD is only suitable for ampullary cancer, small pancreatic head cancer, without direct cancer infiltration of the duodenal bulb or gastric pylorus, and no metastasis to perigastric lymph nodes.

(3) Palliative Bypass Surgery for Unresectable Pancreatic Cancer Due to the difficulty in early diagnosis of pancreatic cancer and the low rate of radical resection, a significant number of cases require certain surgical procedures to alleviate symptoms. The choice of biliary-enteric bypass depends on the tumor location. For tumors at the distal bile duct, either choledochojejunostomy or cholecystojejunostomy can be performed, preferably using a Roux-en-Y loop to reduce retrograde infection. As long as the bile duct is significantly dilated, even if it contains "white bile," it does not hinder postoperative jaundice relief. If the tumor is near the bile duct entrance into the pancreas, a side-to-end choledochojejunostomy with a Roux-en-Y loop is preferred to prevent tumor progression along the common bile duct to the cystic duct opening, rendering the bypass ineffective. Additionally, if the tumor is considered advanced with an expected survival of less than one year, a simpler biliary-enteric drainage—such as a hepatic duct T-tube bridging jejunostomy—can be performed. This involves placing a T-tube into the common hepatic duct, passing it through the transverse mesocolon into the jejunum 20 cm distal to the ligament of Treitz, and securing it properly. The advantages of this procedure are: ① simplicity and ease of execution; ② effective jaundice relief. Bile flow through the T-tube stimulates the jejunum, promoting early peristalsis and accelerating bile drainage via siphon action, aiding digestion and absorption. By the time long-term foreign body effects arise, the patient would likely have succumbed to tumor progression. As for gastrojejunostomy, the indications are: ① clinical symptoms or signs of duodenal obstruction; ② radiographic or endoscopic evidence of duodenal stenosis, rigidity, or cancerous infiltration; ③ intraoperative findings of duodenal stenosis or compression.

(4) Radiation Therapy The tumoricidal dose for pancreatic cancer is relatively high, while the radiation tolerance of surrounding organs such as the stomach, small intestine, liver, kidneys, and spinal cord is relatively low, posing challenges for radiotherapy. In recent years, with the development of intraoperative radiation therapy and multi-field external beam radiotherapy under CT-guided precise planning, radiation therapy has become one of the primary treatment modalities for pancreatic cancer.

Intraoperative radiotherapy uses 10-20MV high-energy electron beams. After fully exposing the tumor mass and removing as much tumor tissue as possible while displacing surrounding normal tissues, the corresponding applicator is accurately positioned on the tumor. A single large dose of 15-25Gy is delivered during surgery, with an irradiation time of approximately 4-6 minutes. External radiotherapy is mainly used preoperatively and postoperatively (including supplemental external radiotherapy after intraoperative irradiation), and also serves as palliative treatment for advanced-stage pancreatic cancer that is no longer suitable for surgery. CT-based precise localization is used to develop radiation therapy plans, ensuring high-dose irradiation to the pancreatic cancer site while providing better protection to surrounding normal tissues. Using 10MV X-rays, anterior abdominal field plus bilateral field isocentric irradiation is performed, delivering 180-200cGy per fraction, 5 fractions per week, with a total dose of 40-60Gy over 4-6 weeks. Treatment can be administered continuously or in divided courses.

(5) Chemotherapy The issue of chemotherapy for pancreatic cancer has not received sufficient attention from clinicians for a long time. Compared to other tumors, the effectiveness of chemotherapy for pancreatic cancer is unsatisfactory, mainly due to two reasons: on one hand, the biological characteristics of the tumor make it less sensitive to chemotherapy, and the lack of ideal observation indicators in research has led to limited interest among clinicians. On the other hand, pancreatic cancer patients often experience nausea, vomiting, anorexia, weight loss, and malabsorption, making it difficult for them to tolerate systemic chemotherapy.

1. Systemic Chemotherapy for Pancreatic Cancer: Many literature reports have documented clinical trials of combination chemotherapy for pancreatic cancer. The more effective combination chemotherapy regimens include: 5-Fu + MMC, 5-Fu + MMC + Streptozotocin, and 5-Fu + ADM + MMC. The response rates for these combination therapies can reach around 40%, significantly higher than single-agent chemotherapy, and patient survival is notably prolonged. MFA regimen usage:

MMC 10mg/m ² , IV on day 1;

5-Fu 600mg/m ² , IV infusion on days 1, 8, 29, and 36;

ADM 30mg/m ² , IV on days 1 and 29.

Repeat at week 9. Efficacy: CR + PR is 39%.

2. Regional Chemotherapy for Pancreatic Cancer: Regional chemotherapy for pancreatic cancer involves administering high-dose chemotherapy drugs through the main blood supply to the pancreas. The theoretical basis includes: ① The poor efficacy of systemic chemotherapy may be due to the limited amount of drugs reaching pancreatic cancer tissue, whereas regional chemotherapy allows high concentrations of drugs to directly target the tumor. ② Systemic chemotherapy is limited by the systemic toxic side effects of the drugs, whereas regional chemotherapy primarily acts on the pancreatic cancer tissue, significantly reducing systemic toxicity and allowing for increased drug dosages. In summary, regional chemotherapy enables more targeted drug delivery, increases the dosage of chemotherapy drugs, enhances therapeutic efficacy, and significantly reduces toxic side effects.

bubble_chart Prevention

The early detection and diagnosis of pancreatic cancer have always been issues that people strive to explore and resolve. The author believes that the following aspects of work should be addressed.

(1) Doctors should identify suspicious individuals, i.e., high-risk groups, among the general population. This is a very challenging task because patients exhibit neither specific symptoms nor specific signs, relying entirely on the doctor's high vigilance. Doctors must be "attentive." The symptoms patients can provide include only upper abdominal distension and fullness, sometimes with a sensation of bloating surpassing pain, along with other nonspecific symptoms such as indigestion, weight loss, and "sudden-onset diabetes." When clinicians cannot find other diseases to explain these symptoms, and after symptomatic treatment, these symptoms either fail to improve or worsen, clinicians should boldly suspect pancreatic cancer.

(2) Popularize cancer prevention knowledge, conduct regular routine physical examinations, and implement secondary prevention.

(3) Conduct modern high-tech investigations for high-risk individuals, such as the comprehensive application of B-ultrasound, ERCP, MRI, selective abdominal angiography, and the recently developed cancer gene testing.