Pancreatic Cancer Treatment

I. Overview
Cancer of the pancreas is a common pancreatic tumor with a high degree of malignancy, and in recent years, its incidence has been on the rise both at home and abroad. More than half of pancreatic cancers are located in the head of pancreas, and about 90% are ductal adenocarcinomas originating from the epithelium of the ducts.
In order to further standardize the diagnosis and treatment of pancreatic cancer in China, improve the level of pancreatic cancer treatment in medical institutions, improve the prognosis of pancreatic cancer patients, and protect medical quality and medical safety, this specification is formulated.
Diagnostic techniques and applications
(A) High risk factors. Old age, history of smoking, high-fat diet, and overweight body mass index are risk factors for pancreatic cancer, and exposure to chemicals such as beta-naphthylamine and benzidine can lead to increased incidence.
(II) Clinical manifestations.
1. Most patients with pancreatic cancer lack specific symptoms and initially present only with upper abdominal discomfort and vague pain, which are easily confused with other digestive system diseases. When patients have pain in the lower back, the tumor invades the retroperitoneal plexus, which is an advanced manifestation.
2. 80-90% of pancreatic cancer patients have wasting and weight loss in the early stage of the disease.
3.Symptoms such as indigestion, vomiting and diarrhea often appear.
4.Patients over 40 years old with any of the following symptoms should be highly suspected of pancreatic cancer, and if they are smokers, they should pay more attention to.
(1) Obstructive jaundice of unknown origin.
(2) Recent unexplained weight loss >10%.
(3) Recent unexplained epigastric or low back pain.
(4) Recent vague and unexplained dyspepsia with normal endoscopy.
(5) Sudden onset of diabetes without predisposing factors, such as family history, obesity.
(6) Sudden onset of unexplained steatorrhea.
(7) Episodes of spontaneous pancreatitis.
(3) Physical examination.
1. Patients with pancreatic cancer lack specific physical signs at the early stage of the lesion, and most of them are in the progressive or advanced stage when the signs appear.
2. Jaundice. Jaundice is a common physical sign of pancreatic head cancer patients, which is manifested as yellowing of skin and mucous membrane all over the body, whitening of stool, yellowing of urine and itching of skin.
3.Abdominal mass. Patients with pancreatic cancer with palpable abdominal masses are mostly in advanced stages and rarely can be removed by radical surgery.
(D) Imaging examination.
1.B-type ultrasonography: It is the first choice for pancreatic cancer diagnosis. It is easy to operate, non-invasive, non-radioactive, and can be observed in multiple axes, and can better show the internal structure of the pancreas, whether there is obstruction in the bile duct, the site of obstruction, and the cause of obstruction. The limitation is that the field of view is small, and it is sometimes difficult to observe the pancreas, especially the tail of the pancreas, due to the influence of gas and body size in the stomach and intestinal tract.
2.CT examination: It is the best non-invasive imaging examination method to examine the pancreas and is mainly used for the diagnosis and staging of pancreatic cancer. Plain scan can show the size and location of the lesion, but it cannot accurately diagnose the pancreatic lesion qualitatively, and the relationship between the tumor and the surrounding structures is poor. Enhancement scan can better show the size, location, morphology, internal structure and relationship with surrounding structures of the pancreatic mass. It can accurately determine the presence of liver metastasis and show enlarged lymph nodes.
3.MRI and magnetic resonance pancreaticobiliary imaging (MRCP) examination: it is not used as the first choice method to diagnose pancreatic cancer, but when patients are allergic to CT-enhanced contrast agent, MR can be used instead of CT scan for diagnosis and clinical staging; in addition, MRCP has obvious advantages for the presence or absence of biliary tract obstruction and the site and cause of obstruction, and it is safe compared with ERCP and PTC, and for pancreatic head cancer. MR can be a useful supplement to CT scan.
4.Upper gastrointestinal tract imaging: It can only show indirect signs caused by compression and invasion of the gastrointestinal tract by some advanced pancreatic cancer and is not specific. At present, it has been replaced by cross-sectional imaging.
(E) Blood immunobiochemical examination.
1. Blood biochemical examination: There is no specific blood biochemical change in the early stage, but the obstruction of bile ducts by tumor may cause elevation of blood bilirubin, accompanied by enzymatic changes such as glutamic aminotransferase and glutamic oxalacetic aminotransferase. Forty percent of pancreatic cancer patients have elevated blood glucose and abnormal glucose tolerance.
2. Blood tumor markers: CEA and CA19-9 are elevated in the serum of pancreatic cancer.
(F) Histopathological and cytological diagnosis. Histopathological or cytological examination can determine the diagnosis of pancreatic cancer. It can be obtained by preoperative/intraoperative cytological aspiration, biopsy, or referral to a higher level hospital with appropriate conditions for endoscopic ultrasound aspiration/biopsy.
(VII) Differential diagnosis of pancreatic cancer.
1. Chronic pancreatitis: Chronic pancreatitis is a recurrent progressive and extensive pancreatic fibrotic lesion that leads to stenosis and obstruction of the pancreatic duct, obstruction of pancreatic juice drainage, and dilatation of the pancreatic duct. The main manifestations are abdominal pain, nausea, vomiting and fever. The clinical manifestations of pancreatic cancer and epigastric discomfort, indigestion, diarrhea, loss of appetite and weight loss can be distinguished as follows.
(1) Chronic pancreatitis has a slow onset, long history, often recurrent, acute attacks can appear elevated blood and urine amylase, and rarely jaundice symptoms.
(2) CT examination of the chest shows irregular contours of the pancreas, nodular elevation, and uneven density of the pancreatic parenchyma.
(3) Plain film of abdomen and CT examination of pancreatic area in patients with chronic pancreatitis can help to diagnose calcification points.
2.Pot belly cancer: Pot belly cancer occurs at the intersection of common bile duct and pancreatic duct. Jaundice is the most common symptom, which can appear at the early stage of tumor development. The differentiation is as follows.
(1) Intermittent jaundice may appear due to tumor necrosis and detachment.
(2) Duodenal hypotension angiography can show filling defect and mucosal destruction of duodenal papilla “bilateral sign”.
(3) Ultrasound, CT, MRI, ERCP and other examinations can show dilated pancreatic duct and bile duct, low bile duct obstruction, “double duct sign”, and occupying lesions in the jugular abdomen.
3.Cystic adenoma and cystic adenocarcinoma of the pancreas: cystic tumors of the pancreas are rare clinically and occur mostly in female patients. The clinical symptoms, imaging examination, treatment and prognosis are different from those of pancreatic cancer. Ultrasound and CT can show cystic lesions and regular cystic cavity in the pancreas, while cystic lesions and irregular cavity in pancreatic cancer only appear when the center is necrotic.
4.Other: It includes some rare pancreatic lesions, which are more difficult to be diagnosed clinically.
Classification and staging of pancreatic cancer
(1) Histological types of pancreatic cancer. Refer to the 2006 WHO histological classification of pancreatic cancer (Annex 1).
(2) Staging of pancreatic cancer.
IV. Treatment
(A) Treatment principles. The treatment of pancreatic cancer mainly includes surgery, radiation therapy, chemotherapy and interventional therapy. Comprehensive treatment is the basis of treatment for any stage of pancreatic cancer, but the principle of individualized treatment should be adopted for each case, according to the physical condition, tumor site, invasion, jaundice and liver and kidney function level of different patients, the existing treatment methods should be applied in a planned and reasonable manner, in order to cure and control the tumor to the greatest extent, reduce complications and improve the quality of life of patients. For patients to be treated with radiotherapy or chemotherapy, Karnofsky (Annex 2) or ECOG score (Annex 3) should be done.
(B) Surgical treatment.
1. Principles of surgical treatment.
Surgical resection is the best treatment for pancreatic cancer patients, however, more than 80% of pancreatic cancer patients lose the opportunity of surgery due to late stage of the disease, and surgery for these patients does not improve the survival rate of patients. Therefore, before treating patients, the necessary imaging examinations and assessment of their general condition should be completed, and the treatment team, including multidisciplinary treatment teams including diagnostic imaging, chemotherapy and radiotherapy, mainly in abdominal surgery, should determine the resectability of the tumor and develop specific treatment plans. The following principles should be followed in surgery.
(1) Tumor-free principle: including the principle of tumor non-contact, the principle of whole tumor resection and the blockage of tumor supply vessels.
(2) Adequate extent of resection: the extent of pancreaticoduodenectomy includes 1/2-1/3 of the distal stomach, the lower part of the common bile duct and/or gallbladder, the head of the pancreas with the incisional margin to the left of the superior mesenteric vein/3 cm from the tumor, all of the duodenum, and 15 cm of the proximal segment of the jejunum; adequate resection of the fascia in front of the pancreas and the soft tissue behind the pancreas. Tissue in the region of the hooked region with local lymphatic fluid return, and the nerve plexus in the region. The loose connective tissue around large blood vessels, etc.
(3) Safe margins: pancreaticoduodenectomy for pancreatic head cancer requires attention to six margins, including the pancreas (pancreatic neck), common bile duct (common hepatic duct), stomach, duodenum, retroperitoneum (refers to skeletal clearance of the superior mesenteric artery), and other soft tissue margins (such as posterior pancreatic), among which the margins of the pancreas should be greater than 3 cm, and frozen pathological examination of the margins can be performed during surgery to ensure adequate margins.
(4) Lymph node dissection: the ideal histological examination should include at least 10 lymph nodes. If there are less than 10 lymph nodes, although the pathological examination is negative, the N grade should be pN1 instead of pN0. The peri-pancreatic region includes the lymph nodes around the abdominal aorta. metastasis of the para-aortic lymph nodes is one of the causes of postoperative recurrence.
2. Preoperative yellowing reduction.
(1) The main purpose of preoperative yellowing reduction is to relieve symptoms such as pruritus and cholangitis, as well as to improve liver function and reduce surgical mortality.
(2) For patients with severe symptoms, accompanied by fever, sepsis and septic cholangitis, preoperative yellow reduction is feasible.
(3) Yellowing can be reduced by drainage and/or stent placement, and cholecystostomy is feasible in hospitals without conditions.
(4) Generally, after 2 weeks of the reduction, the bilirubin will drop by more than half of the initial value, liver function will be restored and body temperature and blood count will be normal when the tumor is removed again.
3. Indications for radical surgical resection.
(1) Age <75 years old, good general condition.
(2) Pancreatic cancer with clinical stage II or below.
(3) No liver metastasis and no ascites.
(4) The cancer is confined to the pancreas and does not invade important vessels such as the mesenteric portal vein and superior mesenteric vein.
(5) No distant spread and metastasis.
4.Surgical methods.
(1) Pancreaticoduodenectomy is feasible when the tumor is located in the head and neck of the pancreas.
(2) If the tumor is located in the tail of the pancreatic body, pancreatic body tail plus splenectomy can be performed.
(3) If the tumor is large and the scope includes the head, neck and body of the pancreas, total pancreatectomy is feasible.
5.Stump anastomosis technique after pancreatic resection.
The purpose of post-pancreatic resection stump management is to prevent pancreatic leakage, and pancreatic-intestinal anastomosis is the commonly used anastomosis, and there are various anastomoses for pancreatic-intestinal anastomosis, and maintaining anastomotic blood flow is the key to reduce the occurrence of pancreatic leakage.
6. The problem of palliative surgery.
For patients with preoperative unresectable pancreatic cancer, if jaundice and gastrointestinal obstruction are also present, palliative surgery is feasible if systemic conditions allow, and biliary and gastrointestinal anastomoses are performed.
7. Management of complications and principles of treatment.
(1) Postoperative bleeding: postoperative bleeding is acute within 24 hours after surgery and delayed bleeding beyond 24 hours. It mainly includes abdominal bleeding and gastrointestinal bleeding.
(1) abdominal bleeding: mainly due to incomplete intraoperative hemostasis, the illusion of bleeding point hemostasis in the intraoperative hypotensive state or ligature line detachment, electrocoagulation scab detachment reasons, insufficient pre-closing abdominal examination, coagulation mechanism disorder is also one of the causes of bleeding. The main prevention and control methods are strict hemostasis during surgery, careful examination before closing the abdomen, important vascular sutures, and preoperative correction of coagulation function. When abdominal bleeding occurs, great importance should be attached to it. Small amounts can be observed by hemostatic transfusion, and in large amounts, surgical hemostasis is performed as soon as possible while correcting microcirculatory disturbances.
② Gastrointestinal bleeding: stress ulcer bleeding, mostly occurs more than 3 days after surgery. Its prevention and control is mainly preoperative correction of the patient’s nutritional status, to minimize the impact of surgery and anesthesia, treatment is mainly conservative treatment, the application of hemostatic drugs, acid suppression, gastrointestinal decompression, can be injected through the gastric tube ice positive renal saline gastric lavage, but also by gastroscopy to stop bleeding, angiography embolization to stop bleeding, by conservative invalid can be surgical treatment.
(2) pancreatic fistula: where 7 days after surgery still drainage of fluid containing amylase should be considered the possibility of pancreatic fistula, Johns Hopkins criteria is the content of pancreatic enzymes in the abdominal drainage fluid is greater than three times the serum value, the daily drainage is greater than 50 ml. pancreatic fistula management is mainly adequate drainage, nutritional support.
(3) Gastroparesis.
(1) There is no unified standard for gastroparesis, and the commonly used diagnostic criteria are confirmed by examination that there is no obstruction of the gastric outflow tract; gastric fluid >800ml/d for more than 10 days; no obvious abnormalities in water-electrolyte and acid-base balance; no underlying diseases that cause gastric weakness; and no use of smooth muscle contraction drugs.
②Diagnosis is mainly based on medical history, symptoms and signs, gastrointestinal imaging, gastroscopy and other examinations.
(③The treatment of gastroparesis is mainly adequate gastrointestinal decompression, enhanced nutritional psychotherapy or psychological suggestion therapy; application of gastrointestinal motility drugs; treatment of underlying disorders and disorders of nutritional metabolism; gastroscopy can be tried and repeatedly and rapidly inflated and discharged into the stomach, and treatment can be repeated for 2-3 days.
(iii) Chemotherapy.
The purpose of chemotherapy is to prolong survival and improve the quality of life.
1.Adjuvant chemotherapy.
Adjuvant chemotherapy after pancreatic cancer surgery can prolong survival. The commonly used chemotherapy drug is gemcitabine 1000mg/m2 intravenous drip >30 minutes, once a week, with 2 weeks stopping 1 week, 21 days a cycle, a total of 4 cycles (12 weeks).
Adjuvant chemotherapy precautions: adjuvant chemotherapy for pancreatic cancer should be started about 1 month after radical surgery; preparation before adjuvant chemotherapy includes abdominal pelvic enhanced CT scan, chest front and side views, peripheral blood routine, liver and kidney function, electrocardiogram and tumor markers CEA, CA19-9, etc. Timely observation and treatment of chemotherapy-related adverse reactions in chemotherapy.
2. Palliative chemotherapy.
Same as adjuvant chemotherapy.
3.Effect of treatment.
The efficacy evaluation of chemotherapy should refer to WHO efficacy evaluation criteria for solid tumors (Annex 4) or RECIST efficacy evaluation criteria (Annex 5).
(iv) Radiation therapy.
Radiation therapy is mainly used for the comprehensive treatment of inoperable locally advanced pancreatic cancer, the comprehensive treatment of residual or recurrent tumor cases after surgery, and the palliative reduction treatment of advanced pancreatic cancer.
1.Treatment principles.
(1) Simultaneous chemoradiotherapy based on 5-fluorouracil or Kenze.
(2) For locally advanced inoperable resectable pancreatic cancer without distant metastases, if the patient’s general condition allows, synchronized chemoradiotherapy should be given in the hope of obtaining a chance of surgical resection or prolonging the patient’s survival time.
(3) Patients with residual tumor in non-radical resection should be given postoperative chemoradiotherapy.
(4) If intraoperative tumor is found to be inoperable or inoperable, intraoperative local irradiation can be considered together with postoperative chemoradiotherapy.
(5) Patients without distant metastases after radical resection of pancreatic cancer can be considered for postoperative chemoradiotherapy.
(6) In case of inoperable advanced pancreatic cancer with severe abdominal pain or pain caused by metastases in bone or other areas, which seriously affects the quality of life of patients, synchronized chemoradiotherapy or radiotherapy alone can play a good role in palliation and disease reduction if the patient’s physical condition allows.
(7) Postoperative synchronized radiotherapy should be carried out after the patient’s physical condition has basically recovered from 4-8 weeks after surgery.
(8) Three-dimensional conformal or intensity modulated conformal radiotherapy should be used to improve the accuracy of treatment and to protect the important normal tissues and organs around the pancreas, and conventional radiotherapy can be considered for the palliative reduction treatment of patients with bone metastases.
2. Protection.
Using conventional radiotherapy techniques, attention should be paid to the protection of lung, heart, esophagus and spinal cord in order to avoid serious radiation damage to important organs of the body.
3.Effectiveness of treatment.
The evaluation of the efficacy of chemotherapy should refer to the WHO criteria for evaluating the efficacy of solid tumors or RECIST.
(E) Staging treatment pattern of pancreatic cancer.
1.Surgically resectable pancreatic cancer can be considered for 4-8 weeks postoperatively supplemented with concurrent chemoradiotherapy.
2.Surgeable pancreatic cancer with tumor residual after surgery is recommended to be treated with synchronized chemoradiotherapy for 4-8 weeks after surgery.
3.If the tumor is found to be inoperable or inoperable, intraoperative local irradiation can be considered together with postoperative synchronized chemoradiotherapy.
4.Inoperable resectable locally advanced pancreatic cancer, without jaundice and obvious abnormal liver function, and in better physical condition, puncture biopsy is recommended and then synchronized chemoradiotherapy is given.
5.Patients with locally advanced inoperable, with jaundice and obvious abnormalities of liver function, after bile duct built-in stent or surgery to release jaundice obstruction and improve liver function, if the patient’s physical condition allows, synchronized chemoradiotherapy (5-Fu/gemcitabine) is recommended/chemotherapy alone.
6.Patients with post-local recurrence, without jaundice and obvious abnormal liver function, and in better physical condition, it is recommended that (5-Fu/gicitabine) synchronized chemoradiotherapy, and those who have biliary obstruction and abnormal liver function, first release the biliary obstruction and improve liver function before considering treatment.
7. When inoperable advanced pancreatic cancer presents with severe abdominal pain, pain caused by metastases in bone or other sites, which seriously affects the patient’s quality of life, synchronized chemoradiotherapy or radiotherapy alone can be considered to reduce the patient’s symptoms and improve the quality of life if the patient’s physical condition allows.
(F) Interventional treatment.
1.Interventional treatment principles.
(1) Have a digital subtraction angiography machine.
(2) Must strictly grasp the clinical indications.
(3) must emphasize the standardization and individualization of treatment.
2. Indications for interventional treatment.
(1) Locally advanced pancreatic cancer that cannot be surgically resected according to imaging estimation.
(2) Pancreatic cancer that has lost the chance of surgery due to medical reasons.
(3) Pancreatic cancer with liver metastasis.
(4) Control of pain, bleeding and other disease-related symptoms.
(5) Perfusion chemotherapy as a special form of neoadjuvant chemotherapy.
(6) Postoperative prophylactic infusion chemotherapy or adjuvant chemotherapy.
(7) Obstructive jaundice (drainage, internal stent placement).
3. Contraindications to interventional therapy.
(1) Relative contraindications.
(1) Mild allergy to contrast media.
(ii) KPS score <70.
(3) Those with bleeding and coagulation dysfunctional diseases that cannot be corrected and obvious bleeding tendency.
④White blood cells <4000, platelets <70,000.
(2) Absolute contraindications.
(①Severe hepatic and renal dysfunction: total bilirubin > 51umol/L, ALT > 120U/L.
(2) Large amount of ascites, systemic multiple metastases.
(iii) Systemic failure.
4. Interventional treatment operation specification.
(1) Selectively place the catheter in the celiac artery and superior mesenteric artery respectively for action pulse imaging, and if the tumor blood supply vessel is visible, perfuse chemotherapy through this artery.
(2) If no tumor-supplying artery is seen, the target vessel will be determined according to the location, invasion and blood supply of the tumor. In principle, pancreatic head and pancreatic neck tumors should be treated by infusion chemotherapy via gastroduodenal artery; pancreatic tail tumors should be treated by infusion chemotherapy via celiac artery, superior mesenteric artery or splenic artery.
(3) If liver metastasis is present, hepatic artery infusion chemotherapy or/and embolization therapy should be administered simultaneously.
(4) Drug administration: usually platinum, adriamycin, gemcitabine alone or in combination. The dosage of drugs is decided according to the patient’s body surface area, liver and kidney function, blood routine and other indicators.
5.The “individualized” program based on transarterial interventional therapy (TAIT).
(1) Patients with obstructive jaundice may undergo internal stenting.
(2) Patients with abdominal or retroperitoneal lymph node metastases that cause symptoms can be combined with radiation therapy.
(vii) Supportive therapy.
The purpose of supportive therapy is to reduce symptoms and improve the quality of life.
1. Pain control. Pain is one of the most common symptoms of pancreatic cancer. Firstly, the cause of pain should be clarified, and surgical assistance is often required for acute cases such as digestive tract obstruction. Secondly, the degree of pain should be clarified. According to the degree of pain, patients should take opiate painkillers orally on time and in sufficient amount. For mild pain, oral anti-inflammatory drugs such as anti-inflammatory pain, paracetamol and aspirin can be given; for moderate pain, weak morphine-like drugs such as codeine can be combined with non-steroidal anti-inflammatory drugs, commonly used aminophenazone and lofenophenazone, 3-4 times a day; for severe pain, oral morphine should be applied promptly, and if necessary, radiotherapy department should be requested to assist in pain relief; avoid intramuscular injection of dulcolax alone, etc. Pay attention to the timely treatment of adverse reactions of oral pain medication such as nausea and vomiting, constipation, dizziness and headache, etc.
2.Improve cachexia. Commonly use methylhydroxyprogesterone or megestrol to improve appetite, pay attention to nutritional support, timely detection and correction of liver and kidney insufficiency and water and electrolyte disorders.
V. Treatment flow and follow-up
(1) Pancreatic cancer treatment process.
The general procedure of pancreatic cancer diagnosis and treatment (Annex 6).
(B) Follow up.
Patients with new pancreatic cancer should establish a complete case file and related information, and conduct regular follow-up and corresponding examination after treatment. The follow-up should be every 3 months within 2 years and every 6 months after 2 years after treatment, with review of blood routine, liver and kidney function, serum tumor markers, abdominal CT/B ultrasound and chest X-ray until 5 years, and then once a year with review of blood routine, liver and kidney function, serum tumor markers, abdominal CT/B ultrasound and chest X-ray.
Follow-up visits were conducted 3 to 6 weeks after interventional treatment, and the efficacy was determined using the internationally accepted criteria for evaluating the efficacy of solid tumor treatment. The treatment interval is usually 1 month to 1.5 months, or the time to repeat TAIT is determined by the time of pain recurrence of the patient.