pancreatic cancer



Overview

Definition

Cardia cancer, also known as esophagogastric junction cancer, or esophagogastric junction cancer, is a malignant tumor that occurs at the esophagogastric junction.

Most of them belong to adenocarcinoma within about 2 cm below the esophagogastric junction line.

Staging and classification

Gross staging (Borrmann staging)

Type I: elevated type;

Type II: limited ulcerated type;

Type III: infiltrating ulcerated type;

Type IV: diffuse infiltrating type.

Histopathologic types

The histopathological types of cardia cancer are similar to that of gastric cancer, mostly adenocarcinoma of various types (small cell carcinoma, adenosquamous carcinoma are rare, squamous carcinoma is rare), while the vast majority of esophageal cancers are squamous carcinomas (adenocarcinoma percentage <3%).

The main types are papillary adenocarcinoma, tubular adenocarcinoma, mucinous adenocarcinoma, imprinted cell carcinoma, small cell carcinoma, squamous carcinoma and undifferentiated carcinoma.

Incidence

Bulk statistical analysis shows that the incidence rate of cardia cancer is about half of that of esophageal cancer and accounts for 16.1% to 41.5% of gastric cancer.

Causes

Causes

The exact cause of pancreatic cancer is still unknown and may be related to the following factors:

People who consume certain foods, vegetables and drinking water with high levels of nitrosamine compounds have a high incidence of the disease.

Frequent consumption of moldy food can induce pancreatic cancer or squamous cancer, and there is a synergistic cancer-promoting effect between mold and nitrosamines.

Low content of trace elements molybdenum, copper, zinc and nickel in the external environment of human body can easily induce it.

Consumption of hot, spicy, coarse and hard food, smoking, drinking and nutritional deficiencies are related to the development of the disease.

Genetic susceptibility, people with family history of pancreatic cancer or stomach cancer may be more likely to develop pancreatic cancer.

Chronic inflammation of the esophagus such as reflux esophagitis, pancreatic achalasia, pancreatic mucosal epithelial hyperplasia.

Pathogenesis

The pathogenesis of cardia cancer is not clear, and there may be the following possibilities:

It is believed that cardia cancer originates from the neck stem cells of cardia glands, which have multidirectional differentiation potential and can form adenocarcinoma with characteristics of cardia or glandular epithelium.

Ulcers, polyps, and atrophic gastritis in the cardia may develop into atypical hyperplasia and eventually progress to cardia cancer.

Symptoms

If the lesion is located in the lower part of the esophagus, the cardia gradually narrows, and symptoms that closely resemble those of esophageal cancer appear.

If the lesion is located in the fundus of the stomach, there may be no symptoms at the initial stage, which may delay the diagnosis and treatment.

With the development of the lesion, the patient may have foreign body sensation, choking sensation, difficulty in swallowing and pain when eating. Symptoms may vary in severity.

Another initial symptom is vomiting blood or tarry stools, which may be accompanied by shock and severe anemia.

Early symptoms

Early symptoms are inconspicuous, non-specific and easily overlooked, usually lasting more than 3 months.

Discomfort or pain behind the sternum, characterized by intermittent or rapid feeding aggravation.

Foreign body sensation when swallowing food, especially when swallowing dry and hard food may have a foreign body sensation, the symptoms are mild and occur intermittently, and often fixed in one area.

Stagnation of the food mass during swallowing, when swallowing food seems to be stagnant in a certain part of the body for a while, and only after the development of the lesion is gradually obvious.

A feeling of distension or constriction in the chest, often accompanied by dryness of the throat.

Intermittent epigastric fullness, noticeable when eating dry food.

Intermediate and Late Symptoms

Common mid-stage symptoms: difficulty swallowing, vomiting, pain and weight loss.

Late stage: anemia, hypoproteinemia, and cachexia may be present (mainly characterized by lack of appetite, extreme lethargy, weakness, anemia, and a state of generalized exhaustion). ..

If there are abdominal masses, hepatomegaly, ascites and pelvic masses, there may be persistent vague pain in the epigastrium and lower back, which indicates that there are metastases to the abdominal organs and there is no chance of surgical treatment.

Complications

Most are complications of tumor invasion of esophagus and its compression symptoms.

Esophageal-tracheal fistula, mediastinal abscess, pneumonia, lung abscess and aortic perforation and hemorrhage may occur when the tumor invades adjacent organs.

Compression of metastatic lymph nodes on the trachea may cause dyspnea, compression of the recurrent laryngeal nerve may cause hoarseness, and compression of the phrenic nerve may cause diaphragmatic dyskinesia and disorders.

Consultation

Department of Medicine

General Surgery

When imaging tests reveal a metastatic lymph node in the stomach or esophagogastric junction, or when a gastroscopic biopsy suggests malignancy, you should consult a general surgery department or a gastrointestinal surgery department in a timely manner.

Gastroenterology

When there is unexplained weight loss, epigastric discomfort or hidden pain, anorexia, black stools and other manifestations, you should go to the Department of Gastroenterology as soon as possible.

If you have chronic atrophic gastritis, gastric ulcer, or gastric polyps, you should have regular follow-ups.

Preparation

Consultation: Registration, Preparation of Documents, Frequently Asked Questions

Tips for Consultation

Cardia cancer, with no specific symptoms in early stage, is easy to be overlooked. Therefore, if you have a family history of gastric cancer or live in an area with high incidence of gastric or esophageal cancer, etc., you should have a regular medical checkup for cancer prevention.

Medical Preparation Checklist

Symptom list

Especially, you need to pay attention to the time of symptom onset, special performance, etc.

Is there any discomfort or pain behind the sternum and for how long?

Is there any foreign body sensation or obstruction when swallowing food?

Is there intermittent epigastric fullness and discomfort, noticeable when eating dry food?

Medical History Checklist

Is there a family history of malignant tumors of the GI tract?

Any Helicobacter pylori (Hp) infection?

Any drug or food allergies?

Any gastric diseases such as chronic atrophic gastritis or gastric ulcer?

Checklist

Examination results in the past 6 months, which can be brought to the doctor’s office

Specialized tests: gastroscopy and biopsy, tumor markers, Helicobacter pylori (Hp) test.

Laboratory Tests: blood routine, urine routine, stool routine, blood biochemistry test

Imaging tests: X-ray barium contrast, CT, magnetic resonance imaging (MRI), PET-CT.

Diagnosis

Diagnosis is based on

Medical history

There may be a history of Helicobacter pylori infection.

History of gastric related diseases: e.g. chronic inflammation of esophagus such as reflux esophagitis, pancreatic achalasia, pancreatic mucosal epithelial hyperplasia.

Family history of tumor, etc.

Clinical manifestations

In the early stage, there may be retrosternal discomfort or pain, or foreign body sensation when swallowing food.

Common symptoms in the middle stage: dysphagia, vomiting, pain and weight loss.

Late stage: there may be anemia, hypoproteinemia, emaciation and cachexia.

Laboratory Tests

Biochemical tests

Including serum pepsinogen I (PG I), serum pepsinogen II (PG II), serum gastrin 17 (G-17) test.

It is a non-invasive, safe and economical examination method.

It can be used for the auxiliary diagnosis of cardia cancer.

Tumor markers

CA72-4, CEA and CA19-9 are helpful for auxiliary diagnosis, efficacy judgment and follow-up monitoring of gastric cancer.

CA125: It is auxiliary diagnosis for peritoneal metastasis of gastric cancer.

AFP: It has certain diagnostic and prognostic value for special pathological types of gastric cancer.

Blood routine and fecal routine

Blood routine: gastric cancer patients often have anemia and hemoglobin will be reduced.

Stool routine: some patients may have positive fecal occult blood test, which suggests that it is currently accompanied by active bleeding and needs to stop bleeding in time.

Gastroscopy

Gastroscopy is the necessary examination to confirm the diagnosis of gastric cancer (“gold standard”), which can determine the location of the tumor and obtain tissue specimens for pathological biopsy.

Imaging examination

Ultrasound endoscopy

It is a detection method combining endoscopic technology and ultrasound technology.

It is used to assess the extent of invasion and lymph node metastasis.

Ultrasound-guided fine-needle aspiration biopsy can also be performed, which helps with preoperative staging and accurately predicts the likelihood of endoscopic treatment.

Barium X-ray

The advantage of this examination is that it is simple, non-invasive, economical and can detect gastric lesions; the disadvantage is that it is difficult to distinguish its benign or malignant nature, and its diagnostic value for early gastric cancer is limited.

CT examination

It is the preferred clinical staging method, and is usually used to scan the thoracic, abdominal and pelvic cavities in a wide range.

It helps doctors to judge the tumor site, the relationship between the tumor and the surrounding organs (such as liver, pancreas, diaphragm, colon, etc.) or blood vessels and distinguish the tumor from local lymph nodes, which can help to judge the staging of the tumor.

Magnetic resonance imaging (MRI) examination

MRI may be considered for those who are allergic to CT contrast.

MRI can also be used to determine the presence or absence of peritoneal metastasis.

MRI, especially enhanced MRI, is the first choice or important supplementary examination for liver metastasis of pancreatic cancer.

Bone nuclear scan

Short for bone scan, it is a routine examination used to determine bone metastasis of pancreatic cancer.

When bone scanning suggests suspected bone metastasis, MRI, CT or PET-CT shall be carried out to verify the suspected area.

Positron emission tomography (PET-CT)

It can assist in the staging of cardia cancer and early detection of abnormal metabolic foci, thus detecting tumor metastasis and so on.

The cost of this examination is high, and it is generally not routinely used.

Pathological diagnosis

Histologic examination

Specimen type

Histologic examination of cardia pathology is generally divided into two types: small specimen and large specimen.

In general, large specimens are those obtained after surgical resection of cancer, while small specimens are endoscopic biopsy specimens, endoscopic mucosal resection/endoscopic submucosal dissection (EMR/ESD) specimens.

Contents of pathology report

What is more important is the pathology and histology examination of the large specimen of cardia cancer, that is, the pathology report after cardia cancer surgery, and the contents of the report mainly include:

Histologic typing: to determine whether cardia cancer is adenocarcinoma, mucinous adenocarcinoma, or imprinted cell carcinoma, etc.

Histological grading: according to the differentiation degree of the glands of pancreatic cancer, it is divided into highly differentiated, moderately differentiated and lowly differentiated, and the prognosis of lowly differentiated is relatively poor.

Staging of cardia cancer: TNM staging jointly formulated by the American Cancer Consortium (AJCC) and the International Union Against Cancer (UICC) is generally used.

Immunohistochemistry

Immunohistochemistry examination, referred to as immunohistochemistry (IHC), is mainly used for guiding treatment and prognosis judgment of cardia cancer. In the pathology report, a certain immunohistochemical index is expressed or positive, usually represented by “+”. The following immunohistochemical tests are usually required:

HER2: when the indicator is “3+”, it suggests that molecular targeted therapy can be used; when the HER2 result is “2+”, it is necessary to do further in situ hybridization testing.

Mismatch repair proteins: including MLH1, PMS2, MSH2, MSH6, when all 4 indicators are positive “+”, it represents microsatellite stabilization and relatively good prognosis.

PDL-1: When this indicator is positive “+”, it suggests the ability to use partial immunotherapy drugs, such as pabolizumab.

Staging

The staging of cardia cancer helps to reasonably formulate treatment plans, correctly evaluate the curative effect and judge the prognosis.

TNM staging

Currently, TNM staging of pancreatic cancer is a staging system jointly formulated by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC), which is mainly based on the three elements of T, N and M. The TNM will be appended with Arabic numerals from 1 to 4, etc., and the bigger the number, the more serious the tumor is in general.

T: represents the extent of the primary tumor, mainly referring to the size of the primary tumor foci and the degree of extravasation.

N: represents the situation of regional lymph node metastasis, including the regional extent of metastasis.

M: represents the situation of distant metastasis.

Overall staging

According to different TNM staging, the overall clinical staging (prognostic grouping) of the patient is finally determined, which is indicated by the Roman letters I, II, III and IV.

The staging of pancreatic cancer is complicated, so it is recommended to consult the consulting physician in detail.

Differential diagnosis

Cancer of the cardia generally needs to be differentiated from cardia dystrophy, stenosis caused by chronic inflammation of the lower esophagus, smooth muscle tumor of the cardia, and cardia polyps, etc. It is often difficult to distinguish cardia cancer from other diseases by clinical manifestations.

It is usually difficult to differentiate by clinical manifestations, and barium meal imaging of digestive tract or endoscopic examination is usually needed to confirm the diagnosis.

Treatment

Surgery

It is recognized as the preferred method.

Main applicable situations:

Those whose diagnosis has been confirmed by barium meal X-ray, endoscopy biopsy and pathologic cytology.

Abdominal ultrasound, CT examination or laparoscopy to exclude lymph node and abdominal organs metastasis.

The patient’s general condition is still good, without major cardiac, pulmonary or other organs serious comorbidities.

Endoscopic treatment

Endoscopic ultrasound is required to determine the depth of tumor invasion before surgery.

Applicable cases

Early-stage cancer or severe atypical hyperplasia with lesions limited to the mucosal and submucosal layers of the esophagus, without lymph node or distant organ metastasis, with a diameter of <1cm, and with confined lesions and clear borders.

Treatment method

Endoscopic mucosal resection or endoscopic submucosal dissection can be chosen.

Endoscopic mucosal resection

Endoscopic mucosal resection refers to the endoscopic removal of mucosal lesions in whole or in pieces, and is used for the diagnosis and treatment of superficial tumors of the gastrointestinal tract.

Endoscopic submucosal dissection

Endoscopic submucosal dissection is a method of endoscopically separating the tissues between the mucosal layer and the intrinsic muscular layer gradually by using a special electrosurgical cutter according to the lesions of different parts, sizes and infiltration depths, and finally peeling off the lesion mucosa and submucosa completely.

Endoscopic palliative care

Endoscopic palliative treatments include argon ion beam coagulation, laser, electrocoagulation, thermal probe, radiofrequency ablation, cryotherapy and photodynamic therapy.

Argon ion beam coagulation: with the help of argon ion beam electrical conduction will be high-frequency electrical energy transfer to the target tissue of the treatment method. It can effectively stop extensive bleeding in a short time and is non-toxic to the human body.

Photodynamic therapy: it is a treatment method utilizing photodynamic effect, with the advantages of small trauma, low toxicity and wide application range.

Radiofrequency ablation: it can be used to treat early cardia cancer, cancerous stenosis and re-obstruction after stenting, and its curative effect is quick, safe and reliable.

Endoscopic dilatation therapy: for those who have metastasis of cardia cancer in the advanced stage with other organ diseases or those who cannot be operated due to the limitation of systemic conditions, endoscopic dilatation therapy to improve the obstruction is a kind of effective palliative treatment, which is applicable to all types of esophageal stenosis.

Endoscopic placement of metal stents: For those with severe stenosis and inoperable esophageal-tracheal fistula, endoscopic placement of metal stents can significantly relieve symptoms and improve the quality of life, but the disadvantage is that the stent may displace, and a few patients, especially those who have been treated with chemotherapy, may be complicated by bleeding.

Drug therapy

Chemotherapy

Chemotherapy for cardia cancer is ineffective, and combination chemotherapy is mostly used.

Usually refer to the chemotherapy regimen of gastric cancer for treatment, commonly used first-line treatment regimen:

FP regimen: fluorouracil combined with cisplatin.

XP program: capecitabine combined with cisplatin.

SP regimen: Tegio combined with cisplatin.

FOLFOX regimen: fluorouracil and oxaliplatin.

Targeted therapy

Trastuzumab

For patients with human epidermal growth factor receptor 2 (HER2) overexpression (usually “3+” on immunohistochemical staining or “2+” on immunohistochemical staining and positive FISH test in the pathology report) of adenocarcinoma of the esophagogastric junction, the combination of trastuzumab is recommended in addition to chemotherapy. Trastuzumab is recommended in combination with chemotherapy.

Apatinib

Apatinib mesylate is a new drug independently developed in China.

It is mainly used for third-line and above third-line treatment for patients with esophagogastric junction adenocarcinoma who are in good condition when receiving Apatinib.

Immunotherapy

Relay immunotherapy: a large number of immune cells with anti-tumor effect can be infused. Interleukin 2 is widely used in clinical practice.

Non-specific biological response modulation therapy: achieve therapeutic purpose by enhancing the overall immune function of the body. Commonly used in clinic are BCG vaccine, mushroom polysaccharide and so on.

Interferon γ, tumor necrosis factor α, etc. have also achieved certain efficacy.

Prognosis

Survival

There is no authoritative survival statistics of cardia cancer, and cardia cancer is generally regarded as a special type of gastric cancer, and the survival period of cardia cancer can be roughly inferred through the survival analysis of gastric cancer. The total survival time of patients can be roughly predicted by the 5-year survival rate (referring to the proportion of patients whose tumors survive for more than 5 years after various comprehensive treatments).

5-Year Survival Rate of Stomach Cancer

Early gastric cancer has a good prognosis, with the 5-year survival rate of intramucosal cancer patients being more than 91% and that of submucosal cancer being 80%-90%.

Domestic statistics show that the 5-year survival rate of gastric cancer stages I, II, III and IV are 92.6%, 76.2%, 40.8% and 6% respectively.

Special Reminder

The 5-year survival rate is only used for clinical research and does not represent the specific survival time of an individual. The patient’s individual expected survival time is influenced by a number of factors.

The probability of recurrence after 5 years is very low and is generally considered clinically cured.

Prognostic factors

The prognosis of cardia cancer mainly depends on various factors such as tumor characteristics, patient condition and treatment methods.

Tumor aspects include the degree of tumor differentiation, general type, tumor size and location, infiltration depth, lymph node metastasis, and tumor infiltration and growth mode.

Patients under 30 years of age have a high degree of tumor malignancy and a poor prognosis.

Daily

Daily Management

Family care

Understanding the characteristics of cancer: family members can understand and learn about pancreatic cancer through various ways in order to take better care of the patient.

Emotional support: patients with pancreatic cancer often have some psychological problems or emotional changes, as family members, they should pay attention to providing emotional support, explaining relevant knowledge to patients and informing them of the necessity of treatment, and helping them to build up confidence in healing and optimistic attitude towards life.

Diversion of attention: Family members can encourage patients to relax by doing moderate exercise, watching movies, listening to light music, reading books, taking a walk in the park, etc. to promote mental health.

Lifestyle

For patients with pancreatic cancer, a healthy lifestyle can reduce recurrence and lower the risk of death.

Ensure sleep: patients should rest more and ensure enough sleep.

Participate in physical activities appropriately: aerobic exercises suitable for patients include walking, cycling, yoga and so on, which can be chosen according to their own preferences, and insist on 3 to 5 times a week.

Pay attention to the observation of stools: If black stools are found, it is recommended to consult a doctor to clarify whether gastrointestinal bleeding has occurred.

Use health supplements with caution: Get nutrition from food and avoid relying on nutritional supplements. Routine intake of nutraceuticals for cancer control is not recommended.

Daily diet

Gradual transition to other diets with a focus on soft foods.

Increase nutrition in moderation, especially in the postoperative period. Regular weight monitoring should be conducted to encourage smaller meals, chewing and swallowing, and referral to dietitian or nutrition department for individualized counseling if necessary.

Avoid raw, cold, hard, spicy, alcohol and other stimulating foods.

Avoid foods that are easily bloated, such as legumes.

Avoid excessively sweet foods.

Relieve the fear of eating and ensure adequate nutrition.

Daily medication

After removal of pancreatic cancer, it will have some influence on daily medication, and it is recommended to prefer liquid dosage form of medication.

Solid dosage: ordinary tablets and capsules, etc. The tablets need to be crushed as much as possible.

Capsule preparation: the capsule shell needs to be removed to make a paste or dissolved into water for taking.

Enteric or slow-release preparations: take as normal, not crushed.

Follow-up

Regular follow-up is required after treatment.

The purpose of review is to monitor the efficacy of treatment and to detect tumor recurrence and metastasis at an early stage.

The examination is based on imaging tests, such as chest CT, abdominal CT or ultrasound.

Due to the individual differences in disease and physical condition among patients, the time of follow-up examinations should be strictly in accordance with the doctor’s instructions. The following are just general principles.

Follow-up after early radical surgery

Frequency of follow-up: every 3 months for 2 years, every 6 months for 3 to 5 years, and every 1 year after 5 years.

Follow-up content: hematological examination (blood routine, biochemistry, tumor markers, such as CEA, CA19-9, CA72-4, CA125, etc.), weight monitoring, the frequency of monitoring is the same as clinical examination.

Ultrasonography: 1 time every 6 months.

Thoracic and abdominal CT examination: 1 time every 6 months within 2 years. Thereafter, once a year.

Gastroscopy: once a year (anytime when CEA indicates abnormality).

Follow-up after progressive radical surgery and unresectable palliative care

Frequency of follow-up/monitoring: every 3 months for the first 2 years, then semi-annually until the 5th year.

Follow-up/monitoring content: hematological examination (blood routine, biochemistry, tumor markers, such as CEA, CA19-9, CA72-4, CA125, etc.), body weight monitoring, ultrasound or thoracic or abdominal CT examination once every half a year (when CEA suggests abnormality).

Prevention

General prevention

Pay attention to dietary health, eat more foods rich in vitamins and proteins (e.g. apples, bananas, grapes, pears, radishes, vegetables, tomatoes, etc.), and eat less pickled foods and no moldy foods.

Pay attention to dietary hygiene, do a good job of preventing mold in food and fruits, and pay attention to the hygiene of drinking water.

Develop good eating habits, have three regular meals, eat not too fast, too hot, too hard, avoid overeating.

Avoid drinking a lot of alcohol and excessive smoking.

Actively treat precancerous gastric diseases and precancerous lesions, such as gastric ulcer, chronic atrophic gastritis, and gastric polyps.

High incidence areas and high-risk groups should be regularly screened for gastric cancer.

Avoid taking long-term oral medications that are irritating to the stomach.

Eradicate Helicobacter pylori in time.

Regular gastric cancer screening

Serologic Screening

Serum pepsinogen (PG) test

PG can be divided into PGⅠ and PGⅡ.

China’s gastric cancer screening adopts PGⅠconcentration≤70 μg/L and PGⅠ/PGⅡ≤3.0 as the criteria for high-risk group of gastric cancer.

Serum gastrin 17 (G-17) test: elevated index suggests the risk of gastric cancer.

Hp infection test: Positive test indicates the presence of Hp infection and the risk of gastric cancer. It mainly includes serum Hp antibody test and urea breath test (UBT).

Endoscopic screening

Commonly used are electronic gastroscopy screening and magnetic capsule gastroscopy screening.

Electronic gastroscopy

It is the main diagnostic tool for gastric cancer.

It can observe the whole picture of intragastric mucosa, lesion location, morphology, scope, bleeding, ulcer formation and so on.

Tumor margin tissue or tissue suspected to be tumor can be taken for pathological examination.

Magnetic Capsule Gastroscopy (MCE)

It is a new generation of active capsule endoscopy that successfully combines capsule endoscopy (CE) technology and magnetic control technology.

Principle: A method of examining gastrointestinal tract lesions by placing a miniature camera and radio transmitter inside a capsule and swallowing it.

Advantages: painless, convenient, high diagnostic accuracy.

Limitations: Biopsy is currently not possible.