Small intestinal adenocarcinoma

　　First, etiology

　　The etiology of small intestinal adenocarcinoma is not yet clear. The traditional concept of related risk factors and geographical distribution believes that it is similar to colon cancer, but recent multi-center studies in Europe have shown that its occurrence may be related to alcohol consumption and certain professions, but not smoking. Common risk factors include Crohn's disease, celiac disease, neurofibromatosis, and urinary diversion surgery. The occurrence of small intestinal adenocarcinoma is similar to the adenoma-adenocarcinoma sequence of colon cancer, with adenoma being a common precancerous disease, among which familial adenomatous polyposis (FAP) is the most common to become cancerous.

　　But clinical observations have found that 65% of duodenal adenocarcinoma occurs around the Vater ampulla, 22.5% occurs in the superior ampulla near the duodenal papilla, and mainly in the descending part as well. The reason for the high incidence of ampullary cancer is unknown, but the ampulla area marks the junction of the foregut and midgut, and it is very likely that the mucosa in this junction area has less resistance to diseases than other parts of the duodenum. Some people also believe that adenocarcinoma at the proximal duodenum and jejunum may be related to the degradation products and carcinogenic effects of certain bile acids (such as deoxycholic acid, primary bile acid, etc.) in the bile under the action of bacteria.

　　Long-term Crohn's disease can lead to adenocarcinoma (incidence rate 3% to 60%), mainly located in the ileum, the risk of canceration in Crohn's disease is 300 to 1000 times higher than that in the normal control group. It is reported that about 30% of cases occur in the intestinal segment where bypass surgery is performed due to Crohn's disease. The incidence of small intestinal adenocarcinoma in cases after celiac disease and colorectal cancer surgery is significantly higher than that in the normal control group. The possibility of duodenal adenocarcinoma in cases with familial adenomatous polyposis and Gardner's syndrome is also significantly higher than that in the normal control group.

　　The occurrence of small intestinal adenocarcinoma is often accompanied by genetic changes, such as the activation of oncogenes and the deletion of tumor suppressor genes. Sutter reported that in 6 cases of small intestinal adenocarcinoma, 5 cases had a point mutation at the 12th codon of the K-ras gene; Hidalgo found that 5% to 10% of adenocarcinoma cells had overexpression of p53 protein, and the expression intensity was significantly related to the degree of differentiation, invasion, metastasis, and prognosis of small intestinal cancer.

　　Second, pathogenesis

　　1. Pathological morphology

　　Small intestinal adenocarcinoma originates from the mucosa of the small intestine, developing from the mucosa through the submucosa to the muscular layer and serous layer, while expanding around. The length of the invaded part of the intestinal tube by small intestinal adenocarcinoma is generally only 4-5cm, rarely exceeding 10cm, so it is rarely seen in clinical practice that patients seek medical attention due to abdominal masses.

　　(1) Gross morphology: Gross pathological specimens can be divided into three types:

　　① Annular infiltrative adenocarcinoma: Also known as the stenotic type, the lesion grows along the circumferential axis of the intestinal tube, finally forming a circumferential lesion, narrowing the intestinal lumen, thickening and hardening the intestinal wall, and prone to cause intestinal stricture and obstruction.

　　② Polypoid papillary cancer: More common, protruding into the intestinal lumen, prone to cause intussusception, and can gradually infiltrate the intestinal wall to cause annular stricture.

　　③ Ulcerative cancer: As the lesion progresses deeper, the mucosa appears erosive, followed by ulceration, forming an ulcer. This type is prone to cause chronic gastrointestinal bleeding and even perforation leading to peritonitis; it may also be that before perforation, the adjacent intestinal tubes have already adhered, so after perforation, they are connected to form an internal fistula.

　　(2) Tissue morphology: The microscopic feature is the formation of adenoid structures of unequal size and shape. The proliferating glands are sometimes very dense, so close to each other that the interstitium is difficult to see. The gland cells are larger and more deeply stained. The nuclei are of uneven size and polarity is disordered, and nuclear division is common.

　　2. Tissue type

　　According to cell morphology and degree of differentiation, it can be divided into high, medium, and low differentiated adenocarcinoma, mucinous adenocarcinoma, and undifferentiated cancer, among which well-differentiated adenocarcinoma is the most common.

　　3. Metastatic pathways

　　Cancer spread can be through direct invasion or regional lymphatic vessels, metastasizing to mesenteric lymph nodes, liver, peritoneum, and other abdominal organs. Duodenal adenocarcinoma can metastasize to lymph nodes under the pylorus, pancreatic head, porta hepatis, and paravertebral aorta. Advanced cancer foci can penetrate the intestinal wall and invade adjacent organs.

　　4. Pathological staging

　　According to the Duke's staging system revised by AstlerColler, small intestinal adenocarcinoma is divided into four stages and six grades.

　　1. Gastrointestinal bleeding

　　It is relatively common, and most cases are chronic blood loss, mainly manifested as melena. Chronic chronic blood loss can lead to anemia.

　　2. Jaundice

　　The mass compresses the common bile duct or the duodenal papilla, causing bile duct obstruction and obstructive jaundice.

　　1. Abdominal pain

　　It is generally chronic abdominal pain, which is not closely related to diet. In the early stage, it is relatively mild and is often misdiagnosed as 'gastric pain'. The pain is usually located in the upper middle abdomen or slightly to the right, presenting as persistent dull pain, colicky pain, or hidden pain, which gradually worsens, leading to decreased appetite, weight loss, fatigue, and complications such as intestinal obstruction. In cases of intestinal perforation, the pain is severe.

　　2. Obstructive symptoms

　　It is often one of the main reasons for patients to seek medical attention. The annular stenosis lesion often presents with chronic incomplete intestinal obstruction as the main manifestation. The mass grows infiltratively, making the intestinal lumen rigid and narrow, causing intestinal obstruction. Patients often have vomiting, abdominal distension, and the vomitus contains gastric contents, bile, or blood.

　　3. Gastrointestinal bleeding

　　It is relatively common. The surface of ulcerative adenocarcinoma may have bleeding due to vascular erosion and ulceration, which can cause intermittent or persistent gastrointestinal bleeding. Most cases are chronic blood loss, mainly manifested as melena. When the lesion involves larger blood vessels, there may be massive bleeding, manifested as hematemesis or hematochezia, with stools appearing black or dark red, and even leading to hypovolemic shock. Chronic chronic blood loss can lead to anemia.

　　4. Abdominal mass

　　The volume of small intestinal adenocarcinoma is generally not large, and it rarely appears as a mass. There are reports that about 1/3 of patients can palpate an abdominal mass when they seek medical attention, which may be an expanded and thickened intestinal tract at the site of obstruction. Masses that grow outward can also be palpated sometimes, and they may be tender. Masses in emaciated patients have clear boundaries.

　　5. Jaundice

　　About 80% of duodenal descending tumor cases present with jaundice as the main symptom. The mass compresses the common bile duct or the duodenal papilla, causing bile duct obstruction and obstructive jaundice. In the early stage, it presents with fluctuating symptoms, and in the later stage, it presents with persistent symptoms that gradually deepen.

　　6. Signs and symptoms

　　Patients may present with weight loss, anemia, abdominal tenderness, which is often located at the site of the mass. In the late stage, abdominal masses can be palpated. In cases with intestinal obstruction, there may be intestinal type and peristaltic waves, hyperactive bowel sounds, and peritoneal irritation signs in cases of intestinal perforation. Liver metastasis may sometimes be palpable as an enlarged liver.

　　1. Avoid long-term consumption of alcoholic beverages, quit smoking and drinking habits, and do not overeat pickled vegetables, sour, spicy and irritating foods. Ban the consumption of moldy foods. It is especially important for those with chronic pharyngitis to develop good dietary hygiene habits, such as eating less meat and more vegetables, and consuming fresh fruits and vegetables.

　　2. During the cold season, maintain appropriate temperature and humidity indoors and pay attention to air circulation. The ideal room temperature is 20℃, and avoid covering yourself with too many blankets during sleep to prevent overheating or excessive dryness, which may cause discomfort in the throat. Do not sleep with your head facing the wind, and rest for a while after strenuous labor before taking a cold shower. For those with acute pharyngitis caused by colds or flu, drink plenty of hot water or ginger soup to induce sweating and increase urination. Pay attention to bowel movements and treat acute inflammation promptly to prevent it from becoming chronic. Organs with chronic lesions are more prone to malignant transformation.

　　3. Strengthen labor protection. Proper handling is required for harmful gases and dust in the production process, such as silica dust, ammonia chloride, bromine, iodine, etc. Workers who have long-term contact with harmful chemical gases should wear gas masks and protective isolation clothing, etc.

　　4. Strengthen physical fitness, enhance physical exercise. Commonly use cold water to wash the face and body, prevent colds, have work and rest, live a regular life, and do outdoor activities in the morning or after work.

　　1. Histopathological examination

　　For duodenal adenocarcinoma, duodenal fluid cytology examination can be performed, but due to the low success rate of duodenal drainage, it is time-consuming, and the patient's pain is great, making it difficult to cooperate. Currently, it is rarely used.

　　2. Blood routine examination

　　It can be found that there is microcytic anemia.

　　3. Fecal occult blood test

　　It can be positive.

　　4. Serum bilirubin test

　　Tumors at the ampulla of the duodenum can cause an increase in serum conjugated bilirubin.

　　In terms of diet, attention should be paid to reasonable nutrition, with food being as diverse as possible. Eat more high-protein, vitamin and trace element-rich, low animal fat, easily digestible foods, as well as fresh fruits and vegetables. Avoid long-term consumption of alcoholic beverages, quit smoking and drinking habits, do not overeat pickled vegetables, sour, spicy and irritating foods, and avoid eating moldy foods.

　　Avoid staying up late, avoid fatigue, and avoid drastic changes in mood.

　　1. Treatment

　　Adenocarcinoma of the small intestine is not sensitive to radiotherapy and not sensitive to chemotherapy. Only a few cases can be controlled by chemotherapy to alleviate symptoms. Fluorouracil (5-Fu), mitomycin (MMC), or cisplatin (DDP) can be given. Therefore, surgery is the main treatment for adenocarcinoma of the small intestine, with radiotherapy and chemotherapy having poor effects. The principle of surgical treatment is to perform a complete resection of the tumor segment of the intestine and the corresponding mesentery and regional lymph nodes, sometimes requiring the resection of involved adjacent organs. The range of the resected intestinal segment should be determined according to the blood supply after ligation of the blood vessels, but at least 10 cm above the normal intestinal segment near and far from the tumor edge should be resected.

　　Duodenal adenocarcinoma should undergo pancreatectomy with duodenectomy and jejuno-pancreatic anastomosis, biliary jejunostomy, and gastrojejunal anastomosis. Some people believe that early adenocarcinoma of the first, third, and fourth segments of the duodenum can be treated by resection of the tumor segmental intestine, which has a small scope and less impact. Opponents argue that the resection is not thorough enough. If the patient's condition is good, with an age not exceeding 70 years and a constitution that can tolerate the pancreatoduodenectomy, the radical resection is effective. Adenocarcinoma of the jejunum and ileum should be cleared of fat and lymphatic tissue around the superior mesenteric artery and vein. Adenocarcinoma of the distal ileum should undergo radical right hemicolectomy.

　　The treatment of small intestinal adenocarcinoma is mainly surgical. The basic principle of surgery is to resect the intestinal segment where the tumor is located, the corresponding mesentery, and the lymph nodes. Small intestinal cancer is different from leiomyosarcoma, with strong infiltrative ability, often involving the main trunk of the superior mesenteric artery or vein, or fixed on the abdominal aorta or inferior vena cava, which cannot be separated, and only palliative shunting surgery can be performed. Therefore, for those with advanced tumors that cannot be resected, bypass surgery can be performed to alleviate symptoms, and interventional treatment can be performed to control the growth of the tumor.

　　For jejunoileal adenocarcinoma, intestinal segment resection should be performed at a distance of more than 10cm from the proximal and distal edges of the tumor mass. The vessels in this segment of the intestinal tract (the origin of the vessels in this segment is divided from the superior mesenteric artery and vein) should be ligated, the mesentery in this segment should be cleared, and the lymphatic fatty tissue around the superior mesenteric artery and vein should be cleaned. Due to the need to protect the superior mesenteric artery and vein, the scope of cleaning is limited. The lymphatic drainage of the distal ileum is along the ileocolic artery to the root of the mesentery, and it is difficult to thoroughly clean the regional lymph nodes if the ileocolic artery is preserved. Therefore, a right hemicolectomy is required. If there is widespread metastasis found during surgery, palliative resection can be performed if the local condition of the tumor allows. For those who cannot be resected and have obstruction, bypass surgery should be performed.

　　For poorly differentiated small intestinal cancer, chemotherapy and radiotherapy have certain effects, so appropriate chemotherapy and radiotherapy should be supplemented after surgery.

　　2. Prognosis

　　At the time of diagnosis of small intestinal adenocarcinoma, regional lymph node and liver metastases are often present, and radical resection is often not possible, with a poor prognosis. There are reports of surgical treatment for 298 cases of small intestinal adenocarcinoma, of which only 50.7% were able to undergo radical resection, 10.7% were palliative resection, 16.8% were bypass surgery, and the rest could only be treated with simple laparotomy. The 5-year survival rate after small intestinal adenocarcinoma resection in China is 19% to 31%, and the 5-year survival rate after radical resection is 34% to 41%. Zar summarized 923 cases of small intestinal adenocarcinoma, with a 5-year and 10-year survival rate of 39% and 37% respectively for those located in the duodenum, and 46% and 41% respectively for those located in the jejunum and ileum. The 5-year survival rate of women is slightly higher than that of men.