One. Definition and epidemiology
Familial adenomatous polyposis (FAP) is a group of autosomal dominant syndromes characterized by multiple colorectal adenomas. Its global incidence is 1/7000~1/10000 of births. It is a type of hereditary colorectal cancer, accounting for about 1% of colorectal cancer. Polyps in this disease mostly appear in adolescents, and only a few begin to grow in childhood, and there is no polyp growth in infancy, so it is not a congenital disease.
In the past, the disease was often called multiple polyposis of the colon, hereditary polyposis coli, familial multiple polyposis, and familial polyposis of the colon. of the colon FPC), adenomatous polyposis coli (adenomatous polyposis coli), now considering that this disease has a genetic family history, adenoma is not limited to the colon, this disease often manifests as a group of diseases, so it is often called For familial adenomatous polyposis.
FAP has the same effect on gender. The ratio of male to female is 1:1. Most cases show a high degree of autosomal dominant inheritance, which conforms to Mendelian law. The penetrance rate is 70% to 95%. Sporadic cases account for about 1/ 3. Adult FAP patients will have a family history of their parents, and half of their children will have FAP, which involves several generations. It is generally believed that by the age of 40 or at the age of the oldest disease in the family plus the age of 10, no adenoma will appear even if there is a family history. There are no regional and ethnic differences in the disease. The average age of adenoma is about 16 years old, and the age of colorectal cancer is about 40 years old.
In 1986, it was discovered that the occurrence of FAP was closely related to the malformation of chromosome 5. In 1987, Bodmer used RFLP to determine that the gene related to FAP was located at position 5 of chromosome. In 1991, the APC (adenomatous polyposis coli) gene was isolated and located exactly 5q21, which is a tumor suppressor gene, is closely related to the inheritance of FAP. It is currently believed that some other polyp-related syndromes, including Gardner syndrome, Turcot syndrome with central nervous system medulloblastoma, mild phenotypic familial adenomatous polyposis (attenuated familiar adenomatous poplyposis, AAPC), hereditary flat polyp Syndrome, juvenile polyposis (J-P syndrome), Cowden disease, Muri-Torre syndrome, etc., are all related to mutations in the APC gene, so they are called special types of familial adenomatous polyposis.
In 1987, a linkage analysis study found that the gene that plays a major role in the onset of FAP was located on the long arm of chromosome 5. Then in 1991, the pathogenic gene of the disease: APC gene was discovered through positional cloning in some FAP patients. Since then, more than 500 different germ cell APC mutations have been discovered in the FAP family. Based on the characteristics of DNA deletions (terminal chain mutations, such as small insertions or deletions, point mutations and large deletions), no apc protein or missing apc protein is formed from the mutant allele due to insufficient APC activity levels in colonic epithelial cells . APC mutations without missense are clearly related to the FAP phenotype, but some APC amino acid variants (such as I1307K, E1317Q) have been considered as possible susceptibility alleles for colorectal adenoma and cancer.
The APC gene encodes the amino acid sequence of 2834, which belongs to the Wnt information transmission pathway of vertebrates. In this pathway, the APC protein combines with β-catenin and lymphoid enhancer factor (LEF-1) to regulate its downstream target genes . At the same time, β-catenin can activate the tight junctions between epithelial cells controlled by E-cadherin, maintain the cytoskeleton and polarity, bind to microtubules, and affect embryonic cell movement and embryo formation. It is an important tumor suppressor Genes belong to the so-called "Gatekeeper" genes. In FAP patients, the inactivation of the APC gene initiates the development of colorectal cancer along the normal mucosa-hyperplasia-adenoma-carcinoma multi-stage and multi-step pattern. Ki-ras, TP53, MCC and other important oncogenes and tumor suppressor genes have mutated successively. Most sporadic colorectal cancers also follow this pattern. In most cases, loss of heterogeneity (LOH) of the APC gene initiates this cancerous process.
There are many ways of APC gene mutation. The most common APC gene mutation is a change in the gene sequence, which leads to the early appearance of the stop code and produces a non-functional truncated protein. More than 80% of FAP patients can detect mutations in the APC gene, but about 20% of patients fail to find APC gene mutations using existing genetic testing techniques. In 2003, the biallelic germ cell mutation of the excision repair gene MYH was first reported in APC-negative FAP patients. This finding suggests that gene defects as a recessive feature cause polyp phenotypic behavior in these families. Therefore, cases of MYH-associated polyps (MAP) appear in sporadic patients or patients whose relatives are implicated in the family. Most Caucasian patients have MYH deficiency with one of two mutations (Y165C and G382D) in at least one allele. These mutations affect the MYH amino acid residues retained through evolution and attenuate the enzymatic activity of equivalent proteins. About 20% of FAP patients do not have germ cell APC mutation and family history, which is consistent with the recessive inheritance of biallelic MYH mutation.
3. Pathological characteristics
Most of the colorectal polyps in FAP patients are densely growing, and the entire large intestine lumen is full of polypoid adenomas of different sizes (Figure 1). There are also polyps in some patients who have sporadic growth, with only dozens of polyps in the entire large intestine. The histology of polyps is a typical tubular adenoma, and villous adenomas may also appear, but simple villous adenomas are rare, and should be regarded as mixed adenomas, which are broad-based at first and gradually become pedicled polyps. In a few cases, there are hyperplastic polyps mixed between adenomatous polyps, so the clinical manifestations are various forms. The size of polyps varies from a few millimeters to a few centimeters, with more than 0.5-1cm. The number of polyps is at least 100, mostly between 300 and 3000, and up to 5000. When the number is large, they are densely distributed in a carpet pattern, and normal mucosa is almost invisible. Large polyps often have erosions and bleeding. If ulcers are formed, Almost 100% malignant change. The rectum is the most common site, followed by the sigmoid colon, descending colon, and transverse colon. Some patients tend to decrease close to the proximal colon, and most polyps do not involve the small intestine.
100% of FAP polyps become malignant. It usually takes about 15 years for polyps to become malignant. If they are not treated in time, about 50% of patients will become cancerous at the age of 20, about 75% of patients will become cancer at the age of 35, and about 90 at the age of 45. % Of patients develop cancer, and almost all develop into cancer after the age of 50. Without colon resection, the risk of colon cancer is 100%, which slightly increases the risk of extracolonic cancers, including duodenal cancer, thyroid cancer, hepatoblastoma, osteoma, gastric cancer, pancreatic cancer, and desmoid tumors (Table 1).
The diagnosis of FAP includes clinical and genetic diagnosis. The diagnosis of FAP is clinically based. The main role of genetic testing as a diagnostic test is to predict genetic heterogeneity when the diagnosis of genetic disease is used as the first step in the treatment of affected patients and their entire families. According to international guidelines, the diagnosis of FAP must meet one of the following conditions: 1. There are more than 100 adenomas; 2. In patients with family history or genetic predisposition, the number of adenomas is more than 20. This means that the diagnosis of FAP does not require a family history of polyposis and/or colorectal cancer for an individual. When suspecting this disease, it is important to determine the number and nature of polyps. At the same time, the manifestations of some other diseases, including intestinal (upper gastrointestinal polyps) and extraintestinal (dermoid cysts, sclerofibromatosis, osteoma, dental disease, congenital retinal pigment epithelial cell hyperplasia) are not Should be ignored. When patients present with non-specific colorectal cancer "polyps", the phenotype of these diseases may become an important clue for the diagnosis of FAP.
Attenuated FAP (AFAP) is mild and still increases the risk of CRC. The total number of polyps is usually 10-100. AFAP usually develops after the age of 25, mainly manifested as proximal colon or total colon polyps.
The FAP genetic test only detects a single gene (APC); however, multiple mutations in this gene have been confirmed (allelic heterogeneity) and approximately 96% are missing genes. At the same time, not all families are related to chromosome 5q. Currently in the United States, DNA testing for FAP patients and their family members, and even babies before birth (through amniocentesis), has tended to be commercialized. The FAP detection generally follows the following rules: First, use IVSP to locate the mutation site, and then use DNA sequencing to accurately describe the first family member with the disease. If the IVSP test is negative, then DNA sequencing of the APC gene is allowed. When the mutation in the family has been identified, the testing of other at-risk family members can only be done with IVSP.If the mutation in the first patient is obtained through DNA sequencing, it is reasonable for other at-risk individuals to continue to use the genetic testing method. When the mutation has not been identified (the mutation is not detected), the negative result may be true negative (in any related gene, there is no susceptible gene mutation that can be identified by prior knowledge and technology), or false negative (undetected mutation may be Exist in known or unknown genes). If someone has colorectal cancer, this will also be a false negative in familial colorectal cancer syndrome or a single case. People with a strong family history are more likely to have false negatives. The result of "undetected mutation" is the most likely to be misunderstood and easily leads to inappropriate genetic counseling. A classic study of FAP mutation detection shows that in about one-third of cases, the doctor's interpretation of the test results is incorrect. False negative results are the main reason for interpretation errors. Some doctors do not realize that negative results (DNA changes that are not detected) may indicate false negative results because the APC mutations in family members that have been onset have not been identified in advance.
The main diagnostic methods are:
1. Digital rectal examination: Since FAP polyps are most often seen in the rectum, a simple digital rectal examination can provide a preliminary diagnosis for the next step.
2. Electronic colonoscopy and barium enema: you can understand the extent of the lesion and get a biopsy to clarify the nature of the tumor.
3. Fiber gastroscopy and duodenoscopy: you can understand whether there are polyps in the stomach and duodenum.
4. Ophthalmoscopy: Because FAP coexists with congenital retinal pigment epithelial hyperplasia (CHRPE), it has a high degree of diagnostic sensitivity and specificity. Therefore, ophthalmoscopy can be classified as a screening or screening for members of the family who have not yet had a colonic adenoma Diagnostic means.
5. X-ray, CT or MRI: can understand extracolonic manifestations such as bone tumors and central nervous system tumors.
6. Peripheral blood APC gene detection: it can be used as a means of genetic diagnosis.
Five, clinical manifestations
The most prominent clinical feature of this disease is multiple colorectal adenomatous polyps, which can be divided into three stages clinically: preclinical stage, adenoma stage and cancer stage. The preclinical stage refers to the period before the appearance of adenoma; when adenoma appears, it enters the hidden period of the adenoma stage, with a median age of 16.5 years. When intestinal symptoms appear, it enters the symptomatic stage of the adenoma stage, and the median age is 29 years old; cancer stage refers to the stage from the diagnosis of colorectal cancer to death. The median age of colorectal cancer is 36 to 40 years.
Common symptoms of the disease include:
1. Abdominal pain: it is a dull pain in the abdomen. Individual patients have intussusception due to large polyps. The patient has abdominal pain, bloating, nausea, vomiting and other intestinal obstruction symptoms. Some intussusception can be reset by itself and the symptoms are relieved, but the intussusception Can be repeated.
2. Diarrhea or frequent and loose stools: Diarrhea is mucus, which is characterized by the discharge of a large amount of odorless mucus after getting up in the morning. In severe cases, it will cause water and electrolyte disturbances. As polyps increase and increase, symptoms worsen and defecation Sometimes polyps can be seen protruding from the anal opening.
3. Hematochezia: It is more common, often showing mucus and blood in the stool. At this time, the polyps are often malignant. Sometimes there is a large amount of blood in the stool. The blood in the stool is mostly intermittent. There is a feeling of falling in the anus.
4. Weight loss, anemia, fatigue: It suggests that polyps may have become cancerous.
Air-barium double contrast imaging of this disease shows that the intestine has dense small filling defects with petal-like edges. After the barium is emptied, messy honeycomb changes can be seen. The normal mucosal folds disappear, the intestine is rigid, but the intestinal cavity is mostly not narrow. Electronic enteroscopy shows that the large intestine polyps are mostly soybean-sized, hemispherical or broad-based. It is difficult to see the normal mucosa in the intestinal tube where the polyps are densely distributed. Among the small polyps, there are often short pedicles or wide-basal pedicle polyps that are scattered. They are lobulated or villous, with congestion, edema, erosion, bleeding, etc., and small polyps are mostly without congestion or edema.
In addition to the symptoms of the large intestine, FAP also has some extraintestinal manifestations:
1. Congenital hypertrophy of the retinal pigment epithelium (CHRPE): the combined incidence rate of it and FAP is 87%, and 50% of the family members may be accompanied by CHRPE, which can be used as a characteristic of early diagnosis According to the basis, its predicted value reaches 100%. This type of fundus lesions is manifested as flat lesions with clear deep boundaries of the retina, accompanied by pigment changes. When the retina of both eyes has lesions at the same time, it indicates that the FAP gene is inherited.
2. Gastric and duodenal polyps: About 50% of FAP patients are accompanied by adenomas in the gastric body and fundus region, called fundus gland polyps, which are pathologically hyperplastic polyps, and reports of cancer are rare, so usually No special treatment is required.Unlike the fundus gland polyps, most of the polyps near the pylorus of the gastric antrum are adenomas, which are precancerous lesions, and should be completely removed after biopsy to prevent cancer. Duodenal polyps are adenomatous polyps, which usually occur in the second or third segment of the duodenum, including the ampulla of Vater. There can be as many as 50, with a diameter of 3 to 5 mm. Adenomas can sometimes be small and difficult It is found that it can sometimes be so large that it covers a part of the duodenal intestine. Duodenal adenomas are prone to cancer. The literature reports that the risk of duodenal cancer in FAP patients is 4%; if the duodenal adenoma is severe or high-risk, the canceration rate can be as high as 25%. Therefore, even if the duodenal papilla looks normal, biopsy of the duodenal papilla and large or suspected cancerous duodenal polyps should be performed regularly.
3. Hepatofetal tumor: It is a rare pediatric tumor, with an incidence rate of 1 in 100,000 under 15 years of age. Giardiello and others investigated the family of Johns Hopkins Polyposis Registry and believed that both FAP and Gardner syndrome can be typical When hepatoblastoma occurs, they estimated that the relative risk of hepatoblastoma in APC gene mutation carriers from birth to 4 years old is 3.3/1000/year.
4. Osteoma: Osteoma of the mandible can be seen in more than 90% of patients with FAP, which is also a characteristic manifestation of this disease.
5. Central nervous system tumors: most common in the brain, a few in the spinal cord, most pathologically glioblastoma. The incidence of medulloblastoma in the central nervous system of FAP patients is 92 times that of normal people.
Other special types of FAP include:
1. Gardner syndrome: The first triad of colonic polyposis reported by Gardner and Richards, namely multiple colon polyps, multiple osteoma and skin and soft tissue tumors. Multiple osteomas mainly occur in the face and long bones, and the above-face and mandibular osteomas account for 76% to 90%. Long bones often develop benign bone tumors or exostoses. Common skin and soft tissue tumors are epidermoid cysts, fibroids and sarcomas, neurofibromas, latent pilose cysts and so on. Multiple large sebaceous cysts on the face and limbs are a feature of this disease. Mesenteric ligamentoid tumor is the main cause of death in patients with Gardner syndrome.
2. Turcot syndrome with cerebral medulloblastoma: In Turcot syndrome characterized by central nervous system tumors and intestinal polyps, the number of colorectal adenomas is small, and some patients are complicated by hepatic nodular hyperplasia and multiple skin damage including Mucosal coffee spots, basal cell nevi and cancer, seborrheic keratosis. Turcot syndrome is genetically different from FAP, and it may disappear in offspring. Compared with FAP, its clinical manifestations have more specific manifestations: (1) The number of polyps in the large intestine is less, generally 20-100; (2) The polyps are larger, generally larger than 3cm in diameter; (3) Cancerous Earlier, 70% to 100% of patients may develop cancer in the second 10 years or the third 10 years.
3. Hereditary flat polyp syndrome and mild phenotypic familial adenomatous polyposis: the two have been considered to be independent hereditary polyposis, and they have been confirmed to belong to the FAP subclass caused by different mutation sites of the APC gene. Hereditary flat adenoma syndrome (hereditary flat adenoma syndrome) is characterized by a small number of intestinal polyps, which are flat. The so-called mild phenotypic familial adenomatous polyposis coli (Attenuated adenomatous polyposis coli, AAPC or attenuated form of familial adenomatous polyposis) is characterized by a small number of intestinal polyps and a late occurrence of colorectal cancer. Polyps are more likely to occur in the proximal colon. The age of onset of colorectal cancer is 12 to 15 years later than FAP and 10 years earlier than sporadic cancer. In addition, there are more polyps in the upper gastrointestinal tract.
4. Juvenile polyposis (J-P syndrome): It is an autosomal dominant gastrointestinal epithelium with malignant transformation syndrome. The incidence rate is 1/100000. The surface of a typical polyp is covered with normal intestinal mucosa, so the appearance is smooth, the interstitial composition of the polyp is dominant, there are cysts of different sizes, there is no smooth muscle in the central cord, and it is vascular fibrous tissue. It is characterized by multiple, hamartomatous polyps involving the colorectal (98%), stomach (14%), and small intestine (9%), often accompanied by a family history of juvenile polyposis. Hematochezia in children before the age of 10 is a typical clinical symptom of adolescent polyposis. According to the location of the disease, it can be divided into several subtypes: (1) familial juvenile gastric polyposis confined to the stomach; (2) familial juvenile colon polyposis confined to the colon; (3) extensive familial juvenile gastrointestinal polyposis disease.
5. Peutz-Jeghers Syndrome (Peutz-Jeghers Syndrome, PJS): It is a rare chromosomal dominant inheritance syndrome with an incidence rate of 1/20000. Dark spots on the skin are the most prominent feature of PJS patients. Dark spots are usually located on the lips, around the eyes and nose, around the anus, and on the fingers (toes). So far there is no report showing that PJS dark spots can become cancerous. Gastrointestinal polyps usually occur in the small intestine. The colon and stomach are relatively rare. Microscopically, it can be seen that the mucosal muscle hyperplasia is dendritic interspersed between the gland ducts, which is an important basis for the pathological diagnosis of PJS (PJS polyps). Patients often have abdominal pain due to small intestinal polyps, and obstruction may occur in severe cases. The clinical manifestations are bloody stools, abdominal pain and anemia (about 25%), sometimes complicated by intussusception and intestinal obstruction.
6. Cowden syndrome: It was first reported by Lloyd and Dennis in 1963 and named Cowden syndrome according to the patient's last name. Subsequent reports have confirmed that the syndrome is an autosomal dominant syndrome characterized by multiple hamartomas. Verrucous papules on the skin and oral cavity are typical clinical manifestations of this disease. Some patients are prone to malignant tumors, most commonly breast cancer, thyroid cancer, and endometrial cancer.
7. Hereditary sclerofibromatosis: or hereditary aggressive fibromatosis, hereditary ligamentoid fibroma. Characterized by intractable and aggressive local growth, it is more common in the anterior abdominal wall, abdominal surgical incision, scapula, small mesenteric and retroperitoneum, especially in postoperative, trauma and postpartum patients. The tumor does not metastasize, but the boundary is not Qing is infiltrating and expansive growth, local manifestation is malignant, after resection, it is easy to recur and compress adjacent structures and organs. Histopathology is fibroblast and glial fiber hyperplasia. Colorectal polyps and bone tumors are rare in patients. They often have a family history of colorectal adenomatous polyposis and colorectal cancer, without congenital retinal pigment epithelial hypertrophy.
Surgical treatment is currently the best way to treat this disease. Early radical/preventive surgical treatment is generally advocated for confirmed patients.
There are reports showing that genes are related to phenotypes, so different APC gene mutation positions produce different clinical manifestations, which provide clinicians with a certain reference. Surgical preventive surgery before the age of 25 or at the time of diagnosis is believed to reduce the risk of colorectal cancer in patients with adenoma. The choice of different surgical treatments (total colectomy versus total colorectal resection) mainly depends on the severity of rectal polyps. When the number of rectal polyps is relatively small, it is controversial whether to accept total colorectal resection. If the APC mutation is at codon 1309, it indicates that this gene type is related to a serious colorectal phenotype and has a high risk factor for cancer. It should be accepted at this time Total colorectal resection.
Carriers of tumor susceptibility genes often live in a psychologically unstable state. Therefore, relieving patients' anxiety about cancer is often cited as the reason for preventive surgery. For familial adenomatous polyposis with genetic mutations with high tumor risk, surgery is the only effective way to reduce tumor occurrence and relieve tumor-related anxiety in patients. The basis of FAP's colorectal cancer treatment is preventive surgical resection. Flexible sigmoidoscopy can be used to guide the timing of surgical intervention when the patient is younger. Colorectal cancer in APC gene carriers usually does not appear in infancy and early adolescence. Patients with known APC gene mutations, FAP patients, or first-degree relatives of patients with known APC gene mutations begin to undergo soft sigmoidoscopy at the age of 10-12. If colon polyps are found or there are known APC gene mutations, follow-up and colonoscopy should be performed once a year. Usually, in the late teens or early twenties, patients will have diffuse polyposis and cannot be fully evaluated by colonoscopy. Therefore, if there are too many polyps that cannot be safely treated, surgical treatment is recommended.
The choice and timing of surgical treatment must be individualized according to the needs of the patient and the experience of the surgeon. The main surgical methods are:
1. Total colorectal resection and permanent ileostomy (total proctocolectomy and permanent ileostomy, TPC): This is the most promising surgical procedure for curing. It is a traditional classic surgery with the best thoroughness and the worst postoperative function. This procedure is not easily accepted by young patients because it requires an ileostomy. Therefore, it is usually reserved as an option for patients with locally advanced rectal cancer or loss of anal sphincter function. At present, this method is rarely used.
2. Total colectomy and ileorectal anastomosis (total colectomy and ileorectal anastomosis, IRA): preserve 7-10 cm of rectum during the operation, cut the rest of the colon and rectum, and perform ileorectal anastomosis.This method has little surgical damage, preserves defecation, urination and sexual function, and has low complications. However, the retained rectum must be followed up regularly, and the polyps found should be electrocautery or surgically removed in time. According to reports, the incidence of rectal stump cancer was 13% to 55% after 25 years of follow-up. Patients receiving IRA must undergo routine follow-up through endoscopic examination of rectal tissue at least every six months, and chemical preventive treatment must be applied after surgery. This procedure is suitable for adolescent patients or elderly patients, patients with few intestinal polyps. During the follow-up, other operations can be performed depending on the condition.
3. Total colon resection, rectal mucosal stripping, ileal pouch-anal anastomosis (IPAA): This operation has become the main surgical procedure for the treatment of FAP, which can preserve the anus and have relatively good bowel function, but The operation is more complicated, and the surgical mortality and postoperative complications rate are high (10%-44%), including anastomotic fistula, pelvic infection, anastomotic stricture, anal fistula, pouch-vaginal fistula, pouchitis, pouch polyps and Cancer etc. IPAA is suitable for most patients with FAP and IRA should be reserved for patients with less than 10 polyps in the rectal stump. Patients who choose IPAA are at risk of ileal pouch polyps and pouchitis. Patients must be urged to perform endoscopic bag evaluation every two years.
In general, TPC, IPAA, and IRA are considered safe, low postoperative complications, and acceptable functional preservation. However, different surgical procedures have different indications, and different centers may have preferences. The patient's genetic mutation, clinical manifestations and surgeon's experience are important factors to guide surgical selection.
Seven, chemical prevention
Since the 1980s, the status of NSAID in the prevention and treatment of colorectal cancer and colorectal adenoma, especially FAP adenoma, has gradually attracted attention. The molecular mechanism of regulating tumor growth is mainly to inhibit the activity of Cyclooxygenase-2 (COX-2). Traditional NSAIDs such as sulindac also inhibit the continuous expression of COX-1 in normal cells of the digestive tract, so there are many side effects, including digestive tract discomfort and ulcers. It inhibits COX-2 and inhibits prostaglandin synthesis to promote polyps regression, can also inhibit the proliferation of cancer cells, increase the apoptosis of mucosal epithelial cells, and can also reduce the proliferation of duodenal polyps.
Giardiello reported that sulindac 150mg twice a day treated FAP for 9 months, the number of adenomas decreased by 56%, the diameter decreased by 65%, no adenomas completely retreated, and the adenoma grew again after stopping treatment for 3 months. However, sulindac can turn the adenoma from a prominent shape to a flat shape. Although it is still a precancerous lesion of CRC, it is more difficult to find and remove under optical colonoscopy. In the United States, 150 mg of sulindac twice a day is mainly used to control polyposis in patients with FAP who still retain the rectum, but they should still be followed up annually. Celecoxib is a selective Cox-2 inhibitor, which can reduce gastrointestinal side effects and retreat adenomas at a dose of 400 mg twice a day. However, the FDA has recently withdrawn the indication of celecoxib for the treatment of FAP. The clinical benefit was not confirmed by post-market research.
8. Screening and follow-up
People at high risk of FAP usually need to undergo annual colonoscopy monitoring from 10-15 years old until 35 years old, and then check once every 3 years. The clinical significance of FAP genetic testing lies in deciding which family members should receive high-density colorectal examinations when they are teenagers. Since laboratory tests may not be 100% correct, some scholars have suggested that all relatives should People who are considered to be at high risk (the relatives who have a first-degree blood relationship with FAP patients have a 50% risk). (Table 1)
Genetic testing is very important. As mentioned above, if the APC gene is present, 50% of the previous high-risk population has not inherited the mutation from their parents, and even if the MYH gene is present, the probability of FAP is low (it requires both parents to carry the MYH mutation gene ).
Genetic testing also has a bad influence on clinical work. First, genetic testing is often misinterpreted by clinicians (Giardiello counts 30% of APC test results are misinterpreted); secondly, both positive and negative results may cause psychological stress.
Routine endoscopic monitoring of the upper gastrointestinal tract usually starts from 20-25 years old, and the duodenal ampulla is the key monitoring object. The monitoring interval depends on the severity of duodenal polyps (Spigelman score). The incidence of duodenal cancer increases with the increase of Spigelman score. Duodenal cancer is difficult to treat endoscopically. The risk of the onset of duodenal lesions depends on the location of the APC gene mutation (1400-1580 codons), however, there is no definite clinical suggestion.
Parenteral examinations such as thyroid examination in female patients should also be included. In the follow-up, various examination and analysis methods can be used comprehensively, such as physical examination, colonoscopy, ophthalmology examination, radiology scores of teeth and mandible, molecular genetic testing, etc.
Colonoscopy should be checked every 3 to 6 months after IPAA and IRA. For rectal adenomas, endoscopic ablation can be performed. If adenomas cannot be prevented by ablation or chemoprevention, surgical resection of the rectum should be considered. Once FAP is diagnosed, it is necessary to check the gastroscope every 1 to 3 years. It is best to check the duodenal ampulla with a side-view mirror.
Table 1 Cancer risk, related genes and management recommendations of FAP
The life expectancy of untreated FAP patients is 42 years. Since FAP patients have a 100% risk of colorectal cancer, the life span of patients undergoing colectomy is greatly extended. The main causes of death in FAP patients after colectomy are upper gastrointestinal tumors and sclerofibroma. The cumulative probability of developing other malignant tumors other than colorectal cancer is 11% before the age of 50, and 52% before the age of 75, most of which are periampullary carcinoma. The incidence of duodenal or periampullary adenocarcinoma in FAP patients is 4% to 12%. Sclerofibroma can occur in 20% of FAP patients, and mainly occurs after colectomy.
About the Author
Zuo Zhigui (Unit: Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University)