Perianal tumors

　　1. Causes of disease

　　1. Factors of infection:HPV infection is associated with the occurrence of genital condyloma acuminatum, and HPV can have a latent period of up to 40 years in the body, thus increasing the incidence of squamous cell carcinoma. There is a significant association between squamous cell carcinoma and a history of genital condyloma acuminatum (relative risk coefficient for males is 26.9, for females is 32.5), while transitional cell carcinoma is not related. PCR detection of HPV-DNA (especially HPV-16) shows that more than 80% of the squamous cell anal canal carcinoma tissues are positive. The positivity rate in male homosexuals with anal epithelial cell carcinoma can also reach 80%. In female patients and male homosexuals, high oncogenic type HPV infection is more common (especially HPV-13 and HPV-16), and most of them are positive in anal canal carcinoma tissues, while skin cancer around the anus is rarely positive. It can be seen that anal canal carcinoma is similar to cervical cancer, in which HPV is involved in the occurrence of tumors. HPV-16 antibodies can be detected in the serum of 55% of patients with anal canal carcinoma, so HPV-16 antibodies may be used as a tumor marker for anal canal carcinoma. In female patients without genital warts, anal cancer is related to herpes simplex virus type 1 (relative risk coefficient 4.1) and chlamydia trachomatis (relative risk coefficient 2.3); while in male patients without genital warts, it is related to gonorrhea (relative risk coefficient 17.2).

　　In patients with HIV infection, the incidence of anal squamous intraepithelial lesions (ASIL) and squamous cell carcinoma is also high. The relative risk coefficient for developing anal cancer after HIV infection is 84.1 in male homosexuals and 37.8 in non-homosexuals; while the relative risk coefficient for anal cancer before the onset of AIDS is 13.9-27.4. In addition, it has been found that 20%-45% of HIV-positive male patients have ASIL and high-grade anal squamous intraepithelial lesions, which are considered to be precancerous lesions. Recent research shows that, regardless of homosexuals or bisexuals, HIV infection facilitates HPV infection and promotes the pathogenic effect of HPV. Statistics show that 93% of HIV-positive male patients can detect HPV DNA in anal tissue, while only 61% of HIV-negative patients do. The above information indicates that HIV infection promotes the replication of HPV with carcinogenic properties, and HIV can promote HPV-related diseases (such as ASIL and squamous cell carcinoma).

　　2. Smoking:It has been reported that smoking has a synergistic effect on the pathogenic role of HPV, but there are also opposing reports. A recent study has shown that there is a significant correlation between perianal cancer (perianal cancer) and smoking in premenopausal women and women with a late first menstrual period; there is no correlation in male and postmenopausal patients. It is therefore speculated that the role of smoking in the pathogenesis of perianal cancer may be related to anti-estrogenic effects.

　　3. Influence of related diseases:Studies have shown that some benign anorectal diseases are related to the occurrence of perianal cancer, such as anal fistula, anal fissure, perianal abscess, and hemorrhoids. In the first year after the occurrence of these benign diseases, the relative risk coefficient for perianal cancer is high (12.0), and then it decreases significantly. Some people believe that these diseases may be complications of perianal cancer, but case-control studies show that this possibility is very small.

　　In addition, some literature reports indicate a certain correlation between health search, inflammatory bowel disease, and perianal cancer; immunosuppression after renal transplantation can increase the opportunity for HPV infection by 100 times, thus also increasing the incidence of perianal cancer.

　　2. Pathogenesis

　　1. Biological characteristics:Squamous cell carcinoma originates from the anal epithelial layer. Since the anal epithelium originates from the ectoderm of the embryo, squamous cell carcinoma shows more characteristics of skin adenocarcinoma and less of rectal adenocarcinoma. HPV with strong carcinogenic types (mainly HPV-13 and HPV-16) can integrate with the DNA of anal squamous cells, thereby playing an important role in the occurrence of anal cancer, with integrated HPV-16 found in more than 80% of anal cancers.

　　目前，尚未发现遗传易感体质，但在肛管癌发生中可检测到有p53和c-myc表达的基因异常。

　　2、组织学类型

　　（1）组织类型：鳞状细胞癌（也称表皮样癌）是最常见的组织类型，约占肛周肿瘤的80％。发生在肛门周围的肿瘤多数为角化上皮且分化良好；而位于肛管部位的肿瘤则多为非角化上皮且分化差。起源于肛管上部齿状线周围的肿瘤多为混合性，可同时有腺癌和鳞状细胞癌，也称之为移行癌性、泄殖腔源性癌或基底细胞癌，这三种术语实际上是同一个概念，但基底细胞癌目前最为常用。

　　基底细胞癌占肛门表皮样癌的40％，但按照不同的评价标准，这一比例可能有所差别。从临床和预后的角度，这二种类型的差别没有相关性，因此治疗上是基本相同的。

　　在基底细胞癌中，小细胞癌恶性程度较高，这种类型与小细胞肺癌相似，很容易转移扩散。

　　肛门腺癌很少见（文献报道一般为5％～10％，最多为18％），文献报道的病例均为来源于肛瘘和低位直肠肿瘤的胶样癌。

　　（2）癌前状态：在80％的肛管鳞状细胞癌中，可见到重度不典型增生和原位癌，尤其是来源于肛周移行区的鳞状细胞癌更为常见。肛门鳞状上皮内损害是另一种癌前病变；Bowen样丘疹病和Bowen’s病是常见的癌前疾病。

　　（3）ICD-O分类：国际肿瘤学疾病分类。

　　3、特殊类型：肛周区域的一些少见的组织亚型包括小细胞癌、淋巴瘤、恶性黑色素瘤和平滑肌肉瘤。恶性黑色素瘤占肛周癌的1％～4％，占所有恶性黑色素瘤的1％～2％，多数仅在显微镜下观察到色素沉着，少数肉眼可见。肛门恶性黑色素瘤容易和血栓性痔核相混淆，因而易延误诊断。

　　4、组织学分级：肛周癌的组织病理学分级如下：

　　G1：分化良好。

　　G2：中度分化。

　　G3：低分化。

　　G4：未分化。

　　由大肠埃希杆菌或厌氧菌等引起的肛管直肠周围脓肿易并发肛瘘，一旦出现有肛门附近有脓性分泌物流出的孔道，就需要警惕已合并本病。对于体质低下，以及长期使用免疫抑制剂患者，由于抗感染治疗效果差，感染容易蔓延，甚至进入血液循环并发菌血症，可以出现高热表现，故临床上应引起重视。

　　1. Symptoms

　　1. The symptoms of perianal cancer are often non-specific, common symptoms include hematochezia, perianal itching and discomfort. The symptoms often appear intermittently, making it difficult to alert the patient. 70% to 80% of perianal cancer cases were initially diagnosed as benign diseases. Bowen's disease is often accompanied by persistent perianal itching. Patients with Paget's disease may have no symptoms or may present with perianal itching and hemorrhagic erythema. Perianal cancer is often associated with diseases such as Paget's disease, mucosal leukoplakia, anal fissure, anal fistula, hemorrhoids, etc., making the diagnosis of perianal cancer more difficult and leading to misdiagnosis. Due to these reasons, timely early diagnosis cannot be made, which leads to rapid progression of the disease (60% to 70% of patients have a tumor diameter greater than 4cm), and then gradually appear defecation pain and changes in defecation habits, which indicates that the lesion damage is often significant, and in the advanced stage, there may be symptoms such as anal incontinence or rectovaginal fistula.

　　2. Anal canal cancer often presents as infiltrative ulcers in the anal canal, with slightly harder edges of the ulcers; in the upper anal canal, the tumor may sometimes present as polypoid, but the peripheral infiltrative changes are still visible.

　　3. Tumors occurring in the lower anal canal often progress quickly, with obvious symptoms, with obvious masses visible in the anal area, or masses located in the posterior part of the vagina, which often involves the anal orifice, distal rectum, and other adjacent tissues and organs (such as the vagina, prostate, etc.). In 15% to 20% of patients, the tumor can involve the pelvis-rectal space, which can manifest as perianal abscess or fistula.

　　4. Perianal cancer can also be accompanied by enlargement of the inguinal lymph nodes, which may be the first manifestation. At this time, the patient may have no symptoms at all, but the enlargement of the inguinal lymph nodes is often misdiagnosed as inflammatory lymphadenopathy or hernia, leading to a delay in the timely treatment of perianal cancer.

　　5. In some individual cases, liver metastasis has occurred when the perianal cancer was diagnosed.

　　2. Clinical staging

　　1. Staging criteria

　　(1) Determining the location

　　Perianal tumors mainly include two clinical types: anal canal tumors and tumors occurring in the surrounding tissues of the anal margin. However, the boundaries of these two sites and the tumors are sometimes difficult to distinguish, so the relevant data reports may not be consistent.

　　According to the standards of the International Union Against Cancer and the American Cancer Society in 1987, the anal margin area refers to the junction of the skin creases and the anal mucosa or slightly distal area.

　　The anal canal refers to the area from the anal-rectal ring to the anal margin. The mucosa is齿状 due to the pressure of the internal anal sphincter. It includes the transitional epithelium and the anal vermillion line, but the two sides of the anal margin area have no clear definition, and the length of the anal transition part is not completely consistent, it can be above or below the anal vermillion line.

　　(2) Staging methods

　　There are various methods for staging anal canal cancer, but there is no unified staging method. Clinical staging is mainly based on the depth of tumor infiltration after surgery; ultrasonic staging (proposed in 1991) is mainly based on ultrasonic reconstruction images, and the depth of invasion is determined according to the size, volume of the tumor, and the condition of perianal lymph nodes. The IUAC/AJCC standard considers the tumor in the anal margin area to be a skin cancer.

　　(3) Perianal skin cancer TNM staging.

　　(4) Anal margin tumor staging.

　　(5) Anal canal cancer TNM staging.

　　2. The judgment of clinical staging

　　(1) The basis for clinical staging

　　Accurate clinical staging depends on reasonable and correct examinations. Anorectal digital examination and rectaloscopy are of great value in understanding the position and size of perianal tumors. Palpation of surrounding tissues through the vagina is very helpful in understanding whether the lesion has invaded, especially in judging whether the rectovaginal side is invaded and whether there is lymph node enlargement. If the patient feels significant pain during the examination, it can be considered to perform the examination under anesthesia; for enlarged inguinal lymph nodes, fine needle aspiration biopsy can also be performed; for highly suspected lesions, if the puncture results are negative, surgical biopsy should be performed.

　　(2) Clinical staging of anal canal cancer

　　Endoscopic ultrasound (EUS) can understand the depth of lesion invasion and the condition of surrounding lymph nodes. The judgment of tumor invasion depth based on surgical operation is often affected by tissue edema and inflammation, and there may be some errors. EUS is more accurate in judging staging and can measure the size of lymph nodes. If the lymph nodes are larger than 1 cm, it can be considered as a sign of metastasis. In addition, fine needle aspiration biopsy can also be performed on enlarged lymph nodes under EUS.

　　Although EUS is often used for staging studies, to make the staging more accurate, sometimes it is necessary to rely on other examinations, such as transvaginal ultrasound, which is of great significance for judging whether the rectovaginal wall is invaded.

　　Abdominal and pelvic CT is helpful to understand whether there is metastasis in the liver, pelvic organs, internal iliac lymph nodes, etc., MRI is more accurate than CT, and chest X-ray examination is sometimes necessary.

　　(3) Re-staging

　　After the completion of treatment, it is recommended to perform clinical and endoscopic assessment through the anal canal again, which is of great value in understanding whether there is recurrence, etc. When performing endoscopic ultrasound through the anal canal, due to anal fibrosis, the patient's tolerance may be poor, and it is often difficult to distinguish between tumor recurrence and scar at this time.

　　After radiotherapy, it is not recommended to perform biopsy directly, because perianal tumors often regress slowly (sometimes requiring 2 months), and radiotherapy also easily produces radiation injury, and biopsy may cause chronic anal fistula; for residual tissue after surgery, detailed clinical examination should be performed, and if recurrence is suspected, multiple-site biopsy should be considered. If the patient has significant pain, these examinations should be performed under anesthesia.

　　Prognosis

　　Perianal tumors are prone to invade the anal sphincter muscle and cause symptoms, but in the early stage, the symptoms are often non-specific and easily ignored by patients and doctors, leading to delayed diagnosis. Therefore, most patients (60% to 70%) have progressed to an advanced stage by the time of definite diagnosis; 15% to 20% of patients find that the vagina, urethra, prostate, bladder, sacrum, or ilium has been invaded. Anal canal cancer, local lymph nodes are easily invaded, and the tumor can spread along the perianal lymphatic vessels. Distal anal canal cancer is prone to metastasize to inguinal lymph nodes, and proximal anal canal cancer is prone to metastasize to pelvic lymph nodes (such as pararectal and internal iliac lymph nodes), and finally to abdominal lymph nodes, among which about 25% involve both sides of the lymph nodes. Hematogenous dissemination is rare (less than 10%), and the main distant metastatic sites are the liver, lungs, and skin.

　　Many factors can affect the prognosis, such as the histological type of the tumor, the age and gender of the patient, the tumor staging, whether there is metastasis, and whether the tumor is sensitive to chemotherapy or radiotherapy. These may all be independent factors affecting prognosis. In evaluating prognosis, there is no significant correlation between squamous cell carcinoma and tumor staging. However, the pathological tissue grade is related to prognosis, with 75% of patients with low differentiation having a 5-year survival rate, while only 24% of patients with high differentiation. The exact cause of this situation is still unclear. The prognosis of adenocarcinoma is poor with radiotherapy, and may even be lower than that of rectal cancer, but the prognosis can be improved if radiotherapy and chemotherapy are used. For adenocarcinoma at the anal margin, the main factors affecting prognosis are whether the lymph nodes are invaded.

　　1. CEA detection:Its clinical significance is extremely limited, the positive rate is not high, and there is no direct relationship between the increase level and the development and staging of the tumor. It may be helpful for diagnosing liver metastasis and monitoring tumor recurrence. The expression of squamous cell carcinoma antigen has high sensitivity and specificity in anal canal cancer, but is not related to tumor staging, and its clinical application is limited. The detection of HPV antigen and other reports have clinical value that needs further research.

　　2. Biopsy:Any suspicious lesions in the anal canal and around the anus should undergo biopsy. If suspicious lymph nodes in the inguinal region are found, biopsy should also be performed. Histological examination can also distinguish squamous cell carcinoma from adenocarcinoma. For patients with obvious pain, biopsy should be performed under anesthesia; for enlarged inguinal lymph nodes, fine needle aspiration biopsy can also be performed; for highly suspicious lesions, if the needle biopsy results are negative, surgical biopsy should be performed.

　　3. Modern imaging:Modern imaging methods such as liver B-ultrasound, CT, and lung X-ray examination can easily detect the presence of liver and lung metastasis, and are also relatively accurate.

　　1. Dietetic recipe for perianal tumor

　　1. Sea cucumber stewed with Chinese yam and American ginseng

　　Prescription and usage: Use 96 grams of sea cucumber, 10 grams of American ginseng (separately packaged, only cook for 15 minutes), 250 grams of pork backbone, 65 grams of Chinese yam, and appropriate amounts of salt and peanut oil. First, cut the sea cucumber into small pieces, put it with the chopped pork backbone into a large pot, add Chinese yam and an appropriate amount of water, and simmer over low heat for 1 hour after the water boils. Then add slices of American ginseng, wolfberry, vegetable oil, and salt, and continue to simmer for another 15 minutes. Drink the soup in portions and eat the sea cucumber.

　　Efficacy: Prevents and treats cancer, invigorates Qi and nourishes blood.

　　Evaluation: Sea cucumber has a mild property, rich in protein, calcium, and iron. The mucopolysaccharides it contains can effectively enhance the body's immune function, inhibit the growth and prevent the metastasis of tumor cells, and the海参素(algin) it contains also has anticancer effects; American ginseng is slightly bitter and sweet, with a cool property, and has the efficacy of nourishing Qi and Yin, clearing fire and generating saliva, especially suitable for those with deficiency of both Qi and Yin after radiotherapy and chemotherapy, who experience fatigue, thirst, dry tongue, and dizziness; Chinese yam has a sweet and neutral taste, invigorates Qi and nourishes Yin, benefits the spleen and kidneys; Chinese wolfberry has a sweet and neutral taste, nourishes blood and benefits essence, improves eyesight and protects the liver, and can alleviate the damage to the liver caused by chemotherapy drugs. Accompanied by pork backbone, which is good for reinforcing the bone marrow, it has the effects of preventing and treating cancer, invigorating Qi and nourishing blood.

　　2. Stir-fried eggplant, chicken tail mushroom, and goose blood

　　Prescription and method: 125 grams of eggplant (cleaned, with skin, cut into pieces), 150 grams of chicken tail mushroom (cleaned, cut into segments), 96 grams of goose blood. First, stir-fry the eggplant and chicken tail mushroom with peanut oil and appropriate salt over low heat until they are seven or eight degrees of maturity, then add the goose blood and stir-fry quickly, and serve with a plate. Take 1 to 2 doses a day, and can be used continuously for 7 to 10 days, or can be alternated with other anti-cancer and anti-cancer therapeutic recipes.

　　Effectiveness: Nourishing the blood, preventing and treating cancer.

　　Evaluation: Eggplant is sweet and cool, rich in vitamin A, C, and E. The solanine contained in it can inhibit the formation of digestive tract tumors and promote defecation, and has the effects of preventing and treating cancer; chicken tail mushroom is sweet and cool, with a protein content of more than 21%, containing 8 essential amino acids and various vitamins. It can induce the synthesis of interferon, thus playing a role in preventing cancer, and has an auxiliary therapeutic effect on breast cancer, lymphoma, etc.; goose blood is slightly salty, containing vitamins and hemoglobin, which has a certain auxiliary therapeutic effect on esophageal cancer. The three are cooked into a dish, which can not only be used as a health-preserving and anti-cancer product, but also as an effective therapeutic recipe for esophageal cancer and colorectal cancer.

　　Second, what foods are good for perianal tumors

　　1. Increase the intake of foods that are beneficial for anti-cancer, such as buckwheat, Job's tears, hedgehog mushrooms, dregs, chrysanthemum, sea cucumber, figs, sesame, sea buckthorn, etc.

　　2. Provide adequate calories and protein for patients, and eat more high-quality protein foods such as milk, eggs, fish, and poultry.

　　3. Increase the intake of foods that can enhance immunity, such as mushrooms, mushrooms, black fungus, silver ear, etc.

　　Third, what foods should not be eaten for perianal tumors

　　1. Avoid smoking, alcohol, and spicy and刺激性 foods.

　　2. Avoid greasy, fried, moldy, and salted foods.

　　3. Avoid foods that are likely to cause heat, such as rooster and goose.

　　Maintain personal hygiene, homosexuals should pay attention to hygiene issues, avoid anal mucosal injury and induce infection. Those with symptoms such as hematochezia, perianal itching and discomfort should seek medical attention in a timely manner, investigate the cause, actively treat the primary anal disease, and avoid delay. For those with perianal abscesses, active anti-infection treatment should be carried out, and incision and drainage surgery should be performed after the abscess is localized to release the pus.