Anal and Rectal Malignant Melanoma

　　Pathogenesis

　　The disease originates from the malignant transformation of melanocytes. Melanocytes or their precursor cells originate from neural crest cells of the ectoderm and migrate to the skin, eyes, mucosal surfaces, and nervous system during embryonic development. Under the influence of certain factors, such as hormone metabolism disorders, chemical stimulation, and high-energy radiation damage, melanocytes overproliferate and undergo malignant transformation. Some people believe that the anal and rectal junction belongs to stratified squamous epithelium, accumulating a large number of melanocytes, which is the histological basis for the occurrence of anal and rectal melanoma. Therefore, it is currently generally believed that anal melanoma is primary, but there is a divergence of opinion on whether rectal melanoma is primary or secondary, with most people believing that rectal melanoma is the result of the malignant transformation of melanocytes in the anal area and its upward extension, which should be considered as metastasis. The microscopic characteristics are mainly: tumor cells are similar to nevus cells,呈多角形、梭形或多边形，nuclei are large,畸形,泡状，nucleoli are prominent, mitotic figures are not fixed, cytoplasm is generally scarce. Most can find varying amounts of melanin granules.

　　This disease can show distant metastasis in the early stage, and hemotransmission is its main mode of metastasis, and it can also be lymphatic metastasis. It often metastasizes to distant organs. For example, in a comprehensive report of 72 cases in China, 46 cases were found to have metastasis at diagnosis, accounting for 63.9%, including 10 cases in the liver, 6 cases in the spleen, 23 cases in abdominal lymph nodes, 3 cases in skin and soft tissue, 1 case in the brain, 3 cases of vaginal invasion.

　　1. Colonic obstruction:It is one of the late complications of anal and rectal malignant melanoma, which can occur suddenly or gradually. It is often caused by tumor proliferation blocking the intestinal lumen or narrowing of the intestinal lumen, or due to acute inflammation, congestion, edema, hemorrhage, etc., at the tumor site.

　　2. Intestinal perforation:There are two situations of perforation in anal and rectal malignant melanoma: perforation occurs locally in the tumor; perforation of the proximal colon, which is a complication of tumor obstruction. After perforation, clinical manifestations can include diffuse peritonitis, localized peritonitis, or formation of local abscesses. Diffuse peritonitis often accompanied by toxic shock, with a very high mortality rate.

　　The prognosis of anal and rectal malignant melanoma is not related to the patient's gender and age, but is closely related to the course of the disease, the extent of tumor infiltration, differentiation degree, and whether there is metastasis.

　　1. Symptoms of prolapse:A black mass in the anal area prolapses out, which is small in the early stage and can be retracted spontaneously, but it increases in size later and needs to be retracted by hand.

　　2. Hematochezia:The tumor is located low, easily subject to fecal friction or trauma and bleeding, mostly fresh blood, or with black effusion, foul smell.

　　3. Symptoms of anal and rectal irritation:Due to the tumor protruding into the rectal ampulla, stimulating the rectal wall receptors, patients often feel discomfort and a sense of dropping in the anal area, changes in defecation habits, and alternating constipation and diarrhea.

　　4. Tumor:Generally 3-6 cm in size, located near the anal verge, presenting as nodular, polypoid, hard, most of which are purple-black or brown-black.

　　5. Anal pain:It is a common symptom of malignant melanoma. When the tumor ulcerates, becomes infected, or invades the surrounding tissue around the anus, it can cause anal pain.

　　The gross appearance of rectal melanoma is generally below 80%, and most are small melanoma or pigment-free melanoma, which are often misdiagnosed. Final diagnosis often requires pathological examination. Since junctional nevi around the anal area are common, when the size of a mole is greater than 0.5 cm, it should be highly suspected. For pigment-free tumors (accounting for 1/3), Massobn-Fonlana melanotic silver staining method or dopa staining, tyrosinase reaction can also be used for diagnosis.

　　Since the etiology of anal and rectal malignant melanoma is not fully understood, there is no special preventive method yet. The following preventive measures are mainly aimed at reducing the chance of malignancy and early detection and treatment of patients.

　　1. Actively prevent and treat rectal polyps, anal fistula, anal fissure, ulcerative colitis, and chronic intestinal inflammation. For multiple polyps and papillary polyps, once the diagnosis is clear, early surgery should be performed to reduce the chance of malignancy.

　　2. Have a diverse diet, develop good eating habits, do not have a preference for certain foods, do not picky eat, and do not consume high-fat, high-protein diets for a long time. Eating fresh vegetables rich in vitamins and fiber regularly may be important for preventing cancer.

　　3. Prevent constipation and keep the bowels open.

　　4. Pay high attention to regular cancer screening, always be aware of self-examination, increase vigilance, and seek treatment in a timely manner after discovering 'warning signals' to achieve early detection and early treatment, thereby improving the survival rate of anal and rectal malignant melanoma.

　　1. Histopathological examination:It is the main basis for diagnosis. Since the melanoma is very small or pigment-free, the entire tumor should be excised during sampling to avoid iatrogenic spread and low diagnostic accuracy of biopsy. For pigment-free melanoma, Massobn-Fonlana melanotic silver staining method or dopa staining, tyrosinase reaction, and other methods can assist in pathological diagnosis.

　　2. Anoscope examination:It can be seen that there are purple-black or brown-black protruding tumors near the anal verge, generally 3-6 cm in size, resembling a mushroom umbrella in shape, with a short and wide stalk, or nodular, resembling cauliflower.

　　First, dietary therapy after chemotherapy for anal and rectal malignant melanoma

　　1. Malignant melanoma patients often develop melanoma from moles on the body, which is usually based on physical weakness, deficiency of both Qi and blood, or insufficient kidney Qi. After serious illness, or after surgery and chemotherapy, the physical condition becomes even weaker. Therefore, regulating diet and strengthening nutrition becomes particularly important. The spleen is responsible for transportation and transformation, and is the source of Qi and blood. To replenish both Qi and blood, it is necessary to first invigorate the spleen and open the stomach to nourish Qi and blood. The following dietary options can be chosen:

　　(1) Ginseng porridge: 3g of ginseng powder (or 15g of Codonopsis pilosula), appropriate amount of rock sugar, 100g of good rice, cooked as porridge and eaten regularly.

　　(2) Astragalus porridge: 50g of Astragalus membranaceus, decocted in water to make the porridge, 100g of good rice, appropriate amount of brown sugar, 3g of bran powder, cooked together as porridge.

　　(3) Angelica sinensis and Astragalus steam chicken: 20g of Angelica sinensis, 100g of Astragalus membranaceus, 1 hen, cooked together and served in portions.

　　(4) Ginseng and jujube rice: 3g of ginseng (or 15g of Codonopsis pilosula), 20g of jujube, 250g of good rice, 50g of sugar. Ginseng and jujube are chopped and steamed together, the rice is cooked, and sugar is added and served in portions.

　　(5) Atractylodes and jujube cake: 30g of Atractylodes macrocephala, 250g of jujube, chicken gallbladder, dried ginger, flour, oil, salt, and other spices in appropriate amounts. The drugs are ground into powder or cut into very fine pieces, mixed with flour and spices, fried into cakes, and eaten in portions.

　　2. Malignant melanoma patients often have symptoms of kidney deficiency. For insufficient liver and kidney, the following dietary options can be chosen:

　　(1) Cordyceps and goji berry: 10g of Cordyceps sinensis, 20g of goji berries, 100g of lean pork, 250g of eggs, appropriate amount of spices, cooked and served in portions.

　　(2) Goji berry porridge: 30g of goji berries, 100g of good rice, cooked together as porridge.

　　(3) Walnut duck: 200g of walnut kernel, 100g of chicken meat, 150g of water chestnut, 1 duck, a little cooking wine, appropriate amount of oil and salt, cooked together and served in portions.

　　3. For the toxic and stasis symptoms in malignant melanoma patients, the following dietary options can be chosen:

　　(1) Garlic porridge: 30g of purple garlic skin, 100g of good rice, cooked together as porridge.

　　(2) Asparagus and mushroom soup: 200g of asparagus, 100g of mushrooms, simmered with low heat, can be seasoned with appropriate spices for eating.

　　(3) Bamboo shoot porridge: 60g of bamboo shoot powder, 100g of good rice, cooked together as porridge.

　　Two, what foods are good for anal and rectal malignant melanoma?

　　1. It is advisable to eat more high-quality protein foods to enhance the body's immunity, such as lean meat, eggs, milk, fresh fish, and soy products.

　　2. It is advisable to eat more foods rich in fiber, which can significantly reduce the incidence of colon cancer.

　　3. Cancer is hard as stone, related to phlegm and qi stagnation, so it is advisable to eat foods with softening, expectorant, and dissipating effects; the pathogenesis of cancer is also often related to qi stagnation and blood stasis, so it is advisable to take foods with the effect of promoting blood circulation and removing blood stasis; the onset of cancer is also related to heat-toxin, so it is advisable to eat foods with the effect of clearing heat and detoxifying. Traditional Chinese medicine believes: 'Where evil accumulates, the qi must be deficient.' For cancer patients, it is advisable to strengthen the body and remove evil, so it is advisable to eat some foods that nourish yin and replenish qi, and invigorate the body.

　　Three, what foods should be avoided for anal and rectal malignant melanoma?

　　1. Avoid foods that may cause allergic reactions. Such as fish, shrimp, crab, chicken heads, pork heads, goose meat, chicken wings, chicken feet, etc., which may worsen the itching and inflammation in the genital area.

　　2. Try to eat less spicy and stimulating foods. For example: onions, pepper, chili, Sichuan pepper, mustard greens, fennel.

　　3. Avoid eating fried and greasy foods. Such as fried dough sticks, butter, butter, chocolate, etc., these foods have the effect of increasing dampness and heat, which is not conducive to the treatment of the disease.

　　4. Quit smoking, alcohol, and coffee, as well as other stimulant beverages.

　　First, treatment

　　Early treatment is recommended for this disease, but it is difficult to cure.

　　1. Surgical treatment:Patients with early visits are treated with abdominal perineal resection of the rectum. It is generally not necessary to perform inguinal lymph node dissection. For those with distant metastasis, palliative tumor resection is performed.

　　2. Chemotherapy:For disseminated lesions, chemotherapy is the main treatment method, and some patients can achieve remission. For patients who have undergone surgery, chemotherapy can be used as an adjuvant treatment.

　　(1) Single drug use: Effective drugs include cisplatin (cis-diamminedichloroplatinum), dacarbazine (chloroethylnitrosourea), carmustine (carmustine), lomustine (cyclohexyl nitrosourea), semustine (methylcyclohexyl nitrosourea), actinomycin D (actinomycin), hydroxyurea (HV), vinorelbine (vinblastine amide), vinblastine sulfate (vinblastine), and vincristine, etc. Dacarbazine has certain efficacy for recurrent malignant melanoma. The administration method is 2-4.5mg/(kg·d) added to a 5% glucose solution for intravenous infusion, for 10 consecutive days, followed by a rest period of 18 days as one course. The side effects include bone marrow suppression, gastrointestinal reactions, and symptoms similar to the common cold. The administration method of carmustine is 2.5mg/(kg·d) added to 200-500ml of 5% glucose solution or normal saline for intravenous infusion, once a week, for 3 weeks as one course. If local external circulation heating is performed at the same time as the use of anticancer drugs, the efficacy can be improved.

　　(2) Combined chemotherapy: The efficacy of combined chemotherapy with two or more drugs is better than that of single drug use. Commonly used combinations include dacarbazine, nitrosourea drugs, cisplatin, and vinblastine drugs. Common chemotherapy regimens include: ① Carmustine 125mg, intravenous infusion, on the 1st and 2nd days of the first 6 weeks; dacarbazine 200mg, intravenous infusion, from the 1st to the 5th day; vincristine 1-2mg, intravenous injection, on the 1st and 8th days, repeated every 3 weeks, for 3-4 cycles. ② Cisplatin 100mg/m2, intravenous infusion, on the 1st day; carmustine 125mg, intravenous infusion, on the 5th and 12th days; dacarbazine 200mg/m2, intravenous infusion, from the 6th to the 10th day; vincristine 1-2mg, intravenous injection, on the 4th and 11th days, repeated every 3 weeks, for 3-4 cycles.

　　3. Radiotherapy:Radiation therapy is not sensitive to melanoma, but some reports indicate that combined radiotherapy and heat therapy can improve the efficacy.

　　4. Immunotherapy:Immunotherapy has a certain therapeutic effect on melanoma, commonly using the BCG (dried freeze-dried Mycobacterium bovis BCG) scarification method on the skin or local injection into the tumor nodule. It is believed that BCG (dried freeze-dried Mycobacterium bovis BCG) can cause the body's lymphocytes of melanoma patients to aggregate in tumor nodules, stimulating the patient to produce a strong immune response. There are also tumor vaccines, cowpox virus, short rod vaccine, levamisole, interferon, and others that can also achieve certain effects. In recent years, some authors have proven that estrogen receptors exist in human melanoma cells, and estrogen-based drugs are used for treatment.

　　II. Prognosis

　　Due to the high malignancy and early metastasis of the disease, the prognosis is extremely poor, and the effects of various treatments are not very ideal. Literature reports that the average postoperative survival period is 12 months to 1.5 years, so some authors believe that local resection is not worse than abdominal perineal resection and apronectomy APR (Table 1).

　　Brady et al. (1995) reported the experience of treating 85 cases of anal canal rectal melanoma at the Memorial Sloan-Kettering Cancer Center over 64 years (1929-1993). There were 46 female and 39 male patients. The average age was 60 years (27-85 years). The average survival period was 15 months, and the 5-year survival rate was 17%. Among the 71 patients who underwent surgery, the 5-year survival rate of APR was 27%, while that of local resection was 5%, indicating that the APR surgery was effective. There were 10 long-term survivors (follow-up 5-22.5 years), all of whom were female, 9 of whom underwent APR (8 with negative lymph nodes, 1 with positive). One patient underwent local extensive resection. The size of the tumor: for long-term survivors of APR, the average was 2.5cm, and for those who did not survive long-term, it was 4.5cm. Brady believed that for locally small anal canal rectal melanomas without lymph node metastasis, APR surgery should be the first choice. Wanebo et al. believed that the main factors affecting the prognosis of this disease were the size and depth of the tumor invasion. When the depth of tumor invasion exceeds 2mm, most patients have difficulty surviving for more than 2 years after surgery. Among the 36 cases reported by them, the average survival period of patients after local resection was 21.5 months, and the average survival period of patients with abdominal perineal resection and negative inguinal lymph nodes was 16 months, and that with positive nodes was 7 months.

　　The main factors affecting prognosis are the depth of tumor invasion. If the depth of the tumor exceeds 1.7mm or more, the 5-year survival rate is 0.85%, 85% die within two years. Especially for patients with intra-abdominal visceral metastasis, even if the metastatic lesion can be removed, the average survival period is only 8 months. Comprehensive treatment with early diagnosis and early surgery as the main measures is the main measure to improve survival rate.