Invasive squamous cell carcinoma of the vulva

　　1. Etiology

　　The etiology of invasive squamous cell carcinoma of the vulva has not been fully clarified, but some risk factors related to the etiology have been identified, such as sexually transmitted diseases, viral infections, weakened immune function, chronic vulvar skin diseases, smoking, and so on.

　　Two, Pathogenesis

　　Pathology of vulvar invasive squamous cell carcinoma:

　　1. Grossly

　　It is similar to the early invasive squamous cell carcinoma of the vulva in the early stage, and small superficial, elevated hard ulcers or small hard nodules may appear in the vulva. In the later stage, large lesions with fusion, infection, necrosis, and hemorrhage may occur. Most of the cancer lesions are accompanied by white lesions or may have erosion and ulceration.

　　2. Under the microscope

　　The maximum diameter of the cancer lesion is >2cm, and the infiltrative depth is >1mm. The histological type of vulvar squamous cell carcinoma is the same as that of early invasive squamous cell carcinoma. Similarly, when performing pathological histological examination, attention should be paid to the size, number, infiltrative depth of the stroma, pathological grade, whether there is invasion of lymph vessels or blood vessels, and the coexisting other vulvar diseases, etc.

　　Vulvar invasive squamous cell carcinoma can be complicated with the following diseases:

　　1. As the cancer lesions gradually increase, they can spread to the urethra, perineal body, and vagina, leading to perineal cancer.

　　2. Some advanced patients may develop lung metastasis, so this disease may be complicated with lung cancer.

　　3. Due to decreased resistance, it can lead to imbalance of bacterial colonies inside and outside the body, resulting in infection in the end.

　　The main complications of radiotherapy for vulvar squamous cell carcinoma include: severe vulvar radiation dermatitis, vulvar radiation necrosis, fistula, and urinary tract obstruction.

　　One, Symptoms

　　Long-term refractory vulvar itching is a common symptom in patients with vulvar squamous cell carcinoma. The course of the disease is generally long, and itching is more severe at night. Due to scratching, local ulcers are common, accompanied by vulvar pain, increased secretions, local hemorrhage, and other symptoms. Other symptoms may also appear due to the different locations of the lesions, such as frequent urination, dysuria, urinary burning sensation, and difficulty in urination when the tumor is adjacent to the urethra or when the tumor invades the urethra in late cases.

　　Two, Signs

　　Vulvar invasive squamous cell carcinoma is most commonly located on the labium majus, followed by the labium minus, clitoris, and posterior commissure, especially on the right labium majus, which is more common in the early stage. Local papules, nodules, or small ulcers may appear locally, and the lesions in the late stage are often manifested as ulcerative, cauliflower-like, or乳头-like masses. The surface may have bloody or purulent secretions due to ulceration and secondary infection, and it may be painful to touch. It often coexists with vulvar dystrophic diseases. The clinical morphology of vulvar cancer lesions is variable in shape, size, and color, which can be white, gray, pink, or dark red. The surface can be dry and clean, or there may be secretions and necrosis. The cancer lesions can be solitary or multiple. Solitary lesions can be cauliflower-like or ulcerative, and cauliflower-like lesions that grow outward are usually well-differentiated lesions. Ulcerative cancer lesions show infiltrative growth and are often found in the posterior part of the vulva, commonly invading the Bartholin's glands, perineal body, and ischiorectal fossa. Multiple lesions account for about 1/4 of vulvar cancer. The vulva often has increased pigmentation and is often complicated with vulvar dystrophic diseases. The lesions are diffuse and rarely have obvious small lesions. Sometimes, one or both inguinal groins can be palpated as enlarged, hard, fixed, and non-tender lymph nodes, but it should be noted that not all enlarged lymph nodes are cancer metastases, and the absence of palpable enlarged lymph nodes does not exclude lymph node metastasis. Squamous cell carcinoma originating from the vestibular gland often manifests as a hard edema phenomenon around the labium majus near the labial frenulum, but the surface skin may still be good.

　　3. Metastatic Routes

　　1. Direct Invasion:The tumor can gradually increase and spread to the urethra, perineal body, and vagina; the posterior vulvar tumor tends to invade the vaginal orifice and anus, and advanced cases can invade the pubic bone and extend to the perianal or bladder neck.

　　2. Lymphatic Metastasis:Lymphatic metastasis is the most common and important metastatic pathway, with a lymphatic metastasis rate of 21% to 59%. The route of metastasis is mainly determined by the characteristics of lymphatic drainage, see "Vulvar Early Invasive Squamous Cell Carcinoma".

　　3. Hematogenous Metastasis:Rare, usually seen in advanced patients, and can metastasize to the lung.

　　4. Clinical Staging

　　There are many clinical staging criteria for primary vulvar squamous epithelial carcinoma. Currently, the two main methods widely used are the surgical pathological staging method revised by the International Federation of Gynecology and Obstetrics in 1994, and the TNM staging method of the International Union Against Cancer in 1997. Both methods have their own advantages.

　　1. Epidemiology

　　Vulvar squamous cell carcinoma (invasive squamous cell carcinoma of the vulva) mainly occurs in postmenopausal women, with the incidence rate increasing logarithmically with age. The average age at diagnosis is 50 years in China and 60 years abroad, but there has been a significant trend of youthfulness in the past 20 years. Al-Ghamdi (2001) reported that among patients with vulvar squamous cell carcinoma, about 5% are young patients under 40 years old, with the youngest being only 17 years old.

　　2. Prognosis

　　The prognosis of vulvar squamous cell carcinoma is closely related to the size of the tumor, the depth of invasion, and the presence of lymph node metastasis. Tumors with a maximum diameter ≤2cm, invasion depth ≤1mm, and thickness ≤5mm rarely develop lymph node metastasis and have a good prognosis. Ferenczy believes that the cancer visible clinically includes those with a maximum diameter of 2cm, which almost always show stromal invasion and have already invaded deeply beyond 1mm. Invasion of ≤1mm is often an accidental finding during the examination of in situ carcinoma (VIN). Additionally, it is generally believed that without a complete block check and vertical section of the vulvar cancer, it is difficult to correctly measure the depth of invasion. Factors affecting prognosis are not limited to the size and depth or thickness of the cancer, but also include the presence of lymphovascular tumor thrombi, the degree of differentiation of the cancer, the growth pattern (expansive or invasive), and the stromal response of the host.

　　1, Secretion examination, tumor marker examination.

　　2, Cytological examination

　　For suspected lesions, perform cytological examination, often visible cancer cells. Since vulvar lesions often have concurrent infection, the positive rate is only about 50%.

　　3, Imaging examination

　　To accurately determine the clinical stage before treatment, which is conducive to objectively formulating a treatment plan, it is possible to perform B-ultrasound, CT, MRI, and lymphography of the para-iliac and para-aortic lymph nodes.

　　4, Cystoscopy and rectoscopy

      For some advanced vulvar cancers, it is necessary to perform cystoscopy and rectoscopy to understand the condition of the bladder and rectum.

　　5, Pathological biopsy

　　For all vulvar exophytic lesions, including cauliflower-like lesions, ulcerative lesions, nodular lesions, and white lesions, all require histological examination of living tissue. During biopsy, for widespread erosive lesions without obvious lesions to avoid inaccurate sampling and misdiagnosis, vaginal magnification and (or) 1% toluidine blue (a nuclear stain) can be used for vulvar staining, followed by rinsing with 1% acetic acid, identifying可疑 lesions, and then performing biopsy. Because both inflammation and cancer can show positive results, toluidine blue staining can only be used to select biopsy sites. When sampling lesions with necrosis, sufficient depth should be taken, and sampling should be made at the edge of the necrotic tissue to avoid taking only necrotic tissue, which may affect the results of the examination.

　　First, dietary therapy for vulvar invasive squamous cell carcinoma

　　1, Meat 300 grams, fresh river fish 1 piece (500 grams), white radish 1 piece. Cut the mutton into large pieces and put it in boiling water, cook with sliced radish for 15 minutes, and discard the soup and radish. Put the mutton in a pot, add water (about 2/3 of the pot capacity), scallions, ginger, and wine, and cook until tender. If the soup is too little, add some boiling water. After the fish is fried with soybean oil, put it in the pot with the mutton and cook for 30 minutes. Add salt, coriander, green onion, and chopped scallion to the soup, and it becomes a delicious and tasty mutton and fish soup. It is mainly used for postoperative care after invasive squamous cell carcinoma of the vulva.

　　2, Quail eggs 20 pieces, half an onion, carrot 80 grams, asparagus 80 grams, tomato 4 pieces, green pepper 1 piece. Boil the eggs and use the shell. Cut the vegetables into small pieces. Boil the carrots just until they are tender. In a bowl, put in 200 milliliters of soup base, 40 grams of sugar, 45 milliliters of vinegar, 15 milliliters of wine, 20 grams of tomato sauce, 5 milliliters of sesame oil, 10 grams of soy sauce, and mix well. Heat 30 milliliters of oil in a pot, add the eggs and vegetables and stir-fry for a few seconds, then add the sauce and cook for a while before serving. It is used to treat anemia caused by chronic bleeding from invasive squamous cell carcinoma of the vulva.

　　Second, what are the good foods for vulvar invasive squamous cell carcinoma

　　One fresh mushroom, 90 grams, fried with a suitable amount of vegetable oil and a little salt, then boil in water to make soup for eating. It can be used for gastric cancer and cervical cancer.

　　Appropriate amounts of mushrooms, boil in water, eat cooked, or grind into powder for consumption.

　　Twelve fresh lotus seeds, 20-30 pieces, add an appropriate amount of water, boil slowly to make a thick soup, take 2-3 times a day. It has certain efficacy for gastric cancer and cervical cancer.

　　Drinking wulong tea regularly has a certain anti-cancer effect.

　　Consistently consuming bee milk can enhance the body's immunity and has anti-cancer effects.

　　The chlorophyll in sprouts can prevent colorectal cancer and other cancers.

　　Other milk or goat's milk not only contain a wealth of vitamins but also contain certain anti-cancer substances; fresh vegetables such as radishes, cabbage, pumpkins, green beans, and lettuce have a certain effect on neutralizing nitrosamines in food; carrots, spinach, tomatoes, and seaweed are rich in vitamin A and have a certain anti-cancer effect.

　　Consume moderate amounts of carbohydrates to supplement calories. Patients undergoing high-dose radiotherapy may have their body's carbohydrate metabolism disrupted, causing a sharp drop in glycogen, an increase in lactic acid in the blood, and the inability to reuse it; and insufficient insulin function. Therefore, the effect of glucose supplementation is better, and it is also recommended to eat more foods rich in sugar, such as honey, rice, noodles, potatoes, etc., to supplement calories.

　　Eat more foods with anti-cancer properties, such as turtle, mushrooms, black fungus, garlic, seaweed, bok choy, and royal jelly.

　　The vitamins A and C can prevent cell malignancy and spread, increase the stability of epithelial cells; vitamin C can also prevent the general symptoms of radiation injury and can increase the level of white blood cells; vitamin E can promote cell division and delay cell aging; vitamin B1 can promote appetite in patients and alleviate the symptoms caused by radiotherapy. Therefore, it is recommended to eat more foods rich in these vitamins, such as fresh vegetables, fruits, sesame oil, grains, beans, and animal internal organs.

　　Third, the best foods to avoid for invasive squamous cell carcinoma of the vulva

　　Avoid food that can trigger an allergic reaction. Such as fish, shrimps, crabs, chicken heads, pork heads, goose meat, chicken wings, chicken feet, etc., which can worsen itching and inflammation in the genital area after eating.

　　Avoid astringent and astringent products, which are easy to cause blood stasis. Spicy and warm herbs are beneficial for promoting blood circulation, and can be eaten: but not too much, as excessive spiciness and stimulation will also worsen pain.

　　Eat less or no spinach. If it is necessary to eat it, you can blanch the spinach in hot water first, allowing some oxalic acid to dissolve in the water, and then remove it for eating. In this way, the body can reduce the intake of some oxalic acid.

　　Avoid eating greasy, smoked, and fried foods, as well as alcohol, cigarettes, roosters, lamb, and other warm-temperature causing diseases.

　　5. Avoid eating fried and greasy foods. Such as oil cakes, butter, butter, chocolate, etc., these foods have the effect of moistening and increasing heat, which will increase the secretion of leukorrhea and is not conducive to the treatment of the disease.

　　6. Quit smoking and drinking.

　　1. Treatment

　　The primary treatment for primary vulvar squamous cell carcinoma is surgery. For cases with poor differentiation of the cancer focus tissue and advanced cases, adjuvant radiotherapy or drug chemotherapy can be used. For patients with low immunity or impaired immunity, adjuvant treatment to improve the body's immunity should be used to improve the efficacy.

　　1. Surgical treatment

　　The classic surgical method is radical vulvectomy combined with bilateral inguinal lymph node dissection. The range of vulvar resection includes 3/4 perineum posteriorly, and anteriorly it should reach 3 to 4 cm above the clitoris. During inguinal lymph node dissection, the fat in the inguinal region, including both deep and superficial lymph nodes, should be completely removed. After the skin incision is made, the skin and subcutaneous fat are separated upwards, downwards, left, and right by 3cm each. Then, the fat containing inguinal lymph nodes within this range is removed. The superficial fascia of the abdominal wall is incised, and the superficial lymph nodes are located just below the fascia in the fat layer. In front of the reticular fascia and the iliac fascia, the upper limit of the excision should reach the inguinal ligament, and the lower limit should reach about 2cm near the opening of the adductor canal (hunter canal). The lateral limit should reach the sartorius muscle, and the medial limit should reach the fascia of the adductor longus muscle. After the removal of this fat and lymph nodes, the femoral triangle is exposed, including the femoral artery, vein, and nerves. When removing the lymph nodes around the femoral artery and vein, the operation must be performed carefully to prevent injury to the blood vessels and nerves.

　　As a standard surgical method, radical vulvectomy combined with bilateral inguinal lymph node dissection has always been used as the main treatment for invasive squamous cell carcinoma of the vulva. However, recently, this traditional radical surgical method is facing great challenges. The main reason is that the incidence of squamous cell carcinoma of the vulva is becoming younger and younger, and the diversity of treatment requirements of patients needs to be fully reflected. In addition, through continuous in-depth clinical research, a deeper understanding of the biological behavior of cancer cells - related risk factors of lymph node metastasis patterns has been gained. Therefore, the surgical procedures adopted in surgical treatment tend to be individualized. When formulating an individualized surgical plan, the following factors should be considered: the patient's age, the patient's wishes, the size and location of the cancer focus, and the relationship with adjacent organs; the depth of the cancer focus base infiltration, the degree of cell differentiation, the presence or absence of lymphatic and vascular invasion, the degree of differentiation of tumor cells, the presence or absence of inguinal lymph node metastasis, and the presence or absence of squamous cell carcinoma in other parts of the lower genital tract.

　　The depth of infiltration of the vulvar cancer focus exceeds 2mm or more, the lymph node metastasis rate can reach 11% to 28%. In cases where the lymph vessels or blood vessels around the cancer focus are involved (VSI), the lymph node metastasis rate can be as high as 75%. The lymph node metastasis rate is also high in poorly differentiated tissue of the cancer focus, with G1 at 15%, G2 at 35%, and G3 at 55%. Therefore, for those with a cancer focus base infiltration depth exceeding 2mm, or lymphatic involvement or poor differentiation of the cancer focus tissue, combined radical vulvar surgery should be performed according to the aforementioned principles.

　　If the vulvar cancer focus is located at the midline, especially in the clitoris, its growth pattern is mostly infiltrative, with a high rate of lymph node metastasis and often bilateral. Such patients should undergo extensive vulvar resection and bilateral deep and superficial inguinal lymph node dissection.

　　Invasive vulvar squamous cell carcinoma should undergo radical vulvar surgery and lymphadenectomy of deep and superficial inguinal lymph nodes. Generally, pelvic deep lymph node dissection is not required after surgery, unless there is cancer metastasis in the inguinal lymph nodes. If there is no metastasis in the inguinal lymph nodes, there is generally no metastasis in the pelvic deep lymph nodes. Therefore, pelvic lymph node dissection should not be considered as routine surgery. When there is a suspicion of positive inguinal lymph nodes, frozen section should be performed to determine whether pelvic lymph nodes need to be removed. It can also wait for the routine pathological diagnosis after surgery to perform a second-stage operation. The dissection of inguinal and pelvic lymph nodes is performed simultaneously, which has a wide surgical range, long duration, and much trauma, which will definitely increase the incidence and complications after surgery. If the inguinal lymph nodes are positive, about 25% of patients have positive pelvic lymph nodes. All invasive vulvar squamous cell carcinoma foci in stages II to IV are more than 2cm in size, with a lymph node metastasis rate of more than 30%. All should undergo standard combined radical vulvar cancer surgery, that is, extensive vulvar resection and bilateral inguinal lymph node (and sometimes pelvic lymph node) resection. If the cancer focuses on the urinary meatus, part of the anterior urethra can be resected along with the vulva. If the function of the urethral sphincter is good, the resection of the anterior urethra is within 2cm and will not cause postoperative urinary incontinence. If the cancer focuses on the anterior and lower wall of the vagina, the middle and posterior segment of the urethra, or the bladder neck, when performing combined radical vulvar cancer surgery, the resection of the entire urethra or bladder neck and partial vaginal resection and urethral reconstruction should be performed, and the urethral reconstruction is usually done using part of the bladder wall as the urethra. The urethral orifice can be placed on the lower abdominal wall or at the original urethral orifice of the vulva. There is also the option of resecting the entire urethra and anastomosing the bladder with the cut rectum to allow urine to be excreted through the anus. Then, a transverse incision is made behind the anus to pull out the fully freed and blood-perfused distal end of the sigmoid colon, suture it into the posterior incision of the anus. If the cancer invades the lower posterior wall of the vagina, anal canal, or rectum, it should be considered to perform partial resection of the posterior vaginal wall, anal canal, or rectum and artificial anus reconstruction at the same time as the combined radical vulvar cancer surgery.

　　The surgical technique of combined radical vulvar cancer surgery and pelvic visceral resection can be used for advanced cases, with high surgical difficulty, a large surgical area, many postoperative complications, and a high mortality rate. Therefore, the indication for this surgery should be relatively strict. Without a doubt, some advanced vulvar cancer patients can achieve a longer survival period or cure with effort.

　　Radical surgery for vulvar cancer is not difficult because the surgical field is relatively superficial, easily exposed, and easy to stop bleeding. However, the key is how to promote the rapid healing of the wound after surgery, as the skin has become free, subcutaneous fat has been removed, leaving a large ineffective cavity, which affects the healing of the wound. Vulvar cancer patients often extend their hospital stay due to slow wound healing after surgery. The basic principle to promote wound healing is:

　　Stop bleeding properly during the operation;

　　After the skin is sutured, it should be tightly pressed to ensure that the skin is tightly adhered to the underlying tissue below, leaving no ineffective cavity;

　　③ Place rubber sheets or small rubber tubes for drainage to facilitate the timely removal of oozing blood or fluid under the skin;

　　④ Negative pressure drainage. Connect the rubber tube for drainage to a negative pressure bottle, and suction frequently or at regular intervals to remove as much of the oozing blood and fluid as possible. Generally, drainage is placed for about 10 days;

　　⑤ Prevent infection. As long as the above principles are followed, the wound generally heals within 7-14 days after surgery.

　　⑥ Supportive therapy to promote wound healing.

　　2. Radiotherapy

　　Radiotherapy for invasive vulvar squamous cell carcinoma includes the use of high-energy radiotherapy machines (60Co, 137Cs, linear accelerators, and electron accelerators, etc.) for external radiotherapy and the use of radiotherapy needles (60Co needles, 137Cs needles, 192Ir needles, and Ra needles, etc.) for interstitial implantation therapy. Although vulvar squamous cell carcinoma is sensitive to radiation, the optimal radiotherapy dose for curing vulvar cancer tissue cannot be tolerated by the normal vulvar tissue, so the efficacy is poor. Generally, the vulvar tissue can only tolerate 40-45 Gy, while the effective treatment dose for squamous cell carcinoma is 55-60 Gy. Therefore, the efficacy is not good. Currently, radiotherapy is in a supportive role in the treatment of vulvar squamous cell carcinoma. The overall 5-year survival rate of vulvar squamous cell carcinoma radiotherapy was about 25% before the 1970s, and recent reports have shown some improvement. The 5-year survival rate of stage I-Ⅱ invasive vulvar squamous cell carcinoma can even reach 70%.

　　The indications for radiotherapy in vulvar squamous cell carcinoma can be summarized as:

　　① Cases that cannot be operated on, such as those with high surgical risk, extensive cancer lesions that cannot be removed or are difficult to remove;

　　② Adopting radiotherapy first can allow for a more conservative surgery;

　　③ Cases with a high probability of recurrence, such as lymph node metastasis, finding cancer cells at the specimen margin, lesions close to the urethra, and the proximal rectum, where it is difficult to completely remove the lesions while retaining these sites.

　　④ For patients with positive lymph nodes, supplementary external radiotherapy after surgery may improve survival rates.

　　The main complications of radiotherapy for vulvar squamous cell carcinoma include: severe vulvar radiation dermatitis, vulvar radiation necrosis, urinary fistula, and urinary tract obstruction.

　　3. Chemotherapy

　　There is very little clinical experience with anti-cancer chemotherapy for vulvar squamous cell carcinoma. This is due to the fact that all current anti-cancer drugs have unsatisfactory efficacy against squamous cell carcinoma, while the cure rate of surgery is high; at the same time, vulvar squamous cell carcinoma is more common in elderly patients, and the treatment requirements are not high, among other reasons. Therefore, anti-cancer chemotherapy currently plays a supportive role in the treatment of vulvar squamous cell carcinoma, and is applied to advanced cancer or recurrent cancer.

　　(1)The efficacy of single anti-cancer drugs: The single anti-cancer drugs clinically applied for the treatment of vulvar squamous cell carcinoma include: doxorubicin (adriamycin), bleomycin, methotrexate, cisplatin (cis-platinum), etoposide (podophyllotoxin), mitomycin C, fluorouracil (5-FU), and cyclophosphamide, among which bleomycin, doxorubicin (adriamycin), and methotrexate have better efficacy, with an efficacy rate of about 50%.

　　(2) Combined Antitumor Chemotherapy Regimens and Efficacy: Clinical treatment of vulvar squamous cell carcinoma with combined antitumor chemotherapy regimens includes: bleomycin + mitomycin, fluorouracil (5-FU) + mitomycin and bleomycin + vincristine (vincristine) + mitomycin + cisplatin (cisplatin), etc. There are few cases of vulvar squamous cell carcinoma treated with combined chemotherapy regimens, but currently, the efficacy of bleomycin + mitomycin and fluorouracil (5-FU) + mitomycin is better, with an efficacy rate of about 60%.

　　The combination of antitumor chemotherapy and (or) radiotherapy and surgical treatment for advanced or recurrent vulvar squamous cell carcinoma can be expected to improve the survival rate.

　　II. Prognosis

　　The prognosis of vulvar squamous cell carcinoma is closely related to the size of the tumor, the depth of invasion, and whether there is lymph node metastasis. Tumors with a maximum diameter ≤ 2cm, an invasion depth ≤ 1mm, and a thickness ≤ 5mm rarely occur lymph node metastasis, and the prognosis is good. Ferenczy believes that the cancer visible to the clinic includes those with a maximum diameter of 2cm, which almost always have stromal invasion and have deeply exceeded 1mm. Invasion ≤ 1mm is often an accidental finding when examining in situ cancer (VIN). In addition, it is generally believed that if the entire vulvar cancer is not cut and checked and vertically sliced, it is difficult to correctly measure the depth of invasion, which affects the prognosis. Factors affecting the prognosis are not limited to the size and depth or thickness of the cancer, but also include lymphovascular tumor thrombi, the degree of differentiation of the cancer, the growth pattern (expansive or infiltrative), and the stromal response of the host, such as

　　Wharton et al. reported that if there are less than 3 lymph node metastases, the 5-year survival rate is 68%, and there is no case of deep pelvic lymph node metastasis. If a patient has more than 4 lymph node metastases, 50% of the deep pelvic lymph nodes can metastasize. If both inguinal lymph nodes are positive, 26% of the deep pelvic lymph nodes are positive. The prognosis of deep pelvic lymph node metastasis is poor, and the 5-year survival rate is only 20%.