Clinical analysis of vulvar carcinoma

Objective: The purpose of this study is to understand the incidence, related factors, and the prognosis factors in order to avoid risk, proper method of diagnosis and treatment and reduce complications and provide the basis. Methods: 85 Vulvar cancer (VC) patients treated in our hospital from 2002.10 to 2012.10 were collected and analyzed by retrospective comparative methods. SPSS19.0 application software was used for the statistical analysis. The clinical data are analyzed by chi-square and F test statistic methods. P < 0.05 was a significant difference between the judgment standard. Results: During 10 years, we treated 3391 cases of the primary malignant tumors including 85 VC cases; VC was 2.89% (85/3391). The age was between 24~88 years old, mean was 57.09±12.93 yrs. old, variable age (F=6. 013, P=0.016<0.05). VC had seen more in rural than urban patients. By statistical analysis, region distribution in these two groups was remarkably different=4.16, P=0.045<0.05, but the urban proportion of patients in different years has no difference (χ2=0.080, P=0.777). Conclusion: The number of cases increased progressively in young age. VC patients were more in rural area than urban. High-risk groups Suggested doing regular physical exam. For long-term genital itching, genital tumor, genital ulcers, and other symptoms, should be alert to the possibility of VC. Preoperative diagnosis should be Colposcopic, biopsy in order to improve the accuracy of earlier diagnosis. Postoperative common complications are wound infection. Follow-up rate is low; It is difficult to say statistically survival rate is 5 years.


Introduction
Vulvar cancer (VC) is about 3% to 5% of all primary gynecological malignancies, annual incidence rate is about 2 to 3/10 [1]. The vast majority of vulvar lesion occurs in the genital skin surface with early symptoms like vulvar itching, pain, small excrescence. Early diagnosis rate of Vulvar cancer are increasing nowadays. Vulvar cells similar to a cervical cytology brush (Rovers Medical Devices BV) are expected to become an important tool in the prevention and early diagnosis of vulvar cancer. In addition, CT examination with high specificity in vulvar cancer lymph node metastasis, improve the accuracy of the preoperative diagnosis. The range of options such as surgery, selective sentinel node and inguinal lymph node dissection, therapeutic applications, Chemotherapy or a combination of chemotherapy treatment etc is available. VC originates from 2 different etiologies. A class of histological features of well differentiated keratinizing squamous cell carcinoma: occurs in women over the age of 50 and often concomitant vulva non-neoplastic epithelial lesions (VNED) such as chronic inflammation, genital lichen sclerosis. This types of lesions in the HPV-DNA detection rate is low (<15%). Histological features mostly as epidermal carcinoma (Bowen's carcinoma, warty carcinoma), are common in young women. Epidemiological this type of VC risk factors includes smoking, sexually transmitted diseases (STD), and immune suppression. Most study shows that this type of lesions in the HPV-DNA, especially HPV 16, & 18 accounts for 40% to 51%, often with concomitant cervical lesions [2]. Lymph node metastasis has greater impact on the prognosis of VC. FIGO Committee Gynecologic Oncology Group revised the staging of vulvar cancer lymph node involvement [3]. In the new staging, no lymph node metastasis & invasion of adjacent organs cases regardless of the size of the lesion-divided into phase I . Only invasion of adjacent organs, but no lymph node metastasis were divided into Phase II; lymph node metastasis were divided into Phase III with subdivision of lymph node involvement. Surgery such as genital radical resection + inguinal lymph node resection for the vulvar traditional standard technique, this surgical inguinal lymph node dissection routinely cut off the great saphenous vein stripping fascia lata. This technique has large range of damage, and delayed healing, often appear as a lymphatic retention cyst, lower extremity edema, incontinence, sexual dysfunction, and seriously affecting the quality of life of patients. About 90% of vulvar squamous cell carcinoma, adenocarcinoma, squamous cell carcinoma of all anti-cancer drug sensitivity is lower; the chemo treatment of VC often can be used as a vulvar advanced cancer or recurrent VC. Chemotherapy drugs are mitomycin C (MMC), bleomycin (BLM), cisplatin (DDP), methotrexate (MIX), and cyclohexyl nitrosourea (CCNU). The implementation of concurrent radiotherapy and chemotherapy can achieve better efficacy. 5 -Fluorouracil Gynecology ISSN 2052-6210 doi: 10.7243/2052-6210-1-5 (5-FU) or 5-FU + cisplatin combination chemotherapy is the most commonly used chemotherapy regimens. Hamp [4] identified HPV vaccine is feasible to reduce the reproductive tract disease. Since Merck Gardasil cervical cancer preventive vaccines listed, the vaccine in the prevention of its related vulvar and vaginal intraepithelial neoplasia.The vaccine is beneficial for all young women and even in existing HPV infection. In addition, the treatment of VC can also consider the use of laser-assisted and immunomodulatory drugs combined with chemotherapy treatment achieved satisfactory results. The treatment of VC, surgeons and scholars considered the main problem is how to improve the survival rate, at the same time minimize postoperative complications, improve quality of life & prevention of recurrence. The present study is more focused on the treatment options, but its advantages and feasibility still a large number of evidence-based medicine support. With the sentinel lymph node biopsy technique of continuous research and improvement and development of the genital reconstruction techniques, we have reason to believe it will find the best treatment of VC, so that patients get the maximum therapeutic benefit with minimal trauma.

Materials and methods
With the prior approval from the institution that is a second clinical hospital of Jilin University, Changchun, China, data was collected from 2002-10 to 2012-10; all of the patients admitted with VC. Data was collected from hospital medical records and all patients were confirmed by clinical, pathological diagnosis.

Case inclusion criteria
Diagnosis was confirmed through pathological consultation. All patients (pt.) were newly diagnosed, Pt. with complete clinical and pathological data were collected.

Case exclusion criteria
A high degree of suspicion, without pathological confirmation; Secondary surgery or postoperative adjuvant therapy outside our hospital after primary treatment; and incomplete clinical and pathological data.

Methods
Grouping method: 85 cases of VC patient were grouped according to different criteria. According to admission time adenocarcinoma and sarcoma). Lymph node metastasis into the lymph node positive group and negative group; According to the histological grade is divided into: well differentiated (G1), moderately differentiated (G2) and poorly differentiated (G3) group; Menopause situation is divided into the postmenopausal group and premenopausal group; Classification of weight according to the body mass index (BMI), BMI24 as overweight/obese group.

Clinical and pathological data collection General analysis of the patient
Admission time, Age, Weight, Menarche and age at menopause, Symptoms, Medical history, Co-morbidities, Preoperative laboratory examination, Clinical stage, histology and Pathological findings of the surgical specimens, adverse reaction after chemotherapy, and Comprehensive treatment analysis.

Statistical analysis
The database was established on excel analyzed in SPSS19. Statistical methods χ2 test, P <0.05 database was established on excel and analyzed in SPSS version 19, statically method x 2 test P<0.05 was used to determine significant differences.

Results
In group A the incidence of number cases were 8, (5 rural areas) accounting for 62.50%, in group B 10 cases (rural residents 6) accounted for 60%, group C 11 cases (rural residents 6) accounting for 54.55%, 17 cases in group D (10 in rural areas) accounting for 58.82%, 39 cases in group E (rural area 22) accounting for 56.41%. The number of patients hospitalized increased year by year. There is significant incidence of urban and rural areas of VC (F=4.16, P=0.045<0.05) rural areas are more prone to VC (Figure 1).

History
Menarche of patient was between 11 to 20 years old, mean 16 year old. Total menopausal patient 50 accounting for 58.82%. The higher incidence of VC was seen with postmenopausal case, 7 out of 8 cases accounting for 87.  Table 2).

Complications
According to the body mass index, BMI>24 classified overweight, obese group ( Table 3)

History time
Patients had obvious symptoms before treatment. The time difference of patient visit was a minimum of 10 days, maximum up to 20 weeks. Peak was for 2 months to 1 year ( Table 5).

Lesion location and size
Lesions were distributed in the labia majora, labia minora, perineum, clitoris, urethra, and in patient with advanced disease and it spread to the anal and vaginal wall. According to the location 62 cases i.e., 72.94% of cases accounted for the lateral side of labia, while 23 cases i.e., 27.06% accounted for medial or midline of clitoris and perineum. According to size it is divided into 3 groups that is 2 cm, 2cm-5cm and ≥5cm. patients with lesion size <2cm, 2-5cm, >5cm were 16 (18.82), 59(69.41), 10(11.77) respectively ( Table 6).      in 4 pt. CT diagnosis was consistent with the clinical and pathological report; with coincidence rate of 67 % (4/6). 2 patient diagnosed with MR were also consistent with clinical and pathological judgment. 8 patients underwent inguinal lymph node dissection, a total of 42 lymph node resected. Lymph node metastasis in10 patient size was 6 to 40 mm, median12mm; and lymph node metastasis-free in 32 patients; the size was 5 to12 mm, median 8 mm. The median difference between the two was statistically significance (P = 0. 019 <0.05). CT and MRI tumor stage, tumor location, lymph node involvement and pathologic comparison data as shown in (Table 7).  (Figure 3).

Surgical treatment
In this study, 18 cases of local excision of the genital lesions, including 2 cases of simple resection, 3 were focal resection; another 13 cases of elderly patients aged 71 to 88 years old, accompanied by diabetes, coronary artery disease, hypertension and others. Thus only palliative excision was done. Regarding vulval radical surgery resection was done doi: 10.7243/2052-6210-1-5 with >2 cm of the lesion, the surrounding normal skin, subcutaneous normal tissue of the vulva and try to retain the retained urethra and anus. A total of 39 cases, including 8 cases of the untreated lymph node, 1 case underwent bilateral inguinal lymph node dissection. A total of 21 cases, lymph node was not removed in 1 case, in 20 cases both inguinal lymph nodes was removed ( Table 8).    Table 9. Vulvar extensions of surgical resection and recovery (%).

Impact of surgery on wound healing
Note: I simply lesion resection; II, part of vulvar radical with or without lymph node dissection; III, extensive vulvectomy with or without lymph node dissection.
healing, accounting for 37.66%. 7 cases of wound dehiscence accounting for 9.09%.There was significant influence in the hospitalization time in extensive vulvectomy with or without lymph node dissection (χ2 =14.889, P=0.01<0.05; F=29.308, P=0.000<0.01), and no significant correlation with incision dehiscence of vulvar resection (χ2=2.450, P >0.05) ( Table 9). There was no significant relationship (P>0.05) in patient underwent vulvar resection with lymph node, lesion with wound infection and dehiscence for patient with inguinal node resection, but in patient with inguinal node resection the average hospital stay were prolonged. There is significant influence of lymph node dissection (inguinal) with simple vulvectomy patient in hospital stay T=3.727, P=0.001(0.01) ( Table 10) .

Pathological conditions
In

Discussion
Vulvar cancer is one of malignant tumor of the female genital tract. The incidence rate is about 2 to 3 cases/100,000 [1]. Due to HPV infection and obesity its ratio increased rapidly. In future the rate of VC will continue to rise. The data from the Second Hospital of Jilin University from 1991 to 2010, cases of VC analysis showed same. VC mainly occurred in rural patient but since 1991, the incidence in urban women has also been raised. However the incidence is still higher in rural patient (56.41%) than urban (43.59%). According to previous reports in recent years, there have been significant rising trend of VC in younger age [5]. In this study, the age distribution ranges from 24 to 88-year-old, with average age 57.09 ± 12.93 years old, and with a peak age of 56 to 61-year-old. The mean age of onset at different period from 2002-2012 was 63.38 ± 10.38 years which dropped in 2010-2012 to 54.33 ± 14.86 years. After the statistical analysis, the age of onset of VC declines year by year, this shows consistent ratio with the previously reported literatures. 50 cases with VC were postmenopausal accounting for 58.82%; it's also consistent with the literature [6]. Studies have shown that there is some correlation between white lesion of vulva and progesterone levels. Higher the progesterone levels, higher the risk of white lesions of the vulva while the white vulva is one of the common causes of VC [7]. Studies have shown that HPV infection and VC are closely related to the occurrence of the HPV virus detection rate (40.4%), i.e., common type of HPV 16, 33, and 18 [8]. Lichen sclerosis has 4% to 6% of the possibility of the
* Lymphadenectomy in 51 cases, 10 patients with pathologically confirmed ipsilateral lymph node metastasis, the pathologically confirmed three cases in linear transferred to bilateral lymph node, lymph node negative patients with lymphatic vascular invasion.

Positive Negative
Histological grade  ; routine colposcopy shows the vulval local vascular in a mosaic, intraoperative rapid pathological diagnosis -poorly differentiated vulvar squamous cell carcinoma. Literature prompted the high specificity of CT examination in the judgment of VC lymph node metastasis therefore has an important applications in the preoperative staging [10]. The presence of CT examination overestimates or underestimates the clinical stage possibility. CT should determine the presence or absence of lymph node metastasis, to be based on the number of lymph nodes and the size of the lymph node [11]. Information found metastasis more overlap between lymph node size, but the difference was statistically significant (P = 0. 019). Lymph node enlargement shows the highest incidence of lymph node metastasis. Studies have shown that less than 4 cm, T1 or T2, infiltration depth of less than 1 mm of vulvar squamous cell carcinoma were treated with sentinel lymph node biopsy has better security and accuracy [14][15]. Information has not yet been adopted sentinel lymph node biopsy technique therefore should improve preoperative lymph node biopsy technique. Early VC sentinel lymph node biopsy shows: 1) pathology screening micrometastasis, there are still some difficulties need to develop such as tissue microarray technology, has higher sensitivity. Combination of molecular biology techniques such as RT-PCR detection of sentinel lymph node does not yet have clinical utility [16]. De Hutu suggests that the use of the methilyn blue assay SLN sensitivity of only 60%, hematoxylin-eosin staining sensitivity of 80%. Combined with immunohistochemical techniques for tumor antigens can be detected by the presence of micrometastasis, to achieve tumor "super stage" [17]. The incidence of genital extramammary Paget's disease in this study is consistent with the literature [18]. The disease lesions confined to the epidermis had better prognosis [19]. In research it is still controversial about the margin on the pathological type of operation. Black et al., [20] considered the pathological positive margins leading to post-operative recurrence rate were significantly higher (70% and 38%). In this study patients surgically treated was pathologically confirmed as negative margins. In VC malignant degree of differentiation pathological type differs prognostic factors and treatment are also different. Therefore, tumor biopsy before treatment is still an important method to guide the diagnosis and follow up treatment. The exudation from the incisional operated wound, there are chances of skin infection, cellulitis and formation of lymphatic cyst.
doi: 10.7243/2052-6210-1-5 Therefore to prevent the oozing of blood it is essential to have the proper dressing and drainage of the wound to prevent wound infection and promote wound healing. Often with the 24hours 1-1.5kg weight compression is given to the patient with indwelling drainage tube, should maintain the negative pressure suction for 4-6 days. The negative pressure can be maintained at about 0.98kPa. Drainage bag should be changed daily. The main prediction factors for locally recurrent valvular cancer are 1) operating margin of tumor is near or close, 2) the depth of tumor invasion > 5mm, 3) lymphatic vessel invasion and tumor infiltration growth pattern. The main predictors of groin, pelvis and distant recurrence factors are the numbers of lymph node metastasis and tumor differentiation or histopathological grade [21]. We should strengthen the patient awareness regarding the disease and its outcome. Establish the appropriate follow up file tracing control on the therapeutic effect of disease so as to improve the level of diagnosis and treatment.

Conclusions
Cases of VC in young patient increasing every year. The VC ratio between the urban and rural areas is found to be more in urban patients than rural patients. Incidence of VC was seen in those patients who had hypertension, obesity and diabetes mellitus. Aggressive treatment of high-risk groups should be the primary concern, regular examination is recommended. Symptom such as long term vulvar itching, genital warts, genital ulcers may increase the possibility of VC. Preoperative colposcopy and biopsy can improve the accuracy of early diagnosis. The application of CT and MRI in the preoperative diagnosis should be strengthen. Postoperative complications were mainly wound infection. The follow up rate is low, so it is difficult to analyze the related factors of recurrence and calculate the survival rate in years. With these entire datas prognosis cannot be predicted.