【Abstract】 Objective To investigate the value of prophylactic regional lymph node dissection in the treatment of malignant melanoma. Methods 56 patients with WHO clinical stage Ⅰ, namely, regional lymph nodes not palpable and limb malignant melanoma were randomly divided into the dissection group and the control group cleaning purposes of prophylactic regional lymphadenectomy group of 30 patients, 26 patients of the control group preventive area lymph node dissection, the two groups are at least 2cm border adjuvant treatment of the primary tumor after wide excision and apply the same program. Kaplan  Meier statistics dissection group and the survival rate of the control group, the survival curves were compared to the Log  rank test. Results All patients 11 months to 84 months follow-up, with a median follow-up of 43.5 months, the 5-year survival rate of dissection group and the control group were 64.79% and 33.68%, respectively, the dissection group survival compared with the control group, the survival curve the Log  Rank test compare the significant difference between the two groups (P = 0.0414). Conclusion prophylactic regional lymph node dissection help to improve the survival rate of the WHO staging Ⅰ of malignant melanoma cases.

Key words malignant melanoma; treatment; regional lymph node dissection

 Evaluation of Prophylactic Lymph Node Dissection in Management of Malignant Melanoma

    XIAO Ji  wei, PENG Jun  ping, TANG Ding  bo

    Department of Orthopedics, Sichuan Cancer Hospital, Chengdu 610041, ChinaAbstract: Objective To evaluate the role of prophylactic regional lymph node dissection (LND) in the management of primary malignant melanoma. Methods 56 patients with WHO clinical stage Ⅰ malignant melanoma in the extremity, who had no palpable regional lymph node, were randomly divided into two groups. There were 30 patients in LND group who underwent excision of primary tumor plus LND, whereas 26 patients in control group who underwent excision of primary tumor alone. The excisions of primary tumor for two groups were the wide resections with a margin of at least 2 cm. All patients had the same modality of adjuvant therapy after operation. The overall survival rates for the 2 groups were estimated with the Kaplan  Meier method and the survival curves were compared using the log  rank test. Results The median follow  up for all patients was 43.5 months (range, 11 ~ 84 months). The five  year overall survival rates were 64.79% for LND group and 33.68% for control group, respectively. The Log  rank test (P = 0.0414) showed that there was a statistically significant difference between the two groups.Conclusion Prophylactic regional lymph node dissection may improve the survival rate of surgical management for patients with WHO stage Ⅰ malignant melanoma in the extremity.

    Key words: Malignant melanoma; Management; Lymph node dissection

Malignant melanoma (Malignant melanoma, MM), a high degree of malignancy, easily transferred and lead to death. The lymphatic system is the early transfer of the most important ways, the presence or absence of regional lymph node tumor metastasis and prognosis [1  4]. The clinical manifestations of lymph node metastasis in lymph node painless swelling, palpation palpable. WHO clinical stage [4] for the Phase Ⅱ regional lymph nodes palpable and limbs MM, lymph node dissection (Lymph node dissection, LND) is a therapeutic cleaning, its necessity is obvious, and for WHO clinical stage Ⅰ The cases, LND is considered preventive cleaning, help to improve the prognosis of limbs MM, there has been disagreement on the clinical [2  5]. Prophylactic LND limb MM prognosis of 56 patients with WHO clinical staging the stage Ⅰ limb MM cohort study, reported as follows.

    1 Materials and Methods

    1.1 Clinical data

    January 1995 to June 2006, during the income of my family with pathologically confirmed limbs first diagnosed case of malignant melanoma, select lesions solitary, non-local metastases or satellite lesions, regional lymph node palpation can not palpable, chest abdominal organs and whole body bone by chest radiography, abdominal routine examination of the B-and ECT whole body bone scan showed no tumor metastasis, ie WHO stage Ⅰ of the cases, were randomly divided into a the dissection group or the control group. Total of 56 patients enrolled in the study. General information of the patient, the lesion distribution are shown in Table 1. The two groups were using the same technique of the primary tumor surgically removed, the dissection group cases on the basis of the primary tumor resection preventive regional lymph node dissection, the cases of the control group only underwent primary tumor resection without doing preventive regional lymph node dissection. The same adjuvant therapy after surgery, and follow-up after discharge to patients died or ended in June 2007. Constitute no significant difference between the two groups were comparable. Table 1 clinical data of cases

1.2 Treatment

    1.2.1 The primary tumor resection of the lesions in the extremities, joints cut finger or cut-off toe, cut surface from the lesions of at least 2cm to reach wide excision requirements. Lesions were located in other parts, using the boundary 2 ~ 3cm deeper than wide excision of deep fascia upcoming lesion resection together to do a whole together with the the lesions the outer edge of the range of 2 ~ 3cm edge organizations, and then select the appropriate repair means repair excision caused skin and soft tissue defects. Lesion in the plantar weight-bearing area, the border 2cm wide excision and pedicle flap transfer to repair the skin caused by excision of soft tissue defects. Lesions located in other parts of the limb, using the border for a 3cm wide excision, skin graft to repair the soft tissue of the skin caused by excision and free skin defect.

    1.2.2 regional lymph node dissection enter dissection group of cases, lesions in the lower extremities, the uniform application of the inguinal lymph node dissection in the upper extremity, axillary lymph node dissection. Inguinal lymphadenectomy beyond the anterior superior iliac spine starting from the femoral triangle top 3cm longitudinal curved incision, the femoral triangle plus next to the outside of the midline lymphatic adipose tissue together with the region below the anterior superior iliac spine connection saphenous vein and its branch en bloc, regular cut peel shares sheath, the femoral vessels skeletonized. Starting from near the coracoid ends axillary fold transverse incision, cut off the pectoralis minor muscle axillary lymph node dissection to fully reveal the the axillary vascular, vein the armpit fat lymphoid tissue, together with the head en bloc resection, cut, peel axillary sheath. Whether inguinal lymph node dissection or axillary lymph node dissection should note that the flap at least 3mm thick to prevent flap necrosis. Addition of the small lymphatic simply coagulation processing can, should be given the larger lymphatic fine silk ligature to prevent postoperative lymph leakage. 3 to 5 days after application of plasma drainage tube suction to avoid the accumulation of exudate affect the healing of the incision.

    1.2.3 adjuvant therapy dissection group and the control group patients were in the two weeks after the operation began 6 cycles of adjuvant chemotherapy, the chemotherapy: triazene meters amine 400mg / (m2 · d), for five consecutive days, repeating a cycle of three weeks. Chemotherapy gap period: given interferon α  2b 300 million units intramuscularly 1 day, continuous application of 1 June.

    1.3 statistical methods

    The composition of the two groups, age was used to compare two independent samples of non-parametric tests Mann  Whitney test, gender and location compared using Pearson chi-square test. Projections dissection group and the control group, the survival rate by Kaplan  Meier method and Log  rank test comparing survival curves for the two groups. P <0.05 was considered statistically significant.

    2 Results

    All cases were in the 11 to 84 month follow-up, with a median follow-up time of 43.5 months. During the observation period the number of deaths: dissection group and the control group were 10 cases and 14 patients died of tumor distant metastasis widely; cases of local recurrence: dissection group and the control group were 3 cases (10%) and 2 cases (7.69% ). Survival cases, 4 cases of lacing survival, the remaining 28 cases of tumor-free survival. The 2-year survival rate and the 5-year survival rate: dissection group were 92.98% and 64.79% in the control group were 86.98% and 33.68%. Survival curves Log  Rank test, P = 0.0414, the difference between the two groups was statistically significant, the survival rate of dissection group than the control group, as shown in Figure 1.

    3 Discussion

    Neuroectodermal tissue origin of malignant melanoma in the skin and mucous membranes of the body may be the disease is more common to the skin of the limbs, most by moles from malignant [4]. The incidence of older patients usually middle-aged, young people rarely. In this study, patients aged more up and down in the 46 to 48-year-old, diseased parts, all located in the extremities, more particularly in the extremities and foot. The MM high degree of malignancy, the rapid development, early metastasis, and poor prognosis. Early metastasis through the lymphatic circulation, an important indicator of prognosis great influence on clinical stage, and to guide treatment and prognosis of regional lymph node metastasis. MM staging, mainly the World Health Organization WHO clinical staging of regional lymph node metastasis [4] two, a split three: Ⅰ period limited to in situ, Ⅱ stage has occurred and the American Joint Committee on Cancer AJCC stage (Regional node metastases) but have not yet distant metastases Distant metastases III period has occurred distant metastasis; latter based on the thickness of the lesion, regional lymph node metastasis and distant metastasis with or without 4. Fully the WHO staging the basis for clinical performance, easy to remember, easy application, the AJCC staging a combination of clinical and pathological, more accurate, but also more complex, must be measured through the microscope lesion thickness, clinical applications inconvenient.

    The MM treatment surgery is the most effective and important means of treatment [7]. Chemotherapy, radiotherapy and immunotherapy is also used for MM, but its efficacy is less precise, reported very different [5,8  9,13]. Resection of the primary tumor, lymphatic drainage area of ​​skin and soft tissue the halfway metastases (In  transit metastases) and regional lymph node metastasis, the elimination of in vivo tumor, surgical treatment target. Obviously, only in tumors confined to the regional lymphatic drainage area, has not yet occurred distant metastasis surgery be possible to achieve the goal of complete removal of the tumor in vivo. Therefore, stage Ⅲ patients already exists distant metastasis, surgical treatment is necessarily poor. For such cases, chemotherapy and immunotherapy, systemic treatment is achieving the hope of controlling tumor development [8-9]. Can be speculated that clinical stage is not actually Ⅰ period but Ⅲ period of this study, in some cases due to the lack of clinical micro-metastases (Micrometastases) means check out. In order to achieve the best possible results, this study all cases were applied nitrene meters the amine chemotherapy and interferon immunotherapy.

    Resection of the primary tumor, must be within a distance far enough tumor normal tissue Otherwise, recurrence inevitably. To be selected according to the size of the lesion and the site where the surgical lesions in the extremities, general cut finger or joint amputation lesions were located in other parts of the limbs, and more than 2 ~ 5cm wide excision distance lesion periphery, and then use the skin graft resection caused by other means to repair skin defects. The wider the excision boundary control of tumor recurrence, the better, but more difficult to repair skin defects caused lesions in the foot and other parts due to the limitations of the anatomical structures, excision boundary usually only take 1 ~~ 2cm Otherwise, it is difficult to repair. Yaojun [9] advocated excision of the lesion and surrounding 5cm range. Thomas et al [10] that the excision boundary is 2cm and 2cm above the local recurrence rate and 5-year survival was no significant difference. In this study, the plantar lesions and other parts of the lesions 2cm and 3cm wide excision boundary, follow-up results of the two groups of tumor recurrence rate was lower, quite satisfactory local control and, therefore, I believe that the excision boundary generally need not exceed 3cm.

    Tumor metastases to regional lymph nodes resected surgical lymph node dissection (LND), draining lymph nodes, lymphatic vessels en bloc resection together with adipose tissue. The palpation palpable regional lymph nodes and basically there are tumor metastasis, so for WHO stage Ⅱ MM, regional lymph node dissection are treatment must, WHO stage Ⅰ cases, LND is generally regarded as preventive cleaning. In fact, about 25% palpation of regional lymph node-negative micro-metastases (Micrometastases) [4] Therefore, part of WHO stage Ⅰ cases actually therapeutic regional lymph node dissection cleaning will help to improve the prognosis. Shen et al [2,10  11] supports this view. The study of WHO stage Ⅰ cases preventive regional lymph node dissection, the results of the five-year survival rate was significantly higher, the difference was statistically significant, indicating that the preventative the LND help improve the WHO stage Ⅰ limb MM prognosis.

    Balch [6] that preventive LND does not improve survival, advocates observed to regional lymph nodes and then LND. This is only the primary tumor resection, they will not do LND, etc. observed regional lymph node enlargement only LND approach will undoubtedly bear the risk of delays in treatment. Some scholars [3,12] advocated regional lymph nodes is an important barrier to prevent the proliferation of tumor and infection a human body, should be kept, if the sentinel lymph node (Sentinel lymph node, SLN) tumor metastasis, the entire regional lymph nodes without metastasis thus not necessary LND. By means of dye and isotope tracers to first identify the SLN biopsy, and then decide whether to proceed in accordance with the results of SLN biopsy LND. However, this selective dissection were unable to generally promote the use, because, looking for to determine SLN is not easy, the need for facilities and equipment, and also need to accumulated experience, can not completely avoid the occurrence of an error of judgment. In order to avoid delays in treatment, I believe that more appropriate preventive LND.

    LND easy concurrent flap necrosis, wound infection, postoperative complications such as lymphatic leakage and lymphatic swelling [3,7,13]. Only five cases of this study concurrent flap necrosis, wound infection, cases of lymphatic leakage and lymphadenopathy. Flap necrosis all confined to the incision to the middle of the 1 ~ 3mm wide leather edge, most of them after a short dressing that complete recovery. I understand the LND postoperative complications, patient and further treatment has little effect, it was not difficult to prevention. Too thin to avoid the flap, maintaining a thickness of not less than 3mm, more preferably prevent postoperative flap extensive necrosis. You give proper ligation of the small lymphatic application coagulation burning, the larger lymphatic vessels, and can be effective in preventing the occurrence of postoperative lymph leakage. In addition, after adequate drainage, appropriate antibiotics, is a reliable means to avoid postoperative wound infection and healing to the poor.

    In summary, WHO the stage Ⅰ MM conventional preventive LND can avoid delays in treatment and help to improve the five-year survival rate, and its complications can effectively control.