Common prognostic factors for stage III melanoma patients and for stage I and II melanoma patients with recurrence to their regional lymph nodes.

This study was undertaken in order to identify the prognostic factors for stage III malignant melanoma patients. In addition we compared the survival data of these patients with data from patients presenting with stage I and II disease who subsequently developed a regional nodal recurrence, in order to identify common prognostic factors and to compare the biological behaviour of the two groups. We retrospectively examined two groups of patients. The first consisted of 116 patients with stage III malignant melanoma and the second consisted of 57 patients with stage I and II malignant melanoma that were found to have regional lymph node metastases diagnosed at least 6 months after surgical treatment of their primary lesion. The age of the patients, the number of disease-involved lymph nodes, the site of the primary lesion and the presence or not of palpable lymph nodes proved to be significant prognostic factors of the first group. We also analysed the survival data of the second group and compared it with data from the stage III patients. The 5 year survival starting from the time after diagnosis of the primary lesion was 47.37% compared with 25.86% in stage III patients; however, this difference was not statistically significant. Patients who present with stage III malignant melanoma seem to have a more aggressive phenotype than stage I and II malignant melanoma patients who present with recurrent disease in their regional lymph nodes. Disease behaviour is dictated by the number of disease-involved lymph nodes, the site of the primary lesion and the type of surgical procedure performed (elective or therapeutic lymph node dissection).

Radiation therapy for high grade soft tissue sarcomas of the extremities treated with limb-preserving surgery.

AIM: It is common to use either pre- or post-operative radiation for high grade sarcomas undergoing limb-conserving surgery. Since 1977, we have adopted a selective policy of post-operative radiation, given only in patients with inadequate surgical margins. METHODS: A retrospective review of 114 patients (1977-1995) with high grade adult soft tissue sarcomas of the extremities was carried out. Amputation was required in 10 (9%). Patients with a minimum surgical margin <2 cm (n=33) received adjuvant radiation (29%). RESULTS: No complications occurred in 81/114. Wound complications were infection (14%), seroma (6%), haematoma (4%), dehiscence (4%) and skin edge necrosis (2%). Remedial operations were required in four (3%). Overall, the local recurrence rate was 23/114. Patients with surgery only (n=57) or surgery plus systemic chemotherapy (n=24) manifested local recurrence in 15/81 (19%) and those with surgery plus radiation (n=21) or surgery and radiation and chemotherapy (n=12) suffered local recurrence in 8/33. The local recurrence rate for tumours < or =5 cm was 6/32 and for those >5 cm 17/82, P=1.0. The 5 year survival rate was 60% for tumours < or =5 cm (n=32) and 46% for tumours > or =5 cm (n=82) (P=0.009). CONCLUSIONS: (1) Limb preservation was feasible in 91% of patients. (2) When the local treatment modality was surgery alone ('wide' margins) the local recurrence rate was 19%, and when it was surgery plus radiation (narrow margins) it was 24%. (3) Selective use of radiation (in patients with narrow margins) and reliance on surgery alone in cases amenable to wide resection may be a legitimate alternative to universal application of radiation with conservative resection.

Blood supply of hemipelvectomy flaps: the anterior flap hemipelvectomy.

In posterior flap hemipelvectomy, preservation of the gluteus maximus with the flap guarantees its viability regardless of the level of ligation of the iliac vessels. In anterior flap hemipelvectomy with the quadriceps femoris attached to the flap, the dominant blood supply is through the lateral femoral circumflex branches of the profunda vessels, which is sufficient to maintain the flap.

Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas.

BACKGROUND: The Intergroup Melanoma Surgical Trial began in 1983 to examine the optimal surgical margins of excision for primary melanomas of intermediate thickness (i.e., 1-4 mm). There is now a median 10-year follow-up. METHODS: There were two cohorts entered into a prospective multi-institutional trial: (1) 468 patients with melanomas on the trunk or proximal extremity who randomly received a 2 cm or 4 cm radial excision margin and (2) 272 patients with melanomas on the head, neck, or distal extremities who received a 2 cm radial excision margin. RESULTS: A local recurrence (LR) was associated with a high mortality rate, with a 5-year survival rate of only 9% (as a first relapse) or 11% (anytime) compared with an 86% survival for those patients who did not have a LR (P < .0001). The 10-year survival for all patients with a LR was 5%. The 10-year survival rates were not significantly different when comparing 2 cm vs. 4 cm margins of excision (70% vs. 77%) or comparing the management of the regional lymph nodes (observation vs. elective node dissection). The incidences of LR were the same for patients having a 2 cm vs. 4 cm excision margin regardless of whether the comparisons were made as first relapse (0.4% vs. 0.9%) or at anytime (2.1% vs. 2.6%). When analyzed by anatomic site, the LR rates were 1.1% for melanomas arising on the proximal extremity, 3.1% for the trunk, 5.3% for the distal extremities, and 9.4% for the head and neck. The most profound influence on LR rates was the presence or absence of ulceration; it was 6.6% vs. 1.1% in the randomized group involving the trunk and proximal extremity and was 16.2% vs. 2.1% in the non-randomized group involving the distal extremity and head and neck (P < .001). A multivariate (Cox) regression analysis showed that ulceration was an adverse and independent factor (P = .0001) as was head and neck melanoma site (P = .01), while the remaining factors were not significant (all with P > .12). CONCLUSION: For this group of melanoma patients, a local recurrence is associated with a high mortality rate, a 2-cm margin of excision is safe and ulceration of the primary melanoma is the most significant prognostic factor heralding an increased risk for a local recurrence.

Long-term prognostic significance of HSP-70, c-myc and HLA-DR expression in patients with malignant melanoma.

AIM: Use of molecular markers indicative of the tumour oncogenic potential and host response may enhance our prognostic information for more effective treatment of melanoma patients. The roles of HSP-70 protein, c-myc oncogene and HLA-DR antigen expression were examined in melanoma patients and related to prognostic factors, recurrence rate and long-term survival. METHODS: Forty patients with tumours thicker than 1 mm were included in this study. All had elective node dissection and were followed for at least 7 years. Twenty-two had microscopic nodal metastases. Both primary melanoma tumour and lymph nodes were examined for the immunohistochemical expression of HSP-70 protein, c-myc oncogene and HLA-DR antigen. RESULTS: Eighteen patients had a recurrence (45%) and 23 patients survived overall (57.50%). Positive HSP-70 expression was observed in 52.50% of the primary melanomas and was associated with improved overall survival, especially in the patient group with tumours > or = 1.5 mm (70%vs 26.70%, P=0.0159). C-myc oncogene was overexpressed in 47.50% and HLA-DR antigen in 42.50% of the primary melanomas, but no correlation with survival was observed. The expression profile of these molecular markers in the primary tumour did not predict the status of regional nodes. HLA-DR expression in lymph nodes was observed exclusively in the nodal tissue surrounding the metastatic melanoma tumour in five patients. CONCLUSIONS: The immunohistochemical expression profile of HSP-70 but not of c-myc oncogene or HLA-DR antigen in the primary melanoma tumour could be of certain value in the identification of patients with graver prognosis who may benefit from more aggressive therapeutic strategies.

Abdominoinguinal incision and other incisions in the resection of pelvic tumors.

In the past, sarcomas located in the iliac fossa, in the area over the external iliac vessels, or those in the lesser pelvis with fixation to the lateral wall, were inaccessible through the conventional abdominal incisions, mainly due to a lack of distal exposure. They were often called unresectable or were dealt with by an external hemipelvectomy. The abdominoinguinal incision provides exposure in one continuous field of the lower abdomen and the groin area on the side involved by the tumor, or bilaterally, if needed. It provides control of the vessels proximally and distally and easy identification of the femoral nerve lateral to the femoral artery. A simplified version in the form of an L or a reverse T through transection of the ipsilateral/bilateral rectus abdominis off the pubic crest provides a significantly improved exposure for low pelvic tumors in the midline. This affords the opportunity to perform under direct vision dissection in the area of the obturator nodes and obturator foramen, as well as exposure of the distal portion of the external iliac artery and vein. The technique of internal hemipelvectomy and sacral resection for tumors involving any part of the innominate bone or the sacrum, respectively, also amplify the surgical armamentarium in the resection of pelvic tumors with pelvic wall fixation. These incisions, although developed in the management of soft tissue sarcomas of the pelvis, are applicable for other histologic types of cancer when the biology and stage of the tumor are supportive of surgery for the pelvic disease.

The platysma muscle in neck dissection.

Although the platysma muscle is usually preserved during neck dissection, removal of this muscle is generally considered inconsequential. The present case report shows that sacrifice of the cervical branch of the facial nerve innervating this muscle and removal of the platysma's upper portion impairs the caudal retraction and eversion of the ipsilateral half of the lower lip in grinning or laughing.

Risk of basal cell and squamous cell carcinoma in persons with prior cutaneous melanoma.

BACKGROUND: Melanoma has been associated with an overall increase in actinic tumors, including actinic keratoses, as well as with noncutaneous malignancies. OBJECTIVE: Determine the risk of developing basal cell and squamous cell skin cancer in patients with prior cutaneous melanoma (actinic keratoses not encountered). METHODS: This retrospective study included 1396 white patients with prior cutaneous melanoma followed at the Roswell Park Cancer Institute in the period 1977-1978. The control group was the white population of the Detroit area in the same period (1977-1978). RESULTS: A total of 25 patients (18 males, 7 females) developed 35 basal cell and/or squamous cell carcinomas: 18 developed basal cell carcinomas, 2 squamous cell carcinomas, and 5 both. The calculated odds ratio was 3.49 (males 3.67, females 2.86, 95% confidence interval 1.52-8.00). No correlations were found with age, type, anatomic site, and length of follow-up of cutaneous melanoma. CONCLUSION: A history of cutaneous melanoma significantly increases the risk of basal cell and squamous cell skin cancer.

Intravenous leiomyomatosis with cardiac extension: tumor thrombectomy through an abdominal approach.

Intravenous leiomyomatosis is an uncommon vascular tumor that may be seen with potentially life-threatening symptoms resulting from intracardiac extension. This tumor is frequently misdiagnosed and treated without appropriate preoperative imaging and planning, which at times leads to inadequate treatment and incomplete resections. The appropriate therapy is complete excision of the tumor. We describe a patient who was treated with a new approach involving a single-stage operation without the need for median sternotomy, cardiopulmonary bypass graft, or hypothermic arrest by resection of the tumor from the point of attachment in the abdominal portion of the inferior vena cava.

Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial.

BACKGROUND: Ten- to 15-year survival results were analyzed from a prospective multi-institutional randomized surgical trial that involved 740 stages I and II melanoma patients with intermediate thickness melanomas (1.0 to 4.0 mm) and compared elective (immediate) lymph node dissection (ELND) with clinical observation of the lymph nodes as well as prognostic factors that independently predict outcomes. METHODS: Eligible patients were stratified according to tumor thickness, anatomical site, and ulceration, and then prerandomized to either ELND or nodal observation. By using Cox stepwise multivariate regression analysis, the independent predictors of outcome were tumor thickness (P < .001), the presence of tumor ulceration (P < .001), trunk site (P = .003), and patient age more than 60 years (P = .01). RESULTS: Overall 10-year survival was not significantly different for patients who received ELND or nodal observation (77% vs. 73%; P = .12). Among the prospectively stratified subgroups of patients, 10-year survival rates favored those patients with ELND, with a 30% reduction in mortality rate for the 543 patients with nonulcerated melanomas (84% vs. 77%; P = .03), a 30% reduction in mortality rate for the 446 patients with tumor thickness of 1.0 to 2.0 mm (86% vs. 80%; P = .03), and a 27% reduction in mortality rate for 385 patients with limb melanomas (84% vs. 78%; P = .05). Of these subgroups, the presence or absence of ulceration should be the key factor for making treatment recommendations with regard to ELND for patients with intermediate thickness melanomas. CONCLUSIONS: These long-term survival rates from patients treated at 77 institutions demonstrate that ulceration and tumor thickness are dominant predictive factors that should be used in the staging of stages I and II melanomas, and confer a survival advantage for these subgroups of prospectively defined melanoma patients.

Prognostic factors in malignant melanoma patients with solitary or multiple brain metastases. Is there a role for surgery?

BACKGROUND: The aim of this study is to evaluate the prognostic parameters and treatment modalities of malignant melanoma patients with brain metastases. EXPERIMENTAL DESIGN: a retrospective study with a mean follow-up of 46 months. SETTING: specialized Cancer Center. PATIENTS: the charts of 136 patients, treated in Roswell Park Cancer Institute, for melanoma brain metastases, were analyzed. INTERVENTIONS: all patients were treated surgically and in the majority adjuvant therapy was applied. MEASURES: survival and time of recurrence of patients and possible prognostic factors. RESULTS: PATIENTS who were treated surgically had a better one-year survival rate (28.3%), than patients who received radiotherapy and/or chemotherapy (6.67%) or patients who refused any kind of treatment (3.45%), (p=0.006). Prolonged survival after surgical treatment was found in patients with single metastatic lesions and in patients with multiple metastatic lesions. CONCLUSIONS: Melanoma patients with single metastatic lesions to the brain seem to do better after surgical treatment. The role of surgical intervention in patients with multiple brain metastases needs re-evaluation from a big multicenter, prospective trial.

Study of antiangiogenic agents with possible therapeutic applications in neoplastic disorders and macular degeneration.

Using a previously developed method (Ambrus, et al., 1991), we found that pentoxifylline and thalidomide potentiate each others antiangiogenic effect induced by human malignant melanoma cells in the cornea of Macaca arctoides monkeys.

Thoracoabdominal incisions and resection of upper retroperitoneal sarcomas.

BACKGROUND AND OBJECTIVES: There is a widespread impression among surgeons that a thoracoabdominal incision carries a substantially higher risk of morbidity and possible mortality over abdominal incisions. We decided therefore to critically review our experience of the last 4 years with these incisions. METHODS: This is a retrospective review of all cases of retroperitoneal sarcomas of upper abdominal quadrants in the period May 1995 through February 1999. There were 33 consecutive patients and 34 thoracoabdominal incisions (1 patient had a second operation for recurrence). Their mean age was 54 years, with 13 >60 and 7 >70 years. RESULTS: Eighteen patients were extubated immediately at the end of the procedure and the rest within 24 h. In the majority of instances (32 of 34 or 94%), the patients left the intensive care unit within 48 h. The most common postoperative complication was atelectasis (7 of 34, 21%). There was no postoperative death. The retroperitoneal tumor was resected in all 34 cases (100%). CONCLUSIONS: The thoracoabdominal incision for upper quadrant retroperitoneal sarcomas is tolerated well by the patients with a morbidity similar to that observed after routine abdominal incisions. It allows complete resection of the tumor in most (all in this series) cases.

Desmoid tumour: a pleomorphic lesion.

BACKGROUND: Desmoid tumour (DT) is an uncommon locally invasive non-metastasizing neoplastic lesion. The aetiology of this tumour is unknown and its treatment is controversial. Twelve cases of DT are presented and the literature is reviewed. METHODS: Twelve cases of DT treated at our institution during a 3.5-year period are analysed and the literature reviewed. Ten patients were referred with a primary tumour, one with local recurrence and one patient with a second primary desmoid tumour. One patient had multiple mesenteric DT (familial adenomatous polyposis coli-FAP), and in the remaining 11 patients the tumour was located in the abdominal wall in four, at an extremity in three, in the upper back in two patients, in the pelvis in one and retroperitoneally in one. RESULTS: The largest mesenteric DT was marginally excised en bloc with total jejunectomy. In the remaining 11 DT, complete excision to microscopically tumour-free margins was possible in nine cases and to microscopically involved margins in two cases. At a mean follow-up of 22 months (range 7-38 months), one patient was alive with stable disease (Gardner's syndrome), 10 patients were alive and free of recurrence and one patient (9%) developed local recurrence which was re-excised-she is disease-free 10 months later. CONCLUSIONS: Complete excision is the main modality of treatment for primary and recurrent DT. This is feasible in most cases except for tumours involving the base of the bowel mesentery. Surgical resection alone achieved local control of the tumour in most of the patients in this series (92%).

Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group.

OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Repair after radical groin dissection.

The above-described repair following ilioinguinal dissection with division of the inguinal ligament is essentially a Cooper's ligament repair providing a secure, durable reconstruction. In our experience, there has not been a case of incisional hernia after radical incontinuity groin dissection using the above reconstruction.