Wells Ke

The orderly progression of melanoma nodal metastases

ObjectiveThe aim of this study was to determine the order of melanoma nodal metastases. Summary Background DataMost solid tumors are thought to demonstrate a random nodal metastatic pattern. The incidence of skip nodal metastases precluded the use of sampling procedures of first station nodal basins to achieve adequate pathological staging. Malignant melanoma may be different from other malignancies in that the cutaneous lymphatic flow is better defined and can be mapped accurately. The concept of an orderly progression of nodal metastases is radically different than what is thought to occur in the natural history of metastases from most other solid malignancies. MethodsThe investigators performed preoperative and intraoperative mapping of the cutaneous lymphatics from the primary melanoma in an attempt to identify the “sentinel” lymph node in the regional basin. All patients had primary melanomas with tumor thicknesses > 0.76 mm and were considered candidates for elective lymph node dissection. The sentinel lymph node was defined as the first node in the basin from which the primary site drained. The sentinel lymph node was harvested and submitted separately to pathology, followed by a complete node dissection. The null hypothesis tested was whether nodal metastases from malignant melanoma occurred in equal proportions among sentinel and nonsentinel nodes. ResultsForty-two patients met the criteria of the protocol based on prognostic factors of their primary melanoma. Thirty-four patients had histologically negative sentinel nodes, with the rest of the nodes in the basin also being negative. Thus, there were no skip metastases documented. Eight patients had positive sentinel nodes, with seven of the eight having the sentinel node as the only site of disease. In these seven patients, the frequency of sentinel nodal metastases was 92%, whereas none of the higher nodes had documented metastatic disease. Nodal involvement was compared between the sentinel and nonsentinel nodal groups, based on the binomial distribution. Under the null hypothesis of equality in distribution of nodal metastases, the probability that all seven unpaired observations would demonstrate that involvement of the sentinel node is 0.008.

Intraoperative radiolymphoscintigraphy improves sentinel lymph node identification for patients with melanoma

BACKGROUND The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.

Detection of Submicroscopic Lymph Node Metastases with Polymerase Chain Reaction in Patients with Malignant Melanoma

BackgroundThe presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. MethodsThe assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. ResultsEleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false-negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene sequence.

Redefinition of Cutaneous Lymphatic Drainage With the Use of Lymphoscintigraphy for Malignant Melanoma

Lymphoscintigraphy was performed on 82 patients with melanoma registered at the University Melanoma Clinic. From these data, precise lymphatic drainage basins could be drawn for the head, neck, shoulder, and trunk. These drawings differed significantly from the classic anatomic studies, providing a functional look at the cutaneous lymphatic drainage. This new method correlates much better with clinical experiences and demonstrates much larger areas of ambiguous drainage than previously reported. Data from the lymphoscintigrams also emphasize the individuality of cutaneous lymphatic flow. The implications of these data in planning elective node dissections for intermediate thickness melanomas are obvious, since it is estimated that up to 59% of the dissections for trunk and head and neck primary melanomas may be misdirected if based on classic anatomic studies. The data indicate that all patients with head, neck, and shoulder lesions should undergo lymphoscintigraphy to define possible drainage basins at risk for metastatic disease. Similarly, truncal lesions require scintigrams except when they are within four well-defined areas with an extremely low probability of ambiguous drainage. Lesions in these areas show very reliable and predictable drainage to a single nodal group.

The Use of Intraoperative Radiolymphoscintigraphy for Sentinel Node Biopsy in Patients with Malignant Melanoma

background Selective lymphadenectomy or “sentinel node” biopsy Ms been introduced recently by Morton and colleagues (Arch Surg 1992;127:392–9) to stage patients with intermediate and thick malignant melanomas. It has proven to be an effective way to identify nodal basins at risk for metastasis without the morbidity of a complete lymph node dissection. The majority of biopsies can be performed under local anesthesia with small incisions, but technical difficulties occasionally result in unsuccessful explorations. Identification of the sentinel node can be enhanced by a intraoperative radiolymphoscintigraphy, a technique introduced Alex and Krag (Surg Oncol 1993;137–43) tint uses radiolabeled sulfur colloid and a hand‐held gamma probe. objective We used intraoperative radiolymphoscintigraphy in conjunction with 1% lymphazurin blue dye to define the sentinel node(s) in 148 patients with greater than 0.76 mm in thickness or Clark level TV melanomas. Sentinel lymph nodes were isolated, harvested, and examined using conventional histopathology, and immunohistochemistry for S‐100 and HMB‐45 antibodies. results The overall success rate of sentinel lymph node localization was 97% using a combination of the two techniques. Twenty‐one (34%) patients had micrometastasis, and 17 of these subsequently underwent complete lymph node dissection. A total of 220 of 275 (80%) sentinel nodes harvested were radioactive or “hot” compared with 165 of 275 (60%) with the blue dye alone. Four of the patients with micrometastasis had sentinel nodes positive by gamma probe, but negative by blue dye mapping techniques. conclusion Our results suggest that intraoperative radiolymphosintigraphy using a hand‐held gamma detecting probe improves the identification of sentinel lymph nodes during selective lymphadenectomy. This may reduce the number of “unsuccessful explorations” using the vital blue dye technique for lymphatic mapping, and appeal to a greater variety of surgeons, including dermatologic surgeons.

The use of lymphoscintigraphy in melanoma of the head and neck

Lymphoscintigraphy has been shown to be of assistance in defining the lymphatic drainage pattern of melanoma. In this study, lymphoscintigraphy was performed on 25 patients with primary melanoma (stages I and II at diagnosis) of the head and neck to determine whether the lymphatic drainage seen on lymphoscintigram was the same as the surgeons expected lymphatic drainage. The lymphoscintigrams were discordant in 21 of the patients (84 percent) with drainage to a lymphatic basin not predicted clinically. Based on the discordant lymphoscintigram, a change in surgical therapy occurred in 13 of 21 patients (62 percent). Of the 25 patients, 18 underwent prophylactic node dissections and 7 did not. Of the nodal basins removed, 27 of 38 nodal bases (71 percent) were seen on lymphoscintigraphy. Melanoma metastatic to lymph nodes was removed from nodal basins identified by the lymphoscintigram, but not predicted clinically, in two patients (8 percent). Historical anatomical patterns of lymph drainage and the clinical impression of experienced surgeons cannot reliably predict the pattern of lymphatic drainage in patients with melanoma of the head and neck.

Multiple primary melanomas: Implications for screening and follow-up programs for melanoma

AbstractBackground: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. Methods: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. Results: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p=0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p=0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p=0.002). Conclusions: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination.

Perineal reconstruction after surgical extirpation of pelvic malignancies using the transpelvic transverse rectus abdominal myocutaneous flap

AbstractBackground: The nonhealing perineal wound is often a catastrophic complication after aggressive surgical extirpation of pelvic malignancies. Methods: Eleven patients underwent perineal reconstruction using an inferiorly based transpelvic transverse rectus abdominal myocutaneous (TRAM) flap for large nonhealing postsurgical perineal wounds. After debridement of the perineum, the rectus muscles and their skin islands were mobilized, preserving their inferior epigastric blood supply. The flap was then taken through the midline abdominal incision transpelvically into the perineal defect. The study population was composed of three men and eight women ranging in age from 43 to 76 years (mean 59). The primary diagnosis was recurrent carcinoma of the rectum or anus (n=5), recurrent squamous cell carcinoma of the vulva or cervix (n=4), and recurrent sacral chordoma (n=2). All patients had received adjuvant radiation therapy and all patients had undergone one to four previous attempts at perineal closure. The perineal defect ranged in size from 72 cm2 to 1,250 cm2 (mean 337). Results: There were no perioperative deaths. Ten of the 11 patients (91%) had primary wound healing of the TRAM flap, perineal wound, and donor site. One patient with recurrent chordoma developed recurrent tumor at the suture line 4 months postoperatively. Conclusions: The inferiorly based transpelvic TRAM flap is a safe and effective reconstructive technique for recalcitrant nonhealing perineal wounds after extirpation of pelvic malignancies.

Accurate Nodal Staging of Malignant Melanoma.

The incidence of malignant melanoma is increasing at a faster pace than that of any other cancer in the United States. It is estimated that people born in the year 2000 will have a 1:75 risk of developing melanoma sometime during his or her lifetime. Stimulated by novel lymphatic mapping techniques, the surgical care of the melanoma patient is evolving toward more conservative resections that can provide the same staging information but without the added morbidity of more radical surgeries. This approach promises to yield positive results in the age of health care reform, outcome measurements, and cost:benefit considerations.

Metastatic melanoma with an unknown primary.

An infrequent initial presentation for malignant melanoma is the diagnosis of metastatic disease without a history of an obvious primary lesion. Confusion exists in the literature concerning the workup, treatment, and prognosis of the unknown primary melanoma. A retrospective, computer-aided chart review of 580 consecutively registered patients with melanoma at the University Treatment Center (Tampa, FL), identified 18 patients with an unknown primary presentation. There were 10 males and 8 females with a mean age of 38.4 years. Ninety-four percent of the patients were diagnosed with metastatic disease in a nodal basin, whereas 1 patient had a resected isolated lung mass as the initial presentation. In the patients who presented after having a biopsy of a single positive node for diagnosis, more disease was recovered in the nodal basin with a formal node dissection in 59% of the patients. Actuarial survival curves were constructed for the group with unknown primary melanoma. As a control population, survival curves were constructed of the subpopulation of patients with melanoma who had a known primary and had stage III (regional nodal disease) at diagnosis. There was no difference in survival between those with known and unknown primary melanoma (p = 0.96).