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D L Morton

Publications and source records attributed to D L Morton.

At least 19 recordsLinked to original sources
PubMed2001

Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma.

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. CONCLUSION: This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.

Humans↗
PubMed2001

Carbon dye histologically confirms the identity of sentinel lymph nodes in cutaneous melanoma.

BACKGROUND: False-negative results from lymphatic mapping and sentinel lymphadenectomy (LM/SL) are associated with technical failures in nuclear medicine and surgery or with erroneous histologic evaluation. Any method that can confirm sentinel lymph node (SN) identity might decrease the false-negative rate. Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors, and the authors hypothesized that it could be used for the histologic verification of SNs removed during LM/SL. The current study assessed the clinical utility of carbon dye as a histopathologic adjunct for the identification of SNs in patients with melanoma and correlated the presence of carbon particles with the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph nodes were evaluated for the presence of carbon particles and melanoma cells. If an SN lacked carbon dye in the initial histologic sections, four additional levels were obtained with S-100 protein and HMB-45 immunohistochemistry. Completion lymph node dissection (CLND) was performed if any SN contained melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120 lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of which contained carbon particles. The anatomic location of the carbon particles within these tumor-positive SNs was found to be correlated with the location of tumor cells in the SNs. The presence of carbon particles appeared to be correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028). All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2 contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS: Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs. Carbon particles facilitate histologic evaluation by directing the pathologist to the SNs most likely to contain tumor. The location of carbon particles within SNs may assist the pathologist in the detection of metastases, thereby decreasing the histopathologic false-negative rate of LM/SL and subsequently reducing the same-basin recurrence rate.

Adult↗
PubMed2001

Prognostic significance of circulating microsatellite markers in the plasma of melanoma patients.

PURPOSE: Multiple genetic alterations including loss of heterozygosity (LOH) occur commonly in melanoma tumors. We demonstrated previously free-circulating DNA microsatellites with LOH in the blood of melanoma patients. These LOH markers in plasma may be useful as surrogates for subclinical disease progression. The purpose of this study was to determine whether the presence of circulating tumor microsatellite markers in the preoperative blood from patients with melanoma has prognostic utility. EXPERIMENTAL DESIGN: Plasma was analyzed for the presence of LOH at six chromosome regions, which are common for allelic loss in melanoma tumors, in 57 patients undergoing surgical resection of all of the clinically apparent disease. RESULTS: LOH was detected in 32 of 57 patients (56%). Both LOH incidence and frequency correlated with advancing American Joint Committee on Cancer stage. In patients with American Joint Committee on Cancer stage III, the presence of LOH as an independent variable in preoperative plasma was significantly associated (P = 0.05) with an increased risk of death. Furthermore, LOH at microsatellite marker D1S228 in the plasma of patients with advanced disease correlated significantly (P = 0.0009) with a poorer survival after surgical resection. LOH commonly found in melanoma tumors can be successfully identified in the plasma of a patient, providing a potentially less invasive route for following genetic changes that serve as molecular surrogates for assessing subclinical disease progression. CONCLUSIONS: This study provides evidence that blood testing for circulating tumor genetic markers may provide valuable prognostic information and guide future therapy.

DNA, Neoplasm↗
PubMed2001

Diagnostic laparoscopy and laparoscopic ultrasonography optimize the staging and resectability of intraabdominal neoplasms.

BACKGROUND: Despite technical improvements, preoperative imaging studies often fail to predict intraoperative findings. We investigated the potential use of diagnostic laparoscopy (DL) and laparoscopic ultrasonography (LUS) for the assessment of disease in patients with abdominal neoplasms. METHODS: Fifty consecutive patients with abdominal neoplasms underwent spiral computed tomography with oral and intravenous contrast using 5-mm contiguous sections. In addition, eight patients underwent ultrasonography, six underwent magnetic resonance imaging, and eight underwent positron emission tomography. All patients then underwent DL and LUS using a 7.5-MHz ultrasound probe. RESULTS: There were 29 men and 21 women with a mean age of 63 years (range, 35-84). Most had a diagnosis of colorectal cancer (19 cases), melanoma (12 cases), or hepatoma (five cases). In nine cases (18%), DL revealed peritoneal metastatic implants not shown on preoperative images. In 18 cases (36%), LUS was more accurate than preoperative imaging. Combined DL and LUS findings radically changed the operative management in 16 patients (32%). CONCLUSION: As compared with preoperative imaging, the combination of DL and LUS provides more accurate information regarding staging and resectability. Moreover, it helps to determine the extent of operation and reduces the number of unnecessary laparotomies. DL and LUS should be used as an adjunct to preoperative imaging studies in patients with primary or metastatic intraabdominal neoplasms.

Abdominal Neoplasms↗
PubMed2001

Interleukin-2 binds to ganglioside GD(1b).

We have developed a solid matrix immunoassay to determine the binding of interleukin-2 (IL-2) to specific gangliosides. The assay establishes that recombinant human IL-2 binds to ganglioside GD(1b) but not to any other gangliosides (GM(1), GM(2), GM(3), GD(1a), GD(2), GD(3), and GT(1b)). The binding varies with the ratio of GD1b and IL-2. This assay enables distinguishing the nature of the sugar moiety of the ganglioside recognized by IL-2 and establishes the dosimetry of the ganglioside-IL-2 interaction. Since rIL-2 is administered systematically into stage IV melanoma patients, we have examined 45 tumor biopsies for GD(1b) content. The incidence of GD(1b) in tumor biopsies is 51%. We postulate that GD(1b) associated on the tumor or in the circulation of cancer patients may bind to rIL-2 and prevent the availability of rIL-2 to augment antitumor-immune response.

Binding Sites↗
PubMed2001

Earlier diagnosis of second primary melanoma confirms the benefits of patient education and routine postoperative follow-up.

BACKGROUND: Rising health care costs have caused providers to question the benefit of regular follow-up after treatment for patients with early stage cutaneous melanoma. The authors hypothesized that routine reassessment and careful education of these patients would facilitate earlier diagnosis of a subsequent second primary melanoma, as reflected by reduced thickness of that lesion. METHODS: A prospective melanoma data base was used to identify patients who developed a second primary melanoma after treatment for American Joint Committee on Cancer (AJCC) Stage I or II cutaneous melanoma. After excision of the initial primary melanoma, all patients underwent routine biannual follow-up for new primary lesions. Follow-up consisted of a questionnaire and a complete skin examination by a physician. In addition, patients were regularly educated regarding the increased risk of developing a second melanoma. A paired t test was used to examine AJCC stage, thickness, and level of invasion of the initial melanoma compared with the second primary melanoma. RESULTS: Of 3310 patients with AJCC Stage I or II melanoma, 114 patients (3.4%) developed a second primary melanoma. AJCC staging of both first and second melanomas was available in 82 patients (72%). When the AJCC stages of first and second melanomas were compared, 39 of 82 patients (48%) had lower stage second primary lesions, and 41 (50%) had same-stage second primary lesions. The mean tumor thickness was 1.32 +/- 1.02 mm for the initial melanoma, decreasing to 0.63 +/- 0.52 mm for the second melanoma; in fact, tumor thickness increased in only 4 of 51 patients (8%) whose records contained data for both first and second melanomas. Similarly, the level of invasion decreased in 60% of patients, remained the same in 27% of patients, and increased in only 13% of patients. By paired t test, the differences in AJCC stage, tumor thickness, and level of invasion between first and second melanomas were each highly significant (P = 0.0001). CONCLUSIONS: In this study, the second primary melanoma in patients with a prior cutaneous melanoma was significantly thinner than the initial primary lesion. This is evidence that careful follow-up and patient education allow earlier diagnosis. All patients diagnosed with cutaneous melanoma should be counseled regarding the risks of second melanoma and should undergo lifelong follow-up at biannual intervals.

Adult↗
PubMed2001

Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial.

PURPOSE: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis. PATIENTS AND METHODS: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: beta-chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10(-3) to 10(-4) microg of RNA and one to five tumor cells in 10(7) lymphocytes of healthy donors. RESULTS: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P <.04) with the T stage of the primary tumor. There was 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs. CONCLUSION: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.

Antigens, Neoplasm↗
PubMed2001

Tumor-associated antigen TA90 immune complex assay predicts recurrence and survival after surgical treatment of stage I-III melanoma.

PURPOSE: Immune complexes (IC) containing the tumor-associated antigen TA90 can be identified in the sera of melanoma patients. We have shown that an enzyme-linked immunosorbent assay for TA90-IC can detect subclinical metastasis before surgical treatment of early-stage melanoma. We assayed the TA90-IC levels of postoperative sera from patients with melanoma and evaluated their relationship to recurrence and survival. PATIENTS AND METHODS: Multiple archival serum samples prospectively collected during postoperative surveillance of 166 patients with American Joint Committee on Cancer stage I, II, or III melanoma were analyzed for TA90-IC in a blinded fashion. Results were correlated with disease recurrence and survival determined by database and chart review. RESULTS: TA90-IC status in the early postoperative period was strongly correlated with survival. Five-year overall survival rates were 84% for TA90-IC-negative patients and 36% for TA90-IC-positive patients (P =.0001). Respective 5-year disease-free survival rates were 74% and 24% (P =.0001). The TA90-IC assay was a significant predictor of survival for both stage II and III patients. Multivariate analysis identified TA90-IC status as the strongest independent prognostic factor for both overall and disease-free survival. The TA90-IC assay was elevated in 54 (77%) of 78 patients who developed recurrent disease, becoming positive 19 +/- 7 months before clinical evidence of recurrence. Overall, the assay detected recurrence with a sensitivity of 78% and specificity of 77%. Exclusion of patients receiving postoperative immunotherapy with a polyvalent melanoma cell vaccine increased sensitivity and specificity to 92% and 86%, respectively. CONCLUSION: The TA90-IC assay can accurately predict survival and detect the presence of subclinical disease after surgery for melanoma, which should be useful in selecting patients for adjuvant therapy. Because the TA90-IC assay detected recurrence on an average of 19 months sooner than did routine clinical and radiographic evaluation, it may allow more timely therapeutic interventions.

Antigens, Neoplasm↗
PubMed2001

Surgical resection for metastatic melanoma to the liver: the John Wayne Cancer Institute and Sydney Melanoma Unit experience.

HYPOTHESIS: Metastatic melanoma to the liver is not incurable; complete surgical resection can achieve long-term survival in selected patients. BACKGROUND: Metastases to the liver are diagnosed in 10% to 20% of patients with American Joint Committee on Cancer stage IV melanoma. Surgical resection has not been generally accepted as a therapeutic option, as most patients will have other sites of disease that limit their survival to a median of only 4 to 6 months. However, there is little information on outcomes following resection in those patients with disease limited to the liver. PATIENTS AND METHODS: Review of the prospective melanoma databases at the John Wayne Cancer Institute, Santa Monica, Calif, and the Sydney Melanoma Unit, Sydney, Australia, identified 1750 patients with hepatic metastases, of whom 34 (2%) underwent exploration with intent to resect the metastases. Prognostic factors within the group of patients who underwent resection were examined by univariate and multivariate analysis, and median disease-free survival (DFS) and overall survival (OS) were calculated. RESULTS: Of 34 patients undergoing exploratory celiotomy, 24 (71%) underwent hepatic resection and 10 (29%) underwent exploration but not resection. Eighteen patients (75%) underwent complete surgical resection, while the remaining 6 underwent palliative or debulking procedures with incomplete resection. The operative resections included lobectomy (n=14), segmentectomy (4), nonanatomic resection (5), and extended lobectomy (1). The median number of resected lesions was 1, and median lesion size was 5 cm (range, 0.7-22 cm). The median disease-free interval between initial diagnosis of melanoma and development of hepatic metastases was 58 months (range, 0-264 months). Median DFS and OS estimates in the 24 patients who underwent surgical resection were 12 months (range, 0-147 months) and 28 months (range, 2-147 months), respectively. Five-year DFS and OS in this group were 12% and 29%. Macroscopically, complete resection of disease (P =.001) and histologically negative resection margins (P =.03) significantly improved DFS by univariate analysis. Patients rendered surgically free of disease also tended to have improved OS (P =.06). Median OS was 28 months for patients who underwent surgical resection compared with 4 months for patients who underwent exploration only (P<.001). CONCLUSIONS: Resection of metastatic melanoma to the liver may improve DFS and OS in selected patients, similar to resection of other metastatic sites. Therefore, patients with limited metastatic sites, including the liver, who can be rendered free of disease should be considered for complete surgical resection, as their prognosis is otherwise dismal.

Adult↗
PubMed2001

The clinical utility of multimarker RT-PCR in the detection of occult metastasis in patients with melanoma.

Cutaneous melanoma is characterized by a high propensity for metastasis. Currently, surgical intervention remains the mainstay of therapy. This approach has proven most beneficial when the diagnosis is of early stage primary lesions. Likewise, patients undergoing resection for a solitary site of metastasis have shown a survival advantage. Identification of metastatic disease depends predominantly on radiographic techniques requiring the presence of significant tumor burdens for successful imaging. However, at that time, the role of surgery and/or biochemotherapy may be of limited value. Techniques to identify minimal disease states may permit more accurate assessment of prognosis. The detection of occult tumor cells by RT-PCR in the blood, lymph nodes, and bone marrow of melanoma patients provides one such approach to monitor tumor progression. Single-marker RT-PCR has been used as one such approach but is noted to have limitations in sensitivity and specificity based on the heterogeneity of tumor marker expression among tumors as well as within an individual tumor lesion or among multiple lesions in individual patients. We employed a multimarker reverse transcriptase polymerase chain reaction assay that demonstrates improved sensitivity over a single-marker approach. Currently, the consequences of detecting systemic subclinical metastasis remain unknown pending longer-term follow-up. The detection of occult melanoma cells using molecular techniques in conjunction with known clinicopathologic prognostic factors may provided a novel and efficient approach in monitoring tumor progression and further identify high-risk patients diagnosed early in the disease course.

Biomarkers, Tumor↗
PubMed2001

Validation of lymphatic mapping in colorectal cancer: in vivo, ex vivo, and laparoscopic techniques.

BACKGROUND: The use of lymphatic mapping (LM) is being investigated to improve the staging of colorectal cancer (CRC) and thereby identify patients who might benefit from adjuvant chemotherapy. This study evaluated in vivo, laparoscopic, and ex vivo approaches for the ultrastaging of CRC. METHODS: Seventy-five CRC patients were enrolled in a study of LM with peritumoral injection of isosulfan blue dye. LM was undertaken during open colon resection (OCR) in 64 patients, during laparoscopic colon resection (LCR) in 9 patients, and after specimen removal (ex vivo) in 2 patients. Ex vivo LM was also undertaken in 6 patients after unsuccessful in vivo LM. All nodes were examined by hematoxylin and eosin (H&E) staining; in addition, sentinel lymph nodes (SNs) were multisectioned and examined by immunohistochemical staining with cytokeratin (CK-IHC). RESULTS: At least one SN was identified in 72 patients (96%). In vivo LM identified SNs in 56 of 64 (88%) patients undergoing OCR and in 9 of 9 (100%) patients undergoing LCR. Ex vivo LM was undertaken as the initial mapping procedure in 2 cases of intraperitoneal colon cancer and after in vivo LM had failed in 6 cases of extraperitoneal rectal carcinoma; an SN was identified in 7 of the 8 cases. Focused examination of the SN correctly predicted nodal status in 53 of 56 OCR cases, 9 of 9 LCR cases, and 6 of 7 ex vivo cases. Multiple sections and CK-IHC identified occult micrometastases in 13 patients (17%), representing 10 OCR, 1 LCR, and 2 ex vivo cases. CONCLUSIONS: LM of drainage from a primary CRC can be accurately performed in vivo during OCR or LCR. Ex vivo LM can be applied when in vivo techniques are unsuccessful and may be useful for rectal tumors. During LCR, colonoscopic injection can be used to mark the primary tumor and define the lymphatic drainage so that adequate resection margins are obtained. These LM techniques improve staging accuracy in CRC.

Adult↗
PubMed2001

Serum TA90 antigen-antibody complex as a surrogate marker for the efficacy of a polyvalent allogeneic whole-cell vaccine (CancerVax) in melanoma.

INTRODUCTION: TA90 is a tumor-associated 90-kD glycoprotein antigen expressed on most melanoma cells, including those of CancerVax, a polyvalent allogeneic whole-cell vaccine. Previous studies have shown that a TA90 antigen-antibody immune complex (IC) in the serum of patients with melanoma is a marker of subclinical tumor burden and a strong prognostic factor. We hypothesized that the induction of TA90-IC during postoperative adjuvant CancerVax therapy might indicate vaccine-mediated immune destruction of subclinical melanoma cells with release of TA90, and thereby serve as a surrogate marker of vaccine efficacy. METHODS: From 1993 to 1997, 219 melanoma patients were enrolled in a prospective phase II trial of CancerVax plus bacille Calmette-Guerin (BCG) after complete tumor resection. Coded serum samples were prospectively collected and analyzed for TA90-IC before and 2, 4, 8, 12, and 16 weeks after initiation of CancerVax therapy. TA90-IC seroconverters were those patients whose negative TA90-IC values (< .410) became positive (> or = .410) after initiation of CancerVax treatment. RESULTS: Before CancerVax therapy, 51 patients had positive TA90-IC values and 168 patients had negative TA90-IC values. During CancerVax treatment, all 51 positive patients remained positive, 79 (47%) negative patients seroconverted to positive, and 89 (53%) negative patients remained negative. Seroconverters had higher 2-year rates of disease-free survival (59% vs. 32%; P < .006) and overall survival (78% vs. 63%; P < .02) than did patients whose TA90-IC values remained positive. CONCLUSIONS: CancerVax induces TA90-IC in melanoma patients with subclinical disease. TA90-IC seroconverted patients have significantly improved disease-free and overall survival compared with TA90-IC positive patients. TA90-IC is an important prognostic factor that can serve as a surrogate marker for the clinical efficacy of CancerVax.

Adult↗
PubMed2001

CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer.

BACKGROUND: The immunogenicity of the polyvalent tumor cell vaccine CancerVax has been correlated with the survival of patients receiving active immunotherapy for melanoma. Because the various antigens expressed on the vaccine are common to colon adenocarcinoma cells, we examined the survival impact of immune responses elicited by CancerVax in patients with advanced colon cancer refractory to standard therapy. METHODS: Twenty-seven patients with American Joint Committee on Cancer (AJCC) stage IV colorectal adenocarcinoma were entered prospectively into the study. CancerVax was coadministered with bacille Calmette-Guerin (BCG) for the first 2 weeks of vaccine treatment. Blood was drawn at the start of therapy and every 2 weeks thereafter to measure serum titers of immunoglobulin (Ig)G and IgM against TA90 (a 90-kD immunogen common to colon cancer and CancerVax cells) and against purified protein derivative (PPD), a nontumor control antigen. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) reaction to vaccine cells and to PPD. Mean follow-up time was 17.5 months. RESULTS: There was a significant (P = .0001) increase in anti-TA90 IgG and IgM titers and in DTH response to vaccine cells. Humoral and skin responses to TA90 did not correlate with responses to PPD (P = .199 for IgM, P = .958 for IgG, and P = .149 for DTH). This suggests that these responses are not a manifestation of general immune competence. The median overall survival (OS) was 21.9 months for the entire group. Overall survival was higher among patients whose IgMTA90 titer was >800 (P = .003) or whose disease-free interval exceeded 12 months (P = .031). Multivariate Cox regression analysis-using age, sex, disease-free interval, disease status, extent of metastasis, humoral responses, and DTH responses-found only peak IgMTA90 titer to be a significant predictor of overall survival (P = .0365). CONCLUSIONS: CancerVax can induce measurable humoral and cellular immune responses to tumor-associated antigens in patients with advanced-stage colon cancer. These responses correlate with overall survival. This novel therapeutic regimen for patients with advanced colon cancer merits further investigation.

Adenocarcinoma↗
PubMed2001

Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

BACKGROUND: Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection. METHODS: A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2000. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure. RESULTS: Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases. CONCLUSIONS: In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.

Abdominal Neoplasms↗
PubMed2001

Molecular clonality of in-transit melanoma metastasis.

In-transit melanoma is characterized by an aggressive pattern of recurrence that is associated with a poorer prognosis. Because in-transit melanoma is considered to result from the intralymphatic trapping of melanoma cells between the primary tumor and regional lymph nodes, it provides an excellent model to assess genetic events associated with early metastasis. The hypothesis of this study was to determine whether in-transit metastases are clonal in origin and therefore, may have specific genetic alterations uniquely associated with this disease and the development of early metastasis. This was assessed using loss of heterozygosity (LOH) analysis for specific DNA microsatellite loci. Seventy-nine paraffin-embedded in-transit melanoma lesions from 25 patients (range, 2 to 9 lesions per patient; average, 3.4 lesions per patient) were assessed for LOH using eight microsatellite DNA markers on six chromosomes. In 19 of 25 patients (76%) LOH was demonstrated for at least one marker. The most frequent microsatellite marker demonstrating LOH was D9S157 (56%). Using LOH microsatellite markers to assess intertumor heterogeneity, six of 79 tumors (7.6%) demonstrated different profiles when compared to other lesions from the same patient. In-transit metastases from those patients demonstrating intertumor heterogeneity were further assessed using laser capture microdissection and DNA analysis, and revealed no significant intratumor heterogeneity. In conclusion, LOH was frequently observed in in-transit melanoma metastasis. Based on LOH analysis, in-transit metastases are clonal in origin. The establishment of clinically successful in-transit melanoma metastasis requires specific genetic events that seem to be unique and homogeneous for each patient.

Clone Cells↗
PubMed2001

The use of sentinel lymphadenectomy to identify candidates for postoperative adjuvant therapy of melanoma and breast cancer.

Sentinel lymphadenectomy (SLND) is fast becoming the procedure of choice for staging primary breast carcinoma and melanoma. This simpler and less morbid alternative to standard lymph node dissection can increase the rate of detecting nodal disease. Because the tumor status of the regional lymph nodes remains a significant prognostic tool in both diseases, clinicians may use SLND to facilitate selection of patients for adjuvant chemotherapy. Although SLND has been validated by institutions worldwide, it continues to evolve. The following review will examine current data and controversies surrounding this emerging technology.

Antineoplastic Agents↗
PubMed2001

Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: implications for tumor biology and treatment.

The sentinel lymph node (SN) is the first node on the direct lymphatic drainage pathway from a tumor. Melanoma-associated SNs are the most likely site of early metastases and their immune functions are strikingly down-modulated. We evaluated histologic and cytologic characteristics of 21 SNs and 21 nonsentinel nodes (NSNs) from melanoma patients who had clinically localized (AJCC Stage I--II) primary cutaneous melanoma. SNs showed highly significant reductions in total paracortical area and in the area of the paracortical subsector occupied by dendritic cells. The frequency of paracortical interdigitating dendritic cells (IDCs) was dramatically reduced in SNs, and most IDCs (approximately 99%) lacked the complex dendrites associated with active antigen presentation. The release of immunosuppressive factors from the primary melanoma may induce a localized and specific paralysis in the SN, which prevents the recognition of otherwise immunogenic melanoma antigens by IDCs. This immune paralysis may facilitate the implantation and growth of melanoma cells in the SN. Cytokine therapy may be able to reverse this immune paralysis. These findings have an important practical application in the histopathologic confirmation that a node is truly sentinel. They also offer an hypothesis to explain the failure of the immune surveillance mechanisms to identify and respond to a small primary melanoma that expresses immunogenic tumor antigens.

Antigen-Presenting Cells↗