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R Essner

Publications and source records attributed to R Essner.

At least 19 recordsLinked to original sources
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

Application of an [(18)F]fluorodeoxyglucose-sensitive probe for the intraoperative detection of malignancy.

BACKGROUND: Whole-body positron emission tomography (PET) has been shown to be a highly sensitive method for detecting malignancy not imaged by conventional modalities. We have adapted a hand-held gamma-ray-sensitive probe to detect the radiation emission from the [(18)F]fluorodeoxyglucose (FDG) used in PET imaging. This pilot study was devised to examine the feasibility of using a hand-held probe to intraoperatively differentiate normal from tumor-bearing tissue. MATERIALS AND METHODS: A commercially available gamma probe was adapted to detect the radioactivity released from FDG and examined to determine the in vitro sensitivity for localization of a FDG point source. Eight consecutive patients underwent resection of metastatic colon cancer or melanoma; each received a preoperative injection of 7--10 mCi of FDG. The gamma probe was used to determine radioactive counts per second from tumor and normal tissue, and ratios of tumor to adjacent normal background were calculated. RESULTS: In vitro studies with a FDG point source demonstrated the probe could identify the source with a 50% reduction in maximum counts 1.7 +/- 0.1 cm from the source (full-width half-maximum measurement). Based on the results of their preoperative PET scans 17 tumors were identified from the 8 patients. Of the 17 tumors assessed the in vivo tumor-to-background ratios varied from 1.16:1 to 4.67:1 for the melanoma patients (13 tumors) and from 1.19:1 to 7.92:1 for colon cancer patients (4 tumors). Thirteen tumors were resected; four (2 patients) were unresectable. CONCLUSIONS: This study demonstrates the use of a hand-held gamma-ray-sensitive probe to intraoperatively differentiate the radioactivity released from FDG from tumor-bearing and adjacent normal tissue. While further studies are necessary for us to optimize the use of this probe, the intraoperative detection of FDG-avid malignancies may ultimately improve our ability to completely resect patients with metastatic disease.

Colonic Neoplasms↗
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

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

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↗
PubMed2001

Surgical and molecular approaches to the sentinel lymph nodes.

Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) provides a unique opportunity for assessing potential immunologic interactions between the primary tumor and regional lymph node basin. We performed LM/SL in 24 patients with early-stage melanoma and resected an additional nonsentinel node (non-SN) in each case. Sentinel nodes (SNs) and non-SNs were evaluated by routine pathologic analysis, and a portion of each node was processed for expression of three dendritic markers of activation (CD80, CD86, CD40) and their corresponding T-cell receptors (CTLA-4 and CD28). Twenty (83%) patients had matched SNs and non-SNs. A total of 26 nodal pairs were obtained because one patient had three pairs and two other patients each had two pairs. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of paired SNs and non-SNs demonstrated a marked reduction in semiquantitative expression of CD80 (77%), CD86 (77%), and CD40 (85%), as well as CTLA-4 (88%) and CD28 (85%) in SNs. The diminished expression appeared to be unrelated to B-cell (CD20) and T-cell (CD2) expression. A quantitative reduction in dendritic cell markers in SNs may be important in the immunologic interaction between the primary site and regional lymph node basin and may also provide useful criteria for identifying SNs.

Antigens, CD↗
PubMed2000

Filamentous polymers induced by overexpression of a novel centrosomal protein, Cep135.

A novel 135 kDa centrosomal component (Cep135) was identified by immunoscreening of a mammalian expression library with monoclonal antibodies raised against clam centrosomes. It is predicted to be a highly coiled-coil protein with an extensive alpha-helix, suggesting that Cep135 is a structural component of the centrosome. To evaluate how the protein is arranged in the centrosomal structure, we overexpressed Cep135 polypeptides in CHO cells by transient transfection. HA- or GFP-tagged full (amino acids 1-1144) as well as truncated (#10, 29-1144; Delta3, 29-812) polypeptides become localized at the centrosome and induce cytoplasmic dots of various size and number in CHO cells. Centrosomes are associated with massive approximately 7 nm filaments and dense particles organized in a whorl-like arrangement in which parallel-oriented dense lines appear with a regular approximately 7 nm periodicity. The same filamentous aggregates are also detected in cytoplasmic dots, indicating that overexpressed Cep135 can assemble into elaborate higher-ordered structures in and outside the centrosome. Sf9 cells infected with baculovirus containing Cep135 sequences induce filamentous polymers which are distinctive from the whorl seen in CHO cells; #10 forms highly packed spheroids, but the Delta3-containing structure looks loose. Both structures show an internal repeating unit of dense and less dense stripes. Although the distance between the outer end of two adjacent dense lines is similar between two types of polymers ( approximately 120 nm), the dense stripe of Delta3 polymers ( approximately 40 nm) is wider than #10 ( approximately 30 nm). The light band of Delta3 ( approximately 40 nm) is thus narrower than #10 ( approximately 60 nm). Since thin fibers are frequently seen to extend from one dense line to the next, the coiled-coil rod of Cep135 may span the light band. These results suggest that overexpressed Cep135 assemble into distinctive polymers in a domain-specific manner.

Animals↗
PubMed2000

Principles of sentinel lymph node identification: background and clinical implications.

The management of clinically negative regional lymph nodes in early-stage melanoma has been controversial for many years. While some advocate wide excision of the primary with elective node dissection (ELND), others recommend excision of the primary alone and therapeutic node dissection (TLND) for recurrences in the nodal basin. ELND is based on the concept that metastases occur by passage of the tumor from the primary to the regional nodes and distant sites, in which case early dissection of regional nodes will disrupt metastatic progression and prevent the spread of disease. Advocates of the "wait and watch" approach suggest that regional node metastases are markers for disease progression and that distant disease can occur without node metastases. Four randomized prospective studies comparing ELND and TLND have not demonstrated overall survival advantage for ELND, but suggest that patients with early regional metastases may benefit from ELND. As an alternative, Morton et al., from UCLA and the John Wayne Cancer Institute, devised intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL). These minimally invasive operative procedures allow identification of the first and key (sentinel) lymph node (SN). The technique accurately maps the lymphatics by lymphoscintigraphy, and vital blue dye leads the surgeon to the SN. The pathologist then concentrates on seeking metastases in the nodes most likely to contain metastases. Patients with tumor-positive SN undergo completion lymph node dissection (CLND), while those without SN metastases avoid the complications and costs associated with this procedure. Morton et al., in a report on their initial experience of LM/SL, performed CLND in all cases regardless of SN tumor status and demonstrated the precise staging capacity of the procedure. Since this initial report, numerous studies have validated the accuracy and low morbidity of the procedure. Each center must master a learning phase. The procedure is dependent on the close cooperation of nuclear medicine physicians, surgeons, and pathologists. While LM/SL is now almost standard practice in the US, the results of clinical trials are awaited to determine whether LM/SL can replace ELND and TLND in the management of early-stage melanoma.

Humans↗
PubMed2000

Functional interleukin 4 receptor and interleukin 2 receptor common gamma-chain on human non-small cell lung cancers: novel targets for immune therapy.

OBJECTIVE: The interleukin 4 receptor has been demonstrated on the surface of human non-small cell lung carcinoma cell lines and tumor specimens. Interleukin 4 causes G1-phase cell-cycle arrest of non-small cell lung cancer cell lines expressing the interleukin 4 receptor; the effect directly correlates with the expression of the interleukin 4 receptor and is seen within 48 hours after treatment. We examined signal transduction pathways used by the interleukin 4 receptor that may account for growth arrest of the cell line LUst but had no effect on another non-small cell lung cancer cell line, SK-MES-1. METHODS: Western blot analysis was performed on both LUst and SK-MES-1 cell lines cultured in the presence of interleukin 4 (500 U/mL). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine monoclonal antibodies to specific intracellular proteins. RESULTS: Western blotting of the cell lines with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kd, 100-130 kd, and 65 kd) phosphoproteins seen only in the interleukin 4-treated LUst cell line and not observed in the SK-MES-1 cell lines. Immunoprecipitation and blotting of the LUst cell line with specific secondary antibodies demonstrated that the 140-kd phosphoprotein was the interleukin 4 receptor, the 130-kd phosphoprotein was Janus kinase 1, the 116-kd phosphoprotein was Janus kinase 3, and the 65-kd phosphoprotein was the interleukin 2 receptor gamma-chain. Specific binding was not observed in the non-small cell lung cancer cell line SK-MES-1, suggesting that a functional interleukin receptor gamma-chain was not present. Southern blotting with complementary DNA probes to interleukin 2 receptor gamma-chain confirmed the absence of this receptor on cell line SK-MES-1. CONCLUSIONS: These results suggest that non-small cell lung cancer cells may express functional cytokine receptors, including the interleukin 2 receptor gamma-chain commonly found in association with the lymphocyte interleukin 2 receptor. These receptors may be novel targets for directing cytokine-based immune therapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Judging the therapeutic value of lymph node dissections for melanoma.

BACKGROUND: The management of the regional lymph nodes remains controversial for early-stage melanoma and for those patients with lymph node metastases; American Joint Committee on Cancer stage III. This study examines the importance of quality of the surgical resection measured by the extent of lymph node dissection (quartile of the total number of lymph nodes removed) to determine if this factor is an important prognostic factor for survival. STUDY DESIGN: We reviewed our computer-assisted database of more than 8,700 melanoma patients prospectively collected from 1971 through the present to identify patients who underwent lymph node dissection for stage III melanoma. We included only patients who had their nodal dissections performed at our institute. Patients who underwent sentinel lymph node dissection were excluded. These patients were then analyzed as a group and by individual lymphatic basins: cervical, axillary, and inguinal basins. Univariate and multivariate analyses were used to examine the model that included tumor burden, thickness of the primary melanoma, gender, age, clinical status of the lymph nodes (palpable versus not palpable), and the primary site. The survival and recurrence rates were analyzed using the Cox proportional hazards model. RESULTS: Five hundred forty-eight patients underwent regional lymph node dissections. Of these patients, 214 underwent axillary dissections, 181 inguinal dissections, and 153 cervical dissections. The extent of the nodal dissections was based on the quartile of nodes excised, ranging from 1 to 98 (mean +/- SD = 25.8 +/- 15.8). Patients were stratified by tumor burden and quartile of number of lymph nodes removed. The overall 5-year survival of patients with four or more lymph nodes having tumor and the highest quartile of lymph nodes removed was 44% and was 23% for the lowest quartile of total lymph nodes excised (p = 0.05). By univariate analysis, tumor burden (p = 0.0001), quartile of total lymph nodes removed (p = 0.043), and primary site (p = 0.047) were statistically significant for predicting overall survival. Gender, clinical status of the nodes, primary tumor thickness, age, and dissected basin were not significant (p > 0.05). By multivariate analysis only the tumor burden (p = 0.0001) and quartile of lymph nodes resected (p = 0.044) were statistically significant. CONCLUSIONS: The extent of lymph node dissection for melanoma when analyzed by quartiles is an independent factor in overall survival. This factor appears to be more important with increasing tumor burden in the lymphatic basin. The extent of lymph node dissection should be considered as a prognostic factor in the design of clinical trials that involve stage III melanoma.

Female↗
PubMed2000

Standardized probe-directed sentinel node dissection in melanoma.

BACKGROUND: Radiopharmaceutical agents appear to improve the accuracy of sentinel node (SN) identification in patients with early-stage melanoma, but the optimal radiopharmaceutical agent and its timing from injection to surgery remain controversial. We undertook this investigation to examine the utility of 3 methods of intraoperative lymphatic mapping with radiopharmaceutical-directed sentinel lymphadenectomy (LM/SL). We suspected that concurrent injection of radiopharmaceutical and blue-dye would lead to the greatest success of SN identification. METHODS: The study was composed of 247 consecutive patients who had American Joint Committee on Cancer stage I or II melanoma. Before LM/SL, all patients underwent cutaneous lymphoscintigraphy by 1 of 3 techniques: technetium 99m (Tc 99m) human serum albumin (HSA) injected at least 24 hours before LM/SL (124 patients), Tc 99m filtered sulfur colloid (SC) injected no more than 4 hours before LM/SL (same-day SC, 95 patients), or Tc 99m SC injected at least 18 hours before LM/SL (prior-day SC, 28 patients). At the time of LM/SL, isosulfan blue dye was injected alone (SC groups) or with a second dose of HSA (HSA group). A hand-held gamma probe was used to determine the radioactive (hot) counts of blue-stained and nonstained nodes, and the in vivo and ex vivo node-to-background count ratios of the nodes were compared. RESULTS: Preoperative LS identified 299 drainage basins; LM/SL identified at least 1 SN in 119 (98%) of 121 basins using same-day SC, 142 (97%) of 146 basins using HSA, and 32 (100%) of 32 basins using prior-day SC. There was no difference (P = .62) in the accuracy rate between the 3 techniques. The total number of SNs was 463. Same-day SC yielded higher intraoperative node-to-background count ratios than did either of the other techniques (P < .0001). Same-day SC also had the greatest relative change in radioactivity between the blue sentinel node and the post-excision basin (P < .0001), and the highest rate of SNs that were both blue and hot (in vivo or ex vivo ratio > or = 2, P = .05). CONCLUSIONS: LS and LM/SL performed on the same day with a single injection of filtered Tc 99m SC serves as the most useful method for probe-directed LM/SL. This technique demonstrated the highest in vivo and ex vivo count ratios, fall-off of radioactivity between the excised nodes and post-excision basin, and concordance between blue dye and hot nodes. It should be recommended as the method of choice for probe-directed LM/SL.

Humans↗
PubMed2000

Accuracy of gamma probes in localizing radioactivity: in-vitro assessment and clinical implications.

BACKGROUND: Radioguided surgery (RGS) uses gamma probes to localize radioactive targets. We examined the in-vitro localizing properties of commercially available gamma probes for three common RGS radioisotopes: technetium-99m (99mTc), indium-111 (111In), and iodine-125 (125I). METHODS: The linear and angular localizing properties of five gamma probes were assessed. Radioactive counts in air were obtained at multiple energy threshold settings for each radioisotope. The full width half maximum (FWHM) and angular half maximum (AHM) were calculated to determine localizing accuracy. RESULTS: The FWHM of the five probes ranged from 1.2 to 3.4 cm for 99mTc, 1.8 to 2.7 cm for 111In and 1.6 to 2.8 cm for 125I. AHM of the probes ranged from 20 to 49 degrees for 99mTc, 14 to 35 degrees for 111In, and 18 to 47 degrees for 125I. The ranking of probe accuracy depended on the radioisotope studied. Absolute count rates varied with energy threshold settings for each probe and radioisotope. Probes required individualized energy threshold settings for optimal performance. CONCLUSIONS: The five probes varied in their characteristics for localizing the three radioisotopes. Each probe has particular detection characteristics that may change with different radioisotopes. Differences in radioisotope detection may explain intraoperative variation in localization during lymphatic mapping and sentinel lymph node dissection (LM/SL). Surgeons should be aware of probe performance characteristics before intraoperative use.

Gamma Rays↗
PubMed2000

Stereotactic radiosurgery in the treatment of metastatic disease to the brain.

OBJECTIVE: In recent years, stereotactic radiosurgery has been growing in popularity as a treatment modality for metastatic disease to the brain. The technique has advantages of reduced cost and low morbidity compared with open surgical treatment. Furthermore, it avoids the potential cognitive side effects of fractionated whole-brain radiotherapy. We undertook this study to determine the usefulness of adjuvant radiation therapy and to determine prognostic factors in patients treated with stereotactic radiosurgery. METHODS: We reviewed our series of patients with metastatic tumors treated using gamma knife stereotactic radiosurgery from August 1994 to February 1999. Nonparametric methods were used to compare treatment subgroups by demographic features including age, Karnofsky Performance Scale score, diagnosis, and systemic disease status. Univariate and multivariate analyses of survival and freedom from progression were performed using Kaplan-Meier and Cox proportional hazards regression techniques. RESULTS: This study included 190 patients harboring 431 lesions who were treated in 263 treatment sessions. The median follow-up after radiosurgery was 36 weeks for all patients. The median actuarial survival from the time of radiosurgery in all patients was 34 weeks. When patients were stratified according to tumor histology, those without melanoma had a median survival of 39 weeks, and those with melanoma had a median survival of 28 weeks. The cause of death could be determined in 122 (92%) of the patients known to have died during the data capture period. For patients harboring melanoma, death was attributable to systemic disease in 31 (47%), to central nervous system-related processes in 29 (44%), and to unknown causes in 6 (9%). For non-melanoma patients, death was attributable to systemic disease in 45 (68%), to central nervous system-related processes in 17 (26%), and to unknown causes in 4 (6%). Significantly improved survival (P = 0.002) was observed in patients with controlled systemic disease. No significant difference in survival could be ascertained for patients presenting with up to four lesions, although patients with a total tumor volume greater than 9 cc had shortened survival. No survival benefit could be demonstrated for whole-brain radiotherapy administered either concomitantly or after radiosurgery. CONCLUSION: Factors correlated with significantly improved survival included controlled systemic disease and non-melanoma histology. We found no significant survival benefit that could be discerned from adjuvant whole-brain radiotherapy in this patient group.

Adult↗
PubMed2000

A review of the literature for whole-body FDG PET in the management of patients with melanoma.

BACKGROUND: A review and meta-analysis of the literature on the use of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the detection of recurrent melanoma was conducted. The goals were to evaluate the quality of data reporting and to determine the overall values for the sensitivity and specificity of whole body FDG PET and management changes. METHODS: Guidelines to evaluate reporting within articles were formulated based on the United States medical payer source criteria for assessing studies reporting information on the utilization of new medical technology. A meta-analysis was conducted using methodology described in the peer reviewed literature. RESULTS: Our MEDLINE PLUS search resulted in a universe of 89 total articles. Within these 89, 19 were categorized in our targeted content area of which 13 were selected for analysis in our targeted subset, with the remaining 70 covering 24 different related content areas. Five of 13 (38%) articles in the target subset reported data which was adequate for incorporation into modeling objectives based on PET sensitivity and specificity values, with 1 of 13 (8%) in the same target subset reporting data adequate for modeling based on change-in-management data. Through a meta-analysis of the 13 target articles we determined, within a 95% confidence level, an overall sensitivity of 92% (95% confidence level 88.41%-95.82%) and an overall specificity of 90% (95% confidence level 83.26%-96.05%) as calculated by number of lesions, for FDG PET detecting recurrent melanoma throughout the whole body. Furthermore, limited data available for change-in-management suggests an overall FDG PET directed change-in-management value of 22%. CONCLUSIONS: Our review suggests that improvements can be made to more effectively report the results of these FDG PET studies. The overall values determined through the meta-analysis indicate the potential benefits of using FDG PET as a diagnostic/management tool. Furthermore, these values should prove useful to assessing the cost effectiveness of utilizing FDG PET in the management of recurrent melanoma.

Confidence Intervals↗
PubMed1999

Active specific immunotherapy with polyvalent melanoma cell vaccine for patients with in-transit melanoma metastases.

BACKGROUND: This study was conducted to document the rate, duration, and type of objective response to active specific immunotherapy with a polyvalent melanoma cell vaccine (PMCV) for patients with in-transit melanoma metastases and to identify any acute or chronic toxic effects of PMCV treatment. METHODS: An analysis was conducted of all in-transit melanoma patients seen at the John Wayne Cancer Institute in Santa Monica, California, during the period 1985-1997 who were enrolled in prospective PMCV protocols in the absence of other therapies with possible antitumor activity (n = 54). Clinical response to PMCV was assessed by standard criteria. Survival curves were estimated by the Kaplan-Meier method. Toxicity was graded according to the Eastern Cooperative Oncology Group standard. RESULTS: PMCV produced a 17% (9 of 54 patients) objective response rate with a 13% rate (7 of 54 patients) of complete remission (CR). The median duration of CR was >22 months. Complete response lasting more than 1 year was observed in 4 patients (7.2%); 1 patient remained in remission over 9 years. Median survival was >53 months (i.e., not reached) for responders, 42 months for nonresponders, and 53 months overall. Salvage interventions allowed reinduction with PMCV in 23 of 25 patients, who subsequently remained clinically free of disease for a median of 14 months. Overall toxicity was mild, easily tolerable, and did not significantly change the quality of life. There were no toxic deaths. CONCLUSIONS: PMCV can cause objective complete regression of measurable intransit metastatic melanoma with minimal toxicity, and may prolong patients' median survival.

Cancer Vaccines↗
PubMed1999

Comparison of blue dye and probe-assisted intraoperative lymphatic mapping in melanoma to identify sentinel nodes in 100 lymphatic basins.

OBJECTIVE: To determine whether combining isosulfan blue dye with a radiopharmaceutical agent will increase intraoperative detection of sentinel nodes (SNs) in patients with early-stage melanoma. PATIENTS AND DESIGN: Clinical trial with a consecutive sample. Eighty-seven patients with clinical stage I melanoma underwent preoperative lymphoscintigraphy with 1 of 3 radiopharmaceutical agents to identify the lymphatic basin and the site of the SN. All patients subsequently underwent intraoperative lymphatic mapping and selective lymph node dissection (SLND) with isosulfan blue dye and a radiopharmaceutical agent. A handheld gamma probe determined the radioactive counts over the draining lymph node basins and individual blue-stained lymph nodes before (in vivo) and after (ex vivo) their removal. An irrelevant body site was used as the denominator of a count ratio by which absolute counts were standardized for comparison. Completion lymphadenectomy was undertaken in patients whose SLND specimen had histopathologic evidence of tumor cells. SETTING: Tertiary care cancer center. INTERVENTION: Lymph node sampling. MAIN OUTCOME MEASURE: Accuracy of SN detection by blue dye and radiopharmaceutical techniques. RESULTS: Preoperative lymphoscintigraphic images identified 100 lymph node basins and 135 lymph nodes in 87 patients. All 3 radiopharmaceutical agents were equally effective in imaging the SN before surgery. During SLND, we identified and removed 136 blue-stained and radioactive (hot) SNs and 8 additional non-blue-stained hot nodes from 98 basins (98.0%). Of the 144 excised lymph nodes, 132 nodes (91.7%) from 83 basins had either an in vivo- or an ex vivo-background count ratio of 2:1 or more and 125 nodes (86.8%) from 77 basins had a count ratio of 3:1 or more. Twelve blue-stained SNs had count ratios of less than 2:1. Seventeen SNs (11.8%) from 15 basins contained metastases: 16 were identified with blue dye and probe and 1 was identified with blue dye alone. Four (1.1%) of 377 non-SNs excised during completion lymphadenectomy contained metastases. There have been no lymph node recurrences during mean follow-up of 16.3 months (range, 7-42 months). CONCLUSIONS: The blue dye technique remains the criterion standard for SLND in melanoma. The addition of a radiopharmaceutical tracer serves as a useful adjunct to the visualization of blue-stained SNs.

Female↗
PubMed1999

Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous melanoma.

BACKGROUND: Routine elective superficial parotidectomy for patients with primary cutaneous melanomas of the scalp, auricle, or face has been questioned. We evaluated an alternative, i.e., lymphatic mapping and sentinel lymphadenectomy, for patients with primary cutaneous melanomas draining to the region of the parotid gland. PATIENTS: Retrospective review of our large (>8000 patients) melanoma database identified 39 patients with primary melanomas (American Joint Committee on Cancer stage I or II) of the scalp (n = 19), auricle (n = 11), or face (n = 9) who underwent intraoperative lymphatic mapping to identify a sentinel node (SN) in the region of the parotid gland, between June 1985 and July 1997. RESULTS: A SN was identified in the parotid region of 37 patients (94.9%), four of whom had SN metastases. The mean number of SN obtained was 2.3/patient (range, 1-4/patient). The two patients (5.1%) for whom a parotid-region SN could not be identified underwent superficial parotidectomy during the same operation. Among the 33 patients with tumor-free SN, with a median follow-up period of 33.2 months (range, 1-121 months), there was one (3.1%) intraparotid recurrence; thus, the false-negative rate was 3.1%. The procedure-related surgical morbidity rate was only 2.6% (one case of temporary facial nerve paresis). CONCLUSIONS: For patients with primary melanomas of the scalp, auricle, or face, sentinel lymphadenectomy can be performed accurately in the parotid region and offers a low-morbidity alternative to routine elective superficial parotidectomy.

Adult↗