Biomedical subjects

Richard Essner

Publications and source records attributed to Richard Essner.

12 recordsLinked to original sources

PubMed2003

Role of sentinel lymphadenectomy in thin invasive cutaneous melanomas.

PURPOSE: Regional lymph node status is the strongest prognostic determinant in early-stage melanoma. Lymphatic mapping and sentinel lymphadenectomy (LM/SL) is standard to stage regional nodes because it is accurate and minimally morbid, yet its role for thin (<or= 1.5 mm) primary melanomas is unknown. PATIENTS AND METHODS: Our melanoma database of more than 10,000 patients was reviewed for patients with melanomas <or= 1.50 mm thick who underwent LM/SL. All had lymphoscintigrams and LM/SL via dye alone or with radiopharmaceutical. Patients with tumor-positive sentinel nodes (SNs) underwent completion dissections. RESULTS: Five hundred twelve patients underwent LM/SL. Most were men (57%), and median age was 49 years. Most primary melanomas were on the torso (44%). Twenty-five patients (4.9%) had tumor-positive SNs. The thinnest lesion with a nodal metastasis was 0.35 mm. The SN-negative and SN-positive cohorts were equivalent by sex, but SN+ patients tended to be younger (P =.053), with significantly more SN metastases in those younger than 44 years (P =.005). No consistent pathology among SN-positive primary melanomas was found. Among those with 1.01- to 1.05-mm primaries, 7.1% were SN-positive. Among 272 patients with lesions <or= 1.00 mm, 2.9% had positive SNs and 1.7% with lesions <or= 0.75 mm had SN metastases. All 13 deaths were in SN-negative patients. Median follow-up durations in SN-positive and SN-negative patients were 25 and 45 months, respectively. CONCLUSION: The high nodal positivity rate associated with primary melanomas 1.01 to 1.50 mm thick suggests that LM/SL is indicated in this group. Younger age may be correlated with nodal metastases in patients with lesions <or= 1.00 mm. Lesions <or= 0.75 mm have minimal metastatic potential, and therefore LM/SL is rarely indicated.

Adolescent↗

PubMed2003

Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy.

PURPOSE: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick (> or = 4 mm) primary cutaneous melanoma. PATIENTS AND METHODS: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course. RESULTS: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P =.184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P =.0006 and.006, respectively) but not with maximal IgG response (P =.73 and.95, respectively). Neither response predicted survival in the observation group. CONCLUSION: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.

Adult↗

PubMed2003

Surgical treatment of malignant melanoma.

The surgical management of melanoma has evolved over the last 100 years. when early concepts of lymphatic permeation of the tumors and metastases led surgeons to perform radical operative procedures. Wide excision of primary melanoma is now performed with 1- to 2-cm radial margins, significantly reducing the need for complex plastic closures, skin grafts. and hospital admissions. Although elective lymph node dissection remains controversial as a therapeutic procedure, the development of SL has improved the staging of the regional lymph nodes and diminished the morbidity of lymph node dissection. The role of SL for routine care of melanoma patients remains unknown. Metastasectomy, which is the surgical resection of distant metastases with tumor-free surgical margins, has not been popular for AJCC stage IV patients with multiple metastases, because surgery is considered a local therapy and therefore of little value for management of disseminated disease. Nevertheless, the many reports of long-term survival after resection of distant melanoma metastases to diverse soft tissue and organ sites clearly indicate that this form of cytoreductive surgery can be extremely successful in carefully selected patients. Unlike chemotherapy, complete surgical metastasectomy can rapidly render a patient disease-free with only a short period of postoperative morbidity. Most patients fully recover from the surgical procedure within 6 weeks, returning to most or all activities. The ability to select patients for surgery is based on the development of more sophisticated imaging techniques, which allow better preoperative differentiation of patients with single versus multiple metastases and improve the surgeon's ability to identify and resect multiple metastatic sites. The overall data suggest that patients whose metastases can be completely resected will experience improved overall survival and occasional long-term cure regardless of the metastatic organ site and number of metastases. We believe that increased understanding of the biology of the primary and metastases, dramatic improvement in the accuracy of staging metastatic disease, and better techniques of surgical resection provide the best chance for long-term palliation or cure of melanoma. Cytoreductive surgery should be considered a form of immunotherapy. The long-term clinical benefit of this therapy depends on the patient's immune response to, the surgical reduction in tumor burden: an immune response that controls subclinical micrometastases should optimize postoperative survival.

Humans↗

PubMed2002

Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine.

PURPOSE: The curative effect of surgery in certain patients with metastatic melanoma suggests the presence of endogenous antitumor responses. Because melanoma is immunogenic, we investigated whether a therapeutic cancer vaccine called Canvaxin (CancerVax Corporation, Carlsbad, CA) could enhance antitumor immune responses and thereby prolong survival. PATIENTS AND METHODS: Of 263 patients who underwent complete resection of American Joint Committee on Cancer stage IV melanoma, 150 received postoperative adjuvant vaccine therapy and 113 did not. The overall survival (OS) for the two groups was compared by Cox regression. Further survival analysis was performed by matched-pair analysis according to three prognostic variables: sex, metastatic site, and number of tumor-involved organ sites. RESULTS: Five-year OS rates were 39% for vaccine and 19% for nonvaccine patients. On multivariate analysis, vaccine therapy was the most significant prognostic variable in this cohort (P =.0001). Analysis of 107 matched pairs of vaccine and nonvaccine patients revealed a significant OS advantage for vaccine therapy (P =.0009): 5-year OS was 39% for vaccine patients versus 20% for nonvaccine patients. There was a significant delayed-type hypersensitivity (DTH) response to adjuvant vaccine therapy (P =.0001), and OS was significantly correlated with DTH to vaccine (P =.0001) but not with DTH to purified protein derivative (PPD), a control antigen. CONCLUSION: Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine. The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect. These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma.

Cancer Vaccines↗

PubMed2002

Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine.

PURPOSE: Although the improved overall survival (OS) of patients who receive Canvaxin (CancerVax Corp, Carlsbad, CA) polyvalent vaccine (PV) immunotherapy for metastatic melanoma has been correlated with cellular and humoral immune responses, the mechanisms of vaccine immunotherapy for early-stage melanoma are unclear. Specific immune responses to tumor-associated antigens might correlate with disease-free survival (DFS) and OS in patients receiving adjuvant PV therapy for primary melanoma. PATIENTS AND METHODS: Eighty-three patients received PV plus bacille Calmette-Guérin after wide excision of American Joint Committee on Cancer stage II melanoma. Humoral and cellular responses during the first 12 weeks of adjuvant immunotherapy were assessed by serum antibody titers to a tumor-associated 90-kd glycoprotein antigen (TA90) expressed by PV, and by delayed-type hypersensitivity (DTH) skin testing with PV (PV-DTH). RESULTS: At a median follow-up period of 46.6 months (range, 10.7 to 93.6 months), an increased PV-DTH response seemed to be associated with improved 5-year DFS (54% v 20%) and 5-year OS (75% v 60%), but the correlations were not statistically significant. Anti-TA90 immunoglobulin (Ig) M levels > or = 1:800 were significantly correlated with improved 5-year DFS and improved 5-year OS, and multivariate analysis identified anti-TA90 IgM as an independent prognostic factor for OS and DFS. CONCLUSION: These findings suggest that an increased IgM response in patients receiving PV therapy for stage II melanoma is associated with decreased recurrence and improved survival.

Antibody Formation↗

PubMed2002

Sentinel node biopsy: not only a staging tool?

The management of clinically negative regional lymph nodes in early-stage melanoma has been controversial for at least a century. While some surgeons offer elective lymph node dissection (ELND), others recommend treatment of the primary alone and only perform a therapeutic dissection (TLND) for cases of recurrence in the nodal basin. The rationale for ELND is based on the concept that metastases occur via the sequential passage of tumor from the primary site to the regional lymph nodes and then to more distant sites. If this theory is correct then early dissection of the regional lymph nodes will disrupt the metastatic cascade and prevent further spread of disease. On the other hand, advocates of the "wait and watch" approach suggest that metastases to the regional lymph node basin are only a marker of disease progression and that distant disease can occur in the absence of lymph node metastases. Four randomized prospective studies have examined the efficacy of ELND versus TLND. While all four studies have failed to demonstrate a survival advantage of ELND, there is some suggestion that patients with metastases in the regional basin may benefit from ELND. As an alternative approach to this controversy, Morton and associates at the John Wayne Cancer Institute devised the technique of intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL). This minimally invasive operative procedure allows the surgeon to identify the first or sentinel lymph (SN) in the regional basin. The technique is predicated on accurate mapping of the cutaneous lymphatics by lymphoscintigraphy and the intraoperative use of a vital blue dye to lead the surgeon to the SN and allow the pathologists to identify metastases in the lymph nodes. Patients with tumor-positive dissections would undergo complete lymph node dissection (CLND), and for those without metastases the complications and costs associated with CLND could be avoided. The success of the procedure depends on the completion of a learning phase and on the cooperation of nuclear medicine physicians, surgeons, and pathologists. While this technique has become almost standard practice in the United States and around the world, we await the results of several important clinical trials to determine whether LM/SL will replace ELND or the wait and watch approach in the management of early-stage melanoma.

Humans↗

PubMed2002

Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine correlates with improved survival in recurrent metastatic melanoma.

BACKGROUND: We have observed prolonged survival in patients undergoing vaccine reinduction after resection of recurrent metastatic melanoma and adjuvant polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that reinduction with a more intensive vaccine regimen would re-stimulate specific immune responses that were correlated with survival after recurrence. METHODS: From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent disease was treated with or without vaccine reinduction. Reinduction regimen entailed an increased vaccine frequency and coadministration of two doses of bacille Calmette-Guérin (BCG). PACV Delayed-type hypersensitivity (DTH) responses were prospectively recorded. Survival was defined as the interval from recurrence to death. RESULTS: Ninety-four patients underwent reinduction immunotherapy. DTH responses to PACV before recurrence increased significantly after reinduction therapy (P =.0001). The median survival time was 37 months for reinduced patients and 17 months for other patients. On multivariate analysis, reinduction status remained a significant prognostic variable (P =.0277). In the reinduction group, there was a significant correlation between PACV DTH responses and survival (P =.0178). CONCLUSIONS: Reinduction vaccine regimen can enhance immune responses in previously immunized patients and is associated with prolonged survival after recurrence in patients receiving the same active specific immunotherapy.

Adolescent↗

PubMed2002

Serum TA90 immune complex assay can predict outcome after resection of thick (> or =4 mm) primary melanoma and sentinel lymphadenectomy.

BACKGROUND: We hypothesized that the postoperative serum level of TA90-IC, an immune complex of a 90-kDa tumor-associated antigen and its antibody, might have a significant correlation with recurrence and survival in patients with thick primary melanomas. METHODS: We used our prospective melanoma database to identify all patients who underwent wide local excision and sentinel lymphadenectomy for primary melanomas > or =4 mm and from whom sera had been collected and cryopreserved within 6 months after surgery. These sera were analyzed in a blinded fashion for TA90-IC status by using our double-determinant enzyme-linked immunosorbent assay. Results were correlated with disease-free survival (DFS) and overall survival (OS). Standard prognostic factors for melanoma were then compared with TA90-IC status for the prediction of DFS and OS. RESULTS: The sensitivity and specificity of the TA90-IC assay for predicting recurrence were 70% and 85%, respectively. Five-year DFS and OS rates were higher for the TA90-IC-negative group than the positive group. The differences in DFS and OS between the TA90-IC-negative and -positive groups were significant. At a median follow-up of 25 months, multivariate analysis identified postoperative TA90-IC status and sex as significant predictors of DFS. TA90-IC status was the only independent prognostic factor with multivariate analysis. CONCLUSIONS: TA90-IC status after resection of thick primary melanoma accurately predicts outcome. A positive postoperative TA90-IC level might affect a decision regarding adjuvant therapy, regardless of regional nodal status.

Adult↗

PubMed2002

Prognostic implications of thick (>or=4-mm) melanoma in the era of intraoperative lymphatic mapping and sentinel lymphadenectomy.

BACKGROUND: Lymphatic mapping/sentinel lymphadenectomy (LM/SL) has become a routine part of our treatment algorithm for primary melanoma, yet its role in the management of thick (>or=4-mm) lesions is unknown. METHODS: One hundred twenty-one patients with thick primaries underwent LM/SL at our institute. Survival curves were constructed from Kaplan-Meier estimates and analyzed by Cox proportional hazards methods. RESULTS: Sixty-three percent of patients were men, median age 54 years. The primary tumor sites were trunk (46%), extremities (32%), and head and neck (21%). Primary thickness ranged from 4 to 15 mm (median, 6.0 mm). Forty-five percent of primary tumors were ulcerated. Thirty-five percent of patients had tumor-positive dissections. Median follow-up was 31 months. The overall 5-year survival was no different (P =.726) for ulcerated and nonulcerated lesions. There was no difference (P =.159) in overall survival after tumor-negative (60% +/- 7%) and tumor-positive (50% +/- 10%) dissections. The 5-year disease-free survival was significantly (P =.012) lower in patients with tumor-positive (34% +/- 9%) than tumor-negative (47% +/- 7%) dissections. CONCLUSIONS: Although LM/SL has become a popular technique for staging the regional lymph nodes in early-stage melanoma, our results suggest that sentinel node status is predictive of disease-free survival for thick primary tumors but is not yet reflective of overall survival. The role of LM/SL for patients with thick primary tumors is not clearly defined.

Adult↗

PubMed2002

Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes.

OBJECTIVE: To determine whether adjuvant postoperative active specific immunotherapy with a therapeutic polyvalent vaccine (PV) called Canvaxin can prolong survival following complete resection of melanoma metastatic to regional nodes (American Joint Committee on Cancer [AJCC] stage III melanoma). SUMMARY BACKGROUND DATA: Despite complete lymphadenectomy, 5-year overall survival (OS) for patients with melanoma metastatic to regional lymph nodes is only 20% to 50%, depending on the number of tumor-involved nodes. In 1984, the authors began phase II trials of Canvaxin PV as postsurgical adjuvant therapy for AJCC stage III melanoma. METHODS: Patients who received PV between 1984 and 1998 were compared with patients who did not receive PV postsurgical therapy between 1971 and 1998. The seven covariates recently defined by the AJCC Melanoma Staging Committee (number of metastatic nodes, palpable status, ulceration, age, primary site, pT stage, and gender) were included by Cox regression in a multivariate model of OS. A computerized program matched PV and non-PV patients by these covariates. RESULTS: Of 2,602 patients who underwent complete lymphadenectomy for AJCC stage III melanoma with regional nodal metastases and were followed up by the same team of oncologists between 1971 and 1998, 935 received PV and 1,667 did not. Median OS and 5-year OS were significantly higher in PV than non-PV patients (56.4 vs. 31.9 months and 49% vs. 37%, respectively; P =.0001). When the non-PV patients were matched by the four most significant covariates, 447 matched pairs were formed between patients seen before or after January 1, 1985, and the OS was not different between the two time periods ( P=.789). However, when the PV patients were matched with non-PV patients by six covariates forming 739 pairs, the PV patients survived longer ( P=.0001). Detailed analysis of the 1,505 patients who were seen or who began vaccine therapy within 4 months after lymphadenectomy, and who had more complete data on the seven prognostic covariates showed that median OS and 5-year OS were higher in 445 PV patients than in 1,060 non-PV patients: 70.4 versus 31 months and 52% versus 37%, respectively (P =.0001). Multivariate Cox regression analysis identified six significant prognostic factors: number of metastatic nodes, size of metastatic nodes, pT stage, ulceration, age, and PV therapy. PV therapy reduced the relative risk of death to 0.64 (95% confidence interval, 0.55-0.76) ( P=.0001); sex and site of primary were of borderline significance. CONCLUSIONS: This large single-institution study independently confirmed the significance of prognostic covariates in the new AJCC staging system. By using modern statistical methods that controlled for all known prognostic factors, it also demonstrated PV's ability to significantly enhance OS. A multicenter phase III randomized trial is underway to validate the efficacy of PV as a postsurgical adjuvant.

Aged↗

PubMed2002

Dendritic cell function in sentinel nodes.

Intraoperative lymphatic mapping and sentinel lymphadenectomy has become an increasingly popular technique for staging the regional lymph nodes in early-stage melanoma. This operative technique allows for detailed pathologic analysis of the first (or sentinel) lymph node in direct connection with the primary tumor, and provides a unique opportunity for assessing potential immunologic interactions between the primary tumor and regional lymph node basin. We performed lymphatic mapping and sentinel lymphadenectomy on 25 patients with early-stage melanoma and resected an additional nonsentinel node in each case. Sentinel and nonsentinel nodes were evaluated by routine pathologic analysis. A portion of each node was processed for expression of the dendritic markers of activation CD80, CD86, and CD40, and their corresponding T-cell receptors CTLA-4 and CD28. Of 25 patients undergoing lymphatic mapping and sentinel lymphadenectomy, 20 (80%) had matched sentinel and nonsentinel nodes. A total of 26 matched lymph node sets were obtained: three pairs from one patient and two from an additional two patients. Reverse transcription polymerase chain reaction analyses of corresponding sections of the sentinel and nonsentinel nodes 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 sentinel as compared to nonsentinel nodes. The diminished expression of the dendritic cell markers appeared to be unrelated to the B-cell (CD20) and T-cell (CD2) expression. Lymphatic mapping and sentinel lymphadenectomy allows for detailed pathologic and molecular characterization of sentinel nodes. Our results suggest a quantitative reduction in dendritic cell markers in sentinel as compared to nonsentinel nodes, which may be important in the immunologic interaction between the primary site and regional lymph node basin and may also serve as useful criteria for identifying sentinel nodes.

Antigens, CD↗

PubMedDate not supplied

Advances in FDG PET probes in surgical oncology.

Whole-body positron emission tomography (WB-PET) has been developed as a sensitive, cost-effective method for imaging malignant disease. WB-PET provides complete body imaging with a single scanning approach for a variety of malignancies. With increasing clinical experience, the indications for its use have broadened. This article reviews current uses of the technology and discusses some potential applications, particularly the utility of a commercially available surgical gamma probe for detecting the gamma particles emitted in the decay process of FDG.

Equipment Design↗