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L A Wanek

Publications and source records attributed to L A Wanek.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed2000

Effects of halothane, enflurane, and isoflurane on measurements of Ca(2+) by calcium electrode and aequorin luminescence.

We assessed the possible effects of the volatile halogenated anesthetics halothane, enflurane, and isoflurane on Ca(2+) electrode measurements and on the Ca(2+) sensitivity of the bioluminescent protein aequorin. In Ca(2+)-EGTA buffers of different pCa values (7. 870, 6.726, 6.033, 4.974, 4.038, and 2.995) and in serial Ca(2+) dilutions (10(-4), 10(-3), and 10(-2) M), halothane, enflurane, and isoflurane each caused a concentration-dependent and reversible increase in the absolute value of the negative electrode potential. Isoflurane and enflurane had larger effects than halothane. Neither of these anesthetics changed aequorin luminescence at any pCa tested in the range 2-8. There was no potentiation or inactivation of aequorin luminescence over a period of up to 2 h. These results suggest that (1) halothane, enflurane, and isoflurane interfere with Ca(2+) electrode measurements, most likely by changing the physicochemical properties of the membrane; (2) these anesthetics do not inactivate or otherwise modify the characteristics of the reaction of Ca(2+) with aequorin; and (3) these anesthetics do not change the apparent affinity of EGTA for Ca(2+).

Aequorin↗
PubMed2000

Is adjuvant radiotherapy necessary after positive lymph node dissection in head and neck melanomas?

INTRODUCTION: Postoperative radiotherapy (PR) has been recommended in patients with advanced head and neck melanomas to improve regional control. This study examined the incidence of cervical recurrence among patients who did not receive PR after surgical management of node-positive head and neck melanomas. METHODS: A computerized search of a database listing more than 10,000 patients with melanoma prospectively acquired between 1971 and 1998 identified 217 patients with pathologically positive nodes who had undergone regional lymph node dissection (RLND). Of these patients, 21 had received PR and 196 had not. RESULTS: Median follow-up after RLND was 20 months for nonsurvivors and 32 months for survivors. The overall incidence of cervical recurrence was 14% (27/196). The 5-year cervical recurrence-free survival rate was 83%. Five-year cervical recurrence-free survival rates were 69% vs. 87% for patients with vs. without extranodal disease (P = .004), 96% vs. 81% for patients with nonpalpable vs. palpable nodes (P = .0761), and 82% vs. 91% for patients with one to three positive nodes vs. more than three positive nodes (P = .256). Multivariate analysis, which included the timing of nodal disease presentation and the effect of systemic adjuvant therapy, identified extranodal disease as the only independent predictor of cervical recurrence (P = .034). Cervical recurrence was significantly related to the subsequent occurrence of distant relapse. CONCLUSIONS: The low incidence of cervical recurrence after RLND in patients with node-positive head and neck melanomas does not justify the routine use of PR. The only subset of patients who may benefit from PR are those with extranodal disease.

Adolescent↗
PubMed2000

Can elective lymph node dissection decrease the frequency and mortality rate of late melanoma recurrences?

BACKGROUND: Although more than 90% of the morbidity and mortality from localized cutaneous melanoma occurs in the first decade after initial surgical treatment, melanoma can recur after a 10-year disease-free interval (DFI) with fatal consequences. We reviewed our melanoma data base of more than 8,500 prospectively acquired patients to identify clinicopathological factors that affect the type, rate of occurrence, and outcome of disease recurring 10 years or more after surgical treatment of primary cutaneous melanoma. METHODS: From 1971 to 1997, 1907 melanoma patients treated at our cancer center reached or presented with a DFI of 10 years or more after surgical treatment of clinically localized melanoma. Of these, 217 (11%) patients had recurrences (mean DFI, 182 months). The sites of recurrence were local/in-transit in 26 (12%) patients, regional lymph nodes in 101 (47%) patients, and distant sites in 90 (41%) patients. RESULTS: Univariate and multivariate analysis, using patient age and sex, type of initial treatment, and the site, Breslow thickness, and Clark level of the initial tumor, showed that the type of treatment for the primary tumor was a significant (P = .0005) prognostic factor in the development of late nodal recurrence. Of the 217 patients who had recurrences, 172 (79%) had undergone wide local excision for their primary melanoma, and 45 (21%) had undergone wide local excision plus elective lymph node dissection (ELND). The rates of nodal recurrence were 53% (92 of 172) and 20% (9 of 45), respectively, a significant (P = .0001) difference. When all patients with a DFI of 10 years or more were stratified by type of initial treatment, the ELND group demonstrated a significant improvement in disease-free survival and overall survival. CONCLUSIONS: The risk of late-recurring nodal disease increases and the chance of long-term survival decreases when wide local excision is performed without ELND. With the advent of sentinel lymphadenectomy, ELND can be selectively performed only for those nodal basins with occult tumor cells, thereby decreasing operative morbidity but allowing identification and early removal of nodal micrometastases.

Adolescent↗
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

Effects of halothane and isoflurane on the intracellular Ca2+ transient in ferret cardiac muscle.

BACKGROUND: Halothane and isoflurane depress myocardial contractility by decreasing transsarcolemmal Ca2+ influx and Ca2+ release from the sarcoplasmic reticulum. Decreases in Ca2+ sensitivity of the contractile proteins have been shown in skinned cardiac fibers, but the relative importance of this effect in intact living myocardium is unknown. The aims of this study were to assess whether halothane and isoflurane decrease myofibrillar Ca2+ sensitivity in intact, living cardiac fibers and to quantify the relative importance of changes in myofibrillar Ca2+ sensitivity versus changes in myoplasmic Ca2+ availability caused by these anesthetics. METHODS: The effects of halothane and isoflurane (0-1.5 times the minimum alveolar concentration (MAC) in three equal increments) on isometric and isotonic variables of contractility and on the intracellular calcium transient were assessed in isolated ferret right ventricular papillary muscle microinjected with the Ca2+-regulated photoprotein aequorin. The intracellular calcium transient was analyzed in the context of a multicompartment model of intracellular Ca2+ buffers in mammalian ventricular myocardium. RESULTS: Halothane and isoflurane decreased contractility, time-to-peak force, time to half-isometric relaxation, and intracellular Ca2+ transient in a reversible, concentration-dependent manner. Halothane, but not isoflurane, slowed the increase and the decrease of the intracellular Ca2+ transient. Increasing extracellular Ca2+ in the presence of anesthetic to produce peak force equal to control values increased intracellular Ca2+ to values higher than control values. CONCLUSIONS: Halothane decreases myoplasmic Ca2+ availability more than isoflurane; halothane and isoflurane decrease myofibrillar Ca2+ sensitivity to the same extent; in halothane at 0.5 MAC and isoflurane at 1.0 MAC, the decrease in Ca2+ sensitivity is already fully apparent; halothane decreases intracellular Ca2+ availability more than myofibrillar Ca2+ sensitivity; and isoflurane decreases myoplasmic Ca2+ availability and Ca2+ sensitivity to the same extent, except at 1.5 times the MAC, which decreases Ca2+ availability more.

Aequorin↗
PubMed1999

Lymph node biopsy does not impair survival after therapeutic dissection for palpable melanoma metastases.

BACKGROUND: To determine the effects of disrupting a nodal basin in patients with American Joint Committee on Cancer stage III melanoma with clinically palpable lymph nodes, we studied patients who underwent therapeutic lymph node dissection after excisional lymph node biopsy, after fine-needle aspiration (FNA) biopsy, or without a preoperative biopsy. METHODS: We performed a retrospective review of our patients with American Joint Committee on Cancer stage III melanoma who were treated between January 1972 and June 1995, using data acquired from our 8200-patient database. The study group included 670 patients with melanoma, with known primary tumors, who underwent therapeutic lymph node dissection for palpable nodal metastases diagnosed by open biopsy (227 patients), by FNA (66 patients), or by clinical observation without biopsy (377 patients). Regional node recurrence, 5-year disease-free survival, and overall survival rates were calculated. RESULTS: The same-basin regional node recurrence rates were similar for the three groups (open biopsy, 4.6%; FNA, 3.2%; no biopsy, 4.6%; P = .14). The 5-year disease-free survival rates were 36.8% for the open-biopsy group, 29.6% for the FNA group, and 28.9% for the no-biopsy group (P = .08); corresponding 5-year overall survival rates were 40.6%, 43.9%, and 36.1%, respectively (P = .18). Multivariate analysis failed to identify preoperative biopsy as a significant risk factor. Matched-pair analysis using age, gender, primary tumor site, Breslow thickness, and tumor burden showed no differences in the 5-year disease-free survival rates (33% for the open-biopsy group vs. 27% for the FNA and no-biopsy groups, P = .42) and the 5-year overall survival rates (41% vs. 35%, P = .32). CONCLUSIONS: For patients with melanoma with palpable regional adenopathy, histological confirmation of clinical suspicion with either FNA or excisional lymph node biopsy does not adversely affect survival or recurrence rates.

Biopsy↗
PubMed1997

Metastasis of primary melanoma to two separate lymph node basins: prognostic significance.

BACKGROUND AND METHODS: Depending on the location of the primary lesion, melanoma patients may develop metastases in more than one regional lymph node basin. To determine whether this is prognostically significant, we reviewed our experience with melanoma patients who had undergone regional lymphadenectomy (RLND) in two separate basins. RESULTS: Of 3,603 patients who underwent RLND between April 1971 and January 1993, 406 underwent procedures in two separate basins; of these, 120 (30%) had metastases in both basins and 124 (30%) had metastases in one basin. When calculated from the first positive RLND, 1-year, 3-year, and 5-year survival rates were 82%, 48%, and 33%, respectively, for patients with dual-basin involvement and 88%, 59%, and 48%, respectively, for patients with single-basin involvement (p = 0.0173). Median survival from the first positive RLND was 33.5 months for dual-basin involvement and 56.6 months for single-basin involvement. Univariate analysis demonstrated that Breslow thickness of the primary melanoma, clinical status of the regional lymph nodes, number of positive RLNDs, and tumor burden (total number of positive lymph nodes) were significant indicators of survival. The patient's age and gender, the anatomic location and Clark level of the primary melanoma, the disease-free interval before regional metastasis, and the site and timing of RLNDs were not significant by univariate analysis. Multivariate analysis demonstrated significance for Breslow thickness, number of positive RLNDs, and tumor burden. CONCLUSIONS: The survival rate of melanoma patients with regional metastases in two lymph node basins is lower than that of patients with an equal tumor burden confined to a single basin. This suggests that primary melanomas metastasizing to more than one lymph node basin may have a higher metastatic potential, or that dual-basin involvement may increase the risk of systemic spread. We advocate lymphatic mapping, sentinel node biopsy, and selective lymphadenectomy as a cost-effective technique with little morbidity to identify and manage occult metastases in patients who have two lymph basins at risk.

Adult↗
PubMed1996

Surgical resection for melanoma metastatic to the gastrointestinal tract.

OBJECTIVE: To evaluate the role of surgery in the survival of patients with melanoma metastatic to the gastrointestinal (GI) tract. DESIGN: Retrospective review. SETTING: Tertiary cancer center. PATIENTS: One hundred twenty-four potential surgical candidates with metastatic melanoma in the stomach, small intestine, colon, or rectum. MAIN OUTCOME MEASURES: Operative morbidity and mortality, relief of presenting symptoms, and median and 5-year survival. RESULTS: The median disease-free interval prior to diagnosis of GI tract metastasis was 23.2 months (range, 1-154 months). Patients typically presented with crampy abdominal pain, symptomatic mass, and/or occult GI tract blood loss. Of the 124 patients, 69(55%) underwent surgical exploration of the abdomen, 46 (66%) had curative resection, and 23 (34%) had a palliative procedure. There was only 1 operative death and 1 major operative complication; 67 (97%) of 69 surgical patients experienced postoperative relief of their presenting GI tract symptoms. The median survival in patients undergoing curative resection was 48.9 months, compared with only 5.4 months and 5.7 months in those undergoing palliative procedures and nonsurgical interventions, respectively. By multivariate analysis, the 2 most important prognostic factors for long-term survival were complete resection of GI tract metastases and the GI tract as the initial site of distant metastases. CONCLUSIONS: Almost all patients with melanoma and GI tract metastases can have palliation of symptoms by surgical intervention with minimal morbidity and mortality. The high 5-year survival rate associated with complete surgical resection of GI tract metastases indicates that surgery should be strongly considered for this subgroup of patients with melanoma and distant metastatic disease.

Female↗
PubMed1995

Resection and adjuvant immunotherapy for melanoma metastatic to the lung and thorax.

Although melanoma that metastasizes to distant sites is generally associated with a median survival of only 6 to 8 months, certain metastatic sites including the lung may carry a better prognosis than others. Surgical therapy for pulmonary metastases remains controversial because of the variable survival rates reported for previous small series. To determine the prognosis and optimal management of patients with melanoma with pulmonary metastases, we reviewed our 22-year melanoma database of over 6100 patients. Of 984 patients with metastatic melanoma involving the lung or thorax, 106 underwent resection by posterior lateral thoracotomy or median sternotomy. There were no operative deaths, and the median follow-up period for surgical patients was 55 months. The remaining 878 patients were treated without operation with immunotherapy, chemotherapy, radiation therapy, or a combination. In both treatment groups the male/female ratio was approximately 2:1. The primary lesion's Clark level of invasion and Breslow thickness and the patient's age at diagnosis of metastatic disease were not significantly different between the two groups. The 1-year, 3-year, and 5-year survival rates for surgical patients were 77%, 37%, and 27%, respectively, compared with 32%, 7%, and 3% for nonsurgical patients; these differences were highly significant (p = 0.0001). The highest 5-year survival rate (39%) occurred in those patients with a single metastatic lesion. Sixty-three percent of the surgical patients received some form of immunotherapy, compared with 34% of the nonsurgical patients. Multivariate analysis showed that resection and immunotherapy with a melanoma cell vaccine were both independent predictors of survival (p < 0.0001). These results indicate that the prognosis associated with metastatic melanoma may be less dismal than previously thought when distant metastases involve thoracic sites. We believe that surgical resection is the treatment of choice for patients with melanoma with pulmonary metastases; when combined with immunotherapy, this regimen offers the best chance for long-term survival.

Cancer Vaccines↗
PubMed1995

Prognostic factors in 1,521 melanoma patients with distant metastases.

BACKGROUND: Although over 7,000 people die from malignant melanoma each year, there are limited prognostic data for patients with metastatic disease. A retrospective analysis was undertaken to identify variables that accurately predict outcome and to determine if the survival rate of patients with melanoma treated for distant metastases (American Joint Committee on Cancer [AJCC] stage IV disease) at the authors' institution changed between 1971 and 1993. STUDY DESIGN: Data for 1,521 patients with AJCC stage IV melanoma treated by the staff of the John Wayne Cancer Institute were reviewed, and a univariate and multivariate survival analysis against ten clinical and pathological variables was performed using the Cox proportional hazard regression model. RESULTS: The median survival time of the 1,521 patients was 7.5 months; the estimated five-year survival rate was 6 percent. Three independent variables predicted survival: initial site of metastases (p < 0.0001); disease-free interval before distant metastases (p = 0.0001); and stage of disease preceding distant metastases (p = 0.0001). Patients could be divided into three distinct prognostic groups based on the initial site of metastases: cutaneous, nodal, or gastrointestinal metastases (median survival of 12.5 months; estimated five-year survival rate 14 percent); pulmonary metastases (median survival of 8.3 months; estimated five-year survival rate 4 percent); and metastases to the liver, brain, or bone (median survival of 4.4 months; estimated five-year survival rate 3 percent). There was no significant change in the survival rate of patients with AJCC stage IV melanoma during the 22-year review period. CONCLUSIONS: Despite new treatment options, the survival rate of patients with metastatic melanoma has not changed significantly over the last 22 years; their prognosis remains dismal. The three prognostic variables identified in this study should be considered in the design of future clinical trials.

Adolescent↗
PubMed1994

Application of multistage Markov modeling to malignant melanoma progression.

BACKGROUND: A fundamental research goal in clinical melanoma studies is to understand the natural history of melanoma and its relationship with prognostic factors. The current understanding of melanoma progression and the relationship of risk factors is based on two-stage modeling. METHODS: The authors propose a multistage Markov model for melanoma progression. This model is applied to a data set consisting of approximately 3900 follow-up staging visits of patients with melanoma. The approach takes into account the heavy censoring encountered in this data set and all chronic, subclinically progressive disease. The Markov transition parameters are expressed as Cox regression functions of the relevant prognostic variables. Parameter estimation is achieved by using a missing-data approach. RESULTS: Tumor thickness, level, and site and patient gender and age at diagnosis are independent risk factors in the transition from local to nodal disease. Tumor thickness and level of invasion and patient age are factors in the transition from local disease to dissemination (without intervening involvement of the nodes). Tumor thickness, patient age, primary site, and the number of involved lymph nodes are factors in the transition from nodal disease to dissemination. Transition from dissemination to death is affected by primary thickness, patient gender, number of nodes involved, and site of metastases. CONCLUSION: This multistage analysis contributes to a more accurate understanding of the progress of melanoma and is likely to be applicable to the study of other progressive diseases. Graphic goodness-of-fit results suggest satisfactory predictability of the model to other data sets.

Female↗
PubMed1993

Multivariate analysis of the relationship between survival and the microstage of primary melanoma by Clark level and Breslow thickness.

BACKGROUND: The American Joint Committee on Cancer (AJCC) uses both Breslow thickness and Clark level in its staging system for malignant melanoma. Stage I corresponds to Breslow thicknesses less than 1.5 mm and Clark levels II and III. Stage II corresponds to Breslow thicknesses of at least 1.5 mm and Clark levels IV and V. However, most investigators have found Clark level to be of no prognostic significance once Breslow thickness has been taken into consideration by multivariate analysis. METHODS: The authors examined the prognostic significance of Clark level by studying patients in the large database of the John Wayne Cancer Institute. Among 5575 patients with melanoma seen during the past 20 years, complete data on microstaging by both Clark and Breslow methods were available for 3323 patients. The 5-year survival rates were as follows: Clark II, 95%; III, 81%; IV, 68%; V, 47%. The Breslow thicknesses were as follows: < 0.75 mm, 95%; 0.75-1.49 mm, 85%; 1.5-3.99 mm, 66%; > or = 4.0 mm, 46%. RESULTS: By univariate analysis, both Clark level and Breslow thickness were highly significant prognostic indicators (P < 0.0001). By multivariate analysis, Breslow thickness remained significant (P < 0.0001). However, even when Breslow thickness was included in the model, Clark level also remained highly significant (P < 0.0015). CONCLUSIONS: Decisions regarding therapy for patients with clinical Stage I melanoma should consider both Clark level and Breslow thickness of the primary lesion. When there is a discordance between the two methods of microstaging, the AJCC stage should be amended to reflect the least favorable of the two prognostic indicators.

Humans↗
PubMed1992

Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine.

A new polyvalent melanoma cell vaccine (MCV) was administered to 136 stage IIIA and IV (American Joint Committee on Cancer) melanoma patients. Induction of cell-mediated and humoral immune responses to common melanoma-associated antigens present on autologous melanoma cells was observed in patients receiving the new MCV. This was accompanied by increased activation of tumor-infiltrating lymphocytes. Survival correlated significantly with delayed cutaneous hypersensitivity (p = 0.0066) and antibody responses to MCV (p = 0.0117). Of 40 patients with evaluable disease, nine (23%) had regressions (three complete). From our historical database of 126 stage IIIA and 1275 stage IV melanoma patients, there were no significant changes in the natural history of metastatic melanoma during the past 20 years. Univariate and multivariate analyses demonstrated prognostic significance for site of metastases (p = 0.0001) and immunotherapy with the new MCV (p = 0.0001). Overall our new MCV increased the median and 5-year survival of stage IIIA melanoma patients with regional soft tissue metastases twofold (p = 0.00024), and stage IV patients threefold (p = 0.0001) compared with previous immunotherapy and other treatments.

Adult↗
PubMed1991

Effects of nitrous oxide on contractility, relaxation and the intracellular calcium transient of isolated mammalian ventricular myocardium.

The effects of nitrous oxide on variables of contractility and relaxation were analyzed in isolated ferret right ventricular papillary muscles. Each mechanical variable, in isometric, isotonic, and zero-load-clamped twitches, was compared to the average value of that variable in control conditions (50% nitrogen in oxygen), before and after equilibration with 20%, 30% and 50% nitrous oxide in 50% oxygen. Nitrous oxide caused a concentration-dependent decrease in contractility under all loading conditions, with minor changes in relaxation. The intracellular calcium transient was detected with the Ca(++)-regulated photoprotein aequorin. The change in aequorin luminescence on exposure to nitrous oxide suggests that the negative inotropic effect of nitrous oxide is due to a decrease in calcium availability with no effect on myofibrillar responsiveness to calcium.

Animals↗