Background
Complete lymph node dissection, the current standard treatment for nodal metastasis in melanoma, carries the risk of significant morbidity. Clinically apparent nodal tumor is likely to ...impact both preoperative lymphatic function and extent of soft tissue dissection required to clear the basin. We hypothesized that early dissection would be associated with less morbidity than delayed dissection at the time of clinical recurrence.
Materials and Methods
The Multicenter Selective Lymphadenectomy Trial I randomized patients to wide excision of a primary melanoma with or without sentinel lymph node biopsy. Immediate completion lymph node dissection (early CLND) was performed when indicated in the SLN arm, while therapeutic dissection (delayed CLND) was performed at the time of clinical recurrence in the wide excision-alone arm. Acute and chronic morbidities were prospectively monitored.
Results
Early CLND was performed in 225 patients, and in the wide excision-alone arm 132 have undergone delayed CLND. The 2 groups were similar for primary tumor features, body mass index, basin location, and demographics except age, which were higher for delayed CLND. The number of nodes evaluated and the number of positive nodes was greater for delayed CLND. There was no significant difference in acute morbidity, but lymphedema was significantly higher in the delayed CLND group (20.4% vs. 12.4%,
P
= .04). Length of inpatient hospitalization was also longer for delayed CLND.
Conclusion
Immediate nodal treatment provides critical prognostic information and a likely therapeutic effect for those patients with nodal involvement. These data show that early CLND is also less likely to result in lymphedema.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background For patients with melanoma, if there has been no recurrence of disease 10 years after initial treatment, additional disease is believed to be very unlikely. However, such late recurrences ...are known to occur. The frequency of this phenomenon and its clinical significance are not well characterized due to the difficulty in obtaining relevant data. We examined a large, mature, institutional database to evaluate late recurrence. Study Design The late recurrence cohort was defined as having a disease-free interval of 10 or more years after potentially curative treatment and was compared with an early recurrence cohort recurring within 3 years. Actuarial late recurrence frequency and factors associated with late recurrence were examined. Post-recurrence overall and melanoma-specific survival and prognostic variables were analyzed. Results Among all patients, 408 exhibited late recurrence (mean disease-free interval 15.7 years). For patients who received primary treatment at our institution with 10 or more years follow-up, 327 of 4,731 (6.9%) showed late recurrence. On an actuarial basis, late recurrence rates were 6.8% and 11.3% at 15 and 20 years, respectively, for those with no recurrence at 10 years. Late recurrence was associated with both tumor (thin, non-ulcerated, non-head/neck, node negative) and patient (younger age, less male predominant) characteristics. Multivariate analysis confirmed younger age, thinner and node negative tumors in the late recurrence group. Late recurrences were more likely to be distant, but were associated with better post-recurrence survival on univariate and multivariate analyses. Conclusions Late melanoma recurrence is not rare. It occurs more frequently in certain clinical groups and is associated with improved post-recurrence survival.
Introduction
Historically, the treatment of anorectal melanoma has been abdominoperineal resection (APR), but more recently local resection alone. Although treatment at melanoma centers has become ...less aggressive, the adoption of this approach and related outcomes across the USA is unknown.
Methods
The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients treated for anorectal melanoma (1973–2003). Treatment patterns and survival were studied. Frequency of treatment was compared using the chi-square test; survival was calculated using the Kaplan–Meier method.
Results
The 183 patients identified from the SEER database had a median age of 68 years. Of the 143 patients whose data were included, 51 underwent APR and 92 underwent transanal excision (TAE). Despite similar pathologic characteristics, median survival was similar in the two groups: 16 months for APR and 18 months for TAE (
P
= ns). Five-year survival also was similar in the two groups: 16.8% for APR and 19.3% for TAE (
P
= ns). The rate of APR was 27.0% between 1973 and 1996, as compared with 43.2% between 1997 and 2003 (
P
= ns).
Conclusion
This study, the largest series to analyze widespread practice patterns and outcomes for anorectal melanoma in the USA, did not reveal a survival difference comparing TAE with APR. Moreover, the study did not reveal a trend toward less aggressive surgical resection. Since the extent of surgical intervention did not correlate with survival or extent of primary tumor, APR should be reserved for selected patients in whom TAE is not technically feasible.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sentinel-Node Biopsy or Nodal Observation in Melanoma Morton, Donald L; Thompson, John F; Cochran, Alistair J ...
New England journal of medicine/The New England journal of medicine,
09/2006, Volume:
355, Issue:
13
Journal Article
Peer reviewed
Open access
This large prospective study shows that sentinel-node biopsy can be an important part of the management of intermediate-thickness melanoma of the skin. The biopsy not only yields clinically important ...prognostic information but also identifies patients with nodal metastases whose survival can be prolonged by lymphadenectomy.
Sentinel-node biopsy not only yields clinically important prognostic information but also identifies patients with nodal metastases whose survival can be prolonged by lymphadenectomy. See Video Clip .
In most patients with clinically localized melanoma of intermediate thickness, wide resection is curative, but metastasis to regional nodes develops in 15 to 20%. Since metastasis to a regional node is the most important prognostic factor in early-stage melanoma,
1
,
2
immediate (elective) lymphadenectomy has been advocated to improve tumor staging and possibly survival.
3
,
4
However, this approach exposes patients to complications resulting from the procedure and has not been shown to improve overall survival
5
; in a minority of patients with occult nodal metastases, however, it may have benefit.
3
,
4
We developed a technique for lymphatic mapping and sentinel-node biopsy . . .
The outcomes of patients with melanoma who have sentinel lymph node (SLN) metastases can be highly variable, which has precluded establishment of consensus regarding treatment of the group. The ...detection of high-risk patients from this clinical setting may be helpful for determination of both prognosis and management. We report the utility of multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase III, international, multicenter clinical trial.
Blood specimens were collected from patients with melanoma (n = 331) who were clinically disease-free after complete lymphadenectomy (CLND) before entering onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG placebo trial from 30 melanoma centers (United States and international). Blood was assessed using a verified multimarker RT-qPCR assay (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression analyses were used to evaluate the prognostic significance of CTC status for disease recurrence and melanoma-specific survival (MSS).
Individual CTC biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC status (zero to one positive biomarkers v two or more positive biomarkers) with known clinical or pathologic prognostic variables. However, two or more positive biomarkers was significantly associated with worse distant metastasis disease-free survival (hazard ratio HR = 2.13, P = .009) and reduced recurrence-free survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable analysis.
CTC biomarker status is a prognostic factor for recurrence-free survival, distant metastasis disease-free survival, and MSS after CLND in patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be useful in discriminating patients who may benefit from aggressive adjuvant therapy or stratifying patients for adjuvant clinical trials.
PURPOSE We previously demonstrated a survival advantage for nodal metastasis of melanoma from an unknown primary (MUP) versus melanoma from a known primary (MKP). We hypothesized that this survival ...benefit would extend to MUP patients with distant (stage IV) metastasis. PATIENTS AND METHODS We reviewed prospectively acquired data for 2,247 patients diagnosed with American Joint Committee on Cancer stage IV melanoma at our cancer center between 1971 and 2005. Cox regression analysis in a multivariate model identified prognostic factors significant for survival. MUP and MKP patients were then matched by significant covariates. Overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank analysis. Results There were 1,849 MKP and 398 MUP patients. Multivariate analysis of patients with complete data sets identified known/unknown primary (hazard ratio HR, 1.141; P = .032) and five other significant covariates: age (HR, 1.148; P = .007), sex (HR, 1.17; P = .001), site of metastasis (HR, 1.336; P < .001), number of different metastatic sites (HR, 1.303; P < .001), and decade of diagnosis (HR, 0.713; P < .001). Prognostic matching yielded 392 MUP-MKP pairs. Median OS and 5-year OS rate were significantly greater (P < .001) for MUP patients than for all matched MKP patients or for MKP patients matched by M1 category (for M1b and M1c) or number of metastatic sites. CONCLUSION The survival advantage previously reported for patients with stage III MUP also applies to patients with stage IV MUP. The mechanism responsible for this improved survival may provide clues for more effective treatment of stage IV melanoma and therefore warrants further investigation. The improved results for MUP suggest that these patients deserve aggressive therapy.
Purpose: The CpG island methylator phenotype (CIMP) may be associated with development of malignancy through coordinated inactivation
of tumor suppressor and tumor-related genes (TRG) and methylation ...of multiple noncoding, methylated-in-tumor (MINT) loci.
These epigenetic changes create a distinct CIMP pattern that has been linked to recurrence and survival in gastrointestinal
cancers. Because epigenetic inactivation of TRGs also has been shown in malignant melanoma, we hypothesized the existence
of a clinically significant CIMP in cutaneous melanoma progression.
Experimental Design: The methylation status of the CpG island promoter region of TRGs related to melanoma pathophysiology (WIF1, TFPI2, RASSF1A,
RARβ2, SOCS1, and GATA4) and a panel of MINT loci (MINT1, MINT2, MINT3, MINT12, MINT17, MINT25, and MINT31) in primary and
metastatic tumors of different clinical stages ( n = 122) was assessed.
Results: Here, we show an increase in hypermethylation of the TRGs WIF1, TFPI2, RASSF1A, and SOCS1 with advancing clinical tumor stage.
Furthermore, we find a significant positive association between the methylation status of MINT17, MINT31, and TRGs. The methylation
status of MINT31 is associated with disease outcome in stage III melanoma.
Conclusions: These findings show the significance of a CIMP pattern that is associated with advancing clinical stage of malignant melanoma.
Future prospective large-scale studies may determine if CIMP-positive primary melanomas are at high risk of metastasis or
recurrence.
B7-H3, a cell surface transmembrane glycoprotein, was assessed for its functional and prognostic role in cutaneous melanoma progression. B7-H3 expression in melanoma cells was shown to be related to ...specific downstream signal transduction events as well as associated with functional epigenetic activity. B7-H3 expression and prognostic utility were shown by reverse transcription and real-time PCR and immunohistochemistry analysis on individual melanoma specimens and then verified in clinically annotated melanoma stage III and stage IV metastasis tissue microarrays in a double-blind study. B7-H3 messenger RNA expression was shown to be significantly increased with stage of melanoma (P<0.0001) and significantly associated with melanoma-specific survival in both stage III (P<0.0001) and stage IV (P<0.012) melanoma patients. B7-H3 expression was related to migration and invasion; overexpression of B7-H3 increased migration and invasion, whereas knockdown of B7-H3 reduced cell migration and invasion. MiR-29c expression was shown to inversely regulate B7-H3 expression. Furthermore, we demonstrated that melanoma B7-H3 expression was correlated to phosphorylated signal transducer and activator of transcription-3 activity level in melanoma tissues and cell lines. These studies demonstrate that B7-H3 is a significant factor in melanoma progression and events of metastasis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We documented emergency department (ED) visits for nontraumatic dental problems and identified strategies to reduce ED dental visits.
We used mixed methods to analyze claims in 2010 from a purposive ...sample of 25 Oregon hospitals and Oregon's All Payer All Claims data set and interviewed 51 ED dental visitors and stakeholders from 6 communities.
Dental visits accounted for 2.5% of ED visits and represented the second-most-common discharge diagnosis in adults aged 20 to 39 years, were associated with being uninsured (odds ratio OR = 5.2 reference: commercial insurance; 95% confidence interval CI = 4.8, 5.5) or having Medicaid insurance (OR = 4.0; 95% CI = 3.7, 4.2), resulted in opioid (56%) and antibiotic (56%) prescriptions, and generated $402 (95% CI = $396, $408) in hospital costs per visit. Interviews revealed health system, community, provider, and patient contributors to ED dental visits. Potential solutions provided by interviewees included Medicaid benefit expansion, care coordination, water fluoridation, and patient education.
Emergency department dental visits are a significant and costly public health problem for vulnerable individuals. Future efforts should focus on implementing multilevel interventions to reduce ED dental visits.
Full text
Available for:
CEKLJ, DOBA, FSPLJ, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
PDF
