Clinical significance of microscopic melanoma metastases in the nonhottest sentinel lymph nodes.

IMPORTANCE: A practice gap exists in the surgical removal of sentinel lymph nodes, from removal of only the most radioactive (hottest) lymph node to removal of all lymph nodes with radioactivity greater than 10% of the hottest lymph node. OBJECTIVE: To determine the clinical significance of melanoma in sentinel lymph nodes that are not the hottest sentinel node and to determine the risk for disease progression based on sentinel lymph node status and primary tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS: Consecutive patients with cutaneous melanoma with sentinel lymph nodes resected from January 5, 2004, to June 30, 2008, with a mean follow-up of 59 months, at Massachusetts General Hospital were included in this retrospective review. The last year of follow-up was 2012. The operative protocol led to resection of all sentinel lymph nodes with radioactivity greater than 10% of the hottest lymph node. The number of lymph nodes removed, technetium-99m counts for each sentinel lymph node, presence or absence of sentinel lymph node metastases, primary tumor characteristics, disease progression, and melanoma-specific survival were recorded. MAIN OUTCOMES AND MEASURES: Microscopic melanoma metastases in the hottest and nonhottest sentinel lymph nodes and factors that correlate with disease progression and mortality. RESULTS: A total of 1575 sentinel lymph nodes were analyzed in 475 patients. Ninety-one patients (19%) had positive sentinel lymph nodes. Of these, 72 (79%) had metastases in the hottest sentinel lymph node. Of 19 cases with tumor present, but not in the hottest sentinel lymph node, counts ranged from 26% to 97% of the hottest node. Progression occurred in 43% of patients with sentinel node metastasis, regardless of whether the hottest lymph node was positive. In patients with negative sentinel lymph nodes, 11% developed metastases beyond the sentinel lymph node basin and 3.4% recurred in the basin. Mitogenicity of the primary tumor was associated with mortality (odds ratio, 2.435; 95% CI, 1.351-4.391; P < .001). Removing only the hottest sentinel lymph node would have led to false-negative results in 19 of 475 (4%) of all patients and 19 of 91 patients (21%) with positive sentinel lymph nodes. The 8-year survival in patients with at least 1 positive sentinel lymph node was less than 55%. The presence of more than 1 mitosis per square millimeter in the primary cutaneous melanoma was associated with decreased survival. CONCLUSIONS AND RELEVANCE: Microscopic melanoma metastases was associated with disease progression and mortality, whether present in the hottest sentinel lymph node or not. These observations emphasize the importance of removing the less hot nodes, addressing a practice gap in the surgical approach to patients with melanoma.

Induction of monocyte-to-dendritic cell maturation by extracorporeal photochemotherapy: initiation via direct platelet signaling.

Extracorporeal Photochemotherapy (ECP) is a widely used therapy for cutaneous T cell lymphoma (CTCL). Although the mechanism of clinical action of ECP is not precisely established, previous studies have shown evidence of induction of dendritic cells (DCs). Here we show that, under flow conditions similar to those in post-capillary venules, ECP promotes platelet immobilization and activation, initiating stepwise receptor-ligand interactions with monocytes, which then differentiate into DC. These findings clarify how ECP directly stimulates DC maturation; suggest a new clinically applicable approach to the obtainment of DC; and identify a novel mechanism that may reflect physiological induction of DC.

Influence of race on the management of lower extremity ischemia: revascularization vs amputation.

IMPORTANCE: Among patients presenting with critical lower extremity ischemia, it has been previously documented that white individuals are more likely to undergo revascularization than nonwhite individuals, with the disparity largely attributed to differences in resources and access to care. OBJECTIVE: To investigate the amputation disparity between white and nonwhite patients with critical lower extremity ischemia in more detail using a larger data set than previous studies, with a focus on the role of confounding factors such as access and hospital resources. DESIGN, SETTING, AND PATIENTS: All hospital discharge records from the Nationwide Inpatient Sample of adult patients with the primary diagnosis of critical lower extremity ischemia from 2002-2008 were examined in detail using multiple logistic regression (n = 774,399). MAIN OUTCOMES AND MEASURES: Rates of amputation and revascularization for peripheral vascular disease across race/ethnicity. RESULTS: Controlling for confounding factors, black patients were found to have 1.77 times the odds of receiving an amputation compared with white patients (95% CI, 1.72-1.84; P < .001). Further analysis revealed the black to white odds ratio paradoxically increased with increasing revascularization capacity of the presenting hospital, from a low of 1.43 (95% CI, 1.23-1.65) to a high of 1.98 (95% CI, 1.83-2.24). The amputation disparity also paradoxically increased for patients living in wealthier zip codes. CONCLUSIONS AND RELEVANCE: Black patients have greater odds of undergoing amputation than white patients, even after correcting for an array of confounding parameters. Contrary to current beliefs that the disparity is mainly secondary to differences in access, this study found that the disparity was magnified in settings where resources were greatest. Whether the explanation lies primarily in patient-specific, physician-specific, or institutional-specific factors remains to be determined but is critical to better understanding our health care system and maintaining approaches that are consistently fair and equitable.

Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T-cell lymphoma, graft-versus-host disease, and allografted organ rejection. Its clinical and experimental efficacy in cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the antigen-presenting dendritic cell (DC) differentiation pathway, within a single day, without added cytokines, as determined by enhanced expression of relevant genes. The resulting DCs are capable of processing and presentation of exogenous and endogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of costimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome reveals that activation or suppression of more than 1100 genes produces a reproducible distinctive molecular signature, common to ECP-processed monocytes from normal subjects, and those from patients. Because ECP induces normal monocytes to enter the DC differentiation pathway, this phenomenon is independent of disease state. The efficiency with which ECP stimulates new functional DCs supports the possibility that these cells participate prominently in the clinical successes of the treatment. Appropriately modified by future advances, ECP may potentially offer a general source of therapeutic DCs.

Referring physicians' attitudes toward international interpretation of teleradiology images.

OBJECTIVE: We evaluated referring physician attitudes toward the international interpretation of radiologic images. MATERIALS AND METHODS: A five-question, scenario-based survey describing features of a hypothetic local radiology firm compared with those of its hypothetic overseas counterpart, international radiology, was sent by mail to 350 physicians from a broad range of medical and surgical specialties. One hundred nineteen physicians responded, for a response rate of 34%. Referring physicians were asked to indicate their preference for local versus international interpretation in each scenario using a 5-point Likert scale, with a score of -2 indicating a strong preference for international services, 0 indicating no preference, and 2 indicating a strong preference for local services. RESULTS: When all variables are held to be equal, referring physicians strongly prefer local services (mean score, 1.77; SD, 0.77). When international teleradiology provides either a 2-day faster turnaround time for reports or a 30 dollars lower out-of-pocket cost to the patient, referring physicians still prefer local services, although less than they did with all variables held equal (mean score, 0.42-0.44; SD, 1.30-1.40). When international teleradiology provides both a 2-day faster turnaround time and a 30 dollars lower out-of-pocket cost to the patient, referring physicians preferred international teleradiology, albeit only slightly (mean, -0.25; SD, 1.50). Finally, when the credentials of the international radiologists are perceived to be less than those of the local radiologists, even in the face of faster turnaround time and 30 dollars lower cost to the patient, referring physicians overall strongly prefer local services (mean, 1.51; SD, 0.86). CONCLUSION: Referring physicians prefer local interpretation of radiologic images to international interpretation when all things are equal. However, the timeliness of image interpretation and the cost to the patient are important factors in this decision.