An enhancer variant associated with breast cancer susceptibility in Black women regulates TNFSF10 expression and antitumor immunity in triple-negative breast cancer.

Women of African ancestry have the highest mortality from triple-negative breast cancer (TNBC) of all racial groups. To understand the genomic basis of breast cancer in the populations, we previously conducted genome-wide association studies and identified single nucleotide polymorphisms (SNPs) associated with breast cancer in Black women. In this study, we investigated the functional significance of the top associated SNP rs13074711. We found the SNP served as an enhancer variant and regulated TNFSF10 (TRAIL) expression in TNBC cells, with a significant association between the SNP genotype and TNFSF10 expression in breast tumors. Mechanistically, rs13074711 modulated the binding activity of c-MYB at the motif and thereby controlled TNFSF10 expression. Interestingly, TNFSF10 expression in many cancers was consistently lower in African Americans compared with European Americans. Furthermore, TNFSF10 expression in TNBC was significantly correlated with the expression of antiviral immune genes and was regulated by type I interferons (IFNs). Accordingly, loss of TNFSF10 resulted in a profound decrease in apoptosis of TNBC cells in response to type I IFNs and poly(I:C), a synthetic analogue of double stranded virus. Lastly, in a syngeneic mouse model of breast cancer, TNFSF10-deficiency in breast tumors decreased tumor-infiltrated CD4+ and CD8+ T cell quantities. Collectively, our results suggested that TNFSF10 plays an important role in the regulation of antiviral immune responses in TNBC, and the expression is in part regulated by a genetic variant associated with breast cancer in Black women. Our results underscore the important contributions of genetic variants to immune defense mechanisms.

2020 IDEOM Annual Meeting: Actinic Keratosis Stakeholders Survey Identifies Gaps in Research and Care.

This is a report of the survey results from the International Dermatology Outcome Measures (IDEOM) actinic keratosis (AK) workgroup. The purpose of the survey was to compile a list of gaps within AK care and management that require refinement. The results were discussed at the IDEOM annual meeting held virtually on October 23–24, 2020. This built a framework with which the AK workgroup, which consisted of physicians, patients, and pharmaceutical scientists, discussed at length in their breakout session at the meeting. The electronic survey was distributed to patients, pharmaceutical scientists, and leading physician experts in the field via email on September 22, 2020, with a deadline of October 2, 2020. The survey consisted of three open-ended prompts concerning key gaps and/or unmet needs in (1) the care of AKs, (2) outcome measurement of AKs in clinical trials and, (3) the measurement of AKs in clinical practice. The results were qualitative, with a response rate of 47%. Responses included reform of outcome measures for clinical trials, a methodology for evaluating the efficacy of preventative measures, and a comparison of treatments to establish a treatment protocol, among other efforts. This paper will also provide a brief overview of the current state of the AK outcome measures, emphasizing the heterogeneity of the measures and detailing the AK workgroup's future efforts to create a reliable and applicable core outcome measure set. J Drugs Dermatol. 2022;21(2):128-134. doi:10.36849/JDD.6360.

National utilization patterns of Mohs micrographic surgery for invasive melanoma and melanoma in situ.

BACKGROUND: Although wide local excision continues to be commonly used for melanoma treatment, Mohs micrographic surgery (MMS) for the treatment of melanomas remains controversial. OBJECTIVE: We sought to determine national utilization patterns for MMS in the treatment of invasive melanoma and melanoma in situ. METHODS: A retrospective analysis of patients receiving surgical excision (MMS or wide local excision) for the treatment of invasive melanoma and melanoma in situ was performed using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: A total of 195,768 melanomas were diagnosed from 2003 through 2009 from the 17 SEER registries. Utilization of MMS for invasive melanoma and melanoma in situ increased by 60% from 2003 to 2008. Of all SEER-captured lesions treated by surgical excision in this time period, 3.5% (6872) were excised by MMS. LIMITATIONS: Patient insurance status, physician reimbursement practices, and health care provider type were not addressed in this article. CONCLUSION: Use of MMS for melanoma appears to be increasing. Future studies should explore whether this is associated with better outcomes.

Use of the 40-gene Expression Profile (40-GEP) Test in Medicare-eligible Patients Diagnosed with Cutaneous Squamous Cell Carcinoma (cSCC) to Guide Adjuvant Radiation Therapy (ART) Decisions Leads to a Significant Reduction in Healthcare Costs.

Objective: Adjuvant radiation therapy (ART) is often recommended for high-risk cSCC patients but carries significant costs and risks. This study aims to determine if utilizing the 40-GEP test to guide ART can reduce healthcare costs in cSCC management. Methods: Medical claims data with new diagnoses of cSCC for the 12 months ending June 2022 in the Medicare (≥65 years) population (source: IQVIA claims database) were obtained and normalized to the general population for missingness. CPT codes associated with radiation therapy within one-year post diagnosis were used to establish adjuvant RT use (defined as 'ART'). Average weighted direct costs for four major ART modalities were calculated from published studies and (IQVIA). Sensitivity analysis was used to assess the financial impact of ART treatment using varying distributions of 40-GEP Class results. Results: Normalized medical claims data identified 22,917 Medicare-eligible cSCC patients who received ART within the United States. The weighted average direct cost for ART, which includes the four most used CPT code-defined modalities (IGRT, IMRT, IMPT, and XRT), was $60,693 per patient, amounting to an annual projected ART cost of $1.4 billion. Using the distribution of 40-GEP results from published studies, utilization of a 40-GEP test result to avoid ART in these patients could save up to $972 million in Medicare-eligible population. Sensitivity analysis shows, depending upon the distribution of the 40-GEP results, that for every 10% of Class 2A test results omitting ART, an extra $38-66 million in annual savings is expected. Limitations: Potential limitations include a need for more comprehensive patient information and the cost of ART-related complications. Conclusion: Utilizing the 40-GEP test results to guide ART decision-making would result in material savings to Medicare.

The VEGF-Hypoxia Signature Is Upregulated in Basal-like Breast Tumors from Women of African Ancestry and Associated with Poor Outcomes in Breast Cancer.

PURPOSE: Black women experience the highest breast cancer mortality rate compared with women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry. EXPERIMENTAL DESIGN: We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n = 182) and the University of Chicago (Chicago, IL; n = 161). We also analyzed RNA sequencing data from Nigeria (n = 84) and The Cancer Genome Atlas (TCGA) datasets (n = 863). Patient prognosis was analyzed using multiple datasets. RESULTS: The VEGF-hypoxia signature was highest in the basal-like subtype compared with other subtypes, with greater expression in Black women compared with White women. In TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared with non-necrosis tumors (P < 0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation, and necrosis. T-cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in TCGA dataset. Finally, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (P < 0.0001) and SCAN-B datasets (P = 0.002). CONCLUSIONS: These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora.

Family team conferencing: results and implications from an experimental study in Florida.

This article reports the outcome evaluation findings of an experimental study conducted with families in the child welfare system in Florida. Families were randomly assigned to one of three Family Team Conferencing (FTC) models. In Pathway 1, the comparison model, FTCs were facilitated by case-workers. In Pathway 2, one of two experimental models, FTCs were cofacilitated by caseworkers and a designated/trained facilitator, and included expedited family engagement as well as the provision of FTCs throughout the life of a case. Pathway 3, also an experimental model, had the same components of Pathway 2 but also included family alone time. In approximately three years of the project period, 623 families agreed to participate in the study. Study findings showed no statistically significant change observed for families participating in Pathway 1 FTCs in terms of protective factors, achieving family-defined service and plan-of-care goals, and emotional and behavioral symptomology of children. Cases in Pathway 2 demonstrated significant improvement in family functioning and resiliency, nurturing and attachment, and increasing parents' knowledge about "what to do as a parent." Caregivers and teens in Pathway 3 reported significant improvement in expression of emotional symptomology/problems, conduct problems, hyperactivity, peer problems, and a measure of total difficulties. However, foster care re-entry rates were significantly higher for Pathway 3 than Pathway 2 (but not Pathway 1). Moreover, Pathway 2 and Pathway 3 FTCs had a significant effect on moving the family toward agreed upon service goals. Taken together, these findings suggest that the experimental FTC models in which facilitators were used and family engagement was expedited and sustained through subsequent FTCs demonstrated moderate, yet mixed benefits to children, youth, and families.

Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.

Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.

Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin.

The cytokine thymic stromal lymphopoietin (TSLP) has recently been implicated in the pathogenesis of atopic dermatitis (AD) and other allergic diseases in humans. To further characterize its role in this disease process, transgenic mice were generated that express a keratinocyte-specific, tetracycline-inducible TSLP transgene. Skin-specific overexpression of TSLP resulted in an AD-like phenotype, with the development of eczematous lesions containing inflammatory dermal cellular infiltrates, a dramatic increase in Th2 CD4+ T cells expressing cutaneous homing receptors, and elevated serum levels of IgE. These transgenic mice demonstrate that TSLP can initiate a cascade of allergic inflammation in the skin and provide a valuable animal model for future study of this common disease.

Catastrophic cutaneous carcinomatosis in the non-organ transplant patient.

BACKGROUND: The increased frequency of nonmelanoma skin cancers (NMSCs) in organ transplant recipients has been termed "catastrophic cutaneous carcinomatosis" (CCC). We have treated a cohort of immunocompetent patients with an increased number of NMSCs that meets the definition of CCC whom we have termed "catastrophic cutaneous carcinomatosis-immunocompetent" (CCC-IC). OBJECTIVE: We sought to further understand the epidemiologic characteristics of this subset of immunocompetent patients with a high burden of NMSCs. METHODS: Our pathology database was searched over a 4-year experience of a Mohs surgeon to identify patients with greater than 10 basal cell carcinomas (BCCs) and/or squamous cell carcinomas (SCCs) in a 12-month period who had no underlying systemic cause of immunosuppression or genetic predisposition to form NMSCs. Information regarding the 13 patients who met inclusion criteria was collected by questionnaire and analyzed. RESULTS: There was no statistically significant difference in the constitutional variables of this patient population. Patients with CCC-IC had a SCC:BCC ratio of 2.5:1, similar to what is seen in organ transplant recipients where the SCC:BCC ratio is 2:1 with SCC predominance. There was a statistically significant increase in the number of SCCs in patients with CCC-IC (8.77/patient) as compared with control patients (2.27/patient). Most strikingly, a 13.8-fold higher incidence of malignant melanoma in the CCC-IC group was found as compared with the general population. LIMITATIONS: Limitations to this study include a small sample size and recall bias. CONCLUSION: Our data suggest that patients with CCC-IC have skin cancer profiles of SCC and BCC similar to organ transplant recipients and have a markedly higher incidence of malignant melanoma than the general population. These patients require strict monitoring and combination therapeutic approaches toward management of cutaneous carcinomas.

A randomized controlled trial of oral phosphate binders in the treatment of pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder involving fragmentation and mineralization of elastic fibers predominantly in the skin, eyes, and cardiovascular system. OBJECTIVE: The objective of this study was to assess the efficacy of sevelamer hydrochloride on the reversal of elastic fiber calcification and clinical lesions of PXE. METHODS: This was a randomized, double-blind, placebo-controlled, two-part prospective study. In the first year, 40 patients with PXE were randomized to receive either sevelamer hydrochloride (800 mg by mouth three times daily) or placebo in a 1:1 ratio. In the second year, all patients received sevelamer hydrochloride (800 mg by mouth three times daily). RESULTS: In the first year, the placebo and treatment groups' mean calcium scores decreased from 29.52 to 15.97 (41.93% mean improvement) and 27.48 to 16.75 (38.37% mean improvement), respectively. In the second year, the mean calcium scores decreased to 13.36 (53.94%) and 14.03 (51.35%) in these groups. The mean clinical score in the placebo group decreased from 6.25 to 6.05 at year 1 (2% improvement) whereas the mean clinical score in the sevelamer hydrochloride group decreased from 7.10 to 6.55 (7% improvement). In year 2, the scores in the original placebo and sevelamer hydrochloride groups decreased to 5.33 (14% improvement) and 5.72 (19% improvement), respectively. LIMITATIONS: Magnesium stearate in our placebo and active drugs may have played a confounding role in this study, contributing to the small differences observed in these two groups. CONCLUSION: Sevelamer hydrochloride produced a reduction in both calcification levels and clinical scores; however, this difference was not statistically significant compared with placebo. Future clinical studies should examine the inhibitory role and potential therapeutic effect of magnesium in PXE.

The BRCA1 Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms.

Innate immune defense mechanisms play a pivotal role in antitumor responses. Recent evidence suggests that antiviral innate immunity is regulated not only by exogenous non-self-RNA but also by host-derived pseudogene RNAs. A growing body of evidence also indicates a biological role for pseudogenes as gene expression regulators or immune modulators. Here, we report an important role for BRCA1P1, the pseudogene of the BRCA1 tumor-suppressor gene, in regulating innate immune defense mechanisms in breast cancer cells. BRCA1P1 expresses a long-noncoding RNA (lncRNA) in breast cancer cells through divergent transcription. Expression of lncRNA-BRCA1P1 is increased in breast tumors compared with normal breast tissues. Depletion of BRCA1P1 induces an antiviral defense-like program, including the expression of antiviral genes in breast cancer cells. Furthermore, BRCA1P1-deficient cancer cells mimic virus-infected cells by stimulating cytokines and inducing cell apoptosis. Accordingly, depletion of BRCA1P1 increases host innate immune responses and restricts virus replication. In converse, overexpression of BRCA1P1 reduces cytokine expression in breast cancer cells. Mechanistically, lncRNA-BRCA1P1 is localized in the nucleus, binds to the NF-κB subunit RelA, and negatively regulates antiviral gene expression. Finally, in a xenograft mouse model of breast cancer, depletion of BRCA1P1 stimulates cytokine expression and local immunity, and suppresses tumor growth. Our results suggest an important role for BRCA1P1 in innate immune defense mechanisms and antitumor responses. This mechanism of antiviral immunity regulated by a host-derived pseudogene RNA may guide the development of novel therapies targeting immune responses in breast cancer. SIGNIFICANCE: This study identifies a novel mechanism of innate immunity driven by a host pseudogene RNA that inhibits innate immune defense mechanisms and antitumor responses through regulation of antiviral gene expression.

Transcriptional regulatory code of a eukaryotic genome.

DNA-binding transcriptional regulators interpret the genome's regulatory code by binding to specific sequences to induce or repress gene expression. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation, but this information alone does not reveal if or when transcriptional regulators occupy these binding sites. We have constructed an initial map of yeast's transcriptional regulatory code by identifying the sequence elements that are bound by regulators under various conditions and that are conserved among Saccharomyces species. The organization of regulatory elements in promoters and the environment-dependent use of these elements by regulators are discussed. We find that environment-specific use of regulatory elements predicts mechanistic models for the function of a large population of yeast's transcriptional regulators.

Use of high-frequency, high-resolution ultrasound before Mohs surgery.

BACKGROUND: Although ultrasound imaging is employed ubiquitously today, its use to examine and assess the skin is a relatively new technology. We explored the clinical application and use of high-frequency, high-resolution ultrasound in Mohs micrographic surgery. OBJECTIVE: To evaluate the ability of ultrasound to accurately determine lesion length and width of tumor borders in order to reduce the number of surgical stages. METHODS AND MATERIALS: This was an institutional review board-approved single-center study of 26 Mohs surgery patients. Ultrasound images were taken to record lesion dimensions, and then the investigator documented clinical estimation of the first stage. Extirpation of the tumor and histological analysis were performed thereafter. RESULTS: The results of 20 patients were included in the analysis. A paired-samples t-test revealed no significant difference between clinical and ultrasound widths (t=-1.324, p=.20). Similarly, there was no significant difference between the lengths found from clinical assessment and ultrasound (t=-1.093, p=.29). For different tumor types, there was no significant difference between clinical and ultrasound widths or lengths for basal cell carcinoma (t=-1.307, p=.23; t=-1.389, p=.20) or squamous cell cancer (t=-0.342, p=.73; t=0.427, p=.68). CONCLUSION There is a diagnostic role for high-resolution ultrasound in Mohs surgery regarding the delineation of surgical margins, but its limitations preclude its practical adoption at this time.

Utilization of a new tissue expander in the closure of a large Mohs surgical defect.

BACKGROUND: Malignant proliferating trichilemmal tumor (MPTT) is a rare neoplasm originating in the outer sheath of a hair follicle that often presents as a slowly enlarging, painful, subcutaneous scalp nodule. The authors describe a case of malignant proliferating trichilemmal tumor (MPTT) in an elderly 65-year-old Asian male who presented with a 5.5 x 5.0 cm mass on the posterior scalp. METHODS: The authors present a unique dual approach to treatment of MPTT in both the excision and wound revision phases. First, Mohs micrographic surgery is utilized for more discrete removal of malignant tissue, as opposed to wide excision. Then, a novel device called DermaClose RC is used in wound revision, a device that has proven to be more effective in promoting wound closure than traditional suturing. RESULTS: Mohs micrographic surgery was used to excise the tumor in three stages. The resulting irregular wound measured 6.3 x 5.6 cm, and was repaired with the device. Following the application of the device, the wound reduced in size to 1.5-1.0 cm. Postoperatively, the patient had no evidence of recurrent disease at seven months. CONCLUSION: Use of the DermaClose RC tissue expander following a Mohs surgical procedure provides an effective functional and cosmetic alternative to a skin graft which creates a donor site wound and creates a more complicated, time consuming procedure. The dual approach discussed here-of Mohs micrographic surgery performed in tandem with wound revision via the tissue expanding device is one that may yield promising benefits but warrants further evaluation.

Allergic contact dermatitis: patch testing results at Mount Sinai Medical Center.

Patch testing is an important diagnostic tool commonly used to identify allergens responsible for allergic contact dermatitis, especially in cases where the diagnosis is not clearly apparent. The authors report the patch test results from 2004-2008 and compare the results with the North American Contact Dermatitis Group and Mayo Clinic. Four hundred thirty-four patients with suspected allergic contact dermatitis underwent standardized patch testing with a tray consisting of 50 allergens at Mount Sinai Medical Center. Two hundred ninety patients (66.8%) had positive reactions to at least one allergen. The most frequent contact allergens included nickel sulfate (13%), fragrance mix (9.6%), propylene glycol (7.8%), neomycin sulfate (6.6%), thimerosal (6.4%), bacitracin (6.2%), and sodium gold thiosulfate (5.8%).

A five-patient satisfaction pilot study of calcium hydroxylapatite injection for treatment of aging hands.

BACKGROUND: The process of skin aging is not limited to the face but involves every part of the body, including the hands. A common manifestation of aging of the hands is the loss of volume, which occurs as the skin loses its subcutaneous fat. Injectable dermal fillers have surfaced as a popular method to address such deficiencies. OBJECTIVES: To report the use of calcium hydroxylapatite (CaHA) to address lost volume. METHODS: Five female subjects with soft tissue deficiency of the dorsa of the hands were enrolled at Mount Sinai Medical Center. A solution of CaHA with 2% lidocaine in amounts of 0.3 to 1.0 mL was injected interdigitally at each of three to five insertion sites; the sites were massaged and molded up to three times to ensure an optimal cosmetic end point. Subjects were seen for a follow-up visit after 1, 4, 16, and 24 weeks. RESULTS: With a single injection, all subjects reached their correction goals without requiring any touch-ups. At the 24-week visit, the subjects retained the filling effect, with no adverse events and high patient satisfaction. CONCLUSION: CaHA, a new, easily injectable, safe dermal filler, has emerged as an excellent option for soft tissue augmentation in aging hands.

Six-month safety results of calcium hydroxylapatite for treatment of nasolabial folds in Fitzpatrick skin types IV to VI.

BACKGROUND: Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin. OBJECTIVES: This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin. METHODS: This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gauge needle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary, each subject was offered a touch-up at the conclusion of the 6-month visit. RESULTS: No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded. CONCLUSIONS: People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population.

Combined global localization analysis and transcriptome data identify genes that are directly coregulated by Adr1 and Cat8.

In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in metabolism, mediated in part by global transcriptional changes. Many of the transcription factors that regulate these changes act combinatorially. We have analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors that act during glucose depletion, by combining genome-wide expression and genome-wide binding data. We identified 32 genes that are directly activated by Adr1, 28 genes that are directly activated by Cat8, and 14 genes that are directly regulated by both. Our analysis also uncovered promoters that Adr1 binds but does not regulate and promoters that are indirectly regulated by Cat8, stressing the advantage of combining global expression and global localization analysis to find directly regulated targets. At most of the coregulated promoters, the in vivo binding of one factor is independent of the other, but Adr1 is required for optimal Cat8 binding at two promoters with a poor match to the Cat8 binding consensus. In addition, Cat8 is required for Adr1 binding at promoters where Adr1 is not required for transcription. These data provide a comprehensive analysis of the direct, indirect, and combinatorial requirements for these two global transcription factors.

Cost-benefit analysis of a hospital pharmacy bar code solution.

BACKGROUND: Bar coding can reduce hospital pharmacy dispensing errors, but it is unclear if the benefits of this technology justify its costs. The purpose of this study was to assess the costs and benefits and determine the return on investment at the institutional level for implementing a pharmacy bar code system. METHODS: We performed a cost-benefit analysis of a bar code-assisted medication-dispensing system within a large, academic, nonprofit tertiary care hospital pharmacy. We took the implementing hospital's perspective for a 5-year horizon. The primary outcome was the net financial cost and benefit after 5 years. The secondary outcome was the time until total benefits equaled total costs. Single-variable, 2-variable, and multiple-variable Monte Carlo sensitivity analyses were performed to test the stability of the outcomes. RESULTS: In inflation- and time value-adjusted 2005 dollars, total costs during 5 years were $2.24 million ($1.31 million in 1-time costs during the initial 3.5 years and $342 000 per year in recurring costs starting in year 3). The primary benefit was a decrease in adverse drug events from dispensing errors (517 events annually), resulting in an annual savings of $2.20 million. The net benefit after 5 years was $3.49 million. The break-even point for the hospital's investment occurred within 1 year after becoming fully operational. A net benefit was achieved within 10 years under almost all sensitivity scenarios. In the Monte Carlo simulation, the net benefit during 5 years was $3.2 million (95% confidence interval, -$1.2 million to $12.1 million), and the break-even point for return on investment occurred after 51 months (95% confidence interval, 30 to 180 months). CONCLUSION: Implementation of a bar code-assisted medication-dispensing system in hospital pharmacies can result in a positive financial return on investment for the health care organization.