Assessing the Feasibility of an Alternative Payment Model for Mohs Micrographic Surgery at an Academic Center.

BACKGROUND: Mohs micrographic surgery (MMS) is a cost-effective treatment for nonmelanoma skin cancer that bundles costs for surgical excision, tissue processing, and histopathological interpretation. A comprehensive MMS bundle would include all aspects of an episode of care (EOC), including costs of reconstruction, preoperative, and postoperative care. OBJECTIVE: To assess the feasibility of an alternative payment model for MMS and reconstruction. METHODS: Retrospective chart review and payment analysis for 848 consecutive patients with 1,056 tumors treated with MMS. Average Medicare payment of an EOC was compared with bundles based on specific repair types. RESULTS: The bundle for a flap/graft repair averaged $1,028.08 (confidence interval [CI] 95% $951.37-1,104.79), whereas the bundle for a linear closure (LC) averaged $585.07 (CI 95% $558.75-611.38). The average bundle including all repairs was $730.05 (CI 95% $692.31-767.79), which was statistically significant from both the flap/graft and LC bundles. CONCLUSION: Bundling surgical repairs with MMS based on an average payment does not represent the heterogeneity of the care provided and results in either underpayment or overpayment for a substantial portion of cases. Consequently, EOC payments bundling MMS and surgical repairs would inaccurately reimburse physicians for work completed. Current payment methodology allows for accurate payment for this already cost-effective therapy.

Factors Associated With Patient-Initiated Communication After Mohs Micrographic Surgery.

BACKGROUND: Despite extensive counseling, patients commonly call with postoperative concerns after Mohs micrographic surgery (MMS). OBJECTIVE: We sought to determine the incidence, reasons, and patient and surgical characteristics that lead to patient-initiated communication after MMS. MATERIALS AND METHODS: A retrospective chart review of 1,531 patients who underwent MMS during the observational period was conducted. Demographics and perioperative characteristics of patients who initiated communication were compared with a random sample of matched controls. RESULTS: Of the 1,531 patients who underwent MMS, 263 patients (17.2%) initiated 412 communication encounters within 90 days of surgery. Top reasons for patient-initiated communication included wound concerns, bleeding, and postoperative pain. Female patients and those with a larger surgical defect size (cm) were more likely to call postoperatively. Patients who underwent second intention healing, grafts, and interpolation flaps were more likely to initiate communication compared to patients repaired with a linear closure. CONCLUSION: This study identifies the incidence, reasons, and patient and surgical factors predictive of patient-initiated communication after MMS, which may allow for targeted improvements in postoperative counseling, ameliorating patient anxiety, augmenting patient satisfaction, and improved efficiency for the health care team.

Quantification of noninvasive fat reduction: A systematic review.

BACKGROUND AND OBJECTIVE: Noninvasive fat reduction appears effective, but there are various methods for quantifying changes. The objective of this review is to assess comparative utility measures of subcutaneous fat. STUDY DESIGN/MATERIALS AND METHODS: Articles describing noninvasive fat reduction were searched using MEDLINE, EMBASE, CINAHL and Scopus electronic databases on two dates (January 28, 2014 and February 16, 2016). Titles of studies and abstracts were screened for eligibility. Manual review was performed by two investigators to detect those that: (1) included original data; (2) were randomized controlled trials, or prospective or retrospective cohort studies; (3) quantified fat outcomes; and (4) enrolled at least 10 subjects. RESULTS: Of 1,057 retrieved articles, 36 met criteria. Most reported four or more measurement techniques. Circumference measurements were most commonly cited. Other objective techniques, like caliper thickness, ultrasound, magnetic resonance imaging (MRI), and three-dimensional (3D) photography, were also used. Common subjective methods were evaluation of standardized photographs by blinded raters and patient satisfaction surveys. CONCLUSIONS: For quantifying noninvasive fat reduction, all available methods had significant limitations: photographic comparisons were subjective; circumference or caliper measurements were confounded; ultrasound was operator dependent; MRI was expensive; computed models and simulations were in early development. As new technologies are developed, the need for reliable, accurate and practical measures of subcutaneous fat will increase. Lasers Surg. Med. 50:96-110, 2018. © 2017 Wiley Periodicals, Inc.

Role of Immune Status in Chemotherapy-Induced Transient Acantholytic Dermatosis.

A 79-year-old man with a recent diagnosis of acute myeloblastic leukemia received induction chemotherapy with daunorubicin and cytarabine, plus moxifloxacin and fluconazole prophylaxis. Approximately 2 weeks later, an asymptomatic eruption appeared on his trunk. He then developed a neutropenic fever and was started on aztreonam, vancomycin, voriconazole, and amikacin and was transferred to our facility from an outside hospital. Micafungin was subsequently added, and the patient defervesced within a few days.

Adaptive immune cells temper initial innate responses.

Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment.

Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8(+) T cell-dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.

Hyper innate responses in neonates lead to increased morbidity and mortality after infection.

Neonates suffer high morbidity and mortality in infection, presumably because of the lack of a fully developed adaptive and innate immune system. Evidence of poor innate responses in neonates has been shown by using a model that sensitizes the host to Toll-like receptor (TLR)-mediated inflammation with d-galactosamine (d-GalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS stimulation, and such hypersensitivity extends to other TLR agonists including actual viral infection. Our study reveals that the ensuing inflammatory reaction after d-GalN sensitization reflects preferential toxicity of d-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. We show further that an uncontrolled proinflammatory innate response due to inadequate T cells makes neonates more vulnerable to TLR agonists or viral infection. Remarkably, through transfer of T cells into neonates or depletion of T cells in adult mice, we show that T cells are sufficient and necessary to control the early inflammatory response to LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.

The Navicular Graft for Reconstructing Deep Alar Defects.

The reconstruction of deep nasal ala defects can be challenging. The often thick, sebaceous skin of the nose provides structural support helping maintain the ala shape and nasal patency; loss of this support may result in ala deformity and nasal vestibule collapse. Traditional full-thickness skin grafts of deep alar defects may result in depressed scars. We present a variation of the full-thickness skin graft to repair deeper alar defects, sculpting the graft into a boat-shaped or "navicular" form. This allows for sufficient volume restoration and good cosmesis while avoiding more extensive surgical repairs of the nasal ala. The navicular graft offers several advantages: the avoidance of more extensive procedures involving cartilage grafts and/or flaps, appropriate color/texture match, and volume restoration without pitting, notching, or retraction of nasal structures. In addition, no struts or bolsters are needed.

TNF-alpha induces transient resistance to Fas-induced apoptosis in eosinophilic acute myeloid leukemia cells.

Tumor necrosis factor alpha (TNF-alpha) has been recognized as an activator of nuclear factor kappaB (NF-kappaB), a factor implicated in the protection of many cell types from apoptosis. We and others have presented evidence to suggest that Fas-induced apoptosis may be an important aspect of the resolution of inflammation, and that delayed resolution of inflammation may be directly associated with NF-kappaB-dependent resistance to Fas. Because TNF-alpha activates NF-kappaB in many cell types including inflammatory cells such as eosinophils, we examined effects of TNF-alpha signaling on the Fas-mediated killing of an eosinophilic cell line AML14. While agonist anti-Fas (CH11) treatment induced apoptosis in AML14 cells, no significant cell death occurred in response to TNF-alpha alone. Electrophoretic mobility shift assay (EMSA) revealed that TNF-alpha induced NF-kappaB transactivation in AML14 cells in a time- and dose-dependent fashion, and subsequent supershift assays indicated that the translocated NF-kappaB was the heterodimer p65 (RelA)/p50. Pre-treatment of cells with TNF-alpha dramatically decreased the CH11-induced cell death in a transient fashion, accompanied by suppression of activation of caspase-8 and caspase-3 activation. Inhibition of NF-kappaB transactivation by inhibitors, BAY 11-7085 and parthenolide, reversed the suppression of Fas-mediated apoptosis by TNF-alpha. Furthermore, TNF-alpha up-regulated X-linked inhibitor of apoptosis protein (XIAP) transiently and XIAP levels were correlated with the temporal pattern of TNF-alpha protection against Fas-mediated apoptosis. This finding suggested that TNF-alpha may contribute to the prolonged survival of inflammatory cells by suppression of Fas-mediated apoptosis, the process involved with NF-kappaB transactivation, anti-apoptotic XIAP up-regulation and caspase suppression.

The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity.

The most widely held explanation for the efficacy of local radiotherapy (RT) is based on direct cytotoxicity to cancer cells through the induction of lethal DNA damage. Recent studies have shown that local ablative radiation of established tumors can lead to increased T-cell priming and T-cell-dependent tumor regression, but the underlying mechanism remains unclear. Here, we describe an essential role for type I IFN in local RT-mediated tumor control. We show that ablative RT increases intratumoral production of IFN-ß and, more surprisingly, the antitumor effect of RT is abolished in type I IFN nonresponsive hosts. Furthermore, the major target of RT-induced type I IFN is the hematopoietic compartment. RT drastically enhances the cross-priming capacity of tumor-infiltrating dendritic cells (TIDC) from wild-type mice but not type I IFN receptor-deficient mice. The enhanced cross-priming ability of TIDCs after RT was dependent on autocrine production of type I IFNs. By using adenoviral-mediated expression of IFN-ß, we show that delivery of exogenous IFN-ß into the tumor tissue in the absence of RT is also sufficient to selectively expand antigen-specific T cells leading to complete tumor regression. Our study reveals that local high-dose RT can trigger production of type I IFN that initiates a cascading innate and adaptive immune attack on the tumor.

Do adaptive immune cells suppress or activate innate immunity?

Current dogma holds that the innate immune system primes the adaptive immune system in response to infection, which in turn amplifies innate responses in a positive loop to effectively control pathogens. Therefore, it is accepted in most cases that T-cell deficient hosts die of acute infection because of the impaired ability of the innate immune system to control pathogens. Recent studies, however, reveal that adaptive immune cells actively dampen initial innate responses. In contrast to current understanding, there is now evidence that an insufficient number of T cells results in loss of control of innate immune responses. This raises new questions regarding the, as of yet underappreciated, role of the adaptive immune system in early infection and inflammation.

How often do BRCA mutation carriers tell their young children of the family's risk for cancer? A study of parental disclosure of BRCA mutations to minors and young adults.

PURPOSE: Predictive genetic testing for adult-onset diseases is generally discouraged until the age at which interventions are believed to be helpful. Yet, many BRCA mutation carriers discuss their results with their children. This study describes the prevalence and experiences of parental communication of BRCA results to children under the age of 25 years old. PATIENTS AND METHODS: Forty-two BRCA mutation carriers completed semistructured telephone interviews assessing self-reported disclosure to offspring and parent experiences with disclosure. Qualitative responses were coded for themes. chi(2) tests and logistic regression analyses with robust variance estimates were used to evaluate parent and child characteristics associated with disclosure. RESULTS: Fifty-five percent of parents reported discussing hereditary risk of cancer with at least one child. By parent report, 49% of the 86 offspring learned of their parents genetic test results or the hereditary cancer risk. Offspring age was strongly associated with disclosure (P = .001), and the majority of adolescent and adult children learned of the familial mutation or the hereditary risk of cancer. Parents reported that some offspring did not appear to understand the significance of the information shared, and that some offspring had initial negative reactions to disclosure. Physician (14%) and genetic counselor (21%) involvement in parent decisions to disclose were low. CONCLUSION: Children of BRCA mutation carriers learn of their parents genetic test results many years before preventive interventions are indicated. Further research is needed to examine how young individuals understand this information and its psychosocial impact and influence on subsequent lifestyle and health behaviors.

Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases.

Metastatic disease is the major cause of morbidity and mortality in cancer. Although surgery, chemotherapy, or radiation can often control primary tumor growth, successful eradication of disseminated metastases remains rare. We have now tested whether direct targeting tumor tissues to generate antitumor immune response before surgical excision produces sufficient CTL against micrometastases. One unsolved problem is whether such response allows coming CTL to be educated and then exit the tumor site. Another unsolved problem is whether these CTL can then patrol and effectively eliminate spontaneously metastasized tumor cells in the periphery. In this study, we have shown that adenovirus-expressing TNFSF14 [LIGHT (name derived from homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes); Ad-LIGHT] inoculated directly into primary 4T1 tumor, a highly aggressive, spontaneously metastasizing mammary carcinoma, followed by surgical removal of the primary tumor can eradicate established and disseminated metastatic tumor cells in the peripheral tissues. Furthermore, we clearly show with a fibrosarcoma model Ag104L(d) that local treatment can generate plenty of tumor-specific CTL that exit the primary tumor and infiltrate distal tumors to completely eradicate distal tumors. Therefore, targeting the primary tumor with Ad-LIGHT before surgical excision is a new strategy to elicit better immune response for the eradication of spontaneous metastases.