Frances M. Walocko

Metastatic Merkel cell carcinoma response to nivolumab

BackgroundMerkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with limited treatment options. Several lines of evidence support the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis as a likely contributor to immune evasion in MCC.Case presentationWe report a case of a patient with metastatic MCC with a significant and durable response to nivolumab, a humanized IgG4 monoclonal anti-PD-1 antibody.ConclusionImmunotherapy with PD-1/PD-L1 inhibitors has become a rational and promising treatment option for MCC in the advanced or metastatic disease. Clinical trials are currently in progress to further evaluate these novel therapeutic agents.

Comprehensive molecular profiling of olfactory neuroblastoma identifies potentially targetable FGFR3 amplifications

Olfactory neuroblastomas (ONBs), also known as esthesioneuroblastomas, are malignant round-cell tumors that represent up to 5% of sinonasal malignancies. Despite their aggressive course, molecular studies of ONBs have been limited, and targeted therapies are lacking. To identify potential oncogenic drivers and targetable pathways in ONBs, we characterized 20 ONBs, including archived ONBs profiled by targeted, multiplexed PCR (mxPCR)–based DNA next-generation sequencing (NGS) of the coding sequence of over 400 cancer-relevant genes (n = 16), mxPCR-based RNA NGS of 108 target genes (n = 15), and 2 ONBs profiled by comprehensive hybrid-capture–based clinical grade NGS of >1,500 genes. Somatic mutations were infrequent in our cohort, with 7 prioritized nonsynonymous mutations in 5 of 18 (28%) ONBs, and no genes were recurrently mutated. We detected arm/chromosome-level copy-number alterations in all tumors, most frequently gains involving all or part of chromosome 20, chromosome 5, and chromosome 11. Recurrent focal amplifications, often but not exclusively in the context of arm-level gains, included CCND1 [n = 4/18 (22%) tumors] and the targetable receptor tyrosine kinase FGFR3 [n = 5/18 (28%) tumors]. Targeted RNA NGS confirmed high expression of FGFR3 in ONB (at levels equivalent to bladder cancer), with the highest expression observed in FGFR3-amplified ONB cases. Importantly, our findings suggest that FGFR3 may be a therapeutic target in a subset of these aggressive tumors. Implications: ONBs harbor recurrent chromosomal copy-number changes, including FGFR3 amplification associated with overexpression. Hence, FGFR3 may represent a novel therapeutic target in these tumors. Mol Cancer Res; 15(11); 1551–7. ©2017 AACR.

The potential roles for adipose tissue in peripheral nerve regeneration

This review summarizes current understanding about the role of adipose‐derived tissues in peripheral nerve regeneration and discusses potential advances that would translate this approach into the clinic.

Stacked Thoracodorsal Artery Perforator Flaps for Unilateral Breast Reconstruction.

Summary: The thoracodorsal artery perforator flap is reliable and safe for breast reconstruction, but stacking bilateral thoracodorsal artery perforator flaps for unilateral reconstruction to achieve greater volumes has not been reported. To create a stacked thoracodorsal artery perforator flap, the ipsilateral flap is transferred as an island, and the contralateral flap is transferred as a microvascular free flap. In this article, the authors present their 8-year 14- patient experience with stacked thoracodorsal artery perforator flaps for unilateral breast reconstruction. Patients’ ages ranged from 33 to 72 years (mean, 52.6 years). Mean follow-up time was 48.1 months (range, 1 to 98 months). Flaps measured between 22 × 6 cm and 32 × 8 cm and weighed between 110 and 550 g. Two of the island flaps had steatofibrosis of the distal 3 cm, which was resected and closed directly. The rest of the island flaps and all 14 free flaps healed uneventfully. At the time of follow-up, all flaps appeared healthy, and the reconstructed breast had a similar appearance and volume as the contralateral side. The donor areas had almost no functional deficit, and the final scar was aesthetically acceptable, especially when the ascending oblique design was used. This represents the first description of stacked thoracodorsal artery perforator flaps for unilateral breast reconstruction. This novel addition to the reconstructive surgeon’s selection of methods is a safe and reliable option for large-volume unilateral breast reconstruction. It allows for symmetry without requiring prostheses or reduction of the contralateral side.

Update on sunscreens distributed by major US retailers that meet American Academy of Dermatology recommendations

(n 1⁄4 237), and chloroquine in 62.2% (n 1⁄4 61). Patients on these medications are not mutually exclusive; most patients were taking either hydroxychloroquine or chloroquine in combination with quinacrine. Quinacrine was discontinued more often than other antimalarials because of the cost and barriers to its access (quinacrine 23.4%, n 1⁄4 33; hydroxychloroquine 4.6%, n 1⁄4 11; chloroquine 16.4%, n 1⁄4 10) rather than because of the side effects (quinacrine 30.5%, n 1⁄4 43; hydroxychloroquine 42.6%, n 1⁄4 101; chloroquine 49.2%, n 1⁄4 30) (Table II). Following side effects, quinacrine was restarted in 27.7% (n 1⁄4 13), hydroxychloroquine in 25.7% (n 1⁄4 26), and chloroquine in 16.7% (n 1⁄4 5). There were 2 instances of mild transaminitis and 3 of slight hematologic disturbances not clearly attributable to quinacrine. In prior reports of World War II soldiers, 1/500,000 patients experienced aplastic anemia at dosages exceeding 100 mg/day. Quinacrine safety is thus supported by evidence from this large cohort. Our study is limited by its retrospective methodology. It is crucial to continue to examine the repercussions of the loss of quinacrine availability considering the lack of suitable alternatives.

The role of nicotinamide in acne treatment

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti‐inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patients baseline or performed similarly to another standard‐of‐care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first‐line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.

Acute Calcific Tendinitis of the Index Finger in a Child

Background: Calcific tendinitis is characterized by calcium hydroxyapatite crystal deposition within tendons and is a common cause of musculoskeletal pain in adults. Its clinical manifestations may be acute, chronic, or asymptomatic. Acute calcific tendinitis is self-resolving condition that is rarely reported in the pediatric population and may be overlooked for more common processes, leading to unnecessary treatment. Methods: A chart reivew was performed of a single case of acute calcific tendonitis of the index finger in a child. Results: We describe a case of calcific tendinitis of the index finger in a 9-year-old boy who was referred to us for a second opinion after surgical exploration of an acutely inflamed digit was recommended based on his initial presentation. The calcifications and symptoms resolved over time without operative management. Conclusions: Although rare in children, acute calcific tendinitis can present similar to an infection. However, appropriate managment is non-operative as the symptoms and radiographic findings resolve over time.

Teledermatology Applications in Skin Cancer Diagnosis

Teledermatology has drawn interest in the dermatologic community, because it allows for earlier detection of skin cancer in patients with poor access to health care. Using a combination of dermoscopy and digital photography, teledermatology has demonstrated acceptable concordance with face-to-face clinical diagnoses in multiple settings for pigmented skin lesions. Additional studies on using teledermatology to assess nonpigmented skin lesions are needed. Future advances in mobile teledermatology may help make this technology more widespread and affordable. Although teledermatology is not a replacement for regular total body skin examinations, it is a useful tool to significantly reduce the burden of dermatologic malignancies.

Erratum to: Metastatic Merkel cell carcinoma response to nivolumab

[This corrects the article DOI: 10.1186/s40425-016-0186-1.].

Tissue Engineering Chambers: Potential Clinical Uses and Limitations.

Oxygen delivery is the greatest limiting factor to large-volume tissue engineering. Regenerating post-mastectomy breast tissue requires avascular adipose tissue to be transferred as thin “micro-ribbons” to avoid central necrosis (Khouri et al., 2014). Similarly, scaffold-based constructs lack the central vascularity necessary for large-volume tissue regeneration (Post et al., 2013). The tissue engineering chamber (TEC) induces the recipient bed to regenerate fully vascularized tissue in vivo, thereby providing the oxygen delivery necessary to support large-scale tissue regeneration. In the above article (Morrison et al., 2016), Morrison and colleagues describe the first successful use of TEC to generate well-vascularized, large-volume human adipose tissue in vivo. While TEC-based constructs do not have the same ability as scaffold-based constructs to control the internal structures of regenerated tissues, they still have potential utility in certain clinical scenarios.