Faculty Bibliography

BACKGROUND:Preoperative abdominal computed tomographic angiograms for free flap breast reconstruction improve operative safety and efficiency, but incidental findings are common and potentially affect management. In addition, the authors hypothesized that patients with genetic mutations might have a higher rate of significant findings. The authors present the largest series of computed tomographic angiogram "incidentalomas" in these two populations and an evidence-based algorithm for managing common findings. METHODS:All patients undergoing free flap breast reconstruction at Northwell Health between 2009 and 2017 were eligible. Medical history, perioperative details, and radiology reports were examined with abnormal findings recorded. Published literature was reviewed with radiologists to develop standardized guidelines for incidentaloma management. RESULTS:Of 805 patients included, 733 patients had abdominal imaging. One hundred ninety-five (27 percent) had a completely negative examination. In the remaining 538 patients, benign hepatic (22 percent) and renal (17 percent) findings were most common. Sixteen patients (2.2 percent) required additional imaging (n = 15) or procedures (n = 5). One finding was concerning for malignancy-renal cell carcinoma-which interventional radiology ablated postoperatively. Seventy-nine patients (10.8 percent) had a genetic mutation but were not found to have a statistically significant higher rate of incidentalomas. CONCLUSIONS:The authors' rate of computed tomographic angiography incidental findings (73 percent) is consistent with previous studies, but the rate requiring further intervention (2.2 percent) is lower. Incidental findings were no more common or pathologic among genetic mutation carriers. The authors also introduce an evidence-based algorithm for the management of common incidentalomas. Using these guidelines, plastic surgeons can reassure patients, regardless of mutation status, that incidentalomas are most commonly benign and have minimal impact on their surgical plan.

BACKGROUND:To optimize neovaginal dimensions, several modifications of the traditional penile inversion vaginoplasty are described. Options for neovaginal lining include skin grafts, scrotal flaps, urethral flaps, and peritoneum. Implications of these techniques on outcomes remain limited. METHODS:A systematic review of recent literature was performed to assess evidence on various vaginal lining options as adjunct techniques in penile inversion vaginoplasty. Study characteristics, neovaginal depth, donor-site morbidity, lubrication, and complications were analyzed in conjunction with expert opinion. RESULTS:Eight case series and one cohort study representing 1622 patients used additional skin grafts when performing penile inversion vaginoplasty. Neovaginal stenosis ranged from 1.2 to 12 percent, and neovaginal necrosis ranged from 0 to 22.8 percent. Patient satisfaction with lubrication was low in select studies. Three studies used scrotal flaps to line the posterior vaginal canal. Average neovaginal depth was 12 cm in one study, and neovaginal stenosis ranged from 0 to 6.3 percent. In one study of 24 patients, urethral flaps were used to line the neovagina. Neovaginal depth was 11 cm and complication rates were comparable to other series. Two studies used robotically assisted peritoneal flaps with or without skin grafts in 49 patients. Average neovaginal depth was approximately 14 cm, and complication rates were low. CONCLUSIONS:Skin grafts, scrotal flaps, urethral flaps, and peritoneal flaps may be used to augment neovaginal canal dimensions with minimal donor-site morbidity. Further direct comparative data on complications, neovaginal depth, and lubrication are needed to assess indications in addition to advantages and disadvantages of the various lining options.

Hidradenitis suppurativa (HS) is a prevalent inflammatory skin disease. HS causes deep, painful, recurrent abscesses. African Americans and females are at an increased risk. A lack of effective therapies and limited knowledge about HS pathogenesis contribute to unmet needs. Unlike other common inflammatory skin diseases, there has never been a genome-wide association study (GWAS) conducted for HS. Here, we performed a first GWAS for HS using data from the eMERGE network of electronic health record linked biorepositories (project NT227). We used HS diagnosis codes to identify cases and controls. We estimated ancestry with principal component analysis using a set of 40,156 SNPs. Our final cohort consisted of 600 HS cases and 82,611 controls with comparable multi-ethnic ancestry (lambda=1.005). Our cohort recapitulated HS race and gender predilections with genetically African female participants accounting for 35% of cases, but only 10% of controls. Genotype data for 6 million variants was tested for association, adjusting for five principal components. No locus exceeded our threshold for statistical significance. Importantly, there was no evidence for HLA association supporting classification of HS as inflammatory rather than autoimmune. Several loci approached the significance threshold, suggesting that an expansion in cohort size is needed to provide adequate power to detect associations. Interestingly, the lead SNP at one of the most significant loci (rs11075745; p=8x10^-7) is an eQTL for NFAT5, a mediator of NOTCH signaling whose expression is downregulated in HS lesional skin relative to patient-matched nonlesional skin. The risk allele influences expression in tissue specific manner. Our group is constructing multi-ethnic replication cohorts that will allow us to expand this study in the near future.
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Hidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease affecting human apocrine sweat gland-bearing skin regions. The overall prevalence of HS ranges from 0.05-4.1% with higher occurrence among females and African Americans, and strong associations with smoking and obesity. One unique feature of HS is the development of highly immunogenic keratinized sinus tracts that grow deeply in the dermis which further complicate HS pathogenesis and treatment. Using single cell transcriptomic analyses, we finely dissected different epidermal cell types in the HS lesional skin and revealed significant dysregulation of skin barrier function in the sinus tracts. We demonstrated that sinus tract keratinocytes exhibit dual cell fates of surface epidermis and skin appendages, and derived from progenitors in infundibulum of the apocrine-pilosebaceous unit. By analyzing ligand-receptor expressions between different skin appendages and immune cells, we highlighted Th17 and TNF responses at early and late stages during HS progression, respectively. Our work provides unprecedented understanding of pathological epidermal remodeling in human inflammatory diseases and important implications for therapeutics.
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Hidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease lacking effective therapeutic options due to little understanding of the complex immune response within the lesional skin. Using single-cell transcriptomic analyses, we examined the signature changes in each immune cell types during HS progression, as well as in silico ligand-receptor predictions between different immune cell types to construct the interaction network that contribute to HS pathogenesis. Our results revealed a predominant Th17 response, as well as a distinct regulatory T cells existing in the lesional skin. We found that M1-polarized macrophages likely facilitate chemotaxis and IL1B responses in perilesional skin, while regulate lymphocyte activation and tissue remodeling in the lesional skin. In addition, we identified a significant increase of CCR7 expressing dendritic cells, as well as activated stromal fibroblasts expressing CCR7-ligand CCL19, which together support the organization of tertiary lymphoid organ (TLO)-like aggregates that contribute to persistent local inflammation. Importantly, we demonstrated a dense infiltration of plasma cells near sinus tracts, and that clonal expansion of the plasma cells frequently exists in HS patients. Together, our work provides a comprehensive understanding of immune responses and cytokine networks defining disease chronicity in HS, as well as significant implications for future therapeutics.
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