ABSTRACT:There are 2 to 5 million laparotomies performed in the United States annually. Of these, 250,000 to 350,000 will undergo a ventral hernia repair. Repairs are often complicated by recurrence and infection. These risks are significantly increased in previously infected repairs, with reported recurrence rates varying from 17% to 28% after repair of infected ventral hernias, double the rates reported for first-time uninfected repairs. We describe here a novel treatment strategy involving the creation then use of bilateral prelaminated permanent mesh-reinforced tensor fascia latae flaps for abdominal wall reconstruction in patients who have recurrent ventral hernias and had undergone previous repairs complicated by infection. Previous repairs included anterior components separation, thereby making subsequent fascial release techniques and achievement of a reinforced repair extremely unlikely. Three patients were treated by a single surgeon using this 2-stage technique. There have been no incidences of recurrence and no infections after 2 to 10 years. In these patients, the only conventional option would have been a bridged repair with absorbable mesh. Combining the advantages of permanent mesh and well-vascularized autologous tissue optimizes the repair's tensile strength while mitigating the chance of recurrent infection associated with the use of permanent mesh. We propose that this strategy may be an appropriate treatment option for patients with recurrent ventral hernias that have not responded to other conventional modalities of treatment.

Background: Management of acral lentiginous melanoma (ALM) remains controversial. Traditionally, ALM was managed with digit amputation (DA), resulting in significant morbidity, but recent evidence has advocated for digit sparing management. Furthermore, the significance of nodal metastasis for ALM is not well reported. The aims of this study were to determine if surgical approach for primary ALM impacts outcomes and to evaluate the predictive value of nodal status for ALM. Methods: Patients with localized ALM diagnosed from 1982 to 2017 were retrospectively identified. Clinicopathologic characteristics were correlated with surgical approach, nodal metastasis, overall survival, and recurrence-free survival. Results: There were 47 patients with ALM. Median age was 59 years, and median thickness was 3mm. 51% of patients underwent wide local excision (WLE), 27.9% underwent DA, and 20.9% underwent partial digit amputation (PDA). ALM on the hand versus foot (OR: 12.7, 95%, confidence interval (CI), 2.0-80.1; P = 0.007) and subungual versus nonsubungual location (OR: 28.0, 95% confidence interval, 2.7-295.7; P = 0.006) were significantly associated with surgical approach (DA and PDA versus WLE). There were no significant differences in overall survival or recurrence-free survival between DA, PDA, or WLE cases (P = 0.481 and P = 0.778, respectively). There were no significant differences in overall survival or recurrence-free survival based on nodal status (P = 0.562 and P = 0.136, respectively). Conclusions: No significant differences in overall survival or recurrence-free survival were seen between ALM patients treated with DA, PDA, and WLE. Given these results, PDA or WLE may be options in select patients with digital ALM; however, careful consideration must be taken when deciding on the surgical approach.

Patterns of abdominal fat distribution (for example, a high vs. low visceral adipose tissue [VAT]/[VAT + subcutaneous adipose tissue (SAT)] ratio), independent of obesity, during adolescence carry a high risk for insulin resistance and type 2 diabetes. Longitudinal follow-up of a cohort of obese adolescents has recently revealed that a high ratio (high VAT/[VAT + SAT]) is a major determinant of fatty liver and metabolic impairment over time, with these effects being more pronounced in girls than in boys. To unravel the underlying metabolic alterations associated with the unfavorable VAT/(VAT + SAT) phenotype, we used the 2H2O labeling method to measure the turnover of adipose lipids and cells in the subcutaneous abdominal and gluteal/femoral adipose tissue (SAT) of weight-stable obese adolescent girls with a similar level of obesity but discordant VAT/(VAT + SAT) ratios. Girls with the unfavorable (high VAT/[VAT + SAT]) phenotype exhibited higher in vivo rates of triglyceride (TG) turnover (representing both lipolysis and synthesis at steady state), without significant differences in de novo lipogenesis in both abdominal and gluteal depots, compared with obese girls with the favorable phenotype. Moreover, mature adipocytes had higher turnover, with no difference in stromal vascular cell proliferation in both depots in the metabolically unfavorable phenotype. The higher TG turnover rates were significantly correlated with higher intrahepatic fat stores. These findings are contrary to the hypothesis that impaired capacity to deposit TGs or proliferation of new mature adipocytes are potential mechanisms for ectopic fat distribution in this setting. In summary, these results suggest that increased turnover of TGs (lipolysis) and of mature adipocytes in both abdominal and gluteal SAT may contribute to metabolic impairment and the development of fatty liver, even at this very early stage of disease.

Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA; Program in Microbiology, Yale School of Medicine, New Haven, CT, USA; Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT, USA; Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA and Section of Cardiac Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT, USA

Introduction: Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). Methods: We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. Results: Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. Conclusions: The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.

Introduction: Melanoma in situ (MIS) is an early variant of melanoma in which the disease is limited to the epidermis. Standard therapy is currently surgical excision with at least 5-mm margins. In some instances, there are large or anatomically difficult lesions where complete excision will result in significant esthetic or functional impairment. Our experience has shown a 6-week course to be sufficient in certain patients compared with the suggested 12-week course. In this context, we propose a shortened duration of treatment of positive margins with topical imiquimod and propose an algorithm that results in the least amount of dysfunction for the patient. Methods: Our inclusion criteria were patients undergoing excision of a lesion found to have postsurgical margins, which were positive for MIS. Patients applied 5% imiquimod 3 to 5 times per week for at least 6 weeks at the site of the positive margin(s). Duration and frequency of treatment were titrated based on response. A reexcision skin biopsy using 1-mm margins was performed after residual inflammation subsided. Our endpoints were recurrence and effectiveness with length of treatment. Results: Sixteen patients met our criteria. All patients were found to have MIS in the margins after surgical excision. Twelve of those lesions were classified as MIS in the initial biopsy; the remaining 4 were either melanoma stage T1A or T1B. Mean follow-up time was 14.3 months, and 1 patient was lost to follow-up. We had 3 patients without response, and of these, 1 was found to have atypical squamous cell carcinoma and the other had a recurrence of MIS. Cure rate after use of topical imiquimod was 93.3% (14/15). Discussion: The proposed algorithm for the treatment of residual disease in head and neck melanoma and MIS using topical imiquimod offers various advantages. This anatomical region is cosmetically sensitive, and the option of using 1 mm versus 5 mm reexcision margins after imiquimod treatment yields comparable cure rates with less tissue excised overall. Our algorithm demonstrates that 6 weeks of active inflammation provides comparable results with the traditional 12-week course. This decreased treatment time reduces patient discomfort and improves patient adherence.

BackgroundIncreased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. MethodsWe performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. ResultsWe reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n=16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n=32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n=25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). ConclusionAsymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

Objective: MicroRNAs are short, noncoding RNA molecules that negatively regulate the stability and translational efficiency of target mRNAs. They are critical regulators of growth and development. Our aim was to identify microRNAs involved in the growth and regulation of infantile hemangiomas. In addition, we searched for the presence of Piwi-interacting RNAs in hemangioma tissue as another regulator of infantile hemangiomas. Methods: RNA was extracted from hemangioma specimens from 3 clinical, age-based categories: proliferative (N = 16), quiescent (N = 8), and involuting (N = 9). RNAs from human dermal microvascular endothelial cells were used as controls. MicroRNA microarray was performed, and the expression profiles of the hemangiomas and endothelial cells were compared using the t test. 5' End-labeling of RNA of our hemangioma specimens was performed for Piwi-interacting RNA detection. Results: Analysis confirmed statistically significant downregulated (N = 18) and upregulated (N = 15) microRNAs. Piwi-interacting RNA analysis did not detect Piwi-interacting RNA transcripts in the hemangioma specimens. Conclusions: The differential expression of microRNAs found in our hemangioma specimens provides insight into the regulation of hemangioma formation and proliferation, quiescence, and fibrofatty involution. Piwi-interacting RNA transcripts were not detected in the hemangioma specimens. These novel findings will help in establishing new therapeutic and diagnostic initiatives for these tumors.

Body contouring procedure is a catchall that includes mastopexy, abdominoplasty, liposuction, and lower body lift. It is well known that optimal postoperative pain control decreases hospitalization length of stay and promotes early ambulation, which in turn decreases the incidence of complications. There have been many innovations in pain control beyond opiate medications, including prolonged administration of local anesthesia, regional blocks, and the use of a multimodal regimen which utilizes nonopiates. All approaches aim to decrease oral or intravenous opiate use and, therefore, encourage faster return to normal bowel function and decreased risk of addiction. In this article, the authors focus on opiate alternatives.

Management of prosthetic vascular graft infections caused by Pseudomonas aeruginosa can be a significant challenge to clinicians. These infections often do not resolve with antibiotic therapy alone due to antibiotic resistance/tolerance by bacteria, poor ability of antibiotics to permeate/reduce biofilms and/or other factors. Bacteriophage OMKO1 binding to efflux pump proteins in P. aeruginosa was consistent with an evolutionary trade-off: wildtype bacteria were killed by phage whereas evolution of phage-resistance led to increased antibiotic sensitivity. However, phage clinical-use has not been demonstrated. Here, we present a case report detailing therapeutic application of phage OMKO1 to treat a chronic P. aeruginosa infection of an aortic Dacron graft with associated aorto-cutaneous fistula. Following a single application of phage OMKO1 and ceftazidime, the infection appeared to resolve with no signs of recurrence.

The major drawback of melanoma therapy with BRAF and MAPK inhibitors is the innate and acquired drug resistance. We therefore explored alternative targets and developed a new compound, SAB298, that is a SRC-family kinase (SFK) inhibitor. The drug is cytotoxic to patient-derived melanoma cells regardless of oncogene expression and inhibits tumor growth in vivo. As expected, it inhibited SRC and PI3K activity, and had the additional property of ERBB2 inhibition, that lead to inactivation of the two ERK phosphatases PP2A and SHP2. In 57% of the melanoma cell lines tested, the consequent increase in ERK activity lead to proteolytic degradation of its substrate, the lineage specific transcription factor MITF, likely contributing to growth arrest. Treatment with a combination of SAB298 and AZD6244 (selumetinib), induced a synergistic growth inhibition, suggesting that the new compound could be used in the clinic as a substitute for, or in combination with MAPK inhibitors.