No abstract

Successful management of epithelial skin cancers with imiquimod 5% cream (Aldara®), an immunomodulatory agent, led to speculation that it may promote an immune response against melanoma. Studies, mostly case reports, have assessed the value of imiquimod as a topical treatment for dermal melanoma metastases that prove difficult to manage surgically. The precise value of imiquimod, however, in treatment of dermal and subcutaneous metastases remains unclear. A case at our institution elucidates histopathologically that subcutaneous metastases may progress despite excellent treatment of superficial dermis in the same location. In preparation for a clinical trial using imiquimod to treat patients with dermal melanoma metastases, we have treated several patients off protocol. We present a case report in which the observed changes are documented photographically and histologically. The patient experienced dramatic improvement in the locally treated dermis with concurrent regional treatment failure in the subcutaneous space. Our experience supports growing evidence that imiquimod for some provides an effective option for dermal disease. The unique histological documentation we provide regarding the differential effectiveness of imiquimod in treating various tissue components may help guide future investigations regarding optimal clinical application of imiquimod therapy for melanoma metastases.

BACKGROUND Minimally invasive component separation (CS) with inlay bioprosthetic mesh (MICSIB) is a recently developed technique for abdominal wall reconstruction that preserves the rectus abdominis perforators and minimizes subcutaneous dead space using limited-access tunneled incisions. We hypothesized that MICSIB would result in better surgical outcomes than would conventional open CS. STUDY DESIGN All consecutive patients who underwent CS (open or minimally invasive) with inlay bioprosthetic mesh for ventral hernia repair from 2005 to 2010 were included in a retrospective analysis of prospectively collected data. Surgical outcomes including wound-healing complications, hernia recurrences, and abdominal bulge/laxity rates were compared between patient groups based on the type of CS repair: MICSIB or open. RESULTS Fifty-seven patients who underwent MICSIB and 50 who underwent open CS were included. The mean follow-ups were 15.2±7.7 months and 20.7±14.3 months, respectively. The mean fascial defect size was significantly larger in the MICSIB group (405.4±193.6 cm2 vs. 273.8±186.8 cm2; p =0.002). The incidences of skin dehiscence (11% vs. 28%; p=0.011), all wound-healing complications (14% vs. 32%; p=0.026), abdominal wall laxity/bulge (4% vs. 14%; p=0.056), and hernia recurrence (4% vs. 8%; p=0.3) were lower in the MICSIB group than in the open CS group. CONCLUSIONS MICSIB resulted in fewer wound-healing complications than did open CS used for complex abdominal wall reconstructions. These findings are likely attributable to the preservation of paramedian skin vascularity and reduction in subcutaneous dead space with MICSIB. MICSIB should be considered for complex abdominal wall reconstructions, particularly in patients at increased risk of wound-healing complications.

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold–stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model—hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber—provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects.

Background: The infected abdomen poses substantial challenges to surgeons, and often, both temporary and definitive closure techniques are required. We reviewed the options available to close the abdominal wall defect encountered frequently during and after the management of complicated intra-abdominal infections. Methods: A comprehensive review was performed of the techniques and literature on abdominal closure in the setting of intra-abdominal infection. Results: Temporary abdominal closure options include the Wittmann Patch, Bogota bag, vacuum-assisted closure (VAC), the AbTheraÔ device, and synthetic or biologic mesh. Definitive reconstruction has been described with mesh, components separation, and autologous tissue transfer. Conclusion: Reconstructing the infected abdomen, both temporarily and definitively, can be accomplished with various techniques, each of which is associated with unique advantages and disadvantages. Appropriate judgment is required to optimize surgical outcomes in these complex cases.

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh-non-cross-linked porcine acellular dermal matrix (ncl-PADM)-used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5 · 10 4 cells/cm 2 ) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2 · 4 cm) were created and repaired with ASC-seeded (n = 31) and control (n = 32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group ( p < 0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points ( p < 0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group ( p < 0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes.

Antibiotic de-escalation was not associated with increased mortality rates, but the duration of antibiotic use was longer in this group. Greater mortality rates were observed in the non-deescalated group, but this likely owes at least in part to their relatively greater severity of disease classification (APACHE II). Further investigation will help evaluate whether antibiotic de-escalation will improve the quality of patient care.

Laparoscopic ventral hernia repair reportedly yields lower postoperative complications than open repair. We hypothesized that patients undergoing laparoscopic repair would have lower postoperative infectious outcomes. Also, certain preoperative patient characteristics and preoperative hernia characteristics are hypothesized to increase complication risk in both groups. All ventral hernia repairs performed at University of Virginia from January 2004 to January 2006 were reviewed. Primary outcomes included wound healing complications and hernia recurrence. Categorical data were analyzed with χ2 and Fisher's exact tests. Continuous variables were evaluated with independent t tests and Mann-Whitney U tests. Multivariable logistic regression was performed. A total of 268 repairs (110 open, 158 laparoscopic) were evaluated. Patient and hernia characteristics were similar between groups, though the percents of wound contamination (5.4% vs 0.6%; P = 0.02) and simultaneous surgery (7.2% vs 0%; P = 0.001) were greater in the open procedures. Univariate analysis also revealed that open cases had a greater incidence of postoperative superficial surgical site infection (SSI) (30.0% vs 10.7%; P < 0.0001). Multivariable analysis revealed that both diabetes and open repair were associated with an increased risk of superficial SSI ( P = 0.019; odds ratio = 3.512; 95% confidence interval = 1.229–10.037 and P = 0.001; odds ratio = 4.6; 95% confidence interval = 1.9–11.2, respectively). Laparoscopic ventral hernia repair yielded lower rates of postoperative superficial SSI than open surgery. Other pre-operative patient characteristics and preoperative hernia characteristics, with the exception of diabetes, were not found to be associated with an increased risk of postoperative complications.