Challenges in Breast Evaluation: Breast Asymmetry, Macromastia, and the Surgically Altered Breast.

Many breast conditions that warrant referral to a plastic surgeon may first be identified in a routine gynecologic or primary care setting. These range from asymmetric anomalies and macromastia to sequelae of previous aesthetic and reconstructive procedures. The purpose of this reference article is to provide an overview of common breast deformities and discuss their unique challenges in evaluation.

Connexin 43-Based Therapeutics for Dermal Wound Healing.

The most ubiquitous gap junction protein within the body, connexin 43 (Cx43), is a target of interest for modulating the dermal wound healing response. Observational studies found associations between Cx43 at the wound edge and poor healing response, and subsequent studies utilizing local knockdown of Cx43 found improvements in wound closure rate and final scar appearance. Further preclinical work conducted using Cx43-based peptide therapeutics, including alpha connexin carboxyl terminus 1 (αCT1), a peptide mimetic of the Cx43 carboxyl terminus, reported similar improvements in wound healing and scar formation. Clinical trials and further study into the mode of action have since been conducted on αCT1, and Phase III testing for treatment of diabetic foot ulcers is currently underway. Therapeutics targeting connexin activity show promise in beneficially modulating the human body's natural healing response for improved patient outcomes across a variety of injuries.

Axillary Lymphadenectomy and Wound Complications in Implant-Based Breast Reconstruction.

BACKGROUND: The most common method of breast reconstruction in the United States today is implant-based reconstruction. However, reported complication rates are high, from 30% to 50%. Thus, it is important for reconstructive surgeons to identify factors associated with or contributing to wound complications after breast reconstruction. This study sought to identify associations between axillary lymph node dissection and postoperative wound complications in implant-based breast reconstruction. METHODS: A retrospective chart review was performed of subjects undergoing breast oncologic and reconstructive surgery by a single breast surgeon and reconstructive surgeon, respectively, from 2013 to 2016. Medical records were reviewed of 273 subjects with 338 reconstructed breasts. Data were recorded on the extent of axillary node dissection and subsequent wound complications including seroma requiring percutaneous drainage, seroma requiring open drainage, wound dehiscence requiring local wound care, wound dehiscence requiring operative revision, implant exposure, and implant loss. RESULTS: Analysis of the data demonstrated an increase in complication rates with extent of axillary lymph node dissection; however, these rates did not reach statistical significance. Statistically significant associations, however, were identified between wound complication rates and other known risk factors including increasing age and body mass index, as well as smoking status. CONCLUSIONS: Although an association between increasing complication rates and the extent of lymph node dissection has previously been reported, this study failed to demonstrate a statistically significant association with logistic regression analysis.

Evidence-Based Practice in Liposuction.

BACKGROUND: The goal of this study is to examine the existing peer reviewed literature comparing modern adjunctive techniques in liposuction including laser-assisted liposuction (LAL) and ultrasound-assisted liposuction (UAL) to standard suction-assisted liposuction (SAL). We intend to interpret these findings into a literature-based clinical application to influence practice patterns. METHODS: A literature review was conducted using a keyword search in PubMed. Keyword search items included liposuction, lipoplasty, suction assisted liposuction, ultrasound assisted liposuction, laser assisted liposuction, tumescent, liposuction comparison, liposuction review, and combinations therein. Exclusion criteria included articles with a primary focus on histologic effects of energy devices, primary animal models, primary opinion papers with no reference to available data, and industry-sponsored publications. Inclusion criteria included articles with direct comparison of liposuction modalities, randomized or blinded studies, and studies with objective outcomes. RESULTS: Twenty-five articles that met the inclusion criteria comparing SAL to UAL or LAL out of 9972 articles identified were obtained. The selected literature was assigned into 3 categories: evidence demonstrating an advantage of 1 modality (SAL, UAL, or LAL) over another, evidence that showed no benefit of 1 modality over another, and evidence that demonstrated risks of complications of 1 modality over another. CONCLUSIONS: The benefits of UAL and LAL over SAL include the following: (1) UAL over SAL in the treatment of gynecomastia, (2) LAL and UAL over SAL with decreased hemoglobin/hematocrit in high-volume lipoaspirates, and (3) LAL over SAL with skin tightening in select areas specifically the submental area. Otherwise, the literature demonstrates equivocal results among the described techniques with no clear benefit to set one apart from the other. There appears to be no demonstrable added benefit to the addition of either UAL or LAL that would urge a change in practice patterns outside the exceptions listed.

A Multicenter Randomized Controlled Trial Evaluating a Cx43-Mimetic Peptide in Cutaneous Scarring.

The transmembrane protein Cx43 has key roles in fibrogenic processes including inflammatory signaling and extracellular matrix composition. aCT1 is a Cx43 mimetic peptide that in preclinical studies accelerated wound closure, decreased inflammation and granulation tissue area, and normalized mechanical properties after cutaneous injury. We evaluated the efficacy and safety of aCT1 in the reduction of scar formation in human incisional wounds. In a prospective, multicenter, within-participant controlled trial, patients with bilateral incisional wounds (≥10 mm) after laparoscopic surgery were randomized to receive acute treatment (immediately after wounding and 24 hours later) with an aCT1 gel formulation plus conventional standard of care protocols, involving moisture-retentive occlusive dressing, or standard of care alone. The primary efficacy endpoint was average scarring score using visual analog scales evaluating incision appearance and healing progress over 9 months. There was no significant difference in scar appearance between aCT1- or control-treated incisions after 1 month. At month 9, aCT1-treated incisions showed a 47% improvement in scar scores over controls (Vancouver Scar Scale; P = 0.0045), a significantly higher Global Assessment Scale score (P = 0.0009), and improvements in scar pigmentation, thickness, surface roughness, and mechanical suppleness. Adverse events were similar in both groups. aCT1 has potential to improve scarring outcome after surgery.

Opening the Debate: How to Fulfill the Need for Physicians' Training in Circadian-Related Topics in a Full Medical School Curriculum.

BACKGROUND: Circadian rhythms are daily changes in our physiology and behavior that are manifested as patterns of brain wave activity, periodic hormone production, recurring cell regeneration, and other oscillatory biological activities. Their importance to human health is becoming apparent; they are deranged by shift work and jet-lag and in disparate conditions such as insomnia, sleep syndromes, coronary heart attacks, and depression, and are endogenous factors that contribute to cancer development and progression. DISCUSSION: As evidence of the circadian connection to human health has grown, so has the number of Americans experiencing disruption of circadian rhythms due to the demands of an industrialized society. Today, there is a growing work force that experiences night shift work and time-zone shifts shaping the demands on physicians to best meet the needs of patients exposed to chronic circadian disruptions. The diverse range of illness associated with altered rhythms suggests that physicians in various fields will see its impact in their patients. However, medical education, with an already full curriculum, struggles to address this issue. SUMMARY: Here, we emphasize the need for incorporating the topic of circadian rhythms in the medical curriculum and propose strategies to accomplish this goal.

Cell-populated collagen lattice contraction model for the investigation of fibroblast collagen interactions.

The fibroblast-populated collagen lattice (FPCL) was intended to act as the dermal component for "skin-equivalent" or artificial skin developed for skin grafting burn patients. The "skin-equivalent" was clinically unsuccessful as a skin graft, but today it is successfully used as a dressing for the management of chronic wounds. The FPCL has, however, become an instrument for investigating cell-connective tissue interactions within a three-dimensional matrix. Through the capacity of cell compaction of collagen fibrils, the FPCL undergoes a reduction in volume referred to as lattice contraction. Lattice contraction proceeds by cell-generated forces that reduce the water mass between collagen fibers, generating a closer relationship between collagen fibers. The compaction of collagen fibers is responsible for the reduction in the FPCL volume. Cell-generated forces through the linkage of collagen fibers with fibroblast's cytoskeletal actin-rich microfilament structures are responsible for the completion of the collagen matrix compaction. The type of culture dish used to cast FPCL as well as the cell number will dictate the mechanism for compacting collagen matrices. Fibroblasts, at moderate density, cast as an FPCL within a petri dish and released from the surface of the dish soon after casting compact collagen fibers through cell tractional forces. Fibroblasts at moderate density cast as an FPCL within a tissue culture dish and not released for 4 days upon release show rapid lattice contraction through a mechanism of cell contraction forces. Fibroblasts at high density cast in an FPCL within a petri dish, released from the surface of the dish soon after casting, compact a collagen lattice very rapidly through forces related to cell elongation. The advantage of the FPCL contraction model is the study of cells in the three-dimensional environment, which is similar to the environment from which these cells were isolated. In this chapter methods are described for manufacturing collagen lattices, which assess the three forces involved in compacting and/or organizing collagen fibrils into thicker collagen fibers. The clinical relevance of the FPCL contraction model is related to advancing our understanding of wound contraction and scar contracture.

Complex abdominal wall reconstruction: an outcomes review.

BACKGROUND: Complex abdominal wall reconstruction (AWR) remains challenging. Techniques for repair are numerous and include primary fascial approximation, separation of components (SOC), and use of various biologic and synthetic meshes. Given the vast expanse of available techniques and lack of consistent algorithms, an analysis of outcomes in AWR is presented. METHODS: A retrospective review was performed of complex AWRs performed by 2 surgeons at a single institution from July 2008 to October of 2011. Outcome differences for hernia repairs specifically addressing SOC with an acellular dermis inlay (retrorectus), underlay, or overlay mesh, as well as interposition biologic mesh placement were included. RESULTS: A total of 66 patients were identified. The average body mass index in this population was 35.5 kg/m. The average age was 53.7 years, with 62% females and 38% males. The overall rate of tobacco use history was 48%. Twenty-eight percent were diabetic. The overall hernia recurrence rate was 16%. Patients having SOC with inlay (retrorectus) mesh had a hernia recurrence rate of 9%. Hernia recurrence in those with SOC and biologic mesh reinforcement as an underlay or onlay was 12%; in those without mesh reinforcement, 22%; and for those with a biologic mesh interposition, 40%. CONCLUSIONS: The results of this review show that hernia recurrence rates are decreased with primary fascial repair. Further reduction occurs when biologic mesh reinforcement is used. The lowest recurrence rates were seen in the group with SOC and a porcine biologic mesh inlay. Abdominal wall reconstruction is challenging and with continued outcomes review a refined algorithm can be achieved. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic: III.

Analysis of clinically significant seroma formation in breast reconstruction using acellular dermal grafts.

With a rise in tissue expander-based breast reconstructions (TEBRs) using acellular dermal matrix (ADM), we have seen an increase in ADM-specific complications. In this study, we aimed to evaluate clinically significant seroma (CSS) formation-defined by the need for a drainage procedure-to determine if there was a difference in incidence between product types: AlloDerm (AL), DermaMatrix (DM), and FlexHD (FHD). This was a retrospective review of consecutive patients who underwent TEBR at a single institution. The total number of reconstructed breasts was separated into the following 4 groups according to the product type: AL, DM, FHD, or no ADM. We identified the total number of CSSs and compared these data between product types. A logistic regression was performed in an attempt to identify independent risk factors associated with seroma formation. In total, we identified 284 consecutive TEBRs. Overall, there were 17 (7.7%) seromas in 220 breast reconstructions in which ADM was used. When comparing the number of CSS between groups-AL (n = 2, 4.0%), DM (n = 6, 5.4%), FHD (n = 9, 14.75%), and no ADM (n = 1, 1.5%)-we found a significant difference in seroma incidence between product types (P = 0.016). Multivariate analysis identified a strong trend toward FHD as an independent predictor of seroma formation (P = 0.061). Our review suggests that there is strong trend in CSS formation with the use of FHD as compared to other product types and reconstructions in which no ADM was used.

Capsular contracture after breast reconstruction: collagen fiber orientation and organization.

BACKGROUND: Breast implant capsular contracture is a common complication of implant-based breast reconstruction. To develop nonsurgical interventions to combat breast capsular contractures, a clearer understanding of the process is required. Comparing breast implant-related capsular contracture to the fibrotic scarring process, the hypothesis is that these processes differ with regard to the compaction of collagen fibers within the connective tissue matrix. METHODS: Morphologic differences in the connective tissue matrix by light, polarized light, and fluorescence microscopy documents these differences. Discarded Baker grade II and III periimplant capsules harvested during routine breast reconstructive operations were used for the evaluation. RESULTS: Within severe breast capsule contractures, light microscopy revealed the absence of mast cells, whereas polarized light microcopy showed that collagen fiber bundles were consolidated into thick cable-like structures. In less severe breast capsules, mast cells were present, whereas thick cable-like collagen structures were absent. By fluorescence microscopy, fibroblast populations associated with severe contractures were oriented perpendicular to the long axis, suggesting a spiral orientation in the compaction of these cable-like structures. These findings were absent in less severe contractures. CONCLUSIONS: To the authors' knowledge, these histologic findings in breast implant capsules are unreported and unique when compared with other fibrotic contractures. Elucidating the biological mechanisms involved in the reorganization of collagen fiber bundles that lead to implant-related capsular contracture is a critical step for developing strategies to treat and control breast capsule contractures.

Nurse training with simulation: an innovative approach to teach complex microsurgery patient care.

Simulation has become an integral part of education at all levels within the medical field. The ability to allow personnel to practice and learn in a safe and controlled environment makes it a valuable tool for initial training and continued competence verification. An area of specific interest to the reconstructive microsurgeon is assurance that the nursing staff has adequate training and experience to provide optimum care for microsurgery patients. Plastic surgeons in institutions where few microsurgeries are performed face challenges teaching nurses how to care for these complex patients. Because no standard exists to educate microsurgery nurses, learning often happens by chance on-the-job encounters. Outcomes, therefore, may be affected by poor handoffs between inexperienced personnel. Our objective is to create a course that augments such random clinical experience and teaches the knowledge and skills necessary for successful microsurgery through simulated patient scenarios. Quality care reviews at our institution served as the foundation to develop an accredited nursing course providing clinical training for the care of microsurgery patients. The course combined lectures on microsurgery, pharmacology, and flap monitoring as well as simulated operating room, surgical intensive care unit, postanesthesia care unit, Trauma Bay, and Floor scenarios. Evaluation of participants included precourse examination, postcourse examination, and a 6-month follow-up. Average test scores were 72% precourse and 92% postcourse. Educational value, effectiveness of lectures and simulation, and overall course quality was rated very high or high by 86% of respondents; 0% respondents rated it as low. Six-month follow-up test score average was 88%. Learning to care for microsurgery patients should not be left to chance patient encounters on the job. Simulation provides a safe, reproducible, and controlled clinical experience. Our results show that simulation is a highly rated and effective way to teach nurses microsurgery patient care. Simulated patient care training should be considered to augment the clinical experience in hospitals where microsurgery is performed.

Complications in tissue expander breast reconstruction: a comparison of AlloDerm, DermaMatrix, and FlexHD acellular inferior pole dermal slings.

Acellular dermal matrix (ADM) is frequently used in tissue expander breast reconstruction (TEBR) for coverage of the inferior pole. Several published studies have suggested increased rates of complications with the use of ADM. It is unknown, however, if the type of ADM used for TEBR impacts complication rates. The aim of this study is to compare 3 different types of ADM for TEBR in regard to clinically significant complications, specifically infection. We performed a retrospective analysis of primary breast cancer-related TEBR with or without ADM. Exclusion criteria consisted of prior major breast surgery, inadequate data, or loss to follow-up. Reconstructions were grouped by dermal sling type, AlloDerm, DermaMatrix (DM), FlexHD (FHD), or no ADM. Complications included cellulitis, abscess, seroma, expander leak or puncture, skin necrosis, wound dehiscence, or hematoma. Those requiring admission to hospital or reoperation were considered significant. Of 284 breasts reconstructed, 49 used AlloDerm, 110 used DM, 62 used FHD, and 64 used no ADM. The total complication rate with AlloDerm was 22% [95% confidence interval (CI), 11-34], with DM was 15% (95% CI, 8-21), and with FHD was 18% (95% CI, 8-28) (P=0.47). Infectious complication rates for AlloDerm, DM, and FHD were equal at 10% (P=0.97). The total complication rate of all ADM reconstructions as a grouped cohort was 17% compared to 11% without ADM (P=0.48). The overall incidence of infectious complications with ADM was 10% compared to 2% without ADM (P=0.09). There is no difference in the clinically significant overall complication rate or incidence of infection between AlloDerm, DM, and FHD. Isolating infectious complications, there is a trend toward increased incidence with ADM compared to reconstructions without.

Technique for seroma drainage in implant-based breast reconstruction.

Seromas are a common complication associated with breast reconstructive surgery. In expander based breast reconstructions, a seroma can pose a particularly difficult problem related to final tissue envelope shape as well as an increase in the risk of infection and possible tissue necrosis. Unfortunately, the literature describes few non-image related techniques to drain a seroma with a breast implant in place. We present a technique to drain a seroma associated with expander based breast reconstruction in conjunction with expander inflation, minimizing the risk of expander puncture, utilizing the same equipment necessary for expander inflation in the office. The benefit to this technique is that diagnostic and therapeutic imaging is not necessary and the risk of expander damage is minimized.

Pedicled rectus femoris flap for coverage of complex open pelvic fractures.

Complex open pelvic fractures are highly morbid injuries. Distant soft tissue transfer is often necessary for reconstruction. We report two cases of traumatic open pelvic fractures in which a pedicled rectus femoris flap was used for soft tissue coverage. Two patients presented with complex open pelvic fractures resulting from blunt trauma. In both patients a pedicled rectus femoris flap was used to reconstruct the full thickness soft tissue defect. Both patients had complete soft tissue coverage of the anterior pelvic defect allowing definitive pelvic fracture fixation. No significant donor site morbidity was associated with either patient post operatively. The well described pedicled rectus femoris flap's reliable anatomy, ease of harvest, and versatility as well as acceptable donor site morbidity makes this flap ideal for the reconstruction of complex open anterior pelvic fractures with full thickness soft tissue defects when other local flaps or free tissue transfer is not an option.

Rat mast cells enhance fibroblast proliferation and fibroblast-populated collagen lattice contraction through gap junctional intercellular communications.

BACKGROUND: Mast cells' association with fibrosis is known, but the mechanics of that association are unclear. The hypothesis is that mast cells promote fibroblast profibrotic activities through heterocellular gap junctional intercellular communications. Casting populated collagen lattices with both human mastocytoma cell line (HMC-1), an established mast cell line, and fibroblasts enhances lattice contraction via gap junctional intercellular communications. Unfortunately, in monolayer culture, HMC-1 cells and fibroblasts do not form heterocellular gap junctional intercellular communications. Freshly isolated rat peritoneal mast cells, however, establish these communications with fibroblasts in monolayer culture. Isolated rat peritoneal mast cells, however, survive only 7 days. Establishing a rat mast cell line that grows in the same medium as fibroblasts advances the study of mast cell-fibroblast interactions. HMC-1 cells thrive without supplements, suggesting that they release the factor(s) necessary for their viability. Spent HMC-1 medium may contain the factor(s) that generate a viable rat mast cell line. METHODS: Rat peritoneal-isolated mast cells grew in culture medium containing spent HMC-1 medium for 4 weeks. At 4 weeks, rat mast cells (RMC-1) were successfully maintained in Dulbecco's Modified Eagle Medium with 10% serum. RESULTS: RMC-1 cells formed heterocellular gap junctional intercellular communications with fibroblasts, enhancing both fibroblast proliferation and co-cultured RMC-1/fibroblast/populated collagen lattice contraction. Enhanced fibroblast proliferation and lattice contraction failed to occur by including RMC-1 cells unable to establish gap junctional intercellular communications with fibroblasts, but cell proliferation was not affected by including degranulated RMC-1 cells. CONCLUSION: Heterocellular gap junctional intercellular communications with mast cells increase in fibroblast proliferation and fibroblast PCL contraction, two hypertrophic scar fibroblast activities.

Plastic surgery within the Veterans Affairs Medical System: proposed modified indications for operative procedures.

Many plastic surgery procedures span the divide between aesthetic ("cosmetic") and reconstructive surgery. However, definitions and guidelines may be inconsistent, which may decrease patients' access to legitimate procedures. The article aims to assist Veterans' Health Administration-affiliated plastic surgeons in continuing to provide optimal care to the Nation's Veterans and family members, and should be regarded as an open discussion.

Soft-tissue defects and exposed hardware: a review of indications for soft-tissue reconstruction and hardware preservation.

BACKGROUND: Traditionally, management of exposed hardware has included irrigation and débridement, intravenous antibiotics, and likely removal of the hardware. Increasingly, the goal of wound closure without hardware removal using plastic surgical techniques of soft-tissue reconstruction has been emphasized. Identification of parameters for retaining exposed hardware may assist surgeons with management decisions and outcomes. METHODS: A current literature review was performed to identify parameters with prognostic relevance for management of exposed hardware before soft-tissue reconstruction. RESULTS: The following parameters were identified as important for the potential salvage of exposed hardware with soft-tissue coverage: hardware location, infection, duration of exposure, and presence of hardware loosening. CONCLUSIONS: Management of exposed hardware has included the removal of the hardware. However, if certain criteria are met--specifically, stable hardware, time of exposure less than 2 weeks, lack of infection, and location of hardware--salvage of the hardware with plastic surgical soft-tissue coverage may be a therapeutic option.

Metabolic and functional characterization of human adipose-derived stem cells in tissue engineering.

BACKGROUND: The use of adipose-derived stem cells for tissue engineering involves exposing them to metabolically adverse conditions. This study examines the metabolism, proliferation, and differentiation of adipose-derived stem cells under various conditions. METHODS: Adipose-derived stem cells were cultured in 16 media conditions containing 0.6, 2.4, 4.3, or 6.1 mM glucose; 0.1, 2.5, 4.1, or 6.1 mM glutamine; and then grown in either 0.1% or 20% oxygen. Conditioned media were collected and assayed for glucose, lactate, and pyruvate. Cell proliferation and cell death were measured at several time points. Osteogenic differentiation was analyzed by alizarin red staining/quantification and alkaline phosphatase activity, measured weekly over 4 weeks. RESULTS: Adipose-derived stem cells remained metabolically active in all nutrient and oxygen conditions tested. Glucose consumption and lactate production increased under hypoxic conditions, but pyruvate consumption was jointly dependent on oxygen and glucose concentration. The 20% oxygen environment produced greater proliferation and cell death compared with the hypoxic environment. Osteogenic differentiation of adipose-derived stem cells was observed only when glucose and/or oxygen concentrations were physiologically normal to high. CONCLUSIONS: Adipose-derived stem cells are an excellent source of multipotent cells and are capable of advancing current tissue engineering methodologies. These data show that adipose-derived stem cells remain viable under adverse conditions of low glucose, glutamine, and oxygen concentrations. However, there are variable levels of differentiation in the various culture conditions, which could lead to challenges in de novo osteogenesis and other forms of tissue engineering. Therefore, these results should be used in developing specific strategies to ensure successful application of adipose-derived stem cells in bone engineering and similar applications.

Calmodulin-myosin light chain kinase inhibition changes fibroblast-populated collagen lattice contraction, cell migration, focal adhesion formation, and wound contraction.

Wound healing requires fibroblast migration, synthesis of new extracellular matrix, and organization of that matrix, all of which depend upon myosin ATPase activation and subsequent cytoplasmic actin-myosin contraction. Myosin ATPase activity is optimized by phosphorylation of myosin light chain at serine 19. Several different signaling pathways can perform that phosphorylation, the focus here is calcium saturated calmodulin dependent -myosin light chain kinase (CaM-MLCK). It is proposed that CaM-MLCK phosphorylation of myosin light chain and subsequent myosin ATPase activation affects granulation tissue fibroblast behavior and contributes to wound contraction. Myosin ATPase activity generates actin-myosin contraction within fibroblasts. Myosin ATPase activity is involved in ATP-induced cell contraction, the generation of focal adhesions, fibroblast migration, fibroblast populated collagen lattice (FPCL) contraction, and wound contraction. The MLCK inhibitors ML-9 and ML-7 inhibited ATP-induced cell contraction, fibroblast migration, FA formation, and FPCL contraction. The calmodulin inhibitors W7 and fluphenazine blocked rat open wound contraction. In addition, fluphenazine delayed re-epithelialization. These findings support the idea that fibroblast CaM-MLCK activity is essential for tissue repair. We speculate that inhibition of CaM-MLCK may reduce or prevent detrimental fibrotic contracture.

Mast cells promote fibroblast populated collagen lattice contraction through gap junction intercellular communication.

The release of mast cell granules is commonly associated with inflammation and fibrosis. However, does direct communication between mast cells and fibroblasts through gap junction intercellular communication (GJIC) occur? Fibroblast populated collagen lattice (FPCL) cast with mast cells show enhanced lattice contraction. Do released granules or GJIC between mast cells and fibroblasts promote enhanced lattice contraction? Mast cells preloaded with a fluorescent dye that readily passes through gap junctions were cast in FPCL. Dye passed from mast cells into fibroblasts within these cocultured mast cell-FPCLs. Fatty acid amide hydrolase inhibitor blocks the breakdown of oleamide, which is a potent endogenous inhibitor of GJIC. GJIC was blocked for 3 days when mast cells were pulsed for 3 hours with fatty acid amide hydrolase inhibitor. Mast cells pretreated with fatty acid amide hydrolase inhibitor cast in cocultured mast cell-FPCLs failed to enhance cocultured lattice contraction. Mast cell-FPCLs made with mouse fibroblasts unable to generate GJIC failed to show enhanced lattice contraction. Degranulated mast cells were equal to intact mast cells at enhancing cocultured mast cell-FPCL contraction. The supernatant from degranulated mast cells had no effect upon FPCL contraction. Therefore, enhanced mast cell-FPCL contraction appears to be independent of mast cell granules, but dependent upon GJIC between fibroblasts and mast cells. We speculate that mast cell-fibroblast GJIC may play a role in fibrosis.