Feasibility and acceptability of a pilot tailored text messaging intervention for adolescents and young adults completing cancer treatment.

PURPOSE: Despite cure, adolescents and young adults (AYA) who complete cancer treatment remain at risk for numerous physical and psychological late effects. However, engagement in recommended follow-up care, knowledge of cancer treatment history and risks, and adoption of health promoting behaviors are often suboptimal. The pilot randomized controlled trial assessed the feasibility and acceptability of a text messaging intervention (THRIVE; Texting Health Resources to Inform, motiVate, and Engage) designed to promote well-being, and health knowledge and behaviors. METHODS: Sixty-one AYA who recently completed cancer therapy enrolled and were randomized to receive THRIVE (n = 31) or an AYA survivor handbook (n = 30). Participants from both groups completed baseline measures and follow-up surveys 16 weeks later. AYA randomized to THRIVE received one to two health-related text messages per day over 16 weeks. RESULTS: THRIVE demonstrated a high level of acceptability and feasibility. Exploratory analyses highlighted promising improvements in knowledge, fruit/vegetable intake, and perceptions of health vulnerability. CONCLUSIONS: Text messaging is an acceptable and feasible intervention approach for improving well-being and health of AYA survivors. Future research is needed to test the impact of text messaging in a larger trial, including whether or not such an intervention can improve clinical outcomes, such as survivors' engagement in follow-up care.

Oxidative Stress Alters Angiogenic and Antimicrobial Content of Extracellular Vesicles and Improves Flap Survival.

Extracellular vesicles (EVs) secreted from adipose-derived mesenchymal stem cells (ADSCs) (ADSC-EVs) improve flap survival after ischemia-reperfusion injury. Exposure of parent ADSCs to oxidative stress has been shown to enhance this effect, but mechanisms are unclear. We aimed to determine whether angiogenesis-promoting protein and microRNA (miRNA) content is altered in EVs after preconditioning with hydrogen peroxide (H2O2 ADSC-EVs) and whether H2O2 ADSC-EVs can increase viability of random pattern skin flaps. METHODS: EVs secreted by human ADSCs were isolated after culture in EV-depleted medium ± H2O2. Nanoparticle tracking analysis determined size and concentration of purified EVs. Mass spectrometry and small RNA next-generation sequencing were performed to compare proteomic and miRNA profiles. ADSC-EVs, H2O2 ADSC-EVs, or vehicle were injected into random pattern skin flaps of BALB/c mice (4-5 mice per group). Viable and necrotic areas were measured on day 7, and tissues underwent histologic analysis. RESULTS: Angiogenic and antimicrobial protein content of EVs was altered with H2O2 preconditioning. Functional enrichment analysis identified constitutive photomorphogenesis 9 signalosome (known to direct vascular endothelial growth factor production) as the major enriched Gene Ontology term unique to H2O2 ADSC-EVs. Two miRNAs were increased, and 12 (including 10 antiangiogenic miRNAs) were reduced in H2O2 ADSC-EVs. Enhanced viability (P < 0.05) of flaps treated with H2O2 ADSC-EVs compared with vehicle corresponded to increased capillary density in the H2O2 group (P < 0.001). CONCLUSION: Altered protein and miRNA content in ADSC-EVs after H2O2 pretreatment likely contributes to enhanced therapeutic effects on flap survival observed in preclinical models.

Evaluation of a Novel Hybrid Viable Bioprosthetic Mesh in a Model of Mesh Infection.

BACKGROUND: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of material used. Our laboratory previously showed that augmenting acellular bioprosthetic mesh with allogeneic mesenchymal stem cells (MSC) enhances resistance to bacterial colonization in vivo and preserves mesh integrity. This study's aim was to determine whether augmentation of non-crosslinked porcine dermis (Strattice) with commercially available, cryopreserved, viable MSC-containing human placental tissue (Stravix) similarly improves infection resistance after inoculation with Escherichia coli (E. coli) using an established mesh infection model. METHODS: Stravix was thawed per manufacturer's instructions and 2 samples were tested for cell viability using a Live/Dead Cell assay at the time of surgery. Rats (N = 20) were implanted subcutaneously with 1 piece of Strattice and 1 piece of hybrid mesh (Strattice + Stravix sutured at the corners). Rats were inoculated with either sterile saline or 106 colony-forming units of E. coli before wound closure (n = 10 per group). At 4 weeks, explants underwent microbiologic and histologic analyses. RESULTS: In E. coli-inoculated animals, severe or complete mesh degradation concurrent with abscess formation was observed in 100% (10/10) hybrid meshes and 90% (9/10) Strattice meshes. Histologic evaluation determined that meshes inoculated with E. coli exhibited severe acute inflammation, which correlated with bacterial recovery (P < 0.001). Viability assays performed at the time of surgery failed to verify the presence of numerous live cells in Stravix. CONCLUSIONS: Stravix cryopreserved MSC-containing human umbilical tissue does not improve infection resistance of a bioprosthetic mesh in vivo in rats after inoculation with E. coli.

Caregiver distress and patient health-related quality of life: psychosocial screening during pediatric cancer treatment.

BACKGROUND: Reports of acceptability of psychosocial screening are limited, and the utility of screening in identifying risk factors for health-related quality of life (HRQL) of children with cancer has not been established. This study aimed to assess acceptability of screening for parents and evaluate associations between family risk factors and patient HRQL in the first year post-diagnosis. PROCEDURE: Sixty-seven parents of children with cancer completed the Psychosocial Assessment Tool (family risk), Distress Thermometer (caregiver distress), Posttraumatic Stress Disorder Checklist-Civilian 6 (caregiver traumatic stress), PedsQL 4.0 (parent-proxy report of patient HRQL) and four acceptability questions via a tablet (iPad). RESULTS: Patients (Mage = 9.5 SD = 5.5 years) were equally distributed across major pediatric cancer diagnoses. The majority of parents endorsed electronic screening as acceptable (70%-97%). Patient gender, diagnosis, intensity of treatment and time since diagnosis were not significantly correlated with family risk, caregiver distress, traumatic stress, or patient HRQL. The full regression model predicting total HRQL was significant (R2 = .42, F(4,64) = 10.7, p = .000). Age (older) was a significant covariate, family risk and caregiver distress were significant independent predictors of poorer total HRQL. The full regression models for physical and psychosocial HRQL were significant; age and caregiver distress were independent predictors of physical HRQL, and age and family risk were independent predictors of psychosocial HRQL. CONCLUSIONS: Screening is acceptable for families and important for identifying risk factors associated with poorer patient HRQL during childhood cancer treatment. Targeted interventions addressing family resource needs as well as parent distress identified through screening may be effective in promoting patient HRQL. Copyright © 2016 John Wiley & Sons, Ltd.

Bone Marrow-Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection.

BACKGROUND: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow-derived MSCs improves infection resistance in vivo after inoculation with Escherichia coli (E. coli). METHODS: Rat bone marrow-derived MSCs at passage 3 were seeded onto bovine pericardium and cultured for 7 days before implantation. Additional rats (n = 24) were implanted subcutaneously with MSC-seeded or unseeded mesh and inoculated with 7 × 10(5) colony-forming units of E. coli or saline before wound closure (group 1, unseeded mesh/saline; group 2, unseeded mesh/E. coli; group 3, MSC-seeded mesh/E. coli; 8 rats per group). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. RESULTS: MSC-seeded meshes inoculated with E. coli demonstrated superior bacterial clearance and preservation of mesh integrity compared with E. coli-inoculated unseeded meshes (87.5% versus 0% clearance; p = 0.001). Complete mesh degradation concurrent with abscess formation was observed in 100% of rats in the unseeded/E. coli group, which is in contrast to 12.5% of rats in the MSC-seeded/E. coli group. Histologic evaluation determined that remodeling characteristics of E. coli-inoculated MSC-seeded meshes were similar to those of uninfected meshes 4 weeks after implantation. CONCLUSIONS: Augmenting a bioprosthetic material with stem cells seems to markedly enhance resistance to bacterial infection in vivo and preserve mesh integrity.

Engagement and experience with cancer-related follow-up care among young adult survivors of childhood cancer after transfer to adult care.

PURPOSE: Young adult survivors (YAS) of childhood cancer require annual adult-focused, cancer-related follow-up given their risk for late effects of treatment. This study describes perception of and engagement with adult-focused, cancer-related follow-up care and general health care among YAS formally transferred to adult care from pediatric survivorship care. METHODS: YAS transferred from pediatric survivorship care in the prior 1-5 years completed measures indicating engagement with cancer-related follow-up care, other health care utilization, content of communication by providers, quality of cancer-related care, and satisfaction with health care in the prior year. RESULTS: Eighty YAS (M age = 27.7 years, M time since diagnosis = 10.4 years) participated. Just over half of YAS surveyed (n = 44, 55%) endorsed continuing cancer-related follow-up care since transfer. Those with cancer-related follow-up endorsed seeing subspecialty survivorship providers (n = 16, 44%) and primary care providers (n = 22, 50%) or utilizing a shared care model (n = 6, 14%). About a third of YAS endorsed seeing subspecialists (n = 29, 36%) or using other support services (n = 22, 27%). YAS-perceived content of communication varied significantly depending on care model with less cancer-related content being discussed by primary care providers, though perceived quality of cancer-related care and satisfaction with health care was generally favorable. CONCLUSIONS: YAS report less than optimal engagement in cancer-related follow-up care and communication in their health care encounters. IMPLICATIONS FOR CANCER SURVIVORS: Young adult survivors should receive anticipatory guidance about expectations for delivery and content of adult-focused cancer-related follow-up care.

An experimental comparison of the effects of bacterial colonization on biologic and synthetic meshes.

PURPOSE: Biologic meshes are being used with increasing frequency to repair contaminated abdominal wall defects despite high long-term recurrence and infection rates associated with their use. Recent clinical reports describing the success of lightweight, macroporous synthetic meshes in contaminated ventral hernia repairs have led some surgeons to challenge the belief that synthetics are contraindicated in contaminated fields. We aimed to determine whether a frequently used biologic mesh (Strattice(TM)) is more resistant to bacterial colonization than macroporous synthetic mesh (Parietex(TM) Progrip(TM)) after inoculation with two common pathogens. METHODS: Rats (n = 48) were implanted subcutaneously with Strattice(TM) or Progrip(TM). Meshes were inoculated with sterile saline or a suspension containing 10(6) colony-forming units of Staphylococcus aureus or Escherichia coli prior to wound closure (n = 8 per subgroup). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. RESULTS: Progrip(TM) demonstrated superior bacterial clearance compared to Strattice(TM) (E. coli, 88 vs. 17% clearance, p = 0.03; S. aureus, 75 vs. 50%, p = 0.61; combined bacterial strains, 81 vs. 36%, p = 0.02; respectively). In the Strattice(TM) group, severely degraded meshes were observed in 100% of animals inoculated with E. coli (but 0% inoculated with S. aureus). In contrast, all Progrip(TM) meshes remained intact regardless of inoculum. Scores for neovascularization were higher in the synthetic group irrespective of contamination (p < 0.05). CONCLUSIONS: Biologic meshes may not be more resistant to bacterial colonization than reduced-weight synthetics, and their resistance may differ in response to different pathogens. The routine use of biologics in contaminated ventral hernia repair should be questioned, particularly in the presence of E. coli.

Effect of cross-linked and non-cross-linked acellular dermal matrices on the expression of mediators involved in wound healing and matrix remodeling.

BACKGROUND: Molecular mechanisms that direct the extent of the foreign body reaction to implanted biological meshes and their subsequent incorporation are poorly understood. The purpose of this study was to compare the influence of non-cross-linked human dermis (AlloDerm) with that of cross-linked porcine dermis (Permacol) on the expression of genes critical for wound healing and tissue remodeling in a rat ventral hernia model. METHODS: Full-thickness abdominal wall defects were repaired with AlloDerm, Permacol, or suture repair with no mesh (n = 10 rats per group). Explants were harvested 90 days after repair and divided for histologic, immunohistochemical, and gene expression analyses. Real-time quantitative polymerase chain reaction arrays were used to profile the expression of 84 wound healing-associated genes at the tissue/mesh interface. RESULTS: Both meshes induced the differential expression (≥ 3-fold change relative to suture repair, p ≤ 0.01) of extracellular matrix components, remodeling enzymes, and inflammatory cytokines. Genes most markedly up-regulated included matrix metalloproteinase-9 (Permacol, 66-fold; AlloDerm, 19-fold) and chemokine (C-C motif) ligand 12 (Permacol, 24-fold; AlloDerm, 71-fold). Immunohistochemistry using antibodies against matrix metalloproteinase-9 and chemokine (C-C motif) ligand 12 confirmed differential expression at the protein level (p < 0.001). Histologically, AlloDerm demonstrated overall better remodeling characteristics than Permacol. CONCLUSIONS: Permacol elicits increased protease expression and reduced cellular and vascular infiltration compared with AlloDerm 90 days after implantation, indicative of delayed remodeling induced by cross-linking. Increased understanding of the host response to implanted materials ultimately will enable the development of improved meshes with enhanced wound healing properties and fewer graft-related complications.

Evaluation of Six Split-thickness Skin Graft Donor-site Dressing Materials in a Swine Model.

BACKGROUND: Numerous dressings for split-thickness skin graft donor sites are commercially available with no conclusive evidence-based consensus regarding the optimal dressing choice. This study was conducted to identify which of 5 commonly used materials promotes wound healing most effectively for use on split-thickness donor sites in comparison with our standard dressing, Xeroform (petrolatum gauze). METHODS: Twenty-four partial-thickness wounds were created on the backs of 4 pigs using a dermatome. Wounds (n = 4 per dressing type per pig) were treated with Xeroform, Opsite (polyurethane film), Kaltostat ( calcium sodium alginate), DuoDERM (hydrocolloid), Aquacel (hydrofiber), and Mepilex (silicone foam). Full-thickness skin samples were excised at 3 or 5 days and evaluated histologically for reepithelialization and inflammation. Comparisons also included incidence of infection, ease of use, and cost analyses. RESULTS: DuoDERM elicited the greatest percent reepithelialization (81%) and Mepilex the lowest (33%) after 3 days (P = 0.004). All dressings demonstrated complete reepithelialization except Mepilex (85%) at 5 days. There were no infections and inflammation was mild among all treatments. Mepilex was easiest to use, whereas Aquacel, Kaltostat, and Opsite were most difficult (P = 0.03). Xeroform was most cost-effective and Aquacel most expensive. Combined scoring revealed DuoDERM = Xeroform > Opsite = Mepilex > Kaltostat > Aquacel. CONCLUSIONS: DuoDERM and Xeroform were most effective overall. DuoDERM tended to outperform all dressings in reepithelialization at 3 days, while Xeroform was least expensive, easy to use, and demonstrated rapid reepithelialization. These findings suggest that Xeroform may be preferred for use on large donor-site areas. DuoDERM may be more appropriate for small donor sites when healing time is a priority.

Biocompatibility comparison of novel soft tissue implants vs commonly used biomaterials in a pig model.

OBJECTIVE: To develop a model to evaluate biocompatibility, integration, and substrate independence of novel porous bioscaffolds for maxillofacial and plastic reconstruction using sphere-templated angiogenic regeneration technology compared with currently available synthetic and biologic soft tissue implants. STUDY DESIGN: A prospective pilot study using animals. SETTING: Military medical center. SUBJECTS AND METHODS: Five pigs underwent dorsal subcutaneous implantation of a polypropylene-based material coated with precision pore silicone granules (sphere-templated scaffold), expanded polytetrafluoroethylene, human dermis, and porcine dermis. Sham and undissected sites were also used as controls. Specimens were harvested 7, 21, 90, and 180 days after surgery and evaluated histologically for inflammation, neovascularization, and collagen deposition. RESULTS: All materials and sham sites induced a mild to moderate inflammation that decreased over time, except for human dermis, which elicited a moderate to severe inflammatory response. The responses were varied and measurable using subjective scoring methods. The sphere-templated scaffold demonstrated numerous foreign body giant cells adjacent to the silicone granules, which were not seen in any of the other specimens. CONCLUSION: Subjective scoring of pathology slides and measurement of capsule thickness appeared to show differences between the materials, but these differences require a larger number of subjects and proper statistical analysis to assess. The robust foreign body reaction elicited by the polypropylene/silicone-based scaffold argues against the use of this material in future studies. The authors advocate using inert biodegradable substances for future bioscaffold constructs.

Influence of a new monofilament polyester mesh on inflammation and matrix remodeling.

ABSTRACT Synthetic mesh is widely used for hernia repairs, but mesh-induced chronic inflammatory responses may lead to postoperative complications. We previously showed an elevated response to multifilament polyester (PE) versus monofilament polypropylene (PP) and polytetrafluoroethylene (PTFE) meshes, but it is unclear whether this discrepancy is due to the differences in chemical composition or filament structure. This study compares the influence of a newly available monofilament PE mesh to that of multifilament PE, monofilament PP, and monofilament PTFE on the expression of genes important in inflammation and extracellular matrix remodeling in a rat model. Full thickness abdominal wall defects were corrected with onlay repair or suture repair with no mesh. Explants were harvested 7 or 90 days after repair and divided for histology and mRNA analyses using real-time quantitative polymerase chain reaction arrays to profile expression at the tissue-mesh interface. Monofilament PE elicited a reduced foreign body reaction compared to multifilament PE, corresponding with reduced mRNA expression of important inflammatory cytokines and matrix metalloproteinases (MMPs). Unexpectedly, monofilament PE also resulted in markedly reduced mRNA expression of tumor necrosis factor and MMPs 3 and 9 compared to the widely-used monofilament PP mesh. Findings from this study revealed that both chemical composition and filament structure are important mesh characteristics that may affect a patient's wound healing response and clinical outcome, and should be considered by the surgeon when choosing a particular mesh. Although clinical studies are warranted, results in a rodent model suggest that monofilament PE may be more beneficial than the multifilament form for certain hernia repairs.

Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles.

Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals.

Inflammatory cytokine and matrix metalloproteinase expression induced by collagen-coated and uncoated polypropylene meshes in a rat model.

OBJECTIVE: The objective of the study was to compare the influence of collagen-coated vs uncoated polypropylene meshes on the expression of genes critical for wound healing. STUDY DESIGN: In 54 rats, abdominal wall defects were created, repaired by polypropylene sutures, and covered by an overlay of coated polypropylene (n = 20), uncoated polypropylene (n = 18), or no mesh (n = 16). Explants were harvested 7 or 90 days after repair and divided for histological, immunohistochemical, and messenger ribonucleic acid (mRNA) analyses. Real-time quantitative polymerase chain reaction arrays were used to profile the expression of 84 genes at the tissue-mesh interface. RESULTS: One week after implantation, coated mesh elicited a slightly greater inflammatory response and increased mRNA expression of 4 proinflammatory cytokines compared with uncoated mesh. Both materials, however, induced a comparable expression of cytokines and matrix metalloproteinases relative to suture repair 90 days after implantation. CONCLUSION: Collagen-coated polypropylene mesh induces elevated inflammatory cytokine expression compared with uncoated mesh early in the healing process, but the response to both meshes is similar 90 days after implantation.

Influence of mesh materials on the expression of mediators involved in wound healing.

The use of synthetic mesh for ventral hernia repair is widely accepted, but mesh-induced inflammatory responses may lead to postoperative complications. Molecular mechanisms that direct the extent of the foreign body reaction to implanted materials are poorly understood. This study compares the influence of three macroporous meshes on the expression of genes critical for wound healing and extracellular matrix remodeling in a rat model. Full thickness abdominal wall defects were corrected with polypropylene, polyester, polytetrafluoroethylene (PTFE), or suture repair with no mesh. Explants were harvested 7 or 90 days after repair and were divided for histological, immunohistochemical, and mRNA analyses. Real-time quantitative polymerase chain reaction arrays were used to profile the expression of 84 genes involved in angiogenesis at the tissue-mesh interface. Evaluation of gene expression profiles and histologic specimens revealed that polypropylene and polyester induced a greater and more persistent inflammatory response than PTFE, which elicited a response most similar to that induced by suture repair. Mesh implantation induced the differential expression (>3-fold change and p < .01) of genes encoding inflammatory cytokines, growth factors, and extracellular matrix proteins relative to suture repair without mesh. Genes most markedly upregulated included the neutrophil chemoattractant CXCL2 and matrix metalloproteinases 3 and 9. Polyester induced the greatest number of differentially expressed genes relative to suture repair both at 7 and 90 days after implantation. Results from this study suggest that the particular type of mesh used in a hernia repair may affect the patient's wound healing response and clinical outcome.

Effect of estrogen replacement on the histologic response to polypropylene mesh implanted in the rabbit vagina model.

OBJECTIVE: The aim of this study was to determine the effect of estrogen replacement after ovariectomy on the histologic response to polypropylene mesh implanted in rabbit vagina. STUDY DESIGN: Thirty rabbits were assigned to 5 groups: sham laparotomy, ovariectomy, ovariectomy-preoperative estrogen, ovariectomy-postoperative estrogen, or ovariectomy-preoperative and postoperative estrogen. Rabbits underwent sham surgery or ovariectomy and were infused with vehicle or 17beta-estradiol (200 microg/d) for 4 weeks ("preoperative" estrogen). Polypropylene mesh was implanted in the posterior vaginal wall, and rabbits were infused with vehicle or "postoperative" estrogen for an additional 8 weeks. Grafts were harvested and underwent histologic evaluation. RESULTS: Vaginal atrophy in ovariectomized rabbits was reversed by estrogen replacement. Scores for inflammation (P = .33) and neovascularization (P = .23) at the graft site were not different among estrogen replacement groups, but estrogen administration was associated with increased collagen deposition (P = .005). CONCLUSION: Estrogen replacement administered for 8 weeks postoperatively increases collagen deposition into polypropylene mesh.

Biomechanical properties of synthetic and biologic graft materials following long-term implantation in the rabbit abdomen and vagina.

OBJECTIVE: We sought to evaluate the effects of anatomic location and ovariectomy on biomechanical properties of synthetic and biologic graft materials after long-term implantation. STUDY DESIGN: A total of 35 rabbits underwent ovariectomy or sham laparotomy and were implanted with polypropylene (PP) mesh (n = 17) or cross-linked porcine dermis (PS) (n = 18) in the vagina and abdomen. Grafts were harvested 9 months later and underwent mechanical properties testing. RESULTS: After implantation, PS was similar in strength (P = .52) but was twice as stiff as PP (P = .04) and had a maximal elongation only half that of PP (P < .001). Degradation of PS was associated with decreased ultimate tensile strength (P = .03) and elastic modulus (P = .046). Vaginal PP grafts shrunk more (P < .001) and were less stiff than abdominal PP grafts (P = .049) but were not different in strength (P = .19). Ovariectomy had no effect (P > .05). CONCLUSION: Cross-linked PS undergoes long-term degradation resulting in compromised biomechanical properties and thus is likely inferior to lightweight PP meshes for pelvic organ prolapse and incontinence procedures.

Long-term histologic response to synthetic and biologic graft materials implanted in the vagina and abdomen of a rabbit model.

OBJECTIVE: We sought to evaluate the effects of graft type, site of implantation, and ovariectomy on the long-term histologic response to graft materials used in pelvic reconstructive surgery. STUDY DESIGN: In all, 45 rabbits underwent ovariectomy or sham laparotomy and were implanted with polypropylene (PP) mesh (n = 23) or cross-linked porcine dermis (PS) (n = 22) in the vagina and abdomen. Grafts were harvested 9 months later and were processed for histology to evaluate the host inflammatory response and degree of tissue incorporation within the grafts. RESULTS: Polypropylene induced a milder (P < .007), more uniform response than PS, whereas PS elicited a more variable response and degraded by 9 months. Vaginal grafts had higher scores for inflammation (P = .005) and neovascularization (P < .001), and had lower scores for fibroblastic proliferation (P < .001) than abdominal grafts. Ovariectomy had no effect (P > .05). CONCLUSION: Synthetic and biologic grafts evoke different foreign body responses, which may have implications for surgical outcomes in women.

Morphological and functional heterogeneity of the mouse intrahepatic biliary epithelium.

Rat and human biliary epithelium is morphologically and functionally heterogeneous. As no information exists on the heterogeneity of the murine intrahepatic biliary epithelium, and with increased usage of transgenic mouse models to study liver disease pathogenesis, we sought to evaluate the morphological, secretory, and proliferative phenotypes of small and large bile ducts and purified cholangiocytes in normal and cholestatic mouse models. For morphometry, normal and bile duct ligation (BDL) mouse livers (C57/BL6) were dissected into blocks of 2-4 microm(2), embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Sizes of bile ducts and cholangiocytes were evaluated by using SigmaScan to measure the diameters of bile ducts and cholangiocytes. In small and large normal and BDL cholangiocytes, we evaluated the expression of cholangiocyte-specific markers, keratin-19 (KRT19), secretin receptor (SR), cystic fibrosis transmembrane conductance regulator (CFTR), and chloride bicarbonate anion exchanger 2 (Cl(-)/HCO(3)(-) AE2) by immunofluorescence and western blot; and intracellular cyclic adenosine 3',5'-monophosphate (cAMP) levels and chloride efflux in response to secretin (100 nM). To evaluate cholangiocyte proliferative responses after BDL, small and large cholangiocytes were isolated from BDL mice. The proliferation status was determined by analysis of the cell cycle by fluorescence-activated cell sorting, and bile duct mass was determined by the number of KRT19-positive bile ducts in liver sections. In situ morphometry established that the biliary epithelium of mice is morphologically heterogeneous, with smaller cholangiocytes lining smaller bile ducts and larger cholangiocytes lining larger ducts. Both small and large cholangiocytes express KRT19 and only large cholangiocytes from normal and BDL mice express SR, CFTR, and Cl(-)/HCO(3)(-) exchanger and respond to secretin with increased cAMP levels and chloride efflux. Following BDL, only large mouse cholangiocytes proliferate. We conclude that similar to rats, mouse intrahepatic biliary epithelium is morphologically and functionally heterogeneous. The mouse is therefore a suitable model for defining the heterogeneity of the biliary tree.

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms.

During cholestatic liver diseases, cholangiocytes express neuroendocrine phenotypes and respond to a number of hormones and neuropeptides by paracrine and autocrine mechanisms. We examined whether the neuroendocrine hormone progesterone is produced by and targeted to cholangiocytes, thereby regulating biliary proliferation during cholestasis. Nuclear (PR-A and PR-B) and membrane (PRGMC1, PRGMC2, and mPRalpha) progesterone receptor expression was evaluated in liver sections and cholangiocytes from normal and bile duct ligation (BDL) rats, and NRC cells (normal rat cholangiocyte line). In vivo, normal rats were chronically treated with progesterone for 1 wk, or immediately after BDL, rats were treated with a neutralizing progesterone antibody for 1 wk. Cholangiocyte growth was measured by evaluating the number of bile ducts in liver sections. The expression of the progesterone synthesis pathway was evaluated in liver sections, cholangiocytes and NRC. Progesterone secretion was evaluated in supernatants from normal and BDL cholangiocytes and NRC. In vitro, NRC were stimulated with progesterone and cholangiocyte supernatants in the presence or absence of antiprogesterone antibody. Aminoglutethimide was used to block progesterone synthesis. Cholangiocytes and NRC express the PR-B nuclear receptor and PRGMC1, PRGMC2, and mPRalpha. In vivo, progesterone increased the number of bile ducts of normal rats, whereas antiprogesterone antibody inhibited cholangiocyte growth stimulated by BDL. Normal and BDL cholangiocytes expressed the biosynthetic pathway for and secrete progesterone. In vitro, 1) progesterone increased NRC proliferation; 2) cholangiocyte supernatants increased NRC proliferation, which was partially inhibited by preincubation with antiprogesterone; and 3) inhibition of progesterone steroidogenesis prevented NRC proliferation. In conclusion, progesterone may be an important autocrine/paracrine regulator of cholangiocyte proliferation.

Transverse cystocele repair with uterine preservation using native tissue.

The goals of this study were to describe the surgical procedure of the transverse cystocele repair with uterine preservation using native tissue and to examine the surgical complications and short-term anatomical outcomes of this operation. Patients who underwent transverse cystocele repair with uterine preservation at our institution were identified by retrospective chart review for the interval from January 2001 to September 2006. Sixty-nine patients were identified. Median point for first postoperative visit was 6.1 weeks (range 3-101 weeks). Average age was 66.6 +/- 13.1 years (range 33-89). Patients undergoing this procedure had no intraoperative complications and high frequency of initial anatomic success (defined as Baden-Walker halfway system grade 0 or 1 for anterior compartment) during a relatively short follow-up interval. Preoperatively, bladder grade averaged 2.6 with postoperative grade averaging 0.02. Based on our initial anatomical findings, we conclude that this surgical approach has merit for a subset of patients with adequate uterine support.