Augmented Reality Microsurgery: Proof of Concept for a Novel Approach to Microsurgical Field Visualization in Plastic Surgery.

BACKGROUND: Microsurgery is conducted on tiny anatomical structures such as blood vessels and nerves. Over the past few decades, little has changed in the way plastic surgeons visualize and interact with the microsurgical field. New advances in augmented reality (AR) technology present a novel method for microsurgical field visualization. Voice- and gesture-based commands can be used in real time to adjust the size and position of a digital screen. Surgical decision support and/or navigation may also be used. The authors assess the use of AR in microsurgery. METHODS: The video feed from a Leica Microsystems OHX surgical microscope was streamed to a Microsoft HoloLens2 AR headset. A fellowship-trained microsurgeon and three plastic surgery residents then performed a series of four arterial anastomoses on a chicken thigh model using the AR headset, a surgical microscope, a video microscope (or "exoscope"), and surgical loupes. RESULTS: The AR headset provided an unhindered view of the microsurgical field and peripheral environment. The subjects remarked on the benefits of having the virtual screen track with head movements. The ability of participants to place the microsurgical field in a tailored comfortable, ergonomic position was also noted. Points of improvement were the low image quality compared with current monitors, image latency, and the lack of depth perception. CONCLUSIONS: AR is a useful tool that has the potential to improve microsurgical field visualization and the way surgeons interact with surgical monitors. Improvements in screen resolution, latency, and depth of field are needed.

Updates on Enhanced Recovery after Surgery protocols for plastic surgery of the breast and future directions.

Introduction: Perioperative pain control is an important component of any plastic surgery practice. Due to the incorporation of Enhanced Recovery after Surgery (ERAS) protocols, reported pain level, opioid consumption, and hospital length of stay numbers have decreased significantly. This article provides an up-to-date review of current ERAS protocols in use, reviews individual aspects of ERAS protocols, and discusses future directions for the continual improvement of ERAS protocols and control of postoperative pain. ERAS components: ERAS protocols have proven to be excellent methods of decreasing patient pain, opioid consumption, and postanesthesia care unit (PACU) and/or inpatient length of stay. ERAS protocols have three phases: preoperative education and pre-habilitation, intraoperative anesthetic blocks, and a postoperative multimodal analgesia regimen. Intraoperative blocks consist of local anesthetic field blocks and a variety of regional blocks, with lidocaine or lidocaine cocktails. Various studies throughout the surgical literature have demonstrated the efficacy of these aspects and their relevance to the overall goal of decreasing patient pain, both in plastic surgery and other surgical fields. In addition to the individual ERAS phases, ERAS protocols have shown promise in both the inpatient and outpatient sectors of plastic surgery of the breast. Conclusion: ERAS protocols have repeatedly been shown to provide improved patient pain control, decreased hospital or PACU length of stay, decreased opioid use, and cost savings. Although protocols have most commonly been utilized in inpatient plastic surgery procedures of the breast, emerging evidence points towards similar efficacy when used in outpatient procedures. Furthermore, this review demonstrates the efficacy of local anesthetic blocks in controlling patient pain.

Impact of Age, Body Mass Index, and Resection Weight on Postoperative Complications in Reduction Mammaplasty.

BACKGROUND: The authors seek to evaluate the impact of age, body mass index (BMI), and resection weight, on postoperative complications in women undergoing primary bilateral reduction mammaplasty. METHODS: A retrospective review of all primary bilateral reduction mammaplasties between February of 2014 and August of 2018 was performed. Patient demographics, medical comorbidities, tobacco use, BMI, operative technique, operative time, resection weight, and complications were reviewed. RESULTS: Two hundred seventy-seven women were included. Mean age was 35.71 years, and BMI was 30.17 kg/m 2 . An inferior pedicle (53.07%) with Wise pattern resection (53.43%) was used most commonly. The minor complication rate was 49.1%, with superficial wounds (42.1%) occurring most commonly. Thirty-three women (11.9%) required greater than 2 months to heal. The major complication rate was 4.31%. BMI was not associated with minor or major complications on univariate analysis ( P = 0.1003 and P = 0.6163), but was associated with wound healing requiring greater than 2 months ( P = 0.0009), longer operative times ( P = 0.0002), and higher resection weights ( P < 0.00001). Greater age was associated with higher minor complication rates ( P = 0.0048). On multivariate analysis, BMI was associated with wound healing requiring greater than 2 months ( P = 0.0137), and age with minor complications ( P = 0.0180). No factors impacted major complication rates. CONCLUSIONS: Women with higher BMI are more likely to require larger resections, longer operative times, and are at higher risk for wound healing requiring greater than 2 months. Although BMI is an important consideration for determining operative candidacy, the benefits of reduction may outweigh these risks in carefully selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Impact of Patient and Operative Factors on Nipple-Areola Complex Sensation after Bilateral Reduction Mammaplasty.

Background: Alteration of nipple-areola complex (NAC) sensation following reduction mammoplasty is commonly reported and may impact patient satisfaction. The goal of this study was to evaluate the patient and procedural factors that influence the rates of subjective NAC sensation change. Methods: A retrospective review of all patients who underwent primary bilateral reduction mammoplasty between January 2014 and August 2018 at the senior author's institution was performed. The primary outcome measured was subjective NAC sensation via digital stimulation of the NAC with the patient reporting sensation as decreased, unchanged, or increased. Results: In total, 274 patients met inclusion criteria. NAC sensation was decreased in 19% of breasts, unchanged in 74%, and increased in 7.3%. Patients who underwent vertical pattern, superomedial pedicle reductions were more likely to report a decrease in sensation than those who underwent Wise pattern, inferior pedicle reductions (26% versus 13%; P = 0.0025). Patients with minor complications were more likely to report decreased NAC sensation than those who did not (23% versus 15%; P = 0.0264). The only factor found to be associated with increased sensation was operative time. Conclusions: Patients were more likely to report decreased sensation if a vertical skin resection, superomedial pedicle was chosen, or if patients experienced a minor complication. The only factor found to correlate with increased NAC sensation was longer operative times.

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices.

PURPOSE: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. MATERIALS AND METHODS: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. RESULTS: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. CONCLUSIONS: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy.

Microsurgery in the era of COVID-19.

The COVID-19 pandemic has presented new challenges to microsurgeons. The virus is highly transmissible, with increased risk during operations that involve the aerodigestive tract. It is important to be able to identify high-risk operations and scenarios to guide management decisions and selection of personal protective equipment. Preoperative testing is a key element in identifying high-risk scenarios, and preoperative testing protocols are essential to maintaining safety in the COVID-19 era. Because COVID-19 can be transmitted via the conjunctiva, adaptations to loupes and microscopes are necessary to safely perform microsurgery in high-risk scenarios. We outline a potential risk stratification algorithm, as well as precautions for each scenario. Potential areas for innovation are also discussed.

"Does ERAS benefit higher BMI patients? A single institutional review".

BACKGROUND: Enhanced recovery after surgery (ERAS) is increasingly used in plastic surgery to optimize patient care. Mitigating the risk of postoperative complications is particularly important in patients with risk factors, such as obesity. The objective of this study is to evaluate the impact of the ERAS pathway in patients, stratified by BMI, undergoing free flap breast reconstruction on length of stay and complications. METHODS: A retrospective review of all patients who underwent abdominally based free flap breast reconstruction from January 2014 to December 2017 was performed. Data collected include participation in the ERAS protocol, patient demographics, length of stay (LOS), complications (minor and major), and 30-day reoperation rates. RESULTS: A total of 123 patients met the inclusion criteria, with 36 non-ERAS and 87 ERAS patients. ERAS patients had a shorter length of stay than non-ERAS patients (4.14 vs. 4.69, p = 0.049). Higher BMI patients progressively benefited from their involvement in an ERAS pathway: class I obese patients had an LOS decrease of 0.99 days (p = 0.048) and class II+ obese patients had an LOS decrease of 1.35 days (p = 0.093). Minor complications, major complications, and reoperation rates were similar between ERAS and non-ERAS patients (p>0.05). CONCLUSION: Utilization of an ERAS protocol for free flap breast reconstruction safely decreases LOS, especially with increasing BMI. Patients benefit from an ERAS protocol without increasing risk of postoperative complications, compared to non-ERAS patients of similar BMIs.

A Protocol for Safe Head and Neck Reconstructive Surgery in the COVID-19 Pandemic.

The COVID-19 pandemic has had significant implications for citizens globally and for the healthcare system, including plastic surgeons. Operations of the upper aerodigestive tract, including head and neck reconstruction and craniomaxillofacial procedures, are of particularly high risk because they may aerosolize the virus and lead to severe surgeon and surgical team illness. Until the virus is eradicated or widespread vaccination occurs, we recommend certain precautions to safely perform these operations. We propose evolving algorithms for head and neck reconstruction and facial trauma surgeries to maintain provider safety. Central to these guidelines are preoperative COVID-19 testing, appropriate personal protective equipment, and operative techniques/principles that minimize operative time and aerosolization of the virus. We aim to provide efficient care to our patients throughout this pandemic, while maintaining the safety of plastic surgeons and other healthcare providers.

Breast Reconstruction in Obese Patients: The Fat Grafted Latissimus versus Abdominal Free Tissue Transfer.

Immediate fat grafting to the pedicled myocutaneous latissimus dorsi (LD) flap has recently gained in popularity as a means to supplement volume for breast reconstruction. The aim of this study is to compare complication rates of the immediately fat-grafted LD to free tissue transfer in the obese population. METHODS: In this retrospective cohort, 82 patients (149 breasts) from 2015 to 2019 were included. Patients underwent either unilateral or bilateral breast reconstruction with either LD with immediate fat grafting or abdominal-based free tissue transfer. Included patients had a body mass index ≥ 30 kg/m2 at the time of surgery. Complication data were recorded as minor, major, and medical complications. Procedure characteristics and postoperative data were also studied. RESULTS: Minor complication rates between the LD with immediate fat grafting and free tissue transfer cases were similar (26.9% versus 26%, respectively). The free tissue transfer group had a significantly higher rate of major complications (20.3% versus 3.8%; P = 0.048) and medical complications (10.6% versus zero). Finally, the LD with immediate fat grafting group had significantly shorter operating room times, hospital length of stay, and fewer donor-site revisions. CONCLUSIONS: LD with immediate fat grafting offers the benefit of a totally autologous reconstruction without the risks of abdominal-based microvascular free tissue transfer or an implant. Favorable complication rates, shorter operative times, and shorter hospital length of stay make this reconstructive option a safe alternative to free tissue transfer in the obese population.

Percutaneous Fasciotomies versus Traditional Keystone Flap: Evaluating Tension in Complex Wound Closure.

BACKGROUND: The keystone flap is a popular reconstructive option for closure of cutaneous defects. Traditionally, this is a perforator-based fasciocutaneous advancement flap that uses both skin incision and fascial release. We propose a limited skin incision technique that utilizes percutaneous fasciotomies to accomplish wound closure. METHODS: Fresh cadavers were used to compare closure techniques in traditional keystone flaps versus percutaneous fasciotomy technique. Each cadaver served as its own control; traditional keystone flaps were performed on the right side, experimental fasciotomy technique on the left. Bilateral large wound defects were created in 6 anatomical locations: anterior leg, lateral thigh, buttocks, lower back, upper back, and brachium. These defects could not be closed primarily, as defined by tension >25 Newtons or rupture of a 2-0 nylon suture. Twenty-four flaps were created. Keystone flaps were designed on the right side using a 1:1 ratio of defect size to flap width, incorporating both skin and fascial incisions. On the left, percutaneous fasciotomies were drawn using a mirror template and performed through two small access incisions. If wound closure could not be achieved by fasciotomy alone, additional incisional release was performed incrementally until closure was obtained. The tension of closure was measured using a PESOLA (10 N, 25 N) tensiometer (Chandelle, Switzerland), and the average of three recordings was used. Tension was measured at various stages of flap development including: keystone flap (posterior fascia, lateral fascia, V-Y skin closure) versus percutaneous fasciotomy (posterior fascia, lateral fascia, posterior skin). Statistical analysis was completed using Wilcoxon Signed Rank test to compare the two techniques. RESULTS: Lower tension closures were achieved through release of the posterior fascia in the traditional keystone flap compared to the percutaneous fasciotomy technique. These differences in tension were statistically significant (P < 0.001). Release of the lateral fascia in the keystone flap resulted in a similar decrease in tension (P < 0.01). The percentage drop in tension before and after each particular intervention was measured. No significant difference was found between these 2 groups. CONCLUSIONS: When compared with the traditional keystone flap, the percutaneous fasciotomy technique displayed higher tensions in closure. However, this technique showed the ability to close defects in certain locations of the body without excessive tension and should be considered as an option in soft-tissue reconstruction.

Pressure ulcers and perineal reconstruction.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Discuss the approach and rationale of pressure sore management, including specific techniques of bone biopsy and postoperative care resulting in a significant reduction in recurrence rates. 2. Develop a surgical plan for reconstructing defects of the perineum, taking into account the local tissue factors and the soft-tissue requirements for reconstruction. SUMMARY: As close as the buttocks and the perineum are anatomically, the clinical settings and the solutions to wound problems in these areas are quite different. The ubiquitous "pressure ulcer" presents more commonly as a clinical management problem than a reconstruction issue. On the other hand, the perineal defect is almost always a reconstruction challenge following tumor ablation. For these reasons, the authors have chosen to separate this Continuing Medical Education offering into two parts. The first part addresses the pressure ulcer, while the latter discusses the perineum.

Long-term (10-year) gastrointestinal and genitourinary toxicity after treatment with external beam radiotherapy, radical prostatectomy, or brachytherapy for prostate cancer.

Objective.To examine gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated in 1999 with external beam radiotherapy (RT), prostate interstitial brachytherapy (PI) or radical prostatectomy (RP). Methods. TThe records of 525 patients treated in 1999 were reviewed to evaluate toxicity. Late GI and GU morbidities were graded according to the RTOG late morbidity criteria. Other factors examined were patient age, BMI, smoking history, and medical co-morbidities. Due to the low event rate for late GU and GI toxicities, a competing risk regression (CRR) analysis was done with death as the competing event. Results. Median follow-up time was 8.5 years. On CRR univariate analysis, only the presence of DM was significantly associated with GU toxicity grade >2 (P = 0.43, HR 2.35, 95% Cl = 1.03-5.39). On univariate analysis, RT and DM were significantly associated with late GI toxicity. On multivariable analysis, both variables remained significant (RT: P = 0.038, HR = 4.71, CI = 1.09-20.3; DM: P = 0.008, HR = 3.81, 95% Cl = 1.42-10.2). Conclusions. Late effects occur with all treatment modalities. The presence of DM at the time of treatment was significantly associated with worse late GI and GU toxicity. RT was significantly associated with worse late GI toxicity compared to PI and RP.

Wound microenvironment sequesters adipose-derived stem cells in a murine model of reconstructive surgery in the setting of concurrent distant malignancy.

BACKGROUND: It is unclear whether mesenchymal stem cells that are applied to regenerate wound tissues can migrate to existing tumors and enhance their growth. The authors investigated whether adipose-derived stem cells had any effect on the growth and progression of distant tumors when applied to a skin wound. METHODS: The authors subcutaneously injected murine 4T1 breast cancer cells into all BALB/c-nu/nu mice. After tumor injection, mice were randomized to five groups (five mice per group) based on the means of co-introduction of green fluorescent protein-labeled adipose-derived stem cells, if any. In group 1, adipose-derived stem cells were combined and co-injected subcutaneously. In group 2, they were injected subcutaneously at a distant anatomical site. In group 3, they were injected intravenously. In group 4, they were delivered via a human acellular dermal matrix to a distant skin wound. In group 5, no adipose-derived stem cells were introduced. RESULTS: After 2 weeks, tumor volume increased in group 1 (356.5 ± 44.4 mm(3)), followed by group 3 (256.6 ± 47.1 mm(3)) and then group 2 (201.6 ± 28.6 mm(3)). In group 4, in which adipose-derived stem cells carried on acellular dermal matrix were applied to a wound distant to the primary tumor, the tumor volume was 143.8 ± 50.9 mm(3), which was similar to that observed in the control group (group 5; 167.8 ± 29.9 mm(3)). CONCLUSIONS: The authors' findings suggest that the wound microenvironment can retain adipose-derived stem cells, preventing their homing and stromal contribution to a distant neoplastic focus. These findings are an important first step in establishing the feasibility and safety of utilizing adipose-derived stem cell therapy for reconstructive surgery in the setting of malignancy.

Fibroblasts share mesenchymal phenotypes with stem cells, but lack their differentiation and colony-forming potential.

BACKGROUND INFORMATION: Although MSCs (mesenchymal stem cells) and fibroblasts have been well studied, differences between these two cell types are not fully understood. We therefore comparatively analysed antigen and gene profiles, colony-forming ability and differentiation potential of four human cell types in vitro: commercially available skin-derived fibroblasts [hSDFs (human skin-derived fibroblasts)], adipose tissue-derived stem cells [hASCs (human adipose tissue-derived stem cells)], embryonic lung fibroblasts (WI38) and dermal microvascular endothelial cells [hECs (human dermal microvascular endothelial cells)]. RESULTS: hSDFs, hASCs and WI38 exhibited a similar spindle-like morphology and expressed same antigen profiles: positive for MSC markers (CD44, CD73 and CD105) and fibroblastic markers [collagen I, HSP47 (heat shock protein 47), vimentin, FSP (fibroblast surface protein) and αSMA (α smooth muscle actin)], and negative for endothelial cell marker CD31 and haemopoietic lineage markers (CD14 and CD45). We further analysed 90 stem cell-associated gene expressions by performing real-time PCR and found a more similar gene expression pattern between hASCs and hSDFs than between hSDFs and WI38. The expression of embryonic stem cell markers [OCT4, KLF4, NANOG, LIN28, FGF4 (fibroblast growth factor 4) and REST] in hASCs and hSDFs was observed to differ more than 2.5-fold as compared with WI38. In addition, hSDFs and hASCs were able to form colonies and differentiate into adipocytes, osteoblasts and chondrocytes in vitro, but not WI38. Moreover, single cell-derived hSDFs and hASCs obtained by clonal expansion were able to differentiate into adipocytes and osteoblasts. However, CD31 positive hECs did not show differentiation potential. CONCLUSIONS: These findings suggest that (i) so-called commercially available fibroblast preparations from skin (hSDFs) consist of a significant number of cells with differentiation potential apart from terminally differentiated fibroblasts; (ii) colony-forming capacity and differentiation potential are specific important properties that discriminate MSCs from fibroblasts (WI38), while conventional stem cell properties such as plastic adherence and the expression of CD44, CD90 and CD105 are unspecific for stem cells.

PSA bounce and biochemical failure after brachytherapy for prostate cancer: a study of 820 patients with a minimum of 3 years of follow-up.

PURPOSE: To determine clinical or dosimetric factors associated with a prostate-specific antigen (PSA) bounce, as well as an association between a PSA bounce and biochemical relapse-free survival (bRFS), in patients treated with iodine-125 brachytherapy. METHODS AND MATERIALS: A variety of clinical and treatment factors were examined in 820 patients who had a minimum of 3 years of PSA follow-up with T1-T2cN0M0 prostate cancer. Four different PSA threshold values were used for defining a PSA bounce: a PSA rise of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL. RESULTS: A PSA bounce of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL was noted in 247 patients (30.1%), 161 (19.6%), 105 (12.8%), and 78 (9.5%), respectively. The median time to the first PSA rise was 17.4, 16.25, 16.23, and 15.71 months, respectively, vs. 34.35 months for a biochemical failure (p < 0.0001). A PSA rise of ≥ 0.2 ng/mL was the only definition for which there was a significant difference in bRFS between bounce and non-bounce patients. The 5-year bRFS rate of patients having a PSA bounce of ≥0.2 was 97.7% vs. 91% for those who did not have a PSA bounce (p = 0.0011). On univariate analysis for biochemical failure, age, risk group, and PSAs per year had a statistically significant correlation with PSA bounce of ≥ 0.2 ng/mL. On multivariate analysis, age and PSAs per year remained statistically significant (p < 0.0001 and p = 0.0456, respectively). CONCLUSIONS: A bounce definition of a rise ≥ 0.2 ng/mL is a reliable definition among several other definitions. The time to first PSA rise is the most valuable factor for distinguishing between a bounce and biochemical failure.

Adipose tissue-derived stem cells enhance bioprosthetic mesh repair of ventral hernias.

BACKGROUND: Bioprosthetic mesh used for ventral hernia repair becomes incorporated into the musculofascial edge by cellular infiltration and vascularization. Adipose tissue-derived stem cells promote tissue repair and vascularization and may increase the rate or degree of tissue incorporation. The authors hypothesized that introducing these cells into bioprosthetic mesh would result in adipose tissue-derived stem cell engraftment and proliferation and enhance incorporation of the bioprosthetic mesh. METHODS: Adipose tissue-derived stem cells were isolated from the subcutaneous adipose tissue of syngeneic Brown Norway rats, expanded in vitro, and labeled with green fluorescent protein. Thirty-six additional rats underwent inlay ventral hernia repair with porcine acellular dermal matrix. Two 12-rat groups had the cells (1.0 x 10(6)) injected directly into the musculofascial/porcine acellular dermal matrix interface after repair or received porcine acellular dermal matrix on which the cells had been preseeded; the 12-rat control group received no stem cells. RESULTS: At 2 weeks, adipose tissue-derived stem cells in both stem cell groups engrafted, survived, migrated, and proliferated. Mean cellular infiltration into porcine acellular dermal matrix at the musculofascial/graft interface was significantly greater in the preseeded and injected stem cell groups than in the control group. Mean vascular infiltration of the porcine acellular dermal matrix was significantly greater in both stem cell groups than in the control group. CONCLUSIONS: Preseeded and injected adipose tissue-derived stem cells engraft, migrate, proliferate, and enhance the vascularity of porcine acellular dermal matrix grafts at the musculofascial/graft interface. These cells can thus enhance incorporation of porcine acellular dermal matrix into the abdominal wall after repair of ventral hernias.

Five year biochemical recurrence free survival for intermediate risk prostate cancer after radical prostatectomy, external beam radiation therapy or permanent seed implantation.

OBJECTIVE: To compare biochemical recurrence-free survival (bRFS) for patients with intermediate-risk prostate cancer treated by retropubic radical prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), external beam radiation therapy (RT), or permanent seed implantation (PI). METHODS: Patients treated for intermediate-risk prostate cancer per National Comprehensive Cancer Network guidelines from 1996 to 2005 were studied. Variables potentially affecting bRFS were examined using univariate and multivariate Cox regression analysis. Five-year bRFS rates were calculated by actuarial methods; bRFS was calculated using Kaplan-Meier analysis. Nadir +2 definition of biochemical failure was used for RT and PI patients; a PSA ≥ 0.4 ng/mL was used for radical prostatectomy (RP) patients. Time to initiation of salvage therapy was compared for each treatment group using the Kruskal-Wallis test. RESULTS: Nine-hundred seventy-nine patients were analyzed with a median follow-up of 65 months. Five years bRFS rate was 82.8% for all patients (89.5% PI, 85.7% RT, 79.9% RRP, and 60.2% LRP). Patients treated by LRP had significantly worse bRFS than RT (P < .0001), PI (P < .0001), or RRP patients (P = .0038). Treatment modality (P < .0001) and average number of PSA tests per year (P < .0001) were the only independent predictors of bRFS on multivariate analysis. Median time to initiation of salvage therapy from time of treatment was 28.6 months for all patients (26.1 RP, 21.0 LRP, 47.4 PI, 47.8 RT; P < .0001). CONCLUSIONS: Patients with intermediate-risk prostate cancer choosing PI, RT, or RRP appear to have improved 5-year bRFS and delayed salvage therapy compared with LRP.

Endothelial and stem cell interactions on dielectrophoretically aligned fibrous silk fibroin-chitosan scaffolds.

Regenerative tissue engineering requires biomaterials that would mimic structure and composition of the extracellular matrix to facilitate cell infiltration, differentiation, and vascularization. Engineered scaffolds composed of natural biomaterials silk fibroin (SF) and chitosan (CS) blend were fabricated to achieve fibrillar nano-structures aligned in three-dimensions using the technique of dielectrophoresis. The effect of scaffold properties on adhesion and migration of human adipose-derived stem cells (hASC) and endothelial cells (HUVEC) was studied on SFCS (micro-structure, unaligned) and engineered SFCS (E-SFCS; nano-structure, aligned). E-SFCS constituted of a nano-featured fibrillar sheets, whereas SFCS sheets had a smooth morphology with unaligned micro-fibrillar extensions at the ends. Adhesion of hASC to either scaffolds occurred within 30 min and was higher than HUVEC adhesion. The percentage of moving cells and average speed was highest for hASC on SFCS scaffold as compared to hASC cocultured with HUVEC. HUVEC interactions with hASC appeared to slow the speed of hASC migration (in coculture) on both scaffolds. It is concluded that the guidance of cells for regenerative tissue engineering using SFCS scaffolds requires a fine balance between cell-cell interactions that affect the migration speed of cells and the surface characteristics that affects the overall adhesion and direction of migration.

Human tissue-resident stem cells combined with hyaluronic acid gel provide fibrovascular-integrated soft-tissue augmentation in a murine photoaged skin model.

BACKGROUND: Transplantation of adipose tissue-resident mesenchymal stem cells has been found to contribute to the establishment of a supportive fibrovascular network. The authors sought to evaluate the potential of human adipose tissue-derived stem cells to integrate with nonanimal stabilized hyaluronic acid as a novel injectable soft-tissue filler. METHODS: Cell proliferation was measured by bromodeoxyuridine incorporation. Interactions of adipose tissue-derived stem cells with hyaluronic acid were documented by scanning electron microscopy. The effect of this combination on procollagen mRNA was assessed by real-time polymerase chain reaction. The potential therapeutic effects were evaluated in an athymic murine photoaged skin model by histology and by high-resolution magnetic resonance imaging. Angiogenesis was assessed by microvessel density analysis. RESULTS: Under in vitro culture conditions, the authors found an equal proliferation capacity of adipose tissue-derived stem cells grown on hyaluronic acid versus controls. Scanning electron microscopy showed enhanced establishment of complex microvillous networks in adipose tissue-derived stem cells adherent to hyaluronic acid compared with controls. Adipose tissue-derived stem cells and hyaluronic acid induced a significant increase in procollagen 1-alpha-2 mRNA expression compared with controls. In an athymic murine photoaged skin model, injection of this combination ablated photoinduced skin wrinkles. Magnetic resonance imaging revealed a consistent and stable volume fill by adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid at 3 weeks. Adipose tissue-derived stem cells actively incorporated into the hyaluronic acid fill and showed an organized fibrovascular network at 3 weeks. CONCLUSION: The combination of adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid holds promise as a tool with which to achieve lasting volume fill in reconstructive surgical soft-tissue augmentation.

The importance of serum prostate-specific antigen testing frequency in assessing biochemical and clinical failure after prostate cancer treatment.

OBJECTIVES: To assess the relationship between prostate-specific antigen (PSA) testing frequency and biochemical failure (bF) and clinical failure (cF). METHODS: The records of 5616 patients with low-, intermediate-, or high-risk prostate cancer treated (brachytherapy, external beam radiotherapy, or surgery) between 1996 and 2007 were reviewed. Factors influencing bF and cF were recorded including age, initial PSA, androgen deprivation, race, clinical stage, biopsy Gleason score, and the frequency of follow-up PSA testing. Univariate and multivariate analyses were performed to assess the effect of these factors on bF and cF. Sensitivity and specificity were calculated to determine the optimal frequency of PSA testing. RESULTS: The median follow-up is 45 months. The median number of PSA tests per year before the occurrence of bF and cF is 1.9 for both endpoints. The multivariate analysis of factors significantly associated with bF and cF demonstrate that PSA frequency, initial PSA, clinical stage, and biopsy Gleason score are independently predictive of outcome. PSA testing achieves the best sensitivity and specificity when 2 PSA tests are drawn per year for both bF (sensitivity = 66.3%, specificity = 58.0%) and cF (sensitivity = 75.1%, specificity = 60.3%). CONCLUSIONS: The frequency of PSA testing is strongly associated with the detection of bF and cF. Because it is a variable that can be controlled, PSA testing frequency should be standardized to minimize spurious conclusions from studies with bF and cF endpoints. The sensitivity and specificity can be optimized by obtaining 2 PSA tests per year.