Picosecond lasers in cosmetic dermatology: where are we now? An overview of types and indications.

Q-switched lasers have undeniably revolutionized the field of laser dermatology since four decades ago. Just as the first-generation laser emits its photonic signal in a few nanoseconds, the picosecond laser delivers pulse widths of at least ten times shorter. These devices offer a powerful tool for treating a wide range of skin conditions with a minimal downtime for visible improvement. For the current study, a literature research was performed on the dermatological applications of picosecond laser. The literature searched on this topic between 1999 and 2023 accessible through various platforms produce a result of 62 articles. The included studies have discussed the application of picosecond laser technology in tattoo removal, treatment of epidermal and dermal pigmentation, and collagen remodeling. After sifting the data from the articles into tables, the results were discussed in detail. The study shows a lot of evidence towards the efficacy of picosecond laser, yet it draws attention to its downsides.

Laser interstitial thermotherapy (LITT) for breast cancer: dosimetry optimization and numerical simulation.

Surgical treatment is standard for the treatment of small breast cancers. Due to the pain and esthetic sequelae that can follow surgery, minimally invasive treatments are under investigation. Our aim was to conduct a dosimetry study of laser interstitial thermotherapy. Turkey tissue was used as an ex vivo model, and mammary glands from ewes were used as in vivo models. We used two different wavelength lasers (805 nm and 980 nm). Two types of fiber from two different manufacturers were used: bare fibers with a diameter of 600 µm and diffusing fiber. The diffusing fibers were 5 mm and 10 mm in length. We also used a computerized model to predict thermal damage and to correlate with the ex vivo and in vivo procedures using a constant and variable coefficient. The mathematical model was based on the finite element method for solving light distribution, bio-heat, and thermal damage equations. Based on our ex vivo and in vivo experiments, we found that the optimal configuration for this treatment was the use of the 980-nm laser at 4 W with bare fibers for a minimum treatment time of 150 s. We also developed a predictive mathematical model that showed good predictability of necrosis in line with the experimental data. Laser treatment is a promising therapy for small breast lesions. However, further development of treatment guidance is necessary to support its use in clinical practice.

Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial.

PURPOSE: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection. METHODS: Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death. RESULTS: There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months). CONCLUSIONS: This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.

Novel Therapies Boosting T Cell Immunity in Epstein Barr Virus-Associated Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumour of the head and neck affecting localised regions of the world, with the highest rates described in Southeast Asia, Northern Africa, and Greenland. Its high morbidity rate is linked to both late-stage diagnosis and unresponsiveness to conventional anti-cancer treatments. Multiple aetiological factors have been described including environmental factors, genetics, and viral factors (Epstein Barr Virus, EBV), making NPC treatment that much more complex. The most common forms of NPCs are those that originate from the epithelial tissue lining the nasopharynx and are often linked to EBV infection. Indeed, they represent 75-95% of NPCs in the low-risk populations and almost 100% of NPCs in high-risk populations. Although conventional surgery has been improved with nasopharyngectomy's being carried out using more sophisticated surgical equipment for better tumour resection, recent findings in the tumour microenvironment have led to novel treatment options including immunotherapies and photodynamic therapy, able to target the tumour and improve the immune system. This review provides an update on the disease's aetiology and the future of NPC treatments with a focus on therapies activating T cell immunity.

Combination of High Dose Hypofractionated Radiotherapy with Anti-PD1 Single Dose Immunotherapy Leads to a Th1 Immune Activation Resulting in a Complete Clinical Response in a Melanoma Patient.

The development of immunotherapy has recently modified the anti-tumor therapeutic arsenal; particularly, immune checkpoint inhibitors have led to a significant increase in overall survival. The current challenge is now to select good responder patients by identifying early biomarkers to propose therapeutic combinations that potentiate the efficacy of the therapy. Here we report the case of a 60-year-old man with superficial melanoma treated with high-dose hypo fractionated radiotherapy (H-SRT) combined with a single dose of anti-PD1 immunotherapy (Nivolumab) for a metastatic lymph node recurrence due to cancer progression. In this study, we present the results obtained regarding the activation of the Th1 immune response after H-SRT treatment followed by anti PD-1 therapeutic protocol. These results were correlated with clinical data to identify potential immunological biomarkers of treatment efficacy. This exceptional case report shows that a combination of H-SRT with a single dose of anti-PD1 immunotherapy may allow a better activation of the immune response in favor of a complete clinical response.

Photodynamic therapy for actinic keratosis of the forehead and scalp with the Aktilite CL 128: Is there a cut-off value for PpIX-weighted irradiance for effective treatment?

BACKGROUND/PURPOSE: Photodynamic therapy (PDT) is an established treatment for actinic keratosis (AK). Among the approved protocols in Europe, the most widely used involves irradiation with the Aktilite CL 128 (C-PDT). We aimed to assess the heterogeneity of irradiance over the treatment area when using C-PDT. We also investigated whether there is a cut-off value for protoporphyrin IX (PpIX)-weighted irradiance that may predict the treatment outcome of C-PDT. METHODS: An Ophir PD300 photodiode sensor connected to an Ophir Laser Star power meter was used to measure the irradiance delivered to 114 AKs of the scalp and forehead of 19 patients treated with C-PDT. The PpIX-weighted irradiances were deduced and cross-referenced with the complete responses at 3 months. RESULTS: From the measured irradiances ranging from 0.25 to 60 mW/cm2 (average: 31.94 mW/cm2 ), a standard deviation of 17.17 mW/cm2 was computed. Irradiance heterogeneity over the treatment area during C-PDT was demonstrated. The 66/114 AKs with a complete response at 3 months (57.89%) received a mean PpIX-weighted irradiance of 0.52 mW/cm2 vs 0.56 mW/cm2 for the resistant 48/114 AKs (42.11%). No significant effect of PpIX-weighted irradiance on the complete response at 3 months was found (odds ratio for a 0.1-unit change, 0.96; 95% confidence interval, 0.83 to 1.10; P = 0.53). Therefore, no cut-off value for PpIX-weighted irradiance that predicts treatment outcome could be identified. CONCLUSIONS: A device enabling homogeneous irradiation at a lower irradiance than the Aktilite CL 128 may therefore be suitable. This lower irradiance may further increase the treatment tolerance by patients.

Treatment of telangiectasia on the cheeks with a compact yellow (585 nm) semiconductor laser and a green (532 nm) KTP laser: a randomized double-blinded split-face trial.

OBJECTIVES: The primary objective of this study was to compare a traditional green KTP laser to a new investigational yellow laser (PhotoLase) in the treatment of facial telangiectasia in terms of the treatment outcomes. The secondary objective was to assess the functionality and reliability of the PhotoLase system from the perspective of the user. STUDY DESIGN/METHODS: The study was a randomized split-face double-blinded study that compared the treatment efficacy of the 532-nm KTP laser and the investigational 585-nm PhotoLase laser. One or two treatments were given based on the response of the first treatment. The improvement of telangiectasia was graded according to a 7-point Telangiectasia Grading Scale (TGS) by the subjects and blinded physicians. The subjects assessed the amount of pain during the treatments using Visual Analogue Scale (VAS), and evaluated adverse effects 2-3 days after the treatment(s) using a self-assessment form. RESULTS: At least 50% improvement was seen in 15/18 subjects after the first PhotoLase treatment, and a similar result was observed for KTP, as assessed by the blinded physicians (P = 0.29). In the subjects' assessment, 7/18 subjects had at least 50% improvement after the first PhotoLase treatment, whereas at least 50% improvement was observed for 10/18 subjects in the KTP side, the difference being significant (P = 0.008). The amount of pain was higher with PhotoLase compared to KTP (67.7 vs. 34.6, P < 0.001). There was no difference in the frequency of erythema, crusting or purpura between the devices, but more blistering and less edema were seen after PhotoLase treatment (P < 0.05). Treatment with PhotoLase was evaluated to be 4.7-fold faster than with KTP and the PhotoLase system was more compact, narrower, lighter, and easier to carry than KTP. CONCLUSIONS: The investigational PhotoLase laser enables significantly faster treatments, but the process is somewhat more painful than with KTP, otherwise providing a similar clinical outcome in the treatment of facial telangiectasia. Treatment Protocol Lasers Surg. Med. 51:223-229, 2019. © Wiley Periodicals, Inc.

Photodynamic therapy for glioblastoma: A preliminary approach for practical application of light propagation models.

PURPOSE: Photodynamic therapy (PDT) is a promising treatment modality to be added in the management of glioblastoma multiforme (GBM). Light distribution modeling is required for planning and optimizing PDT. Several models have been developed to predict the light propagation inside biological tissues. In the present study, two analytical methods of light propagation emitted from a cylindrical fiber source were evaluated: a discrete and a continuous method. METHODS: The two analytical approaches were compared according to their fluence rate results. Several cylindrical diffuse lengths were evaluated, and the relative deviation in the fluence rates was estimated. Moreover, a sensitivity analysis was conducted to compute the variance of each analytical model. RESULTS: The discrete method provided fluence rate estimations closer to the Monte-Carlo simulations than the continuous method. The sensitivity study results did not reveal significant differences between the variance of the two analytical models. CONCLUSIONS: Although the discrete model provides relevant light distribution, the heterogeneity of GBM tissues was not considered. With the improvement in parallel computing that drastically decreased the computing time, replacing the analytical model by a Monte-Carlo GPU-accelerated code appeared relevant to the GBM case. Nonetheless, the analytical modeling may still function in the optimization algorithms, which might be used in the Photodynamic treatment planning system. Lasers Surg. Med. 50:523-534, 2018. © 2017 Wiley Periodicals, Inc.

MRI assessment of treatment delivery for interstitial photodynamic therapy of high-grade glioma in a preclinical model.

BACKGROUND: High-grade gliomas are primary brain tumors that have shown increasing incidence and unfavorable outcomes. Local control is crucial to the management of this pathology. Photodynamic therapy (PDT), based on the light-induced activation of a photosensitizer (PS), achieves local treatment by inducing selective lesions in tumor tissue. OBJECTIVES: Previous studies have reported the outcomes of PDT for glioblastoma via immunohistological data. Our study aimed to evaluate MRI findings, including diffusion, and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation. MATERIALS AND METHODS: Twenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers. RESULTS: Elevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (P = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm3 versus 2.67 mm3 , P < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (P < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (P = 0.01). CONCLUSION: Diffusion and perfusion MRI revealed histological lesions. Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT. Lasers Surg. Med. 50:460-468, 2018. © 2017 Wiley Periodicals, Inc.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

BACKGROUND: Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. OBJECTIVES: This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. METHODS: The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. RESULTS: The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found. CONCLUSIONS: Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. 50:576-589, 2018. © 2018 Wiley Periodicals, Inc.

Treating hidradenitis suppurativa with photodynamic therapy.

Hidradenitis suppurativa is a chronic, recurring, and disabling inflammatory condition of the skin. There is no cure for hidradenitis suppurativa and treatment must be adapted to each individual patient. Several studies have been published since 2004 on the use of photodynamic therapy to treat hidradenitis suppurativa. The use of superficial or interstitial illumination with 5-amino-levulinic acid (5-ALA) or methylene blue (MB) have been proposed. Injecting 5-ALA or MB followed by illumination with a fiber optic sensor placed inside the lesion appears to be a better method of treating these thick lesions.

A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment.

AIM: Photodynamic therapy (PDT) appears to be a valuable new treatment modality for cancer therapy. Studies have reported successful application of PDT for glioblastoma. Here, we introduce a new device dedicated to intraoperative PDT delivered early after fluoro-guided resection combined with a transfer function that determines the treatment time based on the size of the surgical resection cavity. MATERIALS & METHODS: First, we describe the device, which is composed of a trocar, a balloon filled with a diffusing solution, and a fiber guide in which a cylindrical light diffuser is inserted. Ex vivo experiments were performed to measure the fluence rate inside biological tissues. A calibration factor was defined to convert power measurements into fluence rate values. Calf brains were used to simulate light propagation in human brain tissue, and the photosensitizer administration effect on optical properties was discussed. The temperature elevation during illumination was evaluated. RESULTS: Light power was measured in tissues surrounding the device during ex vivo experiments. Using the previously characterized calibration factor, power measurements were converted to fluence rate values to obtain the transfer function. No thermal elevation was observed during a 2-h temperature test, and the impact of protoporphyrin IX on brain optical properties was considered negligible. CONCLUSION: A discussion of experimental precision is presented. The light duration determined by the abacus had a standard deviation of <1 min. This value is weak compared with the total illumination time necessary to treat one patient. The main advantage of our device lies in its straightforward implementation of intraoperative PDT for neurosurgery with acceptable dosimetry and easy treatment time.

Image-guided surgery in gynecologic oncology.

Image-guided surgery is a relevant way to reduce surgical morbidity and maximize cytoreductive surgery approach especially in ovarian cancer. Sentinel lymph node detection is a promising approach to avoid radical lymph node dissection and is slightly becoming standard in daily practice in endometrial and cervical cancer surgery even if it needs to be evaluated more precisely. Regarding carcinomatosis of ovarian origin, detection and treatment of microscopic disease could be appropriate to avoid local recurrences. Photodiagnosis and photodynamic therapy are innovative techniques that allow to precise limits of excision (fluorescence-guided surgery) and to treat microscopic disease. Further developments of those strategies are necessary to become standard diagnosis tools and treatment options.

Treatment of a vulvar Paget's disease by photodynamic therapy with a new light emitting fabric based device.

INTRODUCTION: The non-invasive vulvar Paget's disease is an intra-epidermal carcinoma with glandular characteristics. It appears like an erythematous plaque. The main symptoms are pruritus and pain. The standard treatment is surgical excision in depth. This treatment is complicated with a severe morbidity and photodynamic therapy can be an alternative choice. However, the pain experienced during the photodynamic treatment of vulvar lesion is intense and leads to a premature interruption of the treatment. The light emitting fabric is a part of a device under clinical evaluation for the treatment of actinic keratosis with photodynamic therapy. We report the observation of a vulvar Paget's disease treated by this device with a satisfactory result and an excellent tolerance. CLINICAL OBSERVATION: The patient has been diagnosed with non-invasive vulvar Paget's disease for 25 years. The disease recurred constantly despite several imiquimod applications, LASER treatments and conventional photodynamic therapy. These procedures were complicated with intense pain. To improve the tolerance, we performed three PDT sessions a month apart using a 16% methyl-aminolevulinate cream (Metvixia® Galderma, Lausanne, Switzerland) with the light emitting fabric at low irradiance (irradiance = 6 mW/cm2 -fluence = 37 J/cm2 ) with a satisfactory result and an excellent tolerance. DISCUSSION: There are no controlled trials evaluating the efficacy of photodynamic therapy in the treatment of vulvar Paget's disease. The treatment and follow-up protocols in the literature are heterogeneous. Pain is the most common side effect with greater intensity for perineal locations where photodynamic therapy is impractical outside of anesthesia or hypnosis. CONCLUSION: We report the case of a multirecidivant non-invasive vulvar Paget's disease treated with a satisfactory result and an excellent tolerance by the new light emitting fabric device. A specific study is required but the light emitting fabric could be indicated for the treatment of Paget disease of perineal location. Lasers Surg. Med. 49:177-180, 2017. © 2017 Wiley Periodicals, Inc.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

OBJECTIVE AND STUDY DESIGN: Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. METHODS: This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. RESULTS: The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. CONCLUSION: This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol) is sufficient (respectively, excessive) to destroy actinic keratosis cells. Lasers Surg. Med. 49:686-697, 2017. © 2017 Wiley Periodicals, Inc.

Interstitial photodynamic therapy and glioblastoma: Light fractionation in a preclinical model.

BACKGROUND: Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a localized treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen, which results in the formation of cytotoxic species. The delivery of fractionated light may enhance treatment efficacy by reoxygenating tissues. OBJECTIVE: To evaluate the efficiency of two light-fractionation schemes using immunohistological data. MATERIALS AND METHODS: Human U87 cells were grafted into the right putamen of 39 nude rats. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomly divided into three groups: without light, with light split into 2 fractions and with light split into 5 fractions. Treatment effects were assessed using brain immunohistology. RESULTS: Fractionated treatments induced intratumoral necrosis (P < 0.001) and peritumoral edema (P = 0.009) associated with a macrophagic infiltration (P = 0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P = 0.024) or 2-fraction group (P = 0.01). Peripheral vascularization increased after treatment (P = 0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P = 0.028). CONCLUSION: Interstitial PDT with fractionated light resulted in specific tumoral lesions. The 5-fraction scheme induced more apoptosis but led to greater peripheral neovascularization. Lasers Surg. Med. 49:506-515, 2017. © 2016 Wiley Periodicals, Inc.

Laser-assisted delivery of vitamin C, vitamin E, and ferulic acid formula serum decreases fractional laser postoperative recovery by increased beta fibroblast growth factor expression.

BACKGROUND AND OBJECTIVE: Laser-assisted drug delivery is an emerging technology to achieve greater penetration by existing topical medications to reach desired targets in the tissue. The objective of this research was to study whether laser-assisted delivery of Vitamin C, E, and Ferulic immediately postoperatively of fractional ablative laser could improve wound healing. Secondary objectives were to evaluate the potential molecular markers involved in this wound-healing process. STUDY DESIGN/MATERIAL AND METHODS: A double blinded, prospective, single center, randomized split face trial of Vitamin C, E, and Ferulic topical formula #740019 to decrease postoperative recovery time in fractional ablative laser resurfacing for photo damage. Fifteen healthy men and women of ages 30-55 years were treated with the Vitamin C, E, and Ferulic acid serum to one side of face and vehicle to the other side of face, within 2 minutes immediately after fractional ablative CO2 laser surgery and daily during the healing process. Patients were evaluated daily on days 1-7 using photographs, patient questionnaires, and molecular evaluation. RESULTS: Clinically, postoperative Vitamin C, E, and Ferulic delivery resulted in decreased edema versus vehicle on postoperative day 7 and decreased erythema versus vehicle on postoperative days 3 and 5. Molecularly, the expression of basic fibroblast growth factor (bFGF) was significantly increased at day 5 on the lesion treated with Vitamin C, E, and Ferulic acid serum compared to vehicle control on the other side. CONCLUSION: This is first study to show that Vitamin C, E, and Ferulic acid correlate with more rapid wound healing post-fractional ablative laser. Elevated bFGF could be involved in the Vitamin C, E, and Ferulic acid-induced rapid wound healing.

Current laser applications in reconstructive microsurgery: A review of the literature.

BACKGROUND: Microvascular surgery has become an important method for reconstructing surgical defects following trauma, tumor resection, or burns. Laser-assisted microanastomoses (LAMA) were introduced by Jain in 1979 in order to help the microsurgeon reduce both operating time and complications. This article reviews the literature on clinical applications of LAMA. METHODS: A Medline literature search was performed and cross-referenced. Articles between 1979 and 2014 were included. Keywords used were laser, laser microanastomoses, laser microanastomosis, LAMA, and microsurgery. RESULTS: Only seven clinical studies using three different wavelengths were found in the literature: 1,064 nm (Nd: YAG), 10,600 nm (CO2), 514 nm (Argon), and 1,950 nm (Diode). Clinical outcomes, type of procedures, laser wavelength and parameters, and possible wider applications in the operating room are discussed in each case. CONCLUSIONS: The success rate for reconstructive free flap surgery and hand surgery achieved with LAMA appears promising. In particular, use of the 1950-nm diode laser for microsurgery is likely to increase in the near future.

Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy.

OBJECTIVE: Ovarian cancer prognosis remains dire after primary therapy. Recurrence rates are disappointingly high as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictive factors of recurrences. Folate receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells. Our aim was to determine if the Fischer model described by Rose et al could be used to evaluate folate-targeted therapies in preclinical studies. METHODS: NuTu-19 epithelial ovarian cancer cell line was used to induce peritoneal carcinomatosis in female Fischer 344 rats. FRα expression by NuTu-19 cells was assessed in vitro by immunofluorescence using "Cytospin®" protocol. In vitro folate-targeted compound uptake by NuTu-19 cells was evaluated by incubation of FRα-positive ovarian cancer cell lines (NuTu-19/SKOV-3/OVCAR-3/IGROV-1) with or without (control) a folate-targeted photosensitizer. Intracellular incorporation was assessed by confocal microscopy. Determination of in vivo FRα tissue expression by several organs of the peritoneal cavity was studied by immunohistochemistry. RESULTS: NuTu-19 cells express FRα which allows intracellular incorporation of folate-targeted compound by endocytosis. FRα is expressed in tumor tissue, ovary, and liver. Peritoneum, colon, small intestine, and kidney do not express the receptor. CONCLUSIONS: Female Fischer 344 rat is an inexpensive reproducible and efficient preclinical model to study ovarian peritoneal carcinomatosis folate-targeted therapies.