Histological changes in facial melasma after treatment with triple combination cream with or without oral tranexamic acid and/or microneedling: A randomised clinical trial.

Background Melasma is an acquired dyschromia with several histologic alterations in the epidermis, basement membrane and upper dermis. The treatment of melasma is challenging due to the irregular response and chronicity of the disease. To date, there are no curative strategies, largely due to the limited understanding of the intrinsic effects of each treatment. Objectives The objective of the study was to evaluate the histological changes promoted by triple combination cream, with or without complementary treatment with microneedling and oral tranexamic acid, in the treatment of melasma. Methods A factorial, randomised, controlled and evaluator-blinded clinical trial was performed involving 64 women with facial melasma, divided in four groups, who underwent 60 days of treatment with triple combination cream alone (control group) or combined with two monthly microneedling sessions (microneedling group), TA 250 mg twice daily (tranexamic acid group), or both tranexamic acid group and microneedling group. The participants underwent biopsy of the area with melasma at inclusion (D1) and D60. The primary outcomes were the variation (D1 × D60) between the variables: Thickness of the epidermis and stratum corneum, stratum corneum compaction and solar elastosis; melanin density in the epidermis and upper dermis; proportion between the extension of the nonintact and intact basement membrane zone; mast cell count in the upper dermis; melanocyte count in the basal layer, pendulum melanocyte count and melanocyte area; immunostaining density of vascular endothelial growth factor; stem cell factor and keratinocyte growth factor. Results One participant in the TG discontinued tranexamic acid due persistent headache; and herpes simplex occurred in three patients after microneedling. The groups showed a 24% (CI95%: 17-35%; P < 0.01) reduction in epidermal melanin density. There was no change in dermal melanin density or the area of melanocytes after treatment. There was an overall 25% (CI95%: 7-42%; P < 0.01) reduction in the number of pendulum melanocytes, especially in the microneedling and tranexamic acid group, that presented a 41% (CI95%: 7-73%; P < 0.01) reduction. The extension of the nonintact basal membrane relative to the intact basal membrane decreased after treatment, especially in microneedling group and microneedling and tranexamic acid group. There was an increase of 13% (CI95%: 5-21%; P = 0.02) in epidermal thickness and 6% (CI95%: 0-22%; P = 0.04) thinning of the stratum corneum in the groups. All groups showed stratum corneum compaction. Solar elastosis improved only in the microneedling group and microneedling and tranexamic acid group. Vascular endothelial growth factor immunostaining increased 14% (CI95%: 4-24%; P = 0.03) in the groups; and stem cell factor increased only in microneedling group. There was no change in the number of mast cells, CD34 and keratinocyte growth factor immunostaining. Limitations The site of biopsy may not represent all of the facial melasma and the immunohistochemical sensitivity of the cytokines does not have a stoichiometric relationship with proteins. Conclusion A greater thickness of the epidermis is associated with melasma bleaching. Dermal melanin seems to have no impact on melasma prognosis. Damage to the skin barrier and stimulus of angiogenesis should be avoided in the treatment of melasma. Microneedling complements the topical treatment of melasma by improving patterns of skin photoaging. Oral tranexamic acid complements the topical treatment of melasma by inhibiting the stem cell factor.

Prophylaxis for mucositis induced by ambulatory chemotherapy: systematic review.

AIM: The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory antineoplastic chemotherapy. BACKGROUND: Oral mucositis in patients undergoing chemotherapy is a side effect that can impact the quality of treatment and can interfere with eating and therapeutic adherence. DESIGN: Quantitative systematic review. DATA SOURCES: Relevant databases were searched, from January 2002-July 2013, by using the combination of the keywords mucositis, stomatitis, neoplasms, antineoplastic agents, drug therapy, prevention and control and chemotherapy. REVIEW METHODS: Two researchers independently read the titles and abstracts from every cross-reference. The quality of the included studies was analysed by the Jadad Scale and the Cochrane Collaboration Risk of Bias Tool. Data were extracted from the selected studies with a data collection form developed specifically for this purpose. RESULTS: Of the 23 controlled clinical trials that were identified in this study, five articles evaluated the use of oral cryotherapy to prevent oral mucositis and three studies analysed the prophylactic use of glutamine. Interventions of protocols for oral care, palifermin, allopurinol and chlorhexidine were evaluated by two articles each. Interventions of zinc sulphate, amifostine, chewing gum, sucralfate, recombination human intestinal trefoil factor, kefir and vitamin E were evaluated by one article each. CONCLUSION: There is strong evidence that cryotherapy can prevent oral mucositis arising from ambulatory treatment with 5-flurouracil chemotherapy. Other interventions, although showing positive results in preventing oral mucositis, require further study to confirm their conclusions.

Synergism between keratinocyte growth factor and carboxymethyl chitosan reduces pericardial adhesions.

BACKGROUND: Mesothelial injury is the pivot in the development of adhesions. An increase in the proliferation of mesothelial cells was verified by in vitro studies with the use of keratinocyte growth factor (KGF). This study investigated the influence of KGF associated with thermo-sterilized carboxymethyl chitosan (NOCCts) in the reduction of pericardial adhesions. METHODS: An induction model of pericardial adhesion was carried out in 24 pigs. Animals were randomly allocated to receive topical application of KGF, KGF + NOCCts, NOCCts, or saline (control). At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histologic sections were stained with sirius red for a morphometric evaluation using a computer-assisted image analysis system. Cytokeratin AE1/AE3 immunostaining were employed to identify mesothelial cells. RESULTS: The severity score expressed in median (minimum to maximum), in relation to the control group (17 [15 to 18]), was lower in the KGF + NOCCts group (7 [6 to 9], p < 0.01) followed by the KGF group (11.5 [9 to 12], 0.01 < p < 0.05) and the NOCCts group (12 [9 to 14], p > 0.05). The dissection time was significantly lower in the KGF + NOCCts group (7.1 + or - 0.6 vs 33.9 + or - 9.2 minutes, p < 0.001). A significantly less sharp dissection was also required in the KGF + NOCCts group. In the adhesion segment, a decreased collagen proportion was found in the KGF + NOCCts group (p < 0.05). Mesothelial cells were present more extensively in groups in which KGF was delivered (p = 0.01). CONCLUSIONS: The use of KGF associated with NOCCts resulted in a synergic action that decreases postoperative pericardial adhesions in a highly significant way.

Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions.

BACKGROUND: Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions. METHODS: Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system. RESULTS: The severity score was lower in the KGF group than in the control group (11.5 vs 17, p=0.005). The dissection time was lower in the KGF group (9.2+/-1.4 min vs 33.9+/-9.2 min, p=0.004) and presented a significant correlation with the severity score (r=0.83, p=0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly lower in the KGF group than in the control group. CONCLUSION: The stimulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies.