Nanze Yu

Marjolin’s ulcer: a preventable malignancy arising from scars

BackgroundMarjolin’s ulcer (MU) is a rare malignancy arising from various forms of scars. This potentially fatal complication typically occurs after a certain latency period. This article attempts to reveal the importance of the latency period in the prevention and early treatment of the malignancy.MethodsA retrospective review of 17 MU patients who underwent surgical procedures between June of 2005 and December 2011 was conducted. Etiology of injuries, latency period, repeated ulceration, and outcomes were recorded. This observational report reveals characteristics of patients who develop MU.ResultsAn incidence of 0.7% of MU was found amongst patients complaining of existing scars in our study; burns and trauma were the most common etiology of MU. The mean latency period was 29 years (SD = 19) and the mean post-ulceration period was 7 years (SD = 9). Statistical analysis revealed a negative correlation between the age of patients at injury and the length of latency period (r = −0.8, P <0.01), as well as the lengths of pre-ulceration and post-ulceration periods (r = −0.7, P <0.01).ConclusionsPatients experience different lengths of pre- and post-ulceration periods during the latency period. Younger patients tend to have a longer latency period. Skin breakdown on chronic scars and chronic unhealed ulcers are two main sources of MU. MU may be preventable with a close surveillance of the ulcer during the latency period.

A Systemic Review of Autologous Fat Grafting Survival Rate and Related Severe Complications

Objective: Clinical application of autologous fat grafting (AFG) is quickly expanding. Despite the widely acceptance, long-term survival rate (SR) of AFG remains a question not yet solved. Meanwhile, although rare, severe complications related to AFG including vision loss, stroke even death could be seen in the literature. Data Sources: A comprehensive research of PubMed database to June 2013 was performed according to guidelines of the American Society of Plastic Surgeons Fat Graft Task Force Assessment Methodology. Articles were screened using predetermined inclusion and exclusion criteria. Study Selection: Data collected included patient characteristics, surgical technique, donor site, recipient site, graft amount, and quantified measurement methods. Patient cohorts were pooled, and SR was calculated. All the severe complications were also summarized according to the different clinical characteristics. Results: Of 550 articles, 16 clinical articles and 10 animal studies met the inclusion criteria and provided quantified measurement methods. Totally, 596 patients were included. SR varied from 34% to 82% in breast and 30–83% in the facial area. Nude mice were applied to investigate human fat grafting SR (38.3–52.5% after 15 weeks). Rabbits were commonly used to study animal AFG SR (14.00–14.56% after 1-year). Totally, 21 severe complications were reported, including death (2), stroke (10), vision loss (11, 8 of which accompanied with stroke), sepsis (3), multiple abscess (1) and giant fat necrotic cyst (2). Ten of these complications happened within 10 years. Conclusions: There is no unified measurement method to evaluate fat graft SR until now and no clinical evidence to show better SR according to different donor and recipient cite. Body mass index change between pre- and postoperation may be the bias factor in evaluating fat SR. Fat embolisms of the ophthalmic artery and the middle cerebral artery are the most severe complication of AFG and still lack of effective treatment.

MicroRNA-181b negatively regulates the proliferation of human epidermal keratinocytes in psoriasis through targeting TLR4.

Our study aims to explore the role of microRNA‐181b (miR‐181b) and TLR in the regulation of cell proliferation of human epidermal keratinocytes (HEKs) in psoriasis. Twenty‐eight patients diagnosed with psoriasis vulgaris were selected as a case group with their lesional and non‐lesional skin tissues collected. A control group consisted of 20 patients who underwent plastic surgery with their healthy skin tissues collected. Real‐time quantitative fluorescence polymerase chain reaction (RT‐qPCR), in situ hybridization and immunohistochemistry were used to detect the expressions of miR‐181b and TLR4 in HEKs of healthy skin, psoriatic lesional skin and non‐lesional skin respectively. The 3′ untranslated region (3′UTR) of TLR4 combined with miR‐181b was verified by a dual‐luciferase reporter assay. Western blotting and bromodeoxyuridine were applied for corresponding detection of TLR4 expression and cell mitosis. The expression of miR‐181b in HEKs of psoriatic lesional skin was less than healthy skin and psoriatic non‐lesional skin. In psoriatic lesional and non‐lesional skin, TLR4‐positive cell rates and the number of positive cells per square millimetre were higher than healthy skin. The dual‐luciferase reporter assay verified that miR‐181b targets TLR4. HEKs transfected with miR‐181b mimics had decreased expression of TLR4, along with the decrease of mitotic indexes and Brdu labelling indexes. However, HEKs transfected with miR‐181b inhibitors showed increased TLR4 expression, mitotic indexes and Brdu labelling indexes. HEKs transfected with both miR‐181b inhibitors and siTLR4 had decreased mitotic indexes and Brdu labelling indexes. These results indicate that miR‐181b can negatively regulate the proliferation of HEKs in psoriasis by targeting TLR4.

MiR-26a inhibits proliferation and migration of HaCaT keratinocytes through regulating PTEN expression

MicroRNAs (miRNAs) have been shown to be associated with differentiation, migration and apoptosis in keratinocyte. Although it has been reported that microRNA-26a (miR-26a) plays important roles in tumor cells, its biological functions in keratinocytes are still not well elucidated. In this study, we confirmed expression of miR-26a in human keratinocytes using RT-PCR and further studied the role of miR-26a in cell proliferation and cell migration. Ectopic expression of MiR-26a mimic or inhibitor increased or decreased miR-26a expression respectively in HaCaT cells. Proliferation of HaCaT keratinocyte can be suppressed or promoted by overexpression or down-expression of miR-26a. In scratch wound-healing assay and Boyden chamber cell migration assay, upregulating miR-26a expression blocked cell migration, while downregulating miR-26a expression enhanced the migration. Using quantitative RT-PCR (qRT-PCR) and western blot, we further discovered that both mRNA and protein level of phosphatase and tensin homolog deleted from chromosome 10(PTEN) were regulated by miR-26a in HaCaT cells. Meanwhile the level of active form of AKT was also regulated by the miR-26a. In rescue experiment, knockdown of PTEN in the miR-26a mimic transduced cells recovered the migration ability of HaCaT cells. Together these results suggest that miR-26a modulates the proliferation and migration of keratinocytes via regulating PTEN/AKT signaling pathway.

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Objective: This study aims to investigate the effects of CDKN2A (p16^INK4A/p14^ARF) over-expression on the proliferation and migration of human melanoma A375 cells. Methods: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16^INK4A and p14^ARF groups. The expression of CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) mRNA and protein was detected by qRT-PCR and Western blotting. CCK-8, flow cytometry and Transwell assays were applied to observe cell proliferation, the cell cycle and apoptosis, and migration and invasion, respectively. The model of subcutaneous xenografts in nude mice was established to measure cell growth in vivo. Results: Compared with pigmented nevi tissues, CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) mRNA and protein expression were significantly decreased in melanoma tissues. CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) over-expression inhibited proliferation, migration, invasion and progression from G0/G1 to S phase of A375 cells and xenograft tumor growth, but promoted apoptosis. Conclusion: Our study demonstrated that over-expression of CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) suppressed proliferation and migration of human melanoma A375 cells.

Complication Rate of Autologous Cartilage Microtia Reconstruction: A Systematic Review

Background: Autologous cartilage has been widely accepted as the frame material of ear reconstruction for patients with microtia. Although rare, there are multiple complications related with the surgical reconstruction techniques. The authors performed a systematic review of the English literature of microtia reconstruction to determine significant surgical factors that are predictors of postoperative complications. Methods: A PubMed search using the terms “ear reconstruction” and “microtia” was conducted. Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, surgical techniques, the incidence of all kinds of complications, and the specific postoperative morbidity. Patient cohorts were pooled, and the incidence of complications was calculated. Significant predictors such as the use of tissue expander, simultaneously mid-ear reconstruction, with/without skin graft, and different fascia coverage were analyzed by chi-square test. Result: Of 320 articles found, 60 met the inclusion criteria. Totally 9415 patients with microtia were analyzed in this review with 1525 cases with complications. The overall complication incidence is 16.2% in average with a range of 0–72.9%. There was no significant difference when comparing the overall complication rate between with/without preexpansion 2-stage and multiple-stage techniques or with/without mid-ear reconstruction simultaneously. Conclusion: Although there is little agreement in literature regarding risk factors for complications, the authors were able to demonstrate several significant predictors by systematically analyzing 60 articles. Improved knowledge of the incidence of different complications related with various surgical methods can help surgeons provide improved preoperative counseling and take measures to minimize the risk.

Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway

In the present study, we analyzed the role of microRNA-194 circulating regulated human melanoma cell growth. We found that microRNA-194 expression was markedly suppressed in human melanoma patients, compared with negative control group. Next, disease-free survival (DFS) and overall survival (OS) of high expression in human melanoma patients was higher than those of low expression in human melanoma patients. MicroRNA-194 overexpression inhibited cell proliferation, induced apoptosis, increased caspase-3/−9 activities and promoted Bax/Bcl-2 of human melanoma cells. Furthermore, microRNA-194 overexpression also suppressed PI3K/AKT/FoxO3a signaling pathway and induced p53/p21 signaling pathway. PI3K inhibitor, suppressed PI3K, phosphorylation-AKT, FoxO3a protein expression and increased the effects of microRNA-194 overexpression on cell growth, apoptosis, caspase-3/−9 activities and Bax/Bcl-2 protein expression of human melanoma cells through the induction of p53/p21 signaling pathway. Taken together, these data indicate that circulating microRNA-194 regulated human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway.

Incidence of lower limb lymphedema after vulvar cancer: A systematic review and meta-analysis

Background: Lower limb lymphedema (LLL) is an important concern for patients with vulvar cancer. Studies of the incidence of vulvar cancer-related lymphedema and its risk factors have substantially increased in the new millennium. Objectives: This article is a meta-analysis that aimed to systematically evaluate the incidence of LLL and its risk factors related to vulvar cancer. Data sources: Data were collected from eligible studies from PubMed, ScienceDirect, and Web of Science. Synthesis methods: Random effects models were used to calculate a pooled overall estimate of LLL incidence, and subgroup analyses were performed to assess the effects of different study designs, countries of study origin, diagnostic methods, and extent of lymph node surgery. Risk factors for lymphedema were also evaluated. Results: Twenty-seven studies met the inclusion criteria for the assessment of lymphedema incidence with a pooled estimate of 28.8% [95% confidence interval (CI) 22.1–35.5]. The estimate was 16.7% (95% CI 9.7–23.7) when data were restricted to prospective cohort studies (7 studies). The incidence of LLL was increased by approximately 5-fold in women who underwent inguinofemoral lymph node dissection compared to those who underwent sentinel lymph node biopsy. The reported risk factors included wound infection, inguinofemoral lymphadenectomy, older age, body mass index (BMI), and radiation therapy. Conclusions: Approximately 3 in 10 women who survive vulvar cancer will develop lower limb lymphedema. More studies are needed to improve the understanding of its risk factors and to develop prevention and management strategies to alleviate this distressing disorder.

Upregulation of Serum miR-10b Is Associated with Poor Prognosis in Patients with Melanoma

Aberrant expression of microRNAs (miRNAs) are believed to play a central role in the initiation and development of cancer. The aim of our study was to determine the clinical significance of serum miR-10b in melanoma. A total of 85 and 30 serum samples were obtained from patients with melanoma and healthy volunteers respectively. qRT-PCR was performed to evaluate the expression level of miR-10b in the melanoma cell lines and the serum samples from the participants. Then the clinical significance of serum miR-10b was further determined. Our results showed that the expression level of miR-10b was significantly increased in metastasis melanoma cells and melanoma patients compared to their respective controls. In addition, serum miR-10b expression level was able to discriminate melanoma patients from healthy volunteers as well differentiate melanoma patients at different clinical stage with high accuracy. Moreover, upregulation of serum miR-10b was positively associated with enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. Finally serum miR-10b was an independent prognostic factor for melanoma. Collectively, our study suggests that serum miR-10b level is upregulated in melanoma and associated with poor prognosis. It may be used as a potential prognostic biomarker for melanoma.

Radiation Therapy in Keloids Treatment: History, Strategy, Effectiveness, and Complication

Objective: Radiation therapy combined with surgical excision was considered as one of the most effective treatment plans for keloid lesions. However, there was no unanimity found over present literatures regarding the issue on optimized treatment strategy for keloids. We here provide a comprehensive review over this issue and emphasize on the influencing factors. Data Sources: The data analyzed in this review were searched from articles included in PubMed and EMBASE databases. Study Selection: The original articles and critical reviews discussing the application of radiation therapy in keloids treatment were selected for this review. Results: The application of radiation therapy has transitioned from simple superficial X-ray irradiation to brachytherapy. Furthermore, several factors including radiation type, dose, fraction, interval, and complications were reviewed, and the results revealed that these factors were significant toward clinical outcome at various levels. Conclusions: Both past and present evidence support the idea that combination therapy of radiation and surgical therapy is safe and feasible. However, the optimization of treatment strategy was based on different radiation types and should take dose, fractions, interval, and complications into consideration, which will then decrease the rate of recurrence and increase the level of satisfaction.