Clinical Implications of Augmenter of Liver Regeneration in Cancer: A Systematic Review.

BACKGROUND/AIM: Hepatocellular carcinoma is a substantial healthcare burden with high prevalence and poor prognosis. As such, efforts are continually made to uncover molecules relevant in cancer biology, that are exploitable as targets for therapy. The mitochondrion is the powerhouse of the cell and exhibits altered functionality in the malignant state, including aberrant regulation of apoptosis and cellular respiration. Augmenter of liver regeneration (ALR) is a multifunctional mitochondrial protein that demonstrates anti-oxidative and anti-apoptotic properties and plays a key role in liver regeneration. MATERIALS AND METHODS: The present study systematically reviews the available literature on the role of ALR in cancer. RESULTS: Systematic search of PubMed resulted in 12 studies discussing ALR in multiple types of cancer. More specifically, ALR appears to be up-regulated in malignant cells and tissues. Furthermore, treatment of cells with exogenous ALR shows an anti-apoptotic effect while silencing or inhibiting ALR decreases cell and tumor survival. CONCLUSION: ALR clearly plays a role in cancer biology and demonstrates potential as a therapeutic target.

Clinical Features and Treatment of Dermatofibrosarcoma Protuberans Affecting the Vulva: A Literature Review.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade cutaneous neoplasm with a low propensity for metastasis and a high rate of local recurrence. It typically presents as a dermal plaque or nodule on the trunk, limbs, or head and neck region. Vulvar DFSP has also been described, although it is less common. OBJECTIVE: To review the available literature and discuss the clinical course of DFSP affecting the vulva. MATERIALS AND METHODS: We reviewed the existing English-language literature on DFSP of the vulva with respect to clinical presentation, diagnosis, treatment, and outcome. RESULTS: Thirty three case reports and series were included (n = 54 patients). Vulvar DFSP most commonly presents as a slowly enlarging tender or asymptomatic mass on the labia majora, with histological findings of classic DFSP. Most patients were treated with wide local excision. Three patients were treated with Mohs micrographic surgery, which may decrease local recurrence and seems well suited for use in vulvar DFSP. CONCLUSION: This literature review comprehensively reviews and describes the clinical presentation of vulvar DFSP and the treatment options for this rare vulvar neoplasm.

Systematic review of laser therapy in xanthelasma palpebrarum.

Xanthelasma palpebrarum is a benign periorbital xanthoma with substantial cosmetic and psychosocial burden for patients. Treatment modalities should be considered based on efficacy as well as cosmetic outcome. Laser modalities in the treatment of xanthelasma palpebrarum have not been comprehensively reviewed and discussed. Accordingly, this study seeks to systematically and critically review the available literature discussing laser treatment of xanthelasma palpebrarum. PubMed was systematically reviewed for reports on laser therapy in the treatment of xanthelasma palpebrarum. A total of 21 studies were included in this review discussing laser treatment of xanthelasma palpebrarum. Laser types included carbon dioxide, yttrium aluminum garnet, pulsed dye, argon, and a 1450 nm diode laser. The carbon dioxide laser was the most commonly reported modality followed by yttrium aluminum garnet laser. All of the laser modalities offered moderate to excellent clearance rates with minimal side effect profiles. Further large scale studies comparing different laser modalities are required to determine the best laser modality. However, laser modalities as a whole offer a treatment option for xanthelasma palpebrarum, that is, cosmetically excellent with a reasonable side-effect profile.

Clinical features of shiitake dermatitis: a systematic review.

Shiitake dermatitis is a rare cutaneous reaction to lentinan, a polysaccharide component in the cell walls of shiitake mushrooms (Lentinula edodes). Herein, we systematically review the case report and case series English-language literature on shiitake dermatitis, which refers to a total of 50 patients (38 males, 12 females; mean age: 44.58 years). The majority of cases occurred after the consumption of raw mushrooms, whereas 22% of cases were caused by the eating of lightly or undercooked mushrooms. The most common clinical presentations, localized symptoms, and systemic findings include linear flagellated dermatitis (98%), pruritus (78%), and fever, diarrhea, and mucosal ulcers, respectively. The diagnosis of this entity continues to be based on clinical findings as laboratory abnormalities, and the findings of skin biopsies and patch/prick tests are nonspecific and inconsistent. The condition is self-limiting, resolving in approximately 12.5 d without treatment. Based on the included case reports, it appears that medical treatment may slightly shorten the course of disease (to 9-11 d, varying by therapy) but should be considered on an individual patient basis. However, the treatment of symptoms, reassurance, and the avoidance of re-exposure are sufficient treatment recommendations for this condition.

Multinucleate cell angiohistiocytoma.

Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous entity described as grouped erythematous to violaceous papules. Histopathologic findings include vascular proliferations with multinucleate giant cells and dermal fibrosis. We report a case of MCAH in an 83-year-old white man affecting both the right anterior thigh and left posterior calf. Additionally, the pathogenesis of MCAH and different therapeutic modalities are reviewed.

Laser therapy for the treatment of pearly penile papules.

Pearly penile papules (PPP) present as dome-shaped papules of no more than 3 mm in diameter that line the base of the glans of the penis. These benign lesions affect between 14.3 and 48 % of men. While often asymptomatic, PPP can cause a great deal of psychological distress that may warrant treatment. Current treatment options include cryotherapy, electrodessication, and curettage (ED&C). However, these modalities may have considerable adverse cosmetic effects, including scarring, pain, and pigmentary changes. Laser modalities offer clear potential for improved cosmetic outcome in PPP treatment, but is not routinely used. Thus, a systematic review of available literature using the National Library of Medicine database PubMed was completed to find articles relevant to the treatment of PPP with laser and light therapy. The systematic search and screening of articles resulted in inclusion of eight articles discussing a total of 55 patients with PPP treated by laser therapy. The present systematic review found that erbium:yttrium-aluminum-garnet (Er:YAG) and CO2 laser were the most commonly reported (n = 45 and 7, respectively). Furthermore, the use of CO2, Er:YAG, pulsed dye laser, and fractional photothermolysis therapies demonstrated complete clearance of PPP in all cases with minimal complications and discomfort. Thus, based on the currently available evidence, laser therapy is a well-tolerated and efficacious method for treating PPP with minimal long-term adverse effects and a cosmetically desirable outcome. Although the included studies are limited in power, this systematic review offers clinically relevant insight into the potential for laser therapy.

Phototherapy for Pityriasis Lichenoides in the Pediatric Population: A Review of the Published Literature.

BACKGROUND: Pityriasis lichenoides (PL) is a dermatologic disorder that manifests in either the acute (pityriasis lichenoides et varioliformis acuta) or the chronic form (pityriasis lichenoides chronica, also known as parapsoriasis chronica). Traditional first-line therapy consists of corticosteroids or antibiotics; however, these treatments are often accompanied with multiple side effects and may be ineffective. OBJECTIVE: The goal of this study was to review the use of phototherapy for treating PL in the pediatric population. MATERIALS AND METHODS: We performed a systematic review of the literature in the National Library of Medicine's PubMed database and the SCOPUS database discussing phototherapy for treatment of PL in the pediatric population. The following search terms were used: 'pityriasis lichenoides', 'pityriasis lichenoides chronica', 'pityriasis lichenoides et varioliformis acuta', and 'febrile ulceronecrotic Mucha-Habermann disease'. RESULTS: The systematic search and screening of articles resulted in 14 articles including a total of 64 patients with PL treated with phototherapy. Three different modalities were utilized, with five studies using broadband ultraviolet B (BB-UVB) radiation, nine studies utilizing narrowband UVB (NB-UVB), and two studies employing psoralen with ultraviolet A (PUVA) therapy. Overall, the use of BB-UVB had an initial clearance rate of 89.6 % with 23.1 % recurrence, whereas NB-UVB cleared 73 % of the lesions with no recurrence, and PUVA therapy initially cleared 83 % of the lesions with 60 % recurrence. The side-effect profiles were similar and revealed limited toxicity. CONCLUSION: Phototherapy shows promising results and a favorable side-effect profile in the treatment of PL. Ultimately, large randomized controlled trials are needed to determine optimal treatments.

Treatment of Acne Keloidalis Nuchae: A Systematic Review of the Literature.

Acne keloidalis nuchae (AKN) is a chronic inflammatory condition that leads to fibrotic plaques, papules and alopecia on the occiput and/or nape of the neck. Traditional medical management focuses on prevention, utilization of oral and topical antibiotics, and intralesional steroids in order to decrease inflammation and secondary infections. Unfortunately, therapy may require months of treatment to achieve incomplete results and recurrences are common. Surgical approach to treatment of lesions is invasive, may require general anesthesia and requires more time to recover. Light and laser therapies offer an alternative treatment for AKN. The present study systematically reviews the currently available literature on the treatment of AKN. While all modalities are discussed, light and laser therapy is emphasized due to its relatively unknown role in clinical management of AKN. The most studied modalities in the literature were the 1064-nm neodymium-doped yttrium aluminum garnet laser, 810-nm diode laser, and CO2 laser, which allow for 82-95% improvement in 1-5 sessions. Moreover, side effects were minimal with transient erythema and mild burning being the most common. Overall, further larger-scale randomized head to head control trials are needed to determine optimal treatments.

Erythroplasia of Queyrat treated by laser and light modalities: a systematic review.

Erythroplasia of Queyrat (EOQ) is a squamous cell carcinoma in situ most commonly located on the glans penis or prepuce. EOQ accounts for roughly 10 % of all penile malignancies and may lead to invasive squamous cell carcinoma. Standard therapy includes local excision, partial or total penectomy, cryotherapy, and topical cytotoxic agents. Treatment of EOQ has proven to be challenging due to low response rates and recurrence. In addition, radical procedures can significantly affect sexual function and quality of life. Alternative laser treatments and photodynamic therapy (PDT) offer promising results for treating EOQ. A systemic review of the literature was performed for articles discussing laser and light therapy for EOQ. Among the patients treated with the CO2 laser, 81.4 % of cases had complete remission after one session of treatment. Patients treated with PDT presented with more variable results, where 62.5 % of those treated with methyl aminolevulinate photodynamic therapy (MAL-PDT) achieved complete remission. Aminolevulinic acid (ALA-PDT) treatment showed a similar rate of remission at 58.3 %. One study utilized the Nd:YAG laser, which resulted in a recurrence of the lesion in four of the five patients treated. Of the methods reviewed, the CO2 laser offered the most promising results with a cosmetically excellent prognosis. Further studies with larger power and longer follow-up times are needed to determine the optimal treatment regimen for this penile malignancy.

Laser and light therapies for the treatment of nail psoriasis.

Psoriatic involvement of the nail is notoriously refractory to conventional therapy. Nail psoriasis has a high incidence amongst patients with psoriasis. It remains a significant cosmetic problem and thus, has a significant impact on quality of life. More recently, light and laser therapies have emerged as modalities for treatment of nail psoriasis. In this study, the efficacies of light and laser therapies are systematically reviewed. Light therapies involve ultraviolet light (with or without photosensitizers) or intense pulsed light. Alternatively, laser therapy in nail psoriasis is primarily administered using a 595-nm pulsed dye laser. These modalities have demonstrated significant improvement in psoriatic nail lesions, and even complete resolution in some cases. Both laser and light modalities have also been tested in combination with other systemic or topical therapeutics, with variable improvement in efficacy. Both laser and light therapies are generally well tolerated. Side-effects of light therapies include hyperpigmentation, itching and erythema; whereas, side-effects of laser therapy are more frequent and include pain, purpura/petechiae and hyperpigmentation. Patterns of response to therapy were also seen based on presenting characteristics of the nail lesions: subungual hyperkeratosis and onycholysis appeared to be the most responsive to therapy, while nail pitting was the most resistant. Light or laser therapies have the potential to be an efficient and cost-effective in-office based treatment for nail psoriasis. However, more large-scale clinical trials are needed to assess their efficacy, particularly in combination with other therapeutic modalities.

A decade of burn unit experience with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Clinical pathological diagnosis and risk factor awareness.

Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) is a rare and often fatal spectrum of mucocutaneous diseases usually attributable to severe adverse drug reactions. Burn units are referral centers for patients at the most extreme end of the disease continuum. Our burn center admits a much higher percentage of TEN (>30% BSA) cases than reported in most prior reviews. The purpose of this study was to analyze the diagnostic and prognostic value of variables collected on referred SJS/TEN patients. We retrospectively analyzed 94 patients admitted to our unit with a presumptive SJS/TEN diagnosis made in most cases by the referring center. Most of the diagnoses were clinical. Fifty of the 94 patients underwent biopsy when the clinical diagnosis was questionable. Of the 50 patients who underwent biopsy, 18 (36%) received an alternative diagnosis. Analysis was therefore limited to 76 patients, i.e. 44 patients felt to have firm clinical diagnoses plus 32 patients with diagnoses confirmed by biopsy. Mean age was 54.3 years (17-93) and overall gender ratio was 43 F vs. 33 M (56.6% vs. 43.4%). Mean LOS was 15.2 days (1-48) and overall mortality was 23.7% (18/76). Univariate analysis revealed percent body surface area (%BSA) did not show statistically significant association with mortality. Histopathological correlation for diagnosis is not standardized across institutions worldwide. Due to challenges in the diagnosis of SJS/TEN and the high incidence of error in clinical diagnosis, it is recommended that all patients with presumed SJS/TEN receive skin biopsies with H&E and direct immunofluorescence. We propose a diagnostic approach in order to address this need. Lack of association between %BSA and mortality suggests that all biopsy-proven SJS/TEN cases belong in specialty centers due to the unstable nature of the disease and risk for rapid progression.

Association of high mobility group BOX-1 and receptor for advanced glycation endproducts with clinicopathological features of haematological malignancies: a systematic review.

High-mobility group box 1 (HMGB1) is a versatile protein with nuclear and extracellular functions. In the extracellular milieu, HMGB1 binds to several receptors, notably the receptor for advanced glycation end-products (RAGE). The expressions of HMGB1 and RAGE have been described in a variety of cancers. However, the clinical values of HMGB1 and RAGE in haematological malignancies have yet to be evaluated. A systematic search through PubMed and the Web of Science for articles discussing the role of HMGB1 and RAGE in haematological malignancies produced 15 articles. Overexpression of HMGB1 was reported to be associated with malignancy and, in certain studies, poor prognosis and tumour aggressiveness. Only one included study investigated the clinical value of RAGE, in which no significant difference was found between expression of RAGE in CLL neoplastic cells and nonmalignant controls. The discussed associations of HMGB1 and RAGE with clinicopathological characteristics of patients with haematological malignancies warrants further investigation into the prognostic and diagnostic value of both of these molecules.

Cutaneous expression of TREM, vitamin D receptor and HMGB1 in vitamin D deficiency.

Signaling pathways of the vitamin D receptor (VDR) and the triggering receptor expressed on myeloid cells (TREM) have been independently implicated in the biology of numerous of cutaneous pathologies. There is substantial evidence for possible crosstalk between these pathways, though the relationship between VDR and TREMs remains unclear. In this study, we characterize the effects of vitamin D-deficiency and sufficiency on the cutaneous expression of TREM-1, TREM-2, VDR, HMGB1, and RAGE. Cutaneous tissue isolated from Yucatan microswine were immunohistochemically evaluated for epidermal expression of TREM-1, TREM-2, VDR, HMGB1, and RAGE. The swine were fed a vitamin D-deficient or vitamin D-sufficient diet to examine the role of vitamin D state on levels of these markers. In vitamin D-sufficient animals, keratinocytes exhibited elevated levels of TREM-1, TREM-2. Additionally, TREM-1 expression predominated in basal cells, whereas TREM-2 levels were higher in keratinocytes, regardless of vitamin D state. Levels of HMGB1 and RAGE did not differ by vitamin D state. VDR expression was consistently higher in the cytoplasm and nuclei of basal cells, when compared to keratinocytes. Our findings suggest a role of vitamin D in signaling of TREM pathways. Additionally, the TREM ratio may play a role in keratinocyte differentiation and should be explored further. Possible signaling crosstalk between these pathways has a potential role in progression of cutaneous malignancies and other inflammatory pathologies.

Diagnostic value of tumor antigens in malignant pleural effusion: a meta-analysis.

The diagnostic value of tumor markers, carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 19-9, CA 125, cytokeratin fragment (CYFRA), and neuron-specific enolase (NSE) in pleural fluid to differentiate between benign and malignant pleural effusion (MPE) has not yet been clearly established. A review of English language studies using human subjects was performed. Sensitivity and specificity values of the chosen tumor markers were pooled using a random effects model to generate hierarchical summary receiver operator curves to determine the diagnostic performance of each tumor marker. A total of 49 studies were included in the final analysis. Pooled sensitivity and specificity values for chosen tumor markers for diagnosing MPE are as follows: CEA, 0.549 and 0.962; CA 15-3, 0.507 and 0.983; CA 19-9, 0.376 and 0.980; CA 125, 0.575 and 0.928; CYFRA, 0.625 and 0.932; NSE, 0.613 and 0.884. The use of individual tumor markers in diagnosing MPE has many benefits (cost, invasiveness, and so forth). Although these tumor markers exhibit high specificity, the low sensitivity of each marker limits the diagnostic value. We conclude that tumor markers used individually are of insufficient diagnostic accuracy for clinical use. Tumor markers used in various combinations or from serum may have some potential worth further investigation.

Decreased accumulation of cadmium in Drosophila selected for resistance suggests a mechanism independent of metallothionein.

Heavy metals, including cadmium, are common contaminants in environments subject to human activity. Responses to exposure in the fruit fly, Drosophila melanogaster, are dosage-dependent and resistance is selectable. While metallothionein-mediated sequestration has been extensively studied as a mechanism of cadmium resistance, a link between selection for resistance and an increased accumulation of cadmium has yet to be demonstrated. To address this need, we have selected wild-type flies for cadmium resistance for 20 generations and tested metal content using mass spectrometry. Resistant flies were observed to contain lower levels of cadmium, arguing for a mechanism of cadmium resistance that is not mediated by increased sequestration. This, coupled with genetic evidence suggesting the involvement of factors located on the X chromosome, suggests a gene other than metallothionein may be involved in resistance in this line.