Nuclear Localization of Yes-Associated Protein Is Associated With Tumor Progression in Cutaneous Melanoma.

Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, western blotting, viability assays, wound healing assays, verteporfin treatment, and xenograft assays were conducted using melanoma cell lines B16F1 and B16F10 subjected to YapS127A transfection and siYap knockdown. Nuclear YAP localization was identified in 63 tumors (45.0%) and was more frequent than cytoplasmic YAP in acral lentiginous and nodular subtypes (P = .007). Compared with cytoplasmic YAP melanomas, melanomas with nuclear YAP had higher mitotic activity (P = .016), deeper invasion (P < .001), and more frequently metastasized to lymph nodes (P < .001) and distant organs (P < .001). Patients with nuclear YAP melanomas had poorer disease-free survival (P < .001) and overall survival (P < .001). Nuclear YAP was an independent risk factor for distant metastasis (hazard ratio: 3.206; 95% CI, 1.032-9.961; P = .044). Proliferative ability was decreased in siYapB16F1 (P < .001) and siYapB16F10 (P = .001) cells and increased in YapS127AB16F1 (P = .003) and YapS127AB16F10 (P = .002) cells. Cell cycle analysis demonstrated relative G1 retention in siYapB16F1 (P < .001) and siYapB16F10 (P < .001) cells and S retention in YapS127AB16F1 cells (P = .008). Wound healing assays showed that Yap knockdown inhibited cell invasion (siYapB16F1, P = .001; siYapB16F10, P < .001), whereas nuclear YAP promoted it (YapS127AB16F, P < .001; YapS127AB16F1, P = .017). Verteporfin, a direct YAP inhibitor, reduced cellular proliferation in B16F1 (P = .003) and B16F10 (P < .001) cells. Proliferative effects of nuclear YAP were confirmed in xenograft mice (P < .001). In conclusion, nuclear YAP in human melanomas showed subtype specificity and correlated with proliferative activity and proinvasiveness. It is expected that YAP becomes a useful prognostic marker, and its inhibition may be a potential therapy for melanoma patients.

Exploring Molecular Genetic Alterations and RAF Fusions in Melanoma: A Belvarafenib Expanded Access Program in Patients with RAS/RAF-Mutant Melanoma.

BACKGROUND: Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP). PATIENTS AND METHODS: Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib. RESULTS: Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses. CONCLUSIONS: Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.

Looking Beyond the Hutchinson Sign: A Retrospective Study of Clinical Factors Indicating the Presence and Invasiveness of Nail Unit Melanoma in Patients With Longitudinal Melanonychia.

BACKGROUND: The data underlying this article are available in the article.Longitudinal melanonychia (LM) presents a challenge because nail unit melanoma (NUM) must be considered as a differential diagnosis. Because nail matrix biopsy may result in nail dystrophy, it is important to distinguish NUM from LM. OBJECTIVE: To provide evidence of previously reported clinical factors indicative of NUM in patients with LM. METHODS: This was a retrospective study of patients who presented with LM and had biopsy-confirmed NUM from 2005 to 2021. Benign LM was either confirmed by biopsy or considered benign if followed without the need for biopsy. Clinical factors associated with LM and NUM were compared by multivariate regression. RESULTS: A total of 177 patients (97 LM and 80 NUM) were included. Multivariate regression showed that high band color intensity (p = .0031), variegation (p = .0005), nail plate splitting (p = .0017), Hutchinson sign (p = .0027), and band change (p = .001) correlated with malignancy. Nail plate splitting was associated with Breslow thickness. CONCLUSION: Malignancy should be suspected and biopsy performed in patients with LM and high band color intensity, variegation, nail plate splitting, Hutchinson sign, and band change.

Successful treatment of xanthoma disseminatum with pulsed dye laser: A case report.

Xanthoma disseminatum is a rare form of non-Langerhans cell histiocytosis with limited treatment options due to its unknown aetiology and diffuse skin lesions. This case report presents the successful treatment of a 31-year-old male with severe pan-facial xanthoma disseminatum lesions following a facial burn and traumatic brain injury resulting from a car accident. After 5 sessions of monthly pulsed dye laser treatment, there was a clinically significant reduction in the lesions. Over the course of 3 years, the patient underwent a series of monthly pulsed dye laser treatments, and the lesions were almost cleared. These findings suggest that pulsed dye laser therapy may offer an effective treatment option for managing xanthoma disseminatum. This is the first report on use of the pulsed dye laser for treatment of xanthoma disseminatum.

Risk of recurrence of nail unit melanoma after functional surgery versus amputation.

BACKGROUND: Minimally invasive nail unit melanoma (NUM) can be treated with functional surgery (FS) instead of amputation. OBJECTIVE: To determine risk factors associated with recurrence in NUM. METHODS: We retrospectively reviewed patients with NUM between 2008 and 2022 at a tertiary referral center. Multivariable Cox regression models adjusted for male sex and Breslow thickness (BT) were generated. Receiver operating characteristic analysis was performed to determine optimal cut-off points of the BT for stratifying recurrence risk. RESULTS: We evaluated 140 NUM cases (33 amputation and 107 FS). The mean BT values were 3.14 ± 2.62 mm (amputation) and 0.70 ± 1.36 mm (FS). Recurrence occurred in 10 (30.30%) patients with amputation and 23 (21.5%) with FS. Distant disease occurred in 10 (30.30%) patients with amputation and 8 (7.48%) with FS. Male sex, greater BT, amelanotic color, ulcers, and nodules were associated with greater risk for recurrence or distant disease. A BT of 0.8 mm was deemed the optimal cut-off for stratifying recurrence risk after surgery (odds ratio, 5.32; 95% CI, 2.04-13.85). LIMITATIONS: Small sample. CONCLUSION: FS can be considered for NUM with a BT < 0.8 mm, providing an amputation-sparing benefit. However, NUM with risk factors for recurrence requires patient counselling and close follow-ups.

Mohs Micrographic Surgery With Digital Pathology Improves Surgical Quality and Efficiency: A Retrospective Cohort Study.

BACKGROUND: Mohs micrographic surgery, involving pathology of the surgical margin, has the lowest recurrence rate for skin cancer. Moreover, because of technological advances, digital pathology systems are gradually being adopted in hospitals. Yongin Severance Hospital was the first hospital to construct a fully digitalized pathology system in Korea. OBJECTIVE: To evaluate the efficiency and characteristics of the digital pathology system for Mohs micrographic surgery. METHODS: The medical records of 80 patients with skin cancer who underwent Mohs micrographic surgery from March 2020 to August 2022 were analyzed for the number of frozen margins, number of stages, operation time, and recurrence rate to compare cases based on the pathology system. RESULTS: Overall, 23 and 57 patients were examined using the conventional and digital pathology systems, respectively. The mean number of final stages was 0.494 lower ( p -value = .008), the time from the previous to the next stage was 0.687-fold shorter ( p = .002), and the rate of switching from positive to negative margins was 1.990 times higher ( p = .044) in the digital than the conventional group. LIMITATIONS: Retrospective single-center experience; short follow-up time. CONCLUSION: Digital pathology reduces operative time and increases accuracy in Mohs micrographic surgery.

A nomogram combining clinical factors and biomarkers for predicting the recurrence of high-risk cutaneous squamous cell carcinoma.

BACKGROUND: Although determining the recurrence of cutaneous squamous cell carcinoma (cSCC) is important, currently suggested systems and single biomarkers have limited power for predicting recurrence. OBJECTIVE: In this study, combinations of clinical factors and biomarkers were adapted into a nomogram to construct a powerful risk prediction model. METHODS: The study included 145 cSCC patients treated with Mohs micrographic surgery. Clinical factors were reviewed, and immunohistochemistry was performed using tumor tissue samples. A nomogram was constructed by combining meaningful clinical factors and protein markers. RESULTS: Among the various factors, four clinical factors (tumor size, organ transplantation history, poor differentiation, and invasion into subcutaneous fat) and two biomarkers (Axin2 and p53) were selected and combined into a nomogram. The concordance index (C-index) of the nomogram for predicting recurrence was 0.809, which was higher than that for the American Joint Committee on Cancer (AJCC) 7th, AJCC 8th, Brigham and Women's Hospital, and Breuninger staging systems in the patient data set. CONCLUSION: A nomogram model that included both clinical factors and biomarkers was much more powerful than previous systems for predicting cSCC recurrence.

First-line pembrolizumab versus dabrafenib/trametinib treatment for BRAF V600-mutant advanced melanoma.

BACKGROUND: Limited data are available to assist the selection between immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors as first-line treatment for patients with BRAF-mutant advanced malignant melanoma. OBJECTIVE: To investigate the outcomes associated with first-line pembrolizumab or dabrafenib/trametinib treatment for advanced melanoma with activating BRAF V600 mutation. METHODS: Data of patients with BRAF V600-mutant melanoma who were treated with first-line pembrolizumab (n = 40) or dabrafenib/trametinib (n = 32) were analyzed. Tumor response, progression-free survival, and overall survival were evaluated. Immune evasion accompanied with emerging resistance to BRAF/mitogen-activated protein kinase kinase inhibitors was assessed. RESULTS: A longer overall survival was observed after first-line pembrolizumab treatment than after first-line dabrafenib/trametinib treatment (hazard ratio = 2.910, 95% CI: 1.552-5.459), although there were no significant differences in progression-free survival (P = .375) and response rate (P = .123). Emergence of resistance to dabrafenib/trametinib co-occurred with immune evasion, enabling melanoma cells to escape recognition and killing by Melan-A-specific CD8+ T cells. LIMITATIONS: Analysis was conducted in a retrospective manner. CONCLUSION: Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600-mutant melanoma.

A Novel Method of Steroid Delivery to Improve the Efficacy of Intralesional Injection in Keloid Treatment.

BACKGROUND: Keloids are a chronic disease and cause pain, pruritus, and limitation of motion. Intralesional corticosteroid injection is the first-line treatment, but its effects can be limited, even with repeated injections. OBJECTIVE: To investigate the efficacy and safety of a tunneling method of corticosteroid injection compared with conventional intralesional injection. MATERIALS AND METHODS: A retrospective review was conducted of keloid patients treated with intralesional corticosteroid injection by conventional and tunneling methods. RESULTS: A total of 119 cases of keloid were included in the study. Among 78 patients treated with 20 mg/mL triamcinolone, the Investigators' Global Assessment effectiveness score and Observer Scar Assessment Scale (OSAS) score were significantly higher in the tunneling group than the conventional group at 1 month. At 6 months, the tunneling group showed significantly higher effectiveness in the OSAS score than the conventional group. In the tunneling group, the interval between treatments was significantly longer than in the conventional group. The occurrence of side effects was lower in the tunneling method group than in the conventional method group. CONCLUSION: This study reveals the benefits of the tunneling method over the conventional method for therapeutic effect and side effects in keloid treatment.

Hypopigmentation in Extramammary Paget Disease Is an Important Prognostic Factor for High Recurrence Rate and Poor Surgical Outcome.

BACKGROUND: Several studies have reported the presence of hypopigmentation in extramammary Paget disease (EMPD). However, an in-depth analysis regarding its clinical implication is lacking. OBJECTIVE: To evaluate the clinical characteristics of EMPD in the Korean population and to determine the implication of hypopigmentation on clinical outcomes. METHODS: We retrospectively reviewed 124 cases of EMPD who underwent surgical treatment from a single tertiary hospital from December 2005 to March 2019. Baseline characteristics of the patients and hypopigmentation patterns were analyzed. Moreover, the number of stages of Mohs micrographic surgery (MMS) and recurrence rate were evaluated in relation to the hypopigmentation. RESULTS: A total of 67.7% (n = 84) of the patients showed hypopigmentation. The adjusted odds ratio for recurrence in the hypopigmented group was 5.980, which was statistically significant (95% confidence interval = 1.347-26.553, p-value = 0.019). Furthermore, the average number of MMS stages was 2.92 in the hypopigmentation group, compared with 1.82 in the nonhypopigmentation group (p-value = .0016). CONCLUSION: Hypopigmented lesions may disguise the tumor margin, thus raising the recurrence rate after surgery and the number of stages of MMS. The hypopigmentation status must be considered when deciding the surgical margin.

Slow Mohs Micrographic Surgery for Acral Melanoma Treatment in Korean Patients.

BACKGROUND: Obtaining conventional wide surgical margins is challenging in melanomas occurring at anatomically complex sites (e.g., hands and feet). OBJECTIVE: We investigated the potential benefits of slow Mohs micrographic surgery (MMS) for acral melanomas. MATERIALS AND METHODS: This single-center retrospective study investigated 210 patients who underwent slow MMS (n = 66) or wide local excision (WLE, n = 144) for melanomas during 2005 to 2015. Slow MMS was used for melanomas in anatomically complex locations and for high-risk lesions. RESULTS: Acral melanoma (166/210) was the most common lesion observed in patients, in addition to head and neck (21/210) and trunk (23/210) melanomas. Slow MMS was more commonly performed for acral, and head and neck melanomas (32.5% and 52.4%, respectively) than for trunk melanomas (4.3%, p = .002). Local recurrence of acral melanomas occurred in 3.7% of patients after slow MMS and in 10.7% of patients after WLE. Multivariate analysis showed comparable prognostic outcomes between slow MMS and WLE used for acral melanomas. Compared with WLE, slow MMS resulted in a smaller postoperative defect after acral lesion excision (p < .001). CONCLUSION: Slow MMS is an effective alternative to WLE for acral melanomas in anatomically complex sites, as evidenced by superior outcomes and maximum tissue conservation.

Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations.

BACKGROUND: Predicting the recurrence of localized melanoma is important; however, studies investigating risk factors for recurrence of localized melanoma are lacking in Asian populations. OBJECTIVE: To identify risk factors for recurrence of localized melanoma in Korean patients. METHODS: We retrospectively reviewed patients with cutaneous melanoma without evidence of metastasis from 2000 to 2017. Logistic and Cox regression analyses were conducted for recurrence. The average follow-up time was 46.2 months. RESULTS: We reviewed the data of 340 patients diagnosed with cutaneous melanoma and staged as melanoma in situ, stages I and II. Acral melanoma (70.3%, 239/340) was the predominant subtype. Ninety-two patients (27.1%) had a recurrence after primary melanoma removal (29 local recurrences, 49 regional metastases, and 28 distant metastases). Some patients had multiple types of recurrence at the same time. Male sex (P = .030) and Breslow thickness greater than 1 mm (P = .008) correlated with an increased risk of recurrence. Breslow thickness greater than 2.5 mm in males and greater than 4 mm in females showed a higher predictive value for recurrence than traditional stages IIB and IIC (hazard ratio 3.743 vs 2.972). LIMITATIONS: This was a single-center retrospective study. CONCLUSION: In patients with localized cutaneous melanoma, male sex and Breslow thickness are the most important prognostic factors for recurrence in Korean populations. Different cutoff values of Breslow thickness may better predict recurrence according to sex.

Advantages of A Hairline Incision for the Excision of Forehead Lipomas.

BACKGROUND: Direct incision (DI) for forehead lipoma removal has a considerable risk of damaging the vertical vessels and leaving a visible scar. OBJECTIVE: To evaluate the usefulness of the hairline incision (HI) in minimizing scars and neurovascular damage. PATIENTS AND METHODS: Retrospective analysis was done for 30 patients with forehead lipomas who underwent excision between 2011 and 2019 at the Severance Hospital of the Yonsei University Health System, Seoul, Korea. Fourteen patients underwent DI, and 16 underwent HI. Comparison of the cosmetic outcomes, complications, and patient's subjective satisfaction was performed. RESULTS: In the HI group, superior cosmetic outcomes, including patients' subjective satisfaction and photographic assessment findings, were observed. In the DI group, there were 2 cases of skin necrosis with scarring change and 3 cases of recurrence. Periorbital edema was the most common complication in the HI group, which spontaneously resolved within 1 week. CONCLUSION: Hairline incision using a loupe should be considered as a first-line treatment in the removal of forehead lipomas, because it enables complete removal of lipoma with few complications and minimal scarring. Validation of our treatment algorithm requires further exploration.

Long-term outcomes of laser treatment for congenital melanocytic nevi.

BACKGROUND: Although various laser treatments have been tried for congenital melanocytic nevi (CMNs), only small retrospective studies with short-term follow-up had been done to assess outcomes. OBJECTIVE: We analyzed the long-term outcomes of laser treatment for CMN and compared these outcomes with those of a combination treatment including partial excision and lasers. METHODS: Patients with CMN treated with lasers were retrospectively reviewed, and patients with >3 years of follow-up were grouped as the long-term follow-up group. RESULTS: A total of 67 cases of CMN were reviewed. Among 20 patients (20/52, 38.5%) with near total clearance during laser-only treatment, 11 patients were in the long-term follow-up group, and 5 of 11 showed repigmentation. In total, 15 patients showed repigmentation regardless of clearance, and the mean period until repigmentation was 3.93 years from the initial treatment. Patients with partial excision and laser combination treatment showed higher Investigator's Global Assessment scores, fewer laser treatments, and shorter treatment periods compared with patients with laser-only treatment. LIMITATIONS: This is a retrospective study, and various laser devices were used. CONCLUSION: More than 4 years of follow-up is required to evaluate the efficacy of lasers in CMN, and partial excision and laser combination treatment might be an effective treatment option.

Comparison of treatment options for small to medium congenital melanocytic nevi: A retrospective review of 119 cases.

OBJECTIVES: For small to medium sized congenital melanocytic nevi (CMN), the treatment of choice is staged surgical excision. Ablative lasers or pigment-specific lasers have also been recommended for lesions difficult for surgical removal or to avoid surgery. In this study, we retrospectively analyzed the results of several treatment options for CMN to find out the optimal treatment method. METHODS: Patients with small to medium sized CMN were retrospectively reviewed. Treatment options were categorized into four groups: (i) Excision only; (ii) Excision followed by scar laser; (iii) Excision followed by pigment-specific laser; and (iv) Laser only. Treatment response was assessed by investigator's global assessment (IGA) score on a seven-point scale. RESULTS: A total of 119 cases were included. Lesions were most commonly located on the face (59/119, 49.6%), measured 2 ∼ 10 cm in size (72/119, 60.5%), and treated with excision only (50/119, 42.0%). Among treatment options, excision followed by scar laser showed the highest IGA score of 6.38. Options including surgical methods showed higher IGA scores compared to laser-only treatment (P < 0.01). Staged excisions and single excisions showed no difference in IGA scores. Patient satisfaction scores increased after scar laser treatment of the staged excision scar. CONCLUSIONS: For the treatment of small to medium sized CMN, treatment strategies including surgical methods are cosmetically superior to laser-only treatment. Also, the combination of surgical excision with scar laser has the potential for better clinical outcomes and patient satisfaction. Lasers Surg. Med. 51:62-67, 2019. © 2018 Wiley Periodicals, Inc.

Comparative Effects of Topical 0.2% Sirolimus for Angiofibromas in Adults and Pediatric Patients with Tuberous Sclerosis Complex.

BACKGROUND: Recent reports have suggested that the topical formulation of sirolimus is effective in treating facial angiofibromas in tuberous sclerosis complex (TSC). Here, we determined the safety and efficacy of 0.2% topical sirolimus for the treatment of facial angiofibroma and compared its effects based on age. METHOD: This was a retrospective study which involved 36 TSC patients with facial angiofibromas who were treated with 0.2% sirolimus ointment. Its effect was evaluated using the Facial Angiofibroma Severity Index (FASI). In order to observe its comparative effect based on patient age, a subgroup analysis was performed, between the adult group (> 18 years old) and the pediatric group (≤18 years old). RESULTS: The total FASI as well as its subcategories (erythema, size, and extent) showed statistically significant improvements after the topical treatment with 0.2% sirolimus ointment (FASI before treatment: 7.2 ± 1.1, FASI after treatment: 4.4± 1.4, p < 0.001). Among the subcategories of FASI, the erythema was most significantly reduced with the fastest response to the treatment. In a subgroup analysis, the pediatric group showed significantly greater improvements in FASI (improvement of FASI in the pediatric group = 49.7 ± 12.2%, adult group = 27.9 ± 15.6%, p < 0.001). The serial improvement analysis also showed that the pediatric group achieved a consistently greater improvement in FASI at all visits. Its 1-year application in 3 patients demonstrated a continuous maintenance effect. No significant adverse effects were observed. CONCLUSION: 0.2% sirolimus ointment is safe and effective for facial angiofibromas. Considering its higher efficacy in younger patients, an early initiation of the treatment is recommended.

Periorbital Syringomas Treated With an Externally Used 1,444 nm Neodymium-Doped Yttrium Aluminum Garnet Laser.

BACKGROUND: The 1,444 nm wavelength is also well absorbed in water making it a possible setting for treatment of cystic lesions such as eccrine hydrocystomas and syringomas. OBJECTIVE: The authors aimed to investigate the efficacy of an externally used 1,444 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for the treatment of periorbital syringomas. METHODS AND MATERIALS: Nineteen patients with periorbital syringomas were treated twice with the externally used 1,444 nm Nd:YAG laser at 2-month intervals. Laser fluences were delivered to each papule with pulse energy of 160 mJ, 1.6 W of power, and at a 10 Hz pulse rate. Clinical improvement and patient satisfaction were assessed at 2 and 6 months after each treatment. Side effects were also examined. RESULTS: Clinical improvement of >50% was observed in 68.4% of individuals at 2 months after first treatment (2FT) and in all patients at 6 months after second treatment (6ST). Patient satisfaction of no less than "satisfied" was recorded for 63.2% of patients at 2FT, and in 89.5% of patients at 6ST. Erythema was observed in 63.2% of patients but only at 2FT. CONCLUSION: Externally used 1,444 nm Nd:YAG laser treatment may represent an effective and safe approach for the treatment of periorbital syringomas, resulting in good satisfaction and minimal side effects.

Investigation on the Cutaneous Change Induced by Face-Lifting Monodirectional Barbed Polydioxanone Thread.

BACKGROUND: Owing to its potentially greater mechanical force on the implanted tissue, barbed thread is frequently used in face-lifting procedures. However, the long-term durability thereof remains controversial. Moreover, reports on underlying histologic and molecular changes resulting from face-lifting procedures are scarce. OBJECTIVE: To evaluate histologic and molecular changes induced by absorbable, barbed face-lifting thread in an animal model. MATERIALS AND METHODS: Fragments of monofilament, monodirectionally barbed polydioxanone thread were implanted in dorsal skin from 12 guinea pigs. Tissue samples were harvested at 1, 3, and 7 months thereafter. Histopathologic analysis and quantification of Type 1 collagen and transforming growth factor beta 1 (TGF-ß1) levels were performed. RESULTS: Implantation of a single fragment induced fibrous capsule around the thread. Tissue reactions were strongest at 1 month after implantation, showing marked infiltration of inflammatory cells and fibroblasts, which gradually decreased. On molecular analysis, Type 1 collagen and TGF-ß1 levels were significantly increased, compared to normal skin, throughout the 7-month study period. CONCLUSION: Our results suggest that implantation of barbed thread induces strong anchorage to skin tissue. Quantitative analysis of collagen and its downstream signaling molecule TGF-ß supports the long-term durability of the thread. Therefore, the authors expect potential beneficial effect for rejuvenation on its clinical application.

Metastatic melanomas of unknown primary show better prognosis than those of known primary: a systematic review and meta-analysis of observational studies.

BACKGROUND: Melanoma of unknown primary (MUP) is a condition of metastatic melanoma without a primary lesion. OBJECTIVE: We sought to identify the prognosis of MUP compared with melanoma of known primary (MKP). METHODS: We searched for observational studies containing at least 10 patients with MUP from MEDLINE and EMBASE from inception to December 22, 2012. The outcomes of interest were overall and disease-free survival; meta-analyses of hazard ratio stratified by stage using a random effects model were performed. In addition, second systematic review identified risk factors influencing the survival of patients with MUP. RESULTS: Eighteen studies including 2084 patients with MUP and 5894 with MKP were included. MUP had a better overall survival compared with MKP in stage III (15 studies; hazard ratio 0.83, 95% confidence interval 0.73-0.96, P = .010) and stage IV (6 studies; hazard ratio 0.85, 95% confidence interval 0.75-0.96, P = .008). Secondly, 22 studies including 3312 patients with MUP were reviewed, and increased stage and old age were the risk factors in patients with MUP. LIMITATIONS: Diverse observational studies were reviewed, and selection and reporting biases are possible. CONCLUSIONS: The current meta-analyses suggest better survival outcomes in patients with MUP than those in patients with MKP with the same corresponding tumor stage.