Augmented decision-making for acral lentiginous melanoma detection using deep convolutional neural networks.

BACKGROUND: Several studies have achieved high-level performance of melanoma detection using convolutional neural networks (CNNs). However, few have described the extent to which the implementation of CNNs improves the diagnostic performance of the physicians. OBJECTIVE: This study is aimed at developing a CNN for detecting acral lentiginous melanoma (ALM) and investigating whether its implementation can improve the initial decision for ALM detection made by the physicians. METHODS: A CNN was trained using 1072 dermoscopic images of acral benign nevi, ALM and intermediate tumours. To investigate whether the implementation of CNN can improve the initial decision for ALM detection, 60 physicians completed a three-stage survey. In Stage I, they were asked for their decisions solely on the basis of dermoscopic images provided to them. In Stage II, they were also provided with clinical information. In Stage III, they were provided with the additional diagnosis and probability predicted by the CNN. RESULTS: The accuracy of ALM detection in the participants was 74.7% (95% confidence interval [CI], 72.6-76.8%) in Stage I and 79.0% (95% CI, 76.7-81.2%) in Stage II. In Stage III, it was 86.9% (95% CI, 85.3-88.4%), which exceeds the accuracy delivered in Stage I by 12.2%p (95% CI, 10.1-14.3%p) and Stage II by 7.9%p (95% CI, 6.0-9.9%p). Moreover, the concordance between the participants considerably increased (Fleiss-κ of 0.436 [95% CI, 0.437-0.573] in Stage I, 0.506 [95% CI, 0.621-0.749] in Stage II and 0.684 [95% CI, 0.621-0.749] in Stage III). CONCLUSIONS: Augmented decision-making improved the performance of and concordance between the clinical decisions of a diverse group of experts. This study demonstrates the potential use of CNNs as an adjoining, decision-supporting system for physicians' decisions.

Non-melanoma skin cancer as a clinical marker for internal malignancies: a nationwide population-based cohort study.

INTRODUCTION: Non-melanoma skin cancers (NMSCs) are the most common cancers in the world, but the risk of internal malignancy in patients with NMSC has not been well investigated. OBJECTIVES: We aimed to assess the risk of internal malignancy in patients with NMSC compared with controls without NMSC in Korean population. METHODS: This nationwide cohort study, compared 27 259 NMSC patients with 54 518 matched controls without NMSC, 40 years or older using the data from Korea Health Insurance Review and Assessment Service from 2007 to 2016. The first 2 years were washout period, and we followed the patients for 8 years to observe the development of any internal malignancies after a diagnosis of NMSC. The Cox proportional hazard model was used to determine the hazard ratios (HRs) for developing internal malignancies. RESULTS: The overall risk of internal malignancies at all sites was 2727.7 and 1392.4 per 100 000 person-years for the patients with NMSC and controls, respectively. The risk was significantly higher in the patients with NMSC (HR 1.866, 95% confidence interval [CI] 1.768-1.970). Bone cancer showed the highest risk (HR 12.745, 95% CI 6.288-25.834), followed by nasal cavity and larynx (HR 10.279, 95% CI 6.178-7.103), oral cavity and pharynx (HR 10.211, 95% CI 7.375-14.137), anus and anal canal (HR 8.147, 95% CI 3.893-17.051) and cervical (HR 5.900, 95% CI 3.694-9.423) cancers with risks greater than fivefold higher in NMSC patients compared with the controls. The risks of cancers of the thorax, oesophagus, breast, lung, stomach, thyroid gland and non-Hodgkin's lymphoma were also statistically higher in the patients with NMSC. In contrast, the risks of cancers of the colon and rectum were found to be significantly decreased in the patients with NMSC (HR 0.765, 95% CI 0.657-0.890). CONCLUSION: Patients with NMSC require careful screening and follow-up for internal malignancy.

A multicentre, open, investigator-initiated phase IV clinical trial to evaluate the efficacy and safety of ingenol mebutate gel, 0·015% on the face and scalp, and 0·05% on the trunk and extremities, in Korean patients with actinic keratosis (PERFECT).

BACKGROUND: Ingenol mebutate gel is a novel, field-directed topical treatment for actinic keratosis (AK). Most pivotal studies have targeted Western populations. No clinical study has been conducted to investigate its efficacy and safety in Asian populations. OBJECTIVES: To evaluate the efficacy and safety of ingenol mebutate gel for treating AK of face/scalp and trunk/extremities in a large Asian (Korean) population. PATIENTS AND METHODS: In this multicentre, open-label, interventional, parallel-group, prospective phase IV study (PERFECT, trial registration no.: NCT02716714), the eligible patients were allocated into either the face/scalp or the trunk/extremities group, according to their selected treatment area location. After application of ingenol mebutate gel, the participants were followed up for 6 months. The primary efficacy endpoint was complete clearance (CC) of AK lesions in the selected treatment area at day 57. Quality of life was evaluated using Skindex-29. Safety endpoints included local skin responses, scar, pigmentation, pain and adverse events. RESULTS: In total, 78·1% [95% confidence interval (CI) 66·86-86·92%] of subjects had CC at day 57, with 76·6% (95% CI 64·31-86·25%) in the face/scalp group and 88·9% (95% CI 51·75-99·72%) in the trunk/extremities group. Among them, CC was sustained in 88·9% (48 of 54, 95% CI 77·37-95·81%) at month 6. The local skin responses significantly increased 1 day after the treatment compared with baseline, and decreased afterwards. Among the total subjects, 7·8% (6 of 77) had hyperpigmentation on the application area. Scars were not reported. CONCLUSIONS: Ingenol mebutate is effective for the treatment of AK in Asians, with tolerable safety profiles.

Mohs micrographic surgery for dermatofibrosarcoma protuberans: comparison of frozen and paraffin techniques.

BACKGROUND: Due to the propensity for local recurrence, Mohs micrographic surgery (MMS) has been suggested for the treatment of dermatofibrosarcoma protuberans (DFSP) and it has shown improved clinical outcomes. Recently, some authors suggested that MMS using paraffin-embedded sections (paraffin MMS) is superior in DFSP treatment compared with the conventional frozen MMS method. However, there have been no studies comparing frozen and paraffin MMS for the treatment of DFSP. OBJECTIVES: To compare the outcomes between DFSP patients who underwent frozen MMS and paraffin MMS. METHODS: Seventy-one DFSP patients treated with frozen MMS (n = 30) or paraffin MMS (n = 41) from 2003 to 2017 at a single institution were retrospectively reviewed. Recurrence rate and recurrence-free survival between frozen and paraffin MMS were assessed. RESULTS: During the mean follow-up duration of 25.4 months, four patients (frozen MMS, n = 1; and paraffin MMS, n = 3) showed recurrence after MMS. Although the local recurrence rate of the frozen MMS group (3.3%) was lower than that of the paraffin MMS group (7.3%), the difference was not statistically significant. In addition, recurrence-free survival was not significantly different between the two groups (P = 0.168). CONCLUSIONS: Frozen MMS, which has the advantages of shorter surgery time and immediate closure, is as effective as paraffin MMS in the treatment of DFSP.

AMPKα, C/EBPß, CPT1ß, GPR43, PPARγ, and SCD Gene Expression in Single- and Co-cultured Bovine Satellite Cells and Intramuscular Preadipocytes Treated with Palmitic, Stearic, Oleic, and Linoleic Acid.

We previously demonstrated that bovine subcutaneous preadipocytes promote adipogenic gene expression in muscle satellite cells in a co-culture system. Herein we hypothesize that saturated fatty acids would promote adipogenic/lipogenic gene expression, whereas mono- and polyunsaturated fatty acids would have the opposite effect. Bovine semimembranosus satellite cells (BSC) and intramuscular preadipocytes (IPA) were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS)/Dulbecco's Modified Eagle Medium (DMEM) and 1% antibiotics during the 3-d proliferation period. After proliferation, cells were treated for 3 d with 3% horse serum/DMEM (BSC) or 5% FBS/DMEM (IPA) with antibiotics. Media also contained 10 µg/mL insulin and 10 µg/mL pioglitazone. Subsequently, differentiating BSC and IPA were cultured in their respective media with 40 µM palmitic, stearic, oleic, or linoleic acid for 4 d. Finally, BSC and IPA were single- or co-cultured for an additional 2 h. All fatty acid treatments increased (p = 0.001) carnitine palmitoyltransferase-1 beta (CPT1ß) gene expression, but the increase in CPT1ß gene expression was especially pronounced in IPA incubated with palmitic and stearic acid (6- to 17- fold increases). Oleic and linoleic acid decreased (p = 0.001) stearoyl-CoA desaturase (SCD) gene expression over 80% in both BSC and IPA. Conversely, palmitic and stearic acid increased SCD gene expression three fold in co-cultured in IPA, and stearic acid increased AMPKα gene expression in single- and co-cultured BSC and IPA. Consistent with our hypothesis, saturated fatty acids, especially stearic acid, promoted adipogenic and lipogenic gene expression, whereas unsaturated fatty acids decreased expression of those genes associated with fatty acid metabolism.

A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas.

BACKGROUND: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. METHODS: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m(-2) and cisplatin 25 mg m(-2) on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m(-2), cisplatin 20 mg m(-2) and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. RESULTS: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes. CONCLUSION: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.

Comparison of negative pressure wound therapy and secondary intention healing after excision of acral lentiginous melanoma on the foot.

BACKGROUND: Melanoma in dark-skinned individuals often develops in an acral lentiginous fashion on the foot and wide excision usually results in a substantial defect. Various repair methods, including free flap, full-thickness skin graft and secondary intention healing (SIH), are used to repair these defects. Recently, use of negative pressure wound treatment (NPWT) has been shown to accelerate wound healing in different types of wound. OBJECTIVES: To compare the functional and cosmetic results of NPWT and SIH in patients who underwent wide excision of melanomas on the foot. METHODS: The wound defects of 22 patients after wide excision of melanoma on the foot were treated using SIH (n = 13) or NPWT (n = 9). RESULTS: There was no significant difference in time to complete wound healing between the two groups. However, evaluation using the Vancouver Burn Scar Assessment Scale at the time of complete healing showed that the mean score of the NPWT group was significantly lower than that of the SIH group. The NPWT group also had significantly better results than the SIH group in terms of total score, vascularity and height of the scars. As for complications, no wound infection was encountered in the NPWT group, whereas eight of the 13 patients in SIH group had wound infections during the course of treatment despite frequent and meticulous aseptic dressing changes. CONCLUSIONS: These results show that, despite the drawback of rather prolonged healing time, NPWT is an excellent therapeutic option for wounds after wide excision of melanoma on the foot, with acceptable functional and cosmetic outcomes.

Patient perception and knowledge on total joint replacement surgery.

OBJECTIVES: To study patients' perceptions and knowledge about total joint replacement surgery. DESIGN; Cross-sectional survey. SETTING; University teaching hospital, Hong Kong. PATIENTS: Three hundred consecutive patients with the diagnosis of osteoarthritis or inflammatory arthritis attending the out-patient clinic from June 2010 to May 2011. MAIN OUTCOME MEASURES: Patients' knowledge and how they got the knowledge about total joint replacement surgery, and concerns about the outcome of such operations. RESULTS: Whilst 94% of the patients knew about total joint replacement surgery, 77% obtained such knowledge from their friends and relatives. The three most common concerns related to this type of operation were whether they might: be wheelchair bound after surgery (64%), need to be taken care of by others for more than 3 months (61%), and have post-surgery complications (54%). Most of them recognised the advantages of the surgery, 82% knew about good pain relief after surgery, and 87% realised that total joint replacement surgery could improve their mobility. Patients did not have a realistic idea regarding the survival of the prosthesis; 41% thought the prosthesis might last for less than 10 years and 34% had no idea about its longevity. CONCLUSION; Patients did recognise the advantages of total joint replacement surgery in treating arthritis. However, they had many concerns about its outcome that warrant clarification. Public education on these aspects is necessary to address concerns, and may be achieved in cooperation with the media.

Novel modification of Marcy operation for indirect inguinal hernia reconstituting deep inguinal ring shutter action.

PURPOSE: The two most frequent and significant complications after inguinal hernia repair are hernia recurrence and post-herniorrhaphy chronic pain. To add anatomic and physiologic strength to the tissue repair, especially in indirect inguinal herniorrhaphy, we devised a modification of Marcy operation that can reconstitute inguinal shutter action more efficiently by changing the direction of the sutures vertical to horizontal. METHODS: During 36 months from 1st Jan. 2019, 148cases of 140 patients were operated for Indirect inguinal hernia or Pantaloon hernia (11 cases). 145 indirect inguinal herniorrhaphy were performed exclusively with author's modification of Marcy operation. Hernia recurrence during the follow-up period (3 months-36 months), and postoperative chronic pain at 3 months after herniorrhaphy were analyzed. RESULTS: 104 cases among the 145 indirect inguinal hernia (71.7%) were operated with only deep inguinal ring (DIR) reconstruction as author modified. In 41 cases (28.3%), posterior wall reconstruction was done simultaneously. There was no recurrence or reoperation case during the follow-up period. The incidence of postoperative chronic pain at postoperative 3 months of VAS greater than 3.0 was 2.2% (3 cases). CONCLUSIONS: Author's modification of Marcy operation was feasible anatomically in all indirect inguinal hernia repair, which is theoretically superior to classic Marcy operation in that repositioning the DIR more laterally and securing the obliquity and shutter action of the DIR. Result is at least not inferior in the aspect of short-term recurrence and chronic post-herniorrhaphy pain.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

Synthesis and enhanced electrochemical performance of Li2CoPO4F cathodes under high current cycling.

Lithium cobalt fluorophosphate, Li(2)CoPO(4)F, is successfully synthesized by a solid state reaction under Ar flow at 700 °C. X-ray diffraction and scanning electron microscopic studies are utilized to analyze the structural and morphological features of the synthesized materials, respectively. The presence of fluorine is also supported by energy-dispersive X-ray spectroscopy. The electrochemical properties are evaluated by means of Li/Li(2)CoPO(4)F half-cell configurations in both potentiostatic and galvanostatic modes. The Li/Li(2)CoPO(4)F cell delivers an initial discharge capacity of 132 mA h g(-1) at a current density of 0.1 mA cm(-2) between 2.0 and 5.1 V at room temperature. Due to the higher operating potential of the Co(2+/3+) couple in the fluorophosphate matrix, this cell shows a capacity retention of only 53% after 20 cycles, still the material delivered 108 mA h g(-1) at a high current rate of 1 C. Cyclic voltammetric studies corroborate the insertion and extraction of Li(+) ions by a single phase reaction mechanism during cycling.

Measurements on the routine chest radiograph as prognostic markers in Chinese peritoneal dialysis patients.

BACKGROUND: Fluid overload is a common problem in peritoneal dialysis (PD) patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine chest radiograph are useful indicators of intravascular volume status and may represent important prognostic factors of PD patients. METHODS: We measured VPW and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the thoracic diameter (VPWR). One-year actuarial survival, technique survival, and duration of hospitalization were analyzed. RESULTS: The mean values of VPW, CTR, VPWR were 47.31 ± 4.73 mm, 0.542 ± 0.074, 0.170 ± 0.024, respectively. VPW correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001), body height (r = 0.271; p < 0.001), and Charlson's index score (r = 0.153; p = 0.01). One-year patient survival was 87.8%, and technique survival was 82.2%. None of the radiological measurements had an independent effect on one-year actuarial or technique survival by multivariate analysis. Both CTR and VPWR correlated with the duration of hospitalization (r = 0.192 and 0.186, respectively (p = 0.001 and 0.002). Multivariate regression analysis by log-linear modeling showed that independent predictors of one-year hospitalization were VPWR, serum albumin, and SGA overall score. CONCLUSIONS: In Chinese PD patients, VPW was significantly correlated with age, body weight, body height and Charlson's index score. VPWR was an independent predictor of the duration of hospitalization. Further studies are needed to confirm the prognostic value of these radiographic measurements in PD patients.

Treatment of periorbital wrinkles with 1550- and 1565-nm Er:glass fractional photothermolysis lasers: a simultaneous split-face trial.

OBJECTIVE: This study aimed to compare the clinical efficacies of 1550- and 1565-nm Er:glass lasers in the treatment of periorbital wrinkles and to evaluate histological changes after treatment. METHODS: Twenty patients received five treatments each at 3-week intervals. The right periorbital area was exposed to the 1550-nm Er:glass laser and the left periorbital area was exposed to the 1565-nm Er:glass laser. Clinical improvement was evaluated by two blinded physicians who assessed comparative photographs using a four-point scale at baseline and 3 months after the final treatments. Skin biopsies were performed in five volunteers before treatment and at 3 months after the final treatment. RESULTS: The mean improvement scores 3 months after treatment with the 1550- and 1565-nm Er:glass lasers were 2.25±0.62 and 2.28±0.59 respectively. Histological examination revealed increased epidermal thickening and decreased solar elastosis 3 months after the final laser treatments. CONCLUSIONS: Both 1550- and 1565-nm Er:glass lasers are safe and effective modalities in the treatment of periorbital wrinkles with no significant differences between the two lasers.

The antimicrobial peptide human cationic antimicrobial protein-18/cathelicidin LL-37 as a putative growth factor for malignant melanoma.

BACKGROUND: Recent evidence suggests cathelicidin LL-37 to be a growth factor for various human cancers such as lung cancer, ovarian cancer and breast cancer. However, the effect of LL-37 against malignant skin cancer has not been reported. OBJECTIVES: To investigate whether the human cathelicidin LL-37 is involved in the carcinogenesis of various skin tumours. METHODS: Human cationic antimicrobial protein-18 (hCAP-18)/LL-37 production in several cell lines including HaCaT, a chronic myelogenous leukaemia (CML) cell line and various melanoma cell lines was examined using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Immunohistochemical analysis of melanoma, nonmelanoma skin cancer and precancerous and benign skin lesions was performed. After adding LL-37 to a melanoma cell line, tumour cell proliferation, migration and invasion were investigated. RESULTS: Human malignant melanoma cell lines overexpressed hCAP-18/LL-37 mRNA and peptide compared with HaCaT and CML cell lines. Immunohistochemistry showed that the peptide was strongly expressed in malignant melanoma and moderately expressed in squamous cell carcinoma, whereas basal cell carcinoma, precancerous lesions and seborrhoeic keratosis showed no or weak expression. LL-37 also stimulated melanoma cell proliferation, migration and invasion in vitro. CONCLUSIONS: Cathelicidin LL-37 was primarily expressed in human malignant skin cancer. LL-37 promoted melanoma cell proliferation, migration and invasion in vitro. We report that an increase in the level of LL-37 is associated with malignant skin tumours such as malignant melanoma. These results highlight the importance of LL-37 in the malignant tendency of skin tumours.