A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Both cardiovascular and cerebrovascular events are decreased following long-term narrowband ultraviolet B phototherapy in patients with vitiligo: a propensity score matching analysis.

BACKGROUND: Systemic effects of long-term narrowband ultraviolet B (NB-UVB) phototherapy have not been well studied in vitiligo patients. An 11-year nationwide population-based retrospective cohort study was conducted using the Korean National Health Insurance claims database (2007-2017). OBJECTIVES: To investigate the effects of long-term NB-UVB phototherapy on the risk of cardiovascular and cerebrovascular events in vitiligo patients. METHODS: This study included vitiligo patients with ≥100 phototherapy sessions (phototherapy group, n = 3229) and <3 phototherapy sessions (no phototherapy group, n = 9687), in which covariables with age, sex, insurance type and comorbidities such as diabetes, hypertension and hyperlipidemia were matched by 1 : 3 propensity score matching. The outcomes of interest were cardiovascular (ischaemic heart disease and myocardial infarction) and cerebrovascular events (cerebrovascular infraction and haemorrhage). Cox proportional hazards models were used to assess the associations between NB-UVB phototherapy and each event. RESULTS: The risk of cardiovascular or cerebrovascular events was significantly decreased in the phototherapy group compared with the no phototherapy group [hazard ratio (HR) 0.637, 95% confidence interval (CI) 0.523-0.776]. Subgroup analysis revealed that the risk of cardiovascular (HR: 0.682, 95% CI: 0.495-0.940) and cerebrovascular events (HR: 0.601, 95% CI: 0.470-0.769) were significantly lower in the phototherapy group than the no phototherapy group, respectively. CONCLUSIONS: Our findings suggest that long-term NB-UVB phototherapy could decrease the risk of cardiovascular and cerebrovascular events in patients with vitiligo.

Ultraviolet photography in vitiligo: image quality, validity and reliability.

BACKGROUND: For clinical care and research in vitiligo, photographs with the use of ultraviolet (UV) light or Wood's lamp are often made. Conventional cameras are insensitive to UV light. The use of a UV camera (UV photography) might improve image quality and ameliorate the assessment of target lesions in vitiligo. OBJECTIVES: To determine image quality and the validity and reliability of UV photography for the assessment of vitiligo target lesions. METHODS: Images of patients with vitiligo were made with UV photography and a conventional camera, and lesions were drawn on graph paper and transparent sheets. Image quality was scored by vitiligo experts and medical interns. The intraclass correlation coefficients (ICCs) of the lesion size determined with UV photography combined with digital surface measurement and the other techniques were hypothesized to be above 0.6. The ICCs between UV images taken by the same physician and between two different physicians were calculated for determining inter- and intra-reliability. RESULTS: In total, 31 lesions of 17 patients were included. Image quality was assessed as good or very good for 100% and 26% for UV photography and the conventional camera, respectively. ICCs of UV photography and the conventional camera, drawing the lesions on transparent sheets and graph paper, were 0.984, 0.988 and 0.983, respectively, confirming our hypotheses. The ICCs of the intra-rater and inter-rater were 0.999 and 0.998, respectively. CONCLUSIONS: The results of this study indicate that the use of UV photography for the assessment of vitiligo lesions improves image quality and is valid and reliable.

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.

[Ethical, pedagogical, socio-political and anthropological implications of quaternary prevention]. / Implications éthiques, pédagogiques, sociopolitiques et anthropologiques de la prévention quaternaire.

The concept of quaternary prevention, resulting from a reflection on the doctor-patient relationship, is presented as a renewal of the ageold ethical requirement: first, a doctor must not harm; second, the doctor must control himself/herself. The origin of the concept, its endorsement by the World Organization of Family Doctors (WONCA) and the European Union of General Practitioners (UEMO), its dissemination, and the debates to which it has given rise, are presented by a panel of authors from 12 countries and 3 continents. This collective text deals more specifically with the ethics of prevention, the importance of teaching Quaternary prevention and Evidence Based Medicine, the social and political implications of the concept of quaternary prevention, and its anthropological dimensions.

Le concept de prévention quaternaire, issu d'une réflexion sur la relation médecin-patient, est présenté d'une part comme un renouvellement d'une exigence éthique séculaire ; d'abord ne pas nuire et d'autre part comme un plaidoyer pour un autocontrôle du médecin. L'origine du concept, son approbation par l'Organisation Mondiale des Médecins de Famille (WONCA) et l'Union Européenne des Médecins Omnipraticiens (UEMO), sa diffusion et les débats auxquels il a donné lieu, sont présentés par un panel d'auteurs de 12 pays et trois continents. Ce texte collectif traite plus spécifiquement de l'éthique de la prévention, de l'importance de l'enseignement de la prévention quaternaire et de la médecine factuelle, des implications sociales et politiques du concept de prévention quaternaire et de ses dimensions anthropologiques.

Incidence of psoriasiform diseases secondary to tumour necrosis factor antagonists in patients with inflammatory bowel disease: a nationwide population-based cohort study.

BACKGROUND: There are increasing reports of paradoxical psoriasiform diseases secondary to anti-tumour necrosis factor (TNF) agents. AIMS: To determine the risks of paradoxical psoriasiform diseases secondary to anti-TNF agents in patients with inflammatory bowel disease (IBD). METHODS: A nationwide population study was performed using the Korea National Health Insurance Claim Data. A total of 50 502 patients with IBD were identified between 2007 and 2016. We compared 5428 patients who were treated with any anti-TNF agent for more than 6 months (anti-TNF group) and 10 856 matched controls who had never taken anti-TNF agents (control group). RESULTS: Incidence of psoriasis was significantly higher in the anti-TNF group (36.8 per 10 000 person-years) compared to the control group (14.5 per 10 000 person-years) (hazard ratio [HR] 2.357, 95% confidence interval [CI] 1.668-3.331). Palmoplantar pustulosis (HR 9.355, 95% CI 2.754-31.780) and psoriatic arthritis (HR 2.926, 95% CI 1.640-5.218) also showed higher risks in the anti-TNF group. In subgroup analyses, HRs for psoriasis by IBD subtype were 2.549 (95% CI 1.658-3.920) in Crohn's disease and 2.105 (95% CI 1.155-3.836) in ulcerative colitis. Interestingly, men and younger (10-39 years) patients have significantly higher risks of palmoplantar pustulosis (HR 19.682 [95% CI 3.867-100.169] and HR 14.318 [95% CI 2.915-70.315], respectively), whereas women and older (≥40 years) patients showed similar rates between the two groups. CONCLUSIONS: The risks of psoriasiform diseases are increased by anti-TNF agents in patients with IBD. Among psoriasiform diseases, the risk of palmoplantar pustulosis shows the biggest increase particularly in male and younger patients.

Prevalence and comorbidities associated with hidradenitis suppurativa in Korea: a nationwide population-based study.

BACKGROUND: The prevalence of hidradenitis suppurativa (HS) in Asia is unknown. The associations between HS and other autoimmune disorders have rarely been reported. OBJECTIVE: We sought to determine the prevalence of and diseases associated with HS using the National Health Insurance (NHI) database. METHODS: We examined Korean NHI claim database data from 2007 to 2016. We enrolled all patients with HS and age- and sex-matched control subjects without HS. We estimated the period prevalence of HS and associated comorbidities in Korea. RESULTS: We identified 28 516 patients with HS (61.3% males and 38.7% females). The period prevalence rate was 0.06%, 55.8 patients (95% confidence interval 55.1-56.4) per 100 000 persons, and the female-to-male ratio was 1 : 1.6. HS patients were at significantly increased risk of rheumatoid arthritis, ankylosing spondylitis, type 1 diabetes, ulcerative colitis, type 2 diabetes, hypertension, hyperlipidaemia, acne conglobata, pilonidal cysts, psoriasis, pyoderma gangrenosum, alopecia areata and vitiligo. CONCLUSION: The overall prevalence of HS in Korea was lower than that in Western populations, and male patients predominated.

Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.

Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples. Results: Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions: The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.

Factors affecting quality of life in patients with vitiligo: a nationwide study.

BACKGROUND: Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. OBJECTIVES: To explore the QoL of patients with vitiligo and to identify factors affecting QoL. METHODS: A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. RESULTS: Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20-84). The median duration of disease was 3·0 years (range 0-60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20-59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. CONCLUSIONS: A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.

Periorbital melasma: Hierarchical cluster analysis of clinical features in Asian patients.

BACKGROUND: Studies have shown melasma lesions to be distributed across the face in centrofacial, malar, and mandibular patterns. Meanwhile, however, melasma lesions of the periorbital area have yet to be thoroughly described. METHODS: We analyzed normal and ultraviolet light-exposed photographs of patients with melasma. The periorbital melasma lesions were measured according to anatomical reference points and a hierarchical cluster analysis was performed. RESULTS: The periorbital melasma lesions showed clinical features of fine and homogenous melasma pigmentation, involving both the upper and lower eyelids that extended to other anatomical sites with a darker and coarser appearance. The hierarchical cluster analysis indicated that patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face. Significant differences between cluster 1 and cluster 2 were found in lateral distance and inferolateral distance, but not in medial distance and superior distance. Comparing the two clusters, patients in cluster 2 were found to be significantly older and more commonly accompanied by melasma lesions of the temple and medial cheek. CONCLUSION: Our hierarchical cluster analysis of periorbital melasma lesions demonstrated that Asian patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face.