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PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481 ).

BACKGROUND: Endothelial activation and insult may contribute to the aggressive clinical course of small-cell lung cancer (SCLC); however, no predictive biomarker for this pathogenesis has been identified. OBJECTIVE: To evaluate the clinical impact of the endothelial activation and stress index (EASIX) in SCLC. METHODS: In this retrospective study, the EASIX was calculated from measurements of serum lactate dehydrogenase, creatinine, and platelet levels. A total of 264 patients with SCLC treated with platinum-based chemotherapy were stratified into high and low EASIX groups. RESULTS: Complete and objective response rates in the limited-stage (LD) were 19.5% vs. 33.3% (P= 0.050) and 85.4% vs. 97.9% (P= 0.028) in the high and low EASIX groups, respectively. There was no significant difference in the response rate between the two groups in the extensive-stage (ED). The median overall survival was 9.8 vs. 40.5 months in LD (P< 0.001) and 7.2 vs. 11.9 months in ED (P< 0.001) in the high and low EASIX groups, respectively. In multivariate analyses, a high EASIX level was an independent prognostic factor for worse progression-free and overall survival irrespective of stage. CONCLUSION: EASIX may be a potential predictive biomarker of SCLC.

Background: This multicenter study investigated the predictive value of baseline AFP and on-treatment AFP response for survival in hepatocellular carcinoma (HCC) patients with regorafenib. Materials & methods: A total of 578 patients with HCC treated with regorafenib from 12 institutions in South Korea and Italy were included. Baseline AFP (cutoff, 400 ng/ml) and AFP response (20% reduction from baseline) were analyzed for overall survival (OS) and progression-free survival (PFS). Results: Baseline AFP below 400 ng/ml was a significant factor that was independently associated with longer OS and PFS. AFP response was also a significant factor independently associated with longer OS and PFS. Conclusion: Baseline AFP and AFP response may be used as prognostic factors for survival in HCC treated with regorafenib.

Background: Opioids are effective analgesics for cancer pain and refractory non-cancer pain. Although they are essential medication, problematic issues on aberrant behavior and adverse events have rapidly emerged as social problems in Korea. This study aimed to describe the mechanisms, efficacy, and adverse events, especially how to deal with opioid dependency.Current Concepts: Opioid-induced aberrant behavior includes physical and psychological dependences (addiction), abuse, and diversion (giving prescribed opioids to another person). Most physicians are unfamiliar with how to handle patients presenting these problematic issues. Physical and psychological dependences develop through different pathophysiologic mechanisms, i.e., noradrenergic and dopaminergic pathways, respectively. Motivational enhancement therapy, psychosocial support, substitution therapy with buprenorphine, and adjunctive medications, including alpha-2 adrenergic agonist, antidepressants, and non-steroidal antiinflammatory drugs, are the mainstay of treatment for opioid dependency. Constipation, nausea/vomiting, drowsiness/sedation, delirium, itching sensation, voiding difficulty, dry mouth, opioid-induced hyperalgesia, and respiratory depression are well-known physical side effects of opioid consumption.Discussion and Conclusion: Research on the development history, epidemiology of opioid dependency, and its treatment are warranted to avoid an opioid crisis in Korea. Above all, thorough knowledge for physicians and patients is urgently needed.

Background The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. Patients and methods Eighty mPAC patients (age, 19–75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1–2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1–28 every 6 weeks. Results Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p Conclusion Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.

Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1–8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6–22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

Purpose Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated prescription patterns and impact on the survival and the venous thromboembolism (VTE) of MA in patients with advanced cancer.Methods In this study, a Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric, colorectal, and pancreatobiliary cancers from July 2014 to December 2015.Results A total of 5,920 patients were included in this study. In total, 66.9% of the patients were prescribed MA. Pancreatobiliary cancer, older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 42.2% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups. Among the 4,081 patients included in the analysis for VTE incidence, 5.4% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis.Conclusions This study demonstrated that most patients with advanced gastrointestinal and pancreatobiliary cancer required MA prescription. The difference in the incidence of VTE was modest between the MA and non-MA prescription groups (not at the level of statistical significance on multivariate analyses).

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.

157 Background: There is a rarity of evidence for retreatment with oxaliplatin for metastatic colorectal cancer (mCRC), especially in combination with bevacizumab. This is a retrospective study of second line bevacizumab (Bev) plus FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-containing chemotherapy. Methods: Patients with age older than 18 and histologically confirmed metastatic colorectal cancer treated with second line bevacizumab plus FOLFOX in a single institute between 2015 and 2020 were enrolled. History of previous adjuvant chemotherapy regimens in patients with metachronous metastatic colorectal cancer was analyzed. Progression-free survival (PFS) and overall survival (OS) of the second line treatment were calculated using Kaplan-Meier method and compared between patients pretreated with adjuvant oxaliplatin (ReOx) and oxaliplatin-naive patients (control) with the log rank test. Results: A total of 72 patients were included. 23 patients (ReOx) were pretreated with adjuvant oxaliplatin and 49 patients (control) were oxaliplatin-naive before the second line treatment. There was a tendency of younger age in the ReOx group, but not statistically significant. Liver metastasis was significantly more frequent in the control group. The median PFS and OS in the ReOx group and the control group were 4.3 months (95% confidence interval [CI], 3.67–21.50) versus 5.5 months (95% CI, 4.23–8.20, hazard ratio [HR] = 0.84), and 10.5 months (95% CI, 5.40–30.37) versus 9.4 months (95% CI, 6.00–14.9, HR = 1.01) respectively. There was no significant difference of PFS ( p= 0.523) and OS ( p= 0.9745) between two groups. Conclusions: This study suggests a potential survival benefit of bevacizumab plus FOLFOX for mCRC patients previously treated with adjuvant oxaliplatin-containing treatment comparable to oxaliplatin-naive patients. [Table: see text]

304 Background: The characteristics and prognosis of de novo metastatic gastric cancer and recurrent metastatic gastric cancer have not yet been elucidated. Here, we compare prognosis and characteristics of patients with de novo versus recurrent gastric cancer. Methods: This retrospective study included 301 advanced pathologically confirmed gastric cancer patients who received palliative chemotherapy between 2012 and 2022. The de novo cohort was included of patients who presented with distant metastasis at diagnosis and recurrent metastatic cohort was composed of patients with metastasis after curative gastrectomy. We analyzed prognostic association by Cox regression and compared survival time of both cohorts using the Kaplan-meire method. Results: A total of 167 de novo and 112 recurrent patients were included. There were no differences noted among the patients with de novo disease and recurrent metastatic disease with respect to age, sex, ECOG, primary cancer location and pathologic features. Patients in the recurrent group versus de novo group were longer duration of chemotherapy (1.16 ± 1.18 years versus 0.85 ± 0.84, P = 0.01) and lower mean body mass index. (20.22 ± 2.78 versus 21.93 ± 3.38, p < 0.001) The median overall survival in the de novo group was 11.6 versus s 14.4 months in the recurrent group. ( P = 0.02) In a multivariate analysis, the age of 70 years or older at the time of stage 4 diagnosis was independently associated with shorter survival. Conclusions: De novo and recurrent metastatic gastric cancer characterize distinguished subpopulations. And advanced gastric cancer with distant recurrence has significantly better survival versus those with de novo cohort. This differences between de novo and recurrent gastric cancer could facilitate discussions about patient selection of clinical trial and help with advanced personalized treatment. [Table: see text]

Although palliative sedation (PS) is a common practice in the palliative care of cancer patients in Western countries, there is little related research on the practice in Korea. PS can be classified into several categories according to sedation level and continuity. PS is clearly distinct from euthanasia. While euthanasia is illegal and regarded as unethical in Korea, there is little ethical and legal controversy about PS in terms of the doctrine of double effect. Most studies have asserted that PS does not shorten the survival of terminal cancer patients. Since preference for PS heavily depends on stakeholder value, it should be preceded by shared decision-making through full communication among the patient, family members, and medical team. This is a narrative review article analyzing previous studies, especially from the three Eastern Asian countries, Korea, Japan and Taiwan, which share similar cultures compared with Western countries. Practical issues concerning PS—for example, prevalence, type and dosage of medications, salvage medication, timing of its initiation, and assessment—are described in detail.

The risk of opioid-related aberrant behavior (OAB) in Korean cancer patients has not been previously evaluated. The purpose of this study is to investigate the Opioid Risk Tool (ORT) in Korean cancer patients receiving opioid treatment.Data were obtained from a multicenter, cross-sectional, nationwide observational study regarding breakthrough cancer pain. The study was conducted in 33 South Korean institutions from March 2016 to December 2017. Patients were eligible if they had cancer-related pain within the past 7 days, which was treated with strong opioids in the previous 7 days.We analyzed ORT results of 946 patients. Only one patient in each sex (0.2%) was classified as high risk for OAB. Moderate risk was observed in 18 males (3.3%) and in three females (0.7%). Scores above 0 were primarily derived from positive responses for personal or familial history of alcohol abuse (in men), or depression (in women). In patients with an ORT score of 1 or higher (n = 132, 14%), the score primarily represented positive responses for personal history of depression (in females), personal or family history of alcohol abuse (in males), or 16-45 years age range. These patients had more severe worst and average pain intensity (proportion of numeric rating scale ≥ 4: 20.5% vs. 11.4%,The score of ORT was very low in cancer patients receiving strong opioids for analgesia. Higher pain intensity may associate with positive response to one or more ORT item.

Government healthcare expenditure is rising in Korea, and the costs incurred by patients in Korea exceed those incurred by patients in other Organization for Economic Co-operation and Development countries. Despite the increasing health expenditure, patient demand for services is increasing as well, so it is now becoming recognized that cancer care needs to be balanced. The most important measure in cancer care optimization is to provide high-quality care while keeping costs sustainable. The Korean Cancer Association considers the current situation of cancer therapy in Korea the foremost issue, which has led to the implementation of the nationwide ‘Right Decisions in Cancer Care’ initiative. This initiative is based on the concepts of medical professionalism in that it should be led by physicians working in the field of oncology, that education should be offered to patients and clinicians, and that it should influence healthcare policy. In this article, we introduce the nationwide ‘Right Decision in Cancer Care’ initiative and highlight the five initial items on its agenda. The agenda is open to expansion and update as the medical environment evolves and additional clinical evidence becomes available.

A caregiver’s prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers’ prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers. This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers’ awareness of the prognosis. Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients’ QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients’ prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024). Caregivers’ prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.

Objectives Enterococcus pRE25 is a conjugative and mobilising multiresistance plasmid from Enterococcus faecalis RE25. pRE25-like enterococcal plasmid pWZ909 mediates the delivery of vancomycin resistance to methicillin-resistant Staphylococcus aureus via a Tn1546-like transposon. However, whether pRE25-like elements contribute to multidrug resistance in Staphylococcus spp. has not yet been investigated. Here we describe the first detection of multiresistance pRE25-like elements in the chromosomal DNA of multidrug-resistant Staphylococcus pseudintermedius (MDRSP). Methods A total of 46 MDRSP clinical strains were isolated from canine pyoderma in Korea. Their genetic characteristics were analysed by multilocus sequence typing (MLST) and PCR targeting pRE25-like elements. Whole-genome sequencing (WGS) was performed on four isolates. Results WGS detected that the chromosomal 22-kb pRE25-like elements contained five antimicrobial resistance genes [cat, erm(B), aphA-3, aadK and sat4], IS1252, IS256, and a toxin–antitoxin system within copies of IS1216. BLASTn alignment analysis revealed that 84% of the chromosomal 22-kb pRE25-like elements sequence is homologous (99.8% identity) to the enterococcal pRE25 plasmid sequence. PCR assay showed that 52.2% of MDRSP isolates were positive for pRE25-like elements and were presumed to contain pRE25-like elements (pRE25 group). The sequence types (STs) of the pRE25 group were diverse, with 18 STs identified, among which 12 STs were first reported in Korea. Conclusion Enterococcal pRE25-like elements are suspected to be widespread in MDRSP isolated from companion dogs in Korea. Considering that companion dogs live in a closely shared environment with humans, continuous surveillance of pRE25-like elements is needed for other staphylococci commonly isolated from humans.

Little has been determined regarding the association between patients’ and families’ illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers. Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results. Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients’ illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC. Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.

Background: To investigate the characteristics of cancer survivors and the effects of the services of the Korean Cancer Survivorship Center Pilot Project launched by the South Korean government on distress.Methods: A prospective observational cohort study was performed in cancer survivors who completed primary treatment. Cancer survivors’ distress and symptoms such as fatigue, pain, depressive mood, anxiety, and insomnia were evaluated by well-trained nurses. Regarding to their needs, medical and psychosocial support services were provided. Results: This study included 1,921 cancer survivors, with a mean age of 57.3 years (68.7% females). The breast cancer was most common, followed by stomach and colorectal cancer. Psychosocial and medical support decreased the percentage of the high-distress group from 50.9% to 30.5% and decreased the percentage of cancer survivors with high scores in fatigue, pain, anxiety, depressive mood, and insomnia. The independent predictors of a low distress level after the use of the services were older age, the relief of fatigue, pain, and insomnia.Conclusions: This study showed that psychosocial and medical support is associated with the lower distress and physical and mental symptoms of cancer survivors. Psychosocial and medical support could contribute to distress relief in cancer survivors. Further management strategies for fatigue, pain, and insomnia are required.

Background Cancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies. Methods A total of 267 patients diagnosed with diffuse large B‐cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil–lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3‐CXI or PM‐CXI. Using sex‐specific cutoff values for CXI, the patients were categorized as follows: (i) high‐CXI group (high L3‐CXI and high PM‐CXI), (ii) intermediate‐CXI group (high L3‐CXI and low PM‐CXI), and (iii) low‐CXI group (low L3‐CXI and low PM‐CXI). Results Complete responses to R‐CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high‐CXI, intermediate‐CXI, and low‐CXI groups, respectively (P

Cold atmospheric plasma (CAP) is a new generation medical therapeutic option for bacterial infections. CAP causes physical cell wall rupture and DNA damage, therefore making it highly useful in the treatment of various conditions such as skin infections.The antimicrobial activity of cold atmospheric microwave plasma (CAMP) against major strains in canine skin infections was tested and the difference in antimicrobial activity between the antibiotic-resistant and antibiotic-susceptible strains of Staphylococcus pseudintermedius was evaluated.American Type Culture Collection (ATCC) strains (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) and clinical isolates identified as methicillin-resistant S. pseudintermedius (n = 27) and methicillin-susceptible S. pseudintermedius (n = 13) were exposed to CAMP for 10 s, 30 s and 60 s. Afterwards, the bacterial survival rate was confirmed.Gram-negative bacteria (P. aeruginosa and E. coli) were more susceptible than Gram-positive bacteria (S. aureus and S. pseudintermedius) for the same duration of CAMP exposure. Only the Gram-negative bacteria were completely killed after 60 s exposure. In S. pseudintermedius isolates, CAMP exposure had similar antibacterial effects regardless of antibiotic resistance.CAMP has sufficient antimicrobial activity against major bacterial strains that cause pyoderma and otitis externa in dogs, and may be an alternative therapeutic option for S. pseudintermedius skin infections, for which antibiotics often are ineffective because of antimicrobial resistance in clinical veterinary medicine.Le CAP (Cold atmospheric plasma) est une nouvelle génération de traitement pour les infections bactériennes. CAP cause une rupture physique de la paroi et endommage l’ADN, le rendant ainsi hautement utile pour le traitement d’atteintes variées telles que les infections bactériennes. HYPOTHÈSES/OBJECTIFS: L’activité antimicrobienne de CAMP (cold atmospheric microwave plasma) contre des souches majeures des infections cutanées canines a été testée et la différence d’activité antimicrobienne entre les souches résistances ou sensibles aux antibiotiques de Staphylococcus pseudintermedius a été évaluée. MATÉRIELS ET MÉTHODES: Les souches ATCC (American Type Culture Collection) (Staphylococcus aureus, Pseudomonas aeruginosa et Escherichia coli) et les souches cliniques isolées de S. pseudintermedius identifiées comme résistantes à la méticiline (n = 27) S. pseudintermedius sensibles à la méticiline (n = 13) ont été exposées à CAMP pendant 10 s, 30 s et 60 s. Ensuite, le taux de survie bactérien a été confirmé. RÉSULTATS: Les bactéries Gram-négatives (P. aeruginosa et E. coli) étaient plus sensibles que les bactéries Gram-positives (S. aureus et S. pseudintermedius) pour la même durée d’exposition au CAMP. Seules les bactéries Gram-négatives étaient complètement tuées après 60s d’exposition. Dans les souches de S. pseudintermedius, l’exposition à CAMP avait des effets antibactériens similaires au regard de la résistance antibiotique.Le CAMP a une activité antimicrobienne suffisante contre les souches bactériennes majeures causant pyodermite et otite externe chez le chien et peut être une option thérapeutique alternative pour les infections cutanées à S. pseudintermedius pour laquelle les antibiotiques sont souvent inefficaces en raison de résistances antimicrobiennes en médecine vétérinaire clinique.INTRODUCCIÓN: el plasma atmosférico frío (CAP) es una opción terapéutica médica de nueva generación para las infecciones bacterianas. El CAP provoca la ruptura física de la pared celular y el daño al DNA, por lo que es muy útil en el tratamiento de diversas afecciones, como las infecciones de la piel. HIPÓTESIS/OBJETIVOS: se probó la actividad antimicrobiana del plasma de microondas atmosférico frío (CAMP) contra las principales cepas en las infecciones cutáneas caninas y se evaluó la diferencia en la actividad antimicrobiana entre las cepas resistentes y sensibles a los antibióticos de Staphylococcus pseudintermedius. MÉTODOS Y MATERIALES: cepas de la American Type Culture Collection (ATCC) (Staphylococcus aureus, Pseudomonas aeruginosa y Escherichia coli) y aislados clínicos identificados como S. pseudintermedius resistente a meticilina (n = 27) y S. pseudintermedius sensible a meticilina (n = 13) fueron expuestos a CAMP durante 10 s, 30 s y 60 s. Posteriormente, se valoró la tasa de supervivencia bacteriana. RESULTADOS: las bacterias Gram negativas (P. aeruginosa y E. coli) fueron más susceptibles que las bacterias Gram positivas (S. aureus y S. pseudintermedius) durante la misma duración de exposición a CAMP. Solo las bacterias Gram negativas murieron por completo después de 60 s de exposición. En los aislados de S. pseudintermedius, la exposición a CAMP tuvo efectos antibacterianos similares independientemente de la resistencia a los antibióticos. CONCLUSIONES E IMPORTANCIA CLÍNICA: CAMP tiene suficiente actividad antimicrobiana contra las principales cepas bacterianas que causan pioderma y otitis externa en perros, y puede ser una opción terapéutica alternativa para las infecciones cutáneas por S. pseudintermedius, para las cuales los antibióticos a menudo son ineficaces debido a la resistencia a los antimicrobianos en medicina veterinaria.Kaltes atmosphärisches Plasma (CAP) zählt zu einer neuen Generation an medizinischen Behandlungsoptionen für bakterielle Infektionen. CAP verursacht eine physische Zellwandruptur und eine DNA Schädigung, was es in der Folge bei der Behandlung verschiedener Erkrankungen wie Hautinfektionen sehr wirkungsvoll macht.Die antimikrobielle Wirksamkeit von kaltem atmosphärischem Mikrowellenplasma (CAMP) wurde gegenüber wichtigen Stämmen bei Hautinfektionen des Hundes getestet und der Unterschied der antimikrobiellen Aktivität zwischen den Antibiotika-resistenten und den Antibiotika-empfindlichen Stämmen von Staphylococcus pseudintermedius evaluiert.Stämme (Staphylococcus aureus, Pseudomonas aeruginosa und Escherichia coli) aus der American Type Culture Collection (ATCC) und klinische Isolate, die als Methicillin-resistente S. pseudintermedius (n = 27) und Methicillin-empfindliche S. pseudintermedius (n = 13) isoliert worden waren, wurden CAMP für 10 s, 30 s und 60 s ausgesetzt. Danach wurde die bakterielle Überlebensrate bestätigt.Gram-negative Bakterien (P. aeruginosa und E. coli) waren empfindlicher als Gram-positive Bakterien (S. aureus und S. pseudintermedius) bei gleich langer Dauer der Exposition zu CAMP. Nur die Gram-negativen Bakterien waren nach einer 60 s dauernden Exponierung völlig abgetötet. In S. pseudintermedius Isolaten zeigte die Exponierung unabhängig von der antibiotischen Resistenz zu CAMP eine ähnliche antibakterielle Wirkung.CAMP zeigt eine ausreichende antimikrobielle Aktivität gegenüber bakteriellen Stämmen, die eine Pyodermie und eine Otitis externa bei Hunden verursachen und könnte eine alternative therapeutische Option für Hautinfektionen durch S. pseudintermedius darstellen, für die Antibiotika aufgrund der antimikrobiellen Resistenz in der klinischen Veterinärmedizin oft unwirksam sind.背景: 低温大気圧プラズマ (CAP) は、細菌感染症に対する新世代の治療法として注目されている。CAPは、物理的な細胞壁破壊とDNAの損傷を引き起こすため、皮膚感染症などの様々な症状の治療に非常に有用である。 仮説・目的: 本研究の目的は、犬の皮膚感染症における主要な菌株に対する低温マイクロ波プラズマ (CAMP) の抗菌活性を試験し、Staphylococcus pseudintermediusの抗生物質耐性菌株および抗生物質感受性菌株間の抗菌活性の違いを評価することであった。 材料・方法: American Type Culture Collection(ATCC) 株 (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli)と、メチシリン耐性S. pseudintermedius(n = 27)およびメチシリン感受性S. pseudintermedius(n = 13)と同定された臨床分離株をCAMPに10秒、30秒、60秒曝露し、その後、細菌の生存率を確認した。 結果: グラム陰性菌 (P. aeruginosaおよびE. coli) は、同じCAMP曝露時間でもグラム陽性菌 (S. aureusおよびS. pseudintermedius) よりも感受性が高かった。60秒の曝露で完全に死滅したのはグラム陰性菌のみであった。S. pseudintermedius分離菌では、CAMP曝露は抗生物質耐性にかかわらず同様の抗菌効果を示した。 結論および臨床上の重要性: CAMPは犬膿皮症および外耳炎の原因となる主要な細菌株に対して十分な抗菌活性を有しており、臨床獣医学では抗菌剤耐性のために抗生物質が効かないことが多いS. pseudintermedius皮膚感染症の代替治療法となる可能性がある。.背景: 大气低温等离子体(CAP)是新一代细菌感染的药物治疗选择。CAP引起物理性细胞壁破裂和DNA损伤, 因此使其在皮肤感染等多种疾病的治疗中非常有用。 假设/目的: 检测了大气低温微波等离子体(CAMP)对犬皮肤感染中主要菌株的抗菌活性, 并评价了假中间型葡萄球菌的抗生素耐药性和抗生素敏感性菌株之间的抗菌活性差异。 方法和材料: 将美国典型培养物保藏中心(ATCC)菌株 (金黄色葡萄球菌、铜绿假单胞菌和大肠埃希菌) 和鉴定为耐甲氧西林假中间型链球菌(n = 27)和甲氧西林敏感假中间型链球菌(n = 13)的临床分离株暴露于CAMP 10s、30s和60s后, 证实了细菌存活率。 结果: 在相同的CAMP暴露时间内, 革兰氏阴性菌 (铜绿假单胞菌和大肠埃希菌) 比革兰氏阳性菌 (金黄色葡萄球菌和假中间型链球菌) 更敏感。暴露60s后仅完全杀灭革兰氏阴性菌。在假中间型链球菌分离株中, 无论抗生素耐药性如何, CAMP暴露均具有相似的抗菌作用。 结论和临床重要性: CAMP对引起犬脓皮病和外耳炎的主要细菌菌株具有足够的抗菌活性, 可能是假中间型葡萄球菌皮肤感染的替代治疗选择, 在临床兽药中, 由于抗菌药物耐药性, 抗生素通常无效。.O plasma atmosférico frio (PAF) é uma opção terapêutica de nova geração para infecções bacterianas. O PAF causa ruptura física da parede celular e danos ao DNA, sendo, portanto, altamente útil no tratamento de várias condições, como infecções de pele. HIPÓTESE/OBJETIVOS: A atividade antimicrobiana do plasma atmosférico frio de microondas (PAFM) contra as principais cepas em infecções cutâneas caninas foi testada e a diferença na atividade antimicrobiana entre as cepas de Staphylococcus pseudintermedius resistentes a antibióticos e suscetíveis a antibióticos foi avaliada. MÉTODOS E MATERIAIS: Cepas da American Type Culture Collection (ATCC) (Staphylococcus aureus, Pseudomonas aeruginosa e Escherichia coli) e isolados clínicos identificados como S. pseudintermedius resistente à meticilina (n = 27) e S. pseudintermedius sensível à meticilina (n = 13) foram expostos ao PAFM por 10 s, 30 s e 60 s. Posteriormente, a taxa de sobrevivência bacteriana foi confirmada.As bactérias Gram-negativas (P. aeruginosa e E. coli) foram mais suscetíveis do que as bactérias Gram-positivas (S. aureus e S. pseudintermedius) para a mesma duração da exposição PAFM. Apenas as bactérias Gram-negativas foram completamente mortas após 60 s de exposição. Nos isolados de S. pseudintermedius, a exposição ao PAFM teve efeitos antibacterianos semelhantes, independentemente da resistência aos antibióticos. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: PAFM tem atividade antimicrobiana suficiente contra as principais cepas bacterianas que causam piodermite e otite externa em cães, e pode ser uma opção terapêutica alternativa para infecções cutâneas por S. pseudintermedius, para as quais os antibióticos muitas vezes são ineficazes devido à resistência antimicrobiana na medicina veterinária.

The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RICTOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), adavosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. Significance: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility. This article is highlighted in the In This Issue feature, p. 1325

Purpose A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. Materials and methods Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. Results In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. Conclusion Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

Context Limited information is available regarding the detailed clinical patterns of palliative sedation (PS), that is, the symptom control rate, salvage medication, and the effectiveness of intermittent PS (IPS) versus continuous PS (CPS). Objectives The primary aim was to investigate clinical outcomes of PS in a real clinical setting. Methods Clinical information was prospectively collected for patients who were treated according to a prescribed protocol and assessment tools in a hospice unit affiliated with a tertiary cancer center between September 2015 and March 2017. Data were analyzed retrospectively. Midazolam was used as the first medication for PS, and propofol and phenobarbital were subsequently used as salvage medications. Indications of PS, the depth of sedation, the quality of sleep, and the level of consciousness were assessed. Results A total of 306 patients were enrolled, 89 of whom (29.1%) received PS. No difference in survival time was found between patients with and without PS (median survival, 34.0 vs 25.0 days, P = 0.109). Delirium was the most common indication of PS. The symptoms of 73 (82.0%) of 89 patients with PS were relieved with midazolam. Twelve (75.0%) of 16 midazolam-failure patients responded to propofol, five of whom (31%) exhibited respiratory depression. Of the 89 patients receiving PS, 61 (68.5%) received IPS and 28 patients (31.5%) received CPS. The median survival times from PS initiation to death were six days in the IPS group and one day in the CPS group (P Conclusion The refractory symptoms of end-of-life patients with cancer can ultimately be relieved with various medications for PS. IPS may improve the consciousness level of patients with delirium.

Background Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. Patients and methods In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1–14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. Results In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was −12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P Conclusion XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. Trial Registration This study was registered in ClinicalTrials.gov (number NCT01470443).

Background/Aims Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). Methods Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient’s clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. Results Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. Conclusions Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.

Background: Although biliary tract cancer (BTC) has a very aggressive nature, some patients maintain a relatively good performance status after failure with first-line treatment of gemcitabine plus cisplatin (GC). Thus, tolerable, feasible, and useful second-line treatments are needed for these patients. We investigated the efficacy of capecitabine plus oxaliplatin (XELOX) as a second-line therapy for patients with advanced BTC who failed first-line GC treatment. Methods: In this prospective, phase II trial, we investigated XELOX (capecitabine 1,000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as a second-line treatment, given every 3 weeks, totaling 8 cycles in patients with metastatic BTC who failed first-line GC treatment. The primary outcome was progression-free survival (PFS). Results: From December 2015 to November 2016, 50 patients with metastatic intrahepatic or extrahepatic cholangiocarcinoma or gall bladder (GB) cancer were enrolled. The regimen was well tolerated. Toxicities mainly consisted of grade 1 or 2 events, and thrombocytopenia and neuropathy had the highest incidence. In intent-to-treat analysis, one complete response (CR) and six partial responses (PRs) were recorded with XELOX treatment. The overall response rate and the disease control rate from the intent-to-treat analysis were 14% and 52%, respectively. With a median follow-up of 15.6 months, PFS after XELOX was a median of 15.4 weeks (95% CI, 8.5-22.3). This PFS value supported the statistical hypothesis of this study. The median overall survival was 32.7 weeks (95% CI, 21.4-43.9). Conclusion: This phase II trial showed that XELOX treatment was efficacious and had a tolerable toxicity profile in patients with advanced BTC who failed first-line treatment of gemcitabine and cisplatin.

ObjectivesTo investigate the associations between heavy metal exposure and serum ferritin levels, physical measurements and type 2 diabetes mellitus (DM).DesignA retrospective cohort study.SettingChangwon, the location of this study, is a Korean representative industrial city. Data were obtained from medical check-ups between 2002 and 2018.ParticipantsA total of 34 814 male subjects were included. Of them, 1035 subjects with lead exposure, 200 subjects with cadmium exposure and the 33 579 remaining were assigned to cohort A, cohort B and the control cohort, respectively. Data including personal history of alcohol and smoking, age, height, weight, the follow-up duration, haemoglobin A1c (HbA1c), fasting blood sugar (FBS), ferritin levels, and lead and cadmium levels within 1 year after exposure were collected.Primary outcome measureIn subjects without diabetes, changes in FBS and HbA1c were analysed through repeated tests at intervals of 1 year or longer after the occupational exposure to heavy metals.ResultsIn Cohort A, DM was diagnosed in 33 subjects. There was a significant difference in lead concentrations between the subjects diagnosed with DM and those without DM during the follow-up period (3.94±2.92 mg/dL vs 2.81±2.03 mg/dL, p=0.002). Simple exposure to heavy metals (lead and cadmium) was not associated with DM in Cox regression models (lead exposure (HR) 1.01, 95% CI: 0.58 to 1.77, p 0.971; cadmium exposure HR 1.48, 95% CI: 0.61 to 3.55, p=0.385). Annual changes in FBS according to lead concentration at the beginning of exposure showed a positive correlation (r=0.072, p=0.032).ConclusionOur findings demonstrated that simple occupational exposure to heavy metals lead and cadmium was not associated with the incidence of DM. However, lead concentrations at the beginning of the exposure might be an indicator of DM and glucose elevations.