Impact of primary prophylaxis by pegfilgrastim in diffuse large B-cell lymphoma treated with R-CHOP.

Febrile neutropenia (FN) and chemotherapy-induced neutropenia (CIN) are common conditions that lead to dose reduction or delayed chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). Primary prophylaxis (PP) with long-acting granulocyte colony-stimulating factor (G-CSF) was introduced in South Korea in 2014. We aimed to investigate the effects of PP on FN-related hospitalization and death in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Korean individuals (n = 11,491) with incident DLBCL and receiving R-CHOP during 2010-2016 were followed for FN-related hospitalization and mortality. The PP exposure group (patients during 2014-2015, n = 3599), patients during 2010-2016 (n = 11,491), and patients receiving PP during 2014-2016 (n = 4421) were compared with the non-exposure group (patients during July 2011-June 2013, n = 3017), patients in 2013 (n = 1596), and patients not receiving PP during 2014-2016 (n = 1289), respectively. Multivariable-adjusted hazard ratios (HRs) were calculated using the Cox model. The PP exposure group had 16% lower FN-related hospitalizations than the non-exposure group (HR = 0.84, P < 0.001). PP exposure had no beneficial effect on 1-year (HR = 0.98, P = 0.782) and 5-year mortality (HR = 0.97, P = 0.474). Patients in 2014 (HR = 0.85, P < 0.001), 2015 (HR = 0.88, P = 0.003), and 2016 (HR = 0.80, P < 0.001) had a decreased risk of FN-related hospitalizations compared with those in 2013. Among patients receiving their first R-CHOP cycle during 2014-2016, the HR for FN-related hospitalization was 0.90 (P = 0.014) in PP users compared with non-users. PP with a long-acting G-CSF lowered the FN-related hospitalization risk but did not benefit survival in patients with DLBCL receiving R-CHOP.

Cancer-Oriented Comprehensive Nursing Services in Republic of Korea: Lessons from an Oncologist's Perspective.

Background and objectives: As is well known, cancer patients require extensive medical attention as they undergo surgery, chemotherapy, radiotherapy, and supportive care. The importance of high-quality cancer-directed nursing, combined with precision medicine, to maximize their survival outcomes and help them achieve a better quality of life cannot be overemphasized. In this context, we offered a new cancer-oriented comprehensive nursing system to our inpatients and reviewed its clinical outcomes in comparison with those from the preexisting general cancer ward. Materials and Methods: From March 2019 to February 2020, a total of 102 cancer patients and 42 nurses were enrolled in this pilot study. We aimed to analyze their performance in three main categories: structure, process, and patient/nurse outcomes. Results: First, structural (nurse staffing and environment) upgrades were installed in the cancer-oriented comprehensive nursing ward, including an improved nurse-patient ratio (1:8 in the comprehensive ward as compared with 1:14 in the general ward), wider space between beds (1.5 m versus 1.0 m), fully automatic beds with fall prevention sensors, etc. Second, the nursing process was improved (missed care 0.1 event/month vs. 1.3 event/month). Third, both patient and nurse outcomes showed preferable results in the comprehensive ward. The patient satisfaction level was higher in the comprehensive nursing ward than in the general ward (willing to revisit: 91.7% and 78.4%, respectively; willing to recommend to others: 95.0% and 76.8%, respectively). Pressure ulcers, as a patient safety indicator, were also decreased (0.3 events/month vs. 0.8 events/month). However, the fall incidence was similar in both groups (1.6 events/month vs. 1.5 events/month). In terms of nurse outcomes, turnover intention was stabilized and nurses' job satisfaction in the comprehensive ward was superior to that of their counterparts. Conclusions: Our study was a pilot study to demonstrate that cancer patient-oriented comprehensive nursing services can be helpful in improving the quality of cancer treatment and nurses' job satisfaction. Continued interest in and efforts to improve nursing care delivery are also crucial in achieving and maintaining the best possible cancer patient care.

Identification and functional validation of HLA-C as a potential gene involved in colorectal cancer in the Korean population.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study. RESULTS: We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher's exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P < 10-6) and two suggestive functional loci on HLA-C and NUTM1 (10-6 ≤ P < 10-4). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways. CONCLUSIONS: Exome array CRC case-control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways.

Impact of overweight and obesity on the risk of hepatocellular carcinoma: a prospective cohort study in 14.3 million Koreans.

BACKGROUND: Whether obesity and being overweight, defined by body mass index (BMI), increase hepatocellular carcinoma (HCC) has been less apparent in Asian populations. METHODS: Overall, 14,265,822 Korean adults who underwent routine health examinations during 2003-2006 were followed up for HCC. Multivariable-adjusted hazard ratios (HRs) associated with BMI were calculated. RESULTS: During 13.7 years (mean) of follow-up, 47,308 individuals developed HCC. HRs of HCC associated with BMIs of 25.0-26.4, 26.5-27.9, 28.0-29.4, 29.5-30.9 and ≥31 kg/m² compared to those for 23.5-24.9 kg/m² were 1.05, 1.20, 1.39, 1.59 and 2.13, respectively. For BMI < 25 kg/m², linear associations were not apparent. For BMI ≥ 25 kg/m2, the HR per 5 kg/m2 increase in BMI was 1.60 (total), 1.60 (men), and 1.59 (women). The corresponding HRs were 1.56, 1.61 and 1.60 for individuals aged <45, 45-64 and ≥65 years, respectively. Further adjustment for alanine transaminase (ALT) levels substantially reduced the HRs for high BMI, especially in men and younger adults. CONCLUSIONS: Overweight and obesity clearly increase HCC risk in Koreans. ALT levels are a mediator of the impact of obesity, but it may not accurately predict high BMI-induced liver damage that can potentially progress to HCC, especially in women and older adults.

Prognostic implications of immune classification using IDO1 expression in extrahepatic bile duct carcinoma.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine and induces immune tolerance in tumor cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. Therefore, the present study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. An immunohistochemical microarray analysis of IDO1 expression was performed for 76 surgically resected cases of EHBDC. CD8+ tumor infiltrating lymphocytes (TILs) were also investigated through a combination analysis with IDO1 expression. IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001) and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high/CD8low subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with IDO1high/CD8high, IDO1low/CD8high and IDO1low/CD8low subgroups. High IDO1 expression was associated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic and predictive tool in patients with EHBDC.

Novel Biomarker Panels Discriminating between Pancreatic Ductal Adenocarcinoma and Extrahepatic Bile Duct Carcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic bile duct carcinoma (EBDC) are distinct entities with different clinicopathological implications. Therefore, research to differentiate between the two diseases is compulsory. In this study, four biomarkers were selected (Hippocalcin-like 1 (HPCAL1); annexin A10 (ANXA10); MUC5AC; sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)) and focus was placed on clarifying the diagnostic performance of each biomarker and pioneering novel-combined biomarker panels to discriminate between PDAC and EBDC. PROCEDURES: An immunohistochemical microarray analysis of HPCAL1, ANXA10, MUC5AC, and ATP1B1 was conducted for surgically resected 55 PDACs and 77 EBDCs. The diagnostic performance discriminating between PDAC and EBDC was evaluated using four biomarkers and the combined biomarker panels. RESULTS: PDACs exhibited more positive expressions for HPCAL1, ANXA10, and MUC5AC, whereas EBDCs exhibited more ATP1B1-positive expressions. The PDAC panel with the best diagnostic performance was the profile of (+ in ≥ 2 among HPCAL1, ANXA10, MUC5AC)/ATP1B1-. The immunophenotype pattern of (- in ≥ 1 among HPCAL1, ANXA10, MUC5AC)/ATP1B1+ is the EBDC panel with the most excellent discriminating power. CONCLUSION: The suggested combined biomarker panels demonstrate the distinguishing diagnostic ability between PDAC and EBDC is better than previous studies. Therefore, for differentiation between PDAC and EBDC, these panels are expected to help unravel the clinicopathological enigma as promising biomarker panels in the future.

Comparison of Sinusoidal Obstruction Syndrome in Gastric Cancer Patients Receiving S-1/oxaliplatin Versus Capecitabine/oxaliplatin.

BACKGROUND/AIM: Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS). PATIENTS AND METHODS: We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients. RESULTS: SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX. CONCLUSION: S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.

Physical and Psychological Factors Affecting Falls in Older Patients with Arthritis.

As the population ages, falls are becoming one of the leading causes of morbidity and mortality. Joint disease (either osteoarthritis or rheumatoid arthritis) is a well-known predictor of falls, and these medical conditions increase in accordance with the aging population. This study aimed to describe individual, physical, and psychological characteristics between older adults with and without a fall history. Further, we aimed to identify statistically significant physical or psychological factors associated with falls by controlling individual variables. We analyzed data from the 2014 Survey of Living Conditions and Welfare Needs of Korean Older Adults. Adults aged 65 years or over with doctor-diagnosed joint disease were eligible. A total of 2707 women and 784 men (n = 3491) were enrolled. Of these, 1174 patients suffered a fall within a year (average number of falls = 2.4). We adopted individual variable-adjusted models and found that limited activities of daily living (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.04-1.87), fear of falling (OR 7.18, 95% CI 4.26-12.09), and depression (OR 1.28, 95% CI 1.09-1.50) significantly increased fall risks on logistic regression analysis. Our findings suggest that physical and psychological factors, especially the fear of falling, need to be addressed to prevent falls in elderly patients with arthritis.

Physical and Psychological Factors Associated with Poor Self-Reported Health Status in Older Adults with Falls.

Background: Previous studies have proposed various physical tests for screening fall risk in older adults. However, older adults may have physical or cognitive impairments that make testing difficult. This study describes the differences in individual, physical, and psychological factors between adults in good and poor self-rated health statuses. Further, we identified the physical or psychological factors associated with self-rated health by controlling for individual variables. Methods: Data from a total of 1577 adults aged 65 years or over with a history of falls were analyzed, using the 2017 National Survey of Older Persons in South Korea. Self-reported health status was dichotomized as good versus poor using the 5-point Likert question: "poor" (very poor and poor) and "good" (fair, good, and very good). Results: Visual/hearing impairments, ADL/IADL restriction, poor nutrition, and depression were more frequently observed in the group with poor self-rated health. Multivariable logistic regression revealed that poor self-reported health was significantly associated with hearing impairments (OR: 1.51, 95% CI 1.12-2.03), ADL limitation (OR: 1.77, 95% CI 1.11-2.81), IADL limitation (OR: 2.27, 95% CI 1.68-3.06), poor nutrition (OR: 1.36, 95% CI 1.05-1.77), and depression (OR 3.77, 95% CI 2.81-5.06). Conclusions: Auditory impairment, ADL/IADL limitations, poor nutrition, and depression were significantly associated with poor self-reported health. A self-rated health assessment could be an alternative tool for older adults who are not able to perform physical tests.