Purpose: The prognosis of young colorectal cancer (CRC) patients has not fully been addressed. The prognostic significance of systemic inflammatory markers was examined in those patients. Methods: A total of 965 patients with resectable CRC were divided into young (≤ 50 years, n = 101) and old groups (>51 years, n = 864). Neutrophil-to-lymphocyte ratio (NLR) > 5, derived NLR (dNLR) > 3, lymphocyte-to-monocyte ratio (LMR) < 2, platelet-to-lymphocyte ratio (PLR) > 150, and prognostic nutritional index (PNI) < 45 were analyzed for prognosis.Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test. A multivariate analysis was performed using a Cox proportional hazards regression model. Results: In the young group, NLR > 5, LMR < 2, and PNI < 45 were significantly associated with OS with univariate analyses. dNLR > 3 and those markers showed significance for PFS. LMR < 2 was a significant marker for poor PFS (hazard ratio [HR], 5.81; P = 0.020) in the multivariate analysis. In the old group, all inflammatory markers were significantly associated with OS and PFS with univariate analyses. LMR < 2 (HR, 2.66; P = 0.016) and PNI < 45 (HR, 2.14; P = 0.016) were independently associated with OS in multivariate analyses. PLR > 150 (HR, 1.45; P = 0.036) and PNI < 45 (HR, 1.73; P = 0.002) were significant markers for PFS. Conclusion Systemic inflammation might be one of biologic factors that influence on prognosis of young CRC.

Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods: We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results: Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusions: This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.

Background/Aims: Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. Methods: This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. Results: Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. Conclusions Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.

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.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant diseases. While continued efforts have been focused on GC treatment, the introduction of trastuzumab marked the beginning of a new era of target-specific treatments. Considering the diversity of mutations in GC, satisfactory results obtained from various target-specific therapies were expected, yet most of them were unsuccessful in controlled clinical trials. There are several possible reasons underlying the failures, including the absence of patient selection depending on validated predictive biomarkers, the inappropriate combination of drugs, and tumor heterogeneity. In contrast to targeted agents, immuno-oncologic agents are designed to regulate and boost immunity, are not target-specific, and may overcome tumor heterogeneity. With the successful establishment of predictive biomarkers, including Epstein-Barr virus pattern, microsatellite instability status, and programmed death-ligand 1 (PD-L1) expression, as well as ideal combination regimens, a new frontier in the immuno-oncology of GC treatment is on the horizon. Since the field of immuno-oncology has witnessed innovative, practice-changing successes in other cancer types, several trials on GC are ongoing. Among immuno-oncologic therapies, immune checkpoint inhibitors are the mainstay of clinical trials performed on GC. In this article, we review target-specific agents currently used in clinics or are undergoing clinical trials, and highlight the future clinical application of immuno-oncologic agents in inoperable GC.
Biomarkers ; Herpesvirus 4, Human ; Immunotherapy ; Microsatellite Instability ; Mortality ; Patient Selection ; Population Characteristics ; Stomach Neoplasms* ; Trastuzumab

PURPOSE: Because data as a basis for the determination of proper age and modality for screening of colorectal neoplasms is lacking, we evaluated detection rates and anatomical distribution of colorectal neoplasms according to age in healthy individuals who underwent total colonoscopy for health checkup. METHODS: A total of 16,100 cases that had received the colonoscopic examination from January to December in 2014 were analyzed. The total number of individuals who received total colonoscopy were divided by the number of individuals harboring colorectal adenoma to calculate the detection rate of colorectal adenoma. Individuals ≤50 years old were classified as young-age group and aged >50 were old-age group. Differences in anatomical locations of colorectal neoplasms were analyzed in the 2 age groups by chi-square test. Risk factors for colorectal adenoma in each age group were analyzed using univariate and multivariate logistic regression analyses. RESULTS: Detection rates of colorectal adenoma were 13.7% in all cases and 12.8% for those in their 40′s. The main anatomical location of colorectal adenoma was proximal colon in both age groups (P < 0.001). Hyperplastic polyp was mainly distributed to the distal colon in both age groups (P < 0.001). Distal colon was the major site for colorectal cancer in the old-age group (P = 0.001). Proximal location of neoplasms was a risk factor for colorectal adenoma in both age groups with multivariate analysis. CONCLUSION: These data could be the bases for earlier initiation of screening for colorectal neoplasms with total colonoscopy to detect clinically significant colorectal polyps.
Adenoma ; Colon ; Colonoscopy ; Colorectal Neoplasms ; Humans ; Logistic Models ; Mass Screening ; Multivariate Analysis ; Polyps ; Risk Factors

PURPOSE: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. MATERIALS AND METHODS: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. RESULTS: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. CONCLUSIONS: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Adenocarcinoma ; Alkaline Phosphatase ; Appetite ; Aspartate Aminotransferases ; Clinical Decision-Making ; Disease Progression ; Double-Blind Method ; Drug Therapy ; Esophagogastric Junction ; Factor Analysis, Statistical* ; Humans ; L-Lactate Dehydrogenase ; Lymphocytes ; Mass Screening ; Neoplasm Metastasis ; Neutrophils ; Prognosis ; Proportional Hazards Models ; Quality of Life ; Sodium ; Stomach Neoplasms*

Standard endocrine therapy and chemotherapy can induce long-term remission in breast cancer patients; however, breast cancer can recur at any site. Pulmonary nodules with lymphadenopathy in advanced cancer patients are likely to be assumed as metastases. A 44-year-old woman with a history of breast cancer was presented to our institution with abnormal findings on 18-fluorodeoxyglucose positron emission tomography imaging, which suggested lung metastasis. She had previously been diagnosed with breast cancer (T1N2M0, Stage IIIa, intraductal carcinoma, triple negative cancer). Histological analysis of the mediastinal lymph node biopsy demonstrated sarcoidosis, showing a chronic, non-caseating, granulomatous inflammation. Our case highlights the need for non-malignant diagnoses in those with prior malignancies, and the need for histological evaluations in the event of first recurrence following potentially curative therapy.
Adult ; Biopsy ; Breast Neoplasms* ; Carcinoma, Intraductal, Noninfiltrating ; Diagnosis ; Drug Therapy ; Female ; Humans ; Inflammation ; Lung ; Lymph Nodes ; Lymphatic Diseases ; Neoplasm Metastasis* ; Positron-Emission Tomography ; Recurrence ; Sarcoidosis ; Sarcoidosis, Pulmonary*

OBJECTIVE: The purpose of this study was to determine the incidence and risk factors of infections associated with implantable venous access ports (IVAPs). MATERIALS AND METHODS: From August 2003 through November 2011, 1747 IVAPs were placed in our interventional radiology suite. One hundred forty four IVAPs were inserted in patients with hematologic malignancy and 1603 IVAPs in patients with solid tumors. Among them, 40 ports (23 women and 17 men; mean age, 57.1 years; range, 13-83) were removed to treat port-related infections. We evaluated the incidence of port-related infection, patient characteristics, bacteriologic data, and patient progress. Univariable analyses (t test, chi-square test, and Fisher's exact test) and multiple logistic regression analyses were used to determine the risk factors for IVAP related infection. RESULTS: Overall, 40 (2.3%) of 1747 ports were removed for symptoms of infection with an incidence rate of 0.067 events/1000 catheter-days. According to the univariable study, the incidences of infection were seemingly higher in the patients who received the procedure during inpatient treatment (p = 0.016), the patients with hematologic malignancy (p = 0.041), and the patients receiving palliative chemotherapy (p = 0.022). From the multiple binary logistic regression, the adjusted odds ratios of infection in patients with hematologic malignancies and those receiving palliative chemotherapy were 7.769 (p = 0.001) and 4.863 (p = 0.003), respectively. Microorganisms were isolated from 26 (65%) blood samples, and two of the most causative organisms were found to be Staphylococcus (n = 10) and Candida species (n = 7). CONCLUSION: The underlying hematologic malignancy and the state of receiving palliative chemotherapy were the independent risk factors of IVAP-related infection.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Catheter-Related Infections/*epidemiology/microbiology ; Catheters, Indwelling/*adverse effects ; Female ; Hematologic Neoplasms/drug therapy ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/drug therapy ; Palliative Care/statistics & numerical data ; Retrospective Studies ; Risk Factors ; Vascular Access Devices/*adverse effects ; Young Adult

Advanced gastric cancer with skeletal muscle metastasis is a rare occurrence. Here, we report a rare case of gastric carcinoma with psoas muscle metastasis. This patient had advanced gastric carcinoma and complained of inability to extend the left hip joint due to pain. Because magnetic resonance imaging (MRI) revealed an iliopsoas mass showing heterogeneous signal intensity with fluid collection and enhancement around the mass, we speculated that the mass was an intramuscular metastatic tumor from primary gastric carcinoma as well as an intramuscular abscess. Histopathologically, the patient had a metastasis from primary gastric adenocarcinoma. Therefore, the patient was treated with radiotherapy and subsequent chemotherapy.
Abscess ; Adenocarcinoma ; Hip Joint ; Humans ; Magnetic Resonance Imaging ; Muscle, Skeletal ; Muscles ; Neoplasm Metastasis ; Psoas Muscles ; Stomach Neoplasms