Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment.
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Aged ; Blood Glucose ; Diabetes Mellitus/drug therapy* ; Female ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Lung Neoplasms/drug therapy*

3.38, PLR >210, CA125 >365, advanced stage, suboptimal disease, serous type, and ascites were significant predictive factors for platinum resistance. However, only NLR >3.38 and advanced stage were independent predictive factors with an adjusted odds ratio of 1.880 and 3.333, respectively. Regarding factors associated with poor survival outcomes, only PLR >210 and advanced stage were independent factors, with a hazard ratio of 1.578 and 3.994, respectively.CONCLUSION: High NLR and advanced stage were potential independent predictive factors for platinum resistance, whereas high PLR and advanced stage were potential independent predictive factors for poor survival outcomes.]]>
Ascites ; Blood Platelets ; Drug Therapy ; Fallopian Tubes ; Female ; Humans ; Lymphocytes ; Medical Records ; Multivariate Analysis ; Neutrophils ; Odds Ratio ; Ovarian Neoplasms ; Platinum ; Prognosis ; Retrospective Studies ; ROC Curve

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult

PURPOSE: The role of the host immunologic environment is crucial in cancer progression. Recent studies revealed that neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), are possible surrogate markers of outcome in various cancers. In breast cancer, the therapeutic effect of neoadjuvant chemotherapy (NAC) differs in patients, and higher response rate reflects better outcomes. This study aimed to determine the predictive value of peripheral blood NLR and PLR for NAC response along with their prognostic role in breast cancer. METHOD: A total of 105 patients with breast cancer treated with NAC between 2009 and 2017 were analyzed retrospectively. NAC response and prognosis (disease-free-survival [DFS], progression-free-survival [PFS] and overall survival [OS]) according to NLR and PLR were evaluated. According to the optimal cut-off values for NAC response obtained from receiver operating characteristic (ROC) curves, patients satisfying both low NLR and PLR levels (low-ratio group) were compared to those who did not (high-ratio group). RESULTS: The NLR cut-off value was ≤ 2.21 (area under the ROC curve [AUC], 0.617; 95% confidence interval [CI], 0.517–0.710; p=0.030) with 94.1% sensitivity and 38.0% specificity. The PLR cut-off value was ≤ 143.36 (AUC, 0.618; 95% CI, 0.518–0.711; p = 0.040) with 85.3% sensitivity and 39.4% specificity. The low-ratio group demonstrated a better NAC response (p = 0.006) in multivariate analysis than the high-ratio group. The low-ratio group showed better DFS and PFS (p = 0.046 and p = 0.040, respectively) and longer OS (p = 0.078) in univariate survival analysis than the high-ratio group. In multivariate analysis, the low-ratio group had significantly better PFS (p = 0.049) and higher DFS (p = 0.054) than the high-ratio group. CONCLUSIONS: The combination of NLR and PLR showed improved prediction of NAC response, revealing their potential as screening tools, significant prognostic role in breast cancer patients who receive NAC. Further studies with subgroup analysis, larger population and longer follow up duration are required.
Biomarkers ; Blood Cell Count ; Breast Neoplasms ; Breast ; Drug Therapy ; Follow-Up Studies ; Humans ; Mass Screening ; Methods ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity

Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the immune microenvironment, tumor mutational burden (TMB), expression level of immune checkpoint proteins, and molecular subtypes of cancers. Along with the Cancer Genome Project, various open access databases, including The Cancer Genome Atlas and Gene Expression Omnibus, provide large volumes of data, which allow researchers to explore responsive or resistant biomarkers of immune checkpoint inhibitors. In this review, we introduced some methodologies on database selection, biomarker screening, current progress of immune checkpoint blockade in solid tumor treatment, possible mechanisms of drug resistance, strategies of overcoming resistance, and indications for immune checkpoint inhibitor therapy.
Biomarkers, Tumor ; blood ; immunology ; Data Mining ; Drug Resistance, Neoplasm ; Humans ; Immunotherapy ; Mutation ; Neoplasms ; genetics ; therapy ; Tumor Microenvironment

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl^-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl^-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.
Aged ; Androgen Antagonists/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Cholesterol/blood* ; Drug Therapy, Combination ; Humans ; Leuprolide/therapeutic use* ; Male ; Middle Aged ; Prostatic Neoplasms/pathology* ; Quality of Life ; Receptors, LHRH/agonists* ; Republic of Korea ; Testosterone/blood* ; Treatment Outcome ; Triglycerides/blood*

Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.
Androgen Antagonists ; adverse effects ; Blood Glucose ; drug effects ; Body Composition ; drug effects ; Cardiovascular System ; drug effects ; Cholesterol ; blood ; Humans ; Male ; Prostatic Neoplasms ; blood ; drug therapy

PURPOSE: To evaluate parameters for determining repeat prostate biopsy in patients with 5α-reductase inhibitor (5ARI) treatment after initial negative biopsy. MATERIALS AND METHODS: From January 2007 to December 2015, patients who underwent a repeat prostate biopsy after an initial negative biopsy were enrolled from multiple institutions. Serial prostate-specific antigen (PSA) levels after the initial biopsy were analyzed for PSA kinetics. Clinicopathologic variables were evaluated according to the use of 5ARIs after the initial negative biopsy. RESULTS: Of 419 patients with initial negative biopsies (median age=67.0 years, median PSA=6.31 ng/mL), 101 patients (24.1%) were diagnosed with prostate cancer at the repeat biopsy. An increase in PSA level at 18 months, compared to that at 6 months, was a predictor of a positive repeat biopsy. However, the use of 5ARIs was not identified as a predictor. Of 126 patients receiving 5ARI treatment after the initial biopsy, 30 (23.8%) were diagnosed with prostate cancer at the repeat biopsy. Increase in PSA level at more than two time points after 6 months of 5ARI treatment (odds ratio=4.84, p=0.005) was associated with cancer detection at the repeat biopsy. There were no significant 5ARI group-related differences in the detection rates of prostate and high-grade cancers (Gleason score ≥7). CONCLUSION: The effects of 5ARIs on prostate cancer detection and chemoprevention remain uncertain. However, more than two increases in PSA level after 6 months of 5ARI treatment may indicate the presence of prostate cancer.
5-alpha Reductase Inhibitors/*therapeutic use ; Aged ; *Biopsy ; Follow-Up Studies ; Humans ; Kinetics ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/blood/*drug therapy/*pathology

BACKGROUND/AIMS: Venous thromboembolic events (VTEs) are common events in patients with advanced cancer. We analyzed the clinical characteristics of VTEs in advanced pancreatic and biliary tract cancer to determine the clinical significance, especially in palliative settings. METHODS: Seventy-nine patients with advanced pancreatic cancer or biliary tract cancer who had thromboembolic events were retrospectively reviewed. We investigated the correlation between clinical course and thromboembolic events, and the laboratory risk factors, such as complete blood count profile. RESULTS: The 79 patients consisted of 40 men (50.6%) and 39 women (49.4%) with a median age of 65 years old (range: 41–80). Forty-three patients (54.4%), had thromboembolic events without any symptoms. Pulmonary thromboembolism occurred in only 31 cases (39.2%), and combined thrombosis at more than two sites occurred in 17 cases (21.5%). Of the 51 patients with active chemotherapy, 45 showed progressive disease. The median survival times were 11.9 weeks in all patients, 15.3 weeks in the treatment group, and 3.4 weeks in the palliative group. There was no difference in survival time between patients treated with dalteparin only and those treated with dalteparin combined with thrombolytic intervention. CONCLUSIONS: VTE can be poor prognostic indicator in pancreatic and biliary tract cacner patients, suggestive of progressive disease and a sign of short life expectancy, requiring hospice and terminal care.
Biliary Tract Neoplasms* ; Biliary Tract* ; Biomarkers* ; Blood Cell Count ; Dalteparin ; Drug Therapy ; Female ; Hospices ; Humans ; Life Expectancy ; Male ; Pancreatic Neoplasms ; Pulmonary Embolism ; Retrospective Studies ; Risk Factors ; Terminal Care ; Thrombosis ; Venous Thromboembolism

To explore the differential expression of serum miRNAs in patients of advanced non- small cell lung cancer (NSCLC) treated by gifitinib before and after acquiring drug resistance.
 Methods: A total of 4 patients with advanced NSCLC from Affiliated Hospital of Yueyang Vocational Technical College, who acquired drug resistance during gefitinib therapy from June 2013 to June 2015, were enrolled. Serum samples were collected before treatment and after acquiring drug resistance. MicroRNA (miRNA) microarray was used to assess the levels and compositions of miRNAs in serum. Real-time RT-PCR was used to validate the results of miRNAs with significant differences in expression. The candidate miRNAs inhibitors and mimics were transfected into lung cancer cells by liposome, and the sensitivity of lung cancer cells to gifitinib was detected.
 Results: The miRNA microarray showed that there were significantly differential expression of miRNAs in serum of NSCLC patients after acquiring drug resistance, and 24 miRNAs were changed in more than 2-fold. Among them, 19 miRNAs were up-regulated and 5 miRNAs were down- regulated (both P<0.05). Especially, the expression of miR-21 in serum of NSCLC patients after obtaining resistance was up-regulated more than 10-fold compared with that before treatment. The results of RT-PCR was consistent with the results of miRNA microarray. The up-regulation of miR-21 in lung cancer cells could elevate the half maximal inhibition concentration (IC50) of gefitinib, and the down-regulation of miR-21 in lung cancer cells could reduce the IC50 of gefitinib (both P<0.05).
 Conclusion: There is differential expression of miRNAs in serum of NSCLC patients before treatment and after acquiring drug resistance during gefitinib therapy. The up-regulation of miR-21 may be involved in regulating the acquiring drug resistance of gefitinib.
Antineoplastic Agents ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Lung Neoplasms ; drug therapy ; MicroRNAs ; blood ; genetics