Credé maneuver to adjust tape tension during trans-obturator tape mid-urethral sling in mixed urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To evaluate the efficacy of intraoperative extrinsic manual bladder compression (Credé maneuver) for trans-obturator tape adjustment during mid-urethral sling surgery in women with stress urinary incontinence and those with mixed urinary incontinence. METHODS: The study included 148 randomly selected women who underwent mid-urethral sling surgery with trans-obturator tape for stress urinary incontinence between January 2016 and May 2017. Subgroup analysis of 66 women with mixed urinary incontinence included 43 patients from the Credé maneuver group and 23 from the non-Credé maneuver group. In the Credé maneuver group, the pattern of urine leakage was determined during the Credé maneuver, and tape tension was adjusted according to the pattern. RESULTS: The cure rate was 86.6% and improved rate was 11.9% in the Credé maneuver patients. The cure rate was 50.6% and improved rate was 38.3% in the non-Credé maneuver patients. The success rate was significantly higher in the Credé than in the non-Credé maneuver group (p = 0.023). In subgroup analysis of patients with mixed urinary incontinence, the cure rate was 81.4% and improved rate was 16.3% in the Credé maneuver group. The cure rate was 43.5% and improved rate was 47.8% in the non-Credé maneuver group. The cure rate was significantly higher in the Credé maneuver group (p = 0.007). CONCLUSIONS: Intraoperative trans-obturator tape adjustment using the Credé maneuver to identify the leaking pattern significantly improved the success rate in women with mixed urinary incontinence, and Credé maneuver-directed adjustment significantly improved the cure rate.

Early venous thromboembolism at the beginning of palliative chemotherapy is a poor prognostic factor in patients with metastatic pancreatic cancer: a retrospective study.

BACKGROUND: This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. METHODS: A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. RESULTS: VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (< 135 mmol/L) and high Khorana score (≥3) were strong predictive factors of early VTE (odds ratio [OR] 5.109; 95% confidence interval [95% CI] = 1.010-25.845; p = 0.049 for Khorana score, OR 10.304; 95% CI = 1.036-102.466; p = 0.047) for hyponatremia). CONCLUSIONS: Our study demonstrated that occurrence and detection of VTE in the early period of chemotherapy was the most significant VTE-related prognostic factor in patients with metastatic pancreatic cancer receiving chemotherapy. Prediction using the Khorana score and serum Na levels would be helpful in early diagnosis of VTE.

Hedgehog signaling pathway as a potential target in the treatment of advanced gastric cancer.

The sonic hedgehog signaling pathway is critical for cell proliferation, cell differentiation, and organ development during embryogenesis. Aberrant activation of the sonic hedgehog pathway has been associated with a variety of human cancers. Currently, there is no target molecular drug that clinically affects sonic hedgehog activation in patients with gastric cancer. In this review, we will focus on the current clinical treatment options for advanced gastric cancer and discuss the sonic hedgehog signaling pathway. We also review our understanding of the role of sonic hedgehog signaling in advanced gastric cancer progression. Finally, we will describe current known molecular pathways that crosstalk with the sonic hedgehog pathway in cancer stem cells.

Iron chelator-induced apoptosis via the ER stress pathway in gastric cancer cells.

Many reports have shown the anticancer effects of iron deficient on cancer cells, but the effects of iron-chelators on gastric cancer have not been clearly elucidated. Recently, we reported that iron chelators induced an antiproliferative effect in human malignant lymphoma and myeloid leukemia cells. In the present study, we investigated the antitumor activity of these two iron-chelating agents, deferoxamine (DFO) and deferasirox (DFX), with gastric cancer cell lines, and their apoptosis-inducing effects as the potential mechanism. We found that iron chelators displayed significant antiproliferative activity in human gastric cancer cell lines, which may be attributed to their induction of G1 phase arrest and apoptosis. We also found that iron chelators induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in gastric cancer cells. Taken together, our data suggest that iron chelators induced apoptosis in gastric cancer, involving ROS formation ER stress and JNK activation.

Prognostic Factors and Skeletal-Related Events in Patients with Small Cell Lung Cancer with Bone Metastases at the Time of Diagnosis.

BACKGROUND/OBJECTIVE: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. MATERIALS AND METHODS: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. RESULTS: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). CONCLUSION: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea.

OBJECTIVE: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). METHODS: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m2 and cyclophosphamide, 600 mg/m2 every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. RESULTS: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. CONCLUSION: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

A Prognostic Index to Identify Patients With Intrahepatic Cholangiocarcinoma Who Could Benefit From Gemcitabine Plus Cisplatin.

Biliary tract cancer is a heterogenous group. Gemcitabine plus cisplatin has been the standard chemotherapy for advanced biliary tract cancer, but there is lack of evidence on treatment in patients with intrahepatic cholangiocarcinoma (IHC). We analyzed 29 patients with only IHC who received gemcitabine plus cisplatin between June 2010 and February 2013. The median age was 63 years (range, 40-78 years), and Eastern Cooperative Oncology Group performance status of all patients was <2. The median progression-free survival and median overall survival (OS) were 4.3 and 7.3 months, respectively. Multivariate analysis showed that platelet count (≤180 × 10 per liter), metastatic site of more than 2, and albumin level (≤3.5 g/dL) were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: zero or 1 (good prognostic group), 2 (intermediate group), or 3 (poor prognostic group). The median OS for good (n = 15), intermediate (n = 10), and poor (n = 4) prognostic group was 10.5, 6.1, and 1.6 months, respectively (P < 0.005). Relatively better prognosis of the good prognosis group comparing to other prognosis groups can be expected from the prognostic model established in this study by analyzing patients with IHC treated with gemcitabine.

Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.

BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation.

Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres' cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

Glucocorticoid-induced diabetes mellitus in patients with lymphoma treated with CHOP chemotherapy.

PURPOSE: Glucocorticoid-induced diabetes mellitus (GDM) is a major complication arising from corticosteroid administration, but there is lack of studies on GDM attributing to CHOP chemotherapy. We studied the incidence and risk factors for GDM development in patients with lymphoma during CHOP chemotherapy. METHODS: We analyzed 80 patients with lymphoma treated with a CHOP regimen with or without rituximab between 2004 and 2012 at the University of Tsukuba hospital. Patients with a known history of DM were excluded. Diagnosis of DM was performed according to the American Diabetes Association's criteria. RESULTS: Among the 80 patients, 26 (32.5 %) developed GDM. We found that age ≥ 60 years, glycated hemoglobin (HbA1c) levels >6.1 %, body mass index (BMI) >30 kg/m(2), prednisolone administration prior to chemotherapy, history of hypertension or hypertension at admission, and the presence of metabolic syndrome were significant (p ≤ 0.05) factors associated with GDM development by univariate analysis. Multivariate analysis revealed that age ≥ 60 years [p<0.05; hazard ratio (HR)=3.59; 95 % confidence interval (CI), 1.22-10.51], HbA1c levels >6.1 % (p<0.05; HR=9.35; 95%CI, 1.45-60.34), and BMI >30 kg/m(2) (p=0.052; HR=6.27; 95%CI, 0.98-40.00) were independently significant association factors. CONCLUSION: The results suggest a guideline for plasma glucose monitoring during CHOP chemotherapy in patients with no history of DM.

Intra-operative cardiac arrests during liver transplantation - a retrospective review of the first 15 yr in Asian population.

Although many report intra-operative cardiac arrests (ICAs) in liver transplantation (LT), the incidence, major causes, and outcome remain unclear. We aimed to investigate retrospectively, the incidence, nature, and outcome of ICA in Asian population and to identify risk factors for ICA. Consecutive 1071 LTs in an institution during 1996-2011 (adult 920, pediatric 151/living donor liver transplantation, LDLT 841, deceased donor liver transplantation, DDLT 230) were reviewed. ICA occurred in 14 adult LTs (1.5%), but none in pediatrics. ICA occurred 1.0% and 3.3% in LDLT and DDLT, respectively. Stages of ICA incidence were three at pre-anhepatic, one at anhepatic, and 10 at neohepatic stage. Post-reperfusion syndrome (PRS) with hyperkalemia and bleeding were the major causes of ICA. While LDLT showed miscellaneous causes for ICA at various stages, DDLT incurred ICAs at neohepatic stage only. Interestingly, we did not find pulmonary thromboembolism (PTE) to incur ICA. Risk factor analysis showed no association of pre-operative patient condition, donor types, and intra-operative parameters. In this review, the incidence of ICA was low in Asian population with LDLT predominance, and while PTE was not the cause of ICA, the neohepatic stage with PRS and bleeding was the most vulnerable period to anticipate ICA.

Role of phloretin as a sensitizer to TRAIL-induced apoptosis in colon cancer.

Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL-induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL- and phloretin-treated HT-29-Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin- and TRAIL-treated HT-29-Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP-ribose) polymerase, and caspase-3, -8 and -9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl-1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl-1 in phloretin- and TRAIL-treated HT-29-Luc cells resulted in increased cell survival. Treatment of HT-29-Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl-1 expression compared with that in cells treated with CHX alone, while Mcl-1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl-1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL-induced apoptosis in colon cancer cells.

Analysis of Factors Affecting Neutralizing Antibody Production after COVID-19 Vaccination Using Newly Developed Rapid Point-of-Care Test.

(1) Objective: To investigate the factors that affect rates of neutralizing antibody production and duration after vaccination using the newly developed SARS-CoV-2 POCT. (2) Methods: The production of immunoglobulin and neutralizing antibody in clinical subjects who completed various vaccines was analyzed using the POCT, the semi-quantitative was interpreted by measurement application, and the quantified neutralizing antibody titers were using the ELISA. (3) Results: According to the clinical performance analysis of the POCT, the clinical sensitivity and the specificity were 96.8% (90/93) and 97.7% (167/171), respectively, for the S1 RBD IgG antibody. The clinical sensitivity was 92.22% (83/90), and the clinical specificity was 100.00% (174/174) for neutralizing antibodies. Factors influencing antibody production were analyzed using the whole blood of the five types of second-completed vaccinators (N = 736, 20−80 years old). General and neutralizing antibody and showed significant differences in age (p < 0.0001), vaccine type (p < 0.0001), inoculation interval (p < 0.0001), pain score (p < 0.0001), diabetes (p < 0.0001), and hypertension (p = 0.002). The gender (p = 0.021) and chronic fatigue (p = 0.02) did not show the significance. (4) Conclusions: An acquisition of immunoglobulin and neutralizing antibody varies according to vaccine type, age, days after vaccination, pain degree after vaccination, and underlying diseases. The POCT used in this study will be utilized for clinical recommendations such as deciding whether to receive additional vaccines through the immediate rapid determination of neutralizing antibody generation in the clinical site.

Novel Use of Hydromorphone as a Pretreatment Agent: A Double-blind, Randomized, Controlled Study in Adult Korean Surgical Patients.

BACKGROUND: Hydromorphone is a potent µ-opioid selective agonist that has an onset time within 5 minutes and reaches peak effect between 10 and 20 minutes. However, it may show immediate analgesic effect to rocuronium-induced pain because of its peripheral analgesic property and also may attenuate noxious stimuli from tracheal intubation during induction. The opioid receptors are known to be present in peripheral sensory nerve terminals as well as in the dorsal root ganglion and the central terminal of primary afferent nerves. Therefore, we hypothesized that hydromorphone may be considered a potent pretreatment or adjuvant drug during the induction of anesthesia with its peripherally and centrally mediated analgesia. OBJECTIVE: The aim of this study was to compare the effects of pretreatment with hydromorphone in reducing rocuronium-induced withdrawal movements and hemodynamic changes during tracheal intubation with the effects of fentanyl and normal saline. METHODS: In this double-blind, randomized, controlled study, consecutive adult patients aged 20 to 70 years who were scheduled to undergo general anesthesia for elective gastric or colorectal surgery at the Samsung Seoul Hospital (Seoul, Republic of Korea) were randomly assigned to receive 5 mL hydromorphone 0.03 mg/kg or fentanyl 2 µg/kg or normal saline. Thirty seconds after administering the study drug, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After loss of consciousness, rocuronium 0.6 mg/kg was injected and immediate withdrawal movements were recorded. Two minutes after rocuronium injection, tracheal intubation was performed and hemodynamic changes were observed. RESULTS: A total of 194 patients were enrolled, with 65 in the hydromorphone group, 67 in the fentanyl group, and 62 in the saline group. The overall incidence of withdrawal movements was significantly lower in the hydromorphone group (2 patients; 3.1%) and the fentanyl group (5 patients; 7.5%) (both, P < 0.001) than in the saline group (36 patients; 58.1%). The mean arterial pressure (MAP) and heart rate (HR) after intubation (median [interquartile range]) in the fentanyl group (101.5 [84-115] mm Hg; 93.5 [82-102] beats per minute [bpm]) and the hydromorphone group (93.0 [83-106] mm Hg; 90.0 [86.3-93.6] bpm) were significantly lower than these measures in the saline group (111.5 [105-123] mm Hg; 103.5 [96-113] bpm) (fentanyl group MAP and HR, P < 0.001; hydromorphone group MAP and HR, P < 0.001). CONCLUSIONS: Pretreatment with hydromorphone and fentanyl may have similar effectiveness in reducing withdrawal movements in response to rocuronium injection pain and inducing immediate general anesthesia.

Tailored Therapy Based on Molecular Characteristics in Endometrial Cancer.

Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.

Prognostic implication of systemic inflammatory markers in young patients with resectable colorectal cancer.

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.

Preferences for life-sustaining treatment in Korean adults: a cross-sectional study.

OBJECTIVES: Life-sustaining treatment is any treatment that serves to prolong life without reversing the underlying medical conditions, and includes cardiopulmonary resuscitation, mechanical ventilation, haemodialysis and left ventricular assist devices. This study aimed to investigate the thoughts on life-sustaining treatment of Koreans and to assess the factors associated with deciding to not receive life-sustaining treatment if they develop a terminal disease. DESIGN: Cross-sectional study. SETTING: Guro-gu centre for dementia from 1 May 2018 to 31 December 2019. PARTICIPANTS: In total, 150 individuals participated in this study. OUTCOME MEASURES: The questionnaire consisted of self-report items with some instructions, demographic characteristics, thoughts on life-sustaining treatment and psychosocial scales. The preferences of the participants were investigated on the assumption that they develop terminal cancer. The psychosocial scales included the Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Connor-Davidson Resilience Scale and Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: We classified our participants into two groups: individuals who wanted to receive life-sustaining treatment (IRLT) and individuals who wanted to not receive life-sustaining treatment (INLT). There were twice as many participants in the INLT group than there were in the IRLT. In making this decision, the INLT group focused more on physical and mental distress. Additionally, 32.7% of participants responded that terminal status was an optimal time for this decision, but more participants want to decide it earlier. The GAD-7 and PHQ-9 scores were significantly higher in the INLT group than in the IRLT group. However, the INLT group had significantly lower MSPSS family scores. CONCLUSION: Our findings can help assess issues regarding advance directives and life-sustaining treatment, and will be a reference for designing future studies on this issue.

Inflammatory markers as prognostic indicators in pancreatic cancer patients who underwent gemcitabine-based palliative chemotherapy.

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. CONCLUSION: 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.

Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma.

Signaling through the Notch1 receptor has a pivotal role in early thymocyte development. Gain of Notch1 function results in the development of T-cell acute lymphoblastic leukemia in a number of mouse experimental models, and activating Notch1 mutations deregulate Notch1 signaling in the majority of human T-cell acute lymphoblastic leukemias. Notch2, another member of the Notch gene family, is preferentially expressed in mature B cells and is essential for marginal zone B-cell generation. Here, we report that 5 of 63 (approximately 8%) diffuse large B-cell lymphomas, a subtype of mature B-cell lymphomas, have Notch2 mutations. These mutations lead to partial or complete deletion of the proline-, glutamic acid-, serine- and threonine-rich (PEST) domain, or a single amino acid substitution at the C-terminus of Notch2 protein. Furthermore, high-density oligonucleotide microarray analysis revealed that some diffuse large B-cell lymphoma cases also have increased copies of the mutated Notch2 allele. In the Notch activation-sensitive luciferase reporter assay in vitro, mutant Notch2 receptors show increased activity compared with wild-type Notch2. These findings implicate Notch2 gain-of-function mutations in the pathogenesis of a subset of B-cell lymphomas, and suggest broader roles for Notch gene mutations in human cancers.

Pulmonary function is implicated in the prognosis of metastatic non-small cell lung cancer but not in extended disease small cell lung cancer.

BACKGROUND: The impacts of pulmonary function in patients with metastatic non-small cell lung cancer (NSCLC) and extended disease stage small cell lung cancer (SCLC-ED) treated with palliative chemotherapy remain to still be determined. METHODS: Results of spirometry performed in 449 patients with either stage IV NSCLC (n=313) or SCLC-ED (n=136) at diagnosis were reviewed retrospectively. Overall survival (OS) was estimated using the Kaplan-Meier method and compared via a log-rank test. Multivariate analysis was performed using a Cox proportional hazards regression model. RESULTS: The presence of chronic obstructive pulmonary disease (COPD) was not a risk factor for OS in either NSCLC or SCLC. However, NSCLC patients with COPD with a forced expiratory volume in one second (FEV1) value of less than 80% predicted were associated with a worse OS in both univariate and multivariate analyses [hazard ratio (HR): 1.43; 95% confidence interval (CI): 1.04-1.97; P=0.03]. Intriguingly, only the OS of NSCLC patients treated with chemotherapeutic agents was affected by the airflow limitation FEV1 value of less than 80% predicted (P=0.02). Patients with an FEV1 value of less than 80% predicted treated with targeted agents were not associated with OS (P=0.24). On the other hand, NSCLC patients with COPD were significantly linked to the occurrence of pulmonary complications during palliative therapy (P=0.01) but not associated with death resulting from pulmonary complications (P=0.22). CONCLUSIONS: Careful attention is required when chemotherapeutic agents are administered to patients with metastatic NSCLC with accompanying COPD with a FEV1 value of less than 80% predicted.