Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

Background: Nonobstetric surgery is sometimes required during pregnancy, and neck abscess or facial bone fracture surgery cannot be postponed in pregnant women. However, dental surgery can be stressful and can cause inflammation, and the inflammatory response is a well-known major cause of preterm labor. Propofol is an intravenous anesthetic commonly used for general anesthesia and sedation. Studies investigating the effect of propofol on human amnion are rare. The current study investigated the effects of propofol on lipopolysaccharide (LPS)-induced inflammatory responses in human amnion-derived WISH cells. Methods: WISH cells were exposed to LPS for 24 h and co-treated with various concentrations of propofol (0.01–1 μg/ml). Cell viability was measured using the MTT assay. Nitric oxide (NO) production was analyzed using a microassay based on the Griess reaction. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE 2), p38, and phospho-p38 was analyzed using western blotting. Results: Propofol did not affect the viability and NO production of WISH cells. Co-treatment with LPS and propofol reduced COX-2 and PGE 2 protein expression and inhibited p38 phosphorylation in WISH cells. Conclusion Propofol does not affect the viability of WISH cells and inhibits LPS-induced expression of inflammatory factors. The inhibitory effect of propofol on inflammatory factor expression is likely mediated by the inhibition of p38 activation.

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: Preterm labor and miscarriage may occur in stressful situations, such as a surgical operation or infection during pregnancy. Pharyngeal and buccal abscess and facial bone fractures are inevitable dental surgeries in pregnant patients. Remifentanil is an opioid analgesic that is commonly used for general anesthesia and sedation. Nonetheless, no study has investigated the effects of remifentanil on amniotic epithelial cells. This study evaluated the effects of remifentanil on the factors related to uterine contraction and its mechanism of action on amniotic epithelial cells.METHODS: Amniotic epithelial cells were preconditioned at various concentrations of remifentanil for 1 h, followed by 24-h lipopolysaccharide (LPS) exposure. MTT assays were performed to assess the cell viability in each group. The effects of remifentanil on factors related to uterine contractions in amniotic epithelial cells were assessed using a nitric oxide (NO) assay, western blot examinations of the expression of nuclear factor-kappa B (NF-κB), cyclooxygenase 2 (COX2), and prostaglandin E2 (PGE₂), and RT-PCR examinations of the expression of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α).RESULTS: Remifentanil did not affect viability and nitric oxide production of amniotic epithelial cells. Western blot analysis revealed that remifentanil preconditioning resulted in decreased expressions of NF-κB and PGE2 in the cells in LPS-induced inflammation, and a tendency of decreased COX2 expression. The results were statistically significant only at high concentration. RT-PCR revealed reduced expressions of IL-1β and TNF-α.CONCLUSION: Preconditioning with remifentanil does not affect the viability of amniotic epithelial cells but reduces the expression of factors related to uterine contractions in situations where cell inflammation is induced by LPS, which is an important inducer of preterm labor. These findings provide evidence that remifentanil may inhibit preterm labor in clinical settings.
Abortion, Spontaneous ; Abscess ; Anesthesia, General ; Blotting, Western ; Cell Survival ; Cyclooxygenase 2 ; Cytokines ; Dinoprostone ; Epithelial Cells ; Facial Bones ; Female ; Humans ; Inflammation ; Interleukins ; Lipopolysaccharides ; NF-kappa B ; Nitric Oxide ; Obstetric Labor, Premature ; Pregnancy ; Tumor Necrosis Factor-alpha ; Uterine Contraction

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

BACKGROUND/AIMS: This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. METHODS: This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/-2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. RESULTS: SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 10³/µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 10³/µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). CONCLUSIONS Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

An 87-year-old woman was referred for the extraction of residual teeth and removal of tori prior to prosthetic treatment. After surgery under general anesthesia, the surgical tape was removed to detach the bispectral index sensor and the hair cover. After the surgical tape was removed, skin injury occurred on the left side of her face. After epidermis repositioning and ointment application, a dressing was placed over the injury. Her wound was found to have healed completely on follow-up examination. Medical adhesive related skin injury (MARSI) is a complication that can occur after surgery and subjects at the extremes of age with fragile skin are at a higher risk for such injuries. Careful assessment of the risk factors associated with MARSI is an absolute necessity.
Adhesives ; Aged, 80 and over ; Anesthesia, General ; Bandages ; Epidermis ; Female ; Follow-Up Studies ; Hair ; Humans ; Risk Factors ; Skin ; Surgical Tape ; Tooth ; Wounds and Injuries