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Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arrhythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity induced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64-year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum electrolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and high-degree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic complications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

Background The clinical features and therapeutic strategies for gastric cancer with positive peritoneal washing cytology but without visible gross peritoneal metastasis have not been defined. The aim of this study was to evaluate the effect and clinical prognostic value of postoperative chemotherapy in gastric cancer patients with positive peritoneal washing cytology without gross peritoneal metastasis who underwent radical D2 gastrectomy in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods Intraoperative peritoneal washing cytology was performed in 285 patients who underwent radical D2 gastrectomy between April 2004 and May 2016. Of them, 88 patients with positive cytology but without gross peritoneal metastasis were included in the study. In total, 64 patients received postoperative chemotherapy, whereas 24 patients underwent surgery only. Results Most gastric cancer patients with positive cytology without gross peritoneal metastasis demonstrated pT4 and/or pN3 disease. Postoperative chemotherapy improved DFS and OS compared to surgery only in gastric cancer patients with positive cytology without gross peritoneal metastasis (median DFS 11.63 vs. 6.98 months, p p p p

Background Extrapulmonary neuroendocrine carcinoma (EP-NEC) is an aggressive type of cancer with poor prognosis. Although several biological and histological markers are prognostic factors in NEC, the correlation between prognosis and systemic inflammation markers, such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), is unclear. This study evaluated the association between NLR or PLR and median overall survival (OS) or progression-free survival (PFS) in EP-NEC. Methods We retrospectively analyzed the clinical data from patients with unresectable or metastatic EP-NECs who received platinum-based chemotherapy at Chonnam National University Hwasun Hospital from August 2007 to March 2019. The cut-off values for NLR and PLR were 3 and 160, respectively. Results In total, 38 patients were analyzed. Both NLR and PLR at diagnosis had no significant associations with the response to initial chemotherapy. However, in the high-PLR group, median overall survival (OS) and progression-free survival (PFS) were poorer than those in the low-PLR group (high vs. low: 10.6 vs. 17.1 months, log-rank p = 0.007 and 4.1 vs. 9.3 months, log-rank p = 0.032, respectively). However, the high-NLR group had insignificantly poorer median OS and PFS than the low-NLR group. In the multivariate analysis, high PLR and LDH were independent prognostic factors for median OS and PFS. Conclusions High PLR was associated with shorter survival of EP-NEC patients receiving platinum-based chemotherapy. Therefore, PLR may be an independent prognostic factor in EP-NEC.

4060 Background: Anti-EGFR therapy has been used as a standard treatment for metastatic colon cancer, but the innate resistance is still issues of increasing significance. Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cell proliferation, invasion and anti-apoptosis, through the pathway of MAPK-ERK and PI3K-AKT. We investigated potential crosstalk between FGFR4 and EGFR signaling to identify new resistant mechanism of anti-EGFR therapy and how to overcome it in colon cancer. Methods: RNA-Seq was used to identify the associated signal pathway and down targets induced by FGFR4. Molecular studies including RTK array, RT-qPCR, western blotting were performed to validate the interaction between FGFR4 and EGFR signaling in vitro and in vivo. Next, the effect of FGFR4 in cetuximab resistance was investigated in vitro and in colon cancer patients. Results: FGFR4 overexpression in colon cancer cells activates downstream signaling, such as, PI3K/Akt and RAS/RAF/Erk pathway. Gene Ontology (GO) analysis from RNA-seq revealed that differentially expressed genes (DEGs) altered by expression of FGFR4 were related to biological functions, including cell proliferation, epidermal growth factor receptor signaling, NIK/NF-kB signaling, interferon-gamma signaling, wound healing. RT–qRCR showed that FGFR4 promotes the EGFR and ErbB3 by inducing the expression of EGFR ligands such as AREG, BTC, EREG, HBEGF. In vivo tumorigenesis, we found that FGFR4 promotes tumor growth and high expression of AREG in xenograft tumors. FGFR4 expression reduced the sensitivity to cetuximab in colon cancer cells and synergistic effect was shown when treated with FGFR4 inhibitor with cetuximab. A positive correlation between FGFR4 and AREG expression was observed in cancer, but not in normal tissues and high FGFR4 or AREG expression showed significantly inferior overall survival than low expression in patients treated with cetuximab for metastatic colon cancer. Conclusions: We demonstrated a pivotal mechanism of FGFR4 in colon cancer progression and cetuximab resistance through inducing AREG. Our data point to FGFR4 as a new biomarker to predict cetuximab response and dual targeting of FGFR4 and EGFR may be a promising treatment modality for colon cancer.

The equivalent of a thick lens is a lens which has the same power of refraction and paraxial imaging characteristics for a reference ray, but with a different axial thickness. In this study, thick lenses of an optical system were converted to their equivalent lenses referenced to pupil imaging. Aberration changes due to the lens conversion were compared to the general equivalent lens conversion referenced to object imaging.Keywords: Equivalent lens, Lens conversion, Pupil imaging, Optical system designOCIS codes: (080.2740) Geometric optical design; (080.3630) Lenses; (220.3620) Lens system design