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Combination treatment with hypomethylating agents (HMAs) and venetoclax is being used increasingly in elderly patients with acute myeloid leukemia (AML). Venetoclax with HMAs has been reported to be associated with tumor lysis syndrome (TLS) in AML patients with high leukemic burden. We present a case of an elderly AML patient with low leukemic burden who developed TLS while receiving venetoclax and azacitidine (AZA). A 74-year-old man with newly diagnosed AML with NPM1 mutation received combination therapy with venetoclax and AZA in an outpatient clinic. Within 12 hours after starting venetoclax and AZA, the patient was admitted to the emergency room with fever, general weakness, and laboratory findings consistent with TLS. Based on our results, we recommend monitoring at the start of the treatment with venetoclax and HMAs to prevent and control TLS regardless of the leukemic burden and favorable genetic risk.

54 Background: We aimed to retrospectively analyze the efficacy and toxicity of capecitabine, as a salvage treatment, in metastatic colorectal cancer (mCRC) that progressed after prior standard 5FU included chemotherapies. Methods: From January 1, 2008, to December 31, 2017, patients with mCRC, age ≥ 18, who received capecitabine as third- or fourth-line treatment at five different centers in South Korea, were included. All had disease progression on prior palliative chemotherapies including 5FU, oxaliplatin, and/or irinotecan. Results: A total of 131 patients were analyzed with a median age of 62 (range, 35-87). Almost all patients were exposed to prior 5FU (100%), irinotecan (100%), and oxaliplatin (98.5%). Patients were treated with cetuximab (26.7%), or bevacizumab (45.8%) before capecitabine. The median and mean duration from the last 5FU exposure to capecitabine start were 21 and 67.3 days, respectively (range, 5-1322). The objective response rate (ORR) of capecitabine was 3.6%, and the disease control rate was 30.4%. The median progression free survival (mPFS) and median overall survival (mOS) was 2.77 (95% CI, 2.495-3.045) and 9.60 months (95% CI, 7.625-11.575), respectively. There was a significant difference in efficacy according to the duration from the last 5FU exposure to the time of starting capecitabine. Compared to patients who started capecitabine earlier than 67 days after the last 5-FU administration, those who started capecitabine later than that time showed higher ORR (11.1% vs 1.2%; p-value = 0.043), mPFS (4.430 (95% CI, 2.274-6.586) vs 2.570 months (95% CI, 2.326-2.814); p-value = 0.011), and mOS (14.070 (95% CI, 5.627-22.513) vs 9.500 months (95% CI, 7.370-11.630, p-value = 0.021) (Table). 68.7% patients experienced any grade of adverse events, but only 4.6% complained grade 3 or higher. There was no treatment related death. Conclusions: Capecitabine showed modest antitumor activity with good tolerability in mCRC patients whose disease progressed after oxaliplatin and/or irinotecan. It could be considered as an alternative treatment option for mCRC patients, especially for those who have longer treatment free interval after 5FU based chemotherapies. [Table: see text]

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.

We have designed a fiber probe based optical diagnose system for detection of interspecies transmissibility. We have showed the optical performance to measure the optical signal of the target sample by using the manufactured fiber probe. We have confirmed the capability of our system to be utilized to biomedical diagnose applications.

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

This paper studied the training methods less affected by the emotional variation for the development of the robust speech recognition system. For this purpose, the effect of emot ional variations on the speech signal were studied using speech database containing various emotions. The performance of the speech recognition system trained by using the speech signal containing no emotion is deteriorated if the test speech signal contains the emotions because of the emotional difference between the test and training data. In thi s study, it is observed that vocal tract length of the speaker is affected by the emotional variation and this effect is one of the reasons that makes the performance of the speech recognition system worse. In this paper, vocal tract normalization method is used to develop the robust speech recognition system for emotional variations. Experimental resul ts from the isolated word recognition using HMM showed that the vocal tract normalization method reduced the er ror rate of the conventional recognition system by 41.9% when emotional test data was used.

Model Predictive Control(MPC) system uses the current input which minimizes the difference between the desired output and the estimated output in the receding horizon scheme. In many cases (for example, system with constraints or nonlinear system), however, it is not easy to find the optimal solution to the above problem. In this paper, we show that real number coding genetic algorithm can be used to solve the optimal problem for MPC effectively. Also, we show by simulation that the real coding algorithm is mote natural and advantageous than the digital coding one.