National Cheng-Kung University Hospital Research Articles

Discrimination early Alzheimer’s disease from mild cognitive impairment by using Easy Z‐score Imaging System for ECD SPECT

AbstractBackgroundProdromal AD progresses to dementia at a higher annual rate. Since cholinesterase inhibitor benefits early AD patients, discrimination between MCI due to AD and non‐MCI due to AD remains important.MethodWe conducted a retrospective study of MCI cases at National Cheng Kung University Hospital (NCKUH) from 2017 to 2019. Those who showed hypometabolism at posterior cingulate cortex, precuneus, or posterior parietal cortex on brain ECD SPECT and EZIS severity greater than 1.19 were categorized as MCI due to AD; in contrast, patients with EZIS severity lesser than 1.19 were categorized as non‐MCI due to AD. Clinical outcomes included deterioration of CASI, MMSE, SB scores and conversion from MCI to dementia.ResultThere was positive correlation between EZIS severity and deterioration of CASI, MMSE, SB according to multiple regression results, indicating EZIS severity could predict cognitive progression in three years follow‐up. There was no difference in dementia conversion rate between two groups either by chi‐square method or Kaplan‐Meier method, and EZIS severity was not a significant variable in binary logistic regression analysis for conversion. However, there was a trend toward greater dementia conversion rate in the EZIS‐favored MCI due to AD group, and in the second half period of follow‐up as seen on Kaplan‐Meier curves.ConclusionDuring three years of follow‐up, MCI patients with greater EZIS severity were significantly associated with worse cognitive assessment scores, and there was a trend toward greater dementia conversion rate based on cutoff value 1.19 of EZIS severity.

The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.

Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear. We recruited exclusively breastfeeding mothers from among the donors of the human milk bank established at National Cheng-Kung University Hospital. The donor mothers provided 35 BM samples at three months (3M; before introducing children to complementary feeding) and 23 BM samples at six months (6M; after introducing children to complementary feeding) postpartum. At both time points, samples from different body sites, including nasal swabs, oral swabs and stool, were collected from the mothers and their infants. Maternal BMI was inversely associated with coagulase-negative Staphylococcus (CoNS) abundance in breastmilk. Staphylococcus caprae representation in BM CoNS showed a negative correlation with Streptococcus abundance. Network analysis revealed that infants fed Staphylococcus-dominated BM had better gut and nasal microbiota networks than infants fed Streptococcus-abundant BM during early infancy. Our work suggests that maternal metabolic status plays a crucial role in Staphylococcus/Streptococcus competition in BM, which in turn can impact the development of the infant microbiota. Our microbiota co-occurrence network analysis might serve as a helpful bioinformatic tool to monitor microbiota maturation during early infancy.

The risk factors of the 72-h unscheduled return visit admission to emergency department in adults below 50 years old

BackgroundAn unscheduled return visit (URV) to the emergency department (ED) within 72-h is an indicator of ED performance. An unscheduled return revisit (URV) within 72-h was used to monitor adverse events and medical errors in a hospital quality improvement program. The study explores the potential factors that contribute to URV to the ED within 72-h and the unscheduled return revisit admission (URVA) in adults below 50 years old.MethodsThe case–control study enrolled 9483 URV patients during 2015–2020 in National Cheng-Kung University Hospital. URVA and URV non-admission (URVNA) patients were analyzed. The Gini impurity index was calculated by decision tree (DT) to split the variables capable of partitioning the groups into URVA and URVNA. Logistic regression is applied to calculate the odds ratio (OR) of candidate variables. The α level was set at 0.05.ResultsAmong patients under the age of 50, the percentage of females in URVNA was 55.05%, while in URVA it was 53.25%. Furthermore, the average age of URVA patients was 38.20 ± 8.10, which is higher than the average age of 35.19 ± 8.65 observed in URVNA. The Charlson Comorbidity Index (CCI) of the URVA patients (1.59 ± 1.00) was significantly higher than that of the URVNA patients (1.22 ± 0.64). The diastolic blood pressure (DBP) of the URVA patients was 85.29 ± 16.22, which was lower than that of the URVNA (82.89 ± 17.29). Severe triage of URVA patients is 21.1%, which is higher than the 9.7% of URVNA patients. The decision tree suggests that the factors associated with URVA are “severe triage,” “CCI higher than 2,” “DBP less than 86.5 mmHg,” and “age older than 34 years”. These risk factors were verified by logistic regression and the OR of CCI was 2.42 (1.50–3.90), the OR of age was 1.84 (1.50–2.27), the OR of DBP less than 86.5 was 0.71 (0.58–0.86), and the OR of severe triage was 2.35 (1.83–3.03).ConclusionsThe results provide physicians with a reference for discharging patients and could help ED physicians reduce the cognitive burden associated with the diagnostic errors and stress.

Island Hopping Transfer for Major Trauma Treatment and 5G Smart Ambulance

<p>成大醫院急診部在2019年提出「特殊傷病患跳島策略」，縮短運送時間，透過連結院前救護和院後治療的方式，讓患者在短時間內得到初步評估和穩定生命跡象，並且安全轉送至醫學中心接受適切治療。自2020年起，已有55位生命徵象不穩定的重大傷病患透過此轉診模式由偏鄉地區轉診至成大，其中有43位存活離開急診並接受後續療。2022年成大急診部與遠傳電信合作，推出2.0版本的跳島策略，透過5G科技導入智慧救護，包括視訊通訊、遠程監控、智慧救護車和智慧穿戴等，提高到院前的醫療品質和效率。期待已此模式當成一個＂pilot study＂；讓5G通訊技術在未來的緊急醫療中扮演更重要的角色，造福更多的病人。</p> <p> </p><p>In 2019, the National Cheng Kung University (NCKU) Hospital Department of Emergency Medicine proposed an “island hopping” strategy for patients with special injuries to shorten patient transportation time. Specifically, through the coordination of prehospital care and posthospital treatment, patients can be assessed and stabilized t an early stage within a short time and transferred safely to a medical center for appropriate treatment. Since 2020, 55 critically injured patients with unstable vital signs have been referred to NCKU Hospital from remote areas through this transfer model, with 43 of them discharged from the emergency department alive and receiving follow-up treatment. In 2022, NCKU Hospital Department of Emergency Medicine collaborated with FarEastone Telecom in formulating Version 2.0 of the island hopping strategy, which incorporates smart emergency care through the use of 5G technology to facilitate the implementation of video communication, remote monitoring, smart ambulances, and smart wearable devices. The smart emergency care model improves the quality and efficiency of prehospital care. This model shall constitute a pilot study for incorporating 5G communication technology as a key instrument for emergency medicine to benefit more patients.</p> <p> </p>

Feature-enhanced adversarial semi-supervised semantic segmentation network for pulmonary embolism annotation

This study established a feature-enhanced adversarial semi-supervised semantic segmentation model to automatically annotate pulmonary embolism (PE) lesion areas in computed tomography pulmonary angiogram (CTPA) images. In the current study, all of the PE CTPA image segmentation methods were trained by supervised learning. However, when CTPA images come from different hospitals, the supervised learning models need to be retrained and the images need to be relabeled. Therefore, this study proposed a semi-supervised learning method to make the model applicable to different datasets by the addition of a small number of unlabeled images. By training the model with both labeled and unlabeled images, the accuracy of unlabeled images was improved and the labeling cost was reduced. Our proposed semi-supervised segmentation model included a segmentation network and a discriminator network. We added feature information generated from the encoder of the segmentation network to the discriminator so that it could learn the similarities between the prediction label and ground truth label. The HRNet-based architecture was modified and used as the segmentation network. This HRNet-based architecture could maintain a higher resolution for convolutional operations to improve the prediction of small PE lesion areas. We used a labeled open-source dataset and an unlabeled National Cheng Kung University Hospital (NCKUH) (IRB number: B-ER-108-380) dataset to train the semi-supervised learning model, and the resulting mean intersection over union (mIOU), dice score, and sensitivity reached 0.3510, 0.4854, and 0.4253, respectively, on the NCKUH dataset. Then we fine-tuned and tested the model with a small number of unlabeled PE CTPA images in a dataset from China Medical University Hospital (CMUH) (IRB number: CMUH110-REC3-173). Comparing the results of our semi-supervised model with those of the supervised model, the mIOU, dice score, and sensitivity improved from 0.2344, 0.3325, and 0.3151 to 0.3721, 0.5113, and 0.4967, respectively. In conclusion, our semi-supervised model can improve the accuracy on other datasets and reduce the labor cost of labeling with the use of only a small number of unlabeled images for fine-tuning.

Psychological Distress and Physical Adverse Events of COVID-19 Vaccination among Healthcare Workers in Taiwan.

The COVID-19 pandemic places high pressure on everyone, including healthcare workers (HCWs), thus causing them to experience psychological distress. HCWs have priority in receiving the COVID-19 vaccine. However, few studies have identified adverse events (AEs) and psychological distress in the HCWs group. Therefore, we investigated the association between psychological distress and AEs and the determinants of protective behaviors in Taiwanese HCWs. A longitudinal measurement was conducted among HCWs at National Cheng Kung University Hospital (NCKUH), Tainan, Taiwan (n = 483, mean age = 37.55 years). All HCWs completed an online questionnaire on psychological distress, COVID-19 vaccination AEs, and protective behaviors. We used generalized estimating equations (GEE) to analyze the correlation between psychological distress and AEs, and used multivariable logistic regressions to explore the predictors of protective behaviors. Depression and distress and anger were significantly associated with various physical AEs (p = 0.045 to p < 0.001). Suicidal thoughts became a significant independent variable of systemic AEs after COVID-19 vaccination (p = 0.014 to p < 0.001). People of older ages or females engaged more in washing their hands, wearing masks, and reducing their presence in crowded places. Suicidal thoughts were related to the occurrence of systemic AEs among HCWs. Doctors performed better at preventive behaviors compared to nurses and other HCWs. HCWs who experienced anxiety and nervousness tended to avoid crowds.

Osteoregenerative efficacy of a novel synthetic, resorbable Ca/P/S-based bone graft substitute in intra- and peri-articular fractures: a brief medical image-based report

BackgroundWhen a fracture goes into or around a joint, it usually damages the cartilage at the ends of bones and other joint tissue. As a result, the affected joints are prone to traumatic arthritis, leading to stiffness. Repairing bone damage, maintaining joint integrity, and avoiding subchondral and metaphyseal defects caused by comminuted fractures is often a great challenge for orthopedic surgeons. Tissue engineering of synthetic bone substitutes has proven beneficial to the attachment and proliferation of bone cells, promoting the formation of mature tissues with sufficient mechanical strength and has become a promising alternative to autograft methods. The purpose of this study is to retrospectively evaluate the clinical outcome and efficacy of a novel synthetic, highly biocompatible, and fully resorbable Ca/P/S-based bone substitute based on medical image findings.Materials and methodsA synthetic, inorganic and highly porous Ca/P/S-based bone-substituting material (Ezechbone® Granule, CBS-400) has been developed by National Cheng-Kung University. We collected fourteen cases of complex intra- and peri-articular fractures with Ezechbone® Granule bone grafting between 2019/11 and 2021/11. We studied the evidence of bone healing by reviewing, interpreting and analyzing the medical image recordings.ResultsIn the present study, CBS-400 was observed to quickly integrate into surrounding bone within three weeks after grafting during the initial callus formation of the early stage of repair. All of these cases healed entirely within three months. In addition, the patient may return to daily life function after 3.5 months of follow-up and rehabilitation treatment.ConclusionsEzechbone® Granule CBS-400 was proved capable of promoting bone healing and early rehabilitation to prevent soft tissue adhesions and joint contractures. Moreover, it has a high potential for avoiding ectopic bone formation or abnormal synostosis.Trial registrationThe Institutional Review Board at National Cheng Kung University Hospital (NCKUH) approved the study protocol (A-ER-109-031, 3-13-2020).

Immediate Ocular Changes After Light-Emitting Diode Displays Exposure-A Preliminary Study.

PurposeComputer vision syndrome (CVS) is one of the most frequently encountered problems among video display terminals (VDT) users, but little is known regarding the short-term effect after exposure to light-emitting diodes (LED). The purpose of this study was to determine if short-term exposure to LED leads to changes in corrected distance visual acuity (CDVA), lipid layer thickness (LLT), blink rates, partial blink ratio, and computer vision syndrome questionnaire (CVS-Q) score.DesignProspective, cross-sectional study.MethodsIn this study, participants were recruited at the National Cheng-Kung University Hospital, a tertiary referral center in southern Taiwan, for examination. Participants were asked to complete the CVS-Q and undergo a series of ocular examinations, including CDVA, LLT, blink rates and partial blink ratio before and after watching an LED display for 15 min. Main Outcome Measures were changes in CDVA, LLT, blink rates, partial blink ratio, and CVS-Q measurements.ResultsIn total, 120 eyes from 60 participants (mean age: 35.7 ± 9.4 years) were included; 31 participants were men (51.7%), and 29 were women (48.3%). The CDVA, LLT, blink rates, and partial blink ratio did not change after watching the LED display. The CVS-Q score significantly improved after short-term LED exposure (P < 0.001). A subgroup analysis of subjects with a baseline LLT of <60 nm or ≥60 nm determined that LLT significantly decreased in individuals with a baseline LLT of ≥60 nm (P = 0.016).ConclusionShort-term use of LED displays reduced LLT in individuals with a baseline LLT of ≥60 nm, despite the visual symptoms of CVS improved subjectively. Therefore, digital device users should be aware of the potential negative effects of LED exposure on the eyes.

Omental Macrophagic "Crown-like Structures" Are Associated with Poor Prognosis in Advanced-Stage Serous Ovarian Cancer.

The tumor microenvironment is a well-recognized framework in which immune cells present in the tumor microenvironment promote or inhibit cancer formation and development. A crown-like structure (CLS) has been reported as a dying or dead adipocyte surrounded by a ‘crown’ of macrophages within adipose tissue, which is a histologic hallmark of the inflammatory process in this tissue. CLSs have also been found to be related to formation, progression and prognosis of some types of cancer. However, the presence of CLSs in the omentum of advanced-stage high-grade serous ovarian carcinoma (HGSOC) has not been thoroughly investigated. By using CD68, a pan-macrophage marker, and CD163, an M2-like polarization macrophage marker, immunohistochemistry (IHC) was performed to identify tumor-associated macrophages (TAMs) and CLSs. This retrospective study analyzed 116 patients with advanced-stage HGSOC who received complete treatment and had available clinical data from July 2008 through December 2016 at National Cheng Kung University Hospital (NCKUH) (Tainan, Taiwan). Based on multivariate Cox regression analysis, patients with omental CD68+ CLSs had poor OS (median survival: 24 vs. 38 months, p = 0.001, hazard ratio (HR): 2.26, 95% confidence interval (CI): 1.41–3.61); patients with omental CD163+ CLSs also had poor OS (median survival: 22 vs. 36 months, HR: 2.14, 95%CI: 1.33–3.44, p = 0.002). Additionally, patients with omental CD68+ or CD163+ CLSs showed poor PFS (median survival: 11 vs. 15 months, HR: 2.28, 95%CI: 1.43–3.64, p = 0.001; median survival: 11 vs. 15 months, HR: 2.17, 95%CI: 1.35–3.47, respectively, p = 0.001). Conversely, the density of CD68+ or CD163+ TAMs in ovarian tumors was not associated with patient prognosis in advanced-stage HGSOC in our cohort. In conclusion, we, for the first time, demonstrate that the presence of omental CLSs is associated with poor prognosis in advanced-stage HGSOC.

Effect of aspirin treatment duration on clinical outcomes in acute coronary syndrome patients with early aspirin discontinuation and received P2Y12 inhibitor monotherapy

Abstract Background/Introduction Recent clinical trials showed that short aspirin duration (1 or 3 months) in dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduced the risk of bleeding and did not increase the ischemic risk compared to 12-month DAPT in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, it is unclear about the optimal duration of aspirin in P2Y12 inhibitor monotherapy. Purpose The purpose of this study was to evaluate the influence of aspirin treatment duration on clinical outcomes in a cohort of ACS patients intolerant to aspirin with early aspirin interruption and received P2Y12 inhibitor monotherapy. Methods From January 1, 2014 to December 31, 2018, we included 498 ACS patients with aspirin stopped for various reasons before 6 months after PCI and received P2Y12 inhibitor monotherapy. The efficacy and safety between the groups of early (≤1 month) and late discontinuation (&amp;gt;1 month) of aspirin were compared in 12-month follow up after PCI. To adjust for potential confounding due to baseline imbalances in study covariates while preserving sample size, we used the inverse probability of treatment weights (IPTW) method based on the propensity score. Results The mean duration of aspirin treatment was 7.52±8.10 days in the early and 98.05±56.70 days in the late discontinuation group (p&amp;lt;0.001). The primary endpoint was the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months. The safety endpoint was major bleeding, defined as BARC 3 or 5 bleeding. In the multivariate Cox proportional-hazards models, there was no difference in the primary endpoint (adjusted hazard ratio 1.19, 95% confidence interval 0.85–1.68) between the groups. The safety outcome of BARC 3 or 5 bleeding was also similar (Figure 1). In conclusion, patients with early discontinuation of aspirin had similar clinical outcomes to those with late discontinuation. Conclusion The risk of major adverse cardiac events was similar between those with aspirin treatment &amp;gt;1 month versus ≤1 month in ACS patients undergoing PCI who cannot tolerate aspirin and received P2Y12 inhibitor monotherapy. Under P2Y12 inhibitor therapy, early discontinuation of aspirin ≤1 month after PCI maybe feasible and safe. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): National Cheng-Kung university hospital Figure 1

Willingness of Taiwan's Healthcare Workers and Outpatients to Vaccinate against COVID-19 during a Period without Community Outbreaks.

To control the spread of the novel coronavirus disease 2019 (COVID-19), COVID-19 vaccination has been quickly developed. However, the COVID-19 pandemic will not be controlled if the COVID-19 vaccination uptake willingness is low. Therefore, the study aim was to explore the COVID-19 vaccination uptake willingness among the outpatient population and healthcare workers in Taiwan during the worldwide pandemic period without community outbreaks. A cross-sectional survey was conducted among healthcare workers (HCWs; n = 500; mean age = 32.96 years) of National Cheng Kung University Hospital (NCKUH) and outpatients (n = 238; mean age = 34.43 years) arriving at NCKUH. We used an online survey conducted between September 24 and 21 November 2020, for healthcare workers, and between 27 October and 31 December 2020, for the outpatient sample. Information regarding willingness to receive vaccination, willingness to rapid test, fear of COVID-19, risk perception, and preventive behaviors was collected in both samples; information regarding willingness to care for patients was collected in healthcare workers. Willingness to receive vaccination was the main variable in the present study; willingness to rapid test, willingness to care for patients, fear of COVID-19, risk perception, and preventive behaviors were the secondary variables in the study. The factors associated with vaccination willingness were identified through logistic regression analysis. The participants’ willingness to receive vaccination was low for both healthcare workers (23.4%) and the outpatient sample (30.7%). Similarly, their willingness to take rapid tests was low (23.6% for healthcare workers and 28.6% for outpatient sample). Risk perception (crude odds ratio (COR) = 1.29; 95% confidence interval (CI) = 1.03, 1.63), willingness to take rapid test (COR = 9.24; 95% CI = 5.76, 14.83), and preventive COVID-19 infection behaviors (COR = 2.32; 95% CI = 1.52, 3.56) were significant factors explaining the healthcare workers’ willingness to receive vaccination. Willingness to take a rapid test (COR = 8.91; 95% CI = 4.71, 16.87) and preventive COVID-19 infection behaviors (COR = 1.69; 95% CI = 1.09, 2.60) were significant factors explaining the outpatient sample’s willingness to receive vaccination. Willingness to vaccinate against COVID-19 among HCWs and outpatients is low due to the relatively safe status of COVID-19 infection in Taiwan. These findings can help policymakers advocate for the effectiveness of and provide transparent information on COVID-19 vaccination uptake in a country/region with a relatively safe COVID-19 outbreak status.

Sequential and co-occurring DNA damage response genetic mutations impact survival in stage III colorectal cancer patients receiving adjuvant oxaliplatin-based chemotherapy

BackgroundCertain sequences of genomic mutations can lead to cancer formation and affect treatment outcomes and drug resistance. We constructed a cancer evolutionary tree using bulk-targeted deep sequencing to explore the impact of sequential and co-occurring somatic mutations on patients with stage III colorectal cancer (CRC).MethodsA total of 108 stage III CRC patients from National Cheng Kung University Hospital (NCKUH) were recruited for this study between Jan. 2014 and Jan. 2019. Clinical information and tumor-targeted deep sequencing data were collected. Phylogenetic trees were reconstructed for evolutionary trajectories. We used a machine learning model for survival analysis.ResultsSix sequential somatic mutations stratified patients into seven subgroups based on survival. Patients carrying sequential germline followed by DNA damage response-related ATM or BRCA2 somatic mutations or non-TP53, APC somatic mutations had a better outcome than those without such mutations. The 4-year recurrence-free survival (RFS) probability was 88% in the low-risk group (G1) and 46% in the high-risk group (G2) (log-rank p-value 2e-05). The predictive efficacy by the area under the curve (AUC) was 0.73, 0.7, 0.797, and 0.88 at 2, 4, 6, and 8 years, respectively. The mutation status of mismatch repair (MMR) genes was not associated with RFS. Different genomic features were found between the groups. The orders of APC, KRAS and APC, BRCA2 sequential somatic mutations were associated with clinical outcomes. The occurrence of somatic mutations in BRCA2, such as TP53 somatic mutations, affected recurrence-free survival.ConclusionsAccording to the evolution model, DNA damage response (DDR)-related ATM or BRCA2 somatic mutations are promising biomarkers for assessing the response of stage III CRC patients to oxaliplatin-based chemotherapy. The sequential order and co-occurring DDR somatic mutations are associated with recurrence-free survival.

0671 Combination Of Transoral Robotic Surgery And Oropharyngeal Myofunctional Therapeutic Training For Patients With Obstructive Sleep Apnea

Abstract Introduction Obstructive Sleep Apnea (OSA) is a type of sleep disorder characterized by intermittent, partial or complete upper airway collapse. Mostly, moderate to severe OSA cases were recommended to treat with continuous positive airway pressure, however, some of them were withdrawn. Transoral robotic surgery (TORS) was considered for OSA patient with tongue base hypertrophy, but the success rate was only 66.9% and the symptoms might relapse because of aging and gaining weights. Myofunctional therapeutic training (MFTT) was also an alternative treatment for patients with mild to moderate OSA. In our study, we investigated the effect of TORS surgery and oropharyngeal MFTT for OSA patients. Methods Seven adult patients were recruited, who were newly diagnosed with moderate to severe OSA (Apnea-hypopnea Index, AHI, 49.8±27.7/h). Polysomnography, questionnaire (Pittsburgh sleep quality index, PSQI; Snore Outcomes Survey, SOS), and the muscle strengths over tongue and jaw-opening were assessed before TORS surgery, 6-week and 18-week after surgery. The components of MFTT program involved jaw opening, tongue protrusion, tongue left, tongue right, tongue up and tongue down. It began at 6th week after surgery and these patients underwent 12 weeks of the home-based oropharyngeal MFTT. During the training intervention period, subjects were interviewed every week for adjusting the treatment intensity. Results Mean age was 45.9 years old (SD 9.8) and body mass index (BMI) was 26.6 (SD 3.6). After combination treatment of TORS surgery and MFTT, AHI-supine was significantly decreased from 66.3/h to 26.8/h (p&amp;lt;0.05). PSQI and SOS scores were significantly improved (-2.1, 28.8, respectively). Compared with different components of MFTT program, muscle strength of tongue protrusion was the only significant predictor of AHI-supine reduction. Conclusion Our study presented that combination of TORS surgery and oropharyngeal MFTT could improve OSA severity and symptoms. Support This work was supported by National Cheng-Kung University Hospital (grant number NCKUH-10802018).

Laparoscopic Splenic Vessels and Spleen Preservation Distal Pancreatectomy Via Inferior-Posterior Splenic Vein Approach.

Preservation of splenic vessels can minimize the risks of splenic infarction and gastric varices in laparoscopic spleen preserving distal pancreatectomy. A well-established procedure would provide high splenic vessels and spleen preservation rate. This study evaluated the outcomes and depending factors of laparoscopic splenic vessels and spleen preservation distal pancreatectomy (LsvspDP) via inferior-posterior splenic vein approach. This retrospective study enrolled patients who underwent LsvspDP via inferior-posterior splenic vein approach in National Cheng-Kung University Hospital from February 2009 to June 2019. The clinic-pathologic data were collected and analyzed. The primary outcome of this study was the learning curve based on the cumulative sum analysis. The secondary outcomes were to evaluate the critical factors for the failure of splenic vessels and spleen preservation. During the study period, a total of 64 patients received LsvspDP attempt. Splenic vessels were successfully preserved in 49 patients and the overall spleen preservation rate was 76.6%. According to cumulative sum analysis, the learning curve of LsvspDP was the 33rd case and several plateaus were observed during the learning curve phase. Old age (P=0.001), tail location (P=0.038), and large tumor (P=0.01) were independent risk factors of failed splenic vessels preservation, whereas the cut-off point of tumor size for prediction of spleen preservation was 5.4 cm. The complication rates were 7.8%, 7.8%, and 12.5% for Clavien grade I, II, and III, respectively, and 0% for Clavien grade IV or V. The rate of postoperative pancreatic fistula-grade B was 14.8%, among which the tail location was lower than the nontail location (0% vs. 24.3%; P=0.008). The mean value of operative time, blood loss, and hospital stay were 198±67 minutes, 139±242 mL, and 8.5±5.6 days, respectively. In LsvspDP, the inferior-posterior splenic vein approach resulted in high splenic vessels and spleen preservation rate. Thirty-three patients were required to overcome the learning curve. Old age, tail location, and large tumor size were independent factors for the failure of splenic vessels preservation, whereas the cut-off value for tumor size was 5.4 cm to predict splenic vessels preservation.

CD40 Pathway and IL-2 Expression Mediate the Differential Outcome of Colorectal Cancer Patients with Different &lt;i&gt;CSF1R&lt;/i&gt; c.1085 Genotypes

Background: Colony-stimulating factor 1 receptor (CSF-1R) acts as the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation , and function of macrophages. Prior studies showed cancer patients harboring germline CSF1R c.1085A>G genetic variant had a better survival. Here, we studied the immune mechanism underlying the different outcomes. Materials and Methods The clinical outcome for CSF1R c.1085 genotype A_A or A_G was analyzed in a colorectal cancer (CRC) cohort. Primary CRC tumor samples were used to study the tumor immune microenvironment by a targeted gene expression assay containing 395 immune-related genes. Immunofluorescent and immunohistochemical staining were used to validate the findings of gene expression. Findings: CRC patients with CSF1R c.1085 genotype A_G had a better disease-free survival and overall survival than those with CSF1R genotype A_A. Compared to the group of patients without CSF1R variant, higher CD40LG expression, a surface marker of T cells, was found in the tumor tissues of patients with CSF1R c.1085 variant. In parallel with the higher CD40LG gene expression, immunofluorescent staining also showed more CD3+CD40L+ T cell infiltrates in tumors with CSF1R c.1085 genotype A_G. Moreover, higher IL-2 expression, known to be regulated by CD40 pathway, was also observed in tumors with CSF1R c.1085 genotype A_G than those with genotype A_A. Interpretation: Higher IL-2 expression generated by the interaction of CD40 ligand and CD40 between T cells and macrophages with CSF1R c.1085 genotype A_G is the potential mechanism explaining why CRC patients with this germline variant had a better clinical outcome. Funding Statement: National Cheng Kung University Hospital and Chi-Mei hospital (CMNCKU10504) and Ministry of Health and Welfare (MOHW108-TDU-B-211-124018 & MOHW108-TDU-B-211-133003). Declaration of Interests: The authors declare no conflicts of interests with relevance to this study. Ethics Approval Statement: These 2 studies were approved by the institutional review board (A-ER-103-395 & A-ER-1040153) of National Cheng Kung University Hospital (NCKUH) and conducted in accordance with the Declaration of Helsinki. Written informed consents were provided by all patients.

Effectiveness and safety of immune checkpoint inhibitors: A retrospective study in Taiwan.

BackgroundSince 2012, several immune checkpoint inhibitors have been approved by the Taiwan FDA for various types of cancer treatment. However, none of them are covered by Taiwan National Health Insurance due to the fact that they are expensive, and there is a lack of clinical evidence as to their effectiveness.ObjectivesThis study was aimed toward an exploration of clinical experiences with use of immune checkpoint inhibitors, including indications, prescription types, drug effectiveness, adverse drug event types, and incidence, all of which shall serve as references for future clinical drug use.MethodsThis is a retrospective study focusing on three immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab), which are available for cancer treatment in Taiwan. We collected data from medical records for the period from January 1st, 2015 to January 12th, 2017 at National Cheng Kung University Hospital (NCKUH), a medical center in southern Taiwan, and recorded these cases until May 31st, 2017. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and adverse drug reaction odds ratios were analyzed using a chi-square analysis.ResultsThe 50 patients under consideration in this study had used any one of the immune checkpoint inhibitors in NCKUH. Non-small cell lung cancer (n = 24, 48%) accounted for the highest percentage, followed by hepatocellular carcinoma (n = 4, 8%). The median OS was not reached, and the PFS for all immunotherapies was 4.9 months. The median OS period and PFS for non-small cell lung cancer (NSCLC) patients were 13 and 4.9 months, respectively, which were similar to those in many clinical trials. For NSCLC patients, the OS and PFS were only 0.63 and 1.37 months for squamous cell type NSCLC, and for patients who were PD-L1 negative, the OS and PFS were only 11.53 and 2.6 months, respectively. The most common adverse events in this study included fatigue (42%), rashes (22%), nausea (20%), and fever (20%), while one patient developed severe deep venous thrombosis and tissue inflammation, which was not confirmed in previous clinical trials.ConclusionsThe histological subtype, the intensity of the PD-L1 expression, and the timing of treatment affected the NSCLC therapeutic results. It is recommended that clinical tests be conducted in order to enhance therapeutic effectiveness. It is expected that more testing, observation-based studies, and research results will validate their efficacy and the tolerance levels of patients.

PO-094 A novel prognostic significance of combination of preoperative systemic immune-inflammation index and monocyte-lymphocyte ratio in upper tract urothelial carcinoma

IntroductionUpper tract urothelial carcinoma (UTUC) is a rare malignancy in urinary system. In order to improve preoperative treatment choice and management of postoperative surveillance, identification of prognostic factors is necessarily required. To our knowledge, the elevation of systemic inflammatory markers may imply the development of an inflammation-associated microenvironment in tumours. The aim of this study is to identify a novel prognosticator, systemic immune-inflammation index (SII, neutrophil x platelet/lymphocyte) and monocyte-lymphocyte ratio (MLR), in patients with UTUC undergoing radical nephroureterectomy (RNU).Material and methodsThe records of 424 patients who underwent RNU at National Cheng-Kung University Hospital, Taiwan from 2007 to 2017 were analysed. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), MLR, and SII for each patient were calculated and their optimal cut-off values were identified by a receiver operating characteristic curve. Sub-classification based on optimal cut-off values of biomarkers was performed. Kaplan–Meier analyses and Cox proportional hazards models evaluated associations with overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Moreover, logistic regression preoperative models were executed for prediction of advanced disease.Results and discussionsThe median follow-up duration was 35 [interquartile range:14–60] months (Mean:40 months). In multivariable analysis, MLR remained the significant association with OS (p=0.014) and SII significantly influenced on both OS and CSS (p=0.030 and p=0.008, respectively). Further Spearman rank correlation between continuous variables of SII and MLR was 0.374 (P<0.001). Concerning combination of SII and MLR on multivariate analysis, simultaneously high level SII and MLR were significantly associated with OS, CSS, and PFS (all, p<0.05). Moreover, logistic regression preoperative models revealed that simultaneously high level SII and MLR was a significant predictor for non-organ-confined (NOC) UTUC (p=0.002). Further Kaplan–Meier analysis showed that high level SII and MLR was significantly linked to poor OS, CSS and PFS only in patients with NOC UTUC (all, p<0.05).ConclusionOur retrospective study underlines the importance of discovering combination of SII and MLR to significantly predict outcomes in patients with UTUC. Simultaneously high SII and MLR may serve as a significant predictive of NOC UTUC and confers the negative impact on outcomes only in NOC UTUC patients.

PO-095 ICOS: a crucial immunomodulator for development of immunotherapy

IntroductionUpper tract urothelial carcinoma (UTUC) is a rare malignancy in urinary system. In order to improve preoperative treatment choice and management of postoperative surveillance, identification of prognostic factors is necessarily required. To our knowledge, the elevation of systemic inflammatory markers may imply the development of an inflammation-associated microenvironment in tumours. The aim of this study is to identify a novel prognosticator, systemic immune-inflammation index (SII, neutrophil x platelet/lymphocyte) and monocyte-lymphocyte ratio (MLR), in patients with UTUC undergoing radical nephroureterectomy (RNU).Material and methodsThe records of 424 patients who underwent RNU at National Cheng-Kung University Hospital, Taiwan from 2007 to 2017 were analysed. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), MLR, and SII for each patient were calculated and their optimal cut-off values were identified by a receiver operating characteristic curve. Sub-classification based on optimal cut-off values of biomarkers was performed. Kaplan–Meier analyses and Cox proportional hazards models evaluated associations with overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Moreover, logistic regression preoperative models were executed for prediction of advanced disease.Results and discussionsThe median follow-up duration was 35 [interquartile range:14–60] months (Mean:40 months). In multivariable analysis, MLR remained the significant association with OS (p=0.014) and SII significantly influenced on both OS and CSS (p=0.030 and p=0.008, respectively). Further Spearman rank correlation between continuous variables of SII and MLR was 0.374 (P<0.001). Concerning combination of SII and MLR on multivariate analysis, simultaneously high level SII and MLR were significantly associated with OS, CSS, and PFS (all, p<0.05). Moreover, logistic regression preoperative models revealed that simultaneously high level SII and MLR was a significant predictor for non-organ-confined (NOC) UTUC (p=0.002). Further Kaplan–Meier analysis showed that high level SII and MLR was significantly linked to poor OS, CSS and PFS only in patients with NOC UTUC (all, p<0.05).ConclusionOur retrospective study underlines the importance of discovering combination of SII and MLR to significantly predict outcomes in patients with UTUC. Simultaneously high SII and MLR may serve as a significant predictive of NOC UTUC and confers the negative impact on outcomes only in NOC UTUC patients.

The Association between Blood Pressure Status and Colorectal Polyps in a Taiwanese Population

Aim : Colorectal cancer is the third most common cancer worldwide, especially in more developed countries. Colorectal adenomas can progress to malignant carcinoma based on the pathogenesis of adenoma-carcinoma sequence. This study was conducted to investigate the association with colorectal polyps of blood pressure status after excluding the confounding effect of anti-hypertensive agents. MATERIALS AND METHODS : A total of 8,700 eligible subjects with age ≥ 18 years were enrolled from the Health Examination Center of National Cheng Kung University Hospital (NCKUH) between June 2001 and August 2009. We categorized colonoscopic findings into four subgroups: polyp-free, non-neoplastic polyps, non-advanced adenomatous polyps, and advanced adenomatous polyps. Subjects were divided into normal blood pressure, prehypertension and hypertension. RESULTS : The subjects were divided into polyp-free (n = 6,773), non-neoplastic polyps (n = 806), non-advanced adenomatous polyps (n = 876), and advanced adenomatous polyps (n = 245). With adjustments for other variables, hypertension was positively related to non-advanced adenomatous polyps (OR: 1.40, 95% CI: 1.14–1.73) and advanced adenomatous polyps (OR: 1.93, 95% CI: 1.37–2.72). Prehypertension was associated with a higher risk of non-neoplastic polyps (OR: 1.20, 95% CI: 1.01–1.43) and non-advanced adenomatous polyps (OR: 1.42, 95% CI: 1.21–1.68), but not associated with advanced adenomatous polyps. CONCLUSION : Hypertension was positively related to an increased risk of non-advanced and advanced adenomatous polyps, but not non-neoplastic polyps. In contrast, prehypertension was associated with a less advanced stage of colon polyps, including non-neoplastic polyps and non-advanced adenomatous polyps, but not associated with advanced adenomatous polyps.

Abstract 1760: High expression of CASZ1 is associated with poor prognosis in ovarian cancer

Abstract Epithelial ovarian cancer (EOC) carries the highest mortality rate of all gynecologic malignancies. This high mortality rate is attributed to the fact that most cases of ovarian cancer are detected at late stages when metastases are already present. We previously demonstrated that castor zinc finger 1 (CASZ1) is up-regulated in EOC cells and promotes EOC cells metastasis. However, the relationship between the ovarian cancer patient’s prognosis and CASZ1 expression is not clear. In the present study, we examined CASZ1 and CA125 expressions in EOC using immunohistochemistry and correlated their expression levels with patient survival. From January 2008 to January 2012, 144 EOC patients who underwent staging or cytoreductive surgery at the National Cheng Kung University Hospital (NCKUH) were consecutively enrolled. Clinical and pathology information, including age, stage, cell type, chemo-response, and survival, was collected from medical charts. The staging met the criteria of the International Federation of Gynecology and Obstetrics Classification (FIGO). Histological classification was defined according to the classification standards of the World Health Organization. The overall survival (OS) was calculated from the date of diagnosis. Progression-free survival (PFS) was measured as the period from surgery to the date of confirmed recurrence or disease progression or to the date of the investigators’ last note of a disease-free status. CASZ1, CA125 expression was evaluated by TissueFaxs microscopy system using an image analysis program. Five fields of the tumor in each slide (corresponding to a mean of 10000 tumors cells per case) were photographed. Images were acquired from using fluorescence-activated cell sorting (FACS)-like tissue cytometry. The percentage of positive cells in each sample was further quantified using TissueQuest software (TissueGnostics, Vienna, Austria). The CASZ1 was significantly upregulated in advanced EOC tissues, compared with early stage tumors. High CASZ1 expression levels were significantly associated with worse EOC clinical characteristics. By univariate survival analysis, high CASZ1 levels significantly correlated with decreased overall survival, progression-free survival. In addition, patients with both high expression with CASZ1 and CA125 carried the worst prognosis. In conclusion, we demonstrate that high expression of CASZ1 levels correlates with an aggressive EOC phenotype and may contribute for poor prognosis in EOC patient. Determination of CASZ1 could be clinically useful in identifying high-risk EOC patients for a more aggressive adjuvant therapy. Citation Format: Yuan-Jhe Chuang, Yu-Ling Liang, Yuh-Ling Chen, Tse-Ming Hong, Keng-Fu Hsu. High expression of CASZ1 is associated with poor prognosis in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1760. doi:10.1158/1538-7445.AM2017-1760