National University Boramae Medical Center Research Articles

Digital droplet PCR-based detection of KRAS, NRAS, and BRAF mutation in plasma samples from patients with colorectal cancer.

e15626 Background: Digital droplet PCR (ddPCR) is known for high sensitivity to detect mutated DNA in plasma. The aim of this study was to investigate the concordance of KRAS, NRAS and BRAF mutation detection in patients with colorectal cancers (CRCs) between plasma samples (PSs) and tissue samples (TSs) in pair. Methods: We prospectively collected paired PS and TS from patients with CRC (N = 200) who underwent surgery or biopsy for metastasis at Seoul National University Boramae Medical Center from Mar 2017 to January 2020. The ddPCR was performed using QX200™ Droplet Digital PCR System (Bio-Rad, USA) according to the manufacturer's recommended protocol with PCR kits developed for each gene (Gencurix, South Korea). Results: A total of 187 TSs and PSs were valid for ddPCR. Among these, 111 had results for KRAS, 51 had results for NRAS and 21 had results for BRAF, which were tested through routine clinical practice (RCP) using the pyrosequencing or Sanger sequencing method. The experiment's outcomes were analyzed for KRAS, NRAS, and BRAF, respectively. The analysis initially compared the results of RCP TS and ddPCR TS, and subsequently, intended to compare the mutation detection rates between TS and PS by comparing the results of ddPCR TS and ddPCR PS for FFPE/PS paired specimens. For KRAS, compared to RCP TS, the sensitivity of ddPCR TS was 100%, specificity was 66.7%, and the overall concordance rate was 79.3%. In TS/PS paired specimens, the sensitivity of ddPCR PS for ddPCR TS results was 38.5%, specificity was 97.6%, and the overall concordance rate was 64.7%. For NRAS, compared to RCP TS, the sensitivity of ddPCR TS was 100%, specificity was 98.0%, and the overall concordance rate was 98.0%. In TS/PS paired specimens, the sensitivity of ddPCR PS for ddPCR TS results was 33.3%, specificity was 100%, and the overall concordance rate was 97.4%. For BRAF, sensitivity of ddPCR TS was not available (no RCP positive sample), specificity was 85.7% compared to RCP, corresponded to a concordance rate of 97.0%. The sensitivity of ddPCR PS for ddPCR TS results was 71.4%, specificity was 100%, and the overall concordance rate was 97.4%. The sensitivity of ddPCR PS for ddPCR TS results was 71.4%, specificity was 100%, and the overall concordance rate was 97.4%. Conclusions: The present study showed that ddPCR has high accuracy in detecting KRAS, NRAS and BRAF mutation in plasma samples from patients with CRC. Analysis of PS could be useful in early response assessment and longitudinal disease monitoring for patient with metastatic CRC with specific mutation.

Clinical validation of a novel circulating tumor DNA methylation assay for predicting recurrence of colorectal cancer in patients with curative-intent surgery by monitoring minimal residual disease.

3620 Background: Circulating tumor DNA (ctDNA)-based liquid biopsy has emerged as a promising tool for early detection and monitoring of cancer. In this study, we developed COLO eDX, a digital-PCR based colorectal cancer (CRC) diagnostic assay using a single CRC-specific methylation biomarker. This study aimed to evaluate the prognostic value as the universal assay for recurrence monitoring in CRC patients with curative-intent surgery. Methods: A total of 116 CRC patients who underwent surgery at Seoul National University Boramae Medical Center were enrolled in the study from Mar 2017 to January 2020. For each patient, postoperative plasma specimens were collected at 7 days and at each regular clinical follow-up visit up to 2 years. The enrolled patients were followed up with radiological and clinical measures for maximally 5 years after surgery. The primary outcome was recurrence-free survival (RFS) according to ctDNA status. Results: The majority of samples collected at 7 days after surgery were ctDNA positive by COLO eDX (65/83, 78.3%) and the ctDNA status was not significantly associated with RFS, suggesting that cancer signatures can still be detected in most cancer patients at least 1 week after surgery. However, ctDNA positivity at 1 month or later was associated significantly worse RFS. In plasma taken between 1- and 9-months after surgery, ctDNA positive group had a significantly higher recurrence rate than ctDNA negative group (hazard ratio [HR], 11.4, 95% confidence interval [CI], 3.8-34.4; P<0.0001). Incorporating serial longitudinal samples, ctDNA status was significantly associated with recurrence (HR, 13.4, 95% CI, 4.3-40.6; P<0.0001). Notably, ctDNA analysis by COLO eDX was a more powerful predictor for predicting recurrence than carcinoembryonic antigen (CEA) assessment (HR, 4.0, 95% CI, 1.4-11.8; P=0.0107 and HR, 1.5, 95% CI, 0.3-8.2; P=0.5949). Conclusions: Postoperative ctDNA monitoring using a CRC-specific epigenetic biomarker-based digital PCR assay is a promising strategy for recurrence prediction and personalized clinical management of CRC through early detection of minimal residual disease (MRD).

Early Clinical Outcomes of Thoracoscopic Major Pulmonary Resection and Thymectomy Using Novel Articulating Endoscopic Forceps.

Video-assisted thoracoscopic surgery (VATS) is recognized as a safe and effective treatment modality for early-stage lung cancer and anterior mediastinal masses. Recently, novel articulating instruments have been developed and introduced to endoscopic surgery. Here, we share our early experiences with VATS major pulmonary resection and thymectomy performed using ArtiSential articulating instruments. At the Seoul Metropolitan Government-Seoul National University Boramae Medical Center, 500 patients underwent VATS pulmonary resection between July 2020 and April 2023, while 43 patients underwent VATS thymectomy between January 2020 and April 2023. After exclusion, 224 patients were enrolled for VATS major pulmonary resection, and 38 were enrolled for VATS thymectomy. ArtiSential forceps were utilized in 35 of the 224 patients undergoing pulmonary resection and in 12 of the 38 individuals undergoing thymectomy. Early clinical outcomes were retrospectively analyzed. No significant differences were observed in sex, age, surgical approach, operation time, histological diagnosis, or additional procedures between the patients who underwent surgery using novel articulating instruments and the group treated with conventional endoscopic instruments for both VATS major pulmonary resection and thymectomy. However, the use of the novel articulating endoscopic forceps was associated with a significantly larger number of dissected lymph nodes (p=0.028) and lower estimated blood loss (p=0.009) in VATS major pulmonary resection. Major pulmonary resection and thymectomy via VATS using ArtiSential forceps were found to be safe and effective, with early clinical outcomes comparable to established methods. Further research into long-term clinical outcomes and cost-effectiveness is warranted.

Abstract A051: Treatment outcome of leptomeningeal metastasis from breast cancer

Abstract Purpose: Leptomeningeal metastasis (LM) is well-known for its dismal prognosis. Despite various treatment approaches, there has been minimal improvement in survival, and the optimal treatment for leptomeningeal metastasis remains uncertain. Our study aimed to report treatment outcomes using different modalities for LM and to identify prognostic factors. Materials and Methods: We analyzed 111 breast cancer patients with LM, who were treated at Seoul National University and Seoul Metropolitan Government Seoul National University Boramae Medical Center between January 2010 and December 2022. The median follow-up period was 4.4 months (range, 0.2 – 125.4 months). Results: The median age was 48 years, with the majority having a Karnofsky performance status below 60 (n = 100, 90.1%). Among the 111 patients, intrathecal chemotherapy was the most commonly used treatment modality (n = 89, 80.2%), followed by radiotherapy (n = 74, 66.7%), and systemic chemotherapy (n = 56, 50.5%). The median freedom from progression was 3.4 months. In multivariate analysis, patients who underwent more than 2 treatment modalities experienced significantly longer progression-free interval (1.8 months vs. 7.4 months, HR = 0.20, p = 0.038). Additionally, patients who underwent excision of the primary breast tumor displayed a tendency for longer progression-free interval (3.1 months vs. 3.4 months, HR = 0.33, p = 0.084). Patients with systemic inflammation index greater than 500 × 103/mm3 at the time of the diagnosis of LM exhibited shorter progression-free interval (3.5 months vs. 2.9 months, HR = 2.88, p = 0.056). There was no difference of progression-free interval according to treatment modalities. Conclusions: The freedom from progression of LM originating from breast cancer was found to be poor, exhibiting less than 4 months. A multimodal approach upon LM and high systemic inflammation index at the time of the diagnosis of LM demonstrated significant difference in prognosis. Further research is warranted to elucidate the clinical implications and develop optimized treatment strategie Citation Format: Suzy Kim, Choong-won Lee. Treatment outcome of leptomeningeal metastasis from breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A051.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of gestational diabetes mellitus: a second analysis based on data from a prospective cohort study.

Although there is strong evidence linking triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to insulin resistance and diabetes mellitus, its clinical importance in pregnant women has not been well determined. This study sought to determine the connection between the TG/HDL-C ratio in the first trimester and the eventual onset of gestational diabetes mellitus (GDM). We performed a secondary analysis of open-access data from a prospective cohort study. This present study included 590 singleton pregnant women at 10-14 weeks who visited the outpatient clinics for prenatal checks and were recorded at Incheon Seoul Women's Hospital and Seoul Metropolitan Government Seoul National University Boramae Medical Center in Korea. A binary logistic regression model, a series of sensitivity analyses, and subgroup analysis were used to examine the relationship between TG/HDL-C ratio and incident GDM. A receiver operating characteristic (ROC) analysis was also conducted to assess the ability of the TG/HDL-C ratio to predict GDM. The mean age of the included individuals was 32.06 ± 3.80 years old. The mean TG/HDL-C ratio was 1.96 ± 1.09. The incidence rate of GDM was 6.27%. After adjustment for potentially confounding variables, TG/HDL-C ratio was positively associated with incident GDM (OR=1.77, 95%CI: 1.32-2.38, P=0.0001). Sensitivity analyses and subgroup analysis demonstrated the validity of the relationship between the TG/HDL-C ratio and GDM. The TG/HDL-C ratio was a good predictor of GDM, with an area under the ROC curve of 0.7863 (95% CI: 0.7090-0.8637). The optimal TG/HDL-C ratio cut-off value for detecting GDM was 2.2684, with a sensitivity of 72.97% and specificity of 75.05%. Our results demonstrate that the elevated TG/HDL-C ratio is related to incident GDM. The TG/HDL-C ratio at 10-14 weeks could help identify pregnant women at risk for GDM and may make it possible for them to receive early and effective treatment to improve their prognosis.

Clinical outcomes after incomplete cycles of R-CHOP for diffuse large B-cell lymphoma: 10 years’ real-world experience in a single institute

Although the current standard of care for diffuse large B-cell lymphoma (DLBCL) is six cycles of rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone combination chemotherapy (R-CHOP), a larger than expected number of patients cannot complete planned six cycles for various reasons in the real world. We aimed to evaluate the prognosis of patients with DLBCL after incomplete treatment by analyzing the chemotherapy response and survival according to the cause of discontinuation and the number of cycles. We analyzed a retrospective cohort of patients diagnosed with DLBCL who underwent incomplete cycles of R-CHOP at Seoul National University Hospital and Boramae Medical Center from January 2010 to April 2019. A total of 1183 patients were diagnosed with DLBCL, of which 260 (22%) did not complete six cycles of R-CHOP. The most common cause of discontinuation of chemotherapy was life-threatening infection, and the most common pathogen was Pneumocystis jirovecii. Overall survival (OS) and progression-free survival (PFS) were significantly better in patients who achieved complete response (CR) or partial response (PR) at the first response evaluation. Patients underwent three or more cycles of chemotherapy had a longer OS than those who did not. In patients with limited-stage disease, consolidative radiotherapy showed a significant improvement in OS and PFS. Advanced stage, high comorbidity score, and poor primary response to chemotherapy were poor prognostic factors in patients with unplanned treatment shortening. This study provides real-world outcomes for patients who could not complete the planned six cycles of R-CHOP.

Abstract 3341: Preliminary clinical validation of COLO eDX, a novel plasma circulating tumor DNA methylation assay for detecting colorectal cancer

Abstract Introduction: Liquid biopsies with cell-free DNA (cfDNA) from plasma, are rapidly emerging as an important and minimally invasive approach for the early diagnosis of cancer. Here we present COLO eDX, as a novel methylation-specific droplet digital PCR (ddPCR)-based colorectal cancer (CRC) diagnostic tool. Methods: During the discovery phase, we analyzed DNA methylome profiles of more than 10,000 samples from CRC, normal colorectal mucosa, and other cancer types (the TCGA and GEO public databases). Through the multi-step biomarker discovery studies, we selected 14 CRC-specific hypermethylated CpG sites. Among them, 2 candidate sites were uniquely methylated in a CRC cell line among tested cancer cell lines from various organs including CRC (HCT-15), 2 hepatocellular carcinomas (Huh7 and SK-HEP-1), 2 lung cancers (A549 and HCC827), bladder cancer (HT-1376), prostate cancer (LNCap clone FGC), and breast cancer (T-47D). Through the methylation-specific ddPCR assay of paired tissue samples from the patients with CRC, we identified that single candidate was specifically hypermethylated in the most tumor tissues regardless of cancer stage. Copy numbers of the target region (TC) were divided by the copy numbers of the internal control (IC) to normalize. Results: We prospectively collected post-operative plasma samples from patients with CRC (N=23) who underwent surgery at Seoul National University Boramae Medical Center. According to the AJCC 8th staging system and risk groups allocation, 3 patients had standard risk and 8 patients had high risk for recurrence, among stage II patients. Among stage III patients, 3 patients had low risk and 6 patients had high risk for recurrence. 3 patients were stage IV at initial presentation. IC value in the stage IV patients (R2 resected) were significantly higher than that other groups (R0 resected), while there was no significant difference among stage II and stage III patients. Recurrence free survival for patients TC or IC value equal or higher than the median and those lower than the median were not statistically different. Since 3 patients in high risk stage III and 4 patients in high risk stage II patients did not receive the recommended adjuvant chemotherapy, comparison of RFS should be interpreted with caution. Conclusion: We have developed and validated the qualitative detection of methylation status of the bisulfite-converted target region in cfDNA. Further studies are warranted to evaluate the impact of COLO eDx on recurrence in a larger cohort of CRC patients. Citation Format: Jin-Soo Kim, Yun Young Lee, Seung Yeon Jung, Mi Young Kim, Rumi Shin, Jin Hyun Park, Joon An, Jinil Han, Seung Chul Heo, Youngho Moon. Preliminary clinical validation of COLO eDX, a novel plasma circulating tumor DNA methylation assay for detecting colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3341.

The Incidence of Brain-Dead Donors Based on Screening and Management Led by Intensivists.

BACKGROUND This study aimed to compare the incidence of brain-dead (BD) donors and potential brain-dead (PBD) donors before vs after the introduction of intensivists. MATERIAL AND METHODS This longitudinal retrospective study was performed between January 2012 and December 2020 at Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Four dedicated intensivists were introduced in January 2016. The periods before and after introduction of the intensivists were defined as the pre-introduction period (2012-2015) and post-introduction period (2016-2020), respectively. RESULTS During the study period, there were 2872 discharges in the Intensive Care Unit, of which there were a total of 113 PBD (3.93%) and 36 BD (1.25%) donors. The number of PBD and BD donors increased in the post-introduction period compared in the pre-introduction period (PBD, 47.84 vs 27.14 per 1000 discharges; BD, 13.59 vs 11.03 per 1000 discharges). Poisson regression analysis showed the annual incidence rate of PBD donors significantly increased post-introduction (PBD, 27.53% vs 48.11%, P=0.044), while those of BD donors were similar between the 2 groups (BD, 11.41% vs 13.9%; P=0.743). The annual incidence rate of the total number of organ donations, multi-organ donations (>3 organs), and donation of organs (heart, lung, and kidney) increased in the post-introduction period compared to that in the pre-introduction period. CONCLUSIONS Our findings suggest a beneficial role of a dedicated intensivist, not only in improving actual organ donation and discovering PBD donors, but also in affecting the yield of the heart and lung transplantation in actual organ donation compared to donors without a dedicated intensivist.

Hepatitis B immunoglobulin prophylaxis for de novo hepatitis B infection in liver transplantation: a 30-year experience

BackgroundDonors positive for hepatitis B core antibody (HBcAb) are an important source of organs in hepatitis B virus (HBV) endemic areas despite the risk of occult infection. We analyzed the long-term outcomes of hepatitis B immunoglobulin in de novo HBV prevention following liver transplantation (LT) using HBcAb-positive grafts.MethodsThe prospectively collected data from 2,201 recipients at Seoul National University Hospital (SNUH) and Seoul National University Boramae Medical Center between 1988 and 2018 were retrospectively reviewed. A total of 1,458 patients were enrolled. Of the 1,458, 478 (32.8%) grafts were core-positive, 152 (10.4%) of which belonged to HBV surface antigen-negative recipients. During the anhepatic phase, hepatitis B immunoglobulin 4,000 IU was administered intravenously and daily until postoperative day 3.ResultsThe 152 patients with hepatitis B surface antigen-negative received HBcAb-positive graft. De novo HBV developed in 21 (13.8%) of these recipients. De novo HBV occurred in 1, 11, 0, and 9 of the 4 HBcAb- and hepatitis b surface antibody (anti-HB)-negative, 49 HBcAb-negative and anti-HB-positive, 1 HBcAb-positive and anti-HB-negative, and 98 HBcAb- and anti-HB-positive recipients, respectively. Patients with higher Model for End-stage Liver Disease (MELD) score (23.8±8.7 vs. 19.5±9.2) or HBcAb-negative recipients (22.6% vs. 9.1%) had a higher risk of de novo infection. The median follow-up and serum HBV surface antigen-positivity detection time was 69 and 18 months, respectively. The median HBV surface antibody titer was 65.0 IU/L at de novo infection. Nineteen patients of 21 were treated with nucleoside analogs (NAs), and seven of 19 achieved seroconversion. No patient died of de novo HBV infection.ConclusionsWith close monitoring of viral serum markers and appropriate initiation of NAs, de novo HBV infection can be prevented and treated appropriately with the hepatitis B immunoglobulin monoprophylaxis protocol.

Outcome after early thrombotic occlusion of arteriovenous fistulas.

Arteriovenous fistulas (AVFs) are considered the first choice for venous access in end-stage renal disease patients, however, they are also known to have a high primary failure rate (early thrombosis and maturation failure). Of these, the outcome of thrombosed immature AVFs is not well known. This study aimed to investigate the outcome of AVFs with early thrombosis. Patients who underwent AVF creation from January 2009 to December 2019 at Seoul National University Hospital or Seoul Metropolitan Government - Seoul National University Boramae Medical Center were retrospectively reviewed. Patients who received salvage operations due to early thrombosis within 30 days after access creation were analyzed. During the study period, a total of 45 patients (radiocephalic 26; brachiocephalic 19) developed early thrombosis and underwent salvage operations. The median age of patients was 61.0 (54.5-69.5) years, and 51.1% were male. The first salvage operation was performed on the median 1.0 (0.0-4.5) day after AVF creation. The most common cause for early thrombosis was venous stenosis (64.4%) and followed by poor arterial inflow (28.9%), especially in radiocephalic AVFs. About 20 AVFs were salvaged to maturation (46.5%). Post-salvage primary patency and secondary patency at 1 year was 72.6% and 100%. In a multivariate logistic regression, significant risk factors for maturation failures were minimum venous outflow diameter ⩽2.5 mm (OR, 4.433; 95% CI, 1.039-18.921; p = 0.044) and lower in patients with hypertension (OR, 0.064; 95% CI, 0.006-0.637; p = 0.019). Thrombosed immature AVFs are associated with a high failure rate after salvage operation. However, if the salvage operation is successfully performed, it is associated with an acceptable 1-year outcome.

Advantages of Metformin Therapy for the Prevention and Mitigation of Diabetic Foot Ulcer in Patients With Diabetic Kidney Disease: A Real-Word Evidence From Large-Scale Cohort

Background: Diabetic foot ulcer (DFU) and diabetic kidney disease (DKD) are diabetes-related microvascular complications strongly correlated with high morbidity and mortality. While metformin potentially confers a wound-healing advantage, there is no well-established clinical evidence. This study investigates the effect of metformin on DFU from large DKD cohort for the first time. Methods: This retrospective cohort study enrolled DKD patients from two South Korean tertiary-referral centers between 2001 and 2016. Primary outcomes were all-cause mortality and DFU events; secondary outcomes included hospitalization, amputation, composite of amputation or vascular intervention, and Wagner Grade≥3. Multivariate cox analysis and propensity score matching (PSM) were used to balance baseline intergroup differences between metformin users and metformin non-users. Findings: Among 10,832 patients (4,748 metformin users; 6,084 metformin non-users), the 117·5±66·9 months follow-up period, all-cause mortality rate and DFU incidence were 37·1%, and 5·2%, respectively. Fully adjusted multivariate Cox analysis showed that metformin users had lower all-cause mortality (adjusted hazard ratio 0·63; 95% confidence interval 0·58–0·68; p<0·001) and DFU events (0·39; 0·31–0·48; p<0·001). After PSM, metformin users showed lower all-cause mortality (0·61; 0·55–0·67; p<0·001), DFU events (0·42; 0·32–0·56; p<0·001), and secondary outcomes. Interpretation: Metformin therapy in DKD patient can lower all-cause mortality, DFU incidence, and DFU progression. Funding Information: This work was partly supported by Institute of Information & Communications Technology Planning & Evaluation project funded by Korean government (Ministry of the Interior and Safety; no.2021-0-01177) and public clinical research grant-in-aid from Seoul Metropolitan Government-Seoul National University Boramae Medical Center (no.04-2021-0042). Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: This study protocol was approved by the Institutional Review Board of SNUH (No. J-2010-119-1166) and BRMH (No. 30-2020-128). The requirement for informed consent was waived by the approving authority due to the study design. All clinical investigations were conducted in accordance with the principles of the Declaration of Helsinki and its 2013 amendment.

Feasibility and Advantages of Transanal Minimally Invasive Surgery (TAMIS) for Various Lesions in the Rectum.

PurposeWe report our experience in the use of transanal minimally invasive surgery (TAMIS) and the feasibility and safety of this surgical technique in operating for various rectal diseases that require a transanal approach.MethodsBetween 2013 and 2019, 30 patients underwent TAMIS for a rectal lesion at Seoul National University Boramae Medical Center. The clinical data including age, gender, body mass index, tumour size, distance from the anal verge, diagnosis, operation time, postoperative complications, duration of hospital stay, and post-operative margin status were obtained retrospectively from the electronic medical records.ResultsThe mean operation time was 52.1±33.5 and the mean duration of hospital stay after surgery was 4.3±4.2 days. Most of the patients had undergone TAMIS for neuroendocrine tumor (NET) (60%) followed by an adenoma (16.7%) and rectal cancer (13.3%). 4 patients (13.3%) had minor complications after TAMIS. 2 patients (50%) had complained of diarrhea, 1 patient (25%) complained of fecal incontinence and 1 patient (25%) been diagnosed fluid in the operation bed.ConclusionTAMIS is a useful method for local excision of rectal lesion located in mid to upper rectum as well as other rectal pathologies that require a transanal approach.

Analysis of Prognosis according to Type of Health Insurance in Five Major Gastrointestinal Cancer Patients in Public Hospitals: Single-institution Retrospective Study

Public hospitals were established to provide high quality medical services to low socioeconomic status patients. This study examined the effects of public hospitals on the treatment and prognosis of patients with five-major gastrointestinal (GI) cancers (stomach cancer, colon cancer, liver cancer, bile duct cancer, and pancreatic cancer). Among the 1,268 patients treated at Seoul National University Boramae Medical Center from January 2010 to December 2017, 164 (13%) were in the medicare group. The data were analyzed to identify and compare the clinical manifestations, treatment modality, and clinical outcomes between the groups. No statistically significant differences in the clinical data (age, sex), treatment method, and five-year survival rate were observed between the health insurance group and medicare group in the five major GI cancer patients. On the other hand, some medicare group patients tended more comorbidities and fewer treatment options than health insurance patients. Public hospitals have a positive effect on the treatment and prognosis in medicare group patients with the five-major GI cancers.

Can the cervical length in mid-trimester predict the use of vacuum in vaginal delivery?

ObjectiveThis study aimed to evaluate whether an increased cervical length (CL) measured in the mid-trimester is associated with vacuum-assisted vaginal delivery.MethodsThis retrospective cohort study included women who delivered vaginally in Seoul National University Bundang Hospital (n=820) and Boramae Medical Center (n=509) between January 2017 and February 2019. Multifetal pregnancies and preterm births before 37 weeks of gestation were excluded. Only those cases in which CL was measured at 18–22 weeks of gestation for the purpose of screening for preterm birth risk in each institution were analyzed (n=537). Other significant risk factors were reviewed.ResultsThe median gestational age at delivery was 39.4 weeks (range, 37.0–41.6 weeks); 18.6% (100/537) were vacuum-assisted delivery. There was no relationship between mid-trimester CL and vacuum-assisted delivery (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.57–1.62), while nulliparity was associated with a higher risk (OR, 3.64; 95% CI, 1.55–8.57) than multiparity. When the population was divided into 3 groups by CL range, vacuum-assisted delivery rates increased as CL length increased in nulliparous women.ConclusionMid-trimester CL did not predict the need for vacuum-assisted vaginal delivery.

Establishment of Optimal Treatment Process in Patient with Severe Acute Cholecystitis

Introduction: Cholecystectomy, including laparoscopic cholecystectomy, is standard treatment in acute cholecystitis. And Percutaneous transhepatic gallbladder drainage (PTGBD) is one treatment option for patients with moderate to severe acute cholecystitis. The purpose of this study is to compare the clinical outcome of upfront surgery between delayed surgery and establishment of optimal treatment process in patient with severe acute cholecystitis. Method: From 2014 to 2017, a total of 248 patients who underwent surgical resection with acute cholecystitis at Samsung Medical Center, Seoul National University Boramae Medical Center, Ilsan Paik Hospital, and Ajou University Hospital were analyzed retrospectively. The patients with grade Ⅱ, Ⅲ according to Tokyo Guideline 2013/2018 and underwent PTGBD insertion before surgery were included. Result: Patients who underwent PTGBD before surgery were older, had more septic condition and more cardiac or cerebrovascular disease and bad performance status, which was defined ASA (American Society of Anesthesiologists Classification) score ≥ 3 and ECOG (Eastern Cooperative Oncology Group) score ≥ 2, than patients who underwent upfront surgery. In postoperative outcomes, the PTGBD group had longer total hospital stay and received more ICU care than upfront surgery group. In multivariable analysis, having previous abdominal operation history, ASA score ≥ 3 and ECOG score ≥ 2 were independent risk factors that increased postoperative hospital stay. Conclusion: PTGBD insertion in severe acute cholecystitis did not affect postoperative complications and duration of postoperative hospital stay. In future, multicenter randomized controlled trial study will be necessary for accurate analysis of the effect of PTGBD insertion in patients with severe acute cholecystitis.

Thromboembolism in Mycobacterium tuberculosis Infection: Analysis and Literature Review.

BackgroundTuberculosis is associated with hypercoagulation; however, there are few reports of cases thromboembolism and tuberculosis at the same time in the real world. The purpose of this study was to report the incidence and clinical course of thromboembolism in patients diagnosed with tuberculosis.Materials and MethodsWe retrospectively analyzed the data of patients who were diagnosed with both tuberculosis and thromboembolism including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT) at Seoul National University Boramae Medical Center from January 2000 through March 2015.ResultsAmong the 7905 tuberculosis patients, 49 (0.6%) exhibited PTE, DVT, or both at or after the time of tuberculosis diagnosis. All patients treated for tuberculosis started with isoniazid, ethambutol, rifampicin, and pyrazinamide. Eight patients were switched to treatment with second-line medication because of resistance or adverse events. About half of the patients (n = 21, 44.7%) had thrombosis at the time of tuberculosis diagnosis. Of 48 patients treated for thromboembolism, 36 received warfarin. A total of 20 patients improved symptom caused by thrombosis, and 10 patients were confirmed cure by image study such as computed tomography or doppler ultrasonography. Eight patients who were treated with warfarin had persistent thrombosis. Five patients (10.2%) experienced major bleeding that required hospitalization. All of these bleeding events were associated with warfarin therapy.ConclusionsCareful attention to PTE/DVT is needed at the time of diagnosis of tuberculosis and during anti-tuberculosis therapy. Warfarin therapy administered with anti-tuberculosis medication requires frequent monitoring to prevent major bleeding.

Development and external validation of a nomogram with inflammatory markers for predicting invasiveness of IPMN

Introduction: Recent studies have reported that inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI), are associated with invasiveness of intraductal papillary mucinous neoplasm (IPMN). This study aimed to develop a new nomogram for predicting invasiveness of IPMN including the inflammatory markers and validation of the nomogram using external cohort. Method: From 1995 to 2016, a total of 365 patients who underwent surgical resection with IPMN at Samsung Medical Center, Seoul National University Boramae Medical Center, Ilsan Paik Hospital, and Dongguk University Ilsan Hospital were analyzed retrospectively to develop nomogram. For external validation of nomogram, data of 384 patients at Seoul National University Hospital were used. Discrimination ability of nomogram was evaluated using calculating the area under the receiver operating curve (AUC). Result: After analysis, high body mass index (BMI), pre-operative serum bilirubin level, CA19-9, NLR, PLR, ALI, main duct type, presence of solid portion and tumor size were identified as risk factors of invasive IPMN. The nomogram was developed including aforementioned factors (Fig 1). After external validation, the value of AUC was calculated 0.649 (95% CI 0.578-0.720, p < 0.001). Conclusion: Up to now, we think this study is the first report to predict and validate externally invasiveness in IPMN including inflammatory markers. This nomogram would be useful for identifying patients with risk of malignancy and selecting patients for surgical resection. Further research is needed to strengthen the predictability of the model.

Application of thermoreversible hydrogel (poloxamer 407) to protect the corneal endothelium during phacoemulsification in porcine and rabbit eyes

To evaluate the effectiveness of thermoreversible (poloxamer) hydrogels as a substitute for ophthalmic viscosurgical devices (OVDs) during phacoemulsification in porcine and rabbit eyes and compare their endothelial protective effect with that of hyaluronic acid-based OVDs. Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea. Experimental study. Fluorescein-stained poloxamer hydrogels (20%, 22%, 24%, and 26% [weight/weight%]) and cohesive (sodium hyaluronate 1.0% [Provisc]) and dispersive (sodium hyaluronate 3.0%-chondroitin sulfate 4.0% [Viscoat]) OVDs were injected into the anterior chamber of porcine eyes incubated at 32°C. In the invitro study, the retention time was measured in 3 groups of 45 porcine eyes during continuous phacoemulsification. In the invivo study, the endothelial cell count (ECC) was measured before and 3days after intermittent phacoemulsification in 12 rabbit eyes randomized to a poloxamer hydrogel or a dispersive OVD group. The optimum concentration of thermosensitive hydrogel was 26%, at which no gel-to-sol phase transition occurred in the anterior chamber, with a 21°C irrigation solution. In the invitro study, the mean retention times were 5.53seconds±1.77 (SD), 125.00±29.34seconds, and 221.53±42.48seconds in the cohesive OVD, dispersive OVD, and 26% poloxamer hydrogel groups, respectively (P<.001). Throughout the 5-minute intermittent phacoemulsification, the 26% poloxamer hydrogel remained in the anterior chamber as a semisolid gel. In the invivo study, the mean decrease in ECC was significantly lower in the 26% poloxamer hydrogel group than in the dispersive OVD group (P=.029). Thermoreversible hydrogels might be suitable substitutes for hyaluronic acid-based OVDs for corneal endothelial protection during phacoemulsification.

Endothelial function estimated by digital reactive hyperemia in patients with atherosclerotic risk factors or coronary artery disease.

Due to the complex profile of atherosclerotic risk factors, an integrated analysis of a specific individual is difficult. Endothelial function reflects a composite of various risk factors, and may be used as an optimal tool to estimate the overall atherosclerotic risk. In this study, we investigated the value of digital Reactive Hyperemia Index (RHI) in an actual population with multiple atherosclerotic risk factors or coronary artery disease (CAD). A total of 417 patients from the Seoul National University Boramae Medical Center RHI registry were enrolled in this study. Patients were enrolled from January, 2013 to July, 2016. RHI was measured using the EndoPAT2000 system (Itamiar Medical Inc. Israel). The mean value of RHI was 1.67±0.48 in total study population. Among various atherosclerotic risk factors, RHI was significantly lower in older (>60years) patients, diabetics, smokers' patients on statin therapy, and those with coronary or cerebrovascular disease. Most of these findings were consistent after adjustment with multiple regression analysis. RHI was significantly associated with CAD, with a hazard ratio of 1.80 (95% confidence interval 1.15-2.80, p=0.010). In the subgroup with CAD, current smoking was the only finding showing a lower RHI. Brachial-ankle pulse wave velocity, which is a surrogate marker of arterial atherosclerotic change, was not correlated with RHI in patients with clinically significant atherosclerotic disease. RHI was significantly reduced by major atherosclerotic risk factors and in clinical atherosclerotic disease. RHI may reflect a composite effect of risk factors pertaining to the endothelial function.

Effects on Periocular Tissues after Proton Beam Radiation Therapy for Intraocular Tumors.

BackgroundTo present our experience on orbital and periorbital tissue changes after proton beam radiation therapy (PBRT) in patients with intraocular tumors, apart from treatment outcomes and disease control.MethodsMedical records of 6 patients with intraocular tumors who had been treated with PBRT and referred to oculoplasty clinics of two medical centers (Seoul National University Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center) from October 2007 to September 2014 were retrospectively reviewed. The types of adverse effects associated with PBRT, their management, and progression were analyzed. In anophthalmic patients who eventually underwent enucleation after PBRT due to disease progression, orbital volume (OV) was assessed from magnetic resonance (MR) images using the Pinnacle3 program.ResultsAmong the six patients with PBRT history, three had uveal melanoma, and three children had retinoblastoma. Two eyes were treated with PBRT only, while the other four eyes ultimately underwent enucleation. Two eyes with PBRT only suffered from radiation dermatitis and intractable epiphora due to canaliculitis or punctal obstruction. All four anophthalmic patients showed severe enophthalmic features with periorbital hollowness. OV analysis showed that the difference between both orbits was less than 0.1 cm before enucleation, but increased to more than 2 cm3 after enucleation.ConclusionPBRT for intraocular tumors can induce various orbital and periorbital tissue changes. More specifically, when enucleation is performed after PBRT due to disease progression, significant enophthalmos and OV decrease can develop and can cause poor facial cosmesis as treatment sequelae.