Publications by authors named "Sang Hyub Lee"

274 Publications

Reply to Drs. Liao and Peng.

Endoscopy 2021 Dec 24;53(12):1291. Epub 2021 Nov 24.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1055/a-1616-0869DOI Listing
December 2021

Gemcitabine plus Nab-paclitaxel as a second-line treatment following FOLFIRINOX failure in advanced pancreatic cancer: a multicenter, single-arm, open-label, phase 2 trial.

Ther Adv Med Oncol 2021 10;13:17588359211056179. Epub 2021 Nov 10.

Pancreaticobiliary Cancer Study Group of Korean Society of Gastrointestinal Cancer, Seoul, Korea.

Background: The aim of this study was to evaluate the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) as second-line chemotherapy following first-line FOLFIRINOX treatment failure in advanced pancreatic cancer.

Methods: This was a multicenter, single-arm, open-label, phase 2 trial done at three tertiary centers in South Korea from May 2018 to December 2019. Eligible patients were aged 20 years or older, had histologically confirmed advanced pancreatic ductal adenocarcinoma, and disease progression after receiving first-line FOLFIRINOX. Patients received a second-line GnP regimen as intravenous nab-paclitaxel at a dose of 125 mg/m and gemcitabine at a dose of 1000 mg/m, on days 1, 8, and 15 every 4 weeks until disease progression or unacceptable toxicity. The primary outcome was survival rate at 6 months and the secondary outcomes were median progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events. This study is registered with Clinicaltrials.gov. (NCT03401827).

Results: Forty patients were enrolled in the study. The survival rate at 6 months was 72.5% [95% confidence interval (CI), 59.9-87.7], achieving superiority over prespecified assumed 6-month OS rate of 20% for best supportive care only ( < 0.001). The median PFS and OS were 5.8 months (95% CI, 4.3-8.7) and 9.9 months (95% CI, 7.5-12.4), respectively. DCR was 87.5% with six partial responses and 29 stable diseases. Grade 3 or higher treatment-related adverse events occurred in 25 (62.5%) patients with the most common being thrombocytopenia, anemia, neutropenia, peripheral neuropathy, and peripheral edema.

Conclusion: GnP demonstrated favorable efficacy with acceptable toxicity in patients with advanced pancreatic ductal adenocarcinoma after FOLFIRINOX failure.
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http://dx.doi.org/10.1177/17588359211056179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591648PMC
November 2021

Role of EUS at high risk for choledocholithiasis without severe cholangitis and visible stone on cross-sectional imaging: A multicenter randomized clinical trial.

Endosc Ultrasound 2021 Nov 8. Epub 2021 Nov 8.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.

Background And Objectives: The prevalence of choledocholithiasis in the high-risk group of choledocholithiasis has been reported to be slightly more than 50% when there is no definite cholangitis. Replacement of diagnostic endoscopic retrograde cholangiography (ERC) with an EUS-first approach may be beneficial in these patients.

Materials And Methods: In this prospective, multicenter study, patients with dilated common bile duct and serum total bilirubin levels of 1.8-4 mg/dL were randomly allocated to undergo either EUS first, followed by subsequent ERC if necessary (EUS group) or ERC only (ERC group). The primary endpoint was the incidence of negative outcomes associated with a false-negative diagnosis of the choledocholithiasis or the endoscopic procedure. The secondary endpoints were the rate of diagnostic ERC and hospital stay length related to the endoscopic procedure.

Results: Of 90 patients who were randomly assigned, the final analysis involved 42 in the EUS group and 44 in the ERC group. The negative outcomes were not significantly different between the EUS and ERC groups (2.4% vs. 6.8%; P = 0.62). The rate of diagnostic ERC was significantly lower in the EUS group (2.4% vs. 47.7%; P < 0.001). The hospital stay length related to the endoscopic procedure was significantly shorter in the EUS group (1.8 ± 1.0 vs. 2.5 ± 1.2 days; P = 0.001).

Conclusion: In selected high-risk choledocholithiasis patients, an EUS-first strategy significantly decreased the rate of diagnostic ERC and hospital stay but did not achieve a significant reduction in negative endoscopic procedure outcomes.
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http://dx.doi.org/10.4103/EUS-D-20-00229DOI Listing
November 2021

Prognosis and Clinical Characteristics of Patients with Pancreatic Ductal Adenocarcinoma Diagnosed by Endoscopic Ultrasonography but Indeterminate on Computed Tomography.

Gut Liver 2021 Oct 7. Epub 2021 Oct 7.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea.

Background/aims: Endoscopic ultrasonography (EUS) provides high-resolution images and is superior to computed tomography (CT) scan in diagnosing small pancreatic ductal adenocarcinoma (PDAC). As a result, the use of EUS for early detection of PDAC has attracted attention. This study aimed to identify the clinical and radiological characteristics of patients with PDAC diagnosed by EUS but not found on CT scan.

Methods: The medical records of patients diagnosed with PDAC at 12 tertiary referral centers in Korea from January 2003 to April 2019 were reviewed. This study included patients with pancreatic masses not clearly observed on CT scan but identified on EUS. The clinical characteristics and radiological features of the patients were analyzed, and survival analysis was performed.

Results: A total of 83 patients were enrolled. The most common abnormal CT findings other than a definite mass was pancreatic duct dilatation, which was identified in 61 patients (73.5%). All but four patients underwent surgery. The final pathologic stages were as follows: IA (n=31, 39.2%), IB (n=8, 10.1%), IIA (n=20, 25.3%), IIB (n=17, 21.5%), III (n=2, 2.5%), and IV (n=1, 1.4%). The 5-year survival rate of these patients was 50.6% (95% confidence interval, 38.8% to 66.7%). Elevated liver function testing and R1 resection emerged as significant predictors of mortality in the multivariable Cox regression analysis.

Conclusions: This multicenter study demonstrated favorable long-term prognosis in patients with PDAC diagnosed by EUS but indeterminate on CT scan. EUS should be considered for patients with suspected PDAC but indeterminate on CT scan.
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http://dx.doi.org/10.5009/gnl210123DOI Listing
October 2021

Impact of conversion surgery on survival in locally advanced pancreatic cancer patients treated with FOLFIRINOX chemotherapy.

J Hepatobiliary Pancreat Sci 2021 Sep 27. Epub 2021 Sep 27.

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Locally advanced (unresectable) pancreatic cancer (LAPC) is surgically unresectable and often treated with chemotherapy. Most previous studies, that have evaluated conversion surgery after chemotherapy, included heterogeneous patients and chemotherapy regimens, making it challenging to determine the impact of FOLFIRINOX. The present study evaluated the survival benefit of conversion surgery in patients with LAPC who received FOLFIRINOX chemotherapy, and analyzed the prognostic factors.

Methods: Patients with LAPC who received FOLFIRINOX as first-line therapy for at least four cycles were included. During chemotherapy, surgical eligibility was determined based on radiologic and metabolic response to the treatment. Clinicopathologic characteristics were compared between the curative-intent surgery and non-resection groups, and the prognostic factors were analyzed.

Results: A total of 279 patients were included. The rates of partial response (PR) and stable disease (SD) were 34.1% and 51.4%, respectively, and 16.8% patients underwent curative-intent surgery. The median survival was significantly longer in the resection group than in the non-resection group (56 vs 21 months, P < .001). In a multivariate analysis, curative-intent surgery (HR 0.260; P < .001) was the most important factor.

Conclusions: Conversion surgery after FOLFIRINOX chemotherapy effectively rescues patients with LAPC. Patients without progression after FOLFIRINOX could be considered as potential candidates for conversion surgery.
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http://dx.doi.org/10.1002/jhbp.1050DOI Listing
September 2021

Gallbladder Polyp Classification in Ultrasound Images Using an Ensemble Convolutional Neural Network Model.

J Clin Med 2021 Aug 14;10(16). Epub 2021 Aug 14.

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Differential diagnosis of true gallbladder polyps remains a challenging task. This study aimed to differentiate true polyps in ultrasound images using deep learning, especially gallbladder polyps less than 20 mm in size, where clinical distinction is necessary. A total of 501 patients with gallbladder polyp pathology confirmed through cholecystectomy were enrolled from two tertiary hospitals. Abdominal ultrasound images of gallbladder polyps from these patients were analyzed using an ensemble model combining three convolutional neural network (CNN) models and a 5-fold cross-validation. True polyp diagnosis with the ensemble model that learned only using ultrasonography images achieved an area under receiver operating characteristic curve (AUC) of 0.8960 and accuracy of 83.63%. After adding patient age and polyp size information, the diagnostic performance of the ensemble model improved, with a high specificity of 88.35%, AUC of 0.9082, and accuracy of 87.61%, outperforming the individual CNN models constituting the ensemble model. In the subgroup analysis, the ensemble model showed the best performance with AUC of 0.9131 for polyps larger than 10 mm. Our proposed ensemble model that combines three CNN models classifies gallbladder polyps of less than 20 mm in ultrasonography images with high accuracy and can be useful for avoiding unnecessary cholecystectomy with high specificity.
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http://dx.doi.org/10.3390/jcm10163585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396835PMC
August 2021

Spontaneous rupture of adrenal myelolipoma as a cause of acute flank pain: A case report.

World J Clin Cases 2021 Aug;9(22):6552-6556

Department of Urology, School of Medicine, Kyung Hee University, Seoul 02447, South Korea.

Background: Adrenal myelolipoma is a rare, benign, non-functioning mass that occurs in the adrenal gland. It is composed of an admixture of hematopoietic elements and mature adipose tissue, similar to bone marrow. Even at large sizes, adrenal myelolipomas are usually asymptomatic and often incidentally found by ultrasonography or computed tomography (CT) scan. This paper describes an unusual case of adrenal myelolipoma presenting as flank pain.

Case Summary: A 50-year-old male with severe right flank pain underwent a CT scan revealing a huge mass extending into the suprarenal space. The mass showed a fat component with retroperitoneal hemorrhage. The tumor was treated laparoscopically, and pathologic examination revealed features of myelolipoma originating from the adrenal gland.

Conclusion: Adrenal myelolipomas are generally asymptomatic and can be treated conservatively. However, rupture and hemorrhage of the tumor can cause symptoms requiring surgical removal.
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http://dx.doi.org/10.12998/wjcc.v9.i22.6552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362562PMC
August 2021

Adverse postnatal developmental effects in offspring from humidifier disinfectant biocide inhaled pregnant rats.

Chemosphere 2022 Jan 22;286(Pt 2):131636. Epub 2021 Jul 22.

Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon, Republic of Korea. Electronic address:

Inhalation exposure to polyhexamethylene guanidine phosphate (PHMG-P), one of the primary biocides used in humidifier disinfectants, caused a fatal pulmonary disease in Korea. Pregnant women were also exposed to PHMG-P, and subsequent studies showed that PHMG-P inhalation during pregnancy adversely affects their health and embryo-fetal development. However, the postnatal developmental effects after birth on prenatally PHMG-P-exposed offspring have not yet been investigated. Therefore, in this study, we aimed to examine the postnatal development of prenatally PHMG-P-exposed offspring. Pregnant rats (22 or 24 females per group) were exposed to PHMG-P during pregnancy in a whole-body inhalation chamber at the target concentrations of 0, 0.14, 1.60, and 3.20 mg/m. After parturition, the prenatally exposed offspring were transferred to non-exposed surrogate mothers to minimize the secondary effects of severe maternal toxicities. Postnatal development of offspring was then examined with a modified extended one-generation reproductive toxicity study design. At 3.20 mg/m PHMG-P, increased perinatal death rates and decreased viability index (postnatal survival of offspring between birth and postnatal day 4) were observed. In addition, F1 offspring had lower body weight at birth that persisted throughout the study. PHMG-P-exposed pregnant rats also had severe systemic toxicities and increased gestation period. At 1.60 mg/m PHMG-P, a decreased viability index was also observed with systemic toxicities of PHMG-P-exposed pregnant rats. These results indicate that prenatal PHMG-P exposure adversely affects the offspring's future health and could be used for human risk assessment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131636DOI Listing
January 2022

Clinical Outcomes and Risk Factor Analysis of Patients Presenting with Emphysematous Cystitis: A 15-Year Retrospective Multicenter Study.

Medicina (Kaunas) 2021 May 26;57(6). Epub 2021 May 26.

Department of Urology, College of Medicine, Kyung Hee University, Seoul 02447, Korea.

To investigate the risk factors for emphysematous cystitis (EC) compared to those of acute cystitis (AC) to increase clinicians awareness of the possibility for the aggravation of patient status. We retrospectively reviewed a total of 54 patients who were hospitalized with a diagnosis of EC by abdominal computed tomography (CT) scan from 2006 to 2020. The control group included 92 patients who were hospitalized for the treatment of AC in the same period. We sought to identify the clinical features and predisposing diseases, such as age, sex, diabetes mellitus (DM), hypertension (HTN), cerebrovascular accident (CVA), chronic kidney disease (CKD), neurogenic bladder (NB), history of urinary tract infection (UTI), and emphysematous pyelonephritis (EPN), that were associated with the development of EC. The median (interquartile range (IQR)) age of the patients with EC was older than that of the patients with AC (78.5 (15.3) years (range: 52-100) vs. 70.0 (26.5) years (range: 28-97 years)). Sepsis and mortality occurred only in the EC group (48.1% and 11.1%, respectively). The univariate analysis of predisposing factors revealed that age, DM, HTN, CVA, CKD, and NB were significantly associated with EC. In the multivariate analysis, DM (OR, 6.251; 95% CI, 2.254-17.250; 0.001), CKD (OR, 18.439; 95% CI, 3.421-99.404; 0.001), NB (OR, 7.374; 95% CI, 1.993-27.285; 0.003) were associated with EC. The results of this study revealed that DM, CKD, and NB were significant risk factors for EC. The tendency toward sepsis and high mortality underscore the need for careful observation while treating patients with EC with the risk noted above.
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http://dx.doi.org/10.3390/medicina57060531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229240PMC
May 2021

Comparison between FOLFIRINOX and gemcitabine plus nab-paclitaxel including sequential treatment for metastatic pancreatic cancer: a propensity score matching approach.

BMC Cancer 2021 May 11;21(1):537. Epub 2021 May 11.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.

Background: FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GnP) have been recommended as the first-line chemotherapy for metastatic pancreatic cancer (mPC). However, the evidence is lacking comparing not only two regimens, but also sequential treatment (FFX-GnP vs. GnP-FFX).

Methods: Data of 528 patients (FFX, n = 371; GnP, n = 157) with mPC were collected retrospectively. Propensity score matching was conducted to alleviate imbalance of the two groups. Overall survival (OS), progression free survival (PFS), and toxicity of patients were analyzed.

Results: In the whole population, OS (12.5 months vs. 10.3 months, P = 0.05) and PFS (7.1 months vs. 5.8 months, P = 0.02) were longer in the FFX group before matching and after matching (OS: 11.8 months vs. 10.3 months, P = 0.02; PFS: 7.2 months vs. 5.8 months, P <  0.01). For sequential treatment, OS and PFS showed no significant difference. Interruptions of chemotherapy due to toxicities were more frequent (6.8 vs. 29.3%, P <  0.001) in the GnP group, and cessation of chemotherapy showed a significant association with mortality (z = - 1.94, P = 0.03).

Conclusions: FFX achieved a longer overall survival than GnP in mPC, but not in the comparison for sequential treatment. More frequent adverse events followed by treatment interruptions during GnP might lead to a poor survival outcome. Therefore, FFX would be a better first-line treatment option than GnP for mPC.
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http://dx.doi.org/10.1186/s12885-021-08277-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114681PMC
May 2021

Successful Removal of a Difficult Common Bile Duct Stone by Percutaneous Transcholecystic Cholangioscopy.

Clin Endosc 2021 May 4. Epub 2021 May 4.

Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Common bile duct (CBD) stones are prevalent in 11% to 21% of patients with gallstones and can cause various clinical manifestations, from biliary colic to biliary sepsis. The treatment of choice is endoscopic retrograde cholangiopancreatography, but approximately 5% to 10% of CBD stones are difficult to remove using these conventional endoscopic methods. Although percutaneous transhepatic cholangioscopy and lithotripsy can be used as an alternative, it can be technically demanding and risky if the intrahepatic duct is not dilated. We report a case of a large CBD stone that was successfully removed using percutaneous transcholecystic cholangioscopy.
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http://dx.doi.org/10.5946/ce.2020.301DOI Listing
May 2021

Lasers for the treatment of urinary stone disease.

Investig Clin Urol 2021 05;62(3):241-242

Department of Urology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4111/icu.20210162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100020PMC
May 2021

The Value of Low Prostate Imaging-Reporting and Data System (PI-RADS) Scores in Preventing Unnecessary Prostate Biopsies.

Medicina (Kaunas) 2021 Apr 24;57(5). Epub 2021 Apr 24.

Department of Urology, Kyung Hee University School of Medicine, Seoul 02453, Korea.

: Magnetic resonance imaging (MRI) and the Prostate Imaging-Reporting and Data System (PI-RADS) have become essential tools for prostate cancer evaluation. We evaluated the ability of PI-RADS scores in identifying significant prostate cancer, which would help avoid unnecessary prostate biopsies. : Patients with prostate-specific antigen (PSA) levels ≤ 20 ng/mL, who underwent prostate MRI for evaluation from January 2018 to November 2019, were analyzed. Among them, 105 patients who received transrectal ultrasonography (TRUS)-guided biopsy were included. PSA, PI-RADS scores (low 1-2, high 3-5), biopsy results, and Gleason scores (GS) were evaluated. Biopsies with GS higher than 3 + 4 were considered as significant cancers and biopsies with no cancer or Gleason 3 + 3 were considered insignificant or no cancers. : Among the 105 patients, 45 patients had low PI-RADS and 60 had high PI-RADS scores. There were no patients with significant prostate cancer in the low PI-RADS groups. For the high PI-RADS group, 28 (46.7%) patients had significant cancer and 32 (53.3%) had insignificant or no cancer. The sensitivity and specificity of high PI-RADS to detect significant cancer was 100% and 58.4%, respectively. Positive predictive value was 46.7% and negative predictive value was 100%. : Low PI-RADS scores on MRI did not show significant prostate cancer and surveillance should be considered in selected cases to prevent unnecessary invasive procedures and overdiagnosis.
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http://dx.doi.org/10.3390/medicina57050413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145899PMC
April 2021

Optimal timing of endoscopic retrograde cholangiopancreatography for acute cholangitis associated with distal malignant biliary obstruction.

BMC Gastroenterol 2021 Apr 17;21(1):175. Epub 2021 Apr 17.

Division of Gastroenterology, Department of Internal Medicine, Liver Research Institute, College of Medicine, Seoul National University Hospital, Seoul National University, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: There is a lack of studies regarding the optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with cholangitis caused by distal malignant biliary obstruction (MBO). This study aims to investigate the optimal timing of ERCP in patients with acute cholangitis associated with distal MBO with a naïve papilla.

Methods: A total of 421 patients with acute cholangitis, associated with distal MBO, were enrolled for this study. An urgent ERCP was defined as being an ERCP performed within 24 h following emergency room (ER) arrival, and early ERCP was defined as an ERCP performed between 24 and 48 h following ER arrival. We evaluated both 30-day and 180-day mortality as primary outcomes, according to the timing of the ERCP.

Results: The urgent ERCP group showed the lowest 30-day mortality rate (2.2%), as compared to the early and delayed ERCP groups (4.3% and 13.5%) (P < 0.001). The 180-day mortality rate was lowest in the urgent ERCP group, followed by early ERCP and delayed ERCP groups (39.4%, 44.8%, 60.8%; P = 0.006). A subgroup analysis showed that in both the primary distal MBO group, as well as in the moderate-to-severe cholangitis group, the urgent ERCP had significantly improved in both 30-day and 180-day mortality rates. However, in the secondary MBO and mild cholangitis groups, the difference in mortality rate between urgent, early, and delayed ERCP groups was not significant.

Conclusions: In patients with acute cholangitis associated with distal MBO, urgent ERCP might be helpful in improving the prognosis, especially in patients with primary distal MBO or moderate-to-severe cholangitis.
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http://dx.doi.org/10.1186/s12876-021-01755-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052855PMC
April 2021

Excision Repair Cross-Complementation Group 6 Gene Polymorphism Is Associated with the Response to FOLFIRINOX Chemotherapy in Asian Patients with Pancreatic Cancer.

Cancers (Basel) 2021 Mar 10;13(6). Epub 2021 Mar 10.

Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 03080, Korea.

FOLFIRINOX is currently one of the standard chemotherapy regimens for pancreatic cancer patients, but little is known about the factors that can predict a response to it. We performed a study to discover novel DNA damage repair (DDR) gene variants associated with the response to FOLFIRINOX chemotherapy in patients with pancreatic cancer. We queried a cohort of pancreatic cancer patients who received FOLFIRINOX chemotherapy as the first treatment and who had tissue obtained through an endoscopic ultrasound-guided biopsy that was suitable for DNA sequencing. We explored variants of 148 DDR genes based on whole exome sequencing and performed multivariate Cox regression to find genetic variants associated with progression-free survival (PFS). Overall, 103 patients were included. Among 2384 variants of 141 DDR genes, 612 non-synonymous variants of 123 genes were selected for Cox regression analysis. The multivariate Cox model showed that rs2228528 in was significantly associated with improved PFS (hazard ratio 0.54, = 0.001). The median PFS was significantly longer in patients with rs2228528 genotype AA vs. genotype GA and GG (23.5 vs. 16.2 and 8.6 months; log-rank < 0.001). This study suggests that rs2228528 in could be a potential predictor of response to FOLFIRINOX chemotherapy in patients with pancreatic cancer.
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http://dx.doi.org/10.3390/cancers13061196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998301PMC
March 2021

Risk factors of febrile urinary tract infections following retrograde intrarenal surgery for renal stones.

Medicine (Baltimore) 2021 Apr;100(13):e25182

Department of Urology, School of Medicine, Kyung Hee University.

Abstract: We aimed to evaluate the risk factors of febrile urinary tract infection (UTI) following retrograde intrarenal surgery (RIRS) for treating renal stones.We retrospectively reviewed the data of patients with 10 - 30 mm kidney stones who underwent RIRS from January 2014 to July 2017. Evaluation included age, gender, body mass index, stone size, stone location, and operative time. All surgeries were performed by a single surgeon and ureteral stenting was not done prior surgery. The risk factors of febrile UTI after RIRS were assessed by univariate and multivariate logistic regression analysis.A total of 150 patients were included in the present study, and 17 patients (11.3%) had febrile UTI after RIRS. Mean patient age was 56.64 ± 13.91 years, and both genders were evenly distributed. Mean stone size was 14.16 ± 5.89 mm. and mean operation time was 74.50 ± 42.56 minutes. According to univariate analysis, preoperative pyuria was associated with postoperative febrile UTI. Multivariate logistic regression analysis showed that preoperative pyuria was the only independent risk factor of infectious complications after RIRS (odds ratios 8.311, 95% confidence intervals 1.759 - 39.275, P = .008). Age, gender, body mass index, comorbidity, preoperative bacteriuria, presence of hydronephrosis, renal stone characteristics, and operative time were not associated with febrile UTI after RIRS.Preoperative pyuria was the only risk factor of infectious complications following RIRS. Therefore, careful management after RIRS is necessary especially when preoperative urinalysis shows pyuria.
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http://dx.doi.org/10.1097/MD.0000000000025182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021282PMC
April 2021

Ursodeoxycholic acid for the prevention of gallstone and subsequent cholecystectomy following gastric surgery: A systematic review and meta-analysis.

J Hepatobiliary Pancreat Sci 2021 May 17;28(5):409-418. Epub 2021 Apr 17.

Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Background/purpose: Patients who undergo gastric surgery are prone to form postsurgical gallstones. Debates still exist about the need for prevention and the selection of preventive methods. No studies had been reported comparing the efficacy of prophylactic ursodeoxycholic acid (UDCA) and prophylactic cholecystectomy (PC) for lowering postsurgical gallstone formation and subsequent cholecystectomy (SC) in patients who have undergone gastric surgery.

Methods: We did a systematic review to identify studies from PUBMED, EMBASE, and the Cochrane database through 30 June 2020. We conducted direct and indirect comparisons of each prophylaxis using conventional and network meta-analysis. Studies with patients who have no history of cholecystectomy and who have not had preoperative gallstone were included.

Results: The excellent preventive effects of PC and UDCA were demonstrated for gallstone formation (odds ratio [OR] 0.05, [95% CI 0.01, 0.22] and 0.20, [95% CI 0.16, 0.24], respectively) and the need for SC (OR 0.10, [95% CI 0.02, 0.57] and OR 0.22, [95% CI 0.14, 0.35], respectively) than control group. The UDCA group showed a tendency to generate more gallstones (OR 3.74, [95% CI 0.88, 15.82]) and a greater need for SC (OR 2.19, [95% CI 0.47-10.14]) than did the PC group without statistical significance.

Conclusions: Prophylaxis for gallstone formation may be needed for patients who undergo gastric surgery to reduce troublesome morbidities. Prophylactic UDCA seems to be a reasonable preventive method for postsurgical gallstone formation to ensure clinical benefit while reducing the burden of subsequent cholecystectomy for the patient as compared to a PC.
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http://dx.doi.org/10.1002/jhbp.946DOI Listing
May 2021

Histogram of kidney stones on non-contrast computed tomography to predict successful stone dusting during retrograde intrarenal surgery.

World J Urol 2021 Sep 17;39(9):3563-3569. Epub 2021 Mar 17.

Department of Urology, School of Medicine, Kyung Hee University, Kyung Hee University Medical Center, 23, Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

Purpose: To predict successful dusting of kidney stones during retrograde intrarenal surgery (RIRS) using stone density parameters and histograms measured with non-contrast computed tomography imaging.

Methods: Medical records of 49 patients who underwent retrograde intrarenal surgery between January 2018 and January 2019 at Kyung Hee University Hospital were reviewed, and the data of 55 stones were evaluated. Patient age, sex, mean stone density, the highest and lowest measured Hounsfield unit (HU), standard deviation and range of the measured HUs, volume of the most measured HU, and success of dusting were evaluated. Histograms of the measured HUs were created and cutoff values for successful dusting were analyzed.

Results: Thirty-two stones were successfully dusted during surgery. Dusted stones had a wider range of HU and higher standard deviation. The volume of the most measured HU was smaller in the dusted stones. Successful dusting could be predicted when the volume of the most measured HU was < 8.9 mm, with range ≥ 853, or when the volume of the most measured HU was < 8.9 mm, with range < 853, and the mean stone density was < 355. The histograms of HUs of the dusted stones were wide and rugged, while those of dusting failed stones were narrow and peaked.

Conclusion: Evaluation of stone HU histograms showed differences in distribution and proportion. This will help predict surgical outcomes and prepare for intraoperative complications.
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http://dx.doi.org/10.1007/s00345-021-03659-9DOI Listing
September 2021

Survival Benefit of Intraductal Radiofrequency Ablation for Malignant Biliary Obstruction: A Systematic Review with Meta-Analysis.

Clin Endosc 2021 Jan 15;54(1):100-106. Epub 2021 Jan 15.

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background/aims: Cholangiocarcinoma (CCA) is a rare but aggressive disease with a poor survival. Recent trials have shown improved survival with intraductal radiofrequency ablation (RFA) therapy. We performed a systematic review with meta-analysis to determine the survival benefit of endoscopic RFA for unresectable extrahepatic CCA with malignant biliary obstruction (MBO).

Methods: A systematic search from 1970 to 2020 was performed in MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials. gov. We selected eligible studies reporting relative risks, hazard ratios (HRs), or odds ratios, adjusted by controlling for confounding factors of survival rate and stent patency duration, among patients with extrahepatic CCA with MBO treated with RFA with stent insertion or stent insertion only.

Results: A total of eight trials (three randomized and five nonrandomized) with a total of 420 patients were included in the metaanalysis. Pooled overall survival analysis favored RFA treatment with stent insertion (HR, 0.47; 95% confidence interval [CI], 0.34- 0.64; I2=47%; p=0.09); however, no significant difference was found in the duration of stent patency between the groups (HR, 0.79; 95% CI, 0.57-1.09; I2=7%; p=0.36).

Conclusion: RFA therapy with stent insertion may confer a survival benefit compared with stent insertion only in patients with CCA and MBO.
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http://dx.doi.org/10.5946/ce.2020.254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939762PMC
January 2021

Huge encrusted ureteral stent forgotten for over 25 years: A case report.

World J Clin Cases 2020 Dec;8(23):6043-6047

Department of Urology, School of Medicine, Kyung Hee University, Seoul 02447, South Korea.

Background: Ureteral stent insertion is a relatively non-invasive procedure commonly used in the field of urology to resolve urinary obstruction. However, they are sometimes forgotten and the risk of complications increases with time.

Case Summary: A 43-year-old woman with a history of recurrent urinary tract infections visited our hospital for evaluation of persistent left flank pain, and lower urinary tract symptoms despite anti-biotic treatment. She had received urological surgery in her teens but did not know the details of her surgery. Kidney, ureter, and bladder X-ray and abdominopelvic computed tomography revealed a forgotten left ureteral stent with huge encrustation at both ends and a severely dilated left kidney with parenchymal thinning. In order to remove the ureteral stent, a laparoscopic nephroureterectomy was planned. The ureteral stent was successfully removed, and she was discharged after recovery. The patient was followed up for two years after surgery and did not show any signs of long-term complications.

Conclusion: Long indwelling stents can cause dire complications requiring radical interventions. Stent registry systems, novel stent material development, and proper patient education is important for complication prevention.
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http://dx.doi.org/10.12998/wjcc.v8.i23.6043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723703PMC
December 2020

Author Correction: Layer-controlled single-crystalline graphene film with stacking order via Cu-Si alloy formation.

Nat Nanotechnol 2021 Jan;16(1):114-116

Center for Integrated Nanostructure Physics (CINAP), Institute for Basic Science (IBS), Suwon, Republic of Korea.

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http://dx.doi.org/10.1038/s41565-020-00821-zDOI Listing
January 2021

Differences between Risk Factors for Sepsis and Septic Shock in Obstructive Urolithiasis.

J Korean Med Sci 2020 Nov 9;35(43):e359. Epub 2020 Nov 9.

Department of Urology, School of Medicine, Kyung Hee University, Kyung Hee University Hospital at Gangdong, Seoul, Korea.

Background: Complicated acute pyelonephritis (APN) is a life-threatening condition that requires immediate intervention. This study examined the characteristics of APN occurring as a complication of ureteral stone.

Methods: We retrospectively reviewed 85 patients diagnosed with APN complicated by ureteral stone between December 2006 and July 2017 at our institution. Patients with concomitant renal stone, multiple ureteral stones, ureteral strictures, ureteral cancer, and urogenital anomalies, including vesicoureteral reflux were excluded. Clinical characteristics including age, sex, underlying disease, medical history, stone characteristics, initial laboratory data, and the procedure used to correct urinary obstruction were summarized, and the risk factors associated with sepsis and septic shock were analyzed.

Results: Sepsis was diagnosed at initial presentation in 62 patients, 17 of whom suffered from septic shock. Disease-related death did not occur in any patient. Previous history of stone ( = 0.015), leukocytosis ( < 0.001), elevated C-reactive protein levels ( = 0.006), and low albumin ( = 0.038) were significant risk factors for progression to sepsis. The absence of hypertension ( = 0.047), thrombocytopenia ( = 0.006), decreased erythrocyte sedimentation rate (ESR) ( = 0.003), elevated blood urea nitrogen ( = 0.016), and positive blood culture ( = 0.018) were significant predictors for progression to septic shock. Multivariate analysis revealed that previous history of stone ( = 0.015) was an independent risk factor for sepsis, while the absence of hypertension ( = 0.047), thrombocytopenia ( = 0.013), and decreased ESR ( = 0.009) were risk factors for shock.

Conclusion: The risk factors associated with the progression from APN to sepsis differed from those associated with the progression from sepsis to septic shock. Various factors should be considered while selecting treatment options based on the severity of APN associated with ureteral stone. It should be managed with aggressive treatment and close observation, especially in the presence of risk factors.
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http://dx.doi.org/10.3346/jkms.2020.35.e359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653168PMC
November 2020

A humidifier disinfectant biocide, polyhexamethylene guanidine phosphate, inhalation exposure during pregnancy induced toxicities in rats.

J Hazard Mater 2021 02 25;404(Pt B):124007. Epub 2020 Sep 25.

Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon, Republic of Korea. Electronic address:

Biocides are widely used for their effective antiseptic and disinfectant properties, including polyhexamethylene guanidine phosphate (PHMG-P), which is also used as a biocide as it selectively disrupts bacterial cell membrane. It is used to clean humidifiers commonly used in the dry winter season in South Korea, which exposes people to PHMG-P inhalation. However, comprehensive toxicological data on PHMG-P inhalation exposure, including in pregnant women, and the potential occurrence of lung disease is lacking. Therefore, in this study, we investigated PHMG-P inhalation exposure-induced toxicities in pregnant rats and prenatal development of their conceptus. Pregnant rats were exposed to PHMG-P via inhalation at target concentrations of 0, 0.14, 1.60, and 3.20 mg/m from implantation to nearly parturition (from gestation day 6-20) and then analyzed for relevant abnormalities. Results showed systemic toxicities in the pregnant rats including respiratory function abnormalities, decreased body weight gain, and decreased food consumption at ≥1.60 mg/m. Prenatal development toxicities, including decreased fetal weight with ossification retardations of fetal bones, were observed at 3.20 mg/m. These results will contribute to clarifying the PHMG-P inhalation exposure-induced toxicities during pregnancy and support its risk assessment in humans.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124007DOI Listing
February 2021

Comparison of efficacy between adjuvant chemotherapy and chemoradiation therapy for pancreatic cancer: AJCC stage-based approach.

World J Clin Oncol 2020 Sep;11(9):747-760

Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul 110-744, South Korea.

Background: The adjuvant treatment for patients with resected pancreatic cancer (PC) is not yet standardized. Because the prognosis differs according to the American Joint Committee on Cancer (AJCC) stage, a tailored approach to establish more aggressive treatment plans in high-risk patients is necessary. However, studies comparing the efficacy of adjuvant treatment modalities according to the AJCC stage are largely lacking.

Aim: To compare the efficacy of chemotherapy and chemoradiation therapy according to AJCC 8th staging system in patients with PC who underwent surgical resection.

Methods: A total of 335 patients who underwent surgical resection and adjuvant treatment for PC were included. Patients were divided into three groups: Chemoradiation therapy (CRT) group, systemic chemotherapy (SCT) group and combined treatment of chemoradiation plus chemotherapy therapy (CRT-SCT) group. The primary outcomes were differences in overall survival (OS) between the three groups. The secondary outcomes were differences in recurrence-free survival, recurrence pattern and adverse events between the three groups.

Results: Patients received CRT ( 65), SCT ( 62) and CRT-SCT ( 208). Overall median OS was 33.3 mo (95% confidence interval (CI): 27.4-38.6). In patients with stage I/II, the median OS was 27.0 mo (95%CI: 2.06-89.6) in the CRT group, 35.8 mo (95%CI: 26.9-NA) in the SCT group and 38.6 mo (95%CI: 33.3-55.7) in the CRT-SCT group. Among them, there was no significant difference in OS between the three groups. In 59 patients with stage III, median OS in the SCT group [19.0 mo (95%CI: 12.6-NA)] and the CRT-SCT group [23.4 mo (95%CI: 22.0-44.4)] was significantly longer than that in the CRT group [17.7 mo (95%CI: 6.8-NA); 0.011 and < 0.001, respectively]. There were no significant differences in incidence of locoregional and distant recurrences between the three groups ( 0.158 and 0.205, respectively). Incidences of grade 3 or higher hematologic adverse events were higher in the SCT and CRT-SCT groups than in the CRT group.

Conclusion: SCT and CRT-SCT showed significantly longer OS and recurrence-free survival than CRT in patients with AJCC stage III, while there was no significant difference in OS between the CRT, SCT and CRT-SCT groups in patients with AJCC stage I/II. Different adjuvant therapy according to AJCC stage can be applied in patients with PC.
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http://dx.doi.org/10.5306/wjco.v11.i9.747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522542PMC
September 2020

High platelet-to-lymphocyte ratio is associated with poor prognosis in patients with unresectable intrahepatic cholangiocarcinoma receiving gemcitabine plus cisplatin.

BMC Cancer 2020 Sep 23;20(1):907. Epub 2020 Sep 23.

Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.

Background: Several systemic inflammatory response (SIR) markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and albumin-to-globulin ratio (AGR), have emerged as prognostic markers in various cancers. The aim of this study was to explore the impact of SIR markers on the survival outcomes of unresectable intrahepatic cholangiocarcinoma (IHC) patients.

Methods: Patients with histologically confirmed, unresectable IHC treated with gemcitabine plus cisplatin (GP) chemotherapy in a single tertiary hospital from 2012 to 2016 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were determined using unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis. Time-dependent receiver operating characteristic (ROC) analysis was performed to compare the performance of the SIR markers in predicting OS.

Results: A total of 137 patients received a median of six cycles (interquartile range [IQR], 3-11) of GP chemotherapy with a median observation time of 9.9 months (range, 1.8-54.7 months). The median PFS and OS of all patients were 7.8 months and 9.9 months, respectively. Among the SIR markers, high PLR (> 148) and high NLR (> 5) were associated with a short PFS (Hazard ratio [HR] 1.828, P = 0.006; HR 1.738, P = 0.030, respectively) and short OS (HR 2.332, P < 0.001; HR 2.273, P < 0.001, respectively). Low LMR (< 3.5) and low AGR (< 1.2) were associated with a short OS (HR 2.423, P < 0.001; HR 1.768, P = 0.002, respectively). In multivariable cox-regression analysis, high PLR (HR 1.766, P = 0.009) and distant lymph node (LN) metastasis (HR 2.085, P = 0.001) were associated with a short PFS. High PLR (HR 1.856, P = 0.002) was an independent predictor of a short OS, along with distant LN metastasis (HR 1.929; P < 0.001), low LMR (HR 1.691; P = 0.041), and low level of serum albumin (< 3.5 g/dL) (HR 1.632; P = 0.043). Time-dependent ROC analysis revealed that the area under the curve of PLR for predicting overall survival was greater than that of NLR, LMR, and AGR at most time points.

Conclusions: High PLR was an independent prognostic factor of a short PFS and OS in patients with unresectable IHC receiving GP chemotherapy.
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http://dx.doi.org/10.1186/s12885-020-07390-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510111PMC
September 2020

Efficacy of an internal anchoring plastic stent to prevent migration of a fully covered metal stent in malignant distal biliary strictures: a randomized controlled study.

Endoscopy 2021 06 4;53(6):578-585. Epub 2020 Sep 4.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: Two types of self-expandable metal stents (SEMS) are available for malignant distal biliary obstruction: fully covered SEMS (FCSEMS) and uncovered SEMS. FCSEMS can prevent stent ingrowth, but a major concern is spontaneous migration. This study aimed to determine whether the additional insertion of a double-pigtail plastic stent to anchor the FCSEMS can prevent migration.

Methods: 68 patients with unresectable, malignant, distal, biliary obstruction were included in this multicenter, randomized, superiority trial. The patients were randomly assigned to receive either the FCSEMS plus an anchoring plastic stent (n = 33) or an FCSEMS alone (n = 35). After placement of the FCSEMS, the anchoring stent was inserted inside the FCSEMS. The primary outcome was the rate of stent migration during the 6-month follow-up. The secondary outcomes were stent-related adverse events, stent patency, and survival rates.

Results: The baseline characteristics were similar between the two groups. The rate of stent migration at 6 months was significantly lower in patients with the FCSEMS plus anchoring stent (15 % vs. 40 %;  = 0.02). The mean stent patency was significantly longer in the FCSEMS plus anchoring group (237 days [95 % confidence interval [CI] 199 to 275] vs. 173 days [95 %CI 130 to 217];  = 0.048). There were no significant differences in stent-related adverse events and overall survival rates at 6 months between the two groups.

Conclusions: Our data suggest that the additional double-pigtail plastic stent anchored the FCSEMS to prevent migration and prolonged patency without any serious adverse events.
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http://dx.doi.org/10.1055/a-1256-0571DOI Listing
June 2021

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea.

Korean J Parasitol 2020 Aug 26;58(4):413-419. Epub 2020 Aug 26.

Department of Tropical Medicine and Parasitology and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.
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http://dx.doi.org/10.3347/kjp.2020.58.4.413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462808PMC
August 2020

Functional Evaluation of Upper Urinary Tract with Diuretic Mercaptoacetyltriglycine Renal Scans in Patients with Benign Prostatic Obstruction before and after Surgical Intervention: A Pilot Study.

Biomed Res Int 2020 10;2020:4605683. Epub 2020 Aug 10.

Department of Urology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.

Introduction: We investigated which benign prostatic hyperplasia-related lower urinary parameters are related to upper urinary tract obstruction and whether transurethral prostatectomy could improve upper urinary tract obstruction.

Materials And Methods: Patients with prostate size over 30 g and urodynamically proven bladder outlet obstruction were enrolled in this prospective observational study. Bladder wall thickness and prostate size were measured by ultrasonography. A urodynamic study with laboratory tests including serum creatinine, prostate-specific antigen, and urinalysis was performed. Finally, a diuretic scintigraphy using mercaptoacetyltriglycine was performed. Tests except the urodynamic evaluation were repeated after transurethral prostatectomy.

Results: In total, 24 patients were enrolled, and 19 patients completed the present study. The mean values of age (yrs), prostate size (mL), bladder thickness (mm), bladder compliance (mL/pr), and the bladder outlet obstruction index were 68.42 ± 8.25, 72.29 ± 32.78, 4.42 ± 1.14, 50.17 ± 32.15, and 82.11 ± 34.68, respectively. The mean T (min) was 17.51 ± 16.34 on the left side and 15.30 ± 11.96 on the right side. Statistical analysis showed that bladder compliance and bladder thickness were preoperatively related to upper urinary tract obstruction ( = 0.001 and = 0.007, respectively). Diuretic mercaptoacetyltriglycine scan in 19 patients showed improvement 6 months after prostate surgery. Clinically significant proteinuria was associated with upper urinary tract obstruction, and proteinuria was also improved after prostate surgery.

Conclusion: Storage-phase bladder dysfunction could be a reliable urodynamic factor for the indication of upper urinary tract obstruction in patients with benign prostatic hyperplasia, and upper urinary tract obstruction with subsequent kidney damage could be improved by surgical decompression of benign prostatic obstruction.
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http://dx.doi.org/10.1155/2020/4605683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436344PMC
April 2021

Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX.

Gut Liver 2021 05;15(3):466-475

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background/aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC.

Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment.

Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037).

Conclusions: FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient's general condition and clinical status.
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http://dx.doi.org/10.5009/gnl20070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129663PMC
May 2021

GDC-0980 (apitolisib) treatment with gemcitabine and/or cisplatin synergistically reduces cholangiocarcinoma cell growth by suppressing the PI3K/Akt/mTOR pathway.

Biochem Biophys Res Commun 2020 09 8;529(4):1242-1248. Epub 2020 Aug 8.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Since conventional chemotherapy (gemcitabine and cisplatin) has marginal survival benefit in patients with advanced cholangiocarcinoma (CCA), an effective targeted therapeutic agent is urgently required. Activation of the PI3K/Akt/mTOR signaling pathway is frequently observed in CCA, and thus, PI3K and mTOR are promising therapeutic targets in CCA. Recently a new dual PI3K/mTOR inhibitor GDC-0980 (apitolisib) was introduced. This study was undertaken to examine the activity of apitolisib against CCA cells in vitro and in vivo. Apitolisib treatment strongly reduced Akt and mTOR active phosphorylation levels and attenuated cell growth in two different CCA cell lines (SNU478 and SNU1196). In addition, the cytotoxic activity of apitolisib enhanced the effects of gemcitabine or cisplatin in vitro and increased PARP cleavage. Moreover, we observed these co-treatments significantly reduced colony formation by SNU478 and SNU1196 cells and potently inhibited tumor growth in a mouse xenograft model. The results of the present study show that apitolisib effectively reduces CCA cell growth by suppressing the PI3K/Akt/mTOR pathway. In addition, co-treatments with apitolisib and gemcitabine or cisplatin synergistically enhanced apitolisib activity, which suggests a means of improving the chemotherapeutic sensitivity of CCA.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.011DOI Listing
September 2020
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