1.A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation
Guk Jin LEE ; Hyunho KIM ; Sung Shim CHO ; Hyung Soon PARK ; Ho Jung AN ; In Sook WOO ; Jae Ho BYUN ; Ji Hyung HONG ; Yoon Ho KO ; Der Sheng SUN ; Hye Sung WON ; Jong Youl JIN ; Ji Chan PARK ; In-Ho KIM ; Sang Young ROH ; Byoung Yong SHIM
Journal of Gastric Cancer 2023;23(2):315-327
Purpose:
Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy.
Materials and Methods:
Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level.
Results:
Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020).
Conclusions
After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.
2.Ultrasound diagnosis and treatment of intractable anterior chest pain from golf - A case report –
Jihye PARK ; Su Jin KIM ; Hyunho KIM ; Haesun JUNG ; Hwa Yong SHIN
Anesthesia and Pain Medicine 2023;18(1):65-69
Pleurisy is an inflammation of the parietal pleura and is characterized by pleuritic pain. The most common cause of pleurisy is infection; other causes include rheumatoidarthritis, malignancy, rib fractures, or trauma. Possible causes of chest pain associated withgolf include costochondritis, stress fractures of the ribs, intercostal muscle strain, or, rarely,Tietze’s syndrome and slipping rib syndrome.Case: A 64-year-old female presented with intractable chest pain that began 4 months priorwhile playing golf. No specific cause was found after various examinations. There was persistent pain despite medical treatment. Ultrasonography (US) was performed over the painful areas, which revealed focal pleural effusions. A mixture of ropivacaine and triamcinolonewas injected into the focal pleural effusions using US guidance, which dramatically relievedher pain.Conclusions: This case demonstrates that US can be used as a diagnostic and therapeuticmodality for intractable chest pain with an undetected pathology.
3.Phosphodiesterase-5 Inhibitor Use in Robot Assisted Radical Prostatectomy Patients Is Associated with Reduced Risk of Death: A Propensity Score Matched Analysis of 1,058 Patients
Jongsoo LEE ; Hye Rim KIM ; Ji Eun HEO ; Won Sik JANG ; Kwang Suk LEE ; Sung Ku KANG ; Hyunho HAN ; Young Deuk CHOI
The World Journal of Men's Health 2023;41(4):892-899
Purpose:
We investigated whether the use of a phosphodiesterase-5 inhibitor (PDE5i) after robot assited radical prostatectomy has a survival benefit over non-use patients because there are controversial results on the association between PDE5i use and survival outcomes for prostate cancer patients in literature.
Materials and Methods:
We designed a retrospective, matched, large-sample cohort study of 5,545 patients who underwent robot assisted radical prostatectomy (RARP) during 2013–2021 in a single institute. The exclusion criteria was patients who were aged >70 years at surgery, American Society of Anesthesiologists (ASA) physical status classification grade 4 or 5, history of other malignancies, patients who started PDE5i 6 months after survery and patients with follow up period less than 24 months after surgery. Among the 1,843 included patients, 1,298 were PDE5i users, and 545 were PDE5i non-users. We performed propensity score matching (PSM) of PDE5i users (n=529) with non-users (n=529) by adjusting for the variables of age, Gleason grade group, pathological T stage, preoperative ASA physical status grade, and International Index of Erectile Function score.
Results:
There were no significant difference in patient characteristics according to PSM. Kaplan–Meier curve revealed the difference of overall survival for PDE5i users and non-users (clustered log-rank test p<0.05). In a stratified Cox regression analysis, PDE5i use after RARP was associated with improved overall survival and reduced risk of death (hazard ratio 0.43; confidence interval 0.24–0.79; p=0.007). The limitation of this study was that the indication for the prescription of PDE5i was not given.
Conclusions
PDE5i administration after RARP were associated with overall survival of patients with prostate cancer. A further randomized control trial may reveal whether routine use of PDE5i after prostatectomy can improve survival of prostate cancer patient.
4.In Vivo Feasibility Test of a New Flexible Ureteroscopic Robotic System, easyUretero, for Renal Stone Retrieval in a Porcine Model
Joonhwan KIM ; Hae Do JUNG ; Young Joon MOON ; Hyunho HAN ; Byungsik CHEON ; Jungmin HAN ; Sung Yong CHO ; Joo Yong LEE ; Dong-Soo KWON
Yonsei Medical Journal 2022;63(12):1106-1112
Purpose:
Using a new robotic endoscopic platform system developed for retrograde intrarenal surgery (RIRS) called easyUretero (ROEN Surgical Inc.), we evaluated the feasibility and safety of renal stone retrieval in a porcine model.
Materials and Methods:
Six female pigs were used for our in vivo study. First, 0.3-cm-sized phantom stones were inserted into the kidneys of each pig via the ureteral access sheath. Next, renal stone retrieval was attempted using manual RIRS in three pigs and robotic RIRS in three pigs. Three surgeons performed extraction of 10 stones in each session.
Results:
The mean stone retrieval time by manual RIRS was significantly shorter than that by robotic RIRS (399.9±185.4 sec vs. 1127.6±374.5 sec, p=0.001). In contrast, the questionnaire regarding usability showed high satisfaction in the surgeons’ fatigue category for surgeons using robotic RIRS. The radiation exposure dose was also lower in robotic RIRS than in manual RIRS (0.14 μSv vs. 45.5 μSv). Postoperative ureteral injury assessment revealed Grade 0 in manual RIRS cases and Grades 0, 1, and 2 in robotic RIRS cases.
Conclusion
The easyUretero system is a new robotic RIRS system that was developed in Korea. The results of the present study suggest that using easyUretero for stone retrieval during RIRS is safe and ergonomic.
5.The use of sugammadex in an infant with prolonged neuromuscular blockade - A case report -
Hyunho KIM ; Joonho CHO ; Sangseok LEE ; Yunhee LIM ; Byunghoon YOO
Anesthesia and Pain Medicine 2022;17(1):52-56
Background:
Residual neuromuscular blockade (RNMB) is a frequent event after general anesthesia, which can lead to serious complications, such as upper airway obstruction. Sugammadex is useful in reversing RNMB. However, its use in infants has not yet been approved by the Food and Drug Administration. Therefore, anesthesiologists can be hesitant use it, even in situations where no other choice is available.Case: A two-month-old baby presented to the hospital for umbilical polypectomy. At the end of the surgery, neostigmine was administered. Even after waiting for 30 min and injecting an additional dose of neostigmine, neuromuscular blockade was not adequately reversed. Eventually, sugammadex was administered, and spontaneous breathing returned.
Conclusions
If there were no particular causes of delayed return to spontaneous breathing in infants, RNMB should be considered and reversal with sugammadex would be useful.
6.Association between serum ferritin levels and colorectal cancer risk in Korea
Hyunho KIM ; Kyungdo HAN ; Seung-Hyun KO ; Ho Jung AN
The Korean Journal of Internal Medicine 2022;37(6):1205-1215
Background/Aims:
The concentration of serum ferritin, a storage form of iron, may be associated with carcinogenesis in various cancers. There are only limited studies on the relationship between serum ferritin levels and colorectal cancer (CRC) risk, especially in the Asian population. This study aimed to analyze the association between CRC incidence and serum ferritin levels.
Methods:
This was a national cohort study that used health checkup and insurance claims data of the Korean population. CRC incidence according to the serum ferritin level was analyzed during 2008–2018 in 17,116 participants.
Results:
The hazard ratio (HR) of CRC incidence decreased as serum ferritin levels increased (Q1: HR, 1.000 [95% confidence interval [CI], reference]; Q2: HR, 0.811 [95% CI, 0.558 to 1.178]; Q3: HR, 0.654 [95% CI, 0.442 to 0.968]; Q4: HR, 0.443 [95% CI, 0.285 to 0.687]; p = 0.0026). In subgroup analysis, 40 to 64 years of age, sex, body mass index of < 25 kg/ m2, presence of metabolic syndrome, absence of diabetes mellitus, and absence of anemia had HRs of < 0.5 (95% CI) in the highest quartiles compared with that in the lowest quartiles.
Conclusions
This study shows an inverse association between serum ferritin and CRC risk. Serum ferritin measurement can aid in identifying young adults requiring active CRC screening.
7.Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
Hyunsuk KIM ; Jinmo SUNG ; Ju Young BAE ; Poongyeon LEE ; Yun Kyu OH ; Hyunho KIM
Kidney Research and Clinical Practice 2022;41(6):730-740
Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases, is characterized by the presence of numerous fluid-filled renal cysts and is a leading cause of end-stage renal disease (ESRD). Urinary biomarkers may be useful for predicting the variable course of ADPKD progression from cyst growth to ESRD. Methods: To identify candidate urinary biomarkers of ADPKD progression, we used CRISPR/Cas9 genome editing to generate porcine fibroblasts with mono- and biallelic ADPKD gene knockout (PKD2+/– and PKD2–/–, respectively). We then performed RNA-sequencing analysis on these cells. Results: Levels of osteopontin (OPN), which is expressed by renal epithelial tubular cells and excreted into urine, were reduced in PKD2–/– cells but not in PKD2+/– cells. OPN levels were also reduced in the renal cyst cells of ADPKD patients. Next, we investigated whether OPN excretion was decreased in patients with ADPKD via enzyme-linked immunosorbent assay. OPN levels excreted into renal cyst cell culture media and urine from ADPKD patients were decreased. To investigate whether OPN can predict the rate of ADPKD progression, we compared urinary excretion of OPN in ADPKD patients with slow progression and those with rapid progression. Those with rapid progression had an estimated glomerular filtration rate of >60 mL/min/1.73 m2 . Urinary OPN excretion levels were lower in rapid progressors than in slow progressors. Conclusion: These findings suggest that OPN is a useful urinary biomarker for predicting ADPKD progression.
8.Comparison of Allergenic Properties among Commercially Available House Dust Mite Allergen Extracts in Korea
Ji Tae KIM ; Hyunho KIM ; Sung Hyun KIM ; Dong Jun KIM ; Yeji SHIN ; Jung Dong KIM ; Hangyeol SONG ; Seok Woo JANG ; Deug-chan LEE ; Kyung Hee PARK ; Jae-Hyun LEE ; Kyoung Yong JEONG ; Jung-Won PARK
Yonsei Medical Journal 2021;62(1):86-90
Precise allergy diagnosis and effective allergen specific immunotherapy are largely dependent on the quality of allergen extract. A new extract of Dermatophagoides farinae was commercially developed by Prolagen. The allergenic properties of the new extract were compared with those of other commercial products. The allergenic properties of the new extract were compared according to protein concentration, protein profiles, major allergen (Der f 1) contents, and allergenic potency to those for three commercially available extracts imported in Korea (Jubilant HollisterStier Allergy, Lofarma S.p.A., and Stallergenes Greer). Protein concentrations varied up to 2.62-fold (0.404 to 1.057 mg/mL), and Der f 1 contents varied up to 11.3-fold (3.597 to 40.688 μg/mL). Protein profiles of the extracts showed no major discrepancies, although there were some differences in SDS-PAGE band intensities, reflecting protein concentrations. Allergen potency ranged from 37038 to 60491 PAU/mL. The Prolagen product was highest in terms of protein concentration and allergen potency. The Lofarma product displayed Der f 1 content similar to that in Prolagen (19.4 μg/mg vs. 19.3 μg/mg). Endotoxin levels varied 8.9-fold (1020 to 8985 EU/mL). The newly developed house dust mite extract showed equal or better allergenic properties than available commercial extracts. This new product may be useful for better diagnostics and allergen-specific immunotherapeutics.
9.Effect of single dose preoperative intravenous ibuprofen on postoperative pain and opioid consumption: a systematic review and meta-analysis
Su Yeon KIM ; Sangseok LEE ; Yeji LEE ; Hyunho KIM ; Kye-Min KIM
Korean Journal of Anesthesiology 2021;74(5):409-421
Background:
Ibuprofen, a well-known analgesic, is commonly used as a component of a multimodal analgesic approach for postoperative pain. This systematic review and meta-analysis aimed to investigate whether a single-dose preoperative intravenous ibuprofen can reduce postoperative pain and opioid consumption.
Methods:
PubMed/MEDLINE, Embase, Cochrane Library (CENTRAL), and Web of Science databases were searched to identify relevant studies published up to May 2020. Randomized controlled trials comparing preoperative single-dose intravenous ibuprofen effect with the control group on postoperative pain and opioid consumption after surgery under general anesthesia were included.
Results:
Six studies involving 366 participants were included. Single-dose administration of intravenous ibuprofen preoperatively significantly reduced postoperative pain score on a scale of 0-10 at 1 h (MD: -1.64, 95% CI [-2.56, -0.72], P < 0.001, I2 = 95%), at 4-6 h (MD: -1.17, 95% CI [-2.09, -0.26], P < 0.001, I2 = 94%), and 24 h (MD: -0.58, 95% CI [-0.99, -0.18], P < 0.001, I2 = 90%). Cumulative opioid consumption, presented as fentanyl equivalents, was also reduced significantly in the ibuprofen group compared to placebo group until postoperative 4-6 h (MD: -56.35 μg, 95% CI [-101.10, -11.60], P < 0.001, I2 = 91%) and 24 h (MD: -131.39 μg, 95% CI [-224.56, -38.21], P < 0.001, I2 = 95%).
Conclusions
Preoperative single-dose intravenous ibuprofen can reduce postoperative pain and opioid consumption until 24 h postoperatively. Considering the high heterogeneity and small number of studies included, care should be taken when generalizing these findings.
10.Association between absolute lymphocyte count and overall mortality in patients with surgically resected gastric cancer
Se Jun PARK ; Jinsoo LEE ; Hyunho KIM ; Kabsoo SHIN ; MyungAh LEE ; Jae Myung PARK ; Myung-Gyu CHOI ; Cho Hyun PARK ; Kyo Young SONG ; Han Hong LEE ; In-Ho KIM
The Korean Journal of Internal Medicine 2021;36(3):679-688
Background/Aims:
Lymphocytes are an important component of the cell-mediated immune system. As lymphopenia is reportedly associated with poor prognoses in patients with various cancers, we investigated this notion in patients who underwent curative gastrectomy.
Methods:
We retrospectively analyzed the association between absolute lymphocyte count (ALC) and prognosis in patients with stage I–III gastric cancer who underwent curative surgical resection. Ever lymphopenic patients were defined as those with ALCs < 1,000/μL at any time post-diagnosis except within 30 days post-surgery. Adjusted multivariable regression models were used to evaluate the associations between lymphopenia and overall mortality, gastric cancer-specific mortality, and disease-free survival.
Results:
We investigated 1,222 patients diagnosed between January 2011 and December 2015. Fifty-six patients (4.6%) were lymphopenic at diagnosis and nearly one-quarter (24.8%) were ever lymphopenic with a mean minimum ALC of 640/μL. Older age (odds ratio [OR], 1.02) and higher stage (stage III vs. I; OR, 3.01) were positively associated with ever lymphopenia. On multivariable analysis, ever lymphopenia predicted higher overall mortality (hazard ratio [HR], 1.83; p = 0.008), higher gastric cancer-specific mortality (HR, 1.58; p = 0.048), and shorter disease-free survival (HR, 1.83; p = 0.006). The 5-year gastric cancer-specific mortality rates for ever- and never lymphopenic patients were 10.9% and 3.7%, respectively; their 5-year cumulative recurrence rates were 15.1% and 4.6%, respectively.
Conclusions
This study demonstrate that ever lymphopenia is independent prognostic factor for overall mortality and recurrence in patients with potentially curable gastric cancer; hence, ALCs may be a biomarker for predicting the prognoses of patients with stage I–III gastric cancer who had curative gastrectomy.

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