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Abstract Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) (P

Objective This study was conducted to evaluate the effects of optimal trace mineral levels on the physiological responses, reproductive performance, litter performance, blood profiles and milk composition in gestating sows. Methods A total of 59 multiparous sows (Yorkshire×Landrace) with similar body weight (BW), backfat thickness (BF), and parity were assigned to one of four treatments with 14 or 15 sows per treatment using a completely randomized design. The treatments were 100% (M1), 300% (M3), 600% (M6), and 900% (M9) of the National Research Council (NRC) Nutrient Requirements of Swine. During lactation period, all the sows were fed the same commercial lactation diet. Results No significant differences were observed in the BW, BF, reproductive performance, milk composition, or growth performance of the piglets. On day 70 of gestation, the serum zinc concentration showed a quadratic response to M6 treatment (quadratic, p

Objective This study was conducted to evaluate the short-term effects of dietary selenium supplementation on lactating sows on the physiological response, litter performance, milk composition, and tissue selenium retention in piglets when selenium was provided by different sources and at different levels in a lactation diet. Methods A total of 48 multiparous sows (Yorkshire×Landrace) with average body weight, backfat thickness, and parity were assigned to one of the four treatments with 12 sows per treatment using a 2×2 factorial arrangement in a completely randomized design. Inorganic or organic Se sources were added to the diet at 0.30 ppm and 0.50 ppm Se. Treatments were as follows: i) IS30, basal diet + inorganic Se 0.30 ppm; ii) IS50, basal diet + inorganic Se 0.50 ppm; iii) OS30, basal diet + organic Se 0.30 ppm; and iv) OS50: basal diet + organic Se 0.50 ppm. Results At Day 21 of lactation, a high tendency of litter weight (p = 0.08) and litter weight gain (p = 0.09) were observed when sows were fed an organic Se source. The milk Se concentration in the organic Se treatment was higher than that in the inorganic Se treatment at Day 21 of lactation (p

Objective This study was conducted to evaluate the effects of β-glucan with vitamin E supplementation on the growth performance, blood profiles, immune response, pork quality, pork flavor, and economic benefit in growing and finishing pigs. Methods A total of 140 growing pigs ([Yorkshire×Landrace]×Duroc) were assigned to five treatments considering sex and initial body weight (BW) in 4 replications with 7 pigs per pen in a randomized complete block design. The experimental diets included a corn-soybean meal-based basal diet with or without 0.05% or 0.1% β-glucan and 0.02% vitamin E. The pigs were fed the diets for 12 weeks (phase I, 0 to 3; phase II, 3 to 6; phase III, 6 to 9; phase IV, 9 to 12). The BW and feed intake were measured at the end of each phase. Blood samples were collected at the end of each phase. Four pigs from each treatment were selected and slaughtered for meat quality. Economic benefit was calculated considering the total feed intake and feed price. Pork flavor was analyzed through inosine monophosphate analysis. Results The average daily gain and feed efficiency were improved compared to the control when β-glucan or vitamin E was added. Supplementing 0.05% β-glucan significantly increased the lymphocyte concentration compared to the addition of 0.1% β-glucan and the content of vitamin E in the blood increased when 0.02% vitamin E was added. The treatment with 0.1% β-glucan and 0.02% vitamin E showed the most economic effect because it had the shortest days to market weight and the lowest total feed cost. The addition of β-glucan or vitamin E had a positive role in improving the flavor of pork when considering that the content of inosine monophosphate was increased. However, carcass traits and meat quality were not affected by β-glucan or vitamin E. Conclusion The addition of 0.1% β-glucan with 0.02% vitamin E in growing and finishing pig diets showed great growth performance and economic effects by supplying vitamin E efficiently and by improving the health condition of pigs due to β-glucan.

Objective This study was conducted to evaluate effects of β-glucan with vitamin E supplementation on the growth performance, blood profiles, immune response, fecal microbiota, fecal score, and nutrient digestibility in weaning pigs. Methods A total of 200 weaning pigs with an average body weight (BW) of 7.64±0.741 kg were allotted to five treatment groups and were divided based on sex and initial BW in four replicates with ten pigs per pen in a randomized complete block design. The experimental diets included a corn-soybean meal-based basal diet with or without 0.1% or 0.2% β-glucan and 0.02% vitamin E. The pigs were fed the diets for 6 weeks. A total of 15 barrows were used to evaluate the nutrient digestibility by the total collection method. The BW and feed intake were measured at the end of each phase. Blood samples were collected at the end of each phase, and fecal samples were collected at the end of the experiment. Results The addition of β-glucan with vitamin E to weaning pig feed increased BW, average daily gain, and average daily feed intake. A significant decrease in yeast and mold and Proteobacteria and a tendency for Lactobacillus to increase compared to the control was shown when 0.1% β-glucan and 0.02% vitamin E were added. The fecal score in weaning pigs was lower in the treatments supplemented with 0.1% or 0.2% β-glucan and 0.02% vitamin E compared to the control. In addition, vitamin E was better supplied to weaning pigs by increasing the concentration of α-tocopherol in the blood of weaning pigs when 0.02% vitamin E was supplemented. However, there was no significant difference in either the immune response or nutrient digestibility. Conclusion Inclusion of 0.1% β-Glucan with 0.02% vitamin E in a weaning pig’s diet were beneficial to the growth performance of weaning pigs by improving intestinal microbiota and reducing the incidence of diarrhea.

Objective This study was conducted to evaluate the effects of β-glucan with vitamin E supplementation on the physiological response, litter performance, blood profiles, immune response, and milk composition of lactating sows. Methods A total of 50 multiparous F1 sows (Yorkshire×Landrace) with an average body weight (BW) of 233.6±4.30 kg and an average parity of 4.00±0.307 and their litters were used in this experiment. All sows were allotted to one of five treatments, taking into consideration BW, backfat thickness, and parity in a completely randomized design with 10 replicates. The experimental diets included a corn–soybean meal-based basal diet with or without 0.1% or 0.2% β-glucan and 110 IU vitamin E/kg diet. Results All treatments added with β-glucan or vitamin E were statistically higher in the average daily feed intake (ADFI) of lactating sows compared to those of the control (Diet, p

Background Acute disseminated encephalomyelitis (ADEM)-like white matter disease, a rare complication of coronavirus disease 2019 (COVID-19), is a potentially life-threatening neurological disorder. The objective of this study was to report the successful treatment of post–COVID-19 ADEM with urgent immunotherapy and neurointensive management. Case Report A 53-year-old female patient was referred to our hospital with a 2-day history of progressive mental deterioration and was diagnosed with ADEM after COVID-19. The patient's symptoms worsened despite the administration of high-dose steroids, and targeted temperature management was employed to manage brain edema. Additionally, the neurointensivist decided to use intravenous immunoglobulin early for intractable post–COVID-19 ADEM. Her mental status and neuroimaging findings showed rapid improvement at about 3 months after admission. Conclusion This case highlights that if the patient's symptoms worsen despite high-dose steroid administration in the acute stage, early use of intravenous immunoglobulin is expected to have a positive effect on the prognosis of patients with post–COVID-19 ADEM.

Background/Aims Peritoneal carcinomatosis with malignant ascites is common in patients with advanced gastric cancer (GC). The detection of tumor cells is the gold standard for the diagnosis of malignant ascites; however, it often requires complementary tests because of its low sensitivity. Herein, we measured the levels of tumor markers in the malignant ascites of GC patients (GC-ascites) and benign ascites of liver cirrhosis patients (LC-ascites) to elucidate the diagnostic value of tumor markers in GC-ascites. Materials and Methods The levels of CEA, cancer antigen 72-4 (CA 72-4), CA 19-9, and CA 125 were measured in 138 GC-ascites and 64 LC-ascites samples obtained from the National Biobank of Korea. We performed receiver operating characteristic curve analysis to determine the optimal cutoff value for each tumor marker. Results CEA, CA 72-4, and CA 19-9 levels were significantly higher in GC-ascites than in LC-ascites. There was no difference in tumor marker levels between GC-ascites samples irrespective of cytology. CEA, CA 72-4, and CA 19-9 had sensitivities of 85.5%, 79.0%, and 61.6%, respectively, and specificities of 96.8%, 100.0%, and 89.1%, respectively, for distinguishing GC-ascites samples from LC-ascites samples. The diagnostic accuracy was improved by combining two or more tumor markers. The combination of CEA and CA 72-4 showed the highest sensitivity (86.2%) and specificity (100%). Conclusions Measurement of tumor markers, such as CEA, CA 72-4, and CA 19-9, in ascites samples could help diagnose GC-ascites, and combining two or more tumor markers could further increase the diagnostic yield, even in cytology-negative patients.

Background Acute increased intracranial pressure (IICP) is a life-threatening condition that requires urgent treatment. Rapid IICP with hydrocephalus may be complicated by ischemic stroke, convulsions, loss of consciousness, brain herniation, and death. Extremely rare complications include intracranial vessel entrapment and ischemic stroke due to sudden IICP in cases with benign tumors. Case Report We report a case of bilateral posterior cerebral artery region infarction and complicated hydrocephalus with subependymal giant cell astrocytoma in a patient with tuberous sclerosis. Conclusion We postulate that the temporary IICP induced by seizure led to transient bilateral posterior cerebral artery entrapment, causing ischemic stroke without vascular occlusion.

Introduction: Previous studies have suggested that high glucose (HG) condition shortens the lifespan of worms by increasing glycolytic flux followed by accelerating reactive oxygen species (ROS) production, termed glucose toxicity. This study was designed to investigate the protective effects of the leaves of black bamboo (Phyllostachys nigra var. henosis) on the HG-induced toxicity using Caenorhabditis elegans model system. Methods: To determine the effect of black bamboo leaf extract (BLE) against HG-induced toxicity, lifespan assay was carried out with wild-type and daf-16 null mutant worms under 2% glucose condition. The involvement of DAF-16 was further confirmed by observing fluorescence signal of transgenic mutant carrying DAF-16::GFP transgene. ROS levels and glucose concentration of worms were analyzed using fluorescent probe H2DCF-DA and glucose meter, respectively. Nile-red staining was carried out to evaluate the lipid storage of worms. Intercellular lipid accumulation was measured using Oil-Red O staining method. Results: BLE strongly extended the lifespan of worms under not only normal culture condition but also HG condition. Our additional studies suggested that DAF-16 activation was responsible for BLE-mediated longevity and protective action against glucose toxicity. In addition, HG-fed worms showed increased ROS generation, and it was completely normalized by BLE treatment. Moreover, BLE reduced body glucose concentration and lipid accumulation in HG-fed worms. We further confirmed the inhibitory effect of BLE on lipid storage under HG condition using 3T3-L1 adipocytes. Conclusion: These therapeutic values of BLE on glucose toxicity raise the possibility that BLE might have beneficial effects on the pathogenesis of diabetes mellitus.

ObjectivesAtrial fibrillation (AF) is a well-known etiology of embolic stroke of undetermined source (ESUS), although the optimal detection strategy of AF was not been fully evaluated yet. We assessed AF detection rate by implantable loop recorder (ILR) in patients with ESUS and compared the clinical characteristics and neuroimaging patterns between the patients with AF and AF-free patients.MethodsWe reviewed clinical characteristics and neuroimaging patterns of consecutive patients with who were admitted to our comprehensive stroke center for ESUS and underwent ILR insertion between August 1, 2019, and January 31, 202. The inclusion criteria were (1) 18 years of age or older; (2) classified as having cryptogenic stroke extracted from the group with undetermined stroke according to ESUS International Working Group; and (3) underwent ILR insertion during or after admission due to index ischemic events. Ischemic stroke pattern was classified as (1) tiny-scattered infarction, (2) whole-territorial infarction, (3) lobar infarction and (4) multiple-territorial infarction. Interrogations of data retrieved from the ILR were performed by cardiologists in every month after the implantation.ResultsIn this study, 41 ESUS patients who received an ILR implantation were enrolled (mean age, 64 years; male sex, 65.9%). The rate of AF detection at 6 months was 34% (14 patients), and the mean time from ILR insertion to AF detection was 52.5 days [interquartile range (IQR), 45.0–69.5]. The median initial NIH stroke scale scores were significantly greater in patients with AF than those without AF (6.5 vs. 3.0, p = 0.019). Whole-territorial infarction pattern was significantly more frequent in patients with AF than in those without AF (64.3% vs.11.1%, p = 0.002).ConclusionsHigher covert AF detection rates within the ESUS patients were most often associated with higher NIHSS and whole-territorial infarction patterns on brain imaging.

Web in common bile duct (CBD web) is very rare. It is usually asymptomatic and detected incidentally during surgery for other causes in adults. It can be congenital or acquired, however congenital CBD web is extremely rare. Currently, despite its invasiveness and complications, endoscopic retrograde cholangiopancreatography (ERCP) is considered as a useful diagnostic and therapeutic modality in children with hepatobiliary pancreatic diseases as in adults. Herein we report a case of congenital CBD web presenting with acute pancreatitis and choledocholithiasis in a 4-year-old girl which was diagnosed and treated using balloon dilation under ERCP. After balloon dilation of the web, a common pancreatobiliary channel was observed. To the best of our knowledge, a case of congenital CBD web with pancreatobiliary junctional abnormality treated using ERCP in a child has not been reported to date.

Gout is the most common form of inflammatory arthritis. It occurs when monosodium urate crystals (MSU) are deposited within joints due to hyperuricemia and persistent elevations of serum uric acid levels. Traditional gout treatment such as urate-lowering therapy is difficult to continue for a long period of time due to the risk of side effects. Recent studies have shown that the modulation of MSU-induced inflammatory responses is dependent on the inflammatory cytokine IL-1β, which has a central role in a chain of processes involving multiple cytokines and mediators. In this regard, the NLRP3 inflammasome is known to play a crucial part and thus has been proposed as a novel target in the treatment for gout. However, the biochemical mechanism for NLRP3 inflammasome activation has not yet been clearly elucidated. Therefore, this report can provide an overview of natural extractions targeted to prevent or treat NLRP3 inflammasome-mediated gout in the MSU-induced gout model. In addition, the research and development of such natural products are suggested as a potential strategy in the treatment of gout.

Background/Aims Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. Methods This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. Results Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. Conclusions Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.

Cases showing complications such as esophageal injury, deep neck infection, and mediastinitis caused by accidental ingestion of fish bone are common. But ingestion of fish bone rarely causes perforation of the gastrointestinal tract or an intra-abdominal abscess. We report herein a case of a 78-year-old man with a periumbilical mesenteric abscess caused by fish bone which was ingested unconsciously. The fish bone was found in the terminal ileum and it was removed by colonoscopy. The patient improved and he was discharged after systemic antibiotic therapy. Occasionally, when patients swallow fish bone without a foreign body sensation, clinicians should suspect perforation caused by fish bone in case of an intra-abdominal abscess of unknown cause.

Abstract Background This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. Methods A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. Results VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (

Abstract Background Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12 years in Southeastern Korea. Methods A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB. Results The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study. Conclusions Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered.

Background/Aims: As the elderly population taking antithrombotic therapy (ATT) increases, gastrointestinal (GI) bleeding risk during ATT may likely increase. This study was conducted to evaluate the clinical characteristics of severe upper GI bleeding (UGIB) during ATT. Materials and Methods: Among patients on ATT at Gyeongsang National University Hospital between March 2005 and February 2010, those with severe UGIB requiring endoscopic hemostasis were selected for the study. Their medical records were retrospectively reviewed for clinical variables. Results: Among 59,773 patients taking ATT, 125 (0.21%) developed severe UGIB and comprised 12.8% of the overall endoscopic hemostasis cases (125/978) during the same period. The patients with severe UGIB on ATT were older than the ones not on ATT (68.3 vs. 59.9 years, P＜0.001). The common indications for ATT were cardiovascular (60.8%, 76/125) and cerebrovascular diseases (25.6%, 32/125). Fifty-nine patients (47.2%) were taking two or more agents, 36 (28.8%) were on aspirin monotherapy, while 22 (17.6%) were taking warfarin alone. Aspirin was involved in 68.8% (86/125) of severe UGIB. According to ATT type, the incidence of severe UGIB was 0.48% with warfarin, 0.38% with aspirin, and 0.33% with clopidogrel. The main causes of severe UGIB were gastric (78, 62.4%) and duodenal ulcers (15, 12.0%). UGIB recurred in 11 cases (8.8%), but all were successfully controlled with repeated hemostasis and there was no mortality. Conclusions: The frequency of severe UGIB during ATT was 0.21%. Aspirin was the most common agent leading to severe UGIB, but its incidence was highest with warfarin. Gastric ulcer was the most common focus. Endoscopic hemostasis was effective and safe for UGIB during ATT.

Abstract Background The optimal treatment strategy for biliary tract cancer (BTC) after curative-intent resection remains controversial. The purpose of this study was to evaluate the efficacy of fluoropyrimidine-based adjuvant chemotherapy for BTC patients undergoing microscopically margin-negative (R0) resection. Methods We retrospectively analyzed the clinical data of BTC patients who underwent curative-intent R0 resection. Patients were eligible if they received either fluoropyrimidine-based adjuvant chemotherapy or observation after R0 resection. Results A total of 153 patients were included. In the entire patient cohort, no significant differences were observed in 5-year overall survival (OS) rates (48.4% vs. 39.6%, P = 0.439) or 3-year recurrence-free survival (RFS) rates (49.1% vs. 39.5%, P = 0.299) between patients who received fluoropyrimidine-based adjuvant chemotherapy or observation. However, for patients with stages II and III BTC, chemotherapy significantly improved 5-year OS rate (52.4% vs. 35.6%, P = 0.002) and 3-year RFS rate (55.5% vs. 39.1%, P = 0.021) compared with observation. Conclusion Fluoropyrimidine-based adjuvant chemotherapy may prolong the survival of patients with stages II and III BTC after R0 resection.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aβ and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1β, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.

Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.

Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis. (Korean J Gastroenterol 2016;68:109-113)

Background/Aims: To evaluate the technical feasibility and clinical efficacy of double endoscopic nasobiliary drainage (ENBD) as a new method of draining multiple bile duct obstructions. Methods: A total of 38 patients who underwent double ENBD between January 2004 and February 2010 at the Asan Medical Center were retrospectively analyzed. We evaluated indications, laboratory results, and the clinical course. Results: Of the 38 patients who underwent double ENBD, 20 (52.6%) had Klatskin tumors, 12 (31.6%) had hepatocellular carcinoma, 3 (7.9%) had strictures at the anastomotic site following liver transplantation, and 3 (7.9%) had acute cholecystitis combined with cholangitis. Double ENBD was performed to relieve multiple biliary obstruction in 21 patients (55.1%), drain contrast agent filled during endoscopic retrograde cholangiopancreatography in 4 (10.5%), obtain cholangiography in 4 (10.5%), drain hemobilia in 3 (7.9%), relieve Mirizzi syndrome with cholangitis in 3 (7.9%), and relieve jaundice in 3 (7.9%). Conclusions: Double ENBD may be useful in patients with multiple biliary obstructions.

Renal cell carcinoma (RCC) represents the most common form of kidney cancer, which accounts for 3–5% newly diagnosed cancer cases. Since limited therapies are available for RCC, a search for new options is required. Therefore, in this study, we evaluated the combination effect of cinnamaldehyde (CNM) and hyperthermia treatment. CNM treatment combined with 43 °C hyperthermia synergistically increased cytotoxicity in RCC cell line ACHN cells. Through Western blot assays, we observed increased apoptosis signaling and decreased proliferation/metastasis signaling, along with a repressed heat shock protein 70 level. In flow cytometry analyses, CNM and hyperthermia combination clearly induced apoptosis and mitochondrial potential of ACHN cells, while arresting the cell cycle. Investigation of reactive oxygen species (ROS) suggested a significant increase of ROS generation by CNM and 43 °C hyperthermia co-treatment. We could verify that ROS is crucial in the apoptotic action of combination treatment with CNM and hyperthermia through further experiments regarding an ROS scavenger. Overall, we suggest CNM and hyperthermia combination treatment as an alternative option of anticancer strategies for RCC.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to behave as an attractive anti-cancer agent in various cancers. Despite its promise TRAIL has limitations such as short half-life and rapid development of resistance. In this regard, approaches to sensitizers of TRAIL that can overcome the limitations of TRAIL are necessary. However, the molecular targets and mechanisms underlying sensitization to TRAIL-induced apoptosis are not fully understood. Here, we propose that reactive oxygen species modulator-1 (Romo1) as an attractive sensitizer of TRAIL. Romo1 is a mitochondrial inner membrane channel protein that controls reactive oxygen species (ROS) production, and its expression is highly upregulated in various cancers, including colorectal cancer. In the present study, we demonstrated that Romo1 inhibition significantly increased TRAIL-induced apoptosis of colorectal cancer cells, but not of normal colon cells. The combined effect of TRAIL and Romo1 inhibition was correlated with the activation of mitochondrial apoptosis pathways. Romo1 silencing elevated the protein levels of BCL-2-associated X protein (Bax) by downregulating the ubiquitin proteasome system (UPS). Romo1 inhibition downregulated the interaction between Bax and Parkin. Furthermore, Romo1 knockdown triggered the mitochondrial dysfunction and ROS generation. We validated the effect of combination in tumor xenograft model in vivo. In conclusion, our study demonstrates that Romo1 inhibition induces TRAIL-mediated apoptosis by identifying the novel mechanism associated with the Bax/Parkin interaction. We suggest that targeting of Romo1 is essential for the treatment of colorectal cancer and may be a new therapeutic approach in the future and contribute to the drug discovery.

Despite the importance of radiation therapy, there are few radiation-related markers available for use in clinical practice. A larger catalog of such biomarkers is required to help clinicians decide when radiotherapy should be replaced with a patient-specific treatment. Arachidonate 15-lipoxygenase (15-LOX-1) enzyme is involved in polyunsaturated fatty acid metabolism. When colorectal cancer (CRC) cells were exposed to radiation, 15-LOX-1 was upregulated. To verify whether 15-LOX-1 protects against or induces DNA damage, we irradiated sh15-LOX-1 stable cells. We found that low 15-LOX-1 is correlated with radioresistance in CRC cells. These data suggest that the presence of 15-LOX-1 can be used as a marker for radiation-induced DNA damage. Consistent with this observation, gene-set-enrichment analysis based on microarray experiments showed that UV_RESPONSE was decreased in sh15-LOX-1 cells compared to shCon cells. Moreover, we discovered that the expression of the histone H2A variant macroH2A2 was sevenfold lower in sh15-LOX-1 cells. Overall, our findings present mechanistic evidence that macroH2A2 is transcriptionally regulated by 15-LOX-1 and suppresses the DNA damage response in irradiated cells by delaying H2AX activation.

Reactive oxygen species modulator-1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. However, its clinical implications in colorectal cancer patients are not well-known. For the first time, we investigated the association between Romo1 and the clinical outcomes of colorectal cancer patients.We examined Romo1 expression in resected tumor tissues immunohistochemically and assessed it with histological scores. We conducted survival analyses for patients who had curative resection (n = 190) in accordance with clinical parameters including level of Romo1 expression, and we examined the association between Romo1 expression and cell invasion using Matrigel invasion assay in colorectal cancer cells.We observed significantly longer mean disease-free survival in the low Romo1 group compared with the high Romo1 group (161 vs 127.6 months, p = 0.035), and the median overall survival of the low Romo1 group was significantly longer than that of the high Romo1 group (196.9 vs 171.3 months, p = 0.036). Cell invasiveness decreased in the Romo1 knockdown colorectal cancer cells in contrast to the controlled cells. Romo1 overexpression in tumor tissue was associated with a high lymph node ratio between the metastatic and examined lymph nodes (p = 0.025).Romo1 overexpression in tumor tissue was significantly associated with survival in curatively resected colorectal cancer patients, suggesting Romo1 expression as a potential adverse prognostic marker. Increased Romo1 expression was found to be associated with high lymph node ratio. Cancer invasiveness appeared to be a key reason for the poor survival related to highly expressed Romo1.

Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance.