Factors of Endoscopic Ultrasound-Guided Tissue Acquisition for Successful Next-Generation Sequencing in Pancreatic Ductal Adenocarcinoma

Background/Aims@#Recent advances in understanding the genetics of pancreatic ductal adenocarcinoma (PDAC) have led to the potential for a personalized approach. Several studies have described the feasibility of generating genetic profiles of PDAC with next-generation sequencing (NGS) of samples obtained through endoscopic ultrasound-guided tissue acquisition (EUS-TA). The aim of this study was to find the best EUS-TA approach for successful NGS of PDAC. @*Methods@#We attempted to perform NGS with tissues from 190 patients with histologically proven PDAC by endoscopic ultrasound-guided fine-needle aspiration and endoscopic ultrasound-guided fine-needle biopsy at Samsung Medical Center between November 2011 and February 2015. The medical records of these patients were retrospectively reviewed for parameters including tumor factors (size, location, and T stage), EUS-TA factors (needle gauge [G], needle type, and number of needle passes) and histologic factors (cellularity and blood contamination). The sample used for NGS was part of the EUS-TA specimen that underwent cytological and histological analysis. @*Results@#NGS could be successfully performed in 109 patients (57.4%). In the univariate analysis, a large needle G (p=0.003) and tumor located in the body/tail (p=0.005) were associated with successful NGS. The multivariate logistic regression analysis revealed that the needle G was an independent factor of successful NGS (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; p=0.031). @*Conclusions@#The needle G is an independent factor associated with successful NGS. This finding may suggest that the quantity of cells obtained from EUS-TA specimens is important for successful NGS.

Long-term Outcome of Endoscopic Retrograde Biliary Drainage of Biliary Stricture Following Living Donor Liver Transplantation

Background/Aims@#Biliary strictures remain one of the most challenging aspects after living donor liver transplantation (LDLT). The aim of this study was to assess long-term outcome of endoscopic treatment of biliary strictures occurring after LDLT and to identify risk factors of recurrent biliary strictures following endoscopic retrograde biliary drainage (ERBD) in LDLT. @*Methods@#A total of 1,106 patients underwent LDLT from May 1995 to May 2014. We compared the risk factors between patients with and without recurrent biliary strictures. @*Results@#Biliary strictures developed in 24.0% of patients. Technical success rate of ERBD for biliary stricture after LDLT was 66.2% (145/219). Among 145 patients managed by endoscopic drainage, stricture resolution occurred in 69 with median duration of stent indwelling of 13.6 months (range, 0.5 to 67.3 months), and stricture recurrence was seen in 20 (21.3%) out of 94. The median recurrence-free duration after final endoscopic success was 13.1 months (range, 0.5 to 67.3 months). Older donor age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03 to 1.17; p=0.004) and non-B, non-C liver cirrhosis (HR, 5.10; 95% CI, 1.10 to 25.00; p=0.043) were associated with higher recurrence of biliary stricture. @*Conclusions@#Long-term stricture resolution rate after ERBD insertion for biliary stricture occurring after LDLT was 73.4%. Clinicians should pay careful attention during following-up to decide when to remove ERBD in patients who have factors associated with recurrent biliary strictures.

Present and Future of Endoscopic Ultrasound-Guided Tissue Acquisition in Solid Pancreatic Tumors

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a well-established method for pathological diagnosis of solid pancreatic neoplasm. It can be performed either as EUS-guided fine-needle aspiration (EUS-FNA) or EUS-guided fine-needle biopsy (EUS-FNB). The incidence of adverse events related to EUS-TA is less than 1%. The factors that affect the diagnostic accuracy and specimen adequacy include the techniques used, type and size of the needle, competency of endosonographers, presence of cytopathologists/cytotechnologists, and rapid on-site examination. EUS-TA may contribute to precision medicine through obtaining tissue samples for next-generation sequencing. The current status, several clinical issues for diagnostic yield and adverse events, and future perspectives of EUS-FNA/FNB for diagnosing pancreatic neoplasm have been discussed in this review article.

Risk Factors for Pancreatitis and Cholecystitis after Endoscopic Biliary Stenting in Patients with Malignant Extrahepatic Bile Duct Obstruction

BACKGROUND/AIMS: For the treatment of malignant biliary obstruction, endoscopic retrograde biliary drainage (ERBD) has been widely accepted as a standard procedure. However, post-ERBD complications can affect the lives of patients. The purpose of this study was to identify the predictive factors for these complications, including the patient’s status, cancer status, and stent type.METHODS: This was a retrospective analysis conducted in a single tertiary hospital from January 2007 to July 2017. The following variables were evaluated: sex, age, body mass index, cancer type, history of pancreatitis, gallbladder stone, previous biliary stenting, precut papillotomy, stent type, contrast injection into the pancreatic duct or gallbladder, cystic duct invasion by the tumor, and occlusion of the cystic duct orifice by a metal stent.RESULTS: Multivariate analysis showed that contrast injection into the pancreatic duct was a risk factor for pancreatitis. Patients with a history of bile drainage showed a lower risk of pancreatitis. For cholecystitis, the analysis revealed contrast injection into the gallbladder and cystic duct invasion by the tumor as important predictive factors. Metal stents showed a greater risk of post-procedure pancreatitis than plastic stents, but did not affect the incidence of cholecystitis.CONCLUSIONS: Considering that contrast injection is the most important factor for both complications, a careful approach by the physician is essential in preventing the occurrence of any complications. Further, choosing the type of stent is an important factor for patients at a risk of post-procedure pancreatitis.

Hindfoot Endoscopy for the Treatment of Posterior Ankle Impingement Syndrome: A Comparison of Two Methods (a Standard Method versus a Method Using a Protection Cannula) / 대한족부족관절학회지

PURPOSE: The purpose of this study is to compare the clinical results between two different methods of hindfoot endoscopy to treat posterior ankle impingement syndrome. MATERIALS AND METHODS: Between January 2008 and January 2014, 52 patients who underwent hindfoot endoscopy were retrospectively reviewed. Two methods of hindfoot endoscopy were used; Group A was treated according to van Dijk and colleagues' standard two-portal method, and group B was treated via the modified version of the above, using a protection cannula. For clinical comparison, the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, time required to return to activity, and the presence of complications were used. RESULTS: There was no statistically significant difference in the AOFAS scores at the final follow-up, and there was also no statistically significant difference in the times for the scores to return to the preoperative level. There were no permanent neurovascular injuries and wound problems in either group. CONCLUSION: Use of protection cannula may provide additional safety during hindfoot endoscopy. We could not prove whether protection cannula can provide superior safety for possible neurovascular injury. Considering the possible safety and risk of using additional instrument, the use of this method may be optional.

Experimental infection of dogs with highly pathogenic avian influenza virus (H5N8)

During the highly pathogenic avian influenza (HPAI) H5N8 virus outbreak in Korea, a dog in layer farm contaminated by H5N8 was reported seropositive for HPAI H5N8. To investigate the possibility of adaptation and transmission of HPAI H5N8 to dogs, we experimentally inoculated dogs with H5N8. Viral genes were weakly detected in nasal swabs and seroconversions in inoculated and contact dogs. Although the H5N8 virus did not induced severe clinical signs to dogs, the results suggest that surveillance of farm dogs should continue as a species in which the avian influenza virus may acquire infectivity to mammals through frequent contact with the virus.

Viscerotropic velogenic Newcastle disease virus replication in feathers of infected chickens

Newcastle disease viruses (NDVs) cause systemic diseases in chickens with high mortality. However, little is known about persistence of NDVs in contaminated tissues from infected birds. In this study, we examined viral replication in the feather pulp of chickens inoculated with viscerotropic velogenic NDV (vvNDV) genotype VII. Reverse transcription real-time PCR and immunohistochemistry were used to investigate viral persistence in the samples. vvNDV was detected in the oropharynx and cloaca and viral antigens were detected in the feathers, suggesting that feathers act as sources of viral transmission.

Pneumatosis Cystoides Intestinalis in a Patient with Dermatomyositis: A Case Report and Review of the Literature / 대한내과학회지

Pneumatosis cystoides intestinalis (PCI) is a rare disease with intramural gas formation in the gastrointestinal tract. The causes of PCI are various, and are commonly associated with collagen vascular disease. We present a case of a 48-year-old female with dermatomyositis (DM) who also developed PCI. Her risk of PCI may have been increased by multiple factors such as gender, DM itself, and medications including corticosteroids, methotrexate, and azathioprine. While the cause of, and risk factors for PCI in DM patients are not well known on a global scale, outcomes range from benign to life threatening. Therefore, we present a case study and review the literature to identify candidate risk factors for PCI.

Intranasal Administration Model for Evaluating Protection Against Influenza Virus in Mice

Antiviral activity against Influenza virus of 14 Lactobacillus species isolated from food was monitored. Lactobacillus species were isolated from traditional Korean fermented food. Each live Lactobacillus was administered into the nasal cavity of SPF 6-week-old BALB/c mice. After the Lactobacillus treatment, Influenza virus (A/NWS/33/H1N1) was inoculated to each mouse. Clinical signs and mortality was monitored for 21 days. Each Lactobacillus strain showed various level of antiviral activity against Influenza virus. As a result of this study, this mouse experiment model, including intranasal treatment of live Lactobacillus species, could be effective model in evaluating immunomodulatory response of probiotics against respiratory viruses.

Quantitative measurement of influenza virus replication using consecutive bronchoalveolar lavage in the lower respiratory tract of a ferret model

The ferret is an established animal model of influenza virus infection. Although viral replication in the upper respiratory tract is usually measured with consecutively collected nasal washes, daily evaluation of viral replication in the lung is limited because a large numbers of ferrets need to be sacrificed at consecutive time points. To overcome this limitation, we performed a virus quantification assay using bronchoalveolar lavage (BAL) fluid. This non-invasive BAL technique allows consecutive quantification of virus replication in the lungs of living ferrets. Our method can be used for the longitudinal evaluation of virus tropism in the lower respiratory tract.

Progress and hurdles in the development of influenza virus-like particle vaccines for veterinary use

Virus-like particles (VLPs), which resemble infectious virus particles in structure and morphology, have been proposed to provide a new generation of vaccine candidates against various viral infections. As effective immunogens, characterized by high immunogenicity and safety, VLPs have been employed in the development of human influenza vaccines. Recently, several influenza VLP vaccines have been developed for veterinary use and successfully evaluated in swine, canine, duck, and chicken models. These VLP vaccine candidates induced protective immune responses and enabled serological differentiation between vaccinated and infected animals in conjunction with a diagnostic test. Here, we review the current progress of influenza VLP development as a next-generation vaccine technology in the veterinary field and discuss the challenges and future direction of this technology.

Corrigendum: Clinical Correlation between Serum Cytokeratin-18 and Metabolic Parameters in Patients with Sonographic Non-alcoholic Fatty Liver Disease / 대한소화기학회지

This correction is being published to correct the third author's Korean name.

Clinical Correlation between Serum Cytokeratin-18 and Metabolic Parameters in Patients with Sonographic Non-alcoholic Fatty Liver Disease / 대한소화기학회지

BACKGROUND/AIMS: The serum cytokeratin-18 (CK-18) has been suggested to be a surrogate marker of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the correlation between CK-18 and metabolic parameter in NAFLD patients. Correlation between CK-18 and macronutrient composition was also assessed. METHODS: A total of 212 subjects were recruited. Blood chemistry including fasting glucose, cholesterol level, AST, ALT, and CK-18 were compared. Data on calorie intake and carbohydrate consumption were acquired by five-day-diet diary using 24 hour recall method. RESULTS: Plasma CK-18 were markedly increased in patient with NAFLD compared with control group (420.4+/-282.3 vs. 313.6+/-179, p<0.001). Plasma CK-18 were positively correlated with systolic blood pressure (r=0.130), ALT (r=0.503) and negatively correlated with HDL cholesterol (r=-0.246). NAFLD patients with metabolic syndrome had higher CK-18 level than those without metabolic syndrome (484.0 vs. 372.1 U/L, p=0.021). When NAFLD patients were subdivided into two groups with CK-18 cut-off value of 400 U/L, patients with CK-18 level over 400 U/L showed higher body mass index (28.0+/-4.5 vs. 25.5+/-4.3), subcutaneous abdominal fat (283.5+/-172.2 vs. 195.7+/-147.8), AST (52.7+/-26.3 vs. 40.7+/-23.5) and ALT (102.0+/-52.6 vs. 61.2+/-32.2). Calorie intake (r=0.301) and carbohydrate intake (r=0.305) also showed positive correlation with CK-18. CONCLUSIONS: Plasma CK-18 showed positive correlation with metabolic parameters as well as calorie and carbohydrate intake when its cut-off value of greater than 400 U/L was used.

Hepatocellular Carcinoma Arising from Non-Cirrhotic Non-Alcoholic Steatohepatitis / 이화의대지

The major risk factors of hepatocellular carcinoma include hepatitis B or C virus infection and alcohol consumption in Korea which lead to liver cirrhosis development and progression. However, prevalence of non-alcoholic fatty liver disease related hepatocellular carcinoma is rising worldwide and hepatocellular carcinoma cases in patients with non-cirrhotic non-alcoholic steatohepatitis are increasing. A hypoechoic nodule was incidentally detected in a 52-year-old woman, with no evidence of liver cirrhosis or specific hepatocellular carcinoma findings on radiological examination. Non-cirrhotic non-alcoholic steatohepatitis-associated hepatocellular carcinoma was diagnosed based on clinical, laboratory, and histopathological findings of liver biopsy. To our knowledge, this is the first such case report in Korea.

Papular Mucinosis in a Renal Transplantation Recipient / 대한이식학회지

Papular mucinosis (PM, scleromyxoedema) is a rare dermatologic disease. It is histologically characterized by a focal dermal deposit of mucin within the skin. Although PM is accepted as an idiopathic disease in most cases, some authors argued that it may be a cutaneous manifestation of a systemic disease. Here, we describe a 68-year-old male kidney transplantation recipient with a complaint of intractable itching sensation on the forehead. We diagnosed the skin lesions as PM, which were improved after cyclosporine dose reduction.

The Value of (99m)Tc-HMPAO-WBC Scan in the Diagnosis of Infection after Total Knee Arthroplasty

PURPOSE: The early diagnosis and detection of prosthetic infection after TKA is very important and difficult for deter- mination of the plan in management and reduction of complications. In these reasons, this study was performed to evaluate the usefulness and limitation of (99m)Tc-HMPAO(Technetium (99m)-hexamethyl- propylene amine oxime)-labeled WBC scan in the patients with clinically suspicious prosthetic infection. MATERIALS AND METHODS: The study subjects were 25 patients(3 men and 19 women, mean age: 66.5 years) performed (99m)Tc-HMPAO WBC scan in the patients with clinically suspicious prosthesis infection after TKA from January, 2005 to May, 2007. And in 6 patients who had undergone bilateral arthroplasty, we regarded one patient as two cases. Thus, total 31 prostheses were included in this study. Final diagnosis of infection was based on bacteriological result by intrao- perative cultures, surgical findings, and histological evidence intraoperatively obtained in the suspicious site and clinical follow-up. RESULTS: In the final diagnosis, we confirmed that total 16 prosthetic joints were infected. Of these infected prostheses, increased (99m)Tc-HMPAO WBC scan uptake waspositive in 15, negative in 1. Finally, 15 cases were confirmed as nonin- fected prosthesis, 6 showed positive by (99m)Tc-HMPAO WBC scan uptake, 9 showed negative. Over all sensitivity, speci- ficity, and positive predictive value for diagnosisof infected TKA were 93.75, 60%, and 71.43%. CONCLUSION: (99m)Tc-HMPAO WBC scan was a highly sensitive method for the diagnosis of prosthetic infection after TKA. But low specificity and high false positive of (99m)Tc-HMPAO WBC scan demand more clinical follow-up for confirmed diagnosis. To increase specificity, additionally scan will be needed.

Apoptosis in the meniscus of human osteoarthritic knee / 대한정형외과연구학회지

PURPOSE: The purposes of this study were to examine whether meniscal degeneration in human osteoarthritis(OA) was related with the occurrence of apoptosis, the expression of nitrotyrosine and Fas. MATERIALS AND METHODS: Menisci were obtained from OA patients undergoing total knee replacement arthroplasty and from normal subjects who were operated an above knee amputaton. According to histologic degeneration, menisci were graded to normal, grade 1(mild), grade 2(moderate), and grade 3(severe). Apoptotic cells were identified by TUNEL method and electron microscopy. Meniscal sections were analyzed by immunohistochemistry for the presence of nitrotyrosine and Fas expression. RESULTS: The number of apoptotic cells were significantly increased in OA meniscus compared with normal meniscus(p < 0.05). The number of apoptotic cells were increased with tissue degeneration. On electron microscopy, the typical chromatin condensation in the OA meniscus was shown in apoptotic cell. The number of Fas-expressing cells was significantly higher in the OA meniscus(p < 0.05). Nitrotyrosine immuno reactivity was prominent in the degenerative menisci(p < 0.05). Fas and nitrotyrosine expression were increased with degree of tissue degeneration. An increase in number of apoptotic cells was correlated with tissue degeneration but not with age . CONCLUSION: Apoptosis was suggested as one of the causes in the tissue degeneration of the human OA meniscus. The development of apoptosis in the meniscus may be related with Fas and nitrotyrosine expression but not with age.