Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.

Successful Endoscopic Resection of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Unresponsive to Helicobacter pylori Eradication Therapy.

Eradication of Helicobacter pylori is the first-line treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphomas; however, lesions may persist in 20% of patients after initial treatment, thereby necessitating the use of an additional therapeutic approach. Other treatment options include radiation therapy, chemotherapy, endoscopic resection, rituximab therapy, or watchful waiting. We present a case of localized gastric MALT lymphoma that did not respond to H. pylori eradication therapy. The patient waited for 12 months but the tumor showed no signs of regression endoscopically. Histologic examination revealed residual MALT lymphoma. The tumor was then successfully treated using endoscopic submucosal dissection and the patient remained disease-free for 4 years. To our knowledge, this is the first case in which a gastric MALT lymphoma was treated with endoscopic submucosal dissection. In conclusion, endoscopic resection may be recommended as second-line therapy for properly selected patients with gastric MALT lymphoma as it is effective and minimally invasive.

Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea.

BACKGROUND: The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF complex-related intellectual disability disorders (SSRIDDs). METHODS: Whole-exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were identified and their medical records were retrospectively analyzed. RESULTS: ARID1B, found in eight patients, was the most frequently altered gene. Four patients harbored pathogenic variants in SMARCA4, SMARCB1, ARID2, and SMARCA2. Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B-related nonsyndromic intellectual disability. Another patient harboring the SMARCA2 pathogenic variant was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2, SMARCB1, and SMARCA4 were nontruncating (missense). Frequently observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was observed in half of the patients (6/12). CONCLUSIONS: SSRIDDs have a broad disease spectrum, including NCBRS, CSS, and ARID1B-related nonsyndromic intellectual disability. Thus, SSRIDDs should be considered as a small but important cause of human developmental disorders.

Long-term Outcomes of Undifferentiated-Type Early Gastric Cancer with Positive Horizontal Margins after Endoscopic Resection.

Background/Aims: This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management. Methods: From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46). Results: No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality. Conclusions: UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.

A new simple endoscopic incision therapy for refractory benign oesophageal anastomotic stricture.

Oesophageal anastomotic stricture is a frequent complication after esophagectomy. In most cases, endoscopic bougination or balloon dilation usually resolves anastomotic stricture. However, some refractory oesophageal strictures remain difficult to treat and cause significant morbidity. Recently, successful treatment using endoscopic incisional therapy has been reported in several cases. We report a case of refractory benign oesophageal anastomotic stricture after oesophagectomy. A 72-year-old man underwent three consecutive bouginations. However, he developed progressive stricture. Stricture was successfully treated with an endoscopic knife incision. We performed only three incisions without a cutting method, which was new compared with previous reports. A new simple endoscopic incision technique is effective and safe for stricture management. In conclusion, endoscopic incisional therapy may be recommended as a salvage treatment for properly selected patients with refractory benign stricture who do not respond to conventional therapy.

Can endoscopic ultrasonography (EUS) improve the accuracy of clinical T staging by computed tomography (CT) for gastric cancer?

INTRODUCTION: With the introduction of new therapeutic options for gastric cancer treatment, more precise preoperative staging of gastric cancer is needed. The purpose of this study was to evaluate the role of endoscopic ultrasonography (EUS) for improving the accuracy of clinical T staging by computed tomography (CT) for gastric cancer. MATERIALS AND METHODS: A total of 2636 patients underwent stomach protocol CT (S-CT) and EUS, followed by gastrectomy for primary gastric adenocarcinoma between September 2012 and February 2018 at Seoul National University Hospital. The results of preoperative S-CT and EUS were compared to the postoperative pathologic staging. RESULTS: The overall accuracy of S-CT and EUS for T staging were 69.4% and 70.4%, respectively. When T staging was divided into T1-2 and T3-4 for clinically advanced gastric cancer (AGC), the positive predictive value for T3-4 using S-CT, EUS, and a combination of both modalities was 73.8%, 79.3%, and 85.6%, respectively. In 114 cases of indeterminate lesions between cT1 and cT2 by S-CT, EUS had a better prediction rate than the final decision based on endoscopy or the agreement between the two experts (Match rate: EUS vs. final decision, 69.3% vs. 58.8%). CONCLUSION: EUS can be a complementary diagnostic tool to clinical T staging of gastric cancer by CT for selecting T3-4 lesion.

Preparation and characterization of a soluble eggshell membrane/agarose composite scaffold with possible applications in cartilage regeneration.

Articular hyaline cartilage is an extremely hydrated, not vascularized tissue with a low-cell density. The damage of this tissue can occur after injuries or gradual stress and tears (osteoarthritis), minor damages can be self-healed in several weeks, but major injuries may eventually require surgery. In fact, in this case, because of nature of the cartilage (the absence of cells and vascularization) it is difficult to expect its natural regeneration in a reasonable amount of time. In recent years, cell therapy, in which cells are directly transplanted, has attracted attention. In this study, a scaffold for implanting chondrocytes was prepared. The scaffold was made as a sponge using the eggshell membrane and agarose. The eggshell membrane is structurally similar to the extracellular matrix and nontoxic due to its many collagen components and has good biocompatibility and biodegradability. However, scaffolds made of collagen only has poor mechanical properties. For this reason, the disulfide bond of collagen extracted from the insoluble eggshell membrane was cut, converted into water-soluble, and then mixed with agarose to prepare a scaffold. Agarose is capable of controlling mechanical properties, has excellent biocompatibility, and is suitable for forming a hydrogel having a three-dimensional porosity. The scaffold was examined for Fourier-transform infrared, mechanical properties, biodegradability, and biocompatibility. In in vitro experiment, cytotoxicity, cell proliferation, and messenger RNA expression were investigated. The study demonstrated that the agarose/eggshell membrane scaffold can be used for chondrocyte transplantation.

Simultaneous Quantification of Chloramphenicol, Thiamphenicol, Florfenicol, and Florfenicol Amine in Animal and Aquaculture Products Using Liquid Chromatography-Tandem Mass Spectrometry.

The accumulation of antimicrobial residues in edible animal products and aquaculture products could pose health concerns to unsuspecting consumers. Hence, this study aimed to develop a validated method for simultaneous quantification of chloramphenicol (CAP), thiamphenicol (TAP), florfenicol (FF), and florfenicol amine (FFA) in beef, pork, chicken, shrimp, eel, and flatfish using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Primary-secondary amine (PSA) and MgSO4 were used for sample purification. The analytes were separated on a reversed-phase analytical column. The coefficients of determination for the linear matrix-matched calibration curves were ≥0.9941. Recovery rates ranged between 64.26 and 116.51% for the four analytes with relative standard deviations (RSDs) ≤ 18.05%. The calculated limits of detection (LODs) and limits of quantification (LOQs) were 0.005-3.1 and 0.02-10.4 µg/kg, respectively. The developed method was successfully applied for monitoring samples obtained from local markets in Seoul, Republic of Korea. The target residues were not detected in any tested matrix. The designed method was versatile, sensitive, and proved suitable for quantifying residues in animal-derived products.

Clinical outcomes of endoscopic resection for undifferentiated intramucosal early gastric cancer larger than 2 cm.

BACKGROUND: This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2 cm as the only non-curative factor. METHODS: From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2 cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59 months for recurrence and 90 months for overall survival. RESULTS: Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5- and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. CONCLUSION: The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2 cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status.

Risk factors of lymph node metastasis after non-curative endoscopic resection of undifferentiated-type early gastric cancer.

BACKGROUND: This study aimed to investigate risk factors for lymph node (LN) or distant metastasis after non-curative endoscopic resection (ER) of undifferentiated-type early gastric cancer (EGC). METHODS: Of 1124 patients who underwent ER for undifferentiated-type gastric cancer at 18 tertiary hospitals across six geographic areas in Korea between 2005 and 2014, 634 with non-curative ER beyond the expanded criteria were retrospectively enrolled. According to the treatment after ER, patients were divided into additional surgery (n = 270) and follow-up (n = 364) groups. The median follow-up duration was 59 months for recurrence and 84 months for mortality. RESULTS: LN metastasis was found in 6.7% (18/270) of patients at surgery. Ulcer [odds ratio (OR) 3.83; 95% confidence interval (CI) 1.21-12.13; p = 0.022] and submucosal invasion (OR 10.35; 95% CI 1.35-79.48; p = 0.025) were independent risk factors. In the follow-up group, seven patients (1.9%) developed LN or distant recurrence. Ulcer [hazard ratio (HR) 7.60; 95% CI 1.39-35.74; p = 0.018], LVI (HR 6.80; 95% CI 1.07-42.99; p = 0.042), and positive vertical margin (HR 6.71; 95% CI 1.28-35.19; p = 0.024) were independent risk factors. In the overall cohort, LN metastasis rates were 9.6% in patients with two or more risk factors and 1.2% in those with no or one risk factor. CONCLUSIONS: LVI, ulcer, submucosal invasion, and positive vertical margin are independently associated with LN or distant metastasis after non-curative ER of undifferentiated-type EGC. Surgical resection is strongly recommended for patients with two or more risk factors.

Successful Endoscopic Resection of Residual Colonic Mucosa-Associated Lymphoid Tissue Lymphoma after Polypectomy.

Mucosa-associated lymphoid tissue (MALT) lymphomas are typically found in the stomach, while colonic MALT lymphoma is rarely found. Considering its rarity, definitive treatment of colonic MALT lymphoma has not been established. Different from that in the stomach, Helicobacter pylori infection might play a minor role while determining the treatment of colonic MALT lymphoma. If colonic MALT lymphoma is localized, treatment options are surgical resection, radiation, endoscopic resection, or combination therapy. Here, we report a case of residual colonic MALT lymphoma after endoscopic mucosal resection, which was a 1.5-cm-sized tumor confined to the superficial wall of the rectum. The lesion was successfully treated using the endoscopic submucosal dissection technique. The patient remained disease-free for 4 years. This case provides rationale for endoscopic submucosal dissection treatment as a salvage therapy for residual tumors in properly selected patients with colonic MALT lymphoma.

Comparison between endoscopic submucosal resection and surgery for the curative resection of undifferentiated-type early gastric cancer within expanded indications: a nationwide multi-center study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) has debate due to the risk of lymph node metastasis. We investigated the outcomes of ESD compared to those of surgery for the UD EGC within expanded indication. METHODS: We reviewed 971 UD EGC patients performed ESD across 18 hospitals in Korea and 1812 patients who underwent surgical resection in two hospitals between February 2005 and May 2015. Of these cases, we enrolled a curative resected ESD group of 328 patients and surgery group of 383 cases within an expanded indication. Overall outcomes and one-to-one propensity score-matched (218 ESD group vs 218 surgery group cases) outcomes for these two groups were analyzed. RESULTS: Over the 75.6 month median follow-up period for the 711 enrolled cases, recurrences occurred in 22 patients (6.7%) in the ESD group but not in the surgery group. Overall survival (OS) was higher in the surgery group (p = 0.0316) in all cases, but there was no significant difference after propensity score matching (p = 0.069). According to the histologic type in propensity score matching, the OS of signet ring cell carcinoma and poorly differentiated carcinoma patients did not differ between the ESD and surgery groups (p = 0.1189 and p = 0.3087, respectively). In the surgery group involving expanded criteria, lymph node metastasis was found in six cases (1.56%). CONCLUSIONS: Although ESD shows comparable outcomes to surgery for the UD EGC within expanded indications, appropriate patient selection is needed for the ESD due to the possibility of lymph node metastasis.

Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: a randomized controlled trial.

BACKGROUND AND AIMS: Whether eradication of Helicobacter pylori reduces the incidence of metachronous gastric cancer (MGC) is still debatable. We aimed to evaluate the long-term effect of H pylori eradication on the development of MGC after endoscopic gastric tumor resection. METHODS: We undertook an open-label, prospective, randomized controlled trial at a tertiary hospital in Seoul, Korea. Participants were recruited during April 2005 to February 2011 and followed until December 2016. We assigned 898 patients with H pylori infection treated with endoscopic resection (ER) for gastric dysplasia or early gastric cancer to receive (n =442) or not receive (n =456) eradication therapy using a random-number chart. Eradication group patients received oral omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for a week, whereas control group patients received no H pylori treatment. The primary outcome was the incidence of MGC (intention-to-treat analysis). RESULTS: The 877 patients who attended ≥1 follow-up examination (eradication group, 437; control group, 440) were analyzed. Median follow-up was 71.6 months (interquartile range, 42.1-90.0). MGC developed in 18 (4.1%) eradication and 36 (8.2%) control group patients (log-rank test, P = .01). In our yearly analysis, the effect of eradication showed a significant difference in 5 years after allocation (log-rank test, P = .02). The adjusted hazard ratio for the control group was 2.02 (95% CI, 1.14-3.56; P = .02), compared with the eradication group. CONCLUSIONS: H pylori eradication significantly reduces the incidence of MGC after ER of gastric tumors and should be considered for H pylori-positive gastric tumor patients treated with ER. (Clinical trial registration number: NCT01510730.).

Development and validation of modified QuEChERS method coupled with LC-MS/MS for simultaneous determination of cymiazole, fipronil, coumaphos, fluvalinate, amitraz, and its metabolite in various types of honey and royal jelly.

Over the past few decades, honey products have been polluted by different contaminants, such as pesticides, which are widely applied in agriculture. In this work, a modified EN - quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method was developed for the simultaneous quantification of pesticide residues, including cymiazole, fipronil, coumaphos, fluvalinate, amitraz, and its metabolite 2,4-dimethylaniline (2,4-DMA), in four types of honey (acacia, wild, chestnut, and manuka) and royal jelly. Samples were buffered with 0.2M dibasic sodium phosphate (pH 9), and subsequently, acetonitrile was employed as the extraction solvent. A combination of primary secondary amine (PSA) and C18 sorbents was used for purification prior to liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI+/MS-MS) analysis. The estimated linearity measured at six concentration levels presented good correlation coefficients (R2)≥0.99. The recovery, calculated from three different spiking levels, was 62.06-108.79% in honey and 67.58-106.34% in royal jelly, with an RSD<12% for all the tested compounds. The matrix effect was also evaluated, and most of the analytes presented signal enhancement. The limits of quantification (LOQ) ranged between 0.001 and 0.005mg/kg in various samples. These are considerably lower than the maximum residue limits (MRL) set by various regulatory authorities. A total of 43 market (domestic and imported) samples were assayed for method application. Among the tested samples, three samples were tested positive (i.e. detected and quantified) only for cymiazole residues. The residues in the rest of the samples were detected but not quantified. We concluded that the protocol developed in this work is simple and versatile for the routine quantification of cymiazole, 2,4-DMA, fipronil, coumaphos, amitraz, and fluvalinate in various types of honey and royal jelly.

Molecular Mechanism of Plant Recognition of Extracellular ATP.

Adenosine 5'-triphosphate (ATP), a ubiquitously dispersed biomolecule, is not only a major source of biochemical energy for living cells, but also acts as a critical signaling molecule through inter-cellular communication. Recent studies have clearly shown that extracellular ATP is involved in various physiological processes in plants, including root growth, stomata movement, pollen tube development, gravitropism, and abiotic/biotic stress responses. The first plant purinergic receptor for extracellular ATP, DORN1 (the founding member of the P2K family of purinergic receptors), was identified in Arabidopsis thaliana by a forward genetic screen. DORN1 consists of an extracellular lectin domain, transmembrane domain, and serine/threonine kinase, intracellular domain. The predicted structure of the DORN1 extracellular domain revealed putative key ATP binding residues but an apparent lack of sugar binding. In this chapter, we summarize recent studies on the molecular mechanism of plant recognition of extracellular ATP with specific reference to the role of DORN1.

Clinical Interpretation of Elevated CA 19-9 Levels in Obstructive Jaundice Following Benign and Malignant Pancreatobiliary Disease.

BACKGROUND/AIMS: Elevated carbohydrate antigen (CA) 19-9 level may be unable to differentiate between benign and malignant pancreatobiliary disease with obstructive jaundice. The study aims to determine the clinical interpretation and the diagnostic value of CA 19-9 level in pancreatobiliary diseases with coexistent obstructive jaundice. METHODS: We retrospectively reviewed the data of 981 patients who underwent biliary drainage due to obstructive jaundice following pancreatobiliary disease at Sanggye Paik Hospital for 5 years. 114 patients with serial follow-up data for CA 19-9 level were included in this study (80 patients with malignancy and 34 patients with benign diseases). We compared the levels of CA 19-9 levels and the biochemical value before and after biliary drainage. RESULTS: The rate of CA 19-9 elevation (>37 U/mL) was significantly different between the benign group and the malignant group (59% vs. 90%, p=0.001). Despite the decrease in serum bilirubin after biliary drainage, CA 19-9 levels remained elevated in 12% of patients in the benign group and in 63% of patients in the malignant group (p<0.001). Finally, 12% of patients in the benign group turned out to have malignant disease. A receiver operating characteristic analysis provided a cut-off value of 38 U/mL for differentiating benign disease from malignant disease after biliary drainage (area under curve, 0.787; 95% confidence interval, 0.703 to 0.871; sensitivity, 62%; specificity, 88%). CONCLUSIONS: This study suggested that we should consider the possibility of malignant causes if the CA 19-9 levels remain high or are more than 38 U/mL after resolution of biliary obstruction.